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Sample records for ketogenic diet conserved

  1. Ketogenic diet

    Directory of Open Access Journals (Sweden)

    Tina Bregant

    2009-04-01

    conclusions This review traces a history of ketogenic diet, reviews its uses and side effects, and discusses possible alternatives and the diet’s possible mechanisms of action. We show how to use the diet in practice. Protocol and calculations are presented. We look toward possible future uses of the ketogenic diet, since it is efficient, under doctor’s supervison safe, but very demanding, additional treatment.

  2. Ketogenic Diets and Pain

    Science.gov (United States)

    Masino, Susan A.; Ruskin, David N.

    2014-01-01

    Ketogenic diets are well-established as a successful anticonvulsant therapy. Based on overlap between mechanisms postulated to underlie pain and inflammation, and mechanisms postulated to underlie therapeutic effects of ketogenic diets, recent studies have explored the ability for ketogenic diets to reduce pain. Here we review clinical and basic research thus far exploring the impact of a ketogenic diet on thermal pain, inflammation, and neuropathic pain. PMID:23680946

  3. Ketogenic Diets and Pain

    OpenAIRE

    Masino, Susan A.; Ruskin, David N.

    2013-01-01

    Ketogenic diets are well-established as a successful anticonvulsant therapy. Based on overlap between mechanisms postulated to underlie pain and inflammation, and mechanisms postulated to underlie therapeutic effects of ketogenic diets, recent studies have explored the ability for ketogenic diets to reduce pain. Here we review clinical and basic research thus far exploring the impact of a ketogenic diet on thermal pain, inflammation, and neuropathic pain.

  4. Metabolic Effects of Ketogenic Diets

    OpenAIRE

    J Gordon Millichap

    1989-01-01

    The results of 24 metabolic profiles performed on 55 epileptic children receiving the classical ketogenic diet, the MCT diet, a modified MCT diet, and normal diets are reported from the University Department of Paediatrics, John Radcliffe Hospital, Oxford, England.

  5. Ketogenic Diet in Epileptic Encephalopathies

    OpenAIRE

    Sharma, Suvasini; Tripathi, Manjari

    2013-01-01

    The ketogenic diet is a medically supervised high-fat, low-carbohydrate diet that has been found useful in patients with refractory epilepsy. It has been shown to be effective in treating multiple seizure types and epilepsy syndromes. In this paper, we review the use of the ketogenic diet in epileptic encephalopathies such as Ohtahara syndrome, West syndrome, Dravet syndrome, epilepsy with myoclonic atonic seizures, and Lennox-Gastaut syndrome.

  6. [Epilepsy, cognition and ketogenic diet].

    Science.gov (United States)

    Garcia-Penas, J J

    2018-03-01

    Most individuals with epilepsy will respond to pharmacologic treatment; however, approximately 20-30% will develop medically refractory epilepsy. Cognitive side effects of antiepileptic drugs are common and can negatively affect tolerability, compliance, and long-term retention of the treatment. Ketogenic diet is an effective and well-tolerated treatment for these children with refractory epilepsy without any negative effect on cognition or behavior. To review the current state of experimental and clinical data concerning the neuroprotective and cognitive effects of the ketogenic diet in both humans and animals. In different animal models, with or without epilepsy, the ketogenic diet seems to have neuroprotective and mood-stabilizing effects. In the observational studies in pediatric epilepsy, improvements during treatment with the ketogenic diet are reported in behavior and cognitive function, particularly with respect to attention, alertness, activity level, socialization, and sleep quality. One randomized controlled trial in patients with pediatric refractory epilepsy showed a mood and cognitive activation during ketogenic diet treatment. Ketogenic diet shows a positive impact on behavioral and cognitive functioning in children and adolescents with refractory epilepsy. More specifically, an improvement is observed in mood, sustained attention, and social interaction.

  7. Ketogenic diet for epilepsy treatment

    Directory of Open Access Journals (Sweden)

    Letícia Pereira de Brito Sampaio

    Full Text Available ABSTRACT The ketogenic diet (KD, a high-fat, low-carbohydrate, and adequate-protein diet is an established, effective nonpharmacologic treatment option for intractable childhood epilepsy. The KD was developed in 1921 and even though it has been increasingly used worldwide in the past decade, many neurologists are not familiar with this therapeutic approach. In the past few years, alternative and more flexible KD variants have been developed to make the treatment easier and more palatable while reducing side effects and making it available to larger group of refractory epilepsy patients. This review summarizes the history of the KD and the principles and efficacy of the classic ketogenic diet, medium-chain triglyceride(s (MCT ketogenic diet, modified Atkins diet, and low glycemic index treatment.

  8. The ketogenic diet and epilepsy.

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    Kim, Do Young; Rho, Jong M

    2008-03-01

    The ketogenic diet has long been used to treat medically refractory epilepsy. The mechanisms underlying its clinical effects, however, have remained a mystery. The evidence to date suggests that a fundamental shift from glycolysis to intermediary metabolism induced by the ketogenic diet is necessary and sufficient for clinical efficacy. This notion is supported by a growing number of studies indicating that glucose restriction, ketone bodies and polyunsaturated fatty acids may all play mechanistic roles, possibly by enhancing mitochondrial respiration and ATP production, and decreasing reactive oxygen species production. Recent reports indicate that ketone bodies can reduce oxidative stress and that fatty acid-induced mitochondrial uncoupling may also yield similar protective effects. Ketone bodies may attenuate spontaneous firing of ATP-sensitive potassium channels in central neurons, and pharmacological inhibition of glycolysis has been shown to retard epileptogenesis in a rat kindling model. While the mechanisms underlying the broad clinical efficacy of the ketogenic diet remain unclear, there is growing evidence that the ketogenic diet alters the fundamental biochemistry of neurons in a manner that not only inhibits neuronal hyperexcitability but also induces a protective effect. Thus, the ketogenic diet may ultimately be useful in the treatment of a variety of neurological disorders.

  9. Ketogenic Diet: Effects on Growth

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-12-01

    Full Text Available The effects of the ketogenic diet on growth of 237 children (130 males, 107 females treated for intractable epilepsy has been evaluated in a prospective cohort study (average follow-up 308 days at the Johns Hopkins Hospital, Baltimore, MD.

  10. Ketogenic diet for epilepsy treatment

    OpenAIRE

    Sampaio, Letícia Pereira de Brito

    2016-01-01

    ABSTRACT The ketogenic diet (KD), a high-fat, low-carbohydrate, and adequate-protein diet is an established, effective nonpharmacologic treatment option for intractable childhood epilepsy. The KD was developed in 1921 and even though it has been increasingly used worldwide in the past decade, many neurologists are not familiar with this therapeutic approach. In the past few years, alternative and more flexible KD variants have been developed to make the treatment easier and more palatable whi...

  11. The Ketogenic Diet and Potassium Channel Function

    Science.gov (United States)

    2015-11-01

    1 AWARD NUMBER: W81XWH-13-1-0463 TITLE: The Ketogenic Diet and Potassium Channel Function PRINCIPAL INVESTIGATOR: Dr. Geoffrey Murphy...NUMBER The Ketogenic Diet and Potassium Channel Function 5b. GRANT NUMBER W81XWH-13-1-0463 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Geoffrey Murphy...The overall objective of this Discovery Award was to explore the hypothesis the ketogenic diet (KD) regulates neuronal excitability by influencing

  12. Protein-Losing Enteropathy as a Complication of the Ketogenic Diet

    OpenAIRE

    Ahn, Won Kee; Park, Soyoung; Kim, Heung Dong

    2017-01-01

    The ketogenic diet is an effective treatment for the patients with intractable epilepsy, however, the diet therapy can sometimes be discontinued by complications. Protein?losing enteropathy is a rarely reported serious complication of the ketogenic diet. We present a 16-month-old Down syndrome baby with protein-losing enteropathy during the ketogenic diet as a treatment for West syndrome. He suffered from diarrhea, general edema and hypoalbuminemia which were not controlled by conservative ca...

  13. Nonfasting Versus Initial Fasting Ketogenic Diet

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-02-01

    Full Text Available A retrospective evaluation of the ketogenic diet (KD was conducted comparing efficacy and tolerability of the diet with or without initial fasting and fluid restriction and involving university centers in Seoul, Korea.

  14. Concurrent Anticonvulsant/Ketogenic Diet Efficacy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-09-01

    Full Text Available Researchers at the Johns Hopkins Hospital, Baltimore, studied retrospectively the comparative efficacy of six most frequently used anticonvulsants when employed in combination with the ketogenic diet (KD for treatment of 115 children with epilepsy.

  15. Ketogenic Diet in Neuromuscular and Neurodegenerative Diseases

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    Damiani, Ernesto; Bosco, Gerardo

    2014-01-01

    An increasing number of data demonstrate the utility of ketogenic diets in a variety of metabolic diseases as obesity, metabolic syndrome, and diabetes. In regard to neurological disorders, ketogenic diet is recognized as an effective treatment for pharmacoresistant epilepsy but emerging data suggests that ketogenic diet could be also useful in amyotrophic lateral sclerosis, Alzheimer, Parkinson's disease, and some mitochondriopathies. Although these diseases have different pathogenesis and features, there are some common mechanisms that could explain the effects of ketogenic diets. These mechanisms are to provide an efficient source of energy for the treatment of certain types of neurodegenerative diseases characterized by focal brain hypometabolism; to decrease the oxidative damage associated with various kinds of metabolic stress; to increase the mitochondrial biogenesis pathways; and to take advantage of the capacity of ketones to bypass the defect in complex I activity implicated in some neurological diseases. These mechanisms will be discussed in this review. PMID:25101284

  16. Ketogenic Diet in Refractory Childhood Epilepsy

    Directory of Open Access Journals (Sweden)

    Amerins Weijenberg MD

    2018-05-01

    Full Text Available Background: Ketogenic diet in children with epilepsy has a considerable impact on daily life and is usually adopted for at least 3 months. Our aim was to evaluate whether the introduction of an all-liquid ketogenic diet in an outpatient setting is feasible, and if an earlier assessment of its efficacy can be achieved. Methods: The authors conducted a prospective, observational study in a consecutive group of children with refractory epilepsy aged 2 to 14 years indicated for ketogenic diet. Ketogenic diet was started as an all-liquid formulation of the classical ketogenic diet, KetoCal 4:1 LQ, taken orally or by tube. After 6 weeks, the liquid diet was converted into solid meals. The primary outcome parameter was time-to-response (>50% seizure reduction. Secondary outcome parameters were time to achieve stable ketosis, the number of children showing a positive response, and the retention rate at 26 weeks. Results: Sixteen children were included. Four of them responded well with respect to seizure frequency, the median time-to-response was 14 days (range 7-28 days. The mean time to achieve stable ketosis was 7 days. The retention rate at 26 weeks was 50%. Of the 8 children who started this protocol orally fed, 6 completed it without requiring a nasogastric tube. Conclusions: Introduction of ketogenic diet with a liquid formulation can be accomplished in orally fed children without major complications. It allowed for fast and stable ketosis.

  17. Ketogenic Diet in Refractory Childhood Epilepsy

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    Weijenberg, Amerins; van Rijn, Margreet; de Koning, Tom J.; Brouwer, Oebele F.

    2018-01-01

    Background: Ketogenic diet in children with epilepsy has a considerable impact on daily life and is usually adopted for at least 3 months. Our aim was to evaluate whether the introduction of an all-liquid ketogenic diet in an outpatient setting is feasible, and if an earlier assessment of its efficacy can be achieved. Methods: The authors conducted a prospective, observational study in a consecutive group of children with refractory epilepsy aged 2 to 14 years indicated for ketogenic diet. Ketogenic diet was started as an all-liquid formulation of the classical ketogenic diet, KetoCal 4:1 LQ, taken orally or by tube. After 6 weeks, the liquid diet was converted into solid meals. The primary outcome parameter was time-to-response (>50% seizure reduction). Secondary outcome parameters were time to achieve stable ketosis, the number of children showing a positive response, and the retention rate at 26 weeks. Results: Sixteen children were included. Four of them responded well with respect to seizure frequency, the median time-to-response was 14 days (range 7-28 days). The mean time to achieve stable ketosis was 7 days. The retention rate at 26 weeks was 50%. Of the 8 children who started this protocol orally fed, 6 completed it without requiring a nasogastric tube. Conclusions: Introduction of ketogenic diet with a liquid formulation can be accomplished in orally fed children without major complications. It allowed for fast and stable ketosis. PMID:29872664

  18. [National consensus on the ketogenic diet].

    Science.gov (United States)

    Armeno, Marisa; Caraballo, Roberto; Vaccarezza, María; Alberti, M Julia; Ríos, Viviana; Galicchio, Santiago; de Grandis, Elizabeth S; Mestre, Graciela; Escobal, Nidia; Matarrese, Pablo; Viollaz, Rocío; Agostinho, Ariela; Díez, Cecilia; Cresta, Araceli; Cabrera, Analía; Blanco, Virginia; Ferrero, Hilario; Gambarini, Victoria; Sosa, Patricia; Bouquet, Cecilia; Caramuta, Luciana; Guisande, Silvina; Gamboni, Beatriz; Hassan, Amal; Pesce, Laura; Argumedo, Laura; Dlugoszewski, Corina; DeMartini, Martha G; Panico, Luis

    2014-09-01

    Epilepsy is a chronic disease with onset in infancy affecting 0.5-1% of the population. One third of the patients is refractory to antiepileptic drugs and they pose a challenge for the health care team. The ketogenic diet is an effective, non-pharmacological, alternative treatment for the management of refractory epilepsy. There is a need to establish guidelines for the adequate and increased use of the ketogenic diet in Spanish-speaking countries. The National Committee on the Ketogenic Diet, consisting of paediatric neurologists, clinical nutritionists, and dietitians, of the Argentine Society of Child Neurology has developed this consensus statement to standardize the use of the ketogenic diet based on the literature and clinical experience. Patient selection, pre-treatment family counseling, drug interactions, micronutrient supplementation, adverse effects, and discontinuation of the diet are discussed. The ketogenic diet is an effective treatment for children with refractory epilepsy. Education and collaboration of the patient and their family is essential. The patient should be managed by an experienced multidisciplinary team using a protocol. The formation of a national multidisciplinary team and the publication of this document provide possibilities for new centers to integrate the ketogenic diet into their treatment options.

  19. The Ketogenic Diet: Making a Comeback.

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    Walczyk, Thomas; Wick, Jeannette Y

    2017-07-01

    Americans have embraced a large number of diets in an attempt to manage obesity, improve quality of life, and address specific health problems. Among diets developed to address health problems, the ketogenic diet has had a long and variable history. Developed in the 1920s by a faith healer to help children with epilepsy, this diet induces a state that mimics carbohydrate starvation. As medications became available and effectively addressed seizures, the diet fell out of favor. During the last few decades, researchers and clinicians have learned that it can be useful in children and adults with refractory epilepsy and a variety of other conditions. Once again, pharmacists may encounter patients who are employing dietary management of serious health problems. This very high-fat diet almost eliminates carbohydrates from the patient's food selection. The result is the substitution of ketone bodies as a source of energy. Today's ketogenic diet has been modified with scientifically proven adjustments to increase palatability and help with adherence. Effective for some forms of epilepsy, the ketogenic diet also seems to have some utility in Alzheimer's disease, Parkinson's disease, and glaucoma, and many Americans are using it to lose weight. Consultant pharmacists may field questions about this diet, its potential to correct or alleviate health conditions, and its limitations. The article discusses the ketogenic diet's strengths, limitations, potential mechanisms, and use in a number of conditions with an emphasis on the elderly.

  20. The Ketogenic Diet Improves Recently Worsened Focal Epilepsy

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    Villeneuve, Nathalie; Pinton, Florence; Bahi-Buisson, Nadia; Dulac, Olivier; Chiron, Catherine; Nabbout, Rima

    2009-01-01

    Aim: We observed a dramatic response to the ketogenic diet in several patients with highly refractory epilepsy whose seizure frequency had recently worsened. This study aimed to identify whether this characteristic was a useful indication for the ketogenic diet. Method: From the 70 patients who received the ketogenic diet during a 3-year period at…

  1. A bioenergetics systems evaluation of ketogenic diet liver effects.

    Science.gov (United States)

    Hutfles, Lewis J; Wilkins, Heather M; Koppel, Scott J; Weidling, Ian W; Selfridge, J Eva; Tan, Eephie; Thyfault, John P; Slawson, Chad; Fenton, Aron W; Zhu, Hao; Swerdlow, Russell H

    2017-09-01

    Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for 1 month on a ketogenic or standard chow diet. Compared with the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered. The pattern of changes observed can be used to inform a broader systems overview of how ketogenic diets affect liver bioenergetics.

  2. Protein-Losing Enteropathy as a Complication of the Ketogenic Diet.

    Science.gov (United States)

    Ahn, Won Kee; Park, Soyoung; Kim, Heung Dong

    2017-07-01

    The ketogenic diet is an effective treatment for the patients with intractable epilepsy, however, the diet therapy can sometimes be discontinued by complications. Protein-losing enteropathy is a rarely reported serious complication of the ketogenic diet. We present a 16-month-old Down syndrome baby with protein-losing enteropathy during the ketogenic diet as a treatment for West syndrome. He suffered from diarrhea, general edema and hypoalbuminemia which were not controlled by conservative care for over 1 month. Esophagogastroduodenoscopy and stool alpha-1 antitrypsin indicated protein-losing enteropathy. Related symptoms were relieved after cessation of the ketogenic diet. Unexplained hypoalbuminemia combined with edema and diarrhea during ketogenic suggests the possibility of protein-losing enteropathy, and proper evaluation is recommended in order to expeditiously detect it and to act accordingly. © Copyright: Yonsei University College of Medicine 2017.

  3. Ketogenic diet: Predictors of seizure control.

    Science.gov (United States)

    Agarwal, Nitin; Arkilo, Dimitrios; Farooq, Osman; Gillogly, Cynthia; Kavak, Katelyn S; Weinstock, Arie

    2017-01-01

    The ketogenic diet is an effective non-pharmacologic treatment for medically resistant epilepsy. The aim of this study was to identify any predictors that may influence the response of ketogenic diet. A retrospective chart review for all patients with medically resistant epilepsy was performed at a tertiary care epilepsy center from 1996 to 2012. Patient- and diet-related variables were evaluated with respect to seizure reduction at 1, 3, 6, 9 and 12-month intervals and divided into four possible outcome classes. Sixty-three patients met inclusion. Thirty-seven (59%) reported >50% seizure reduction at 3 months with 44% and 37% patients benefiting at 6-month and 12-month follow up, respectively. A trend toward significant seizure improvement was noted in 48% patients with seizure onset >1 year at 12-month (p = 0.09) interval and in 62% patients with >10 seizure/day at 6-month interval (p = 0.054). An ordinal logistic regression showed later age of seizure to have higher odds of favorable response at 1-month (p = 0.005) and 3-month (p = 0.013) follow up. Patients with non-fasting diet induction were more likely to have a favorable outcome at 6 months (p = 0.008) as do females (p = 0.037) and those treated with higher fat ratio diet (p = 0.034). Our study reports the effectiveness of ketogenic diet in children with medically resistant epilepsy. Later age of seizure onset, female gender, higher ketogenic diet ratio and non-fasting induction were associated with better odds of improved seizure outcome. A larger cohort is required to confirm these findings.

  4. Ketogenic Diet suppresses Alcohol Withdrawal Syndrome in Rats

    DEFF Research Database (Denmark)

    Dencker, Ditte; Molander, Anna; Thomsen, Morgane

    2018-01-01

    , we investigated the potential therapeutic benefit of a ketogenic diet in managing alcohol withdrawal symptoms during detoxification. METHODS: Male Sprague Dawley rats fed either ketogenic or regular diets were administered ethanol or water orally, twice daily for 6 days while the diet conditions were...... maintained. Abstinence symptoms were rated 6, 24, 48, and 72 hours after the last alcohol administration. RESULTS: Maintenance on a ketogenic diet caused a significant decrease in the alcohol withdrawal symptoms 'rigidity' and 'irritability'. CONCLUSION: Our preclinical pilot study suggests that a ketogenic...... diet may be a novel approach for treating alcohol withdrawal symptoms in humans. This article is protected by copyright. All rights reserved....

  5. The Ketogenic Diet: A Practical Guide for Pediatricians.

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    Luat, Aimee F; Coyle, Leigh; Kamat, Deepak

    2016-12-01

    The ketogenic diet is an effective treatment for drug-resistant epilepsies in children. In addition, it is the first-line treatment for some metabolic disorders, such as glucose transporter 1 deficiency syndrome. This article discusses the proposed mechanisms of a ketogenic diet's antiseizure action, its clinical indications, and its contraindications. The steps involved in ketogenic diet initiation, monitoring, and management of its side effects are also discussed. This review provides general pediatricians with the necessary skills to provide comprehensive care of children using the ketogenic diet and counsel their families and caregivers. [Pediatr Ann. 2016;45(12):e446-e450.]. Copyright 2016, SLACK Incorporated.

  6. Ketogenic Diets for Adults With Highly Refractory Epilepsy

    OpenAIRE

    McDonald, Tanya J. W.; Cervenka, Mackenzie C.

    2017-01-01

    The current review highlights the evidence supporting the use of ketogenic diets in the management of drug-resistant epilepsy and status epilepticus in adults. Ketogenic diet variants are compared and advantages and potential side effects of diet therapy are discussed.

  7. Purines and Neuronal Excitability: Links to the Ketogenic Diet

    Science.gov (United States)

    Masino, SA; Kawamura, M; Ruskin, DN; Geiger, JD; Boison, D

    2011-01-01

    ATP and adenosine are purines that play dual roles in cell metabolism and neuronal signaling. Acting at the A1 receptor (A1R) subtype, adenosine acts directly on neurons to inhibit excitability and is a powerful endogenous neuroprotective and anticonvulsant molecule. Previous research showed an increase in ATP and other cell energy parameters when an animal is administered a ketogenic diet, an established metabolic therapy to reduce epileptic seizures, but the relationship among purines, neuronal excitability and the ketogenic diet was unclear. Recent work in vivo and in vitro tested the specific hypothesis that adenosine acting at A1Rs is a key mechanism underlying the success of ketogenic diet therapy and yielded direct evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet revealed an A1R-dependent metabolic autocrine hyperpolarization of hippocampal neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse models with spontaneous electrographic seizures revealed that intact A1Rs are necessary for the seizure-suppressing effects of the diet. This is the first direct in vivo evidence linking A1Rs to the antiepileptic effects of a ketogenic diet. Other predictions of the relationship between purines and the ketogenic diet are discussed. Taken together, recent research on the role of purines may offer new opportunities for metabolic therapy and insight into its underlying mechanisms. PMID:21880467

  8. Ketogenic Diet for Obesity: Friend or Foe?

    Directory of Open Access Journals (Sweden)

    Antonio Paoli

    2014-02-01

    Full Text Available Obesity is reaching epidemic proportions and is a strong risk factor for a number of cardiovascular and metabolic disorders such as hypertension, type 2 diabetes, dyslipidemia, atherosclerosis, and also certain types of cancers. Despite the constant recommendations of health care organizations regarding the importance of weight control, this goal often fails. Genetic predisposition in combination with inactive lifestyles and high caloric intake leads to excessive weight gain. Even though there may be agreement about the concept that lifestyle changes affecting dietary habits and physical activity are essential to promote weight loss and weight control, the ideal amount and type of exercise and also the ideal diet are still under debate. For many years, nutritional intervention studies have been focused on reducing dietary fat with little positive results over the long-term. One of the most studied strategies in the recent years for weight loss is the ketogenic diet. Many studies have shown that this kind of nutritional approach has a solid physiological and biochemical basis and is able to induce effective weight loss along with improvement in several cardiovascular risk parameters. This review discusses the physiological basis of ketogenic diets and the rationale for their use in obesity, discussing the strengths and the weaknesses of these diets together with cautions that should be used in obese patients.

  9. Ketogenic Diet for Obesity: Friend or Foe?

    Science.gov (United States)

    Paoli, Antonio

    2014-01-01

    Obesity is reaching epidemic proportions and is a strong risk factor for a number of cardiovascular and metabolic disorders such as hypertension, type 2 diabetes, dyslipidemia, atherosclerosis, and also certain types of cancers. Despite the constant recommendations of health care organizations regarding the importance of weight control, this goal often fails. Genetic predisposition in combination with inactive lifestyles and high caloric intake leads to excessive weight gain. Even though there may be agreement about the concept that lifestyle changes affecting dietary habits and physical activity are essential to promote weight loss and weight control, the ideal amount and type of exercise and also the ideal diet are still under debate. For many years, nutritional intervention studies have been focused on reducing dietary fat with little positive results over the long-term. One of the most studied strategies in the recent years for weight loss is the ketogenic diet. Many studies have shown that this kind of nutritional approach has a solid physiological and biochemical basis and is able to induce effective weight loss along with improvement in several cardiovascular risk parameters. This review discusses the physiological basis of ketogenic diets and the rationale for their use in obesity, discussing the strengths and the weaknesses of these diets together with cautions that should be used in obese patients. PMID:24557522

  10. Effects of ketogenic diet on vascular function.

    Science.gov (United States)

    Kapetanakis, M; Liuba, P; Odermarsky, M; Lundgren, J; Hallböök, T

    2014-07-01

    Ketogenic diet is a well-established treatment in children with difficult to treat epilepsy. Very little is known about the long-term effects on vascular atherogenic and biochemical processes of this high-fat and low carbohydrate and protein diet. We evaluated 26 children after one year and 13 children after two years of ketogenic diet. High resolution ultrasound-based assessment was used for carotid artery intima-media thickness (cIMT), carotid artery distensibility and carotid artery compliance. Blood lipids including high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol, (LDL-C), total cholesterol (TC), apolipoprotein A (apoA), apolipoprotein B (apoB) and high-sensitivity C-reactive protein (hsCRP) were analysed. A gradual decrease in carotid distensibility and an increase in LDL-C, apoB and the TC:LDL-C and LDL-C:HDL-C ratios were seen at three and 12 months of KD-treatment. These differences were not significant at 24 months. cIMT, BMI and hsCRP did not show any significant changes. The initial alterations in lipids, apoB and arterial function observed within the first year of KD-treatment appear to be reversible and not significant after 24 months of treatment. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  11. Effects of a ketogenic diet on brain metabolism in epilepsy

    DEFF Research Database (Denmark)

    Korsholm, Kirsten; Law, Ian

    2013-01-01

    For a subpopulation of drug-resistant epilepsies, a ketogenic diet constitutes the treatment of choice. A ketogenic diet is a high-fat, low-protein, and low-carbohydrate diet, which induces ketosis. Despite the use in treatment of epilepsy since 1924, the clinical efficacy was not demonstrated...... in a controlled, randomized trial until 2008, showing its capability of reducing seizure frequency with more than 50%. However, the exact mechanism of this form of treatment is still unknown. We report here a patient with drug-resistant epilepsy on a ketogenic diet, where a brain 18F-FDG PET examination...

  12. New insights into the mechanisms of the ketogenic diet.

    Science.gov (United States)

    Boison, Detlev

    2017-04-01

    High-fat, low-carbohydrate ketogenic diets have been used for almost a century for the treatment of epilepsy. Used traditionally for the treatment of refractory pediatric epilepsies, in recent years the use of ketogenic diets has experienced a revival to include the treatment of adulthood epilepsies as well as conditions ranging from autism to chronic pain and cancer. Despite the ability of ketogenic diet therapy to suppress seizures refractory to antiepileptic drugs and reports of lasting seizure freedom, the underlying mechanisms are poorly understood. This review explores new insights into mechanisms mobilized by ketogenic diet therapies. Ketogenic diets act through a combination of mechanisms, which are linked to the effects of ketones and glucose restriction, and to interactions with receptors, channels, and metabolic enzymes. Decanoic acid, a component of medium-chain triclycerides, contributes to seizure control through direct α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor inhibition, whereas drugs targeting lactate dehydrogenase reduce seizures through inhibition of a metabolic pathway. Ketogenic diet therapy also affects DNA methylation, a novel epigenetic mechanism of the diet. Ketogenic diet therapy combines several beneficial mechanisms that provide broad benefits for the treatment of epilepsy with the potential to not only suppress seizures but also to modify the course of the epilepsy.

  13. An Update on the Ketogenic Diet, 2012

    Directory of Open Access Journals (Sweden)

    Ayelet Halevy

    2012-01-01

    Full Text Available The ketogenic diet has been in use for the last 90 years, and its role in the treatment of epilepsy in the pediatric population has been gaining recognition. It can be helpful in many types of epilepsies, even the more severe ones, and has a beneficial effect on the child’s alertness and cognition, which can be impaired by both the condition and the medications needed for controlling it. Parental compliance is good in spite of the inconveniences inherent in following the diet. The significant advancements in understanding the nature of the diet are in better defining when its use is contraindicated and in validating its application in severe epilepsies in infancy, such as infantile spasms. Although most neurologists do not consider it as being the preferred first-line therapy, it is often a reasonable option when two medications have already failed.

  14. Ketogenic diets and physical performance

    Directory of Open Access Journals (Sweden)

    Phinney SD

    2004-08-01

    Full Text Available Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15-25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis.

  15. Ketogenic diets and physical performance

    Directory of Open Access Journals (Sweden)

    Phinney Stephen D

    2004-08-01

    Full Text Available Abstract Impaired physical performance is a common but not obligate result of a low carbohydrate diet. Lessons from traditional Inuit culture indicate that time for adaptation, optimized sodium and potassium nutriture, and constraint of protein to 15–25 % of daily energy expenditure allow unimpaired endurance performance despite nutritional ketosis.

  16. Rationale, Feasibility and Acceptability of Ketogenic Diet for Cancer Treatment.

    Science.gov (United States)

    Chung, Hae-Yun; Park, Yoo Kyoung

    2017-09-01

    Ketogenic diet has been used for more than 80 years as a successful dietary regimen for epilepsy. Recently, dietary modulation by carbohydrate depletion via ketogenic diet has been suggested as an important therapeutic strategy to selectively kill cancer cells and as adjuvant therapy for cancer treatment. However, some researchers insist ketogenic diet to be highly undesirable as ketogenic diet may trigger and/or exacerbate cachexia development and usually result in significant weight loss. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possibility of the use of ketogenic diet for oncology patients. Article search was performed from 1985 through 2017 and finally 10 articles were analyzed. The review focused on the results of human trials for cancer patients and checked the feasibility of using ketogenic diet for cancer patients as adjuvant therapy. The main outcomes showed improvement of body weight changes, anthropometric changes, serum blood profiles, and reduction in novel marker for tumor progression, TKTL1, and increase of ketone body. Lactate concentration was reduced, and no significant changes were reported in the measurements of quality of life. Ketogenic diet may be efficacious in certain cancer subtypes whose outcomes appear to correlate with metabolic status, but the results are not yet supportive and inconsistent. Therefore, it warrants further studies.

  17. Ketogenic diet and astrocyte/neuron metabolic interactions

    OpenAIRE

    Vamecq Joseph; Maurois Pierre; Bac Pierre; Delplanque Bernadette; Pages Nicole

    2007-01-01

    The ketogenic diet is an anticonvulsant diet enriched in fat. It provides the body with a minimal protein requirement and a restricted carbohydrate supply, the vast majority of calories (more than 80-90%) being given by fat. Though anticonvulsant activity of ketogenic diet has been well documented by a large number of experimental and clinical studies, underlying mechanisms still remain partially unclear. Astrocyte-neuron interactions, among which metabolic shuttles, may influence synaptic ac...

  18. Ketogenic diet in endocrine disorders: Current perspectives

    Science.gov (United States)

    Gupta, L; Khandelwal, D; Kalra, S; Gupta, P; Dutta, D; Aggarwal, S

    2017-01-01

    Ketogenic diet (KD) is a high-fat, adequate-protein, and low-carbohydrate diet that leads to nutritional ketosis, long known for antiepileptic effects and has been used therapeutically to treat refractory epilepsy. This review attempts to summarize the evidence and clinical application of KD in diabetes, obesity, and other endocrine disorders. KD is usually animal protein based. An empiric vegetarian Indian variant of KD has been provided keeping in mind the Indian food habits. KD has beneficial effects on cardiac ischemic preconditioning, improves oxygenation in patients with respiratory failure, improves glycemic control in diabetics, is associated with significant weight loss, and has a beneficial impact on polycystic ovarian syndrome. Multivitamin supplementations are recommended with KD. Recently, ketones are being proposed as super-metabolic fuel; and KD is currently regarded as apt dietary therapy for “diabesity.” PMID:29022562

  19. Ketogenic diet in endocrine disorders: Current perspectives

    Directory of Open Access Journals (Sweden)

    L Gupta

    2017-01-01

    Full Text Available Ketogenic diet (KD is a high-fat, adequate-protein, and low-carbohydrate diet that leads to nutritional ketosis, long known for antiepileptic effects and has been used therapeutically to treat refractory epilepsy. This review attempts to summarize the evidence and clinical application of KD in diabetes, obesity, and other endocrine disorders. KD is usually animal protein based. An empiric vegetarian Indian variant of KD has been provided keeping in mind the Indian food habits. KD has beneficial effects on cardiac ischemic preconditioning, improves oxygenation in patients with respiratory failure, improves glycemic control in diabetics, is associated with significant weight loss, and has a beneficial impact on polycystic ovarian syndrome. Multivitamin supplementations are recommended with KD. Recently, ketones are being proposed as super-metabolic fuel; and KD is currently regarded as apt dietary therapy for “diabesity.”

  20. Severe Hypertriglyceridemia in Glut1D on Ketogenic Diet.

    Science.gov (United States)

    Klepper, Joerg; Leiendecker, Baerbel; Heussinger, Nicole; Lausch, Ekkehart; Bosch, Friedrich

    2016-04-01

    High-fat ketogenic diets are the only treatment available for Glut1 deficiency (Glut1D). Here, we describe an 8-year-old girl with classical Glut1D responsive to a 3:1 ketogenic diet and ethosuximide. After 3 years on the diet a gradual increase of blood lipids was followed by rapid, severe asymptomatic hypertriglyceridemia (1,910 mg/dL). Serum lipid apheresis was required to determine liver, renal, and pancreatic function. A combination of medium chain triglyceride-oil and a reduction of the ketogenic diet to 1:1 ratio normalized triglyceride levels within days but triggered severe myoclonic seizures requiring comedication with sultiam. Severe hypertriglyceridemia in children with Glut1D on ketogenic diets may be underdiagnosed and harmful. In contrast to congenital hypertriglyceridemias, children with Glut1D may be treated effectively by dietary adjustments alone. Georg Thieme Verlag KG Stuttgart · New York.

  1. Neurobiochemical mechanisms of a ketogenic diet in refractory epilepsy

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    Patricia Azevedo de Lima

    2014-12-01

    Full Text Available A ketogenic diet is an important therapy used in the control of drug-refractory seizures. Many studies have shown that children and adolescents following ketogenic diets exhibit an over 50% reduction in seizure frequency, which is considered to be clinically relevant. These benefits are based on a diet containing high fat (approximately 90% fat for 24 months. This dietary model was proposed in the 1920s and has produced variable clinical responses. Previous studies have shown that the mechanisms underlying seizure control involve ketone bodies, which are produced by fatty acid oxidation. Although the pathways involved in the ketogenic diet are not entirely clear, the main effects of the production of ketone bodies appear to be neurotransmitter modulation and antioxidant effects on the brain. This review highlights the impacts of the ketogenic diet on the modulation of neurotransmitters, levels of biogenic monoamines and protective antioxidant mechanisms of neurons. In addition, future perspectives are proposed.

  2. Epilepsy characteristics and psychosocial factors associated with ketogenic diet success.

    Science.gov (United States)

    McNamara, Nancy A; Carbone, Loretta A; Shellhaas, Renée A

    2013-10-01

    The ketogenic diet is an effective therapy for childhood epilepsy, but its important impacts on families could affect successful treatment. We assessed medical and psychosocial factors associated with successful ketogenic diet treatment. A total of 23 families of patients treated with ketogenic diet completed questionnaires (30% response), including inquiries about challenges to successful dietary treatments and validated family functioning scales. Of these, 14 were considered successful (diet discontinued once the child was seizure-free or continued as clinically indicated). Family-identified challenges were food preparation time (n = 11) and that the diet was too restrictive (n = 9). Neither Medicaid insurance nor family functioning scale scores were significantly associated with successful treatment. Lower seizure frequency prior to ketogenic diet initiation (P = .02) and postdiet seizure improvement (P = .01) were associated with increased odds of success. Effective ketogenic diet treatment is dictated both by psychosocial and epilepsy-related influences. A focus on understanding the psychosocial issues may help to improve families' experiences and success with the ketogenic diet.

  3. Mitochondrial Profiles and the Anticonvulsant Effect of the Ketogenic Diet

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    J Gordon Millichap

    2006-09-01

    Full Text Available A study of the anticonvulsant effect of the ketogenic diet (KD in adolescent rats, at Emory University and other centers, found that the hippocampus responds by inducing mitochondrial biogenesis, enhancing metabolic gene expression, and increasing energy reserves.

  4. Levels of Antiepileptic Drugs and the Ketogenic Diet

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    J Gordon Millichap

    2006-08-01

    Full Text Available Introduction of the ketogenic diet did not change the plasma levels of antiepileptic drugs in an open study of 51 children (mean age 6.6 years with refractory epilepsy studied at Karolinska University Hospital, Stockholm, Sweden.

  5. Ketogenic Diet in Super-Refractory Status Epilepticus

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    Smith, Garnett; Press, Craig A.

    2017-01-01

    Researchers from the Children’s National Health System in Washington, D.C. studied the feasibility, rate of complications, and effect on seizures of initiating the Ketogenic Diet (KD) in pediatric patients with Super-Refractory Status Epilepticus (SRSE).

  6. Seizure tests distinguish intermittent fasting from the ketogenic diet

    Science.gov (United States)

    Hartman, Adam L.; Zheng, Xiangrong; Bergbower, Emily; Kennedy, Michiko; Hardwick, J. Marie

    2010-01-01

    Summary Purpose Calorie restriction can be anticonvulsant in animal models. The ketogenic diet was designed to mimic calorie restriction and has been assumed to work by the same mechanisms. We challenged this assumption by profiling the effects of these dietary regimens in mice subjected to a battery of acute seizure tests. Methods Juvenile male NIH Swiss mice received ketogenic diet or a normal diet fed in restricted quantities (continuously or intermittently) for ~ 12 days, starting at 3–4 weeks of age. Seizures were induced by the 6 Hz test, kainic acid, maximal electroshock, or pentylenetetrazol. Results The ketogenic and calorie-restricted diets often had opposite effects depending on the seizure test. The ketogenic diet protected from 6 Hz–induced seizures, whereas calorie restriction (daily and intermittent) increased seizure activity. Conversely, calorie restriction protected juvenile mice against seizures induced by kainic acid, whereas the ketogenic diet failed to protect. Intermittent caloric restriction worsened seizures induced by maximal electroshock but had no effect on those induced by pentylenetetrazol. Discussion In contrast to a longstanding hypothesis, calorie restriction and the ketogenic diet differ in their acute seizure test profiles, suggesting that they have different underlying anticonvulsant mechanisms. These findings highlight the importance of the 6 Hz test and its ability to reflect the benefits of ketosis and fat consumption. PMID:20477852

  7. Seizure tests distinguish intermittent fasting from the ketogenic diet.

    Science.gov (United States)

    Hartman, Adam L; Zheng, Xiangrong; Bergbower, Emily; Kennedy, Michiko; Hardwick, J Marie

    2010-08-01

    Calorie restriction can be anticonvulsant in animal models. The ketogenic diet was designed to mimic calorie restriction and has been assumed to work by the same mechanisms. We challenged this assumption by profiling the effects of these dietary regimens in mice subjected to a battery of acute seizure tests. Juvenile male NIH Swiss mice received ketogenic diet or a normal diet fed in restricted quantities (continuously or intermittently) for ∼12 days, starting at 3-4 weeks of age. Seizures were induced by the 6 Hz test, kainic acid, maximal electroshock, or pentylenetetrazol. The ketogenic and calorie-restricted diets often had opposite effects depending on the seizure test. The ketogenic diet protected from 6 Hz-induced seizures, whereas calorie restriction (daily and intermittent) increased seizure activity. Conversely, calorie restriction protected juvenile mice against seizures induced by kainic acid, whereas the ketogenic diet failed to protect. Intermittent caloric restriction worsened seizures induced by maximal electroshock but had no effect on those induced by pentylenetetrazol. In contrast to a longstanding hypothesis, calorie restriction and the ketogenic diet differ in their acute seizure test profiles, suggesting that they have different underlying anticonvulsant mechanisms. These findings highlight the importance of the 6 Hz test and its ability to reflect the benefits of ketosis and fat consumption. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

  8. Ketogenic diets, mitochondria, and neurological diseases

    Science.gov (United States)

    Gano, Lindsey B.; Patel, Manisha; Rho, Jong M.

    2014-01-01

    The ketogenic diet (KD) is a broad-spectrum therapy for medically intractable epilepsy and is receiving growing attention as a potential treatment for neurological disorders arising in part from bioenergetic dysregulation. The high-fat/low-carbohydrate “classic KD”, as well as dietary variations such as the medium-chain triglyceride diet, the modified Atkins diet, the low-glycemic index treatment, and caloric restriction, enhance cellular metabolic and mitochondrial function. Hence, the broad neuroprotective properties of such therapies may stem from improved cellular metabolism. Data from clinical and preclinical studies indicate that these diets restrict glycolysis and increase fatty acid oxidation, actions which result in ketosis, replenishment of the TCA cycle (i.e., anaplerosis), restoration of neurotransmitter and ion channel function, and enhanced mitochondrial respiration. Further, there is mounting evidence that the KD and its variants can impact key signaling pathways that evolved to sense the energetic state of the cell, and that help maintain cellular homeostasis. These pathways, which include PPARs, AMP-activated kinase, mammalian target of rapamycin, and the sirtuins, have all been recently implicated in the neuroprotective effects of the KD. Further research in this area may lead to future therapeutic strategies aimed at mimicking the pleiotropic neuroprotective effects of the KD. PMID:24847102

  9. Renal stone associated with the ketogenic diet in a 5-year old girl with intractable epilepsy.

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    Choi, Ji Na; Song, Ji Eun; Shin, Jae Il; Kim, Heung Dong; Kim, Myung Joon; Lee, Jae Seung

    2010-05-01

    In this paper, we report on a 5-year-old girl who developed a renal stone while following the ketogenic diet to treat refractory seizure disorder. Three months after initiating the ketogenic diet, she developed severe abdominal pain and vomiting. The spot urine calcium-to-creatinine (Ca/Cr) ratio and 24-hour urine evaluation showed hypercalciuria. Computed tomography (CT) imaging revealed a stone in the right ureteropelvic junction, resulting in hydronephrosis of the right kidney. The renal stone disappeared 5 days after conservative treatment; the patient's microscopic hematuria resolved concurrently. In light of this case report, we recommend regularly monitoring the urine Ca/Cr ratio with ultrasonography for further development of renal stones in patients following the ketogenic diet. If these patients exhibit evidence of symptomatic hypercalciuria or cyristalluria, liberalization of fluid restriction and urine alkalization using oral potassium citrate should be considered.

  10. Ketogenic diet in adolescents and adults with epilepsy.

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    Nei, Maromi; Ngo, Ly; Sirven, Joseph I; Sperling, Michael R

    2014-06-01

    The ketogenic diet is an alternative treatment for patients with refractory epilepsy. Most studies to date report dietary response in children. There are limited data evaluating the efficacy of the ketogenic diet in adults. This is a report of the long-term outcome in a largely adult population of patients treated with the ketogenic diet for epilepsy. Twenty-nine adult and adolescent patients (mean age 32 years, range 11-51) were initiated on the ketogenic diet and followed until diet discontinuation. Clinical response and adverse effects were noted during the duration of the diet. Fifty-two percent of patients had a significant reduction in seizure frequency on the ketogenic diet, including 45% with ≥50% reduction in seizure frequency. Thirty-one percent had no improvement, seven percent were unable to successfully initiate the diet, and 10% had a >50% increase in seizure frequency. The diet was continued for a mean of 9 months (range 0.13-35 months), with five patients completing ≥23 months. There was a trend toward better response and better tolerability/longer duration in patients with symptomatic generalized epilepsy. The diet was generally well-tolerated, but undesired weight loss and constipation were the most frequent adverse effects. The ketogenic diet can be used safely in the adult and adolescent population, with a response rate similar to those seen in children. Patient with symptomatic generalized epilepsy may be particularly good candidates for this type of dietary treatment. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  11. Benefits of the nonfasting ketogenic diet compared with the initial fasting ketogenic diet.

    Science.gov (United States)

    Kim, Dong Wook; Kang, Hoon Chul; Park, Jung Chae; Kim, Heung Dong

    2004-12-01

    The ketogenic diet (KD) is traditionally introduced with an initial period of fasting and fluid restriction that is difficult and sometimes complicated by moderate dehydration. This investigation compares the efficacy and tolerability of the nonfasting ketogenic diet (NFKD) and the conventional initial-fasting ketogenic diet (IFKD). Forty-one children with intractable epilepsy were treated with the NFKD, beginning with a gradual increase in calories with no initial fasting or fluid restriction. This NFKD population was compared retrospectively with 83 recent historical control subjects who were treated with the IFKD. Efficacy, tolerability, time until strong ketosis, and occurrence of complications were compared. Fourteen (34.1%) patients became seizure-free for at least 3 months after the NFKD, compared with 29 (34.9%) after the IFKD. There was no significant difference in days until strong urinary ketosis between the 2 groups. The incidence of hypoglycemia was also not significantly different between the groups as most other laboratory findings, although the blood urea nitrogen was elevated in 24.1% of the IFKD group and in only 12.2% of the NFKD patients without statistical significance. Conversely, moderate dehydration was significantly less frequent in the NFKD group (12.2%) than in the IFKD group (62.7%). Finally, these results were reflected to the shortening of the hospitalization period in the NFKD group. These observations suggest that initial fasting and fluid restriction are not essential for the KD and that the tolerability of this treatment may be improved. These data support our intention to conduct a formal, prospective, randomized trial comparing 2 forms of the KD.

  12. Reversal of diabetic nephropathy by a ketogenic diet.

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    Michal M Poplawski

    Full Text Available Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita and Type 2 (db/db diabetes, diabetic nephropathy (as indicated by albuminuria was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined.

  13. Reversal of Diabetic Nephropathy by a Ketogenic Diet

    Science.gov (United States)

    Poplawski, Michal M.; Mastaitis, Jason W.; Isoda, Fumiko; Grosjean, Fabrizio; Zheng, Feng; Mobbs, Charles V.

    2011-01-01

    Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB) reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita) and Type 2 (db/db) diabetes, diabetic nephropathy (as indicated by albuminuria) was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined. PMID:21533091

  14. Valproate effect on ketosis in children under ketogenic diet.

    Science.gov (United States)

    Spilioti, Martha; Pavlou, Evangelos; Gogou, Maria; Katsanika, Irene; Papadopoulou-Alataki, Efimia; Grafakou, Olga; Gkampeta, Anastasia; Dinopoulos, Argyrios; Evangeliou, Athanasios

    2016-07-01

    Although ketogenic diet has been proven useful in the management of intractable seizures, interactions with other medicines have been reported. This study reports two patients on co-administration with ketogenic diet and valproate appearing undesirable side effects after increase or decrease of valproate pharmaceutical levels. Totally 75 patients suffering from drug-resistant epilepsy were treated with ketogenic diet in our departments. Their age varied from 6 months to 9 years. All patients were followed for at least 12 months and up to five years. Clinical and laboratory variables have been regularly assessed. In 75 patients treated with ketogenic diet and valproate at the same time treatment was well tolerated. Two patients presented mild to moderate undesirable effects. In these patients the removal of valproate treatment resulted in an increase of ketosis with respective clinical signs. The conversion of the diet from 4:1 to 1:1 and 2,5:1 respectively resulted in reduction of ketosis and clinical improvement. In the majority of cases co-administration of valproate and ketogenic diet seems to be safe. In two cases, valproate appeared to have a negative effect on ketosis (and weaning it led to over-ketosis). This interaction is worthy of future study. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  15. Ketogenic diet and astrocyte/neuron metabolic interactions

    Directory of Open Access Journals (Sweden)

    Vamecq Joseph

    2007-05-01

    Full Text Available The ketogenic diet is an anticonvulsant diet enriched in fat. It provides the body with a minimal protein requirement and a restricted carbohydrate supply, the vast majority of calories (more than 80-90% being given by fat. Though anticonvulsant activity of ketogenic diet has been well documented by a large number of experimental and clinical studies, underlying mechanisms still remain partially unclear. Astrocyte-neuron interactions, among which metabolic shuttles, may influence synaptic activity and hence anticonvulsant protection. The astrocyte-neuron metabolic shuttles may be themselves influenced by the availability in energetic substrates such as hydrates of carbon and fats. Historically, ketogenic diet had been designed to mimic changes such as ketosis occurring upon starvation, a physiological state already known to exhibit anticonvulsant protection and sometimes referred to as “water diet”. For this reason, a special attention should be paid to metabolic features shared in common by ketogenic diet and starvation and especially those features that might result in anticonvulsant protection. Compared to feeding by usual mixed diet, starvation and ketogenic diet are both characterised by increased fat, lowered glucose and aminoacid supplies to cells. The resulting impact of these changes in energetic substrates on astrocyte/neuron metabolic shuttles might have anticonvulsant and/or neuroprotective properties. This is the aim of this communication to review some important astrocyte/neuron metabolic interactions (astrocyte/neuron lactate shuttle, glutamateinduced astrocytic glycolysis activation, glutamate/glutamine cycle along with the neurovascular coupling and the extent to which the way of their alteration by starvation and/or ketogenic diet might result in seizure and/or brain protection.

  16. A ketogenic diet reduces metabolic syndrome-induced allodynia and promotes peripheral nerve growth in mice.

    Science.gov (United States)

    Cooper, Michael A; Menta, Blaise W; Perez-Sanchez, Consuelo; Jack, Megan M; Khan, Zair W; Ryals, Janelle M; Winter, Michelle; Wright, Douglas E

    2018-08-01

    Current experiments investigated whether a ketogenic diet impacts neuropathy associated with obesity and prediabetes. Mice challenged with a ketogenic diet were compared to mice fed a high-fat diet or a high-fat diet plus exercise. Additionally, an intervention switching to a ketogenic diet following 8 weeks of high-fat diet was performed to compare how a control diet, exercise, or a ketogenic diet affects metabolic syndrome-induced neural complications. When challenged with a ketogenic diet, mice had reduced bodyweight and fat mass compared to high-fat-fed mice, and were similar to exercised, high-fat-fed mice. High-fat-fed, exercised and ketogenic-fed mice had mildly elevated blood glucose; conversely, ketogenic diet-fed mice were unique in having reduced serum insulin levels. Ketogenic diet-fed mice never developed mechanical allodynia contrary to mice fed a high-fat diet. Ketogenic diet fed mice also had increased epidermal axon density compared all other groups. When a ketogenic diet was used as an intervention, a ketogenic diet was unable to reverse high-fat fed-induced metabolic changes but was able to significantly reverse a high-fat diet-induced mechanical allodynia. As an intervention, a ketogenic diet also increased epidermal axon density. In vitro studies revealed increased neurite outgrowth in sensory neurons from mice fed a ketogenic diet and in neurons from normal diet-fed mice given ketone bodies in the culture medium. These results suggest a ketogenic diet can prevent certain complications of prediabetes and provides significant benefits to peripheral axons and sensory dysfunction. Published by Elsevier Inc.

  17. Management of symptomatic cholelithiasis while on ketogenic diet: a case report.

    Science.gov (United States)

    Desai, Amita A; Thompson, Lindsey M; Abdelmoity, Ahmed T; Kayyali, Husam; St Peter, Shawn D

    2014-09-01

    The ketogenic diet is a treatment modality used for patients with refractory epilepsy. Development of cholelithiasis while on the ketogenic diet is a potential side effect that has been described in the literature. There however have not been any reports on the outcomes of continuing the diet after cholecystectomy. We present a 5-year-old boy with history of pharmacologically intractable epilepsy that was well controlled on the ketogenic diet. He underwent laparoscopic cholecystectomy for the development of symptomatic cholelithiasis 12 months after the initiation of ketogenic diet for seizure control. Patient tolerated the surgery well and was able to continue the ketogenic diet postoperatively. There have been no reports describing the continuation of ketogenic diet after cholecystectomy. This child demonstrates the safety of the procedure and the ability to continue the ketogenic diet without further biliary or surgical complications. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. ERGO: a pilot study of ketogenic diet in recurrent glioblastoma.

    Science.gov (United States)

    Rieger, Johannes; Bähr, Oliver; Maurer, Gabriele D; Hattingen, Elke; Franz, Kea; Brucker, Daniel; Walenta, Stefan; Kämmerer, Ulrike; Coy, Johannes F; Weller, Michael; Steinbach, Joachim P

    2014-06-01

    Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3-13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12-124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (pketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet.

  19. ERGO: A pilot study of ketogenic diet in recurrent glioblastoma

    Science.gov (United States)

    RIEGER, JOHANNES; BÄHR, OLIVER; MAURER, GABRIELE D.; HATTINGEN, ELKE; FRANZ, KEA; BRUCKER, DANIEL; WALENTA, STEFAN; KÄMMERER, ULRIKE; COY, JOHANNES F.; WELLER, MICHAEL; STEINBACH, JOACHIM P.

    2014-01-01

    Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3–13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12–124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (pketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet. PMID:24728273

  20. Ketosis, ketogenic diet and food intake control: a complex relationship.

    Science.gov (United States)

    Paoli, Antonio; Bosco, Gerardo; Camporesi, Enrico M; Mangar, Devanand

    2015-01-01

    Though the hunger-reduction phenomenon reported during ketogenic diets is well-known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK) release while reducing orexigenic signals e.g., via ghrelin. However, ketone bodies (KB) seem to be able to increase food intake through AMP-activated protein kinase (AMPK) phosphorylation, gamma-aminobutyric acid (GABA) and the release and production of adiponectin. The aim of this review is to provide a summary of our current knowledge of the effects of ketogenic diet (KD) on food control in an effort to unify the apparently contradictory data into a coherent picture.

  1. The ketogenic diet: metabolic influences on brain excitability and epilepsy

    Science.gov (United States)

    Lutas, Andrew; Yellen, Gary

    2012-01-01

    A dietary therapy for pediatric epilepsy known as the ketogenic diet has seen a revival in its clinical use in the past decade. Though the diet’s underlying mechanism remains unknown, modern scientific approaches like genetic disruption of glucose metabolism are allowing for more detailed questions to be addressed. Recent work indicates that several mechanisms may exist for the ketogenic diet including disruption of glutamatergic synaptic transmission, inhibition of glycolysis, and activation of ATP-sensitive potassium channels. Here we describe on-going work in these areas that is providing a better understanding of metabolic influences on brain excitability and epilepsy. PMID:23228828

  2. Ketogenic Diet Provides Neuroprotective Effects against Ischemic Stroke Neuronal Damages

    Directory of Open Access Journals (Sweden)

    Sheida Shaafi

    2014-12-01

    Full Text Available Ischemic stroke is a leading cause of death and disability in the world. Many mechanisms contribute in cell death in ischemic stroke. Ketogenic diet which has been successfully used in the drug-resistant epilepsy has been shown to be effective in many other neurologic disorders. The mechanisms underlying of its effects are not well studied, but it seems that its neuroprotective ability is mediated at least through alleviation of excitotoxicity, oxidative stress and apoptosis events. On the basis of these mechanisms, it is postulated that ketogenic diet could provide benefits to treatment of cerebral ischemic injuries.

  3. Modified Atkins diet vs classic ketogenic formula in intractable epilepsy.

    Science.gov (United States)

    El-Rashidy, O F; Nassar, M F; Abdel-Hamid, I A; Shatla, R H; Abdel-Hamid, M H; Gabr, S S; Mohamed, S G; El-Sayed, W S; Shaaban, S Y

    2013-12-01

    The study was designed to evaluate the efficacy, safety, and tolerability of the ketogenic diet (KD) whether classic 4:1 formula or the modified Atkins diet (MAD) in intractable childhood epilepsy. Anthropometric measurements and serum lipid profile were measured upon enrollment and after 3 and 6 months in 40 patients with symptomatic intractable epilepsy. Fifteen were given MAD diet, ten were kept on classic 4:1 ketogenic liquid formula, and the rest were allowed to eat as desired. The liquid ketogenic formula group showed significantly higher body mass index compared with those who did not receive KD after 6 months. The lipid profile of KD patients was within normal limits for age and sex during the study period. The rate of change of frequency and severity of seizures showed best improvement in ketogenic liquid formula patients followed by the MAD group than the patients on anti-epileptic medications alone. The KD whether classic 4:1 or MAD is a tolerable, safe, and effective adjuvant therapy for intractable symptomatic childhood epilepsy with limited adverse effects on the growth parameters and accepted changes in the lipid profile. The liquid ketogenic formula patients showed better growth pattern and significantly more seizure control. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Ketogenic diet using a Japanese ketogenic milk for patients with epilepsy: A multi-institutional study.

    Science.gov (United States)

    Kumada, Tomohiro; Imai, Katsumi; Takahashi, Yukitoshi; Nabatame, Shin; Oguni, Hirokazu

    2018-03-01

    In Japan, Meiji 817-B (M817-B), a powdered ketogenic milk, has been available since the ketogenic diet was introduced to infants and tube-fed children with medication-resistant epilepsy in the 1980s. We retrospectively evaluated the efficacy, tolerability, and side effects of the ketogenic diet using M817-B as the main source of daily food intake for patients with epilepsy by sending questionnaires to the members of a subcommittee of the Japan Epilepsy Society that focuses on the proper use of M817-B. A total of 42 patients were enrolled. Age at the initiation of the diet therapy ranged from 3 to 244 months (median, 32.5 months). Thirty-four patients were fed via tube, and the remaining 8 were fed orally. About 93% of patients were able to continue the diet for 1 month, 74% for 3 months, and 64% for 6 months. The median period of continuation was 16 months. One patient was able to continue as long as 7 years. The ketogenic ratio was maintained at about 3.0. The seizure-free rate and responder (>50% seizure reduction) rate were about 10% and 30-40%, respectively during the 12 months on the diet. Mean serum beta-hydroxybutyrate increased to almost 4 mM at 1 month and was maintained during the diet period. Side effects, which required discontinuation of the diet therapy, occurred in 11 of 42 patients and included hypertonia, weight loss, vomiting, hypoglycemia, metabolic acidosis, and hypokalemia. M817-B could be used long-term with demonstrated efficacy in seizure reduction, although there are some side effects that may require cessation of the diet therapy. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  5. Ketogenic Diet Therapy in Infants: Efficacy and Tolerability.

    Science.gov (United States)

    Wirrell, Elaine; Eckert, Susan; Wong-Kisiel, Lily; Payne, Eric; Nickels, Katherine

    2018-05-01

    This study evaluated tolerability and efficacy of the ketogenic diet in infants less than 12 months of age. Infants less than 12 months of age, commencing the ketogenic diet between September 2007 and July 2016 were identified. Records were reviewed for epilepsy details, diet initiation details, efficacy and tolerability. Twenty-seven infants commenced the ketogenic diet (56% male, median age seven months). Median age at seizure onset was 1.9 months and 92% had daily seizures. An epilepsy syndrome was noted in 19 (West-11, epilepsy in infancy with migrating focal seizures-5, early myoclonic encephalopathy-1, Ohtahara-1, Dravet-1). Infants were on a median of two and had failed a median of one medications for lack of efficacy. All initiated a traditional ketogenic diet at full calories without fasting, and all but one started the diet in hospital. Significant hypoglycemia during initiation was seen in two - both had emesis +/- decreased oral intake. Eighty-eight percent developed urinary ketosis by 48 hours and all were successfully discharged on the diet (median ratio 3:1). Of those continuing dietary therapy, responder rates at one, six and 12 months were 68%, 82% and 91%, with 20%, 29% and 27% achieving seizure freedom. By 12 months, two stopped the diet for serious adverse effects, five discontinued for lack of efficacy, six were lost to follow-up and two died of unrelated causes. The ketogenic diet is an effective and well-tolerated treatment for infants with intractable epilepsy. In-hospital initiation is strongly recommended due to risk of hypoglycemia with emesis or reduced intake. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Ketogenic diet alters dopaminergic activity in the mouse cortex.

    Science.gov (United States)

    Church, William H; Adams, Ryan E; Wyss, Livia S

    2014-06-13

    The present study was conducted to determine if the ketogenic diet altered basal levels of monoamine neurotransmitters in mice. The catecholamines dopamine (DA) and norephinephrine (NE) and the indolamine serotonin (5HT) were quantified postmortem in six different brain regions of adult mice fed a ketogenic diet for 3 weeks. The dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindole acetic acid (5HIAA) were also measured. Tissue punches were collected bilaterally from the motor cortex, somatosensory cortex, nucleus accumbens, anterior caudate-putamen, posterior caudate-putamen and the midbrain. Dopaminergic activity, as measured by the dopamine metabolites to dopamine content ratio - ([DOPAC]+[HVA])/[DA] - was significantly increased in the motor and somatosensory cortex regions of mice fed the ketogenic diet when compared to those same areas in brains of mice fed a normal diet. These results indicate that the ketogenic diet alters the activity of the meso-cortical dopaminergic system, which may contribute to the diet's therapeutic effect in reducing epileptic seizure activity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Hepatic Dysfunction as a Complication of Combined Valproate and Ketogenic Diet.

    Science.gov (United States)

    Stevens, Clare E; Turner, Zahava; Kossoff, Eric H

    2016-01-01

    The ketogenic diet has long been shown to be an effective therapy for children with medication-refractory seizures. Most complications of the ketogenic diet include short-lived gastrointestinal disturbances, acidosis, and dyslipidemia. Hepatic dysfunction and pancreatitis are among the less common but more serious complications of the ketogenic diet. Many patients on the ketogenic diet receive adjunct treatment with an anticonvulsant drug, and valproate is frequently used. We describe a child who developed hepatic dysfunction in association with the combined use of valproate and the ketogenic diet. After stopping the valproate and then restarting the ketogenic diet, her liver enzymes normalized, and she was able to achieve markedly improved seizure control and quality of life. Although caution should be advised when using both treatments simultaneously, the development of hepatic dysfunction should not preclude continuation of the ketogenic diet, as the hepatotoxic effects may be completely reversed once the valproate is stopped. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Ketogenic Diet Suppresses Alcohol Withdrawal Syndrome in Rats.

    Science.gov (United States)

    Dencker, Ditte; Molander, Anna; Thomsen, Morgane; Schlumberger, Chantal; Wortwein, Gitta; Weikop, Pia; Benveniste, Helene; Volkow, Nora D; Fink-Jensen, Anders

    2018-02-01

    Alcohol use disorder is underdiagnosed and undertreated, and up to 50% of alcohol-abstinent patients diagnosed with alcohol dependence relapse within the first year of treatment. Current treatments for the maintenance of alcohol abstinence in patients with alcohol use disorder have limited efficacy, and there is an urgent need for novel treatment strategies. Decreased cerebral glucose metabolism and increased brain uptake of acetate were recently reported in heavy drinkers, relative to controls. Given the switch of metabolic fuel from glucose to acetate in the alcohol-dependent brain, we investigated the potential therapeutic benefit of a ketogenic diet in managing alcohol withdrawal symptoms during detoxification. Male Sprague Dawley rats fed either ketogenic or regular diet were administered ethanol or water orally, twice daily for 6 days while the diet conditions were maintained. Abstinence symptoms were rated 6, 24, 48, and 72 hours after the last alcohol administration. Maintenance on a ketogenic diet caused a significant decrease in the alcohol withdrawal symptoms' "rigidity" and "irritability." Our preclinical pilot study suggests that a ketogenic diet may be a novel approach for treating alcohol withdrawal symptoms in humans. Copyright © 2017 by the Research Society on Alcoholism.

  9. The ketogenic diet and other dietary treatments for refractory epilepsy in children

    Directory of Open Access Journals (Sweden)

    Suvasini Sharma

    2014-01-01

    Full Text Available The ketogenic diet is a high-fat, low-carbohydrate, and restricted protein diet that is useful in patients with refractory epilepsy. The efficacy of the ketogenic diet is better than most of the new antiepileptic drugs. Other modifications of the diet are also beneficial, such as the modified Atkins diet and the low glycemic index treatment. There is a lack of awareness of the ketogenic diet as a treatment modality for epilepsy amongst pediatricians and neurologists. In this review, the use of the ketogenic diet and other dietary treatments in refractory epilepsy is discussed. The Indian experience with the use of these dietary treatments is also briefly reviewed.

  10. The ketogenic diet and other dietary treatments for refractory epilepsy in children

    Science.gov (United States)

    Sharma, Suvasini; Jain, Puneet

    2014-01-01

    The ketogenic diet is a high-fat, low-carbohydrate, and restricted protein diet that is useful in patients with refractory epilepsy. The efficacy of the ketogenic diet is better than most of the new antiepileptic drugs. Other modifications of the diet are also beneficial, such as the modified Atkins diet and the low glycemic index treatment. There is a lack of awareness of the ketogenic diet as a treatment modality for epilepsy amongst pediatricians and neurologists. In this review, the use of the ketogenic diet and other dietary treatments in refractory epilepsy is discussed. The Indian experience with the use of these dietary treatments is also briefly reviewed. PMID:25221391

  11. GLUT1 deficiency with delayed myelination responding to ketogenic diet.

    NARCIS (Netherlands)

    Klepper, J.; Engelbrecht, V.; Scheffer, H.; Knaap, M.S. van der; Fiedler, A.

    2007-01-01

    Monitoring effects of a ketogenic diet in GLUT1 deficiency syndrome without seizures is difficult. Neuroimaging is considered uninformative. We report the case of a boy with neurodevelopmental delay, severe ataxia, an E54X-mutation in the SLC2A1 gene (previously GLUT1), and neuroimaging

  12. Antiseizure effects of ketogenic diet on seizures induced with ...

    African Journals Online (AJOL)

    Antiseizure effects of ketogenic diet on seizures induced with pentylenetetrazole, 4-aminopyridine and strychnine in wistar rats. E.O. Sanya, A.O. Soladoye, O.O. Desalu, P.M. Kolo, L. A. Olatunji, J.K. Olarinoye ...

  13. CSF Amino Acids, Pterins and Mechanism of the Ketogenic Diet

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap

    2015-11-01

    Full Text Available Investigators from Hospital Sant Joan de Deu, Barcelona, Spain, studied the relationship between the etiology of refractory childhood epilepsy, CSF neurotransmitters, pterins, and amino acids, and response to a ketogenic diet in 60 patients with refractory epilepsy, 83% focal and 52% idiopathic.

  14. GLUT1 deficiency with delayed myelination responding to ketogenic diet

    NARCIS (Netherlands)

    Klepper, Jörg; Engelbrecht, Volkher; Scheffer, Hans; van der Knaap, Marjo S.; Fiedler, Andreas

    2007-01-01

    Monitoring effects of a ketogenic diet in GLUT1 deficiency syndrome without seizures is difficult. Neuroimaging is considered uninformative. We report the case of a boy with neurodevelopmental delay, severe ataxia, an E54X-mutation in the SLC2A1 gene (previously GLUT1), and neuroimaging

  15. Mechanisms of Action of Antiseizure Drugs and the Ketogenic Diet

    Science.gov (United States)

    Rogawski, Michael A.; Löscher, Wolfgang; Rho, Jong M.

    2016-01-01

    Antiseizure drugs (ASDs), also termed antiepileptic drugs, are the main form of symptomatic treatment for people with epilepsy, but not all patients become free of seizures. The ketogenic diet is one treatment option for drug-resistant patients. Both types of therapy exert their clinical effects through interactions with one or more of a diverse set of molecular targets in the brain. ASDs act by modulation of voltage-gated ion channels, including sodium, calcium, and potassium channels; by enhancement of γ-aminobutyric acid (GABA)-mediated inhibition through effects on GABAA receptors, the GABA transporter 1 (GAT1) GABA uptake transporter, or GABA transaminase; through interactions with elements of the synaptic release machinery, including synaptic vesicle 2A (SV2A) and α2δ; or by blockade of ionotropic glutamate receptors, including α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. The ketogenic diet leads to increases in circulating ketones, which may contribute to the efficacy in treating pharmacoresistant seizures. Production in the brain of inhibitory mediators, such as adenosine, or ion channel modulators, such as polyunsaturated fatty acids, may also play a role. Metabolic effects, including diversion from glycolysis, are a further postulated mechanism. For some ASDs and the ketogenic diet, effects on multiple targets may contribute to activity. Better understanding of the ketogenic diet will inform the development of improved drug therapies to treat refractory seizures. PMID:26801895

  16. Ketogenic diet in 3 cases of childhood refractory status epilepticus

    DEFF Research Database (Denmark)

    Sort, Rune; Born, Alfred P; Pedersen, Karen N.

    2013-01-01

    Refractory status epilepticus (RSE) in children is associated with a significant risk of death or neurological morbidity. Recently attention has been drawn to the ketogenic diet (KD) as an acute treatment, as it has shown promise in controlling seizures in otherwise refractory status epilepticus...

  17. Internist, anesthesiologist and surgeon use of ketogenic diet.

    Science.gov (United States)

    Cenci, Lorenzo; Paoli, Antonio; Omar, Hesham R; Dalvi, Prachiti; Camporesi, Enrico M; Mangar, Devanand; Quartesan, Silvia; Fiorito, Alberto; Bosco, Gerardo

    2018-03-01

    Ketogenic diet is being increasingly utilized in recent decades because of its success as an effective tool for short and intermediate-term weight loss. Promoting physiological ketosis from a drastically low carbohydrate diet is the fundamental basis for this diet regime. Though debated, these diets have been demonstrated to be effective, at least in the short- to medium terms, to manage excess weight, hyperlipidemia, and other cardiovascular risk factors. We reviewed the cardiovascular, metabolic, anesthetic, and postsurgical profiles in the literature and summarized technical issues of anesthesia and surgery along with long-term changes from published papers. Doubts with ketogenic diet were raised due to possible renal damage caused by significant excretion of nitrogen found in animal models, the effects of acidosis, and the concerns of increasing triglycerides and cholesterol levels. Though current literature supports the efficacy of very low carbohydrate keto-diets their potential negative effects on renal function and acidosis are debated. An increase in nitrogen excretion during protein metabolism in the postoperative period could lead to renal damage. Research on the value of ketogenic diets is emerging because of its value in weight loss and in managing other pathologies.

  18. Hepatic fatty acid profile of rats fed a triheptanoin-based ketogenic diet

    OpenAIRE

    Meloi, Ingrid Sofia Vieira de; Ataidei, Terezinha da Rocha; Oliveirai, Suzana Lima de; Bezerra Buenoi, Nassib; Freitasi, Johnnatan Duarte de; Sant'Anai, Antônio Euzébio Goulart

    2015-01-01

    Objective: the aim of this study was to evaluate the influence of consumption of a ketogenic diet supplemented with triheptanoin, a medium-chain anaplerotic triacylglycerol, on the liver fatty acid profile of Wistar rats. Methods: three groups of male Wistar rats (n = 10) were submitted to an AIN-93 control diet, a triheptanoin- based ketogenic diet, or a soybean oil-based ketogenic diet for 60 days. Excised livers were subjected to lipid extraction and methylation to obtain fatty acids methy...

  19. Ketogenic Diets: New Advances for Metabolism-Based Therapies

    Science.gov (United States)

    Kossoff, Eric H.; Hartman, Adam L.

    2014-01-01

    Purpose of review Despite myriad anticonvulsants available and in various stages of development, there are thousands of children and adults with epilepsy worldwide still refractory to treatment and not candidates for epilepsy surgery. Many of these patients will now turn to dietary therapies such as the ketogenic diet, medium-chain triglyceride (MCT) diet, modified Atkins diet, and low glycemic index treatment. Recent Findings In the past several years, neurologists are finding new indications to use these dietary treatments, perhaps even as first-line therapy, including infantile spasms, myoclonic-astatic epilepsy (Doose syndrome), Dravet syndrome, and status epilepticus (including FIRES syndrome). Adults are also one of the most rapidly growing populations being treated nowadays; a group of patients previously not typically offered these treatments. In 2009, two controlled trials of the ketogenic diet were published as well as an International Expert Consensus Statement on dietary treatment of epilepsy. Ketogenic diets are also now being increasingly studied for neurologic conditions other than epilepsy, including Alzheimer disease and cancer. Insights from basic science research have helped elucidate the mechanisms by which metabolism-based therapy may be helpful, both in terms of an anticonvulsant and possibly neuroprotective effect. Summary Dietary therapy for epilepsy continues to grow in popularity worldwide, with expanding use for adults and conditions other than epilepsy. PMID:22322415

  20. Metabolic impact of a ketogenic diet compared to a hypocaloric diet in obese children and adolescents.

    Science.gov (United States)

    Partsalaki, Ioanna; Karvela, Alexia; Spiliotis, Bessie E

    2012-01-01

    The effects of carbohydrate-restricted (ketogenic) diets on metabolic parameters in children have been incompletely assessed. To compare the efficacy and metabolic impact of ketogenic and hypocaloric diets in obese children and adolescents. Fifty-eight obese subjects were placed on one of the two diets for 6 months. Anthropometric measurements, body composition, oral glucose/insulin tolerance test, lipidemic profile, high molecular weight (HMW) adiponectin, whole-body insulin sensitivity index (WBISI), and homeostatic model assessment-insulin resistance (HOMA-IR) were determined before and after each diet. Both groups significantly reduced their weight, fat mass, waist circumference, fasting insulin, and HOMA-IR (p = 0.009 for ketogenic and p = 0.014 for hypocaloric), but the differences were greater in the ketogenic group. Both groups increased WBISI significantly, but only the ketogenic group increased HMW adiponectin significantly (p = 0.025). The ketogenic diet revealed more pronounced improvements in weight loss and metabolic parameters than the hypocaloric diet and may be a feasible and safe alternative for children's weight loss.

  1. Ketogenic diet efficacy in the treatment of intractable epileptic spasms.

    Science.gov (United States)

    Kayyali, Husam R; Gustafson, Megan; Myers, Tara; Thompson, Lindsey; Williams, Michelle; Abdelmoity, Ahmad

    2014-03-01

    To determine the efficacy of the ketogenic diet in controlling epileptic spasms after failing traditional antiepileptic medication therapy. This is a prospective, case-based study of all infants with epileptic spasms who were referred for treatment with the ketogenic diet at our hospital between 2009 and 2012. All subjects continued to have epileptic spasms with evidence of hypsarrhythmia or severe epileptic encephalopathy on electroencephalography despite appropriate medication treatments. The diet efficacy was assessed through clinic visits, phone communications, and electroencephalography. Quality of life improvement was charted based on the caregiver's perspective. Twenty infants (15 males) were included in the study. The mean age at seizure onset was 4.5 months. Age at ketogenic diet initiation was 0.3 to 2.9 years (mean 1.20, standard deviation 0.78). Fifteen patients had epileptic spasms of unknown etiology; three had perinatal hypoxic ischemic encephalopathy, one had lissencephaly, and one had STXBP1 mutation. Fifteen infants failed to respond to adrenocorticotropin hormone and/or vigabatrin before going on the ketogenic diet. Three months after starting the diet, >50% seizure reduction was achieved in 70% of patients (95% CI 48-86). These results were maintained at 6- and 12-month intervals. All eight of the patients followed for 24 months had >50% seizure reduction (95% CI 63-100). At least 90% seizure reduction was reported in 20% of patients at 3 months (95% CI 7-42), 22% (95% CI 8-46) at 6 months, and 35% (95% CI 17-59) at 12 months. The majority of patients (63%) achieved improvement of their spasms within 1 month after starting the diet. Sixty percent of patients had electroencephalographic improvement. All caregivers reported improvement of the quality of life at the 3-month visit (95% confidence interval 81-100). This ratio was 94% at 6 months (95% CI 72-99) and 82% at 12 months (95% CI 58-95). The ketogenic diet is a safe and potentially

  2. Ketosis, ketogenic diet and food intake control: a complex relationship

    Directory of Open Access Journals (Sweden)

    Antonio ePaoli

    2015-02-01

    Full Text Available Though the hunger-reduction phenomenon reported during ketogenic diets is well known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK release while reducing orexigenic signals e.g. via ghrelin. However ketone bodies (KB seem to be able to increase food intake through AMP-activated protein kinase (AMPK phosphorylation, gamma-aminobutyric acid (GABA and the release and production of adiponectin. The aim of this review is to provide an overview of our current knowledge of the effects of ketogenic diet (KD on food control in an effort to unify the apparently contradictory data into a coherent picture.

  3. Ketosis, ketogenic diet and food intake control: a complex relationship

    Science.gov (United States)

    Paoli, Antonio; Bosco, Gerardo; Camporesi, Enrico M.; Mangar, Devanand

    2015-01-01

    Though the hunger-reduction phenomenon reported during ketogenic diets is well-known, the underlying molecular and cellular mechanisms remain uncertain. Ketosis has been demonstrated to exert an anorexigenic effect via cholecystokinin (CCK) release while reducing orexigenic signals e.g., via ghrelin. However, ketone bodies (KB) seem to be able to increase food intake through AMP-activated protein kinase (AMPK) phosphorylation, gamma-aminobutyric acid (GABA) and the release and production of adiponectin. The aim of this review is to provide a summary of our current knowledge of the effects of ketogenic diet (KD) on food control in an effort to unify the apparently contradictory data into a coherent picture. PMID:25698989

  4. Mouse models: the ketogenic diet and polyunsaturated fatty acids.

    Science.gov (United States)

    Borges, Karin

    2008-11-01

    Literature on the anticonvulsant effects of the ketogenic diet (KD) in mouse seizure models is summarized. Recent data show that a KD balanced in vitamin, mineral, and antioxidant content is anticonvulsant in mice, confirming that the KD's effect in mice can be attributed to the composition of the diet and not other dietary factors. Given that the anticonvulsant mechanism of the KD is still unknown, the anticonvulsant profile of the diet in different seizure models may help to decipher this mechanism. The implications of the findings that the KD is anticonvulsant in electrical seizure models are indicated. Further, the potential involvement of polyunsaturated fatty acids (PUFA) in the KD's anticonvulsant mechanism is discussed.

  5. Ketogenic diet guidelines for infants with refractory epilepsy

    OpenAIRE

    van der Louw, E.; van den Hurk, D.; Neal, E.; Leiendecker, B.; Fitzsimmon, G.; Dority, L.; Thompson, L.; Marchio, M.; Dudzinska, M.; Dressler, A.; Klepper, J.; Auvin, S.; Cross, J. H.

    2016-01-01

    BACKGROUND: The ketogenic diet (KD) is an established, effective non-pharmacologic treatment for drug resistant childhood epilepsy. For a long time, the KD was not recommended for use in infancy (under the age of 2 years) because this is such a crucial period in development and the perceived high risk of nutritional inadequacies. Indeed, infants are a vulnerable population with specific nutritional requirements. But current research shows that the KD is highly effective and well tolerated in ...

  6. Cardiopulmonary bypass considerations for pediatric patients on the ketogenic diet.

    Science.gov (United States)

    Melchior, R W; Dreher, M; Ramsey, E; Savoca, M; Rosenthal, T

    2015-07-01

    There is a population of children with epilepsy that is refractory to anti-epileptic drugs. The ketogenic diet, a high-fat, low-carbohydrate regimen, is one alternative treatment to decrease seizure activity. Special considerations are required for patients on the ketogenic diet undergoing cardiopulmonary bypass (CPB) to prevent exposure to glucose substrates that could alter ketosis, increasing the risk of recurrent seizures. A 2-year-old, 9 kilogram male with a history of infantile spasms with intractable epilepsy, trisomy 21 status post tetralogy of Fallot repair, presented to the cardiac operating room for closure of a residual atrial septal defect. All disciplines of the surgical case minimized the use of carbohydrate-containing and contraindicated medications. Changes to the standard protocol and metabolic monitoring ensured the patient maintained ketosis. All disciplines within cardiac surgery need to be cognizant of patients on the ketogenic diet and prepare a modified protocol. Future monitoring considerations include thromboelastography, electroencephalography and continuous glucose measurement. Key areas of focus with this patient population in the cardiac surgical theater are to maintain a multidisciplinary approach, alter the required CPB prime components, address cardiac pharmacological concerns and limit any abnormal hematological occurrences. © The Author(s) 2014.

  7. Effect of One Month Duration Ketogenic and non-Ketogenic High Fat Diets on Mouse Brain Bioenergetic Infrastructure

    Science.gov (United States)

    Selfridge, J. Eva; Wilkins, Heather M.; Lezi, E; Carl, Steven M.; Koppel, Scott; Funk, Eric; Fields, Timothy; Lu, Jianghua; Tang, Ee Phie; Slawson, Chad; Wang, WenFang; Zhu, Hao; Swerdlow, Russell H.

    2014-01-01

    Diet composition may affect energy metabolism in a tissue-specific manner. Using C57Bl/6J mice, we tested the effect of ketosis-inducing and non-inducing high fat diets on genes relevant to brain bioenergetic infrastructures, and on proteins that constitute and regulate that infrastructure. At the end of a one-month study period the two high fat diets appeared to differentially affect peripheral insulin signaling, but brain insulin signaling was not obviously altered. Some bioenergetic infrastructure parameters were similarly impacted by both high fat diets, while other parameters were only impacted by the ketogenic diet. For both diets, mRNA levels for CREB, PGC1α, and NRF2 increased while NRF1, TFAM, and COX4I1 mRNA levels decreased. PGC1β mRNA increased and TNFα mRNA decreased only with the ketogenic diet. Brain mtDNA levels fell in both the ketogenic and non-ketogenic high fat diet groups, although TOMM20 and COX4I1 protein levels were maintained, and mRNA and protein levels of the mtDNA-encoded COX2 subunit were also preserved. Overall, the pattern of changes observed in mice fed ketogenic and non-ketogenic high fat diets over a one month time period suggests these interventions enhance some aspects of the brain’s aerobic infrastructure, and may enhance mtDNA transcription efficiency. Further studies to determine which diet effects are due to changes in brain ketone body levels, fatty acid levels, glucose levels, altered brain insulin signaling, or other factors such as adipose tissue-associated hormones are indicated. PMID:25104046

  8. Ketogenic diet treatment for pediatric super-refractory status epilepticus.

    Science.gov (United States)

    Appavu, Brian; Vanatta, Lisa; Condie, John; Kerrigan, John F; Jarrar, Randa

    2016-10-01

    We aimed to study whether ketogenic diet (KD) therapy leads to resolution of super-refractory status epilepticus in pediatric patients without significant harm. A retrospective review was performed at Phoenix Children's Hospital on patients with super-refractory status epilepticus undergoing ketogenic diet therapy from 2011 to 2015. Ten children with super-refractory status epilepticus, ages 2-16 years, were identified. 4/10 patients had immune mediated encephalitis, including Rasmussen encephalitis, anti-N-methyl-d-aspartate receptor encephalitis, and post-infectious mycoplasma encephalitis. Other etiologies included Lennox Gastaut Syndrome, non-ketotic hyperglycinemia, PCDH19 and GABRG2 genetic epilepsy, New Onset Refractory Status Epilepticus, and Febrile Infection-Related Epilepsy Syndrome. 4/10 patients' EEG features suggested focal with status epilepticus, and 6/10 suggested generalized with status epilepticus. Median hospital length was 61days and median ICU length was 27days. The median number of antiepileptic medications prior to diet initiation was 3.0 drugs, and the median after ketogenic diet treatment was 3.5 drugs. Median duration of status epilepticus prior to KD was 18days. 9/10 patients had resolution of super-refractory status epilepticus in a median of 7days after diet initiation. 8/9 patients were weaned off anesthesia within 15days of diet initiation, and within 1day of achieving ketonuria. 1/10 patients experienced side effects on the diet requiring supplementation. Most patients achieved resolution of status epilepticus on KD therapy, suggesting it could be an effective therapy that can be utilized early in the treatment of children with super refractory status epilepticus. Copyright © 2016. Published by Elsevier Ltd.

  9. Ketogenic Diet in Refractory Childhood Epilepsy : Starting With a Liquid Formulation in an Outpatient Setting

    NARCIS (Netherlands)

    Weijenberg, Amerins; van Rijn, Margreet; Callenbach, Petra M C; de Koning, Tom J; Brouwer, Oebele F

    2018-01-01

    Background: Ketogenic diet in children with epilepsy has a considerable impact on daily life and is usually adopted for at least 3 months. Our aim was to evaluate whether the introduction of an all-liquid ketogenic diet in an outpatient setting is feasible, and if an earlier assessment of its

  10. Will seizure control improve by switching from the modified Atkins diet to the traditional ketogenic diet?

    DEFF Research Database (Denmark)

    Kossoff, Eric H; Bosarge, Jennifer L; Miranda, Maria J

    2010-01-01

    It has been reported that children can maintain seizure control when the ketogenic diet (KD) is transitioned to the less-restrictive modified Atkins diet (MAD). What is unknown, however, is the likelihood of additional seizure control from a switch from the MAD to the KD. Retrospective information...

  11. Is ketogenic diet treatment hepatotoxic for children with intractable epilepsy?

    Science.gov (United States)

    Arslan, Nur; Guzel, Orkide; Kose, Engin; Yılmaz, Unsal; Kuyum, Pınar; Aksoy, Betül; Çalık, Tansel

    2016-12-01

    Long-term ketogenic diet (KD) treatment has been shown to induce liver steatosis and gallstone formation in some in vivo and clinical studies. The aim of this retrospective study was to evaluate the hepatic side effects of KD in epileptic children. A total of 141 patients (mean age: 7.1±4.1years [2-18 years], 45.4% girls), receiving KD at least one year for intractable epilepsy due to different diagnoses (congenital brain defects, GLUT-1 deficiency, West syndrome, tuberous sclerosis, hypoxic brain injury, etc.) were included in the study. Serum triglyceride, cholesterol, aminotransferase, bilirubin, protein and albumin levels and abdominal ultrasonography were recorded before and at 1, 3, 6, and 12 months following after diet initiation. The mean duration of KD was 15.9±4.3months. At one month of therapy, three patients had elevated alanine and aspartate aminotransferase levels. These patients were receiving ketogenic diet for Doose syndrome, idiopathic epilepsy and GLUT-1 deficiency. Hepatosteatosis was detected in three patients at 6 months of treatment. Two of these patients were treated with KD for the primary diagnosis of tuberous sclerosis and one for Landau Kleffner syndrome. Cholelithiasis was detected in two patients at 12 months of treatment. They were receiving treatment for West syndrome and hypoxic brain injury sequelae. Long-term ketogenic diet treatment stimulates liver parenchymal injury, hepatic steatosis and gallstone formation. Patients should be monitored by screening liver enzymes and abdominal ultrasonography in order to detect these side effects. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  12. A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice.

    Science.gov (United States)

    Roberts, Megan N; Wallace, Marita A; Tomilov, Alexey A; Zhou, Zeyu; Marcotte, George R; Tran, Dianna; Perez, Gabriella; Gutierrez-Casado, Elena; Koike, Shinichiro; Knotts, Trina A; Imai, Denise M; Griffey, Stephen M; Kim, Kyoungmi; Hagopian, Kevork; McMackin, Marissa Z; Haj, Fawaz G; Baar, Keith; Cortopassi, Gino A; Ramsey, Jon J; Lopez-Dominguez, Jose Alberto

    2017-09-05

    Calorie restriction, without malnutrition, has been shown to increase lifespan and is associated with a shift away from glycolysis toward beta-oxidation. The objective of this study was to mimic this metabolic shift using low-carbohydrate diets and to determine the influence of these diets on longevity and healthspan in mice. C57BL/6 mice were assigned to a ketogenic, low-carbohydrate, or control diet at 12 months of age and were either allowed to live their natural lifespan or tested for physiological function after 1 or 14 months of dietary intervention. The ketogenic diet (KD) significantly increased median lifespan and survival compared to controls. In aged mice, only those consuming a KD displayed preservation of physiological function. The KD increased protein acetylation levels and regulated mTORC1 signaling in a tissue-dependent manner. This study demonstrates that a KD extends longevity and healthspan in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. The ketogenic diet is effective for refractory epilepsy associated with acquired structural epileptic encephalopathy.

    Science.gov (United States)

    Villaluz, Mel Michel; Lomax, Lysa Boissé; Jadhav, Trupti; Cross, J Helen; Scheffer, Ingrid E

    2018-07-01

    Ketogenic diet therapies have proven efficacy for refractory epilepsy. There are many reports of their use in the genetic developmental and epileptic encephalopathies; however, little attention has been paid as to whether the diet is also effective in individuals with an acquired structural aetiology. We observed remarkable efficacy of the diet in two patients with hypoxic-ischaemic encephalopathy. We then analysed our cases with refractory structural epilepsies of acquired origin to characterize their response to the ketogenic diet. The classical ketogenic diet was implemented with dietary ratios of 3:1 to 4.4:1. Seizure frequency at 1 month, 3 months, 6 months, 1 year, and 2 years was ascertained. A responder was defined as greater than 50% seizure reduction compared to baseline. Seven of the nine patients were responders at 3 months. Somewhat surprisingly we found that the ketogenic diet was effective in patients with a developmental and epileptic encephalopathy due to an acquired structural aetiology. This cohort may not be routinely considered for the ketogenic diet because of their structural and acquired, rather than genetic, basis. The ketogenic diet should be considered early in the management of patients with acquired structural encephalopathies as it can improve seizure control with the potential to improve developmental outcome. The ketogenic diet was effective in children with epilepsy associated with an acquired structural aetiology. © 2018 Mac Keith Press.

  14. Ketogenic diet does not impair spatial ability controlled by the hippocampus in male rats.

    Science.gov (United States)

    Fukushima, Atsushi; Ogura, Yuji; Furuta, Miyako; Kakehashi, Chiaki; Funabashi, Toshiya; Akema, Tatsuo

    2015-10-05

    A ketogenic diet was recently shown to reduce glutamate accumulation in synaptic vesicles, decreasing glutamate transmission. We questioned whether a ketogenic diet affects hippocampal function, as glutamate transmission is critically involved in visuospatial ability. In the present study, male Wistar rats were maintained on a ketogenic diet containing 10% protein and 90% fat with complements for 3 weeks to change their energy expenditure from glucose-dependent to fat-dependent. Control rats were fed a diet containing 10% protein, 10% fat, and 80% carbohydrates. The fat-dependent energy expenditure induced by the ketogenic diet led to decreased body weight and increased blood ketone production, though the rats in the two groups consumed the same number of calories. The ketogenic diet did not alter food preferences for the control or high-fat diet containing 10% protein, 45% fat, and 45% carbohydrates. Anxiety in the open field was not altered by ingestion the ketogenic diet. However, rats fed the ketogenic diet performed better in the Y-maze test than rats fed the control diet. No difference was observed between the two groups in the Morris water maze test. Finally, Western blot revealed that the hippocampal expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor subunit 1 (GluR1) was significantly increased in mice fed a ketogenic diet. These results suggest that hippocampal function is not impaired by a ketogenic diet and we speculate that the fat-dependent energy expenditure does not impair visuospatial ability. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Neuronal-glial interactions in rats fed a ketogenic diet.

    Science.gov (United States)

    Melø, Torun Margareta; Nehlig, Astrid; Sonnewald, Ursula

    2006-01-01

    Glucose is the preferred energy substrate for the adult brain. However, during periods of fasting and consumption of a high fat, low carbohydrate (ketogenic) diet, ketone bodies become major brain fuels. The present study was conducted to investigate how the ketogenic diet influences neuronal-glial interactions in amino acid neurotransmitter metabolism. Rats were kept on a standard or ketogenic diet. After 21 days all animals received an injection of [1-(13)C]glucose plus [1,2-(13)C]acetate, the preferential substrates of neurons and astrocytes, respectively. Extracts from cerebral cortex and plasma were analyzed by (13)C and (1)H nuclear magnetic resonance spectroscopy and HPLC. Increased amounts of valine, leucine and isoleucine and a decreased amount of glutamate were found in the brains of rats receiving the ketogenic diet. Glycolysis was decreased in ketotic rats compared with controls, evidenced by the reduced amounts of [3-(13)C]alanine and [3-(13)C]lactate. Additionally, neuronal oxidative metabolism of [1-(13)C]glucose was decreased in ketotic rats compared with controls, since amounts of [4-(13)C]glutamate and [4-(13)C]glutamine were lower than those of controls. Although the amount of glutamate from [1-(13)C]glucose was decreased, this was not the case for GABA, indicating that relatively more [4-(13)C]glutamate is converted to GABA. Astrocytic metabolism was increased in response to ketosis, shown by increased amounts of [4,5-(13)C]glutamine, [4,5-(13)C]glutamate, [1,2-(13)C]GABA and [3,4-(13)C]-/[1,2-(13)C]aspartate derived from [1,2-(13)C]acetate. The pyruvate carboxylation over dehydrogenation ratio for glutamine was increased in the ketotic animals compared to controls, giving further indication of increased astrocytic metabolism. Interestingly, pyruvate recycling was higher in glutamine than in glutamate in both groups of animals. An increase in this pathway was detected in glutamate in response to ketosis. The decreased glycolysis and oxidative

  16. Sciatic nerve regeneration in rats subjected to ketogenic diet.

    Science.gov (United States)

    Liśkiewicz, Arkadiusz; Właszczuk, Adam; Gendosz, Daria; Larysz-Brysz, Magdalena; Kapustka, Bartosz; Łączyński, Mariusz; Lewin-Kowalik, Joanna; Jędrzejowska-Szypułka, Halina

    2016-01-01

    Ketogenic diet (KD) is a high-fat-content diet with insufficiency of carbohydrates that induces ketogenesis. Besides its anticonvulsant properties, many studies have shown its neuroprotective effect in central nervous system, but its influence on peripheral nervous system has not been studied yet. We examined the influence of KD on regeneration of peripheral nerves in adult rats. Fifty one rats were divided into three experimental (n = 15) and one control (n = 6) groups. Right sciatic nerve was crushed and animals were kept on standard (ST group) or ketogenic diet, the latter was introduced 3 weeks before (KDB group) or on the day of surgery (KDA group). Functional (CatWalk) tests were performed once a week, and morphometric (fiber density, axon diameter, and myelin thickness) analysis of the nerves was made after 6 weeks. Body weight and blood ketone bodies level were estimated at the beginning and the end of experiment. Functional analysis showed no differences between groups. Morphometric evaluation showed most similarities to the healthy (uncrushed) nerves in KDB group. Nerves in ST group differed mostly from all other groups. Ketone bodies were elevated in both KD groups, while post-surgery animals' body weight was lower as compared to ST group. Regeneration of sciatic nerves was improved in KD - preconditioned rats. These results suggest a neuroprotective effect of KD on peripheral nerves.

  17. Reduced pain and inflammation in juvenile and adult rats fed a ketogenic diet.

    Directory of Open Access Journals (Sweden)

    David N Ruskin

    2009-12-01

    Full Text Available The ketogenic diet is a high-fat, low-carbohydrate regimen that forces ketone-based rather than glucose-based cellular metabolism. Clinically, maintenance on a ketogenic diet has been proven effective in treating pediatric epilepsy and type II diabetes, and recent basic research provides evidence that ketogenic strategies offer promise in reducing brain injury. Cellular mechanisms hypothesized to be mobilized by ketone metabolism and underlying the success of ketogenic diet therapy, such as reduced reactive oxygen species and increased central adenosine, suggest that the ketolytic metabolism induced by the diet could reduce pain and inflammation. To test the effects of a ketone-based metabolism on pain and inflammation directly, we fed juvenile and adult rats a control diet (standard rodent chow or ketogenic diet (79% fat ad libitum for 3-4 weeks. We then quantified hindpaw thermal nociception as a pain measure and complete Freund's adjuvant-induced local hindpaw swelling and plasma extravasation (fluid movement from the vasculature as inflammation measures. Independent of age, maintenance on a ketogenic diet reduced the peripheral inflammatory response significantly as measured by paw swelling and plasma extravasation. The ketogenic diet also induced significant thermal hypoalgesia independent of age, shown by increased hindpaw withdrawal latency in the hotplate nociception test. Anti-inflammatory and hypoalgesic diet effects were generally more robust in juveniles. The ketogenic diet elevated plasma ketones similarly in both age groups, but caused slowed body growth only in juveniles. These data suggest that applying a ketogenic diet or exploiting cellular mechanisms associated with ketone-based metabolism offers new therapeutic opportunities for controlling pain and peripheral inflammation, and that such a metabolic strategy may offer significant benefits for children and adults.

  18. [Effectiveness of a ketogenic diet in children with refractory epilepsy: a systematic review].

    Science.gov (United States)

    Araya-Quintanilla, F; Celis-Rosati, A; Rodriguez-Leiva, C; Silva-Navarro, C; Silva-Pinto, Y; Toro-Jeria, B

    2016-05-16

    Epilepsy is a brain disorder that affects both children and adults. From the 1920s the ketogenic diet has gained prestige as another treatment option for patients with refractory epilepsy. A summary of the evidence will be made through a systematic review of randomized clinical trials that have compared a single ketogenic diet with other diet for the management of these patients. To determine the effectiveness of the ketogenic diet in reducing episodes of seizures in patients with refractory epilepsy. The search strategy included randomized controlled trials and controlled clinical trials. Databases used were Medline, LILACS, Central and CINAHL. Six articles that met our elegibility criteria. There is limited evidence that the ketogenic diet compared to the medium-chain triglyceride diet is more effective in reducing the frequency of seizures. There is also moderate evidence that classical ketogenic diet compared to the gradual diet (2.5:1 and 3:1) is more effective in reducing seizures. There is moderate evidence that classical ketogenic diet compared to Atkins diet is more effective in reducing the frequency of seizure. The decision to apply this type of diet should also be based on costs, preferences and safety of treatment. It should also take into account the likelihood that studies have indexing problems have been left out of the review.

  19. The effects of ketogenic diet on oxidative stress and antioxidative capacity markers of Taekwondo athletes.

    Science.gov (United States)

    Rhyu, Hyun-Seung; Cho, Su-Youn; Roh, Hee-Tae

    2014-12-01

    The purpose of this study was to investigate the effects of the ketogenic diet through 3 weeks on oxidative stress and antioxidative capacity markers in Taekwondo athletes. The participants selected for this research were 18 high school taekwondo contestants aged 15-18 who had at least 5 yr of career as contestant. The subjects were randomly assigned to the ketogenic diet (KD) group and the Non ketogenic diet (NDK) group. Body composition and oxidative stress and antioxidative capacity markers (LDH, MDA, ROS, HDL, and SOD) were analysed before and after 3 weeks of ketogenic diet. No significant difference was found between the groups in body composition, ROS and SOD level. The KD group showed an elevated HDL level and NKD group showed an elevated LDH and MDA level after ketogenic diet by 3 weeks. This result suggests that weight loss by 3 weeks of calorie restriction and exercise can cause oxidative stress, and that ketogenic diet can be effective for preventing it. It could also be inferred that ketogenic diet can be effective for increasing blood antioxidative capacity.

  20. Kynurenic Acid and Neuroprotective Activity of the Ketogenic Diet in the Eye.

    Science.gov (United States)

    Zarnowski, Tomasz; Tulidowicz-Bielak, Maria; Zarnowska, Iwona; Mitosek-Szewczyk, Krystyna; Wnorowski, Artur; Jozwiak, Krzysztof; Gasior, Maciej; Turski, Waldemar A

    2017-01-01

    There is growing evidence of the involvement of the kynurenine metabolic pathway and the enhancement of kynurenic acid production in the neuroprotective effects of the ketogenic diet. Here, we review evidence implicating kynurenic acid in the efficacy of ketogenic diet in eye diseases associated with neurodegeneration. Ketogenic diet and ketone bodies that are elevated during exposure to the ketogenic diet each have a neuroprotective effect on retinal ganglion cells in a rat model of Nmethyl- D-aspartate induced neuronal damage. Chronic exposure to ketogenic diet also increases kynurenic acid concentrations in discrete rat brain structures. A non-selective glutamate receptor agonist, glutamate, also decreases the production of kynurenic acid in bovine retinal slices; this effect is attenuated by acetoacetate and β-hydroxybutyrate, two of three ketone bodies overproduced during ketogenic diet. Whether ketogenic diet induced enhancement of kynurenic acid production would translate into a clinically significant improvement in certain eye diseases like glaucoma and retinal neurodegenerations awaits further experimental and clinical verification. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Antiepileptic popular ketogenic diet: emerging twists in an ancient story.

    Science.gov (United States)

    Vamecq, Joseph; Vallée, Louis; Lesage, Florian; Gressens, Pierre; Stables, James P

    2005-01-01

    The antiepileptic activity associated with ketogenic diets (KD) have been known for some time. First reports date back to the Middle Ages and even Biblical times where KD was achieved by fasting (i.e. "water diet") [see Swink, T.D., Vining, E.P.G., Freeman, J.M., 1997. The ketogenic diet: 1997. Adv. Pediatr. 44, 297-329, and references therein]. In the early 20th century, changes in the design of the KD were introduced, shifting the so-called "water diet" to a high-fat diet. Initial clinical evaluations undertaken between the 1920s and 1940s were enthusiastic, but the popularity of the KD was retrograded upon clinical introduction of phenytoin and subsequently other antiepileptic drugs. Today, despite a pharmacological arsenal targeting cerebral receptors and specific events in seizure initiation and development, about 30-40% patients are still refractory to available medications. Thus, the KD has been re-introduced in recent years as an alternative therapy, averring to be efficacious against some instances of resistant or intractable epilepsy. Despite a long historical background and enlarged clinical use, identification of the underlying anticonvulsant mechanisms associated with this nonpharmacological approach is still in stagnation. The present review is an attempt to encourage current research orientation through well-based and directed proposals for putative emerging candidates mediating KD anticonvulsant mechanisms. The reader is provided with a special emphasis on ATP-sensitive and recently cloned two-pore (or tandem) domain potassium channels, as well as several emerging conceptual views and advances such as nuclear receptors, uncoupling proteins and gap junctions that the authors speculate may contribute to understanding the basic mechanisms linked to the KD.

  2. Timeline of changes in appetite during weight loss with a ketogenic diet

    OpenAIRE

    Nymo, Siren

    2017-01-01

    Background/objective: Diet-induced weight loss (WL) leads to increased hunger and reduced fullness feelings, increased ghrelin and reduced satiety peptides concentration (glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK) and peptide YY (PYY)). Ketogenic diets seem to minimise or supress some of these responses. The aim of this study was to determine the timeline over which changes in appetite occur during progressive WL with a ketogenic very-low-energy diet (VLED). Subjects/methods: T...

  3. Are purines mediators of the anticonvulsant/neuroprotective effects of ketogenic diets?

    OpenAIRE

    Masino, Susan A.; Geiger, Jonathan D.

    2008-01-01

    Abnormal neuronal signaling caused by metabolic changes characterizes several neurological disorders, and in some instances metabolic interventions provide therapeutic benefits. Indeed, altering metabolism either by fasting or by maintaining a low-carbohydrate (ketogenic) diet might reduce epileptic seizures and offer neuroprotection in part because the diet increases mitochondrial biogenesis and brain energy levels. Here we focus on a novel hypothesis that a ketogenic diet-induced change in ...

  4. Spanish Ketogenic Mediterranean diet: a healthy cardiovascular diet for weight loss

    Science.gov (United States)

    Pérez-Guisado, Joaquín; Muñoz-Serrano, Andrés; Alonso-Moraga, Ángeles

    2008-01-01

    Background Ketogenic diets are an effective healthy way of losing weight since they promote a non-atherogenic lipid profile, lower blood pressure and decrease resistance to insulin with an improvement in blood levels of glucose and insulin. On the other hand, Mediterranean diet is well known to be one of the healthiest diets, being the basic ingredients of such diet the olive oil, red wine and vegetables. In Spain the fish is an important component of such diet. The objective of this study was to determine the dietary effects of a protein ketogenic diet rich in olive oil, salad, fish and red wine. Methods A prospective study was carried out in 31 obese subjects (22 male and 19 female) with the inclusion criteria whose body mass index and age was 36.46 ± 2.22 and 38.48 ± 2.27, respectively. This Ketogenic diet was called "Spanish Ketogenic Mediterranean Diet" (SKMD) due to the incorporation of virgin olive oil as the principal source of fat (≥30 ml/day), moderate red wine intake (200–400 ml/day), green vegetables and salads as the main source of carbohydrates and fish as the main source of proteins. It was an unlimited calorie diet. Statistical differences between the parameters studied before and after the administration of the "Spanish Ketogenic Mediterranean diet" (week 0 and 12) were analyzed by paired Student's t test. Results There was an extremely significant (p weight (108.62 kg→ 94.48 kg), body mass index (36.46 kg/m2→31.76 kg/m2), systolic blood pressure (125.71 mmHg→109.05 mmHg), diastolic blood pressure (84.52 mmHg→ 75.24 mmHg), total cholesterol (208.24 mg/dl→186.62 mg/dl), triacylglicerols (218.67 mg/dl→113.90 mg/dl) and glucose (109.81 mg/dl→ 93.33 mg/dl). There was a significant (p = 0.0167) reduction in LDLc (114.52 mg/dl→105.95 mg/dl) and an extremely significant increase in HDLc (50.10 mg/dl→54.57 mg/dl). The most affected parameter was the triacylglicerols (47.91% of reduction). Conclusion The SKMD is safe, an effective

  5. Consumption of a low-carbohydrate and high-fat diet (the ketogenic diet) exaggerates biotin deficiency in mice.

    Science.gov (United States)

    Yuasa, Masahiro; Matsui, Tomoyoshi; Ando, Saori; Ishii, Yoshie; Sawamura, Hiromi; Ebara, Shuhei; Watanabe, Toshiaki

    2013-10-01

    Biotin is a water-soluble vitamin that acts as a cofactor for several carboxylases. The ketogenic diet, a low-carbohydrate, high-fat diet, is used to treat drug-resistant epilepsy and promote weight loss. In Japan, the infant version of the ketogenic diet is known as the "ketone formula." However, as the special infant formulas used in Japan, including the ketone formula, do not contain sufficient amounts of biotin, biotin deficiency can develop in infants who consume the ketone formula. Therefore, the aim of this study was to evaluate the effects of the ketogenic diet on biotin status in mice. Male mice (N = 32) were divided into the following groups: control diet group, biotin-deficient (BD) diet group, ketogenic control diet group, and ketogenic biotin-deficient (KBD) diet group. Eight mice were used in each group. At 9 wk, the typical symptoms of biotin deficiency such as hair loss and dermatitis had only developed in the KBD diet group. The total protein expression level of biotin-dependent carboxylases and the total tissue biotin content were significantly decreased in the KBD and BD diet groups. However, these changes were more severe in the KBD diet group. These findings demonstrated that the ketogenic diet increases biotin bioavailability and consumption, and hence, promotes energy production by gluconeogenesis and branched-chain amino acid metabolism, which results in exaggerated biotin deficiency in biotin-deficient mice. Therefore, biotin supplementation is important for mice that consume the ketogenic diet. It is suggested that individuals that consume the ketogenic diet have an increased biotin requirement. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Limited efficacy of the ketogenic diet in the treatment of highly refractory epileptic spasms.

    Science.gov (United States)

    Hussain, Shaun A; Shin, Ji Hyun; Shih, Evan J; Murata, Kristina K; Sewak, Sarika; Kezele, Michele E; Sankar, Raman; Matsumoto, Joyce H

    2016-02-01

    Numerous studies have suggested that the ketogenic diet is effective in the treatment of epileptic spasms, even in refractory cases. However, there has been very limited demonstration of prompt and complete (video-EEG confirmed) response. We set out to describe our center's experience with the ketogenic diet in the treatment of children with highly refractory epileptic spasms, with rigorous seizure outcome assessment. Children treated with the ketogenic diet for epileptic spasms between April, 2010 and June, 2014 were retrospectively identified. Seizure burden was tabulated at baseline and after 1, 3, 6, and 12-months of ketogenic diet exposure. Adverse events were similarly ascertained. We identified a cohort of 22 consecutive patients who received ketogenic diet therapy, with median age of onset of epileptic spasms of 5.2 (IQR 2.0-9.0) months, with diet initiation beginning a median of 26.4 (12.5-38.7) months after onset, and following a median of 7 (IQR 5-7) treatment failures. Only 2 patients exhibited a complete response during ketogenic diet exposure, and response was more reasonably attributed to alternative therapies in both cases. A modest early reduction in seizure frequency was not sustained beyond 1 month of diet exposure. The diet was well tolerated, and continued in 6 patients with subjective and/or partial response. In contrast to prior studies reporting substantial efficacy of the ketogenic diet, our findings suggest limited efficacy, albeit in a highly refractory cohort. Prospective studies in both refractory and new-onset populations, with both video-EEG confirmation of response and rigorous cognitive outcome assessment, would be of great value to more clearly define the utility of the ketogenic diet in the treatment of epileptic spasms. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  7. HEPATIC FATTY ACID PROFILE OF RATS FED A TRIHEPTANOIN-BASED KETOGENIC DIET.

    Science.gov (United States)

    Vieira de Melo, Ingrid Sofia; Da Rocha Ataide, Terezinha; Lima de Oliveira, Suzana; Bezerra Bueno, Nassib; Duarte de Freitas, Johnnatan; Goulart Sant'Ana, Antônio Euzébio

    2015-07-01

    the aim of this study was to evaluate the influence of consumption of a ketogenic diet supplemented with triheptanoin, a medium-chain anaplerotic triacylglycerol, on the liver fatty acid profile of Wistar rats. three groups of male Wistar rats (n = 10) were submitted to an AIN-93 control diet, a triheptanoin- based ketogenic diet, or a soybean oil-based ketogenic diet for 60 days. Excised livers were subjected to lipid extraction and methylation to obtain fatty acids methyl esters, which were subjected to gas chromatography- mass spectrometry. compared to the rats fed the control diet, those fed ketogenic diets showed a significant reduction in the concentrations of 9-hexadecenoic and 9-octadecenoic acids, whereas those fed triheptanoin showed increased levels of octadecanoic acid. changes in the liver fatty acid profiles of the rats fed a triheptanoin-based or a soybean oil-based ketogenic diet did not seem to be related to the dietary fat source, but rather to the characteristics of the ketogenic diets themselves. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  8. Protein-losing enteropathy as a rare complication of the ketogenic diet.

    Science.gov (United States)

    Moriyama, Kengo; Watanabe, Mio; Yamada, Yoshiyuki; Shiihara, Takashi

    2015-05-01

    The ketogenic diet is a valuable therapy for patients with intractable epilepsy, but it can result in a variety of complications that sometimes limits its usefulness. Hypoproteinemia is one of the common adverse effects of this diet, although the underling mechanism is largely unknown except for the diet's reduced protein intake. Only one case of protein-losing enteropathy during the ketogenic diet has been reported. A previously healthy 9-year-old girl experienced fever for 5 days then suddenly developed convulsive seizures that subsequently evolved to severe refractory status epilepticus. After multiple antiepileptic drugs failed to improve the patient's condition, we introduced the ketogenic diet. Although her seizures diminished, her course was complicated by hypoproteinemia. An abdominal dynamic scintigraphy and colonoscopy findings indicated protein-losing enteropathy with nonspecific mucosal inflammation. Her nutritional status deteriorated; thus, we discontinued the ketogenic diet. Her nutritional status gradually improved, whereas her seizures increased. Hypoproteinemia during the ketogenic diet is common, but the underlying etiologies are not well understood. Abdominal dynamic scintigraphy could be valuable for clarifying the etiology of hypoproteinemia during the ketogenic diet. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Efficacy of and Patient Compliance with a Ketogenic Diet in Adults with Intractable Epilepsy: A Meta-Analysis

    OpenAIRE

    Ye, Fang; Li, Xiao-Jia; Jiang, Wan-Lin; Sun, Hong-Bin; Liu, Jie

    2015-01-01

    Background and Purpose Despite the successful use of a ketogenic diet in pediatric epilepsy, its application in adults has been limited. The aim of this meta-analysis was to summarize the findings of relevant published studies in order to identify the efficacy of and compliance with a ketogenic diet and its main subtypes (i.e., classic ketogenic diet and modified Atkins diet) in adults with intractable epilepsy, and to provide useful information for clinical practice. Methods Electronic searc...

  10. Alternative diets to the classical ketogenic diet-Can we be more liberal?

    DEFF Research Database (Denmark)

    Miranda, Maria J; Turner, Zahava; Magrath, Gwyneth

    2012-01-01

    The ketogenic diet (KD), a high-fat, adequate protein, low-carbohydrate diet has been used since 1921 for the treatment of severe medically refractory epilepsy. In the past 15 years, the use of the KD has expanded enormously and a huge amount of clinical evidence of its efficacy is available....... The classical KD is however restrictive and therefore alternative more liberal varieties of the classical KD have been developed within the last 8 years. The purpose of this report is to summarise the principles and evidence of effectiveness of the alternative ketogenic diets: Medium Chain Triglyceride (MCT......)-KD, modified Atkins diet (MAD) and low glycaemic index treatment (LGIT), compared to the classical KD. The clinical evidence to date suggests that the more liberal versions of the classical KD such as MCT KD, MAD and LGIT have an efficacy close to the classical KD; however, no RCT data are available for MAD...

  11. Efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy: a meta-analysis.

    Science.gov (United States)

    Ye, Fang; Li, Xiao-Jia; Jiang, Wan-Lin; Sun, Hong-Bin; Liu, Jie

    2015-01-01

    Despite the successful use of a ketogenic diet in pediatric epilepsy, its application in adults has been limited. The aim of this meta-analysis was to summarize the findings of relevant published studies in order to identify the efficacy of and compliance with a ketogenic diet and its main subtypes (i.e., classic ketogenic diet and modified Atkins diet) in adults with intractable epilepsy, and to provide useful information for clinical practice. Electronic searches of PubMed, EMBASE, Google Scholar, and the ISI Web of Science were conducted to identify studies of the efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy; the included studies were reviewed. Meta-analyses were performed using STATA to determine combined efficacy rates and combined rates of compliance with the ketogenic diet and its main subtypes. In total, 12 studies qualified for inclusion, and data from 270 patients were evaluated.The results of the meta-analysis revealed combined efficacy rates of all types of ketogenic diet, a classical ketogenic diet, and a modified Atkins diet were 42%, 52%, and 34%, respectively; the corresponding combined compliance rates were 45%, 38%, and 56%. The results indicate that a ketogenic diet is a promising complementary therapy in adult intractable epilepsy, and that while a classical ketogenic diet may be more effective, adult patients are likely to be less compliant with it than with a modified Atkins diet.

  12. Recommendations for the clinical management of children with refractory epilepsy receiving the ketogenic diet.

    Science.gov (United States)

    Alberti, María J; Agustinho, Ariela; Argumedo, Laura; Armeno, Marisa; Blanco, Virginia; Bouquet, Cecilia; Cabrera, Analía; Caraballo, Roberto; Caramuta, Luciana; Cresta, Araceli; de Grandis, Elizabeth S; De Martini, Martha G; Diez, Cecilia; Dlugoszewski, Corina; Escobal, Nidia; Ferrero, Hilario; Galicchio, Santiago; Gambarini, Victoria; Gamboni, Beatriz; Guisande, Silvina; Hassan, Amal; Matarrese, Pablo; Mestre, Graciela; Pesce, Laura; Ríos, Viviana; Sosa, Patricia; Vaccarezza, María; Viollaz, Rocío; Panico, Luis

    2016-02-01

    The ketogenic diet, a non-drug treatment with proven effectiveness, has been the most commonly used therapy in the past decade for the management of refractory epilepsy in the pediatric population. Compared to adding a new drug to a pre-existing treatment, the ketogenic diet is highly effective and reduces the number of seizures by 50-90% in approximately 45-60% of children after six months of treatment. For this reason, the Argentine Society of Pediatric Neurology established the Ketogenic Diet Working Group. It is integrated by pediatric dietitians, pediatricians, pediatric neurologists and B.S. in Nutrition, who developed recommendations for the optimal management of patients receiving the classical ketogenic diet based on expert consensus and scientific publications in this field. Sociedad Argentina de Pediatría.

  13. Effect of Combined Ketogenic Diet and Valproate Treatment for Intractable Seizures

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-09-01

    Full Text Available The safety and tolerability of ketogenic diet (KGD and valproate (VPA cotherapy in the treatment of intractable seizures were evaluated retrospectively at the Massachusetts General Hospital, Boston.

  14. Ketogenic Diet in Refractory Childhood Epilepsy: Starting With a Liquid Formulation in an Outpatient Setting.

    Science.gov (United States)

    Weijenberg, Amerins; van Rijn, Margreet; Callenbach, Petra M C; de Koning, Tom J; Brouwer, Oebele F

    2018-01-01

    Ketogenic diet in children with epilepsy has a considerable impact on daily life and is usually adopted for at least 3 months. Our aim was to evaluate whether the introduction of an all-liquid ketogenic diet in an outpatient setting is feasible, and if an earlier assessment of its efficacy can be achieved. The authors conducted a prospective, observational study in a consecutive group of children with refractory epilepsy aged 2 to 14 years indicated for ketogenic diet. Ketogenic diet was started as an all-liquid formulation of the classical ketogenic diet, KetoCal 4:1 LQ, taken orally or by tube. After 6 weeks, the liquid diet was converted into solid meals. The primary outcome parameter was time-to-response (>50% seizure reduction). Secondary outcome parameters were time to achieve stable ketosis, the number of children showing a positive response, and the retention rate at 26 weeks. Sixteen children were included. Four of them responded well with respect to seizure frequency, the median time-to-response was 14 days (range 7-28 days). The mean time to achieve stable ketosis was 7 days. The retention rate at 26 weeks was 50%. Of the 8 children who started this protocol orally fed, 6 completed it without requiring a nasogastric tube. Introduction of ketogenic diet with a liquid formulation can be accomplished in orally fed children without major complications. It allowed for fast and stable ketosis.

  15. The Anticonvulsant Effects of Ketogenic Diet on Epileptic Seizures and Potential Mechanisms.

    Science.gov (United States)

    Zhang, Yifan; Xu, Jingwei; Zhang, Kun; Yang, Wei; Li, Bingjin

    2018-01-01

    Epilepsy is a syndrome of brain dysfunction induced by the aberrant excitability of certain neurons. Despite advances in surgical technique and anti-epileptic drug in recent years, recurrent epileptic seizures remain intractable and lead to a serious morbidity in the world. The ketogenic diet refers to a high-fat, low-carbohydrate and adequate-protein diet. Currently, its beneficial effects on epileptic seizure reduction have been well established. However, the detailed mechanisms underlying the anti-epileptic effects of ketogenic diet are still poorly understood. In this article, the possible roles of ketogenic diet on epilepsy were discussed. Data was obtained from the websites including Web of Science, Medline, Pubmed, Scopus, based on these keywords: "Ketogenic diet" and "epilepsy". As shown in both clinical and basic studies, the therapeutic effects of ketogenic diet might involve neuronal metabolism, neurotransmitter function, neuronal membrane potential and neuron protection against ROS. In this review, we systematically reviewed the effects and possible mechanisms of ketogenic diet on epilepsy, which may optimize the therapeutic strategies against epilepsy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Dispersion durations of P-wave and QT interval in children treated with a ketogenic diet.

    Science.gov (United States)

    Doksöz, Önder; Güzel, Orkide; Yılmaz, Ünsal; Işgüder, Rana; Çeleğen, Kübra; Meşe, Timur

    2014-04-01

    Limited data are available on the effects of a ketogenic diet on dispersion duration of P-wave and QT-interval measures in children. We searched for the changes in these measures with serial electrocardiograms in patients treated with a ketogenic diet. Twenty-five drug-resistant patients with epilepsy treated with a ketogenic diet were enrolled in this study. Electrocardiography was performed in all patients before the beginning and at the sixth month after implementation of the ketogenic diet. Heart rate, maximum and minimum P-wave duration, P-wave dispersion, and maximum and minimum corrected QT interval and QT dispersion were manually measured from the 12-lead surface electrocardiogram. Minimum and maximum corrected QT and QT dispersion measurements showed nonsignificant increase at month 6 compared with baseline values. Other previously mentioned electrocardiogram parameters also showed no significant changes. A ketogenic diet of 6 months' duration has no significant effect on electrocardiogram parameters in children. Further studies with larger samples and longer duration of follow-up are needed to clarify the effects of ketogenic diet on P-wave dispersion and corrected QT and QT dispersion. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Intravenous ketogenic diet therapy for treatment of the acute stage of super-refractory status epilepticus in a pediatric patient.

    Science.gov (United States)

    Lin, Jainn-Jim; Lin, Kuang-Lin; Chan, Oi-Wa; Hsia, Shao-Hsuan; Wang, Huei-Shyong

    2015-04-01

    A ketogenic diet has been used successfully to treat intractable epilepsy. However, the role of early intravenous initiation of ketogenic diet in the acute phase of super-refractory status epilepticus is not well-described. An intravenous ketogenic diet was administered to a boy with super-refractory status epilepticus. At 24 hours after intravenous ketogenic diet, moderate ketosis appeared, and thiamylal was successfully weaned at 70 hours after admission. An intravenous ketogenic regimen led to subsequent ketosis and seizure control in a child with super-refractory status epilepticus. Early induction of ketosis may be a novel strategy to effectively treat super-refractory status epilepticus. Although there are few data regarding the early use of intravenous ketogenic diet in the treatment of super-refractory status epilepticus, it may be considered an alternative option. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Application of a ketogenic diet in children with autistic behavior: pilot study.

    NARCIS (Netherlands)

    Evangeliou, A.; Vlachonikolis, I.; Mihailidou, H.; Spilioti, M.; Skarpalezou, A.; Makaronas, N.; Prokopiou, A.; Christodoulou, P.; Liapi-Adamidou, G.; Helidonis, E.; Sbyrakis, S.; Smeitink, J.A.M.

    2003-01-01

    A pilot prospective follow-up study of the role of the ketogenic diet was carried out on 30 children, aged between 4 and 10 years, with autistic behavior. The diet was applied for 6 months, with continuous administration for 4 weeks, interrupted by 2-week diet-free intervals. Seven patients could

  19. Treatment of Diabetic Mice with a Combination of Ketogenic Diet and Aerobic Exercise via Modulations of PPARs Gene Programs

    Science.gov (United States)

    Xu, Lingyan; Xia, Jie; Wang, Dongmei; Qian, Min

    2018-01-01

    Type 2 diabetes is a prevalent chronic disease arising as a serious public health problem worldwide. Diet intervention is considered to be a critical strategy in glycemic control of diabetic patients. Recently, the low-carbohydrate ketogenic diet is shown to be effective in glycemic control and weight loss. However, hepatic lipid accumulation could be observed in mice treated with ketogenic diet. On the other hand, exercise is a well-known approach for treating nonalcoholic fatty liver disease. We thus hypothesize that the combination of ketogenic diet and exercise could improve insulin sensitivity, while minimizing adverse effect of hepatic steatosis. In order to test this hypothesis, we established diabetic mice model with streptozotocin (STZ) and divided them into control group, ketogenic diet group, and ketogenic diet with aerobic exercise group. We found that after six weeks of intervention, mice treated with ketogenic diet and ketogenic diet combined with exercise both have lower body weights, HbAlc level, HOMA index, and improvements in insulin sensitivity, compared with diabetes group. In addition, mice in ketogenic diet intervention exhibited hepatic steatosis shown by serum and hepatic parameters, as well as histochemistry staining in the liver, which could be largely relieved by exercise. Furthermore, gene analysis revealed that ketogenic diet in combination with exercise reduced PPARγ and lipid synthetic genes, as well as enhancing PPARα and lipid β-oxidation gene program in the liver compared to those in ketogenic diet without exercise. Overall, the present study demonstrated that the combination of ketogenic diet and a moderate-intensity aerobic exercise intervention improved insulin sensitivity in diabetic mice, while avoiding hepatic steatosis, which provided a novel strategy in the combat of diabetes. PMID:29743883

  20. Treatment of Diabetic Mice with a Combination of Ketogenic Diet and Aerobic Exercise via Modulations of PPARs Gene Programs.

    Science.gov (United States)

    Zhang, Qiang; Xu, Lingyan; Xia, Jie; Wang, Dongmei; Qian, Min; Ding, Shuzhe

    2018-01-01

    Type 2 diabetes is a prevalent chronic disease arising as a serious public health problem worldwide. Diet intervention is considered to be a critical strategy in glycemic control of diabetic patients. Recently, the low-carbohydrate ketogenic diet is shown to be effective in glycemic control and weight loss. However, hepatic lipid accumulation could be observed in mice treated with ketogenic diet. On the other hand, exercise is a well-known approach for treating nonalcoholic fatty liver disease. We thus hypothesize that the combination of ketogenic diet and exercise could improve insulin sensitivity, while minimizing adverse effect of hepatic steatosis. In order to test this hypothesis, we established diabetic mice model with streptozotocin (STZ) and divided them into control group, ketogenic diet group, and ketogenic diet with aerobic exercise group. We found that after six weeks of intervention, mice treated with ketogenic diet and ketogenic diet combined with exercise both have lower body weights, HbAlc level, HOMA index, and improvements in insulin sensitivity, compared with diabetes group. In addition, mice in ketogenic diet intervention exhibited hepatic steatosis shown by serum and hepatic parameters, as well as histochemistry staining in the liver, which could be largely relieved by exercise. Furthermore, gene analysis revealed that ketogenic diet in combination with exercise reduced PPAR γ and lipid synthetic genes, as well as enhancing PPAR α and lipid β -oxidation gene program in the liver compared to those in ketogenic diet without exercise. Overall, the present study demonstrated that the combination of ketogenic diet and a moderate-intensity aerobic exercise intervention improved insulin sensitivity in diabetic mice, while avoiding hepatic steatosis, which provided a novel strategy in the combat of diabetes.

  1. Ketogenic diet for high partial pressure oxygen diving.

    Science.gov (United States)

    Valadao, Jason M; Vigilante, John A; DiGeorge, Nicholas W; O'Connor, Sunila E; Bear, Alexandria; Kenyon, Jeffrey; Annis, Heather; Dituri, Joseph; Dituri, Amy E; Whelan, Harry T

    2014-01-01

    A ketogenic diet (KD) may decrease central nervous system oxygen toxicity symptoms in divers, and in view of this implication a feasibility/ toxicity pilot study was performed to demonstrate tolerance of KD while performing normal diving profiles. The exact mechanism of neuroprotection from the KD remains unknown; however, evidence to support the efficacy of the KD in reducing seizures is present in epilepsy and oxygen toxicity studies, and may provide valuable insight in diving activities. Three divers (two males and one female ages 32-45 with a history of deep diving and high pO2 exposure) on the KD made dives to varying depths in Hawaii using fully closed-circuit MK-15 and Inspiration rebreathers. These rebreathers have an electronically controlled set point, allowing the divers to monitor and control the oxygen level in the breathing loop, which can be varied manually by the divers. Oxygen level was varied during descent, bottom depth and ascent (decompression). Divers fasted for 12-18 hours before diet initiation. The ketosis level was verified by urinating on a Ketostix (reagent strips for urinalysis). Ketosis was achieved and was easily monitored with Ketostix in the simulated operational environment. The KD did not interfere with the diving mission; no seizure activity or signs or symptoms of CNS toxicity were observed, and there were no adverse effects noted by the divers while on the KD.

  2. Epilepsy Treatment Simplified through Mobile Ketogenic Diet Planning.

    Science.gov (United States)

    Li, Hanzhou; Jauregui, Jeffrey L; Fenton, Cagla; Chee, Claire M; Bergqvist, A G Christina

    2014-07-01

    The Ketogenic Diet (KD) is an effective, alternative treatment for refractory epilepsy. This high fat, low protein and carbohydrate diet mimics the metabolic and hormonal changes that are associated with fasting. To maximize the effectiveness of the KD, each meal is precisely planned, calculated, and weighed to within 0.1 gram for the average three-year duration of treatment. Managing the KD is time-consuming and may deter caretakers and patients from pursuing or continuing this treatment. Thus, we investigated methods of planning KD faster and making the process more portable through mobile applications. Nutritional data was gathered from the United States Department of Agriculture (USDA) Nutrient Database. User selected foods are converted into linear equations with n variables and three constraints: prescribed fat content, prescribed protein content, and prescribed carbohydrate content. Techniques are applied to derive the solutions to the underdetermined system depending on the number of foods chosen. The method was implemented on an iOS device and tested with varieties of foods and different number of foods selected. With each case, the application's constructed meal plan was within 95% precision of the KD requirements. In this study, we attempt to reduce the time needed to calculate a meal by automating the computation of the KD via a linear algebra model. We improve upon previous KD calculators by offering optimal suggestions and incorporating the USDA database. We believe this mobile application will help make the KD and other dietary treatment preparations less time consuming and more convenient.

  3. The nervous system and metabolic dysregulation: emerging evidence converges on ketogenic diet therapy

    Directory of Open Access Journals (Sweden)

    David N. Ruskin

    2012-03-01

    Full Text Available A link between metabolism and brain function is clear. Since ancient times, epileptic seizures were noted as treatable with fasting, and historical observations of the therapeutic benefits of fasting on epilepsy were confirmed nearly 100 years ago. Shortly thereafter a high-fat, low-carbohydrate ketogenic diet debuted as a therapy to reduce seizures. This strict regimen could mimic the metabolic effects of fasting while allowing adequate caloric intake for ongoing energy demands. Today, ketogenic diet therapy, which forces predominantly ketone-based rather than glucose-based metabolism, is now well-established as highly successful in reducing seizures. More recently, cellular metabolic dysfunction in the nervous system has been recognized as existing side-by-side with nervous system disorders - although often with much less obvious cause-and-effect as the relationship between fasting and seizures. Rekindled interest in metabolic and dietary therapies for brain disorders complements new insight into their mechanisms and broader implications. Here we describe the emerging relationship between a ketogenic diet and adenosine as a way to reset brain metabolism and neuronal activity and disrupt a cycle of dysfunction. We also provide an overview of the effects of a ketogenic diet on cognition and recent data on the effects of a ketogenic diet on pain, and explore the relative time course quantified among hallmark metabolic changes, altered neuron function and altered animal behavior assessed after diet administration. We predict continued applications of metabolic therapies in treating dysfunction including and beyond the nervous system.

  4. Epilepsy of infancy with migrating focal seizures: three patients treated with the ketogenic diet.

    Science.gov (United States)

    Caraballo, Roberto; Noli, Daniel; Cachia, Pedro

    2015-06-01

    We present three patients with epilepsy of infancy with migrating focal seizures treated with the ketogenic diet. Between February 1, 2012 and January 31, 2014, three patients who met the diagnostic criteria for migrating focal seizures in infancy at our department were placed on the ketogenic diet and followed for a minimum of seven months. Two of the three children responded well to the ketogenic diet. One of these patients became seizure-free and his neuropsychological performance also significantly improved. The other child had a seizure reduction of 75% to 99% with only weekly seizures and moderate psychomotor improvement. For these two patients who responded well to the ketogenic diet, hospital admission was not required. The remaining patient had a seizure reduction of less than 50%. Tolerability of the diet was good in all three patients. Early treatment with the ketogenic diet should be considered for epilepsy of infancy with migrating focal seizures to control seizures and status epilepticus, and avoid progressive cognitive impairment.

  5. Ketogenic diet prevents neuronal firing increase within the substantia nigra during pentylenetetrazole-induced seizure in rats.

    Science.gov (United States)

    Viggiano, Andrea; Stoddard, Madison; Pisano, Simone; Operto, Francesca Felicia; Iovane, Valentina; Monda, Marcellino; Coppola, Giangennaro

    2016-07-01

    The mechanism responsible for the anti-seizure effect of ketogenic diets is poorly understood. Because the substantia nigra pars reticulata (SNr) is a "gate" center for seizures, the aim of the present experiment was to evaluate if a ketogenic diet modifies the neuronal response of this nucleus when a seizure-inducing drug is administered in rats. Two groups of rats were given a standard diet (group 1) or a ketogenic diet (group 2) for four weeks, then the threshold for seizure induction and the firing rate of putative GABAergic neurons within the SNr were evaluated with progressive infusion of pentylenetetrazole under general anesthesia. The results demonstrated that the ketogenic diet abolished the correlation between the firing rate response of SNr-neurons and the seizure-threshold. This result suggests that the anti-seizure effect of ketogenic diets can be due to a decrease in reactivity of GABAergic SNr-neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain

    DEFF Research Database (Denmark)

    Lauritzen, Knut H.; Hasan-Olive, Md Mahdi; Regnell, Christine E.

    2016-01-01

    neurons. Here, we examine whether severe neurodegeneration in mutUNG1-expressing mice could be rescued by feeding the mice a ketogenic diet, which is known to have beneficial effects in several neurological disorders. The diet increased the levels of superoxide dismutase 2, and mitochondrial mass, enzymes......, and regulators such as SIRT1 and FIS1, and appeared to downregulate N-methyl-D-aspartic acid (NMDA) receptor subunits NR2A/B and upregulate γ-aminobutyric acid A (GABAA) receptor subunits α1. However, unexpectedly, the ketogenic diet aggravated neurodegeneration and mitochondrial deterioration. Electron...... microscopy showed structurally impaired mitochondria accumulating in neuronal perikarya. We propose that aggravation is caused by increased mitochondrial biogenesis of generally dysfunctional mitochondria. This study thereby questions the dogma that a ketogenic diet is unambiguously beneficial...

  7. How do you keto? Survey of North American pediatric ketogenic diet centers.

    Science.gov (United States)

    Jung, Da Eun; Joshi, Sucheta M; Berg, Anne T

    2015-06-01

    We surveyed ketogenic diet centers in North America about their practices surrounding the ketogenic diet. An internet survey was disseminated via REDCap(©) to North American ketogenic diet centers identified from the Charlie Foundation and Ketocal(©) websites. Fifty-six centers responded. In addition to physicians, nurses and dieticians, ketogenic teams included social workers (39%), feeding specialists (14%), educational liaisons (4%), psychologists (5%), and pharmacists (36%). A child attending school (2%), non-English speaking family (19%), single-parent family (0%), and oral feeding (6%) were rarely considered barriers. Overall, the diet was considered the first or second (0%), third or fourth (67%), fifth or sixth (29%), and last resort treatment (4%) by centers. It was considered the first or second treatment for GLUT1 disease (86%) and third or fourth for Dravet (63%), West (71%), and Doose (65%) syndromes. Ketogenic diet is no longer a last resort option. Traditional barriers do not influence its use. © The Author(s) 2014.

  8. [Efficacy of a ketogenic diet in urological cancers patients : A systematic review].

    Science.gov (United States)

    Maisch, P; Gschwend, J E; Retz, M

    2018-03-01

    Beside the classical anticancer treatment tumor patients try to find proactive alternative therapies to fight their disease. Lifestyle changes such as introducing a ketogenic diet is one of the most popular among them. The German Association of Urological Oncology (AUO, Arbeitsgemeinschaft Urologische Onkologie) presents a systematic review investigating the evidence of ketogenic diet in cancer patients. A systematic literature research was conducted in the databases Medline, Livivo, and the Cochrane Library. Only clinical studies of tumor patients receiving chemotherapy while on a ketogenic diet were included. The assessment of the results was performed according to the predefined primary endpoints overall survival and progression-free survival and secondary endpoints quality of life and reduction of adverse effects induced by cytostatics. Nine studies met the inclusion criteria: eight prospective and one retrospective study case series respectively cohort-studies, with a total of 107 patients. Currently there is no evidence of a therapeutic effect of a ketogenic diet in patients with malignant tumors regarding the clinical outcome or quality of life. Based on the current data, a ketogenic diet can not be recommended to cancer patients because prospective, randomized trials are missing.

  9. The use of a formula-based ketogenic diet in children with refractory epilepsy

    Directory of Open Access Journals (Sweden)

    Letícia Pereira de Brito Sampaio

    Full Text Available ABSTRACT The ketogenic diet (KD is a nonpharmacologic treatment that has been used for refractory epilepsy since 1921. The KD is a high-fat, low-carbohydrate, and restricted protein diet, which is calculated and weighed for each individual patient. Introducing and maintaining the diet for a long time remains a challenge. In this study, we evaluated the acceptability, tolerance, and efficacy of a formula-based KD in 10 children with refractory epilepsy. The ketogenic formula tested herein caused only mild KD-related adverse events and adequate adherence. Moreover, 60% of patients had more than 50% seizure frequency reduction and 10% were seizure-free.

  10. How Can a Ketogenic Diet Improve Motor Function?

    Directory of Open Access Journals (Sweden)

    Charlotte Veyrat-Durebex

    2018-01-01

    Full Text Available A ketogenic diet (KD is a normocaloric diet composed by high fat (80–90%, low carbohydrate, and low protein consumption that induces fasting-like effects. KD increases ketone body (KBs production and its concentration in the blood, providing the brain an alternative energy supply that enhances oxidative mitochondrial metabolism. In addition to its profound impact on neuro-metabolism and bioenergetics, the neuroprotective effect of specific polyunsaturated fatty acids and KBs involves pleiotropic mechanisms, such as the modulation of neuronal membrane excitability, inflammation, or reactive oxygen species production. KD is a therapy that has been used for almost a century to treat medically intractable epilepsy and has been increasingly explored in a number of neurological diseases. Motor function has also been shown to be improved by KD and/or medium-chain triglyceride diets in rodent models of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and spinal cord injury. These studies have proposed that KD may induce a modification in synaptic morphology and function, involving ionic channels, glutamatergic transmission, or synaptic vesicular cycling machinery. However, little is understood about the molecular mechanisms underlying the impact of KD on motor function and the perspectives of its use to acquire the neuromuscular effects. The aim of this review is to explore the conditions through which KD might improve motor function. First, we will describe the main consequences of KD exposure in tissues involved in motor function. Second, we will report and discuss the relevance of KD in pre-clinical and clinical trials in the major diseases presenting motor dysfunction.

  11. Efficacy of the Ketogenic Diet for the Treatment of Refractory Childhood Epilepsy: Cerebrospinal Fluid Neurotransmitters and Amino Acid Levels.

    Science.gov (United States)

    Sariego-Jamardo, Andrea; García-Cazorla, Angels; Artuch, Rafael; Castejón, Esperanza; García-Arenas, Dolores; Molero-Luis, Marta; Ormazábal, Aida; Sanmartí, Francesc Xavier

    2015-11-01

    The mechanisms of the ketogenic diet remain unclear, but several predictors of response have been proposed. We aimed is to study the relationship between the etiology of epilepsy, cerebrospinal fluid neurotransmitters, pterins, and amino acids, and response to a ketogenic diet. We studied 60 patients who began classic ketogenic diet treatment for refractory epilepsy. In 24 of 60 individuals, we analyzed cerebrospinal fluid neurotransmitters, pterins, and amino acids in baseline conditions. Mean age at epilepsy onset was 24 months, 83.3% were focal epilepsies, and in 51.7% the etiology of the epilepsy was unknown. Six months after initiating the ketogenic diet, it was effective (greater than a 50% reduction in seizure frequency) in 31.6% of patients. We did not find a link between rate of efficacy for the ketogenic diet and etiologies of epilepsy, nor did we find a link between the rate of efficacy for the ketogenic diet and cerebrospinal fluid pterins and biogenic amines concentrations. However, we found statistically significant differences for lysine and arginine values in the cerebrospinal fluid between ketogenic diet responders and nonresponders, but not for the other amino acids analyzed. The values of some amino acids were significantly different in relationship with the ketogenic diet efficacy; however, the epilepsy etiology and the cerebrospinal fluid biogenic amine and pterin values were not. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Ketogenic diet improves motor performance but not cognition in two mouse models of Alzheimer's pathology.

    Science.gov (United States)

    Brownlow, Milene L; Benner, Leif; D'Agostino, Dominic; Gordon, Marcia N; Morgan, Dave

    2013-01-01

    Dietary manipulations are increasingly viewed as possible approaches to treating neurodegenerative diseases. Previous studies suggest that Alzheimer's disease (AD) patients present an energy imbalance with brain hypometabolism and mitochondrial deficits. Ketogenic diets (KDs), widely investigated in the treatment and prevention of seizures, have been suggested to bypass metabolic deficits present in AD brain by providing ketone bodies as an alternative fuel to neurons. We investigated the effects of a ketogenic diet in two transgenic mouse lines. Five months old APP/PS1 (a model of amyloid deposition) and Tg4510 (a model of tau deposition) mice were offered either a ketogenic or a control (NIH-31) diet for 3 months. Body weight and food intake were monitored throughout the experiment, and blood was collected at 4 weeks and 4 months for ketone and glucose assessments. Both lines of transgenic mice weighed less than nontransgenic mice, yet, surprisingly, had elevated food intake. The ketogenic diet did not affect these differences in body weight or food consumption. Behavioral testing during the last two weeks of treatment found that mice offered KD performed significantly better on the rotarod compared to mice on the control diet independent of genotype. In the open field test, both transgenic mouse lines presented increased locomotor activity compared to nontransgenic, age-matched controls, and this effect was not influenced by KD. The radial arm water maze identified learning deficits in both transgenic lines with no significant differences between diets. Tissue measures of amyloid, tau, astroglial and microglial markers in transgenic lines showed no differences between animals fed the control or the ketogenic diet. These data suggest that ketogenic diets may play an important role in enhancing motor performance in mice, but have minimal impact on the phenotype of murine models of amyloid or tau deposition.

  13. Ketogenic diet improves motor performance but not cognition in two mouse models of Alzheimer's pathology.

    Directory of Open Access Journals (Sweden)

    Milene L Brownlow

    Full Text Available Dietary manipulations are increasingly viewed as possible approaches to treating neurodegenerative diseases. Previous studies suggest that Alzheimer's disease (AD patients present an energy imbalance with brain hypometabolism and mitochondrial deficits. Ketogenic diets (KDs, widely investigated in the treatment and prevention of seizures, have been suggested to bypass metabolic deficits present in AD brain by providing ketone bodies as an alternative fuel to neurons. We investigated the effects of a ketogenic diet in two transgenic mouse lines. Five months old APP/PS1 (a model of amyloid deposition and Tg4510 (a model of tau deposition mice were offered either a ketogenic or a control (NIH-31 diet for 3 months. Body weight and food intake were monitored throughout the experiment, and blood was collected at 4 weeks and 4 months for ketone and glucose assessments. Both lines of transgenic mice weighed less than nontransgenic mice, yet, surprisingly, had elevated food intake. The ketogenic diet did not affect these differences in body weight or food consumption. Behavioral testing during the last two weeks of treatment found that mice offered KD performed significantly better on the rotarod compared to mice on the control diet independent of genotype. In the open field test, both transgenic mouse lines presented increased locomotor activity compared to nontransgenic, age-matched controls, and this effect was not influenced by KD. The radial arm water maze identified learning deficits in both transgenic lines with no significant differences between diets. Tissue measures of amyloid, tau, astroglial and microglial markers in transgenic lines showed no differences between animals fed the control or the ketogenic diet. These data suggest that ketogenic diets may play an important role in enhancing motor performance in mice, but have minimal impact on the phenotype of murine models of amyloid or tau deposition.

  14. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report

    Directory of Open Access Journals (Sweden)

    Servadei Franco

    2010-04-01

    Full Text Available Abstract Background Management of glioblastoma multiforme (GBM has been difficult using standard therapy (radiation with temozolomide chemotherapy. The ketogenic diet is used commonly to treat refractory epilepsy in children and, when administered in restricted amounts, can also target energy metabolism in brain tumors. We report the case of a 65-year-old woman who presented with progressive memory loss, chronic headaches, nausea, and a right hemisphere multi-centric tumor seen with magnetic resonance imaging (MRI. Following incomplete surgical resection, the patient was diagnosed with glioblastoma multiforme expressing hypermethylation of the MGMT gene promoter. Methods Prior to initiation of the standard therapy, the patient conducted water-only therapeutic fasting and a restricted 4:1 (fat: carbohydrate + protein ketogenic diet that delivered about 600 kcal/day. The patient also received the restricted ketogenic diet concomitantly during the standard treatment period. The diet was supplemented with vitamins and minerals. Steroid medication (dexamethasone was removed during the course of the treatment. The patient was followed using MRI and positron emission tomography with fluoro-deoxy-glucose (FDG-PET. Results After two months treatment, the patient's body weight was reduced by about 20% and no discernable brain tumor tissue was detected using either FDG-PET or MRI imaging. Biomarker changes showed reduced levels of blood glucose and elevated levels of urinary ketones. MRI evidence of tumor recurrence was found 10 weeks after suspension of strict diet therapy. Conclusion This is the first report of confirmed GBM treated with standard therapy together with a restricted ketogenic diet. As rapid regression of GBM is rare in older patients following incomplete surgical resection and standard therapy alone, the response observed in this case could result in part from the action of the calorie restricted ketogenic diet. Further studies are needed

  15. Ketogenic diet effects on cognition, mood, and psychosocial adjustment in children

    NARCIS (Netherlands)

    Lambrechts, D.A.; Bovens, M.J.; Parra, de la N.; Hendriksen, J.G.M.; Aldenkamp, A.P.; Majoie, H.J.M.

    2013-01-01

    Introduction The ketogenic diet (KD) is increasingly used for the treatment of refractory epilepsy. The aim of this study was to evaluate possible adverse effects of the diet on cognition, behavior, psychosocial adjustment, and quality of life in school-aged children and adolescents. Method Fifteen

  16. Neuroactive peptides as putative mediators of antiepileptic ketogenic diets

    Directory of Open Access Journals (Sweden)

    Carmela eGiordano

    2014-04-01

    Full Text Available Various ketogenic diet (KD therapies, including classic KD, medium chain triglyceride administration, low glycemic index treatment, and a modified Atkins diet, have been suggested as useful in patients affected by pharmacoresistant epilepsy. A common goal of these approaches is to achieve an adequate decrease in the plasma glucose level combined with ketogenesis, in order to mimic the metabolic state of fasting. Although several metabolic hypotheses have been advanced to explain the anticonvulsant effect of KDs, including changes in the plasma levels of ketone bodies, polyunsaturated fatty acids, and brain pH, direct modulation of neurotransmitter release, especially purinergic (i.e., adenosine and γ-aminobutyric acidergic neurotransmission, was also postulated. Neuropeptides and peptide hormones are potent modulators of synaptic activity, and their levels are regulated by metabolic states. This is the case for neuroactive peptides such as neuropeptide Y, galanin, cholecystokinin and peptide hormones such as leptin, adiponectin, and growth hormone-releasing peptides (GHRPs. In particular, the GHRP ghrelin and its related peptide des-acyl ghrelin are well-known controllers of energy homeostasis, food intake, and lipid metabolism. Notably, ghrelin has also been shown to regulate the neuronal excitability and epileptic activation of neuronal networks. Several lines of evidence suggest that GHRPs are upregulated in response to starvation and, particularly, in patients affected by anorexia and cachexia, all conditions in which also ketone bodies are upregulated. Moreover, starvation and anorexia nervosa are accompanied by changes in other peptide hormones such as adiponectin, which has received less attention. Adipocytokines such as adiponectin have also been involved in modulating epileptic activity. Thus, neuroactive peptides whose plasma levels and activity change in the presence of ketogenesis might be potential candidates for elucidating the

  17. Ketogenic diet therapy for epilepsy during pregnancy: A case series.

    Science.gov (United States)

    van der Louw, Elles J T M; Williams, Tanya J; Henry-Barron, Bobbie J; Olieman, Joanne F; Duvekot, Johannes J; Vermeulen, Marijn J; Bannink, Natalja; Williams, Monique; Neuteboom, Rinze F; Kossoff, Eric H; Catsman-Berrevoets, Coriene E; Cervenka, Mackenzie C

    2017-02-01

    Evaluation of ketogenic diet (KD) therapies for seizure control during pregnancy when safety and appropriate management become considerations. Until now, no information has been available on seizure reduction and human pregnancy related outcomes in women treated with KD therapies. We describe two cases of pregnant women with epilepsy treated with KD therapy either as monotherapy (Case 1) or as adjunctive therapy (Case 2). Case 1: A 27 year old woman, gravida1, started the classic KD with medium chain triglyceride (MCT) emulsion and 75g carbohydrate-restriction, later reduced to 47g. Glucose levels were 4-6mmol/L and blood ketone levels ranged from 0.2 to 1.4mmol/L. Seizure frequency decreased and seizure-free days increased. Mild side effects included intolerance to MCT, reduced serum carnitine and vitamin levels, and mild hyperlipidemia. Fetal and neonatal growth was normal as was growth and development at 12 months. Case 2: A 36 year-old nulliparous woman was treated with a 20 gram carbohydrate-restricted Modified Atkins Diet (MAD) and lamotrigine, resulting in reduction of seizure frequency to once per month prior to pregnancy. Once pregnant, carbohydrates were increased to 30g. When seizures increased, lamotrigine dose was doubled. Urine ketones trended down during second trimester. A male was born with bilateral ear deformities of unknown significance. The child had a normal neurodevelopment at eight months. Non-pharmacological epilepsy therapies like KD and MAD may be effective during human pregnancy. However, safety still has to be established. Further monitoring to identify potential long term side effects is warranted. Copyright © 2017 British Epilepsy Association. All rights reserved.

  18. Substantial and sustained seizure reduction with ketogenic diet in a patient with Ohtahara syndrome

    Directory of Open Access Journals (Sweden)

    Adithya Sivaraju

    2015-01-01

    Full Text Available Ketogenic diet has been shown to be efficacious in some epileptic encephalopathies but rarely reported as being useful in children with Ohtahara syndrome. This could possibly be attributed to the rarity of the disease and associated short survival period. We report on a 5-year-old child with Ohtahara syndrome, whose seizures failed to improve with all known medications, continued to show persistent suppression-burst pattern on the electroencephalography (EEG and had substantial reduction in seizure frequency for one year post-initiation of ketogenic diet. He has not had a single visit to the emergency room because of seizures in the last one year, and more importantly, there has been a clear improvement noted in his level of interaction and temperament. Patients with Ohtahara syndrome invariably have medically intractable seizures and catastrophic neurodevelopmental outcome. Ketogenic diet is a treatment modality that might be worth considering even in this group of patients.

  19. Early efficacy of the ketogenic diet is not affected by initial body mass index percentile.

    Science.gov (United States)

    Shull, Shastin; Diaz-Medina, Gloria; Wong-Kisiel, Lily; Nickels, Katherine; Eckert, Susan; Wirrell, Elaine

    2014-05-01

    Predictors of the ketogenic diet's success in treating pediatric intractable epilepsy are not well understood. The aim of this study was to determine whether initial body mass index and weight percentile impact early efficacy of the traditional ketogenic diet in children initiating therapy for intractable epilepsy. This retrospective study included all children initiating the ketogenic diet at Mayo Clinic, Rochester from January 2001 to December 2010 who had body mass index (children ≥2 years of age) or weight percentile (those diet initiation and seizure frequency recorded at diet initiation and one month. Responders were defined as achieving a >50% seizure reduction from baseline. Our cohort consisted of 48 patients (20 male) with a median age of 3.1 years. There was no significant correlation between initial body mass index or weight percentile and seizure frequency reduction at one month (P = 0.72, r = 0.26 and P = 0.91, r = 0.03). There was no significant association between body mass index or weight percentile quartile and responder rates (P = 0.21 and P = 0.57). Children considered overweight or obese at diet initiation (body mass index or weight percentile ≥85) did not have lower responder rates than those with body mass index or weight percentiles ketogenic diet. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders.

    Science.gov (United States)

    Augustin, Katrin; Khabbush, Aziza; Williams, Sophie; Eaton, Simon; Orford, Michael; Cross, J Helen; Heales, Simon J R; Walker, Matthew C; Williams, Robin S B

    2018-01-01

    High-fat, low-carbohydrate diets, known as ketogenic diets, have been used as a non-pharmacological treatment for refractory epilepsy. A key mechanism of this treatment is thought to be the generation of ketones, which provide brain cells (neurons and astrocytes) with an energy source that is more efficient than glucose, resulting in beneficial downstream metabolic changes, such as increasing adenosine levels, which might have effects on seizure control. However, some studies have challenged the central role of ketones because medium-chain fatty acids, which are part of a commonly used variation of the diet (the medium-chain triglyceride ketogenic diet), have been shown to directly inhibit AMPA receptors (glutamate receptors), and to change cell energetics through mitochondrial biogenesis. Through these mechanisms, medium-chain fatty acids rather than ketones are likely to block seizure onset and raise seizure threshold. The mechanisms underlying the ketogenic diet might also have roles in other disorders, such as preventing neurodegeneration in Alzheimer's disease, the proliferation and spread of cancer, and insulin resistance in type 2 diabetes. Analysing medium-chain fatty acids in future ketogenic diet studies will provide further insights into their importance in modified forms of the diet. Moreover, the results of these studies could facilitate the development of new pharmacological and dietary therapies for epilepsy and other disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Mithu Storoni

    2015-01-01

    Full Text Available Until recently, multiple sclerosis has been viewed as an entirely inflammatory disease without acknowledgment of the significant neurodegenerative component responsible for disease progression and disability. This perspective is being challenged by observations of a dissociation between inflammation and neurodegeneration where the neurodegenerative component may play a more significant role in disease progression. In this review, we explore the relationship between mitochondrial dysfunction and neurodegeneration in multiple sclerosis. We review evidence that the ketogenic diet can improve mitochondrial function and discuss the potential of the ketogenic diet in treating progressive multiple sclerosis for which no treatment currently exists.

  2. Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice.

    Science.gov (United States)

    Newman, John C; Covarrubias, Anthony J; Zhao, Minghao; Yu, Xinxing; Gut, Philipp; Ng, Che-Ping; Huang, Yu; Haldar, Saptarsi; Verdin, Eric

    2017-09-05

    Ketogenic diets recapitulate certain metabolic aspects of dietary restriction such as reliance on fatty acid metabolism and production of ketone bodies. We investigated whether an isoprotein ketogenic diet (KD) might, like dietary restriction, affect longevity and healthspan in C57BL/6 male mice. We find that Cyclic KD, KD alternated weekly with the Control diet to prevent obesity, reduces midlife mortality but does not affect maximum lifespan. A non-ketogenic high-fat diet (HF) fed similarly may have an intermediate effect on mortality. Cyclic KD improves memory performance in old age, while modestly improving composite healthspan measures. Gene expression analysis identifies downregulation of insulin, protein synthesis, and fatty acid synthesis pathways as mechanisms common to KD and HF. However, upregulation of PPARα target genes is unique to KD, consistent across tissues, and preserved in old age. In all, we show that a non-obesogenic ketogenic diet improves survival, memory, and healthspan in aging mice. Published by Elsevier Inc.

  3. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets

    Science.gov (United States)

    Paoli, A; Rubini, A; Volek, J S; Grimaldi, K A

    2013-01-01

    Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand. PMID:23801097

  4. Ten-year single-center experience of the ketogenic diet: factors influencing efficacy, tolerability, and compliance.

    Science.gov (United States)

    Wibisono, Cinthya; Rowe, Natalie; Beavis, Erin; Kepreotes, Helen; Mackie, Fiona E; Lawson, John A; Cardamone, Michael

    2015-04-01

    To evaluate the efficacy, tolerability, and compliance of 3 ketogenic diets, the classical ketogenic diet, medium-chain triglyceride (MCT), and modified Atkins diet. A single-center, retrospective study of 48 children with intractable epilepsy receiving ketogenic diets from 2003 to 2012. Patient demographics, epilepsy history, nutritional management, and side effects were collated. Compliance and tolerability were assessed by recording reasons for diet modification and cessation. The value of potassium citrate supplementation for preventing nephrolithiasis was reviewed. Median age at ketogenic diet initiation was 3.8 years (IQR: 2.3-7 years). The majority had intractable epilepsy, and 33 of the 48 children (69%) had epileptic encephalopathies. Three (6%) patients became seizure free, 35 (73%) reported Diet duration or ketogenic diet type did not predict reduction in seizures (P = .381; P = .272). Constipation (n = 31, 65%) was very common. Food refusal (n = 3, 6%) and poor parental compliance (n = 5, 10%) were common reasons cited for cessation. There were lower rates of side effects for modified Atkins diet. Diet cessation was greatest for MCT; however, 3 patients on MCT ceased therapy because adequate seizure control was achieved. Nephrolithiasis was reported in 1 patient before potassium citrate was used and 2 patients noncompliant with potassium citrate supplementation developed hypercalciuria. The 3 ketogenic diets were comparably effective in seizure control and generally well-tolerated. Potassium citrate supplementation is an effective prophylactic supplement for the prevention of nephrolithiasis. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  5. Biochemical phenotyping unravels novel metabolic abnormalities and potential biomarkers associated with treatment of GLUT1 deficiency with ketogenic diet.

    Science.gov (United States)

    Cappuccio, Gerarda; Pinelli, Michele; Alagia, Marianna; Donti, Taraka; Day-Salvatore, Debra-Lynn; Veggiotti, Pierangelo; De Giorgis, Valentina; Lunghi, Simona; Vari, Maria Stella; Striano, Pasquale; Brunetti-Pierri, Nicola; Kennedy, Adam D; Elsea, Sarah H

    2017-01-01

    Global metabolomic profiling offers novel opportunities for the discovery of biomarkers and for the elucidation of pathogenic mechanisms that might lead to the development of novel therapies. GLUT1 deficiency syndrome (GLUT1-DS) is an inborn error of metabolism due to reduced function of glucose transporter type 1. Clinical presentation of GLUT1-DS is heterogeneous and the disorder mirrors patients with epilepsy, movement disorders, or any paroxysmal events or unexplained neurological manifestation triggered by exercise or fasting. The diagnostic biochemical hallmark of the disease is a reduced cerebrospinal fluid (CSF)/blood glucose ratio and the only available treatment is ketogenic diet. This study aimed at advancing our understanding of the biochemical perturbations in GLUT1-DS pathogenesis through biochemical phenotyping and the treatment of GLUT1-DS with a ketogenic diet. Metabolomic analysis of three CSF samples from GLUT1-DS patients not on ketogenic diet was feasible inasmuch as CSF sampling was used for diagnosis before to start with ketogenic diet. The analysis of plasma and urine samples obtained from GLUT1-DS patients treated with a ketogenic diet showed alterations in lipid and amino acid profiles. While subtle, these were consistent findings across the patients with GLUT1-DS on ketogenic diet, suggesting impacts on mitochondrial physiology. Moreover, low levels of free carnitine were present suggesting its consumption in GLUT1-DS on ketogenic diet. 3-hydroxybutyrate, 3-hydroxybutyrylcarnitine, 3-methyladipate, and N-acetylglycine were identified as potential biomarkers of GLUT1-DS on ketogenic diet. This is the first study to identify CSF, plasma, and urine metabolites associated with GLUT1-DS, as well as biochemical changes impacted by a ketogenic diet. Potential biomarkers and metabolic insights deserve further investigation.

  6. Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies

    Science.gov (United States)

    Kosinski, Christophe; Jornayvaz, François R.

    2017-01-01

    The treatment of obesity and cardiovascular diseases is one of the most difficult and important challenges nowadays. Weight loss is frequently offered as a therapy and is aimed at improving some of the components of the metabolic syndrome. Among various diets, ketogenic diets, which are very low in carbohydrates and usually high in fats and/or proteins, have gained in popularity. Results regarding the impact of such diets on cardiovascular risk factors are controversial, both in animals and humans, but some improvements notably in obesity and type 2 diabetes have been described. Unfortunately, these effects seem to be limited in time. Moreover, these diets are not totally safe and can be associated with some adverse events. Notably, in rodents, development of nonalcoholic fatty liver disease (NAFLD) and insulin resistance have been described. The aim of this review is to discuss the role of ketogenic diets on different cardiovascular risk factors in both animals and humans based on available evidence. PMID:28534852

  7. Concomitant lamotrigine use is associated with decreased efficacy of the ketogenic diet in childhood refractory epilepsy

    NARCIS (Netherlands)

    E.J.T.M. van der Louw (Elles); Desadien, R. (Raakhee); F.O.L. Vehmeijer (Florianne O.L.); I.H. van der Sijs (Heleen); C.E. Catsman-Berrevoets (Coriene); R.F. Neuteboom (Rinze)

    2015-01-01

    textabstractPurpose Anti-epileptic drugs (AEDs) and the ketogenic diet (KD) are often used concomitantly in children with refractory epilepsy. It has been hypothesised that certain AEDs may interfere with KD. The purpose of this study was to elucidate relationships between efficacy of KD and use of

  8. A randomized controlled trial of the ketogenic diet in refractory childhood epilepsy

    NARCIS (Netherlands)

    Lambrechts, D.A.J.E.; de Kinderen, R.J.A.; Vles, J.S.H.; de Louw, A.J.A.; Aldenkamp, A.P.; Majoie, H.J.M.

    2017-01-01

    Objective: To evaluate the efficacy and tolerability of the ketogenic diet (KD) during the first 4 months of a randomized controlled trial (RCT) in refractory epilepsy patients aged 1–18 years. Methods: Children and adolescents with refractory epilepsy, not eligible for epilepsy surgery, were

  9. The Short-Term Effects of Ketogenic Diet on Cardiac Ventricular Functions in Epileptic Children.

    Science.gov (United States)

    Doksöz, Önder; Çeleğen, Kübra; Güzel, Orkide; Yılmaz, Ünsal; Uysal, Utku; İşgüder, Rana; Çeleğen, Mehmet; Meşe, Timur

    2015-09-01

    Our primary aim was to determine the short-term effects of a ketogenic diet on cardiac ventricular function in patients with refractory epilepsy. Thirty-eight drug-resistant epileptic patients who were treated with a ketogenic diet were enrolled in this prospective study. Echocardiography was performed on all patients before beginning the ketogenic diet and after the sixth month of therapy. Two-dimensional, M-mode, color flow, spectral Doppler, and pulsed-wave tissue Doppler imaging measurements were performed on all patients. The median age of the 32 patients was 45.5 months, and 22 (57.8%) of them were male. Body weight, height, and body mass index increased significantly at the sixth month of therapy when compared with baseline values (P 0.05). Doppler flow indices of mitral annulus and tricuspid annulus velocity of patients at baseline and month 6 showed no significant differences (P > 0.05). Tricuspid annular E/A ratio was lower at month 6 (P 0.05), there was a decrease in Ea velocity and Ea/Aa ratio gathered from tricuspid annulus at month 6 compared with baseline (P ketogenic diet does not impair left ventricular functions in children with refractory epilepsy; however, it may be associated with a right ventricular diastolic dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. The Ketogenic Diet Does Not Affect Growth of Hedgehog Pathway Medulloblastoma in Mice

    Science.gov (United States)

    Dang, Mai T.; Wehrli, Suzanne; Dang, Chi V.; Curran, Tom

    2015-01-01

    The altered metabolism of cancer cells has long been viewed as a potential target for therapeutic intervention. In particular, brain tumors often display heightened glycolysis, even in the presence of oxygen. A subset of medulloblastoma, the most prevalent malignant brain tumor in children, arises as a consequence of activating mutations in the Hedgehog (HH) pathway, which has been shown to promote aerobic glycolysis. Therefore, we hypothesized that a low carbohydrate, high fat ketogenic diet would suppress tumor growth in a genetically engineered mouse model of medulloblastoma. However, we found that the ketogenic diet did not slow the growth of spontaneous tumors or allograft flank tumors, and it did not exhibit synergy with a small molecule inhibitor of Smoothened. Serum insulin was significantly reduced in mice fed the ketogenic diet, but no alteration in PI3 kinase activity was observed. These findings indicate that while the ketogenic diet may be effective in inhibiting growth of other tumor types, it does not slow the growth of HH-medulloblastoma in mice. PMID:26192445

  11. The ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies.

    Science.gov (United States)

    Ville, Dorothée; Chiron, Catherine; Laschet, Jacques; Dulac, Olivier

    2015-07-01

    Hormonal therapy or ketogenic diet often permits overcoming the challenging periods of many epileptic encephalopathies (West and Lennox-Gastaut syndromes and encephalopathy with continuous spike-waves in slow sleep), but relapse affects over 20% of patients. We report here a monocenter pilot series of 42 consecutive patients in whom we combined oral steroids with the ketogenic diet for corticosteroid-resistant or -dependent epileptic encephalopathy. We retrospectively evaluated the effect on seizure frequency, interictal spike activity, neuropsychological course, and steroid treatment course. Twenty-three patients had West syndrome (WS), 13 had encephalopathy with continuous spike-waves in slow sleep (CSWS), and six others had miscellaneous epileptic encephalopathies. All patients succeeded to reach 0.8 to 1.6g/l ketone bodies in the urine following the usual KD regimen. For at least 6 months, 14/42 responded to the addition of the ketogenic diet: 4/23 with WS, 8/13 with CSWS, and 2/6 with miscellaneous epileptic encephalopathies. The addition of the KD allowed withdrawing steroids in all responders. Among them, 10/15 had been patients with steroid-dependent epileptic encephalopathy and 4/27 patients with steroid-resistant epileptic encephalopathy. Therefore, the ketogenic diet can be used successfully in combination with corticosteroids for epileptic encephalopathies. Patients presenting with steroid-dependent CSWS seem to be the best candidates. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Therapeutic Success of the Ketogenic Diet as a Treatment Option for Epilepsy: a Meta-analysis

    Science.gov (United States)

    Li, Hai-feng; Zou, Yan; Ding, Gangqiang

    2013-01-01

    Objective To systematically evaluate therapeutic success of the ketogenic diet (KD) as a treatment option for epilepsy. Methods Using MEDLINE and Google Scholar search, we searched for studies investigating the therapeutic success of ketogenic diet for epilepsy. We estimated therapeutic success rate for ketogenic diet as a treatment option for epilepsy and its 95% CIs using generic inverse variance method. Findings A total of 38 studies met the inclusion criteria. In retrospective studies, the weighted success rate of the patients who take the KD as a treatment option for epilepsy was 58.4% (95% confidence interval (95%CI)=48.7% – 69.9%) at 3 months (n=336); 42.8% (95%CI =36.3% – 50.3%) at 6 months (n=492), and 30.1% (95%CI =24.3% – 37.2%) at 12 months (n=387); in prospective studies, weighted success rate was 53.9% (95%CI 45.5% – 63.8%) at 3 months (n=474); 53.2% (95%CI =44.0% – 64.2%) at 6 months (n=321), and 55.0% (95%CI =45.9% – 65.9%) at 12 months (n=347). Conclusion This meta-analysis provides formal statistical support for the efficacy of the ketogenic diet in the treatment of epileptic patients. PMID:24910737

  13. Ketogenic diet in pyruvate dehydrogenase complex deficiency: short- and long-term outcomes.

    Science.gov (United States)

    Sofou, Kalliopi; Dahlin, Maria; Hallböök, Tove; Lindefeldt, Marie; Viggedal, Gerd; Darin, Niklas

    2017-03-01

    Our aime was to study the short- and long-term effects of ketogenic diet on the disease course and disease-related outcomes in patients with pyruvate dehydrogenase complex deficiency, the metabolic factors implicated in treatment outcomes, and potential safety and compliance issues. Pediatric patients diagnosed with pyruvate dehydrogenase complex deficiency in Sweden and treated with ketogenic diet were evaluated. Study assessments at specific time points included developmental and neurocognitive testing, patient log books, and investigator and parental questionnaires. A systematic literature review was also performed. Nineteen patients were assessed, the majority having prenatal disease onset. Patients were treated with ketogenic diet for a median of 2.9 years. All patients alive at the time of data registration at a median age of 6 years. The treatment had a positive effect mainly in the areas of epilepsy, ataxia, sleep disturbance, speech/language development, social functioning, and frequency of hospitalizations. It was also safe-except in one patient who discontinued because of acute pancreatitis. The median plasma concentration of ketone bodies (3-hydroxybutyric acid) was 3.3 mmol/l. Poor dietary compliance was associated with relapsing ataxia and stagnation of motor and neurocognitive development. Results of neurocognitive testing are reported for 12 of 19 patients. Ketogenic diet was an effective and safe treatment for the majority of patients. Treatment effect was mainly determined by disease phenotype and attainment and maintenance of ketosis.

  14. The Ketogenic Diet Does Not Affect Growth of Hedgehog Pathway Medulloblastoma in Mice.

    Directory of Open Access Journals (Sweden)

    Mai T Dang

    Full Text Available The altered metabolism of cancer cells has long been viewed as a potential target for therapeutic intervention. In particular, brain tumors often display heightened glycolysis, even in the presence of oxygen. A subset of medulloblastoma, the most prevalent malignant brain tumor in children, arises as a consequence of activating mutations in the Hedgehog (HH pathway, which has been shown to promote aerobic glycolysis. Therefore, we hypothesized that a low carbohydrate, high fat ketogenic diet would suppress tumor growth in a genetically engineered mouse model of medulloblastoma. However, we found that the ketogenic diet did not slow the growth of spontaneous tumors or allograft flank tumors, and it did not exhibit synergy with a small molecule inhibitor of Smoothened. Serum insulin was significantly reduced in mice fed the ketogenic diet, but no alteration in PI3 kinase activity was observed. These findings indicate that while the ketogenic diet may be effective in inhibiting growth of other tumor types, it does not slow the growth of HH-medulloblastoma in mice.

  15. Treatment of Diabetic Mice with a Combination of Ketogenic Diet and Aerobic Exercise via Modulations of PPARs Gene Programs

    OpenAIRE

    Zhang, Qiang; Xu, Lingyan; Xia, Jie; Wang, Dongmei; Qian, Min; Ding, Shuzhe

    2018-01-01

    Type 2 diabetes is a prevalent chronic disease arising as a serious public health problem worldwide. Diet intervention is considered to be a critical strategy in glycemic control of diabetic patients. Recently, the low-carbohydrate ketogenic diet is shown to be effective in glycemic control and weight loss. However, hepatic lipid accumulation could be observed in mice treated with ketogenic diet. On the other hand, exercise is a well-known approach for treating nonalcoholic fatty liver diseas...

  16. Ketogenic diets improve behaviors associated with autism spectrum disorder in a sex-specific manner in the EL mouse.

    Science.gov (United States)

    Ruskin, David N; Fortin, Jessica A; Bisnauth, Subrina N; Masino, Susan A

    2017-01-01

    The core symptoms of autism spectrum disorder are poorly treated with current medications. Symptoms of autism spectrum disorder are frequently comorbid with a diagnosis of epilepsy and vice versa. Medically-supervised ketogenic diets are remarkably effective nonpharmacological treatments for epilepsy, even in drug-refractory cases. There is accumulating evidence that supports the efficacy of ketogenic diets in treating the core symptoms of autism spectrum disorders in animal models as well as limited reports of benefits in patients. This study tests the behavioral effects of ketogenic diet feeding in the EL mouse, a model with behavioral characteristics of autism spectrum disorder and comorbid epilepsy. Male and female EL mice were fed control diet or one of two ketogenic diet formulas ad libitum starting at 5weeks of age. Beginning at 8weeks of age, diet protocols continued and performance of each group on tests of sociability and repetitive behavior was assessed. A ketogenic diet improved behavioral characteristics of autism spectrum disorder in a sex- and test-specific manner; ketogenic diet never worsened relevant behaviors. Ketogenic diet feeding improved multiple measures of sociability and reduced repetitive behavior in female mice, with limited effects in males. Additional experiments in female mice showed that a less strict, more clinically-relevant diet formula was equally effective in improving sociability and reducing repetitive behavior. Taken together these results add to the growing number of studies suggesting that ketogenic and related diets may provide significant relief from the core symptoms of autism spectrum disorder, and suggest that in some cases there may be increased efficacy in females. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Medium-chain Triglyceride Ketogenic Diet, An Effective Treatment for Drug-resistant Epilepsy and A Comparison with Other Ketogenic Diets

    Directory of Open Access Journals (Sweden)

    Yeou-mei Christiana Liu

    2013-02-01

    Full Text Available The ketogenic diet (KD is one of the most effective therapies for drug-resistant epilepsy. The efficacy of the medium-chain triglyceride KD (MCTKD is as excellent as the classic KD (CKD, which has been documented in several subsequent retrospective, prospective, and randomized studies. MCT oil is more ketogenic than long-chain triglycerides. Therefore, the MCTKD allows more carbohydrate and protein food, which makes the diet more palatable than the CKD. The MCTKD is not based on diet ratios as is the CKD, but uses a percentage of calories from MCT oil to create ketones. There has also been literature which documents the associated gastrointestinal side effects from the MCTKD, such as diarrhea, vomiting, bloating, and cramps. Therefore, the MCTKD has been an underutilized diet therapy for intractable epilepsy among children.The author has used up to >70% MCTKD diet to maximize seizure control with gastrointestinal side effects optimally controlled. As long as health care professionals carefully manage MCTKD, many more patients with epilepsy who are not appropriate for CKD or modified Atkins diet or low glycemic index treatment will benefit from this treatment. A comparison between the MCTKD and other KDs is also discussed.

  18. Effects of Twenty Days of the Ketogenic Diet on Metabolic and Respiratory Parameters in Healthy Subjects.

    Science.gov (United States)

    Rubini, Alessandro; Bosco, Gerardo; Lodi, Alessandra; Cenci, Lorenzo; Parmagnani, Andrea; Grimaldi, Keith; Zhongjin, Yang; Paoli, Antonio

    2015-12-01

    The effects of the ketogenic diet (KD) on weight loss, metabolic, and respiratory parameters were investigated in healthy subjects. Thirty-two healthy subjects were randomized into two groups. The KD group followed a ketogenic diet for 20 days (KD t 0-t 20), then switched to a low-carbohydrate, no-ketogenic diet for 20 days (KD t 20-t 40), and finally was on a Mediterranean diet (MD) for 2 more months (KD t 40-t 2m). The MD group followed a MD for 20 days (MD t 0-t 20), then followed a MD of 1400 kcal over the next 20 days (MD t 20-t 40), and completed the study with the MD for 2 months (MD t 40-t 2m). Body weight, body fat, respiratory rate, and respiratory gas parameters (including respiratory exchange ratio (RER) and carbon dioxide end-tidal partial pressure (PETCO2), oxygen uptake (VO2), carbon dioxide production (VCO2), and resting energy expenditure (REE)) were measured at each point. A significant decrease (p diets significantly decreased body fat mass, the KD diet overall proved to have a higher percentage of fat loss versus the MD diet. The KD may significantly decrease carbon dioxide body stores, which may theoretically be beneficial for patients with increased carbon dioxide arterial partial pressure due to respiratory insufficiency or failure.

  19. The effects of classic ketogenic diet on serum lipid profile in children with refractory seizures.

    Science.gov (United States)

    Zamani, Gholam Reza; Mohammadi, Mahmoud; Ashrafi, Mahmoud Reza; Karimi, Parviz; Mahmoudi, Maryam; Badv, Reza Shervin; Tavassoli, Ali Reza; Azizi Malamiri, Reza

    2016-12-01

    More than 25 % of children with epilepsy develop refractory seizures unresponsive to both old and new generation anticonvulsants. Since such seizures have a serious negative impact on the quality of life, other treatment options are considered. The ketogenic diet is a well-known treatment for managing refractory seizures, although its mechanism of action is unknown. Studies have shown that this diet is as good as, or better than, any of the newer medications in reducing seizure frequency. However, concerns about adverse effects have been raised. We conducted an open label trial to show the effects of this diet on serum lipid profile. Thirty-three children with refractory epilepsy were treated with the ketogenic diet and were followed for 6 months. Their serum lipid profile was assessed at baseline, and at 3 and 6 months after initiating the diet. Seizure frequency was reduced in 63 % of children (no seizures in 2/33 and reduced >50 % in 19/33). However, after 6 months of administering the diet, median triglyceride was significantly increased (from 84 to 180 mg/dl, P ketogenic diet in children with refractory seizures is effective in seizure reduction, but leads to development of hypercholesterolemia and hypertriglyceridemia.

  20. Use of the ketogenic diet in the neonatal intensive care unit-Safety and tolerability.

    Science.gov (United States)

    Thompson, Lindsey; Fecske, Erin; Salim, Mohammad; Hall, Ara

    2017-02-01

    Drug-resistant epilepsy poses a challenge in neonatal patients, especially those in the neonatal intensive care unit (NICU), who have various secondary comorbidities. We present results of four children with a history of drug-resistant epilepsy for whom a ketogenic diet was initiated and used in the NICU. A nonfasting induction into ketosis over 1-2 weeks was utilized, with gradual increases in the ketogenic ratio every 2-3 days. Data were collected retrospectively from a database, which included medical history, daily progress notes, relevant laboratory data, and imaging and diagnostic information. The ketogenic diet was well tolerated in all cases. The most common side effects observed were constipation, hypoglycemia, and weight loss. Serum β-hydroxybutyrate levels demonstrated improved reliability as a marker of ketosis when compared to urine ketones in this population. Perceived benefits to the infants included improved seizure control, increased alertness, and decreased need for invasive respiratory support. These cases demonstrate that the use of the ketogenic diet for treatment of neonatal encephalopathy and refractory epilepsy can be undertaken safely in the NICU and is well tolerated by carefully screened neonates and infants. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  1. Timeline of changes in appetite during weight loss with a ketogenic diet

    DEFF Research Database (Denmark)

    Nymo, S; Coutinho, S R; Jørgensen, J

    2017-01-01

    BACKGROUND/OBJECTIVE: Diet-induced weight loss (WL) leads to increased hunger and reduced fullness feelings, increased ghrelin and reduced satiety peptides concentration (glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK) and peptide YY (PYY)). Ketogenic diets seem to minimise or supress some...... of these responses. The aim of this study was to determine the timeline over which changes in appetite occur during progressive WL with a ketogenic very-low-energy diet (VLED). SUBJECTS/METHODS: Thirty-one sedentary adults (18 men), with obesity (body mass index: 37±4.5 kg m-2) underwent 8 weeks (wks) of a VLED...... followed by 4 wks of weight maintenance. Body weight and composition, subjective feelings of appetite and appetite-related hormones (insulin, active ghrelin (AG), active GLP-1, total PYY and CCK) were measured in fasting and postprandially, at baseline, on day 3 of the diet, 5 and 10% WL, and at wks 9...

  2. The Effect of the Ketogenic Diet on the Vascular Structure and Functions in Children With Intractable Epilepsy.

    Science.gov (United States)

    Özdemir, Rahmi; Güzel, Orkide; Küçük, Mehmet; Karadeniz, Cem; Katipoglu, Nagehan; Yılmaz, Ünsal; Yılmazer, Murat Muhtar; Meşe, Timur

    2016-03-01

    We aimed to determine the midterm effect of a ketogenic diet on serum lipid levels, carotid intima-media thickness, and the elastic properties of the carotid artery and the aorta in patients with intractable epilepsy. A total of 52 children aged between 12 months and 18 years with intractable epilepsy who started the ketogenic diet from September 2014 to September 2015 were included into this prospective study. Carotid intima-media thickness and the elastic properties of the carotid artery and the aorta were assessed by echocardiography in all cases before beginning of the ketogenic diet and after at least 12 months on the ketogenic diet. Twenty-one patients at the third month and 25 patients at the first year of the ketogenic diet were seizure free. A reduction of greater than 90% in the seizure frequency was achieved in three patients at the sixth month and in five patients at the first year of the treatment. The serum levels of total cholesterol, low-density lipoprotein, and triglyceride were increased significantly at a median of 12.6 months (range: 12 to 13.5 months) of the ketogenic diet treatment, whereas serum levels of high-density lipoprotein did not change. Carotid intima-media thickness, aortic and carotid strain, the stiffness index, distensibility, and elastic modulus did not change after 12 months of the ketogenic diet therapy. Olive oil-based ketogenic diet appears to have no disturbing effect on the carotid intima-media thickness and the elastic properties of the aorta and the carotid artery in epileptic children, although it may be associated with increased concentrations of serum lipids. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Diet and identity: being a good parent in the face of contradictions presented by the ketogenic diet.

    Science.gov (United States)

    Webster, Michelle; Gabe, Jonathan

    2016-01-01

    The ketogenic diet is a high-fat diet used to treat drug-resistant childhood epilepsy. Given that negative meanings tend to be attached to fatty foods and children's food consumption is seen to be the responsibility of parents, the ketogenic diet may be problematic for parenting identity. This article draws upon in-depth semi-structured interviews with 12 parents from 10 families that have a child whose epilepsy is being treated with the ketogenic diet. The main focus of the article is the meanings these parents attached to foods and how they were drawn upon or altered to overcome some of the contradictions presented by the diet. It will be argued that the diet was medicalised and parents came to view food as medicine. When viewing food in this way, negative associations with fat were reversed. Furthermore, parents also used food as a symbol of inclusion and prioritised portion size or the child's enjoyment of food in order to use food as a symbol of love. In turn this enabled parents to feel they were being good parents. Overall, it seems that diet can be medicalised and the identity of the good parent maintained if dietary treatment is successful. © 2015 The Authors. Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for SHIL.

  4. Dietary and medication adjustments to improve seizure control in patients treated with the ketogenic diet

    Science.gov (United States)

    Selter, Jessica H.; Turner, Zahava; Doerrer, Sarah C.; Kossoff, Eric H.

    2014-01-01

    Unlike anticonvulsant drugs and vagus nerve stimulation, there are no guidelines regarding adjustments to ketogenic diet regimens to improve seizure efficacy once the diet has been started. A retrospective chart review was performed of 200 consecutive patients treated with the ketogenic diet at Johns Hopkins Hospital from 2007-2013. Ten dietary and supplement changes were identified, along with anticonvulsant adjustments. A total of 391 distinct interventions occurred, of which 265 were made specifically to improve seizure control. Adjustments lead to >50% further seizure reduction in-18%, but only 3% became seizure-free. The benefits of interventions did not decrease over time. There was a trend towards medication adjustments being more successful than dietary modifications (24% vs. 15%, p = 0.08). No single dietary change stood out as the most effective, but calorie changes were largely unhelpful (10% with additional benefit). PMID:24859788

  5. Dietary and medication adjustments to improve seizure control in patients treated with the ketogenic diet.

    Science.gov (United States)

    Selter, Jessica H; Turner, Zahava; Doerrer, Sarah C; Kossoff, Eric H

    2015-01-01

    Unlike anticonvulsant drugs and vagus nerve stimulation, there are no guidelines regarding adjustments to ketogenic diet regimens to improve seizure efficacy once the diet has been started. A retrospective chart review was performed of 200 consecutive patients treated with the ketogenic diet at Johns Hopkins Hospital from 2007 to 2013. Ten dietary and supplement changes were identified, along with anticonvulsant adjustments. A total of 391 distinct interventions occurred, of which 265 were made specifically to improve seizure control. Adjustments led to >50% further seizure reduction in 18%, but only 3% became seizure-free. The benefits of interventions did not decrease over time. There was a trend towards medication adjustments being more successful than dietary modifications (24% vs 15%, P = .08). No single dietary change stood out as the most effective, but calorie changes were largely unhelpful (10% with additional benefit). © The Author(s) 2014.

  6. Long-term High Fat Ketogenic Diet Promotes Renal Tumor Growth in a Rat Model of Tuberous Sclerosis.

    Science.gov (United States)

    Liśkiewicz, Arkadiusz D; Kasprowska, Daniela; Wojakowska, Anna; Polański, Krzysztof; Lewin-Kowalik, Joanna; Kotulska, Katarzyna; Jędrzejowska-Szypułka, Halina

    2016-02-19

    Nutritional imbalance underlies many disease processes but can be very beneficial in certain cases; for instance, the antiepileptic action of a high fat and low carbohydrate ketogenic diet. Besides this therapeutic feature it is not clear how this abundant fat supply may affect homeostasis, leading to side effects. A ketogenic diet is used as anti-seizure therapy i.a. in tuberous sclerosis patients, but its impact on concomitant tumor growth is not known. To examine this we have evaluated the growth of renal lesions in Eker rats (Tsc2+/-) subjected to a ketogenic diet for 4, 6 and 8 months. In spite of existing opinions about the anticancer actions of a ketogenic diet, we have shown that this anti-seizure therapy, especially in its long term usage, leads to excessive tumor growth. Prolonged feeding of a ketogenic diet promotes the growth of renal tumors by recruiting ERK1/2 and mTOR which are associated with the accumulation of oleic acid and the overproduction of growth hormone. Simultaneously, we observed that Nrf2, p53 and 8-oxoguanine glycosylase α dependent antitumor mechanisms were launched by the ketogenic diet. However, the pro-cancerous mechanisms finally took the ascendency by boosting tumor growth.

  7. A ketogenic diet accelerates neurodegeneration in mice with induced mitochondrial DNA toxicity in the forebrain.

    Science.gov (United States)

    Lauritzen, Knut H; Hasan-Olive, Md Mahdi; Regnell, Christine E; Kleppa, Liv; Scheibye-Knudsen, Morten; Gjedde, Albert; Klungland, Arne; Bohr, Vilhelm A; Storm-Mathisen, Jon; Bergersen, Linda H

    2016-12-01

    Mitochondrial genome maintenance plays a central role in preserving brain health. We previously demonstrated accumulation of mitochondrial DNA damage and severe neurodegeneration in transgenic mice inducibly expressing a mutated mitochondrial DNA repair enzyme (mutUNG1) selectively in forebrain neurons. Here, we examine whether severe neurodegeneration in mutUNG1-expressing mice could be rescued by feeding the mice a ketogenic diet, which is known to have beneficial effects in several neurological disorders. The diet increased the levels of superoxide dismutase 2, and mitochondrial mass, enzymes, and regulators such as SIRT1 and FIS1, and appeared to downregulate N-methyl-D-aspartic acid (NMDA) receptor subunits NR2A/B and upregulate γ-aminobutyric acid A (GABA A ) receptor subunits α 1 . However, unexpectedly, the ketogenic diet aggravated neurodegeneration and mitochondrial deterioration. Electron microscopy showed structurally impaired mitochondria accumulating in neuronal perikarya. We propose that aggravation is caused by increased mitochondrial biogenesis of generally dysfunctional mitochondria. This study thereby questions the dogma that a ketogenic diet is unambiguously beneficial in mitochondrial disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. The ketogenic diet in two paediatric patients with refractory myoclonic status epilepticus.

    Science.gov (United States)

    Caraballo, Roberto Horacio; Valenzuela, Gabriela Reyes; Armeno, Marisa; Fortini, Sebastian; Mestre, Graciela; Cresta, Araceli

    2015-12-01

    We describe two patients with refractory myoclonic status epilepticus treated with the ketogenic diet. Between May 1, 2014 and January 1, 2015, two patients who met the diagnostic criteria for refractory myoclonic status epilepticus, seen at our department, were placed on the ketogenic diet and followed for a minimum of six months. One patient with myoclonic epilepsy of unknown aetiology had a 75-90% seizure reduction, and the other with progressive encephalopathy associated with myoclonic epilepsy had a 50% seizure reduction. Both patients retained good tolerability for the diet. At the last control, one patient had isolated myoclonias and EEG showed occasional generalized spike-and-polyspike waves; the patient is now successfully attending kindergarten. The quality of life of the second patient improved significantly. In both cases, the number of antiepileptic drugs was reduced. The ketogenic diet is an effective and well-tolerated treatment option for patients with refractory myoclonic status epilepticus and should be considered earlier in the course of treatment.

  9. Linear growth of children on a ketogenic diet: does the protein-to-energy ratio matter?

    Science.gov (United States)

    Nation, Judy; Humphrey, Maureen; MacKay, Mark; Boneh, Avihu

    2014-11-01

    Ketogenic diet is a structured effective treatment for children with intractable epilepsy. Several reports have indicated poor linear growth in children on the diet but the mechanism of poor growth has not been elucidated. We aimed to explore whether the protein to energy ratio plays a role in linear growth of children on ketogenic diet. Data regarding growth and nutrition were, retrospectively, collected from the clinical histories of 35 children who were treated with ketogenic diet for at least 6 months between 2002 and 2010. Patients were stratified into groups according to periods of satisfactory or poor linear growth. Poor linear growth was associated with protein or caloric intake of <80% recommended daily intake, and with a protein-to-energy ratio consistently ≤1.4 g protein/100 kcal even when protein and caloric intakes were adequate. We recommend a protein-to-energy ratio of 1.5 g protein/100 kcal be prescribed to prevent growth retardation. © The Author(s) 2013.

  10. Decreased ghrelin and des-acyl ghrelin plasma levels in patients affected by pharmacoresistant epilepsy and maintained on the ketogenic diet.

    Science.gov (United States)

    Marchiò, Maddalena; Roli, Laura; Giordano, Carmela; Trenti, Tommaso; Guerra, Azzurra; Biagini, Giuseppe

    2018-03-23

    The gastric hormones ghrelin and des-acyl ghrelin have been found to be altered in patients treated with antiepileptic drugs. However, it is unknown if these hormones could be modified by other antiepileptic treatments, such as the ketogenic diet. Especially, a reduction in ghrelin levels could be relevant in view of the growth retardation observed under ketogenic diet treatment. For this reason we aimed to determine the changes in ghrelin and des-acyl ghrelin plasma levels in children affected by refractory epilepsy and treated with the ketogenic diet up to 90 days. Both peptides were measured by immunoassays in plasma obtained from 16 children. Ghrelin plasma levels were progressively reduced by the ketogenic diet, reaching a minimum corresponding to 42% of basal levels after 90 days of ketogenic diet (P ketogenic diet (P ketogenic diet administration. Ghrelin and des-acyl ghrelin are downregulated by the ketogenic diet in children affected by refractory epilepsy. Although no significant changes in growth were observed during the short time period of our investigation, the reduction in ghrelin availability may explain the reported growth retardation found in children treated with the ketogenic diet in the long-term. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  11. Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet

    Directory of Open Access Journals (Sweden)

    Seyfried B

    2009-09-01

    Full Text Available Malignant brain tumors are a significant health problem in children and adults and are largely unmanageable. As a metabolic disorder involving the dysregulation of glycolysis and respiration (the Warburg effect, malignant brain cancer can be managed through changes in metabolic environment. In contrast to malignant brain tumors that are mostly dependent on glycolysis for energy, normal neurons and glia readily transition to ketone bodies (β-hydroxybutyrate for energy in vivo when glucose levels are reduced. The transition from glucose to ketone bodies as a major energy source is an evolutionary conserved adaptation to food deprivation that permits the survival of normal cells during extreme shifts in nutritional environment. Only those cells with a flexible genome, honed through millions of years of environmental forcing and variability selection, can transition from one energy state to another. We propose a different approach to brain cancer management that exploits the metabolic flexibility of normal cells at the expense of the genetically defective and less metabolically flexible tumor cells. This approach to brain cancer management is supported from recent studies in orthotopic mouse brain tumor models and in human pediatric astrocytoma treated with calorie restriction and the ketogenic diet. Issues of implementation and use protocols are discussed.

  12. Ketogenic diet metabolites reduce firing in central neurons by opening K(ATP) channels.

    Science.gov (United States)

    Ma, Weiyuan; Berg, Jim; Yellen, Gary

    2007-04-04

    A low-carbohydrate ketogenic diet remains one of the most effective (but mysterious) treatments for severe pharmacoresistant epilepsy. We have tested for an acute effect of physiological ketone bodies on neuronal firing rates and excitability, to discover possible therapeutic mechanisms of the ketogenic diet. Physiological concentrations of ketone bodies (beta-hydroxybutyrate or acetoacetate) reduced the spontaneous firing rate of neurons in slices from rat or mouse substantia nigra pars reticulata. This region is thought to act as a "seizure gate," controlling seizure generalization. Consistent with an anticonvulsant role, the ketone body effect is larger for cells that fire more rapidly. The effect of ketone bodies was abolished by eliminating the metabolically sensitive K(ATP) channels pharmacologically or by gene knock-out. We propose that ketone bodies or glycolytic restriction treat epilepsy by augmenting a natural activity-limiting function served by K(ATP) channels in neurons.

  13. The Effect of Ketogenic Diet on Serum Selenium Levels in Patients with Intractable Epilepsy.

    Science.gov (United States)

    Arslan, Nur; Kose, Engin; Guzel, Orkide

    2017-07-01

    The aim of the present study was to evaluate serum selenium levels in children receiving olive oil-based ketogenic diet (KD) for intractable seizures for at least 1 year. Out of 320 patients who were initiated on KD, patients who continued receiving KD for at least 12 months were enrolled. Sixteen patients who had selenium deficiency at the time of starting KD were excluded. Finally, a total of 110 patients (mean age 7.3 ± 4.2 years) were included. Serum selenium levels were measured at baseline and at 3, 6, and 12 months after treatment initiation by using atomic absorption spectroscopy. Selenium deficiency was defined as a serum selenium level ketogenic diet suggests that patients on this highly prescriptive dietary treatment need close monitoring of this trace element.

  14. Acid–base safety during the course of a very low-calorie-ketogenic diet

    OpenAIRE

    Gomez-Arbelaez, Diego; Crujeiras, Ana B.; Castro, Ana I.; Goday, Albert; Mas-Lorenzo, Antonio; Bellon, Ana; Tejera, Cristina; Bellido, Diego; Galban, Cristobal; Sajoux, Ignacio; Lopez-Jaramillo, Patricio; Casanueva, Felipe F.

    2017-01-01

    Background and Aims Very low-calorie ketogenic (VLCK) diets have been consistently shown to be an effective obesity treatment, but the current evidence for its acid-base safety is limited. The aim of the current work was to evaluate the acid-base status of obese patients during the course of a VLCK diet. Method Twenty obese participants undertook a VLCK diet for 4 months. Anthropometric and biochemical parameters, and venous blood gases were obtained on four subsequent visits: visit C-1 (base...

  15. Acid-base safety during the course of a very low-calorie-ketogenic diet

    OpenAIRE

    Gomez-Arbelaez, Diego; Crujeiras, Ana B.; Castro, Ana I.; Goday Arno, Alberto; Mas-Lorenzo, Antonio; Bellon, Ana; Tejera, Cristina; Bellido, Diego; Galban, Cristobal; Sajoux, Ignacio; Lopez-Jaramillo, Patricio; Casanueva, Felipe F.

    2017-01-01

    BACKGROUND AND AIMS: Very low-calorie ketogenic (VLCK) diets have been consistently shown to be an effective obesity treatment, but the current evidence for its acid-base safety is limited. The aim of the current work was to evaluate the acid-base status of obese patients during the course of a VLCK diet. METHOD: Twenty obese participants undertook a VLCK diet for 4 months. Anthropometric and biochemical parameters, and venous blood gases were obtained on four subsequent visits: visit C-1 (ba...

  16. Usefulness of ketogenic diet in a girl with migrating partial seizures in infancy.

    Science.gov (United States)

    Mori, Tatsuo; Imai, Katsumi; Oboshi, Taikan; Fujiwara, Yuh; Takeshita, Saoko; Saitsu, Hirotomo; Matsumoto, Naomichi; Takahashi, Yukitoshi; Inoue, Yushi

    2016-06-01

    Migrating partial seizures in infancy (MPSI) are an age-specific epilepsy syndrome characterized by migrating focal seizures, which are intractable to various antiepileptic drugs and cause severe developmental delay. We report a case of MPSI with heterozygous missense mutation in KCNT1, which was successfully managed by ketogenic diet. At age 2months, the patient developed epilepsy initially manifesting focal seizures with eye deviation and apnea, then evolving to secondarily generalized clonic convulsion. Various antiepileptic drugs including phenytoin, valproic acid, zonisamide, clobazam, levetiracetam, vitamin B6, and carbamazepine were not effective, but high-dose phenobarbital allowed discontinuation of midazolam infusion. Ictal scalp electroencephalogram showed migrating focal seizures. MPSI was suspected and she was transferred to our hospital for further treatment. Potassium bromide (KBr) was partially effective, but the effect was transient. High-dose KBr caused severe adverse effects such as over-sedation and hypercapnia, with no further effects on the seizures. At age 9months, we started a ketogenic diet, which improved seizure frequency and severity without obvious adverse effects, allowing her to be discharged from hospital. Ketogenic diet should be tried in patients with MPSI unresponsive to antiepileptic drugs. In MPSI, the difference in treatment response in patients with and those without KCNT1 mutation remains unknown. Accumulation of case reports would contribute to establish effective treatment options for MPSI. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  17. Impact of Child Life Services on Children and Families Admitted to Start the Ketogenic Diet.

    Science.gov (United States)

    Kossoff, Eric H; Sutter, Lindsay; Doerrer, Sarah C; Haney, Courtney A; Turner, Zahava

    2017-08-01

    Traditionally the ketogenic diet is started as an inpatient admission to the hospital. Starting in January 2015, child life services were made formally available during ketogenic diet admissions to help families cope. One-page surveys were then provided to 15 parents on the day of discharge and again after 3 months. Every family believed that the child life services were helpful. Children who were developmentally appropriate/mildly delayed had higher parent-reported anxiety scores than those who were moderate to severely delayed (4.4 vs 1.0, P = .02). At 3 months, child life services were deemed very helpful for the parents (mean score: 8.9, range: 5-10), and were more helpful for the parent than the child (mean 6.2, range 1-10, P = .047). One of the most helpful services was a prior phone call to parents 1 week prior. In this small pilot study, child life involvement during the start of the ketogenic diet was highly useful.

  18. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism

    Science.gov (United States)

    Allen, Bryan G.; Bhatia, Sudershan K.; Anderson, Carryn M.; Eichenberger-Gilmore, Julie M.; Sibenaller, Zita A.; Mapuskar, Kranti A.; Schoenfeld, Joshua D.; Buatti, John M.; Spitz, Douglas R.; Fath, Melissa A.

    2014-01-01

    Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2•−and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses. PMID:25460731

  19. Long-term impact of the ketogenic diet on growth and resting energy expenditure in children with intractable epilepsy.

    Science.gov (United States)

    Groleau, Veronique; Schall, Joan I; Stallings, Virginia A; Bergqvist, Christina A

    2014-09-01

    The long-term effects of the ketogenic diet, a high fat diet for treating intractable epilepsy, on resting energy expenditure (REE) are unknown. The aim of this study was to evaluate the impact of 15 months of ketogenic diet treatment on growth and REE in children with intractable epilepsy. Growth, body composition, and REE were assessed at baseline, 3 months and 15 months in 24 children (14 males, 10 females; mean age 5 y 6 mo [SD 26 mo], range 7 mo-6 y 5 mo), 10 with cerebral palsy [CP]). Fifteen were identified as ketogenic diet responders at 3 months and continued on the ketogenic diet until 15 months. These were compared to 75 healthy children (43 males, 32 females; mean age 6 y 3 mo [SD 21 mo] age range 2-9 y). REE was expressed as percentage predicted, growth as height (HAz) and weight (WAz) z-scores, and body composition as fat and fat free mass (FFM). HAz declined -0.2 and -0.6 from baseline to 3 months and 15 months respectively (p = 0.001), while WAz was unchanged. In ketogenic diet responders, FFM, age and CP diagnosis predicted REE (overall R(2) = 0.76, pketogenic diet, linear growth status declined while weight status and REE were unchanged. REE remained reduced in children with CP. © 2014 Mac Keith Press.

  20. Long-term impact of the ketogenic diet on growth and resting energy expenditure in children with intractable epilepsy

    Science.gov (United States)

    GROLEAU, VERONIQUE; SCHALL, JOAN I; STALLINGS, VIRGINIA A; BERGQVIST, CHRISTINA A

    2014-01-01

    AIM The long-term effects of the ketogenic diet, a high fat diet for treating intractable epilepsy, on resting energy expenditure (REE) are unknown. The aim of this study was to evaluate the impact of 15 months of ketogenic diet treatment on growth and REE in children with intractable epilepsy. METHOD Growth, body composition and REE were assessed at baseline, 3 and 15 months in 24 children (14 males, 10 females; mean age 5y 6mo (SD 26mo), range 7mo–6y 5mo), 10 with cerebral palsy [CP]). Fifteen were identified as ketogenic diet responders at 3 months and continued on the ketogenic diet until 15 months. These were compared to 75 healthy children (43 males, 32 females; mean age 6y 3mo [SD 21mo] age range 2–9y). REE was expressed as percentage predicted, growth as height (HAz) and weight (WAz) z-scores, and body composition as fat and fat free mass (FFM). RESULTS HAz declined −0.2 and −0.6 from baseline to 3 and 15 months, respectively (p=0.001), while WAz was unchanged. In ketogenic diet responders, FFM, age and CP diagnosis predicted REE (overall R2=0.76, pketogenic diet, linear growth status declined while weight status and REE were unchanged. REE remained reduced in children with CP. PMID:24749520

  1. SLC6A1 Mutation and Ketogenic Diet in Epilepsy With Myoclonic-Atonic Seizures.

    Science.gov (United States)

    Palmer, Samantha; Towne, Meghan C; Pearl, Phillip L; Pelletier, Renee C; Genetti, Casie A; Shi, Jiahai; Beggs, Alan H; Agrawal, Pankaj B; Brownstein, Catherine A

    2016-11-01

    Epilepsy with myoclonic-atonic seizures, also known as myoclonic-astatic epilepsy or Doose syndrome, has been recently linked to variants in the SLC6A1 gene. Epilepsy with myoclonic-atonic seizures is often refractory to antiepileptic drugs, and the ketogenic diet is known for treating medically intractable seizures, although the mechanism of action is largely unknown. We report a novel SLC6A1 variant in a patient with epilepsy with myoclonic-atonic seizures, analyze its effects, and suggest a mechanism of action for the ketogenic diet. We describe a ten-year-old girl with epilepsy with myoclonic-atonic seizures and a de novo SLC6A1 mutation who responded well to the ketogenic diet. She carried a c.491G>A mutation predicted to cause p.Cys164Tyr amino acid change, which was identified using whole exome sequencing and confirmed by Sanger sequencing. High-resolution structural modeling was used to analyze the likely effects of the mutation. The SLC6A1 gene encodes a transporter that removes gamma-aminobutyric acid from the synaptic cleft. Mutations in SLC6A1 are known to disrupt the gamma-aminobutyric acid transporter protein 1, affecting gamma-aminobutyric acid levels and causing seizures. The p.Cys164Tyr variant found in our study has not been previously reported, expanding on the variants linked to epilepsy with myoclonic-atonic seizures. A 10-year-old girl with a novel SLC6A1 mutation and epilepsy with myoclonic-atonic seizures had an excellent clinical response to the ketogenic diet. An effect of the diet on gamma-aminobutyric acid reuptake mediated by gamma-aminobutyric acid transporter protein 1 is suggested. A personalized approach to epilepsy with myoclonic-atonic seizures patients carrying SLC6A1 mutation and a relationship between epilepsy with myoclonic-atonic seizures due to SLC6A1 mutations, GABAergic drugs, and the ketogenic diet warrants further exploration. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. The use of ketogenic diet in special situations: expanding use in intractable epilepsy and other neurologic disorders

    Science.gov (United States)

    2012-01-01

    The ketogenic diet has been widely used and proved to be effective for intractable epilepsy. Although the mechanisms underlying its anti-epileptic effects remain to be proven, there are increasing experimental evidences for its neuroprotective effects along with many researches about expanding use of the diet in other neurologic disorders. The first success was reported in glucose transporter type 1 deficiency syndrome, in which the diet served as an alternative metabolic source. Many neurologic disorders share some of the common pathologic mechanisms such as mitochondrial dysfunction, altered neurotransmitter function and synaptic transmission, or abnormal regulation of reactive oxygen species, and the role of the ketogenic diet has been postulated in these mechanisms. In this article, we introduce an overview about the expanding use and emerging trials of the ketogenic diet in various neurologic disorders excluding intractable epilepsy and provide explanations of the mechanisms in that usage. PMID:23049588

  3. An acidosis-sparing ketogenic (ASK) diet to improve efficacy and reduce adverse effects in the treatment of refractory epilepsy.

    Science.gov (United States)

    Yuen, Alan W C; Walcutt, Isabel A; Sander, Josemir W

    2017-09-01

    Diets that increase production of ketone bodies to provide alternative fuel for the brain are evolving from the classic ketogenic diet for epilepsy devised nearly a century ago. The classic ketogenic diet and its more recent variants all appear to have similar efficacy with approximately 50% of users showing a greater than 50% seizure reduction. They all require significant medical and dietetic support, and there are tolerability issues. A review suggests that low-grade chronic metabolic acidosis associated with ketosis is likely to be an important contributor to the short term and long term adverse effects of ketogenic diets. Recent studies, particularly with the characterization of the acid sensing ion channels, suggest that chronic metabolic acidosis may increase the propensity for seizures. It is also known that low-grade chronic metabolic acidosis has a broad range of negative health effects and an increased risk of early mortality in the general population. The modified ketogenic dietary treatment we propose is formulated to limit acidosis by measures that include monitoring protein intake and maximizing consumption of alkaline mineral-rich, low carbohydrate green vegetables. We hypothesize that this acidosis-sparing ketogenic diet is expected to be associated with less adverse effects and improved efficacy. A case history of life-long intractable epilepsy shows this diet to be a successful long-term strategy but, clearly, clinical studies are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. The biochemical changes in hippocampal formation occurring in normal and seizure experiencing rats as a result of a ketogenic diet.

    Science.gov (United States)

    Chwiej, Joanna; Skoczen, Agnieszka; Janeczko, Krzysztof; Kutorasinska, Justyna; Matusiak, Katarzyna; Figiel, Henryk; Dumas, Paul; Sandt, Christophe; Setkowicz, Zuzanna

    2015-04-07

    In this study, ketogenic diet-induced biochemical changes occurring in normal and epileptic hippocampal formations were compared. Four groups of rats were analyzed, namely seizure experiencing animals and normal rats previously fed with ketogenic (KSE and K groups respectively) or standard laboratory diet (NSE and N groups respectively). Synchrotron radiation based Fourier-transform infrared microspectroscopy was used for the analysis of distributions of the main organic components (proteins, lipids, compounds containing phosphate group(s)) and their structural modifications as well as anomalies in creatine accumulation with micrometer spatial resolution. Infrared spectra recorded in the molecular layers of the dentate gyrus (DG) areas of normal rats on a ketogenic diet (K) presented increased intensity of the 1740 cm(-1) absorption band. This originates from the stretching vibrations of carbonyl groups and probably reflects increased accumulation of ketone bodies occurring in animals on a high fat diet compared to those fed with a standard laboratory diet (N). The comparison of K and N groups showed, moreover, elevated ratios of absorbance at 1634 and 1658 cm(-1) for DG internal layers and increased accumulation of creatine deposits in sector 3 of the Ammon's horn (CA3) hippocampal area of ketogenic diet fed rats. In multiform and internal layers of CA3, seizure experiencing animals on ketogenic diet (KSE) presented a lower ratio of absorbance at 1634 and 1658 cm(-1) compared to rats on standard laboratory diet (NSE). Moreover, in some of the examined cellular layers, the increased intensity of the 2924 cm(-1) lipid band as well as the massifs of 2800-3000 cm(-1) and 1360-1480 cm(-1), was found in KSE compared to NSE animals. The intensity of the 1740 cm(-1) band was diminished in DG molecular layers of KSE rats. The ketogenic diet did not modify the seizure induced anomalies in the unsaturation level of lipids or the number of creatine deposits.

  5. Resting metabolic rate of obese patients under very low calorie ketogenic diet

    OpenAIRE

    Gomez-Arbelaez, Diego; Crujeiras, Ana B.; Castro, Ana I.; Martinez-Olmos, Miguel A.; Canton, Ana; Ordoñez-Mayan, Lucia; Sajoux, Ignacio; Galban, Cristobal; Bellido, Diego; Casanueva, Felipe F.

    2018-01-01

    Background The resting metabolic rate (RMR) decrease, observed after an obesity reduction therapy is a determinant of a short-time weight regain. Thus, the objective of this study was to evaluate changes in RMR, and the associated hormonal alterations in obese patients with a very low-calorie ketogenic (VLCK)-diet induced severe body weight (BW) loss. Method From 20 obese patients who lost 20.2 kg of BW after a 4-months VLCK-diet, blood samples and body composition analysis, determined by DXA...

  6. Effects of a ketogenic diet on auditory gating in DBA/2 mice: A proof-of-concept study.

    Science.gov (United States)

    Tregellas, Jason R; Smucny, Jason; Legget, Kristina T; Stevens, Karen E

    2015-12-01

    Although the ketogenic diet has shown promise in a pilot study and case report in schizophrenia, its effects in animal models of hypothesized disease mechanisms are unknown. This study examined effects of treatment with the ketogenic diet on hippocampal P20/N40 gating in DBA/2 mice, a translational endophenotype that mirrors inhibitory deficits in P50 sensory gating in schizophrenia patients. As expected, the diet increased blood ketone levels. Animals with the highest ketone levels showed the lowest P20/N40 gating ratios. These preliminary results suggest that the ketogenic diet may effectively target sensory gating deficits and is a promising area for additional research in schizophrenia. Published by Elsevier B.V.

  7. An unfortunate challenge: Ketogenic diet for the treatment of Lennox-Gastaut syndrome in tyrosinemia type 1.

    Science.gov (United States)

    De Lucia, Silvana; Pichard, Samia; Ilea, Adina; Greneche, Marie-Odile; François, Laurent; Delanoë, Catherine; Schiff, Manuel; Auvin, Stéphane

    2016-07-01

    The ketogenic diet is an evidence-based treatment for resistant epilepsy including Lennox-Gastaut syndrome. This diet is based on low carbohydrate-high fat intakes. Dietary treatment is also therapeutic for inborn errors of metabolism such as aminoacdiopathies. We report a child with both Lennox-Gastaut syndrome and tyrosinemia type 1. This epilepsy syndrome resulted form a porencephalic cyst secondary to brain abscesses that occurred during the management of malnutrition due to untreated tyrosinemia type 1. We used a ketogenic diet as treatment for Lennox-Gastaut syndrome taking into account dietary requirements for tyrosinemia type 1. The patient was transiently responder during a 6-month period. This report illustrates that ketogenic diet remains a therapeutic option even when additional dietary requirements are needed. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  8. Metabolic therapy for temporal lobe epilepsy in a dish: investigating mechanisms of ketogenic diet using electrophysiological recordings in hippocampal slices

    Directory of Open Access Journals (Sweden)

    Masahito Kawamura

    2016-11-01

    Full Text Available The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices. Here we review these reports and their relevant mechanistic findings. We acknowledge that a major difficulty in using hippocampal slices is the inability to reproduce precisely the in vivo condition of ketogenic diet feeding in any in vitro preparation, and progress has been made in this in vivo/in vitro transition. Thus far at least three different approaches are reported to reproduce relevant diet effects in the hippocampal slices: (1 direct application of ketone bodies, (2 mimicking the ketogenic diet condition during a whole-cell patch-clamp technique, and (3 reduced glucose incubation of hippocampal slices from ketogenic diet–fed animals. Significant results have been found with each of these methods and provide options for further study into short- and long-term mechanisms including ATP-sensitive potassium channels, vesicular glutamate transporter, pannexin channels and adenosine receptors underlying ketogenic diet and other forms of metabolic therapy.

  9. Metabolic Therapy for Temporal Lobe Epilepsy in a Dish: Investigating Mechanisms of Ketogenic Diet using Electrophysiological Recordings in Hippocampal Slices

    Science.gov (United States)

    Kawamura, Masahito Jr.; Ruskin, David N.; Masino, Susan A.

    2016-01-01

    The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices. Here we review these reports and their relevant mechanistic findings. We acknowledge that a major difficulty in using hippocampal slices is the inability to reproduce precisely the in vivo condition of ketogenic diet feeding in any in vitro preparation, and progress has been made in this in vivo/in vitro transition. Thus far at least three different approaches are reported to reproduce relevant diet effects in the hippocampal slices: (1) direct application of ketone bodies; (2) mimicking the ketogenic diet condition during a whole-cell patch-clamp technique; and (3) reduced glucose incubation of hippocampal slices from ketogenic diet–fed animals. Significant results have been found with each of these methods and provide options for further study into short- and long-term mechanisms including Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, vesicular glutamate transporter (VGLUT), pannexin channels and adenosine receptors underlying ketogenic diet and other forms of metabolic therapy. PMID:27847463

  10. Ketogenic Diet Improves Motor Performance but Not Cognition in Two Mouse Models of Alzheimer’s Pathology

    Science.gov (United States)

    Brownlow, Milene L.; Benner, Leif; D’Agostino, Dominic; Gordon, Marcia N.; Morgan, Dave

    2013-01-01

    Dietary manipulations are increasingly viewed as possible approaches to treating neurodegenerative diseases. Previous studies suggest that Alzheimer’s disease (AD) patients present an energy imbalance with brain hypometabolism and mitochondrial deficits. Ketogenic diets (KDs), widely investigated in the treatment and prevention of seizures, have been suggested to bypass metabolic deficits present in AD brain by providing ketone bodies as an alternative fuel to neurons. We investigated the effects of a ketogenic diet in two transgenic mouse lines. Five months old APP/PS1 (a model of amyloid deposition) and Tg4510 (a model of tau deposition) mice were offered either a ketogenic or a control (NIH-31) diet for 3 months. Body weight and food intake were monitored throughout the experiment, and blood was collected at 4 weeks and 4 months for ketone and glucose assessments. Both lines of transgenic mice weighed less than nontransgenic mice, yet, surprisingly, had elevated food intake. The ketogenic diet did not affect these differences in body weight or food consumption. Behavioral testing during the last two weeks of treatment found that mice offered KD performed significantly better on the rotarod compared to mice on the control diet independent of genotype. In the open field test, both transgenic mouse lines presented increased locomotor activity compared to nontransgenic, age-matched controls, and this effect was not influenced by KD. The radial arm water maze identified learning deficits in both transgenic lines with no significant differences between diets. Tissue measures of amyloid, tau, astroglial and microglial markers in transgenic lines showed no differences between animals fed the control or the ketogenic diet. These data suggest that ketogenic diets may play an important role in enhancing motor performance in mice, but have minimal impact on the phenotype of murine models of amyloid or tau deposition. PMID:24069439

  11. The influence of the ketogenic diet on the elemental and biochemical compositions of the hippocampal formation.

    Science.gov (United States)

    Chwiej, Joanna; Skoczen, Agnieszka; Matusiak, Katarzyna; Janeczko, Krzysztof; Patulska, Agnieszka; Sandt, Christophe; Simon, Rolf; Ciarach, Malgorzata; Setkowicz, Zuzanna

    2015-08-01

    A growing body of evidence demonstrates that dietary therapies, mainly the ketogenic diet, may be highly effective in the reduction of epileptic seizures. All of them share the common characteristic of restricting carbohydrate intake to shift the predominant caloric source of the diet to fat. Catabolism of fats results in the production of ketone bodies which become alternate energy substrates to glucose. Although many mechanisms by which ketone bodies yield its anticonvulsant effect are proposed, the relationships between the brain metabolism of the ketone bodies and their neuroprotective and antiepileptogenic action still remain to be discerned. In the study, X-ray fluorescence microscopy and FTIR microspectroscopy were used to follow ketogenic diet-induced changes in the elemental and biochemical compositions of rat hippocampal formation tissue. The use of synchrotron sources of X-rays and infrared allowed us to examine changes in the accumulation and distribution of selected elements (P, S, K, Ca, Fe, Cu, Zn, and Se) and biomolecules (proteins, lipids, ketone bodies, etc.) with the micrometer spatial resolution. The comparison of rats fed with the ketogenic diet and rats fed with the standard laboratory diet showed changes in the hippocampal accumulation of P, K, Ca, and Zn. The relations obtained for Ca (increased level in CA3, DG, and its internal area) and Zn (decreased areal density in CA3 and DG) were analogous to those that we previously observed for rats in the acute phase of pilocarpine-induced seizures. Biochemical analysis of tissues taken from ketogenic diet-fed rats demonstrated increased intensity of absorption band occurring at 1740 cm(-1), which was probably the result of elevated accumulation of ketone bodies. Moreover, higher absolute and relative (3012 cm(-1)/2924 cm(-1), 3012 cm(-1)/lipid massif, and 3012 cm(-1)/amide I) intensity of the 3012-cm(-1) band resulting from increased unsaturated fatty acids content was found after the treatment

  12. The ketogenic diet as broad-spectrum treatment for super-refractory pediatric status epilepticus: challenges in implementation in the pediatric and neonatal intensive care units.

    Science.gov (United States)

    Cobo, Nicole H; Sankar, Raman; Murata, Kristina K; Sewak, Sarika L; Kezele, Michele A; Matsumoto, Joyce H

    2015-02-01

    Refractory status epilepticus carries significant morbidity and mortality. Recent reports have promoted the use of the ketogenic diet as an effective treatment for refractory status epilepticus. We describe our recent experience with instituting the ketogenic diet for 4 critically ill children in refractory status epilepticus, ranging in age from 9 weeks to 13.5 years after failure of traditional treatment. The ketogenic diet allowed these patients to be weaned off continuous infusions of anesthetics without recurrence of status epilepticus, though delayed ketosis and persistently elevated glucose measurements posed special challenges to effective initiation, and none experienced complete seizure cessation. The ease of sustaining myocardial function with fatty acid energy substrates compares favorably over the myocardial toxicity posed by anesthetic doses of barbiturates and contributes to the safety profile of the ketogenic diet. The ketogenic diet can be implemented successfully and safely for the treatment of refractory status epilepticus in pediatric patients. © The Author(s) 2014.

  13. Ketone Bodies as a Possible Adjuvant to Ketogenic Diet in PDHc Deficiency but Not in GLUT1 Deficiency.

    Science.gov (United States)

    Habarou, F; Bahi-Buisson, N; Lebigot, E; Pontoizeau, C; Abi-Warde, M T; Brassier, A; Le Quan Sang, K H; Broissand, C; Vuillaumier-Barrot, S; Roubertie, A; Boutron, A; Ottolenghi, C; de Lonlay, P

    2018-01-01

    Ketogenic diet is the first line therapy for neurological symptoms associated with pyruvate dehydrogenase deficiency (PDHD) and intractable seizures in a number of disorders, including GLUT1 deficiency syndrome (GLUT1-DS). Because high-fat diet raises serious compliance issues, we investigated if oral L,D-3-hydroxybutyrate administration could be as effective as ketogenic diet in PDHD and GLUT1-DS. We designed a partial or total progressive substitution of KD with L,D-3-hydroxybutyrate in three GLUT1-DS and two PDHD patients. In GLUT1-DS patients, we observed clinical deterioration including increased frequency of seizures and myoclonus. In parallel, ketone bodies in CSF decreased after introducing 3-hydroxybutyrate. By contrast, two patients with PDHD showed clinical improvement as dystonic crises and fatigability decreased under basal metabolic conditions. In one of the two PDHD children, 3-hydroxybutyrate has largely replaced the ketogenic diet, with the latter that is mostly resumed only during febrile illness. Positive direct effects on energy metabolism in PDHD patients were suggested by negative correlation between ketonemia and lactatemia (r 2  = 0.59). Moreover, in cultured PDHc-deficient fibroblasts, the increase of CO 2 production after 14 C-labeled 3-hydroxybutyrate supplementation was consistent with improved Krebs cycle activity. However, except in one patient, ketonemia tended to be lower with 3-hydroxybutyrate administration compared to ketogenic diet. 3-hydroxybutyrate may be an adjuvant treatment to ketogenic diet in PDHD but not in GLUT1-DS under basal metabolic conditions. Nevertheless, ketogenic diet is still necessary in PDHD patients during febrile illness.

  14. Danish study of a Modified Atkins diet for medically intractable epilepsy in children: Can we achieve the same results as with the classical ketogenic diet?

    DEFF Research Database (Denmark)

    Miranda, M. J.; Mortensen, M.; Povlsen, J. H.

    2011-01-01

    Modified Atkins diet (MAD) is a less restrictive variety of the classical ketogenic diet (KD), used for treating patients with medically resistant epilepsy. There are only few reports comparing the two types of diets in terms of seizure reduction and tolerability. We compared the effect of a MAD...

  15. Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet

    OpenAIRE

    Garbow, Joel R.; Doherty, Jason M.; Schugar, Rebecca C.; Travers, Sarah; Weber, Mary L.; Wentz, Anna E.; Ezenwajiaku, Nkiruka; Cotter, David G.; Brunt, Elizabeth M.; Crawford, Peter A.

    2011-01-01

    Low-carbohydrate diets are used to manage obesity, seizure disorders, and malignancies of the central nervous system. These diets create a distinctive, but incompletely defined, cellular, molecular, and integrated metabolic state. Here, we determine the systemic and hepatic effects of long-term administration of a very low-carbohydrate, low-protein, and high-fat ketogenic diet, serially comparing these effects to a high-simple-carbohydrate, high-fat Western diet and a low-fat, polysaccharide-...

  16. From intravenous to enteral ketogenic diet in PICU: A potential treatment strategy for refractory status epilepticus.

    Science.gov (United States)

    Chiusolo, F; Diamanti, A; Bianchi, R; Fusco, L; Elia, M; Capriati, T; Vigevano, F; Picardo, S

    2016-11-01

    Ketogenic diet (KD) has been used to treat refractory status epilepticus (RSE). KD is a high-fat, restricted-carbohydrate regimen that may be administered with different fat to protein and carbohydrate ratios (3:1 and 4:1 fat to protein and carbohydrate ratios). Other ketogenic regimens have a lower fat and higher protein and carbohydrate ratio to improve taste and thus compliance to treatment. We describe a case of RSE treated with intravenous KD in the Pediatric Intensive Care Unit (PICU). An 8-year-old boy was referred to the PICU because of continuous tonic-clonic and myoclonic generalized seizures despite several antiepileptic treatments. After admission he was intubated and treated with intravenous thiopental followed by ketamine. Seizures continued with frequent myoclonic jerks localized on the face and upper arms. EEG showed seizure activity with spikes on rhythmic continuous waves. Thus we decided to begin KD. The concomitant ileus contraindicated KD by the enteral route and we therefore began IV KD. The ketogenic regimen consisted of conventional intravenous fat emulsion, plus dextrose and amino-acid hyperalimentation in a 2:1 then 3:1 fat to protein and carbohydrate ratio. Exclusive IV ketogenic treatment, well tolerated, was maintained for 3 days; peristalsis then reappeared so KD was continued by the enteral route at 3:1 ratio. Finally, after 8 days and no seizure improvement, KD was deemed unsuccessful and was discontinued. Our experience indicates that IV KD may be considered as a temporary "bridge" towards enteral KD in patients with partial or total intestinal failure who need to start KD. It allows a prompt initiation of KD, when indicated for the treatment of severe diseases such as RSE. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  17. The efficacy of the ketogenic diet in infants and young children with refractory epilepsies using a formula-based powder.

    Science.gov (United States)

    Ashrafi, Mahmoud Reza; Hosseini, Seyed Ahmad; Zamani, Gholam Reza; Mohammadi, Mahmoud; Tavassoli, Alireza; Badv, Reza Shervin; Heidari, Morteza; Karimi, Parviz; Malamiri, Reza Azizi

    2017-03-01

    To evaluate the efficacy, safety, and tolerability of a classic 4:1 ketogenic diet using a formula-based powder in infants and children with refractory seizures who are reluctant to eat homemade foods. We conducted an open label trial and administered a ketogenic diet using formula-based power (Ketocal ® ). Twenty-seven infants and children aged between 12 months and 5 years were enrolled who had refractory seizures and were reluctant to eat homemade foods. Of 27 children, 5 were lost to follow-up and 22 were remained at the end of the study. After 4 months, the median frequency of seizures per week was reduced >50% in 68.2% of patients, while 9/22 children (40.9%) showed a 50-90% reduction in seizure frequency per week, and 6/22 children (27.3%) showed more than 90% reduction in seizure frequency per week. Over the study course, 6/22 (27%) children who continued to receive the diet developed constipation, one child developed gastroesophageal reflux, and one child developed hypercholesterolemia. None of these children discontinued the diet because of the complications. Thirteen children and their parents (59%) reported that the diet was palatable and tolerable enough. The ketogenic diet using a formula-based powder (Ketocal ® ) is effective, safe, and tolerable in infants and children with refractory seizures who are reluctant to eat homemade foods according to the rules of the ketogenic diet.

  18. Complications During Ketogenic Diet Initiation: Prevalence, Treatment, and Influence on Seizure Outcomes.

    Science.gov (United States)

    Lin, Abigail; Turner, Zahava; Doerrer, Sarah C; Stanfield, Anthony; Kossoff, Eric H

    2017-03-01

    Many centers still admit children for several days to start the ketogenic diet. The exact incidence of adverse effects during the admission and their potential later impact on seizure reduction has not been widely studied. We performed a retrospective study of children with intractable epilepsy electively admitted for ketogenic diet initiation at our institution from 2011 to 2016. Charts were reviewed for adverse effects during the admission period and then examined for seizure reduction and compliance at three months. A rating scale (1 to 4) was created for severity of any adverse events. A total of 158 children were included, with the mean age 4.6 years. Potentially attributable adverse effects occurred in 126 (80%) children, most commonly emesis, food refusal, and hypoglycemia. Seventy-three (46%) children received some form of intervention by the medical team, most commonly the administration of juice (24%). Younger age was correlated with an increased likelihood of moderate to severe adverse effects during admission, often repeated hypoglycemia (3.6 versus 4.9 years, P = 0.04). Fasting was more likely to result in lethargy and a single blood glucose in the 30 to 40 mg/dL range, but it was not correlated with emesis, repeated hypoglycemia, or higher adverse effect scores. There was no statistically significant correlation between the severity of adverse effects and the three-month seizure reduction. Mild easily treated adverse effects occurred in most children admitted for the ketogenic diet. Younger children were at greater risk for significant difficulties and should be monitored closely. Because fasting led to more lethargy and hypoglycemia, it may be prudent to avoid this in younger children. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Inhibition of Neuroblastoma Tumor Growth by Ketogenic Diet and/or Calorie Restriction in a CD1-Nu Mouse Model.

    Directory of Open Access Journals (Sweden)

    Raphael Johannes Morscher

    Full Text Available Neuroblastoma is a malignant pediatric cancer derived from neural crest cells. It is characterized by a generalized reduction of mitochondrial oxidative phosphorylation. The goal of the present study was to investigate the effects of calorie restriction and ketogenic diet on neuroblastoma tumor growth and monitor potential adaptive mechanisms of the cancer's oxidative phosphorylation system.Xenografts were established in CD-1 nude mice by subcutaneous injection of two neuroblastoma cell lines having distinct genetic characteristics and therapeutic sensitivity [SH-SY5Y and SK-N-BE(2]. Mice were randomized to four treatment groups receiving standard diet, calorie-restricted standard diet, long chain fatty acid based ketogenic diet or calorie-restricted ketogenic diet. Tumor growth, survival, metabolic parameters and weight of the mice were monitored. Cancer tissue was evaluated for diet-induced changes of proliferation indices and multiple oxidative phosphorylation system parameters (respiratory chain enzyme activities, western blot analysis, immunohistochemistry and mitochondrial DNA content.Ketogenic diet and/or calorie restriction significantly reduced tumor growth and prolonged survival in the xenograft model. Neuroblastoma growth reduction correlated with decreased blood glucose concentrations and was characterized by a significant decrease in Ki-67 and phospho-histone H3 levels in the diet groups with low tumor growth. As in human tumor tissue, neuroblastoma xenografts showed distinctly low mitochondrial complex II activity in combination with a generalized low level of mitochondrial oxidative phosphorylation, validating the tumor model. Neuroblastoma showed no ability to adapt its mitochondrial oxidative phosphorylation activity to the change in nutrient supply induced by dietary intervention.Our data suggest that targeting the metabolic characteristics of neuroblastoma could open a new front in supporting standard therapy regimens

  20. Inhibition of Neuroblastoma Tumor Growth by Ketogenic Diet and/or Calorie Restriction in a CD1-Nu Mouse Model.

    Science.gov (United States)

    Morscher, Raphael Johannes; Aminzadeh-Gohari, Sepideh; Feichtinger, René Gunther; Mayr, Johannes Adalbert; Lang, Roland; Neureiter, Daniel; Sperl, Wolfgang; Kofler, Barbara

    2015-01-01

    Neuroblastoma is a malignant pediatric cancer derived from neural crest cells. It is characterized by a generalized reduction of mitochondrial oxidative phosphorylation. The goal of the present study was to investigate the effects of calorie restriction and ketogenic diet on neuroblastoma tumor growth and monitor potential adaptive mechanisms of the cancer's oxidative phosphorylation system. Xenografts were established in CD-1 nude mice by subcutaneous injection of two neuroblastoma cell lines having distinct genetic characteristics and therapeutic sensitivity [SH-SY5Y and SK-N-BE(2)]. Mice were randomized to four treatment groups receiving standard diet, calorie-restricted standard diet, long chain fatty acid based ketogenic diet or calorie-restricted ketogenic diet. Tumor growth, survival, metabolic parameters and weight of the mice were monitored. Cancer tissue was evaluated for diet-induced changes of proliferation indices and multiple oxidative phosphorylation system parameters (respiratory chain enzyme activities, western blot analysis, immunohistochemistry and mitochondrial DNA content). Ketogenic diet and/or calorie restriction significantly reduced tumor growth and prolonged survival in the xenograft model. Neuroblastoma growth reduction correlated with decreased blood glucose concentrations and was characterized by a significant decrease in Ki-67 and phospho-histone H3 levels in the diet groups with low tumor growth. As in human tumor tissue, neuroblastoma xenografts showed distinctly low mitochondrial complex II activity in combination with a generalized low level of mitochondrial oxidative phosphorylation, validating the tumor model. Neuroblastoma showed no ability to adapt its mitochondrial oxidative phosphorylation activity to the change in nutrient supply induced by dietary intervention. Our data suggest that targeting the metabolic characteristics of neuroblastoma could open a new front in supporting standard therapy regimens. Therefore, we propose

  1. Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets.

    Science.gov (United States)

    Seyfried, Thomas N; Kiebish, Michael; Mukherjee, Purna; Marsh, Jeremy

    2008-11-01

    Information is presented on the calorically restricted ketogenic diet (CRKD) as an alternative therapy for brain cancer. In contrast to normal neurons and glia, which evolved to metabolize ketone bodies as an alternative fuel to glucose under energy-restricted conditions, brain tumor cells are largely glycolytic due to mitochondrial defects and have a reduced ability to metabolize ketone bodies. The CRKD is effective in managing brain tumor growth in animal models and in patients, and appears to act through antiangiogenic, anti-inflammatory, and proapoptotic mechanisms.

  2. Anticonvulsant profile of a balanced ketogenic diet in acute mouse seizure models.

    Science.gov (United States)

    Samala, Ramakrishna; Willis, Sarah; Borges, Karin

    2008-10-01

    Anticonvulsant effects of the ketogenic diet (KD) have been reported in the mouse, although previous studies did not control for intake of vitamins, minerals and antioxidants. The aim of this study was to examine the effects of balanced ketogenic and control diets in acute mouse seizure models. The behavior in four mouse seizure models, plasma d-beta-hydroxybutyrate (d-BHB) and glucose levels were determined after feeding control diet, 4:1 and 6:1 KDs with matched vitamins, minerals and antioxidants. Feeding 4:1 and 6:1 KDs ad lib to 3-week-old (adolescent) mice resulted in 1.2-2.2mM d-BHB in plasma, but did not consistently change glucose levels. The 6:1 KD reproducibly elevated the CC50 (current that initiates seizures in 50% mice tested) in the 6-Hz model after 14 days of feeding to adolescent CD1 mice. Higher plasma d-BHB levels correlated with anticonvulsant effects. Despite ketosis, no consistent anticonvulsant effects of KDs were found in the fluorothyl or pentylenetetrazole CD1 mouse models. The 4:1 KD was neither anticonvulsant nor neuroprotective in hippocampus in the C3H mouse kainate model. Taken together, the KD's anticonvulsant effect was limited to the 6-Hz model, required chronic feeding with 6:1 fat content, and was independent from lowering plasma glucose.

  3. KETOGENIC DIET – FROM THE IMPLEMENTATION IN CLINICAL PRACTICE TO NOWADAYS

    Directory of Open Access Journals (Sweden)

    Neli M. Ermenlieva

    2018-02-01

    Full Text Available Introduction: The ketogenic diet (KGD is a high-fat, adequate-protein, low-carbohydrate diet. In 1920`s the diet was developed to treat difficult-to-control epilepsy in children. Nowadays its efficacy has been proven in many other diseases, such as metabolic disorders, brain tumours, autism, Rett syndrome, and in other areas, it has been actively studied. Aim: The aim of this article is to represent the historical review of the therapeutic implication of KGD, as well as to reveal the contemporary clinical trends in which it is being used. Material and Methods: A literature review of 96 scientific reports in English has been made. Results and Discussion: The KGD was developed in the early 1920s. In the period 1970-1990, the therapeutic use of the diet was discontinued, due to the breakthrough of the new anticonvulsants for epilepsy. The interest in KGD was recovered after a meeting of the “American Epilepsy Society” in 1996. The diet demonstrates anticonvulsant efficacy in epilepsy therapy. According to a survey in 2013, the incidence of seizures among half of the number of children was reduced by at least a half, and 15% of them were completely discontinued. The diet is also used in the treatment of metabolic diseases, such as GLUT 1-deficiency syndrome, reducing the incidence of seizures, improving muscle coordination and concentration. It is also effective in pyruvate dehydrogenase deficiency syndrome by replacing the major energy source - glucose with ketones. Along with these, it is also used in patients with autism (in approximately 60% of patients it improves learning ability and social skills, Rett syndrome, Alzheimer's disease, Parkinson's disease, and others. Its mechanism of action is not fully clarified, as well as its degree of effectiveness in some areas. Conclusion: The ketogenic diet is widely implemented worldwide. It comprises a tremendous therapeutic potential that has been growing considerably during the past decades.

  4. The Effects of a Ketogenic Diet on Exercise Metabolism and Physical Performance in Off-Road Cyclists

    Directory of Open Access Journals (Sweden)

    Adam Zajac

    2014-06-01

    Full Text Available The main objective of this research was to determine the effects of a long-term ketogenic diet, rich in polyunsaturated fatty acids, on aerobic performance and exercise metabolism in off-road cyclists. Additionally, the effects of this diet on body mass and body composition were evaluated, as well as those that occurred in the lipid and lipoprotein profiles due to the dietary intervention. The research material included eight male subjects, aged 28.3 ± 3.9 years, with at least five years of training experience that competed in off-road cycling. Each cyclist performed a continuous exercise protocol on a cycloergometer with varied intensity, after a mixed and ketogenic diet in a crossover design. The ketogenic diet stimulated favorable changes in body mass and body composition, as well as in the lipid and lipoprotein profiles. Important findings of the present study include a significant increase in the relative values of maximal oxygen uptake (VO2max and oxygen uptake at lactate threshold (VO2 LT after the ketogenic diet, which can be explained by reductions in body mass and fat mass and/or the greater oxygen uptake necessary to obtain the same energy yield as on a mixed diet, due to increased fat oxidation or by enhanced sympathetic activation. The max work load and the work load at lactate threshold were significantly higher after the mixed diet. The values of the respiratory exchange ratio (RER were significantly lower at rest and during particular stages of the exercise protocol following the ketogenic diet. The heart rate (HR and oxygen uptake were significantly higher at rest and during the first three stages of exercise after the ketogenic diet, while the reverse was true during the last stage of the exercise protocol conducted with maximal intensity. Creatine kinase (CK and lactate dehydrogenase (LDH activity were significantly lower at rest and during particular stages of the 105-min exercise protocol following the low carbohydrate

  5. The effects of a ketogenic diet on exercise metabolism and physical performance in off-road cyclists.

    Science.gov (United States)

    Zajac, Adam; Poprzecki, Stanisław; Maszczyk, Adam; Czuba, Miłosz; Michalczyk, Małgorzata; Zydek, Grzegorz

    2014-06-27

    The main objective of this research was to determine the effects of a long-term ketogenic diet, rich in polyunsaturated fatty acids, on aerobic performance and exercise metabolism in off-road cyclists. Additionally, the effects of this diet on body mass and body composition were evaluated, as well as those that occurred in the lipid and lipoprotein profiles due to the dietary intervention. The research material included eight male subjects, aged 28.3 ± 3.9 years, with at least five years of training experience that competed in off-road cycling. Each cyclist performed a continuous exercise protocol on a cycloergometer with varied intensity, after a mixed and ketogenic diet in a crossover design. The ketogenic diet stimulated favorable changes in body mass and body composition, as well as in the lipid and lipoprotein profiles. Important findings of the present study include a significant increase in the relative values of maximal oxygen uptake (VO2max) and oxygen uptake at lactate threshold (VO2 LT) after the ketogenic diet, which can be explained by reductions in body mass and fat mass and/or the greater oxygen uptake necessary to obtain the same energy yield as on a mixed diet, due to increased fat oxidation or by enhanced sympathetic activation. The max work load and the work load at lactate threshold were significantly higher after the mixed diet. The values of the respiratory exchange ratio (RER) were significantly lower at rest and during particular stages of the exercise protocol following the ketogenic diet. The heart rate (HR) and oxygen uptake were significantly higher at rest and during the first three stages of exercise after the ketogenic diet, while the reverse was true during the last stage of the exercise protocol conducted with maximal intensity. Creatine kinase (CK) and lactate dehydrogenase (LDH) activity were significantly lower at rest and during particular stages of the 105-min exercise protocol following the low carbohydrate ketogenic diet

  6. Effectiveness of the ketogenic diet used to treat resistant childhood epilepsy in Scandinavia

    DEFF Research Database (Denmark)

    Hallböök, Tove; Sjölander, Arvid; Åmark, Per

    2015-01-01

    BACKGROUND: This Scandinavian collaborative retrospective study of children treated with ketogenic diet (KD) highlights indications and effectiveness over two years follow-up. METHODS: Five centres specialised in KD collected data retrospectively on 315 patients started on KD from 1999 to 2009....... Twenty-five patients who stopped the diet within four weeks because of compliance-problems and minor side-effects were excluded. Seizure-type(s), seizure-frequency, anti-epileptic drugs and other treatments, mental retardation, autism-spectrum disorder and motor-dysfunction were identified and treatment......-response was evaluated. RESULTS: An intention-to-treat analysis was used. Responders (>50% seizure-frequency reduction) at 6, 12 and 24 months were 50%, 46% and 28% respectively, seizure-free were 16%, 13% and 10%. Still on the diet were 80%, 64% and 41% after 6, 12 and 24 months. No child had an increased seizure...

  7. Ketogenic diet does not affect strength performance in elite artistic gymnasts

    Directory of Open Access Journals (Sweden)

    Paoli Antonio

    2012-07-01

    Full Text Available Abstract Background Despite the increasing use of very low carbohydrate ketogenic diets (VLCKD in weight control and management of the metabolic syndrome there is a paucity of research about effects of VLCKD on sport performance. Ketogenic diets may be useful in sports that include weight class divisions and the aim of our study was to investigate the influence of VLCKD on explosive strength performance. Methods 8 athletes, elite artistic gymnasts (age 20.9 ± 5.5 yrs were recruited. We analyzed body composition and various performance aspects (hanging straight leg raise, ground push up, parallel bar dips, pull up, squat jump, countermovement jump, 30 sec continuous jumps before and after 30 days of a modified ketogenic diet. The diet was based on green vegetables, olive oil, fish and meat plus dishes composed of high quality protein and virtually zero carbohydrates, but which mimicked their taste, with the addition of some herbal extracts. During the VLCKD the athletes performed the normal training program. After three months the same protocol, tests were performed before and after 30 days of the athletes’ usual diet (a typically western diet, WD. A one-way Anova for repeated measurements was used. Results No significant differences were detected between VLCKD and WD in all strength tests. Significant differences were found in body weight and body composition: after VLCKD there was a decrease in body weight (from 69.6 ± 7.3 Kg to 68.0 ± 7.5 Kg and fat mass (from 5.3 ± 1.3 Kg to 3.4 ± 0.8 Kg p  Conclusions Despite concerns of coaches and doctors about the possible detrimental effects of low carbohydrate diets on athletic performance and the well known importance of carbohydrates there are no data about VLCKD and strength performance. The undeniable and sudden effect of VLCKD on fat loss may be useful for those athletes who compete in sports based on weight class. We have demonstrated that using VLCKD for a

  8. Ketogenic diet does not affect strength performance in elite artistic gymnasts.

    Science.gov (United States)

    Paoli, Antonio; Grimaldi, Keith; D'Agostino, Dominic; Cenci, Lorenzo; Moro, Tatiana; Bianco, Antonino; Palma, Antonio

    2012-07-26

    Despite the increasing use of very low carbohydrate ketogenic diets (VLCKD) in weight control and management of the metabolic syndrome there is a paucity of research about effects of VLCKD on sport performance. Ketogenic diets may be useful in sports that include weight class divisions and the aim of our study was to investigate the influence of VLCKD on explosive strength performance. 8 athletes, elite artistic gymnasts (age 20.9 ± 5.5 yrs) were recruited. We analyzed body composition and various performance aspects (hanging straight leg raise, ground push up, parallel bar dips, pull up, squat jump, countermovement jump, 30 sec continuous jumps) before and after 30 days of a modified ketogenic diet. The diet was based on green vegetables, olive oil, fish and meat plus dishes composed of high quality protein and virtually zero carbohydrates, but which mimicked their taste, with the addition of some herbal extracts. During the VLCKD the athletes performed the normal training program. After three months the same protocol, tests were performed before and after 30 days of the athletes' usual diet (a typically western diet, WD). A one-way Anova for repeated measurements was used. No significant differences were detected between VLCKD and WD in all strength tests. Significant differences were found in body weight and body composition: after VLCKD there was a decrease in body weight (from 69.6 ± 7.3 Kg to 68.0 ± 7.5 Kg) and fat mass (from 5.3 ± 1.3 Kg to 3.4 ± 0.8 Kg p < 0.001) with a non-significant increase in muscle mass. Despite concerns of coaches and doctors about the possible detrimental effects of low carbohydrate diets on athletic performance and the well known importance of carbohydrates there are no data about VLCKD and strength performance. The undeniable and sudden effect of VLCKD on fat loss may be useful for those athletes who compete in sports based on weight class. We have demonstrated that using VLCKD for a relatively

  9. Reduced Mass and Diversity of the Colonic Microbiome in Patients with Multiple Sclerosis and Their Improvement with Ketogenic Diet

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    Alexander Swidsinski

    2017-06-01

    Full Text Available Background: Colonic microbiome is thought to be involved in auto-immune multiple sclerosis (MS. Interactions between diet and the colonic microbiome in MS are unknown.Methods: We compared the composition of the colonic microbiota quantitatively in 25 MS patients and 14 healthy controls.Fluorescence in situ hybridization (FISH with 162 ribosomal RNA derived bacterial FISH probes was used. Ten of the MS patients received a ketogenic diet for 6 months. Changes in concentrations of 35 numerically substantial bacterial groups were monitored at baseline and at 2, 12, and 23/24 weeks.Results: No MS typical microbiome pattern was apparent.The total concentrations and diversity of substantial bacterial groups were reduced in MS patients (P < 0.001. Bacterial groups detected with EREC (mainly Roseburia, Bac303 (Bacteroides, and Fprau (Faecalibacterium prausnitzii probes were diminished the most. The individual changes were multidirectional and inconsistent. The effects of a ketogenic diet were biphasic. In the short term, bacterial concentrations and diversity were further reduced. They started to recover at week 12 and exceeded significantly the baseline values after 23–24 weeks on the ketogenic diet.Conclusions: Colonic biofermentative function is markedly impaired in MS patients.The ketogenic diet normalized concentrations of the colonic microbiome after 6 months.

  10. Environmental Enrichment Mitigates Detrimental Cognitive Effects of Ketogenic Diet in Weanling Rats.

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    Scichilone, John M; Yarraguntla, Kalyan; Charalambides, Ana; Harney, Jacob P; Butler, David

    2016-09-01

    For decades, the ketogenic diet has been an effective treatment of intractable epilepsy in children. Childhood epilepsy is pharmacoresistant in 25-40 % of patients taking the current prescribed medications. Chronic seizure activity has been linked to deficits in cognitive function and behavioral problems which negatively affect the learning abilities of the child. Recent studies suggest the ketogenic diet (KD), a high fat with low carbohydrate and protein diet, has adverse effects on cognition in weanling rats. The diet reduces circulating glucose levels to where energy metabolism is converted from glycolysis to burning fat and generating ketone bodies which has been suggested as a highly efficient source of energy for the brain. In contrast, when weanling rats are placed in an enriched environment, they exhibit increased spatial learning, memory, and neurogenesis. Thus, this study was done to determine if weanling rats being administered a KD in an environmental enrichment (EE) would still exhibit the negative cognitive effects of the diet previously observed. The present study suggests that an altered environment is capable of reducing the cognitive deficits in weanling rats administered a KD. Learning was improved with an EE. The effect of diet and environment on anxiety and depression suggests a significant reduction in anxiety with enrichment rearing. Interestingly, circulating energy substrate levels were increased in the EE groups along with brain-derived neurotrophic factor despite the least changes in weight gain. In light of numerous studies using KDs that seemingly have adverse effects on cognition, KD-induced reductions in excitotoxic events would not necessarily eliminate that negative aspect of seizures.

  11. Can an early 24-hour EEG predict the response to the ketogenic diet? A prospective study in 34 children and adults with refractory epilepsy treated with the ketogenic diet

    NARCIS (Netherlands)

    Ebus, S.C.M.; Lambrechts, D.A.J.E.; Herraets, I.J.T.; Majoie, H.J.M.; Louw, de A.J.A.; Boon, P.; Aldenkamp, A.P.; Arends, J.B.A.M.

    2014-01-01

    Purpose We examined whether early EEG changes in a 24-h EEG at 6 weeks of treatment were related to the later clinical response to the ketogenic diet (KD) in a 6-month period of treatment. Methods We examined 34 patients with heterogeneous epilepsy syndromes (21 children, 13 adults) and found 9

  12. A ketogenic diet rescues hippocampal memory defects in a mouse model of Kabuki syndrome.

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    Benjamin, Joel S; Pilarowski, Genay O; Carosso, Giovanni A; Zhang, Li; Huso, David L; Goff, Loyal A; Vernon, Hilary J; Hansen, Kasper D; Bjornsson, Hans T

    2017-01-03

    Kabuki syndrome is a Mendelian intellectual disability syndrome caused by mutations in either of two genes (KMT2D and KDM6A) involved in chromatin accessibility. We previously showed that an agent that promotes chromatin opening, the histone deacetylase inhibitor (HDACi) AR-42, ameliorates the deficiency of adult neurogenesis in the granule cell layer of the dentate gyrus and rescues hippocampal memory defects in a mouse model of Kabuki syndrome (Kmt2d +/βGeo ). Unlike a drug, a dietary intervention could be quickly transitioned to the clinic. Therefore, we have explored whether treatment with a ketogenic diet could lead to a similar rescue through increased amounts of beta-hydroxybutyrate, an endogenous HDACi. Here, we report that a ketogenic diet in Kmt2d +/βGeo mice modulates H3ac and H3K4me3 in the granule cell layer, with concomitant rescue of both the neurogenesis defect and hippocampal memory abnormalities seen in Kmt2d +/βGeo mice; similar effects on neurogenesis were observed on exogenous administration of beta-hydroxybutyrate. These data suggest that dietary modulation of epigenetic modifications through elevation of beta-hydroxybutyrate may provide a feasible strategy to treat the intellectual disability seen in Kabuki syndrome and related disorders.

  13. The ketogenic diet is well tolerated and can be effective in patients with argininosuccinate lyase deficiency and refractory epilepsy

    NARCIS (Netherlands)

    Peuscher, Rosanne; Dijsselhof, Monique E.; Abeling, Nico G.; van Rijn, Margreet; van Spronsen, Francjan J.; Bosch, Annet M.

    2012-01-01

    Argininosuccinate lyase (ASL) deficiency (MIM 608310, McKusick 207900) is a rare disorder of the urea cycle, which leads to a deficiency of arginine and hyperammonemia. Epilepsy is a frequent complication of this disorder. A ketogenic diet (KD) can be a very effective therapy for refractory

  14. Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder.

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    Newell, Christopher; Bomhof, Marc R; Reimer, Raylene A; Hittel, Dustin S; Rho, Jong M; Shearer, Jane

    2016-01-01

    Gastrointestinal dysfunction and gut microbial composition disturbances have been widely reported in autism spectrum disorder (ASD). This study examines whether gut microbiome disturbances are present in the BTBR(T + tf/j) (BTBR) mouse model of ASD and if the ketogenic diet, a diet previously shown to elicit therapeutic benefit in this mouse model, is capable of altering the profile. Juvenile male C57BL/6 (B6) and BTBR mice were fed a standard chow (CH, 13 % kcal fat) or ketogenic diet (KD, 75 % kcal fat) for 10-14 days. Following diets, fecal and cecal samples were collected for analysis. Main findings are as follows: (1) gut microbiota compositions of cecal and fecal samples were altered in BTBR compared to control mice, indicating that this model may be of utility in understanding gut-brain interactions in ASD; (2) KD consumption caused an anti-microbial-like effect by significantly decreasing total host bacterial abundance in cecal and fecal matter; (3) specific to BTBR animals, the KD counteracted the common ASD phenotype of a low Firmicutes to Bacteroidetes ratio in both sample types; and (4) the KD reversed elevated Akkermansia muciniphila content in the cecal and fecal matter of BTBR animals. Results indicate that consumption of a KD likely triggers reductions in total gut microbial counts and compositional remodeling in the BTBR mouse. These findings may explain, in part, the ability of a KD to mitigate some of the neurological symptoms associated with ASD in an animal model.

  15. The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma.

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    Mohammed G Abdelwahab

    Full Text Available INTRODUCTION: The ketogenic diet (KD is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal® (KC is a nutritionally complete, commercially available 4:1 (fat:carbohydrate+protein ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis causes changes to brain homeostasis that have potential for the treatment of other neurological diseases such as malignant gliomas. METHODS: We used an intracranial bioluminescent mouse model of malignant glioma. Following implantation animals were maintained on standard diet (SD or KC. The mice received 2×4 Gy of whole brain radiation and tumor growth was followed by in vivo imaging. RESULTS: Animals fed KC had elevated levels of β-hydroxybutyrate (p = 0.0173 and an increased median survival of approximately 5 days relative to animals maintained on SD. KC plus radiation treatment were more than additive, and in 9 of 11 irradiated animals maintained on KC the bioluminescent signal from the tumor cells diminished below the level of detection (p<0.0001. Animals were switched to SD 101 days after implantation and no signs of tumor recurrence were seen for over 200 days. CONCLUSIONS: KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas.

  16. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy.

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    Maurer, Gabriele D; Brucker, Daniel P; Bähr, Oliver; Harter, Patrick N; Hattingen, Elke; Walenta, Stefan; Mueller-Klieser, Wolfgang; Steinbach, Joachim P; Rieger, Johannes

    2011-07-26

    Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic) diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2), 3-oxoacid-CoA transferase 1 (OXCT1) and acetyl-CoA acetyltransferase 1 (ACAT1) were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α) pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently target non-oxidative pathways.

  17. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy

    International Nuclear Information System (INIS)

    Maurer, Gabriele D; Brucker, Daniel P; Bähr, Oliver; Harter, Patrick N; Hattingen, Elke; Walenta, Stefan; Mueller-Klieser, Wolfgang; Steinbach, Joachim P; Rieger, Johannes

    2011-01-01

    Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic) diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2), 3-oxoacid-CoA transferase 1 (OXCT1) and acetyl-CoA acetyltransferase 1 (ACAT1) were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α) pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently target non-oxidative pathways

  18. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy

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    Mueller-Klieser Wolfgang

    2011-07-01

    Full Text Available Abstract Background Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. Methods To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. Results The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2, 3-oxoacid-CoA transferase 1 (OXCT1 and acetyl-CoA acetyltransferase 1 (ACAT1 were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. Conclusion In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic

  19. The impact of the ketogenic diet on arterial morphology and endothelial function in children and young adults with epilepsy: a case-control study.

    Science.gov (United States)

    Coppola, Giangennaro; Natale, Francesco; Torino, Annarita; Capasso, Rosanna; D'Aniello, Alfredo; Pironti, Erica; Santoro, Elena; Calabrò, Raffaele; Verrotti, Alberto

    2014-04-01

    The present study aimed to assess the impact of the ketogenic diet on arterial morphology and endothelial function of the big vessels of the neck and on cardiac diastolic function, in a cohort of epileptic children and young adults treated with the ketogenic diet. Patients were recruited based on the following inclusion criteria: (1) patients who were or had been on the ketogenic diet for a time period of at least six months. Each patient underwent measurement of carotid intima media thickness, carotid artery stiffness, echocardiography, and diastolic function assessment. Patients with drug resistant epilepsy, matched for number, age and sex and never treated with ketogenic diet, were recruited as controls. The population study was composed by 43 epilepsy patients (23 males), aged between 19 months and 31 years (mean 11 years). Twenty-three patients were or had been treated with ketogenic diet, and 20 had never been on it (control group). Subjects treated with the ketogenic diet had higher arterial stiffness parameters, including AIx and β-index and higher serum levels of cholesterol or triglycerides compared to those who had never been on the diet (control group) (pketogenic diet, before the increase of the intima media thickness. This supports that arterial stiffness is an early marker of vascular damage. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  20. Urolithiasis on the ketogenic diet with concurrent topiramate or zonisamide therapy

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    Paul, Elahna; Conant, Kerry D.; Dunne, Irie E.; Pfeifer, Heidi H.; Lyczkowski, David A.; Linshaw, Michael A.; Thiele, Elizabeth A.

    2011-01-01

    Summary Children with refractory epilepsy who are co-treated with the ketogenic diet (KD) and carbonic anhydrase inhibitor (CA-I) anti-epileptic medications including topiramate (TPM) and zonisamide (ZNS) are at risk for urolithiasis. Retrospective chart review of all children treated with ketogenic therapy at our institution was performed in order to estimate the minimal risk of developing signs or symptoms of stone disease. Children (N = 93) were classified into groups according to KD +/− CA-I co-therapy. Fourteen patients had occult hematuria or worse, including 6 with radiologically confirmed stones. Three of 6 calculi developed in the KD + ZNS group of 17 patients who were co-treated for a cumulative total of 97 months (3.1 stones per 100 patient months). One confirmed stone was in the KD + TPM group of 22 children who were co-treated for a cumulative total of 263 months (0.4 stones per 100 patient months). All six patients had at least three of five biochemical risk factors including metabolic acidosis, concentrated urine, acid urine, hypercalciuria and hypocitraturia. Standard of care interventions to minimize hypercalciuria, crystalluria and stone formation used routinely by pediatric nephrologists should also be prescribed by neurologists treating patients with combination anti-epileptic therapy. Non-fasting KD initiation, fluid liberalization, potassium citrate prophylaxis as well as regular laboratory surveillance are indicated in this high risk population. PMID:20466520

  1. Ketogenic diet improves behaviors in a maternal immune activation model of autism spectrum disorder.

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    David N Ruskin

    Full Text Available Prenatal factors influence autism spectrum disorder (ASD incidence in children and can increase ASD symptoms in offspring of animal models. These may include maternal immune activation (MIA due to viral or bacterial infection during the first trimesters. Unfortunately, regardless of ASD etiology, existing drugs are poorly effective against core symptoms. For nearly a century a ketogenic diet (KD has been used to treat seizures, and recent insights into mechanisms of ASD and a growing recognition that immune/inflammatory conditions exacerbate ASD risk has increased interest in KD as a treatment for ASD. Here we studied the effects of KD on core ASD symptoms in offspring exposed to MIA. To produce MIA, pregnant C57Bl/6 mice were injected with the viral mimic polyinosinic-polycytidylic acid; after weaning offspring were fed KD or control diet for three weeks. Consistent with an ASD phenotype of a higher incidence in males, control diet-fed MIA male offspring were not social and exhibited high levels of repetitive self-directed behaviors; female offspring were unaffected. However, KD feeding partially or completely reversed all MIA-induced behavioral abnormalities in males; it had no effect on behavior in females. KD-induced metabolic changes of reduced blood glucose and elevated blood ketones were quantified in offspring of both sexes. Prior work from our laboratory and others demonstrate KDs improve relevant behaviors in several ASD models, and here we demonstrate clear benefits of KD in the MIA model of ASD. Together these studies suggest a broad utility for metabolic therapy in improving core ASD symptoms, and support further research to develop and apply ketogenic and/or metabolic strategies in patients with ASD.

  2. Beneficial effect of feeding a ketogenic diet to mothers on brain development in their progeny with a murine model of pyruvate dehydrogenase complex deficiency

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    Lioudmila Pliss

    2016-06-01

    Conclusion: The findings provide for the first time experimental support for beneficial effects of a ketogenic diet during the prenatal and early postnatal periods on the brain development of PDC-deficient mammalian progeny.

  3. The Short-Term Effect of Ketogenic Diet on Carotid Intima-Media Thickness and Elastic Properties of the Carotid Artery and the Aorta in Epileptic Children.

    Science.gov (United States)

    Doksöz, Önder; Güzel, Orkide; Yılmaz, Ünsal; İşgüder, Rana; Çeleğen, Kübra; Meşe, Timur; Uysal, Utku

    2015-10-01

    The aim of this prospective study is to investigate the effect of a 6-month-long ketogenic diet on carotid intima-media thickness, carotid artery, and aortic vascular functions. Thirty-eight drug-resistant epileptic patients who were being treated with ketogenic diet were enrolled. Fasting total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, total cholesterol, and glucose concentrations were measured and echocardiography was performed in all patients before the beginning of ketogenic diet and at the sixth month of treatment. The body weight, height, body mass index, serum levels of triglyceride, total cholesterol, and low-density lipoprotein increased significantly at month 6 when compared to baseline values (P ketogenic diet has no effect on carotid intima-media thickness and elastic properties of the carotid artery and the aorta. © The Author(s) 2015.

  4. Investigating the Ketogenic Diet As Treatment for Primary Aggressive Brain Cancer: Challenges and Lessons Learned

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    Kenneth A. Schwartz

    2018-02-01

    Full Text Available Survival of glioblastoma multiforme (GBM with the current recommended treatment is poor. Reported median survivals are approximately 8–15 months. Based on recent publications from animal models, combining cancer drugs, radiation, and diet-metabolic treatments may be a new route to better survivals. To investigate this possibility, we have begun a clinical trial that has enrolled 15 subjects using a ketogenic diet (KD as an addition to current standard treatments that include surgery, radiation therapy, and chemotherapy. Of the 15 enrolled, 10 completed the protocol. This perspective describes the challenges and lessons learned during this clinical trial and discusses the critical elements that are essential for investigating treatment with a KD. We also reviewed and compared various types of KDs. We believe that the diet selected should be standardized within individual clinical trials, and more importantly, the patients’ blood should be monitored for glucose and ketones twice daily so that the supervising dietitian can work with the patient and their caregivers to make appropriate changes in the diet. Compliance with the diet is best in highly motivated patients who have excellent home support from a family member or a friend who can help to overcome administrative, physical, and cognition deficiencies associated with the disease. Treatment of GBM using a KD represents a reasonable investigative approach. This perspective summarizes the challenges and lessons learned implementing and continuing KD therapy while the patients are concurrently being treated with radiation and chemotherapy.

  5. Ketogenic Diet: An Early Option for Epilepsy Treatment, Instead of A Last Choice Only

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    Huei-Shyong Wang

    2012-02-01

    Full Text Available Ketogenic diet (KD was usually tried as a last resort in the treatment of intractable epilepsy after failure of many antiepileptics and even epilepsy surgery. Glucose transporter-1 deficiency and pyruvate dehydrogenase deficiency must be treated with KD as the first choice because of inborn errors of glucose metabolism. Infantile spasms, tuberous sclerosis complex, Rett syndrome, Doose syndrome, Dravet syndrome, etc., appear to respond to KD, and it has been suggested by the international consensus statement to use KD early. We believe that all patients with epilepsy, except those with contraindicated situations such as pyruvate carboxylase deficiency, porphyria, β-oxidation defects, primary carnitine deficiency, etc., may try KD before trying other regimens.

  6. Ketogenic diet and childhood neurological disorders other than epilepsy: an overview.

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    Verrotti, Alberto; Iapadre, Giulia; Pisano, Simone; Coppola, Giangennaro

    2017-05-01

    In the last years, ketogenic diet (KD) has been experimentally utilized in various childhood neurologic disorders such as mitochondriopathies, alternating hemiplegia of childhood (AHC), brain tumors, migraine, and autism spectrum disorder (ASD). The aim of this review is to analyze how KD can target these different medical conditions, highlighting possible mechanisms involved. Areas covered: We have conducted an analysis on literature concerning KD use in mitochondriopathies, AHC, brain tumors, migraine, and ASD. Expert commentary: The role of KD in reducing seizure activity in some mitochondriopathies and its efficacy in pyruvate dehydrogenase deficiency is known. Recently, few cases suggest the potentiality of KD in decreasing paroxysmal activity in children affected by AHC. A few data support its potential use as co-adjuvant and alternative therapeutic option for brain cancer, while any beneficial effect of KD on migraine remains unclear. KD could improve cognitive and social skills in a subset of children with ASD.

  7. Obesity treatment by very low-calorie-ketogenic diet at two years: reduction in visceral fat and on the burden of disease.

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    Moreno, Basilio; Crujeiras, Ana B; Bellido, Diego; Sajoux, Ignacio; Casanueva, Felipe F

    2016-12-01

    The long-term effect of therapeutic diets in obesity treatment is a challenge at present. The current study aimed to evaluate the long-term effect of a very low-calorie-ketogenic (VLCK) diet on excess adiposity. Especial focus was set on visceral fat mass, and the impact on the individual burden of disease. A group of obese patients (n = 45) were randomly allocated in two groups: either the very low-calorie-ketogenic diet group (n = 22), or a standard low-calorie diet group; (n = 23). Both groups received external support. Adiposity parameters and the cumulative number of months of successful weight loss (5 or 10 %) over a 24-month period were quantified. The very low-calorie-ketogenic diet induced less than 2 months of mild ketosis and significant effects on body weight at 6, 12, and 24 months. At 24 months, a trend to regress to baseline levels was observed; however, the very low-calorie-ketogenic diet induced a greater reduction in body weight (-12.5 kg), waist circumference (-11.6 cm), and body fat mass (-8.8 kg) than the low-calorie diet (-4.4 kg, -4.1 cm, and -3.8 kg, respectively; p ketogenic diet group experienced a reduction in the individual burden of obesity because reduction in disease duration. Very low-calorie-ketogenic diet patients were 500 months with 5 % weight lost vs. the low-calorie diet group (350 months; p ketogenic diet was effective 24 months later, with a decrease in visceral adipose tissue and a reduction in the individual burden of disease.

  8. To treat or not to treat drug-refractory epilepsy by the ketogenic diet? That is the question.

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    Ułamek-Kozioł, Marzena; Pluta, Ryszard; Bogucka-Kocka, Anna; Czuczwar, Stanisław J

    2016-12-23

    Epilepsy is a serious neurologic disorder worldwide which affects about 1% of the population (ca. 50 million people), the highest prevalence occurring in both children and elderly. Apart from idiopathic forms, etiology of the disease involves multiple brain risk factors - the most frequent being cerebrovascular diseases, tumours and traumatic injuries. Several treatment options exist, including, for instance, pharmacotherapy, vagal nerve stimulation or epilepsy surgery. In spite of treatment, about 30% of patients with epilepsy still have seizures and become drug-refractory. This is why other treatment options may be recommended, and ketogenic diet seems a last-chance method, especially in children and adolescents with epilepsy. The diet contains high amounts of fat and low carbohydrates with vitamin supplementation. The elevated concentrations of ketones induced by the diet may result in inhibition of the synaptic activity of glutamate, the mammalian target of the rapamycin pathway, and activation of adenosine triphosphate-sensitive potassium channels. One of the main ketones is acetone, shown to increase the seizure threshold and potentiate the anticonvulsant activity of some antiepileptic drugs. The clinical effectiveness of the ketogenic diet has been confirmed in a number of clinical trials carried out mainly on children. A wider use of the ketogenic diet may be limited by the number of early adverse effects (gastrointestinal distress, acidosis, hypoglycaemia, dehydration and lethargy), and late adverse effects (hyperuricaemia, hyperlipidaemia, kidney stones, easy bruising, and decreases in height and weight). Recently, data are available on the negative impact of the ketogenic diet on the qualitative characteristics of lipoprotein subfractions which points to the atherogenic fenotype as a new side-effect. In conclusion, future research directed to the proper identification of patients (in terms of age, epilepsy type and duration, recommended antiepileptic

  9. A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease

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    Van Leuven Fred

    2005-10-01

    Full Text Available Abstract Background Alzheimer's disease (AD is a progressive neurodegenerative disorder that primarily strikes the elderly. Studies in both humans and animal models have linked the consumption of cholesterol and saturated fats with amyloid-β (Aβ deposition and development of AD. Yet, these studies did not examine high fat diets in combination with reduced carbohydrate intake. Here we tested the effect of a high saturated fat/low carbohydrate diet on a transgenic mouse model of AD. Results Starting at three months of age, two groups of female transgenic mice carrying the "London" APP mutation (APP/V717I were fed either, a standard diet (SD composed of high carbohydrate/low fat chow, or a ketogenic diet (KD composed of very low carbohydrate/high saturated fat chow for 43 days. Animals fed the KD exhibited greatly elevated serum ketone body levels, as measured by β-hydroxybutyrate (3.85 ± 2.6 mM, compared to SD fed animals (0.29 ± 0.06 mM. In addition, animals fed the KD lost body weight (SD 22.2 ± 0.6 g vs. KD 17.5 ± 1.4 g, p = 0.0067. In contrast to earlier studies, the brief KD feeding regime significantly reduced total brain Aβ levels by approximately 25%. Despite changes in ketone levels, body weight, and Aβ levels, the KD diet did not alter behavioral measures. Conclusion Previous studies have suggested that diets rich in cholesterol and saturated fats increased the deposition of Aβ and the risk of developing AD. Here we demonstrate that a diet rich in saturated fats and low in carbohydrates can actually reduce levels of Aβ. Therefore, dietary strategies aimed at reducing Aβ levels should take into account interactions of dietary components and the metabolic outcomes, in particular, levels of carbohydrates, total calories, and presence of ketone bodies should be considered.

  10. Very low-calorie ketogenic diet may allow restoring response to systemic therapy in relapsing plaque psoriasis.

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    Castaldo, Giuseppe; Galdo, Giovanna; Rotondi Aufiero, Felice; Cereda, Emanuele

    2016-01-01

    Psoriasis is a chronic disease associated with overweight/obesity and related cardiometabolic complications. The link between these diseases is likely the inflammatory background associated with adipose tissue, particularly the visceral one. Accordingly, previous studies have demonstrated that in the long-term weight loss may improve the response to systemic therapies. We report a case report of a woman in her 40s suffering from relapsing moderate-to-severe plaque psoriasis and obesity-related metabolic syndrome, in whom adequate response to ongoing treatment with biological therapy (adalimumab) was restored after only 4 weeks of very low-calorie, carbohydrate-free (ketogenic), protein-based diet. Accordingly, through rapid and consistent weight loss, very low calorie ketogenic diet may allow restoring a quick response to systemic therapy in a patient suffering from relapsing psoriasis. This intervention should be considered in overweight/obese patients before the rearrangement of systemic therapy. Nonetheless, studies are required to evaluate whether very low calorie ketogenic diets should be preferred to common low-calorie diets to improve the response to systemic therapy at least in patients with moderate-to-severe psoriasis. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  11. Pediatric patients on ketogenic diet undergoing general anesthesia-a medical record review.

    Science.gov (United States)

    Soysal, Elif; Gries, Heike; Wray, Carter

    2016-12-01

    To identify guidelines for anesthesia management and determine whether general anesthesia is safe for pediatric patients on ketogenic diet (KD). Retrospective medical record review. Postoperative recovery area. All pediatric patients who underwent general anesthesia while on KD between 2009 and 2014 were reviewed. We identified 24 patients who underwent a total of 33 procedures. All children were on KD due to intractable epilepsy. The age of patients ranged from 1 to 15 years. General anesthesia for the scheduled procedures. Patients' demographics, seizure history, type of procedure; perioperative blood chemistry, medications including the anesthesia administered, and postoperative complications. Twenty-four patients underwent a total of 33 procedures. The duration of KD treatment at the time of general anesthesia ranged from 4 days to 8 years. Among the 33 procedures, 3 patients had complications that could be attributable to KD and general anesthesia. A 9-year-old patient experienced increased seizures on postoperative day 0. An 8-year-old patient with hydropcephalus developed metabolic acidosis on postoperative day 1, and a 7-year-old patient's procedure was complicated by respiratory distress and increased seizure activity in the postanesthesia care unit. This study showed that it is relatively safe for children on KD to undergo general anesthesia. The 3 complications attributable to general anesthesia were mild, and the increased seizure frequencies in 2 patients returned back to baseline in 24 hours. Although normal saline is considered more beneficial than lactated Ringer's solution in patients on KD, normal saline should also be administered carefully because of the risk of exacerbating patients' metabolic acidosis. One should be aware of the potential change of the ketogenic status due to drugs given intraoperatively. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. An observational study of sequential protein-sparing, very low-calorie ketogenic diet (Oloproteic diet) and hypocaloric Mediterranean-like diet for the treatment of obesity.

    Science.gov (United States)

    Castaldo, Giuseppe; Monaco, Luigi; Castaldo, Laura; Galdo, Giovanna; Cereda, Emanuele

    2016-09-01

    The impact of a rehabilitative multi-step dietary program consisting in different diets has been scantily investigated. In an open-label study, 73 obese patients underwent a two-phase weight loss (WL) program: a 3-week protein-sparing, very low-calorie, ketogenic diet (Diet) and a 6-week hypocaloric (25-30 kcal/kg of ideal body weight/day), low glycemic index, Mediterranean-like diet (hypo-MD). Both phases improved visceral adiposity, liver enzymes, GH levels, blood pressure and glucose and lipid metabolism. However, the hypo-MD was responsible for a re-increase in blood lipids and glucose tolerance parameters. Changes in visceral adiposity and glucose control-related variables were more consistent in patients with metabolic syndrome. However, in these patients the hypo-MD did not result in a consistent re-increase in glucose control-related variables. A dietary program consisting in a ketogenic regimen followed by a balanced MD appeared to be feasible and efficacious in reducing cardiovascular risk, particularly in patients with metabolic syndrome.

  13. Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) may respond to adjunctive ketogenic diet.

    Science.gov (United States)

    Steriade, Claude; Andrade, Danielle M; Faghfoury, Hanna; Tarnopolsky, Mark A; Tai, Peter

    2014-05-01

    Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome can present management challenges. Refractory seizures and stroke-like episodes leading to disability are common. We analyzed the clinical, electrophysiologic, and radiologic data of a 22-year-old woman with multiple episodes of generalized and focal status epilepticus and migratory cortical stroke-like lesions who underwent muscle biopsy for mitochondrial genome sequencing. Although initial mitochondrial genetic testing was negative, muscle biopsy demonstrated a mitochondrial DNA disease-causing mutation (m.3260A > G). New antiepileptic medications were added with each episode of focal status epilepticus with only temporary improvement, until a modified ketogenic diet and magnesium were introduced, leading to seizure freedom despite development of a new stroke-like lesion, and subsequent decrease in frequency of stroke-like episodes. We propose a metabolic model in which the ketogenic diet may lead to improvement of the function of respiratory chain complexes. The ketogenic diet may lead to improvement of mitochondrial dysfunction in MELAS, which in turn may promote better seizure control and less frequent stroke-like episodes. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  14. The development of tumours under a ketogenic diet in association with the novel tumour marker TKTL1: A case series in general practice.

    Science.gov (United States)

    Jansen, Natalie; Walach, Harald

    2016-01-01

    Since the initial observations by Warburg in 1924, it has become clear in recent years that tumour cells require a high level of glucose to proliferate. Therefore, a ketogenic diet that provides the body with energy mainly through fat and proteins, but contains a reduced amount of carbohydrates, has become a dietary option for supporting tumour treatment and has exhibited promising results. In the present study, the first case series of such a treatment in general practice is presented, in which 78 patients with tumours were treated within a time window of 10 months. The patients were monitored regarding their levels of transketolase-like-1 (TKTL1), a novel tumour marker associated with aerobic glycolysis of tumour cells, and the patients' degree of adherence to a ketogenic diet. Tumour progression was documented according to oncologists' reports. Tumour status was correlated with TKTL1 expression (Kruskal-Wallis test, Pketogenic diet, with one patient experiencing a stagnation in tumour progression and others an improvement in their condition. The adoption of a ketogenic diet was also observed to affect the levels of TKTL1 in those patients. In conclusion, the results from the present case series in general practice suggest that it may be beneficial to advise tumour patients to adopt a ketogenic diet, and that those who adhere to it may have positive results from this type of diet. Thus, the use of a ketogenic diet as a complementary treatment to tumour therapy must be further studied in rigorously controlled trials.

  15. An 8-Week Ketogenic Low Carbohydrate, High Fat Diet Enhanced Exhaustive Exercise Capacity in Mice.

    Science.gov (United States)

    Ma, Sihui; Huang, Qingyi; Yada, Koichi; Liu, Chunhong; Suzuki, Katsuhiko

    2018-05-25

    Current fueling tactics for endurance exercise encourage athletes to ingest a high carbohydrate diet. However, athletes are not generally encouraged to use fat, the largest energy reserve in the human body. A low carbohydrate, high fat ketogenic diet (KD) is a nutritional approach ensuring that the body utilizes lipids. Although KD has been associated with weight-loss, enhanced fat utilization in muscle and other beneficial effects, there is currently no clear proof whether it could lead to performance advantage. To evaluate the effects of KD on endurance exercise capacity, we studied the performance of mice subjected to a running model after consuming KD for eight weeks. Weight dropped dramatically in KD-feeding mice, even though they ate more calories. KD-feeding mice showed enhanced running time without aggravated muscle injury. Blood biochemistry and correlation analysis indicated the potential mechanism is likely to be a keto-adaptation enhanced capacity to transport and metabolize fat. KD also showed a potential preventive effect on organ injury caused by acute exercise, although KD failed to exert protection from muscle injury. Ultimately, KD may contribute to prolonged exercise capacity.

  16. An 8-Week Ketogenic Low Carbohydrate, High Fat Diet Enhanced Exhaustive Exercise Capacity in Mice

    Directory of Open Access Journals (Sweden)

    Sihui Ma

    2018-05-01

    Full Text Available Current fueling tactics for endurance exercise encourage athletes to ingest a high carbohydrate diet. However, athletes are not generally encouraged to use fat, the largest energy reserve in the human body. A low carbohydrate, high fat ketogenic diet (KD is a nutritional approach ensuring that the body utilizes lipids. Although KD has been associated with weight-loss, enhanced fat utilization in muscle and other beneficial effects, there is currently no clear proof whether it could lead to performance advantage. To evaluate the effects of KD on endurance exercise capacity, we studied the performance of mice subjected to a running model after consuming KD for eight weeks. Weight dropped dramatically in KD-feeding mice, even though they ate more calories. KD-feeding mice showed enhanced running time without aggravated muscle injury. Blood biochemistry and correlation analysis indicated the potential mechanism is likely to be a keto-adaptation enhanced capacity to transport and metabolize fat. KD also showed a potential preventive effect on organ injury caused by acute exercise, although KD failed to exert protection from muscle injury. Ultimately, KD may contribute to prolonged exercise capacity.

  17. The Nervous System and Metabolic Dysregulation: Emerging Evidence Converges on Ketogenic Diet Therapy

    Science.gov (United States)

    Ruskin, David N.; Masino, Susan A.

    2012-01-01

    A link between metabolism and brain function is clear. Since ancient times, epileptic seizures were noted as treatable with fasting, and historical observations of the therapeutic benefits of fasting on epilepsy were confirmed nearly 100 years ago. Shortly thereafter a high fat, low-carbohydrate ketogenic diet (KD) debuted as a therapy to reduce seizures. This strict regimen could mimic the metabolic effects of fasting while allowing adequate caloric intake for ongoing energy demands. Today, KD therapy, which forces predominantly ketone-based rather than glucose-based metabolism, is now well-established as highly successful in reducing seizures. Cellular metabolic dysfunction in the nervous system has been recognized as existing side-by-side with nervous system disorders – although often with much less obvious cause-and-effect as the relationship between fasting and seizures. Rekindled interest in metabolic and dietary therapies for brain disorders complements new insight into their mechanisms and broader implications. Here we describe the emerging relationship between a KD and adenosine as a way to reset brain metabolism and neuronal activity and disrupt a cycle of dysfunction. We also provide an overview of the effects of a KD on cognition and recent data on the effects of a KD on pain, and explore the relative time course quantified among hallmark metabolic changes, altered neuron function and altered animal behavior assessed after diet administration. We predict continued applications of metabolic therapies in treating dysfunction including and beyond the nervous system. PMID:22470316

  18. PPARα deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPARγ activation in the liver

    International Nuclear Information System (INIS)

    Oishi, Katsutaka; Uchida, Daisuke; Ohkura, Naoki; Horie, Shuichi

    2010-01-01

    Research highlights: → PPARα deficiency augments a ketogenic diet-induced circadian PAI-1 expression. → Hepatic expressions of PPARγ and PCG-1α are induced by a ketogenic diet. → PPARγ antagonist attenuates a ketogenic diet-induced PAI-1 expression. → Ketogenic diet advances the phase of circadian clock in a PPARα-independent manner. -- Abstract: An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD). To determine whether peroxisome proliferator-activated receptor α (PPARα) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPARα-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPARα-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPARα target genes such as Cyp4A10 and FGF21 was damped in PPARα-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPARα-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPARα activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPARγ and its coactivator PCG-1α were more effectively induced in PPARα-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPARγ antagonist, in both WT and PPARα-null mice. PPARγ activation seems to be involved in KD-induced hypofibrinolysis by augmenting PAI-1 gene expression

  19. Ketogenic diet is antiepileptogenic in pentylenetetrazole kindled mice and decrease levels of N-acylethanolamines in hippocampus

    DEFF Research Database (Denmark)

    Hansen, Suzanne L; Nielsen, Ane H; Knudsen, Katrine E

    2009-01-01

    The ketogenic diet (KD) is used for the treatment of refractory epilepsy in children, however, the mechanism(s) remains largely unknown. Also, the antiepileptogenic potential in animal models of epilepsy has been poorly addressed. Activation of cannabinoid type-1 receptor (CB(1)-R) upon seizure...... activity or type of diet. The level of oleoylethanolamide as well as the sum of N-acylethanolamines were significantly decreased by the KD, but were unaffected by seizure activity. The study shows that the KD had clear antiepileptogenic properties in the pentylenetetrazole kindling model and does...

  20. Ketogenic diet improves forelimb motor function after spinal cord injury in rodents.

    Directory of Open Access Journals (Sweden)

    Femke Streijger

    Full Text Available High fat, low carbohydrate ketogenic diets (KD are validated non-pharmacological treatments for some forms of drug-resistant epilepsy. Ketones reduce neuronal excitation and promote neuroprotection. Here, we investigated the efficacy of KD as a treatment for acute cervical spinal cord injury (SCI in rats. Starting 4 hours following C5 hemi-contusion injury animals were fed either a standard carbohydrate based diet or a KD formulation with lipid to carbohydrate plus protein ratio of 3:1. The forelimb functional recovery was evaluated for 14 weeks, followed by quantitative histopathology. Post-injury 3:1 KD treatment resulted in increased usage and range of motion of the affected forepaw. Furthermore, KD improved pellet retrieval with recovery of wrist and digit movements. Importantly, after returning to a standard diet after 12 weeks of KD treatment, the improved forelimb function remained stable. Histologically, the spinal cords of KD treated animals displayed smaller lesion areas and more grey matter sparing. In addition, KD treatment increased the number of glucose transporter-1 positive blood vessels in the lesion penumbra and monocarboxylate transporter-1 (MCT1 expression. Pharmacological inhibition of MCTs with 4-CIN (α-cyano-4-hydroxycinnamate prevented the KD-induced neuroprotection after SCI, In conclusion, post-injury KD effectively promotes functional recovery and is neuroprotective after cervical SCI. These beneficial effects require the function of monocarboxylate transporters responsible for ketone uptake and link the observed neuroprotection directly to the function of ketones, which are known to exert neuroprotection by multiple mechanisms. Our data suggest that current clinical nutritional guidelines, which include relatively high carbohydrate contents, should be revisited.

  1. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis

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    Humala Nelson

    2006-04-01

    Full Text Available Abstract Background The cause of neuronal death in amyotrophic lateral sclerosis (ALS is uncertain but mitochondrial dysfunction may play an important role. Ketones promote mitochondrial energy production and membrane stabilization. Results SOD1-G93A transgenic ALS mice were fed a ketogenic diet (KD based on known formulations for humans. Motor performance, longevity, and motor neuron counts were measured in treated and disease controls. Because mitochondrial dysfunction plays a central role in neuronal cell death in ALS, we also studied the effect that the principal ketone body, D-β-3 hydroxybutyrate (DBH, has on mitochondrial ATP generation and neuroprotection. Blood ketones were > 3.5 times higher in KD fed animals compared to controls. KD fed mice lost 50% of baseline motor performance 25 days later than disease controls. KD animals weighed 4.6 g more than disease control animals at study endpoint; the interaction between diet and change in weight was significant (p = 0.047. In spinal cord sections obtained at the study endpoint, there were more motor neurons in KD fed animals (p = 0.030. DBH prevented rotenone mediated inhibition of mitochondrial complex I but not malonate inhibition of complex II. Rotenone neurotoxicity in SMI-32 immunopositive motor neurons was also inhibited by DBH. Conclusion This is the first study showing that diet, specifically a KD, alters the progression of the clinical and biological manifestations of the G93A SOD1 transgenic mouse model of ALS. These effects may be due to the ability of ketone bodies to promote ATP synthesis and bypass inhibition of complex I in the mitochondrial respiratory chain.

  2. The effect of ketogenic diet in an animal model of autism induced by prenatal exposure to valproic acid.

    Science.gov (United States)

    Castro, Kamila; Baronio, Diego; Perry, Ingrid Schweigert; Riesgo, Rudimar Dos Santos; Gottfried, Carmem

    2017-07-01

    Autism spectrum disorder (ASD) is characterized by impairments in social interaction and communication, and by restricted repetitive behaviors and interests. Its etiology is still unknown, but different environmental factors during pregnancy, such as exposure to valproic acid (VPA), are associated with high incidence of ASD in children. In this context, prenatal exposure to VPA in rodents has been used as a reliable model of ASD. Ketogenic diet (KD) is an alternative therapeutic option for refractory epilepsy; however, the effects of this approach in ASD-like behavior need to be evaluated. We conducted a behavioral assessment of the effects of KD in the VPA model of autism. Pregnant animals received a single-intraperitoneal injection of 600 mg/kg VPA, and their offspring were separated into four groups: (1) control group with standard diet (C-SD), (2) control group with ketogenic diet (C-KD), (3) VPA group with standard diet (VPA-SD), and (4) VPA group with ketogenic diet (VPA-KD). When compared with the control group, VPA animals presented increased social impairment, repetitive behavior and higher nociceptive threshold. Interestingly, the VPA group fed with KD presented improvements in social behavior. These mice displayed higher scores in sociability index and social novelty index when compared with the SD-fed VPA mice. VPA mice chronically exposed to a KD presented behavioral improvements; however, the mechanism by which KD improves ASD-like features needs to be further investigated. In conclusion, the present study reinforces the potential use of KD as a treatment for the core deficits of ASD.

  3. Is the interaction between fatty acids and tryptophan responsible for the efficacy of a ketogenic diet in epilepsy? The new hypothesis of action.

    Science.gov (United States)

    Maciejak, P; Szyndler, J; Turzyńska, D; Sobolewska, A; Kołosowska, K; Krząścik, P; Płaźnik, A

    2016-01-28

    The effects of a ketogenic diet in controlling seizure activity have been proven in many studies, although its mechanism of action remains elusive in many regards. We hypothesize that the ketogenic diet may exert its antiepileptic effects by influencing tryptophan (TRP) metabolism. The aim of this study was to investigate the influence of octanoic and decanoic fatty acids (FAs), the main components in the MCT diet (medium-chain triglyceride diet, a subtype of the ketogenic diet), on the metabolism of TRP, the activity of the kynurenic pathway and the concentrations of monoamines and amino acids, including branched-chain amino acids (BCAA) and aromatic amino acids (AAA) in rats. The acute effects of FA on the sedation index and hippocampal electrical after-discharge threshold were also assessed. We observed that intragastric administration of FA increased the brain levels of TRP and the central and peripheral concentrations of kynurenic acid (KYNA), as well as caused significant changes in the brain and plasma concentrations of BCAA and AAA. We found that the administration of FA clearly increased the seizure threshold and induced sedation. Furthermore, we have demonstrated that blocking TRP passage into the brain abolished these effects of FA but had no similar effect on the formation of ketone bodies. Given that FAs are major components of a ketogenic diet, it is suggested that the anticonvulsant effects of a ketogenic diet may be at least partly dependent on changes in TRP metabolism. We also propose a more general hypothesis concerning the intracellular mechanism of the ketogenic diet. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Use of the Ketogenic Diet to Treat Intractable Epilepsy in Mitochondrial Disorders

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    Paleologou, Eleni; Ismayilova, Naila; Kinali, Maria

    2017-01-01

    Mitochondrial disorders are a clinically heterogeneous group of disorders that are caused by defects in the respiratory chain, the metabolic pathway of the adenosine tri-phosphate (ATP) production system. Epilepsy is a common and important feature of these disorders and its management can be challenging. Epileptic seizures in the context of mitochondrial disease are usually treated with conventional anti-epileptic medication, apart from valproic acid. However, in accordance with the treatment of intractable epilepsy where there are limited treatment options, the ketogenic diet (KD) has been considered as an alternative therapy. The use of the KD and its more palatable formulations has shown promising results. It is especially indicated and effective in the treatment of mitochondrial disorders due to complex I deficiency. Further research into the mechanism of action and the neuroprotective properties of the KD will allow more targeted therapeutic strategies and thus optimize the treatment of both epilepsy in the context of mitochondrial disorders but also in other neurodegenerative disorders. PMID:28587136

  5. The ketogenic diet as a treatment for traumatic brain injury: a scoping review.

    Science.gov (United States)

    McDougall, Alexandre; Bayley, Mark; Munce, Sarah Ep

    2018-01-01

    Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. The ketogenic diet (KD) has been identified as a potential therapy to enhance recovery after TBI. The purpose of this study is to complete a scoping review and synthesize the evidence regarding the KD and its therapeutic effects in TBI. The methodological framework of Arksey and O'Malley was employed. Databases searched include Medline, EMBASE, CCRCT, CINAHL and WebOfScience. Two reviewers independently screened titles, abstracts and full texts in a two-step screening protocol to determine inclusion. Abstracted data included study setting and therapeutic mechanism. The KD was demonstrated to reduce cerebral oedema, apoptosis, improve cerebral metabolism and behavioural outcomes in rodent TBIs. Additionally, the KD affected rodent TBIs in an age-dependent manner. Due to a lack of relevant outcome measures, the human trials did not establish much evidence with respect to the KD as a treatment for TBI; only its safety was established. The KD is an effective treatment for TBI recovery in rats and shows potential in humans. Future research should aim to better elucidate the KD's mechanisms of action in human TBIs and determine if the KD's effectiveness on clinical outcomes can be reproduced in humans.

  6. Embryonic Lethality of Mitochondrial Pyruvate Carrier 1 Deficient Mouse Can Be Rescued by a Ketogenic Diet

    Science.gov (United States)

    Krznar, Petra; Hörl, Manuel; Ammar, Zeinab; Montessuit, Sylvie; Pierredon, Sandra; Zamboni, Nicola; Martinou, Jean-Claude

    2016-01-01

    Mitochondrial import of pyruvate by the mitochondrial pyruvate carrier (MPC) is a central step which links cytosolic and mitochondrial intermediary metabolism. To investigate the role of the MPC in mammalian physiology and development, we generated a mouse strain with complete loss of MPC1 expression. This resulted in embryonic lethality at around E13.5. Mouse embryonic fibroblasts (MEFs) derived from mutant mice displayed defective pyruvate-driven respiration as well as perturbed metabolic profiles, and both defects could be restored by reexpression of MPC1. Labeling experiments using 13C-labeled glucose and glutamine demonstrated that MPC deficiency causes increased glutaminolysis and reduced contribution of glucose-derived pyruvate to the TCA cycle. Morphological defects were observed in mutant embryonic brains, together with major alterations of their metabolome including lactic acidosis, diminished TCA cycle intermediates, energy deficit and a perturbed balance of neurotransmitters. Strikingly, these changes were reversed when the pregnant dams were fed a ketogenic diet, which provides acetyl-CoA directly to the TCA cycle and bypasses the need for a functional MPC. This allowed the normal gestation and development of MPC deficient pups, even though they all died within a few minutes post-delivery. This study establishes the MPC as a key player in regulating the metabolic state necessary for embryonic development, neurotransmitter balance and post-natal survival. PMID:27176894

  7. Control of seizures by ketogenic diet-induced modulation of metabolic pathways.

    Science.gov (United States)

    Clanton, Ryan M; Wu, Guoyao; Akabani, Gamal; Aramayo, Rodolfo

    2017-01-01

    Epilepsy is too complex to be considered as a disease; it is more of a syndrome, characterized by seizures, which can be caused by a diverse array of afflictions. As such, drug interventions that target a single biological pathway will only help the specific individuals where that drug's mechanism of action is relevant to their disorder. Most likely, this will not alleviate all forms of epilepsy nor the potential biological pathways causing the seizures, such as glucose/amino acid transport, mitochondrial dysfunction, or neuronal myelination. Considering our current inability to test every individual effectively for the true causes of their epilepsy and the alarming number of misdiagnoses observed, we propose the use of the ketogenic diet (KD) as an effective and efficient preliminary/long-term treatment. The KD mimics fasting by altering substrate metabolism from carbohydrates to fatty acids and ketone bodies (KBs). Here, we underscore the need to understand the underlying cellular mechanisms governing the KD's modulation of various forms of epilepsy and how a diverse array of metabolites including soluble fibers, specific fatty acids, and functional amino acids (e.g., leucine, D-serine, glycine, arginine metabolites, and N-acetyl-cysteine) may potentially enhance the KD's ability to treat and reverse, not mask, these neurological disorders that lead to epilepsy.

  8. Non-pharmacologic Therapeutic Alternatives for Children with Pharmacoresistant Epilepsy: Vagus Nerve Stimulation and Ketogenic Diet

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    Sibel K Velioğlu

    2014-06-01

    Full Text Available Approximately 20%-30% of individuals who develop epilepsy will develop medically refractory epilepsy. For this population, ‘‘alternative’’ or nonpharmacologic treatments such as vagus nerve stimulation (VNS and ketogenic diet (KD can be highly efficacious and should be seriously considered. Children and young people with medically-resistant epilepsy and poor candidates for epilepsy surgery may be referred to a tertiary paediatric epilepsy specialist for consideration of introducing VNS or KD. Information on the availability of VNS and KD in children is limited yet, due to the lack of suitably designed clinical studies in this population. VNS, is well-tolerated and effective as add-on therapy for refractory seizures in children. There has been no indication of reduction of effectiveness in long-term, open studies. Complications associated with implantation includes infection at the incision site, rib fractures and transient paralysis of the left vocal cord. Special caution is advised for children with pre-existing sleep apnea, cardiac conduction disorders, and asthma. Decreased seizure severity and recovery time, abolition of daytime drop attacks, and reduced hospitalization due to SE have improved patients’ quality of life. KD, with a nonfat-to-fat ratio of 1: 4 is a nonpharmacologic treatment for children with intractable epilepsy. Recent reports suggest that the benefit of KD is equivalent to any of the new anticonvulsant medications. The KD is difficult to maintain and has common side effects as constipation, acidosis, hypercholesterolemia, kidney stones, and hunger. It seems possible to design a therapy that is less rigorous and intrusive than the current KD, and promising alternative dietary approaches such as the Atkins and Low-glycemic-index (LGI diet are emerging.

  9. Anti-Tumor Effects of Ketogenic Diets in Mice: A Meta-Analysis.

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    Rainer J Klement

    Full Text Available Currently ketogenic diets (KDs are hyped as an anti-tumor intervention aimed at exploiting the metabolic abnormalities of cancer cells. However, while data in humans is sparse, translation of murine tumor models to the clinic is further hampered by small sample sizes, heterogeneous settings and mixed results concerning tumor growth retardation. The aim was therefore to synthesize the evidence for a growth inhibiting effect of KDs when used as a monotherapy in mice.We conducted a Bayesian random effects meta-analysis on all studies assessing the survival (defined as the time to reach a pre-defined endpoint such as tumor volume of mice on an unrestricted KD compared to a high carbohydrate standard diet (SD. For 12 studies meeting the inclusion criteria either a mean survival time ratio (MR or hazard ratio (HR between the KD and SD groups could be obtained. The posterior estimates for the MR and HR averaged over four priors on the between-study heterogeneity τ2 were MR = 0.85 (95% highest posterior density interval (HPDI = [0.73, 0.97] and HR = 0.55 (95% HPDI = [0.26, 0.87], indicating a significant overall benefit of the KD in terms of prolonged mean survival times and reduced hazard rate. All studies that used a brain tumor model also chose a late starting point for the KD (at least one day after tumor initiation which accounted for 26% of the heterogeneity. In this subgroup the KD was less effective (MR = 0.89, 95% HPDI = [0.76, 1.04].There was an overall tumor growth delaying effect of unrestricted KDs in mice. Future experiments should aim at differentiating the effects of KD timing versus tumor location, since external evidence is currently consistent with an influence of both of these factors.

  10. THE KETOGENIC DIET AS A TREATMENT PARADIGM FOR DIVERSE NEUROLOGICAL DISORDERS

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    Jong Min Rho

    2012-04-01

    Full Text Available Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat – or at least ameliorate symptoms of – these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more natural treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component.

  11. Tumor metabolism, the ketogenic diet and β-hydroxybutyrate: novel approaches to adjuvant brain tumor therapy

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    Eric C. Woolf

    2016-11-01

    Full Text Available Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD. The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.

  12. The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer.

    Directory of Open Access Journals (Sweden)

    Angela M Poff

    Full Text Available INTRODUCTION: Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO₂T saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease. METHODS: We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO₂T (2.5 ATM absolute, 90 min, 3x/week. Tumor growth was monitored by in vivo bioluminescent imaging. RESULTS: KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO₂T alone did not influence cancer progression, combining the KD with HBO₂T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls. CONCLUSIONS: KD and HBO₂T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease.

  13. The effect of olive oil-based ketogenic diet on serum lipid levels in epileptic children.

    Science.gov (United States)

    Güzel, Orkide; Yılmaz, Unsal; Uysal, Utku; Arslan, Nur

    2016-03-01

    Ketogenic diet (KD) is one of the most effective therapies for intractable epilepsy. Olive oil is rich in monounsaturated fatty acids and antioxidant molecules and has some beneficial effects on lipid profile, inflammation and oxidant status. The aim of this study was to evaluate the serum lipid levels of children who were receiving olive oil-based KD for intractable seizures at least 1 year. 121 patients (mean age 7.45 ± 4.21 years, 57 girls) were enrolled. At baseline and post-treatment 1, 3, 6, and 12 months body mass index-SDS, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels were measured. Repeated measure ANOVA with post hoc Bonferroni correction was used for data analysis. The mean duration of KD was 15.4 ± 4.1 months. Mean total cholesterol, LDL-cholesterol and triglyceride levels were significantly higher at 1st, 3rd, 6th and 12th months of the KD treatment, compared to pre-treatment levels (p = 0.001), but showed no difference among during-treatment measurements. Mean body mass index-SDS and HDL-cholesterol levels were not different among the baseline and follow-up time points (p = 0.113 and p = 0.067, respectively). No child in this study discontinued the KD because of dyslipidemia. Even if rich in olive oil, high-fat KD causes significant increase in LDL-cholesterol and triglyceride levels. More studies are needed to determine the effect of KD on serum lipids in children using different fat sources in the diet.

  14. Proconvulsant effects of the ketogenic diet in electroshock-induced seizures in mice.

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    Zarnowska, Iwona; Luszczki, Jarogniew J; Zarnowski, Tomasz; Wlaz, Piotr; Czuczwar, Stanislaw J; Gasior, Maciej

    2017-04-01

    Among non-pharmacological treatments, the ketogenic diet (KD) has the strongest demonstrated evidence of clinical success in drug resistant epilepsy. In an attempt to model the anticonvulsant effects of the KD pre-clinically, the present study assessed the effects of the KD against electroshock-induced convulsions in mice. After confirming that exposure to the KD for 2 weeks resulted in stable ketosis and hypoglycemia, mice were exposed to electroshocks of various intensities to establish general seizure susceptibility. When compared to mice fed the standard rodent chow diet (SRCD), we found that mice fed the KD were more sensitive to electroconvulsions as reflected by a significant decrease in seizure threshold (3.86 mA in mice on the KD vs 7.29 mA in mice on the SRCD; P < 0.05) in the maximal electroshock seizure threshold (MEST) test. To examine if this increased seizure sensitivity to electroconvulsions produced by the KD would affect anticonvulsant effects of antiepileptic drugs (AEDs), anticonvulsant potencies of carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and valproate (VPA) against maximal electroshock (MES)-induced convulsions were compared in mice fed the KD and SRCD. We found that potencies of all AEDs studied were decreased in mice fed the KD in comparison to those on the SRCD, with decreases in the anticonvulsant potencies ranging from 1.4 fold (PB) to 1.7 fold (PHT). Finally, the lack of differences in brain exposures of the AEDs studied in mice fed the KD and SRCD ruled out a pharmacokinetic nature of the observed findings. Taken together, exposure to the KD in the present study had an overall pro-convulsant effect. Since electroconvulsions require large metabolic reserves to support their rapid spread throughout the brain and consequent generalized tonic-clonic convulsions, this effect may be explained by a high energy state produced by the KD in regards to increased energy storage and utilization.

  15. Fibrogenic response of hepatic stellate cells in ovariectomised rats exposed to ketogenic diet.

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    Bobowiec, R; Wojcik, M; Jaworska-Adamu, J; Tusinska, E

    2013-02-01

    The discrepancy about the role of estrogens in hepatic fibrogenesis and lack of studies addressed of ketogenic diet (KD) on hepatic stellate cells (HSC), prompted us to investigate the activity of HSC in control, KD- and thioacetamide (TAA)-administrated rats with different plasma concentration of estradiol (E2). HSC were isolated by the collagenase perfusion methods and separated by the Percoll gradient centrifugation. After the 4(th) and 8(th) day of incubation, lysates of HSC and the media were collected for further analysis. The HSC derived from KD-rats released remarkably more transforming growth factor (TGF)-β1 than cells obtained from animals fed with a standard diet. The ovariectomy of KD-rats markedly intensified the secretion of this fibrogenic cytokine on the 8(th) day of incubation (201.33 ±1 7.15 pg/ml). In HSC of rats exposed to E2, the TGF-β1 concentration did not exceed 157 ± 34.39 pg/ml. In respect to the collagen type I, the HSC obtained from ovariectomised KD-rats released an augmented amount of this ECM protein after the 8(th) day of culture (1.83 ± 0.14 U/ml). In the same time, higher quantities of ASMA appeared in the KD rats (1.41 ± 0.3 pg/mg protein). Exposition of rats to E2 did not markedly decrease the amount of ASMA. In summary, KD was able to induce morphological and functional changes in HSC, especially derived from rats deprived of ovarian estrogens. However, the preservation of E2 in ovariectomised rats didn't substantially alter the activation of HSC.

  16. What are the minimum requirements for ketogenic diet services in resource-limited regions? Recommendations from the International League Against Epilepsy Task Force for Dietary Therapy.

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    Kossoff, Eric H; Al-Macki, Nabil; Cervenka, Mackenzie C; Kim, Heung D; Liao, Jianxiang; Megaw, Katherine; Nathan, Janak K; Raimann, Ximena; Rivera, Rocio; Wiemer-Kruel, Adelheid; Williams, Emma; Zupec-Kania, Beth A

    2015-09-01

    Despite the increasing use of dietary therapies for children and adults with refractory epilepsy, the availability of these treatments in developing countries with limited resources remains suboptimal. One possible contributory factor may be the costs. There is often reported a significant perceived need for a large ketogenic diet team, supplements, laboratory studies, and follow-up visits to provide this treatment. The 2009 Epilepsia Consensus Statement described ideal requirements for a ketogenic diet center, but in some situations this is not feasible. As a result, the International League Against Epilepsy (ILAE) Task Force on Dietary Therapy was asked to convene and provide practical, cost-effective recommendations for new ketogenic diet centers in resource-limited regions of the world. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  17. The influence of high fat diets with different ketogenic ratios on the hippocampal accumulation of creatine - FTIR microspectroscopy study

    Science.gov (United States)

    Skoczen, A.; Setkowicz, Z.; Janeczko, K.; Sandt, Ch.; Borondics, F.; Chwiej, J.

    2017-09-01

    The main purpose of this study was the determination and comparison of anomalies in creatine (Cr) accumulation occurring within CA3 and DG areas of hippocampal formation as a result of two high-fat, carbohydrate-restricted ketogenic diets (KD) with different ketogenic ratio (KR). To reach this goal, Fourier transformed infrared microspectroscopy with synchrotron radiation source (SRFTIR microspectroscopy) was applied for chemical mapping of creatine absorption bands, occurring around 1304, 1398 and 2800 cm- 1. The samples were taken from three groups of experimental animals: control group (N) fed with standard laboratory diet, KD1 and KD2 groups fed with high-fat diets with KR 5:1 and 9:1 respectively. Additionally, the possible influence on the phosphocreatine (PhCr, the high energetic form of creatine) content was evaluated by comparative analysis of chemical maps obtained for creatine and for compounds containing phosphate groups which manifest in the spectra at the wavenumbers of around 1240 and 1080 cm- 1. Our results showed that KD2 strongly modifies the frequency of Cr inclusions in both analyzed hippocampal areas. Statistical analysis, performed with Mann-Whitney U test revealed increased accumulation of Cr within CA3 and DG areas of KD2 fed rats compared to both normal rats and KD1 experimental group. Moreover, KD2 diet may modify the frequency of PhCr deposits as well as the PhCr to Cr ratio.

  18. Impact of a ketogenic diet intervention during radiotherapy on body composition: II. Protocol of a randomised phase I study (KETOCOMP).

    Science.gov (United States)

    Klement, Rainer J; Sweeney, Reinhart A

    2016-04-01

    We have found that a ketogenic diet (KD) during the course of radiotherapy (RT) was feasible and led to a preservation or favorable changes of body composition. Based on these observations and theoretical considerations, we initiated a study to investigate the impact of a KD or a ketogenic breakfast intervention in patients undergoing RT. All patients presenting for curative RT with age between 18 and 75, body mass index between 18 and 34 kg/m 2 and a histologically confirmed cancer of the breast, colorectum or head and neck region are considered for inclusion. Exclusion criteria are Karnofsky index radiotherapy fraction after an overnight fast and subsequently ingest a ketogenic breakfast consisting of (i) 50-250 ml of a medium-chain triglyceride drink (betaquick ® , vitaflo, Bad Homburg, Germany) plus (ii) 5-15 g amino acids (MAP, dr. reinwald healthcare gmbh+co kg, Schwarzenbruck, Germany). If willing to undertake a complete KD for the duration of RT, patients are entered into intervention group 2. Intervention group 2 does not have to fast prior to RT fractions but will be supplemented with MAP analogous to intervention group 1. The control group will not receive dietary advice to follow a KD or reduce carbohydrate intake. The objective is twofold: (i) to test whether the ketogenic interventions are feasibly, as measured by the number of dropouts; (ii) to see whether intervention groups 1 and 2 attain a better preservation of BIA phase angle than the control group. Primary endpoints are the feasibility of the interventions (measured through dropout rates), and changes in body weight and composition (measured through BIA). Secondary endpoints are changes in quality of life (EORTC questionnaires) and blood parameters as well as the occurrence and grade of toxicities and grade of regression after surgery in case of colorectal carcinomas. Copyright © 2015 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  19. Efficacy of a ketogenic diet in resistant myoclono-astatic epilepsy: A French multicenter retrospective study.

    Science.gov (United States)

    Stenger, Elodie; Schaeffer, Mickael; Cances, Claude; Motte, Jacques; Auvin, Stéphane; Ville, Dorothée; Maurey, Hélène; Nabbout, Rima; de Saint-Martin, Anne

    2017-03-01

    Recent studies have suggested that the early introduction of a ketogenic diet (KD) could improve seizure control in myoclono-astatic epilepsy (MAE). This multicenter study sought to identify the benefits of KD use on seizure control and epilepsy and on developmental outcomes in children with resistant MAE. Fifty children who were diagnosed with severe MAE in the French network of Reference Centers for Rare Epilepsies and who were treated with KD between 2000 and 2013 were included in this study. The seizure frequency and EEG recordings were assessed two weeks before KD introduction, 2 and 6 months after, and during the last follow-up, which also included an assessment of developmental outcome. Patients had a median follow up of 52 months (range 13-136) and received 4.3 antiepileptic drugs [2-9] before KD introduction. Fifty-four percent (54%) of our patients were seizure-free after 6 months of KD or more, and 86% experienced more than a 70% seizure reduction after 2 months of KD. Forty-four percent (44%) of them had a clear benefit of early KD treatment (after four AEDs failed). Early KD treatment did not result in a greater seizure reduction (p=0.055), but significantly resulted in remission (p<0.028). Fifty percent of patients with resistant MAE had normal development outcomes. Earlier KD treatment, after three AEDs failed, was correlated with a better cognitive outcome (p<0.01). Early introduction of KD treatment in resistant MAE has a strong, persistent anticonvulsant effect with long-term remission and better cognitive outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Effect of classic ketogenic diet treatment on lipoprotein subfractions in children and adolescents with refractory epilepsy.

    Science.gov (United States)

    Azevedo de Lima, Patricia; Baldini Prudêncio, Mariana; Murakami, Daniela Kawamoto; Pereira de Brito Sampaio, Leticia; Figueiredo Neto, Antônio Martins; Teixeira Damasceno, Nágila Raquel

    2017-01-01

    The aim of this study was to evaluate the effects of the classic ketogenic diet (KD) on low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions in children and adolescents with refractory epilepsy. This prospective study recruited children and adolescents of either sex, whose epilepsy was refractory to treatment with multiple drugs. To be included, the patient had to have an indication for treatment with the KD and be treated as an outpatient. At baseline and after 3 and 6 mo of the KD, lipid profile (total cholesterol [TC], triacylglycerols [TG], LDL cholesterol [LDL-C], and HDL cholesterol [HDL-C]), apolipoproteins (apoA-I and apoB), 10 subfractions of HDL, 7 subfractions of LDL, LDL phenotype, and LDL size were analyzed using the Lipoprint system. The lipid profile components (TC, TG, LDL-C, HDL-C, apoA-I, and apoB) increased during the 3-mo follow-up, and remained consistent after 6 mo of treatment. Similarly, non-HDL-C, TC/HDL-C, LDL-C/HDL-C, and apoB/apoA-I ratios, representing atherogenic particles, significantly increased. In contrast, qualitative lipoprotein characteristics progressively changed during the follow-up period. Small LDL subfractions increased, and this profile was related with reduced LDL size (27.3 nm to 26.7 nm). The LDL phenotype became worse; 52.1% of the patients had a non-A phenotype after 6 mo of the KD. Small HDL subfractions decreased only after 6 mo of the KD. KD treatment promotes negative changes in lipoprotein size and phenotype, contributing to atherogenic risk in these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Ketogenic diet in a patient with congenital hyperinsulinism: a novel approach to prevent brain damage.

    Science.gov (United States)

    Maiorana, Arianna; Manganozzi, Lucilla; Barbetti, Fabrizio; Bernabei, Silvia; Gallo, Giorgia; Cusmai, Raffaella; Caviglia, Stefania; Dionisi-Vici, Carlo

    2015-09-24

    Congenital hyperinsulinism (CHI) is the most frequent cause of hypoglycemia in children. In addition to increased peripheral glucose utilization, dysregulated insulin secretion induces profound hypoglycemia and neuroglycopenia by inhibiting glycogenolysis, gluconeogenesis and lipolysis. This results in the shortage of all cerebral energy substrates (glucose, lactate and ketones), and can lead to severe neurological sequelae. Patients with CHI unresponsive to medical treatment can be subjected to near-total pancreatectomy with increased risk of secondary diabetes. Ketogenic diet (KD), by reproducing a fasting-like condition in which body fuel mainly derives from beta-oxidation, is intended to provide alternative cerebral substrates such ketone bodies. We took advantage of known protective effect of KD on neuronal damage associated with GLUT1 deficiency, a disorder of impaired glucose transport across the blood-brain barrier, and administered KD in a patient with drug-unresponsive CHI, with the aim of providing to neurons an energy source alternative to glucose. A child with drug-resistant, long-standing CHI caused by a spontaneous GCK activating mutation (p.Val455Met) suffered from epilepsy and showed neurodevelopmental abnormalities. After attempting various therapeutic regimes without success, near-total pancreatectomy was suggested to parents, who asked for other options. Therefore, we proposed KD in combination with insulin-suppressing drugs. We administered KD for 2 years. Soon after the first six months, the patient was free of epileptic crises, presented normalization of EEG, and showed a marked recover in psychological development and quality of life. KD could represent an effective treatment to support brain function in selected cases of CHI.

  2. Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet.

    Science.gov (United States)

    Schugar, Rebecca C; Huang, Xiaojing; Moll, Ashley R; Brunt, Elizabeth M; Crawford, Peter A

    2013-01-01

    Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666) that is very high in fat (~94% kcal), very low in carbohydrate (~1% kcal), low in protein (~5% kcal), and choline restricted (~300 mg/kg) provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal) and choline contents (300 mg/kg vs. 5 g/kg). C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet - weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction - were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.

  3. Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet.

    Directory of Open Access Journals (Sweden)

    Rebecca C Schugar

    Full Text Available Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666 that is very high in fat (~94% kcal, very low in carbohydrate (~1% kcal, low in protein (~5% kcal, and choline restricted (~300 mg/kg provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal and choline contents (300 mg/kg vs. 5 g/kg. C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet - weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction - were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.

  4. Seizure control and acceptance of the ketogenic diet in GLUT1 deficiency syndrome: a 2- to 5-year follow-up of 15 children enrolled prospectively.

    NARCIS (Netherlands)

    Klepper, J.; Scheffer, H.; Leiendecker, B.; Gertsen, E.; Binder, S.; Leferink, M.; Hertzberg, C.; Nake, A.; Voit, T.; Willemsen, M.A.A.P.

    2005-01-01

    BACKGROUND: GLUT1 deficiency syndrome is caused by impaired glucose transport into the brain resulting in an epileptic encephalopathy, developmental delay, and a complex motor disorder. A ketogenic diet provides an alternative fuel to the brain and effectively restores brain energy metabolism.

  5. Long-term ketogenic diet causes glucose intolerance and reduced β- and α-cell mass but no weight loss in mice

    NARCIS (Netherlands)

    Ellenbroek, Johanne H; van Dijck, Laura; Töns, Hendrica A; Rabelink, Ton J; Carlotti, Françoise; Ballieux, Bart E P B; de Koning, Eelco J P

    2014-01-01

    High-fat, low-carbohydrate ketogenic diets (KD) are used for weight loss and for treatment of refractory epilepsy. Recently, short-time studies in rodents have shown that, besides their beneficial effect on body weight, KD lead to glucose intolerance and insulin resistance. However, the long-term

  6. A ketogenic diet modifies glutamate, gamma-aminobutyric acid and agmatine levels in the hippocampus of rats: A microdialysis study.

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    Calderón, Naima; Betancourt, Luis; Hernández, Luis; Rada, Pedro

    2017-03-06

    The ketogenic diet (KD) is acknowledged as an unconventional option in the treatment of epilepsy. Several lines of investigation point to a possible role of glutamate and gamma-aminobutyric acid (GABA) as main contributors in this protective effect. Other biomolecules could also be involved in the beneficial consequence of the KD, for example, the diamine agmatine has been suggested to block imidazole and glutamate NMDA receptor and serves as an endogenous anticonvulsant in different animal models of epilepsy. In the present report, we have used microdialysis coupled to capillary electrophoresis to monitor microdialysate levels of GABA, glutamate and agmatine in the hippocampus of rats submitted to a KD for 15days compared to rats on a normal rat chow diet. A significant increase in GABA and agmatine levels while no change in glutamate levels was observed. These results support the notion that the KD modifies different transmitters favoring inhibitory over excitatory neurotransmitters. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Ketogenic diet change cPLA2/clusterin and autophagy related gene expression and correlate with cognitive deficits and hippocampal MFs sprouting following neonatal seizures.

    Science.gov (United States)

    Ni, Hong; Zhao, Dong-Jing; Tian, Tian

    2016-02-01

    Because the ketogenic diet (KD) was affecting expression of energy metabolism- related genes in hippocampus and because lipid membrane peroxidation and its associated autophagy stress were also found to be involved in energy depletion, we hypothesized that KD might exert its neuroprotective action via lipid membrane peroxidation and autophagic signaling. Here, we tested this hypothesis by examining the long-term expression of lipid membrane peroxidation-related cPLA2 and clusterin, its downstream autophagy marker Beclin-1, LC3 and p62, as well as its execution molecule Cathepsin-E following neonatal seizures and chronic KD treatment. On postnatal day 9 (P9), 48 Sprague-Dawley rats were randomly assigned to two groups: flurothyl-induced recurrent seizures group and control group. On P28, they were further randomly divided into the seizure group without ketogenic diet (RS+ND), seizure plus ketogenic diet (RS+KD), the control group without ketogenic diet (NS+ND), and the control plus ketogenic diet (NS+KD). Morris water maze test was performed during P37-P43. Then mossy fiber sprouting and the protein levels were detected by Timm staining and Western blot analysis, respectively. Flurothyl-induced RS+ND rats show a long-term lower amount of cPLA2 and LC3II/I, and higher amount of clusterin, Beclin-1, p62 and Cathepsin-E which are in parallel with hippocampal mossy fiber sprouting and cognitive deficits. Furthermore, chronic KD treatment (RS+KD) is effective in restoring these molecular, neuropathological and cognitive changes. The results imply that a lipid membrane peroxidation and autophagy-associated pathway is involved in the aberrant hippocampal mossy fiber sprouting and cognitive deficits following neonatal seizures, which might be a potential target of KD for the treatment of neonatal seizure-induced brain damage. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Does ketogenic diet have any negative effect on cardiac systolic and diastolic functions in children with intractable epilepsy?: One-year follow-up results.

    Science.gov (United States)

    Ozdemir, Rahmi; Kucuk, Mehmet; Guzel, Orkide; Karadeniz, Cem; Yilmaz, Unsal; Mese, Timur

    2016-10-01

    The ketogenic diet (KD) has been referred to as an "effective therapy with side effects" for children with intractable epilepsy. Among the most recognized adverse effects, there are cardiac conduction abnormalities, vascular and myocardial dysfunction. However, very limited and controversial data are available regarding the effects of the KD on cardiac functions. We sought to analyze the mid-term effect of ketogenic diet on cardiac functions in patients with intractable epilepsy who received a ketogenic diet for at least 12months using conventional and relatively new imaging techniques. This prospective study included 61 patients with intractable epilepsy who received ketogenic diet for at least 12months. Clinical examinations, serum carnitine and selenium levels as well as electrocardiographic and echocardiographic examinations were scheduled prior to the procedure and at 1, 3, 6 and 12months. We utilized two-dimensional, M-mode, colored Doppler, spectral Doppler and pulsed wave tissue Doppler imaging techniques to investigate ventricular systolic and diastolic functions of this subgroup of patients. In our study, there was no significant difference after 1year of KD therapy compared to baseline values-except a significantly decreased A wave velocity-in terms of pulse wave Doppler echocardiographic measurements of the diastolic function. The tissue Doppler measurements obtained from the lateral wall of tricuspide and mitral annuli were not different at baseline and at month 12 of the treatment, as well. The ketogenic diet appears to have no disturbing effect on ventricular functions in epileptic children in the midterm. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  9. A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth.

    Science.gov (United States)

    De Feyter, Henk M; Behar, Kevin L; Rao, Jyotsna U; Madden-Hennessey, Kirby; Ip, Kevan L; Hyder, Fahmeed; Drewes, Lester R; Geschwind, Jean-François; de Graaf, Robin A; Rothman, Douglas L

    2016-08-01

    The dependence of tumor cells, particularly those originating in the brain, on glucose is the target of the ketogenic diet, which creates a plasma nutrient profile similar to fasting: increased levels of ketone bodies and reduced plasma glucose concentrations. The use of ketogenic diets has been of particular interest for therapy in brain tumors, which reportedly lack the ability to oxidize ketone bodies and therefore would be starved during ketosis. Because studies assessing the tumors' ability to oxidize ketone bodies are lacking, we investigated in vivo the extent of ketone body oxidation in 2 rodent glioma models. Ketone body oxidation was studied using (13)C MR spectroscopy in combination with infusion of a (13)C-labeled ketone body (beta-hydroxybutyrate) in RG2 and 9L glioma models. The level of ketone body oxidation was compared with nontumorous cortical brain tissue. The level of (13)C-beta-hydroxybutyrate oxidation in 2 rat glioma models was similar to that of contralateral brain. In addition, when glioma-bearing animals were fed a ketogenic diet, the ketone body monocarboxylate transporter was upregulated, facilitating uptake and oxidation of ketone bodies in the gliomas. These results demonstrate that rat gliomas can oxidize ketone bodies and indicate upregulation of ketone body transport when fed a ketogenic diet. Our findings contradict the hypothesis that brain tumors are metabolically inflexible and show the need for additional research on the use of ketogenic diets as therapy targeting brain tumor metabolism. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Decreased health care utilization and health care costs in the inpatient and emergency department setting following initiation of ketogenic diet in pediatric patients: The experience in Ontario, Canada.

    Science.gov (United States)

    Whiting, Sharon; Donner, Elizabeth; RamachandranNair, Rajesh; Grabowski, Jennifer; Jetté, Nathalie; Duque, Daniel Rodriguez

    2017-03-01

    To assess the change in inpatient and emergency department utilization and health care costs in children on the ketogenic diet for treatment of epilepsy. Data on children with epilepsy initiated on the ketogenic diet (KD) Jan 1, 2000 and Dec 31, 2010 at Ontario pediatric hospitals were linked to province wide inpatient, emergency department (ED) data at the Institute for Clinical Evaluative Sciences. ED and inpatient visits and costs for this cohort were compared for a maximum of 2 years (730days) prior to diet initiation and for a maximum of 2 years (730days) following diet initiation. KD patient were compared to matched group of children with epilepsy who did not receive the ketogenic diet (no KD). Children on the KD experienced a mean decrease in ED visits of 2.5 visits per person per year [95% CI (1.5-3.4)], and a mean decrease of 0.8 inpatient visits per person per year [95% CI (0.3-1.3)], following diet initiation. They had a mean decrease in ED costs of $630 [95% CI (249-1012)] per person per year and a median decrease in inpatient costs of $1059 [IQR: 7890; pdiet experienced a mean reduction of 2.1 ED visits per child per year [95% CI (1.0-3.2)] and a mean decrease of 0.6 [95% CI (0.1-1.1)] inpatient visits per child per year. Patients on the KD experienced a reduction of $442 [95% CI (34.4-850)] per child per year more in ED costs than the matched group. The ketogenic diet group had greater median decrease in inpatient costs per child per year than the matched group [pketogenic diet, experienced decreased ED and inpatient visits as well as costs following diet initiation in Ontario, Canada. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Dieta cetogênica no tratamento de epilepsias farmacorresistentes The ketogenic diet on the treatment of drug resistant epilepsies

    Directory of Open Access Journals (Sweden)

    Carla Barbosa Nonino-Borges

    2004-12-01

    Full Text Available A epilepsia é uma condição clínica crônica correspondente a um grupo de doenças que tem em comum crises epilépticas; ela atinge de 0,5% a 1,0% da população dos países desenvolvidos, podendo esta prevalência ser maior nos países em desenvolvimento. Aproximadamente um terço dos pacientes evolui com crises epilépticas intratáveis com medicamentos; em alguns casos, é possível o tratamento cirúrgico. Nos pacientes em que cirurgia não é possível, a dieta cetogênica passa a ser uma opção terapêutica, principalmente em crianças. Espera-se que esta terapia seja eficaz para, pelo menos, um terço dos pacientes, resultando em redução ou controle das crises. No presente trabalho, apresentamos métodos para o preparo e uso a dieta cetogênica. O planejamento da dieta é individualizado, seguindo-se recomendações para o consumo energético e proporções de gorduras, proteínas e carboidratos específicos. Sempre que introduzida a dieta, o paciente deve ser monitorizado, devido à possibilidade de efeitos adversos. A orientação dos pais ou responsáveis sobre a dieta cetogênica, e como ela funciona, proporciona maior aceitação e aderência a esta forma de tratamento da epilepsia.Epilepsy is a chronic condition that affects 0.5% to 1.0% of the population in developed countries. This prevalence may be higher in developing countries. A significant proportion of the patients, nearly one third of them will have their condition evolved into a stage of uncontrolled crises, in some cases, surgical procedure may be indicated. However, for several patients, surgery is not possible. In these cases, ketogenic diet is a therapeutic option, especially for children. It is supposed that nearly one third of the patients that use the ketogenic diet, experience seizure control or reduction in the number of seizures. The current study presents methods of preparing and using ketogenic diet. The diet must be individualized, considering the

  12. Exploring the relationship between preferences for high fat foods and efficacy of the ketogenic and modified Atkins diets among children with seizure disorders.

    Science.gov (United States)

    Amari, Adrianna; Turner, Zahava; Rubenstein, James E; Miller, Jonathan R; Kossoff, Eric H

    2015-02-01

    Previous research has indicated that children with seizures may prefer high fat foods - a preference compatible with ketogenic and modified Atkins dietary therapies. The purpose of this prospective study was to examine the relationship between fat preference and efficacy of therapeutic diets in treating intractable seizures among a pediatric population. Preference for high fat foods was directly assessed in a sample of 30 children prior to commencing either the ketogenic or modified Atkins diet. Seizure control was assessed at 1, 3, 6, and 12 months following diet initiation. Using an intent-to-treat analysis, correlations between fat preference and diet efficacy were examined at each follow-up and across the follow-up period. At individual follow-ups, correlations between fat preference and diet efficacy varied in terms of both strength and significance; however, modest, positive correlations with fat preference were significant when examining high levels of efficacy (100% seizure reduction, ≥90% seizure reduction) across a 1-year follow-up period. These findings provide preliminary evidence that fat preference, when directly assessed, may be a useful predictor of treatment efficacy for the ketogenic and modified Atkins diets; however, further research is necessary. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  13. Efficacy of Modified Atkins Ketogenic Diet in Chronic Cluster Headache: An Open-Label, Single-Arm, Clinical Trial

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    Cherubino Di Lorenzo

    2018-02-01

    Full Text Available IntroductionDrug-resistant cluster headache (CH is still an open clinical challenge. Recently, our group observed the clinical efficacy of a ketogenic diet (KD, usually adopted to treat drug-resistant epilepsies, on migraine.AimHere, we aim to detect the effect of KD in a group of drug-resistant chronic CH (CCH patients.Materials and methodsEighteen drug-resistant CCH patients underwent a 12-week KD (Modified Atkins Diet, MAD, and the clinical response was evaluated in terms of response (≥50% attack reduction.ResultsOf the 18 CCH patients, 15 were considered responders to the diet (11 experienced a full resolution of headache, and 4 had a headache reduction of at least 50% in terms of mean monthly number of attacks during the diet. The mean monthly number of attacks for each patient at the baseline was 108.71 (SD = 81.71; at the end of the third month of diet, it was reduced to 31.44 (SD = 84.61.ConclusionWe observed for the first time that a 3-month ketogenesis ameliorates clinical features of CCH.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT03244735.

  14. Influence of a ketogenic diet, fish-oil, and calorie restriction on plasma metabolites and lipids in C57BL/6J mice

    Science.gov (United States)

    2014-01-01

    Background Diet therapies including calorie restriction, ketogenic diets, and fish-oil supplementation have been used to improve health and to treat a variety of neurological and non-neurological diseases. Methods We investigated the effects of three diets on circulating plasma metabolites (glucose and β-hydroxybutyrate), hormones (insulin and adiponectin), and lipids over a 32-day period in C57BL/6J mice. The diets evaluated included a standard rodent diet (SD), a ketogenic diet (KD), and a standard rodent diet supplemented with fish-oil (FO). Each diet was administered in either unrestricted (UR) or restricted (R) amounts to reduce body weight by 20%. Results The KD-UR increased body weight and glucose levels and promoted a hyperlipidemic profile, whereas the FO-UR decreased body weight and glucose levels and promoted a normolipidemic profile, compared to the SD-UR. When administered in restricted amounts, all three diets produced a similar plasma metabolite profile, which included decreased glucose levels and a normolipidemic profile. Linear regression analysis showed that circulating glucose most strongly predicted body weight and triglyceride levels, whereas calorie intake moderately predicted glucose levels and strongly predicted ketone body levels. Conclusions These results suggest that biomarkers of health can be improved when diets are consumed in restricted amounts, regardless of macronutrient composition. PMID:24910707

  15. A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial.

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    Yancy, William S; Olsen, Maren K; Guyton, John R; Bakst, Ronna P; Westman, Eric C

    2004-05-18

    Low-carbohydrate diets remain popular despite a paucity of scientific evidence on their effectiveness. To compare the effects of a low-carbohydrate, ketogenic diet program with those of a low-fat, low-cholesterol, reduced-calorie diet. Randomized, controlled trial. Outpatient research clinic. 120 overweight, hyperlipidemic volunteers from the community. Low-carbohydrate diet (initially, carbohydrate daily) plus nutritional supplementation, exercise recommendation, and group meetings, or low-fat diet (fat, low-carbohydrate diet group than the low-fat diet group completed the study (76% vs. 57%; P = 0.02). At 24 weeks, weight loss was greater in the low-carbohydrate diet group than in the low-fat diet group (mean change, -12.9% vs. -6.7%; P fat mass (change, -9.4 kg with the low-carbohydrate diet vs. -4.8 kg with the low-fat diet) than fat-free mass (change, -3.3 kg vs. -2.4 kg, respectively). Compared with recipients of the low-fat diet, recipients of the low-carbohydrate diet had greater decreases in serum triglyceride levels (change, -0.84 mmol/L vs. -0.31 mmol/L [-74.2 mg/dL vs. -27.9 mg/dL]; P = 0.004) and greater increases in high-density lipoprotein cholesterol levels (0.14 mmol/L vs. -0.04 mmol/L [5.5 mg/dL vs. -1.6 mg/dL]; P low-density lipoprotein cholesterol level did not differ statistically (0.04 mmol/L [1.6 mg/dL] with the low-carbohydrate diet and -0.19 mmol/L [-7.4 mg/dL] with the low-fat diet; P = 0.2). Minor adverse effects were more frequent in the low-carbohydrate diet group. We could not definitively distinguish effects of the low-carbohydrate diet and those of the nutritional supplements provided only to that group. In addition, participants were healthy and were followed for only 24 weeks. These factors limit the generalizability of the study results. Compared with a low-fat diet, a low-carbohydrate diet program had better participant retention and greater weight loss. During active weight loss, serum triglyceride levels decreased more and high

  16. GAPDH-mediated posttranscriptional regulations of sodium channel Scn1a and Scn3a genes under seizure and ketogenic diet conditions.

    Science.gov (United States)

    Lin, Guo-Wang; Lu, Ping; Zeng, Tao; Tang, Hui-Ling; Chen, Yong-Hong; Liu, Shu-Jing; Gao, Mei-Mei; Zhao, Qi-Hua; Yi, Yong-Hong; Long, Yue-Sheng

    2017-02-01

    Abnormal expressions of sodium channel SCN1A and SCN3A genes alter neural excitability that are believed to contribute to the pathogenesis of epilepsy, a long-term risk of recurrent seizures. Ketogenic diet (KD), a high-fat and low-carbohydrate treatment for difficult-to-control (refractory) epilepsy in children, has been suggested to reverse gene expression patterns. Here, we reveal a novel role of GAPDH on the posttranscriptional regulation of mouse Scn1a and Scn3a expressions under seizure and KD conditions. We show that GAPDH binds to a conserved region in the 3' UTRs of human and mouse SCN1A and SCN3A genes, which decreases and increases genes' expressions by affecting mRNA stability through SCN1A 3' UTR and SCN3A 3' UTR, respectively. In seizure mice, the upregulation and phosphorylation of GAPDH enhance its binding to the 3' UTR, which lead to downregulation of Scn1a and upregulation of Scn3a. Furthermore, administration of KD generates β-hydroxybutyric acid which rescues the abnormal expressions of Scn1a and Scn3a by weakening the GAPDH's binding to the element. Taken together, these data suggest that GAPDH-mediated expression regulation of sodium channel genes may be associated with epilepsy and the anticonvulsant action of KD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Ketogenic diet, high intensity interval training (HIIT) and memory training in the treatment of mild cognitive impairment: A case study.

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    Dahlgren, Kaitlyn; Gibas, Kelly J

    2018-04-11

    Alzheimer's disease (AD) deaths have increased by 89% since 2000. This alarming trajectory of neurological disease highlights the failure of current best practice. Deteriorating brain fuel supply is the nemesis of intact neurological health. Cerebral hypo-metabolism associated with AD occurs years before onset. Both the ketogenic diet and calorie restriction (fasting) lead to a compensatory rise in ketones to improve energy deficits in the brain derived from cerebral insulin resistance. Two forms of ketone bodies, β-hydroxybutyrate and acetoacetate, fuel the brain during starvation, fasting and strenuous exercise. Ketones are neuroprotective agents that shelter the aging brain from memory loss and neurodegeneration. Induced ketone production has been shown to ameliorate mitochondrial function, reduce the expression of apoptotic and inflammatory mediators and provide neuroprotection to cells (Lange et al., 2017). This case study highlights an innovative research design aimed at attenuating memory decline in a 57 year old female previously diagnosed with comorbid mild cognitive impairment (MCI) and metabolic syndrome (MetS). Mild cognitive impairment is a predementia syndrome known to precede AD (Michaud et al, 2017). The 12-week intervention included ketogenic nutrition protocol, high intensity interval training (HIIT) and memory training using the PEAK brain training app. Memory function was assessed via the MoCA (Montreal Cognitive Assessment) pre/post intervention. Physiological biomarkers for MetS including HOMA-IR(homeostatic model assessment of insulin resistance), triglyceride/HDL ratio, HgA1c, fasting triglycerides and HDL were measured pre/post intervention. MoCA baseline score was 22/30 (MCI); post intervention score: 30/30 (normal). MetS biomarker improvements also reflected statistical significance. Copyright © 2018. Published by Elsevier Ltd.

  18. Sex-Specific Life Course Changes in the Neuro-Metabolic Phenotype of Glut3 Null Heterozygous Mice: Ketogenic Diet Ameliorates Electroencephalographic Seizures and Improves Sociability.

    Science.gov (United States)

    Dai, Yun; Zhao, Yuanzi; Tomi, Masatoshi; Shin, Bo-Chul; Thamotharan, Shanthie; Mazarati, Andrey; Sankar, Raman; Wang, Elizabeth A; Cepeda, Carlos; Levine, Michael S; Zhang, Jingjing; Frew, Andrew; Alger, Jeffry R; Clark, Peter M; Sondhi, Monica; Kositamongkol, Sudatip; Leibovitch, Leah; Devaskar, Sherin U

    2017-04-01

    We tested the hypothesis that exposure of glut3+/- mice to a ketogenic diet ameliorates autism-like features, which include aberrant behavior and electrographic seizures. We first investigated the life course sex-specific changes in basal plasma-cerebrospinal fluid (CSF)-brain metabolic profile, brain glucose transport/uptake, glucose and monocarboxylate transporter proteins, and adenosine triphosphate (ATP) in the presence or absence of systemic insulin administration. Glut3+/- male but not female mice (5 months of age) displayed reduced CSF glucose/lactate concentrations with no change in brain Glut1, Mct2, glucose uptake or ATP. Exogenous insulin-induced hypoglycemia increased brain glucose uptake in glut3+/- males alone. Higher plasma-CSF ketones (β-hydroxybutyrate) and lower brain Glut3 in females vs males proved protective in the former while enhancing vulnerability in the latter. As a consequence, increased synaptic proteins (neuroligin4 and SAPAP1) with spontaneous excitatory postsynaptic activity subsequently reduced hippocampal glucose content and increased brain amyloid β1-40 deposition in an age-dependent manner in glut3+/- males but not females (4 to 24 months of age). We then explored the protective effect of a ketogenic diet on ultrasonic vocalization, sociability, spatial learning and memory, and electroencephalogram seizures in male mice (7 days to 6 to 8 months of age) alone. A ketogenic diet partially restored sociability without affecting perturbed vocalization, spatial learning and memory, and reduced seizure events. We conclude that (1) sex-specific and age-dependent perturbations underlie the phenotype of glut3+/- mice, and (2) a ketogenic diet ameliorates seizures caused by increased cortical excitation and improves sociability, but fails to rescue vocalization and cognitive deficits in glut3+/- male mice. Copyright © 2017 Endocrine Society.

  19. Roles of caloric restriction, ketogenic diet and intermittent fasting during initiation, progression and metastasis of cancer in animal models: a systematic review and meta-analysis.

    Science.gov (United States)

    Lv, Mengmeng; Zhu, Xingya; Wang, Hao; Wang, Feng; Guan, Wenxian

    2014-01-01

    The role of dietary restriction regimens such as caloric restriction, ketogenic diet and intermittent fasting in development of cancers has been detected via abundant preclinical experiments. However, the conclusions are controversial. We aim to review the relevant animal studies systematically and provide assistance for further clinical studies. Literatures on associations between dietary restriction and cancer published in PubMed in recent twenty years were comprehensively searched. Animal model, tumor type, feeding regimen, study length, sample size, major outcome, conclusion, quality assessment score and the interferential step of cancer were extracted from each eligible study. We analyzed the tumor incidence rates from 21 studies about caloric restriction. Fifty-nine studies were involved in our system review. The involved studies explored roles of dietary restriction during initiation, progression and metastasis of cancer. About 90.9% of the relevant studies showed that caloric restriction plays an anti-cancer role, with the pooled OR (95%CI) of 0.20 (0.12, 0.34) relative to controls. Ketogenic diet was also positively associated with cancer, which was indicated by eight of the nine studies. However, 37.5% of the related studies obtained a negative conclusion that intermittent fasting was not significantly preventive against cancer. Caloric restriction and ketogenic diet are effective against cancer in animal experiments while the role of intermittent fasting is doubtful and still needs exploration. More clinical experiments are needed and more suitable patterns for humans should be investigated.

  20. Roles of caloric restriction, ketogenic diet and intermittent fasting during initiation, progression and metastasis of cancer in animal models: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Mengmeng Lv

    Full Text Available The role of dietary restriction regimens such as caloric restriction, ketogenic diet and intermittent fasting in development of cancers has been detected via abundant preclinical experiments. However, the conclusions are controversial. We aim to review the relevant animal studies systematically and provide assistance for further clinical studies.Literatures on associations between dietary restriction and cancer published in PubMed in recent twenty years were comprehensively searched. Animal model, tumor type, feeding regimen, study length, sample size, major outcome, conclusion, quality assessment score and the interferential step of cancer were extracted from each eligible study. We analyzed the tumor incidence rates from 21 studies about caloric restriction.Fifty-nine studies were involved in our system review. The involved studies explored roles of dietary restriction during initiation, progression and metastasis of cancer. About 90.9% of the relevant studies showed that caloric restriction plays an anti-cancer role, with the pooled OR (95%CI of 0.20 (0.12, 0.34 relative to controls. Ketogenic diet was also positively associated with cancer, which was indicated by eight of the nine studies. However, 37.5% of the related studies obtained a negative conclusion that intermittent fasting was not significantly preventive against cancer.Caloric restriction and ketogenic diet are effective against cancer in animal experiments while the role of intermittent fasting is doubtful and still needs exploration. More clinical experiments are needed and more suitable patterns for humans should be investigated.

  1. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus

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    Mavropoulos John C

    2008-12-01

    Full Text Available Abstract Objective Dietary carbohydrate is the major determinant of postprandial glucose levels, and several clinical studies have shown that low-carbohydrate diets improve glycemic control. In this study, we tested the hypothesis that a diet lower in carbohydrate would lead to greater improvement in glycemic control over a 24-week period in patients with obesity and type 2 diabetes mellitus. Research design and methods Eighty-four community volunteers with obesity and type 2 diabetes were randomized to either a low-carbohydrate, ketogenic diet (1c. Results Forty-nine (58.3% participants completed the study. Both interventions led to improvements in hemoglobin A1c, fasting glucose, fasting insulin, and weight loss. The LCKD group had greater improvements in hemoglobin A1c (-1.5% vs. -0.5%, p = 0.03, body weight (-11.1 kg vs. -6.9 kg, p = 0.008, and high density lipoprotein cholesterol (+5.6 mg/dL vs. 0 mg/dL, p Conclusion Dietary modification led to improvements in glycemic control and medication reduction/elimination in motivated volunteers with type 2 diabetes. The diet lower in carbohydrate led to greater improvements in glycemic control, and more frequent medication reduction/elimination than the low glycemic index diet. Lifestyle modification using low carbohydrate interventions is effective for improving and reversing type 2 diabetes.

  2. Ketogenic Diet Based on Extra Virgin Coconut Oil Has No Effects in Young Wistar Rats With Pilocarpine-Induced Epilepsy.

    Science.gov (United States)

    Melo, Isabelle T; M Rêgo, Elisabete; Bueno, Nassib B; Gomes, Tâmara C; Oliveira, Suzana L; Trindade-Filho, Euclides M; Cabral, Cyro R; Machado, Tacy S; Galvão, Jaqueline A; R Ataide, Terezinha

    2018-02-01

    This study evaluated the effects of a ketogenic diet (KD) based on extra virgin coconut oil (Cocos nucifera L., VCO), on the treatment of epileptic rats. Two sets of experiments were conducted. First, male Wistar rats underwent induction of status epilepticus (SE) with the administration of pilocarpine intraperitoneally 21 animals reached spontaneous recurrent seizures (SRS) and were randomly allocated to the dietary regimens and video-monitored for 19 days. In the second experiment, 24 animals were randomized immediately after the induction of SE and followed for 67 days. Diets were as follows: Control (AIN-93G; 7% lipid), KetoTAGsoya (KD based on soybean oil; 69.79% lipid), and KetoTAGcoco (KD based on VCO; 69.79% lipid). There were no differences in the latency to the first crisis, total frequency, and duration of the SRS between groups in 2 experiments. The data suggest no effects of KD, with or without VCO, in rats with pilocarpine-induced epilepsy. © 2018 AOCS.

  3. Use of the ketogenic diet to manage refractory epilepsy in CDKL5 disorder: Experience of >100 patients.

    Science.gov (United States)

    Lim, Zhan; Wong, Kingsley; Olson, Heather E; Bergin, Ann M; Downs, Jenny; Leonard, Helen

    2017-08-01

    Pathogenic variants involving the CDKL5 gene result in a severe epileptic encephalopathy, often later presenting with features similar to Rett syndrome. Cardinal features of epilepsy in the CDKL5 disorder include early onset at a median age of 6 weeks and poor response to antiepileptic drugs. The ketogenic diet (KD) was first introduced in the 1920s as a treatment option for refractory epilepsy in children. This study investigated use of the KD in the CDKL5 disorder and its influences on seizures. The International CDKL5 Disorder Database, established in 2012, collects information on individuals with the CDKL5 disorder. Families have provided information regarding seizure characteristics, use, and side effects of the KD treatment. Descriptive statistics and time to event analyses were performed. Clinical vignettes were also provided on patients attending Boston Children's Hospital. Data regarding KD use were available for 204 individuals with a pathogenic CDKL5 variant. Median age of inclusion in the database was 4.8 years (range = 0.3-33.9 years), with median age of 6 weeks (range = 1 day-65 weeks) at seizure onset. History of KD use was reported for 51% (104 of 204) of individuals, with a median duration of use of 17 months (95% confidence interval = 9-24). Changes in seizure activity after commencing KD were reported for two-thirds (69 of 104), with improvements in 88% (61 of 69). Nearly one-third (31.7%) experienced side effects during the diet. At ascertainment, only one-third (32%) remained on the diet, with lack of long-term efficacy as the main reason for diet cessation (51%, 36 of 70). Benefits of KD in the CDKL5 disorder are in keeping with previous trials on refractory epilepsies. However, poor long-term efficacy remains as a significant barrier. In view of its side effect profile, KD administration should be supervised by a pediatric neurologist and specialist dietician. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  4. PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression possibly through PPAR{gamma} activation in the liver

    Energy Technology Data Exchange (ETDEWEB)

    Oishi, Katsutaka, E-mail: k-ooishi@aist.go.jp [Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki (Japan); Uchida, Daisuke [Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki (Japan); Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki (Japan); Ohkura, Naoki [Department of Clinical Molecular Biology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa (Japan); Horie, Shuichi [Department of Clinical Biochemistry, Kagawa Nutrition University, Sakado, Saitama (Japan)

    2010-10-15

    Research highlights: {yields} PPAR{alpha} deficiency augments a ketogenic diet-induced circadian PAI-1 expression. {yields} Hepatic expressions of PPAR{gamma} and PCG-1{alpha} are induced by a ketogenic diet. {yields} PPAR{gamma} antagonist attenuates a ketogenic diet-induced PAI-1 expression. {yields} Ketogenic diet advances the phase of circadian clock in a PPAR{alpha}-independent manner. -- Abstract: An increased level of plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular diseases, and PAI-1 gene expression is under the control of molecular circadian clocks in mammals. We recently showed that PAI-1 expression is augmented in a phase-advanced circadian manner in mice fed with a ketogenic diet (KD). To determine whether peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) is involved in hypofibrinolytic status induced by a KD, we examined the expression profiles of PAI-1 and circadian clock genes in PPAR{alpha}-null KD mice. Chronic administration of bezafibrate induced the PAI-1 gene expression in a PPAR{alpha}-dependent manner. Feeding with a KD augmented the circadian expression of PAI-1 mRNA in the hearts and livers of wild-type (WT) mice as previously described. The KD-induced mRNA expression of typical PPAR{alpha} target genes such as Cyp4A10 and FGF21 was damped in PPAR{alpha}-null mice. However, plasma PAI-1 concentrations were significantly more elevated in PPAR{alpha}-null KD mice in accordance with hepatic mRNA levels. These observations suggest that PPAR{alpha} activation is dispensable for KD-induced PAI-1 expression. We also found that hyperlipidemia, fatty liver, and the hepatic expressions of PPAR{gamma} and its coactivator PCG-1{alpha} were more effectively induced in PPAR{alpha}-null, than in WT mice on a KD. Furthermore, KD-induced hepatic PAI-1 expression was significantly suppressed by supplementation with bisphenol A diglycidyl ether, a PPAR{gamma} antagonist, in both WT and PPAR

  5. Neurobehavioral Deficits in a Rat Model of Recurrent Neonatal Seizures Are Prevented by a Ketogenic Diet and Correlate with Hippocampal Zinc/Lipid Transporter Signals.

    Science.gov (United States)

    Tian, Tian; Ni, Hong; Sun, Bao-liang

    2015-10-01

    The ketogenic diet (KD) has been shown to be effective as an antiepileptic therapy in adults, but it has not been extensively tested for its efficacy in neonatal seizure-induced brain damage. We have previously shown altered expression of zinc/lipid metabolism-related genes in hippocampus following penicillin-induced developmental model of epilepsy. In this study, we further investigated the effect of KD on the neurobehavioral and cognitive deficits, as well as if KD has any influence in the activity of zinc/lipid transporters such as zinc transporter 3 (ZnT-3), MT-3, ApoE, ApoJ (clusterin), and ACAT-1 activities in neonatal rats submitted to flurothyl-induced recurrent seizures. Postnatal day 9 (P9), 48 Sprague-Dawley rats were randomly assigned to two groups: flurothyl-induced recurrent seizure group (EXP) and control group (CONT). On P28, they were further randomly divided into the seizure group without ketogenic diet (EXP1), seizure plus ketogenic diet (EXP2), the control group without ketogenic diet (CONT1), and the control plus ketogenic diet (CONT2). Neurological behavioral parameters of brain damage (plane righting reflex, cliff avoidance reflex, and open field test) were observed from P35 to P49. Morris water maze test was performed during P51-P57. Then hippocampal mossy fiber sprouting and the protein levels of ZnT3, MT3, ApoE, CLU, and ACAT-1 were detected by Timm staining and Western blot analysis, respectively. Flurothyl-induced neurobehavioral toxicology and aberrant mossy fiber sprouting were blocked by KD. In parallel with these behavioral changes, rats treated with KD (EXP2) showed a significant down-regulated expression of ZnT-3, MT-3, ApoE, clusterin, and ACAT-1 in hippocampus when compared with the non-KD-treated EXP1 group. Our findings provide support for zinc/lipid transporter signals being potential targets for the treatment of neonatal seizure-induced brain damage by KD.

  6. Various ketogenic diets can differently support brain resistance against experimentally evoked seizures and seizure-induced elemental anomalies of hippocampal formation.

    Science.gov (United States)

    Chwiej, J; Patulska, A; Skoczen, A; Matusiak, K; Janeczko, K; Ciarach, M; Simon, R; Setkowicz, Z

    2017-07-01

    In this paper the influence of two different ketogenic diets (KDs) on the seizure-evoked elemental anomalies of hippocampal formation was examined. To achieve this purpose normal and pilocarpine treated rats previously fed with one of the two high fat and carbohydrate restricted diets were compared with animals on standard laboratory diet. The ketogenic ratios of the examined KDs were equal to 5:1 (KD1) and 9:1 (KD2). KD1 and standard diet fed animals presented similar patterns of seizure-evoked elemental changes in hippocampal formation. Also the analysis of behavioral data recorded after pilocarpine injection did not show any significant differences in intensity and duration of seizures between KD1 and standard diet fed animals. Higher ketogenic ratio KD2 introduced in the normal hippocampal formation prolonged changes in the accumulation of P, K, Zn and Ca. Despite this, both the intensity and duration of seizures were significantly reduced in rats fed with KD2 which suggests that its saving action on the nerve tissue may protect brain from seizure propagation. Also seizure-evoked elemental anomalies in KD2 animals were different than those observed for rats both on KD1 and standard diets. The comparison of seizure experiencing and normal rats on KD2, did not show any statistically significant differences in elemental composition of CA1 and H hippocampal areas whilst in CA3 area only Zn level changed as a result of seizures. DG was the area mostly affected by seizures in KD2 fed rats but areal densities of all examined elements increased in this hippocampal region. Copyright © 2017 Elsevier GmbH. All rights reserved.

  7. A ketogenic diet in rodents elicits improved mitochondrial adaptations in response to resistance exercise training compared to an isocaloric Western diet

    Directory of Open Access Journals (Sweden)

    Hayden W Hyatt

    2016-11-01

    Full Text Available Purpose: Ketogenic diets (KD can facilitate weight loss, but their effects on skeletal muscle remain equivocal. In this experiment we investigated the effects of two diets on skeletal muscle mitochondrial coupling, mitochondrial complex activity, markers of oxidative stress, and gene expression in sedentary and resistance exercised rats. Methods: Male Sprague-Dawley rats (9-10 weeks of age, 300-325 g were fed isocaloric amounts of either a KD (17 g/day, 5.2 kcal/g, 20.2% protein, 10.3% CHO, 69.5% fat, n=16 or a Western diet (WD (20 g/day, 4.5 kcal/g, 15.2% protein, 42.7% CHO, 42.0% fat, n=16 for 6 weeks. During these six weeks animals were either sedentary (SED, n=8 per diet group or voluntarily exercised using resistance-loaded running wheels (EXE, n=8 per diet group. Gastrocnemius was excised and used for mitochondrial isolation and biochemical analyses. RESULTS: In the presence of a complex II substrate, the respiratory control ratio (RCR of isolated gastrocnemius mitochondria was higher (p<0.05 in animals fed the KD compared to animals fed the WD. Complex I and IV enzyme activity was higher (p<0.05 in EXE animals regardless of diet. SOD2 protein levels and GLUT4 and PGC1α mRNA expression were higher (p<0.05 in EXE animals regardless of diet. CONCLUSION: Our data indicate that skeletal muscle mitochondrial coupling of complex II substrates is more efficient in chronically resistance trained rodents fed a KD. These findings may provide merit for further investigation, perhaps on humans.

  8. Chronic Ketogenic Low Carbohydrate High Fat Diet Has Minimal Effects on Acid-Base Status in Elite Athletes.

    Science.gov (United States)

    Carr, Amelia J; Sharma, Avish P; Ross, Megan L; Welvaert, Marijke; Slater, Gary J; Burke, Louise M

    2018-02-18

    Although short (up to 3 days) exposure to major shifts in macronutrient intake appears to alter acid-base status, the effects of sustained (>1 week) interventions in elite athletes has not been determined. Using a non-randomized, parallel design, we examined the effect of adaptations to 21 days of a ketogenic low carbohydrate high fat (LCHF) or periodized carbohydrate (PCHO) diet on pre- and post-exercise blood pH, and concentrations of bicarbonate (HCO₃ - ) and lactate (La - ) in comparison to a high carbohydrate (HCHO) control. Twenty-four (17 male and 7 female) elite-level race walkers completed 21 days of either LCHF (n = 9), PCHO (n = 7), or HCHO (n = 8) under controlled diet and training conditions. At baseline and post-intervention, blood pH, blood [HCO₃ - ], and blood [La - ] were measured before and after a graded exercise test. Net endogenous acid production (NEAP) over the previous 48-72 h was also calculated from monitored dietary intake. LCHF was not associated with significant differences in blood pH, [HCO₃ - ], or [La - ], compared with the HCHO diet pre- or post-exercise, despite a significantly higher NEAP (mEq·day -1 ) (95% CI = [10.44; 36.04]). Our results indicate that chronic dietary interventions are unlikely to influence acid-base status in elite athletes, which may be due to pre-existing training adaptations, such as an enhanced buffering capacity, or the actions of respiratory and renal pathways, which have a greater influence on regulation of acid-base status than nutritional intake.

  9. Chronic Ketogenic Low Carbohydrate High Fat Diet Has Minimal Effects on Acid–Base Status in Elite Athletes

    Directory of Open Access Journals (Sweden)

    Amelia J. Carr

    2018-02-01

    Full Text Available Although short (up to 3 days exposure to major shifts in macronutrient intake appears to alter acid–base status, the effects of sustained (>1 week interventions in elite athletes has not been determined. Using a non-randomized, parallel design, we examined the effect of adaptations to 21 days of a ketogenic low carbohydrate high fat (LCHF or periodized carbohydrate (PCHO diet on pre- and post-exercise blood pH, and concentrations of bicarbonate [HCO3−] and lactate [La−] in comparison to a high carbohydrate (HCHO control. Twenty-four (17 male and 7 female elite-level race walkers completed 21 days of either LCHF (n = 9, PCHO (n = 7, or HCHO (n = 8 under controlled diet and training conditions. At baseline and post-intervention, blood pH, blood [HCO3−], and blood [La−] were measured before and after a graded exercise test. Net endogenous acid production (NEAP over the previous 48–72 h was also calculated from monitored dietary intake. LCHF was not associated with significant differences in blood pH, [HCO3−], or [La−], compared with the HCHO diet pre- or post-exercise, despite a significantly higher NEAP (mEq·day−1 (95% CI = (10.44; 36.04. Our results indicate that chronic dietary interventions are unlikely to influence acid–base status in elite athletes, which may be due to pre-existing training adaptations, such as an enhanced buffering capacity, or the actions of respiratory and renal pathways, which have a greater influence on regulation of acid–base status than nutritional intake.

  10. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

    International Nuclear Information System (INIS)

    Otto, Christoph; Kaemmerer, Ulrike; Illert, Bertram; Muehling, Bettina; Pfetzer, Nadja; Wittig, Rainer; Voelker, Hans Ullrich; Thiede, Arnulf; Coy, Johannes F

    2008-01-01

    Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT). Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12) or a standard diet (SD group; n = 12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm 3 to 700 mm 3 . The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume). The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in a mouse xenograft model. Further

  11. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

    Directory of Open Access Journals (Sweden)

    Voelker Hans

    2008-04-01

    Full Text Available Abstract Background Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT. Methods Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12 or a standard diet (SD group; n = 12 ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume. Results The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Conclusion Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT

  12. Inflammation-mediated memory dysfunction and effects of a ketogenic diet in a murine model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Do Young Kim

    Full Text Available A prominent clinical symptom in multiple sclerosis (MS, a progressive disorder of the central nervous system (CNS due to heightened neuro-inflammation, is learning and memory dysfunction. Here, we investigated the effects of a ketogenic diet (KD on memory impairment and CNS-inflammation in a murine model of experimental autoimmune encephalomyelitis (EAE, using electrophysiological, behavioral, biochemical and in vivo imaging approaches. Behavioral spatial learning deficits were associated with motor disability in EAE mice, and were observed concurrently with brain inflammation. The KD improved motor disability in the EAE model, as well as CA1 hippocampal synaptic plasticity (long-term potentiation and spatial learning and memory (assessed with the Morris Water Maze. Moreover, hippocampal atrophy and periventricular lesions in EAE mice were reversed in KD-treated EAE mice. Finally, we found that the increased expression of inflammatory cytokines and chemokines, as well as the production of reactive oxygen species (ROS, in our EAE model were both suppressed by the KD. Collectively, our findings indicate that brain inflammation in EAE mice is associated with impaired spatial learning and memory function, and that KD treatment can exert protective effects, likely via attenuation of the robust immune response and increased oxidative stress seen in these animals.

  13. FGF21 is not required for glucose homeostasis, ketosis or tumour suppression associated with ketogenic diets in mice.

    Science.gov (United States)

    Stemmer, Kerstin; Zani, Fabio; Habegger, Kirk M; Neff, Christina; Kotzbeck, Petra; Bauer, Michaela; Yalamanchilli, Suma; Azad, Ali; Lehti, Maarit; Martins, Paulo J F; Müller, Timo D; Pfluger, Paul T; Seeley, Randy J

    2015-10-01

    Ketogenic diets (KDs) have increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. The metabolic benefits of KDs are regularly ascribed to enhanced hepatic secretion of fibroblast growth factor 21 (FGF21) and its systemic effects on fatty-acid oxidation, energy expenditure (EE) and body weight. Ambiguous data from Fgf21-knockout animal strains and low FGF21 concentrations reported in humans with ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating the therapeutic benefits of KDs on metabolism and cancer. We established a dietary model of increased vs decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted of protein or enriched with protein. We furthermore used wild-type and Fgf21-knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumour growth after transplantation of Lewis lung carcinoma cells. Hepatic and circulating, but not adipose tissue, FGF21 levels were profoundly increased by protein starvation, independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycaemia upon protein and carbohydrate starvation and is therefore not needed for the effects of KDs on EE. Furthermore, the tumour-suppressing effects of KDs were independent of FGF21 and, rather, driven by concomitant protein and carbohydrate starvation. Our data indicate that the multiple systemic effects of KD exposure in mice, previously ascribed to increased FGF21 secretion, are rather a consequence of protein malnutrition.

  14. Fibroblast growth factor 21 is not required for glucose homeostasis, ketosis and tumour suppression associated to ketogenic diets in mice

    Science.gov (United States)

    Stemmer, Kerstin; Zani, Fabio; Habegger, Kirk M.; Neff, Christina; Kotzbeck, Petra; Bauer, Michaela; Yalamanchilli, Suma; Azad, Ali; Lehti, Maarit; Martins, Paulo J.F.; Müller, Timo D.; Pfluger, Paul T.; Seeley, Randy J.

    2016-01-01

    AIMS/HYPOTHESIS Ketogenic diets (KDs) increasingly gained attention as effective means for weight loss and potential adjunctive treatment of cancer. Metabolic benefits of KDs are regularly ascribed towards enhanced hepatic secretion of fibroblast growth factor (FGF) 21, and its systemic effects on fatty acid oxidation, energy expenditure and body weight. Ambiguous data from Fgf21 knockout strains and low FGF21 concentrations reported for humans in ketosis have nevertheless cast doubt regarding the endogenous function of FGF21. We here aimed to elucidate the causal role of FGF21 in mediating therapeutic benefits of KDs on metabolism and cancer. METHODS We established a dietary model of increased vs. decreased FGF21 by feeding C57BL/6J mice with KDs, either depleted or enriched with protein, respectively. We furthermore used wild type and Fgf21 knockout mice that were subjected to the respective diets, and monitored energy and glucose homeostasis as well as tumor growth after transplantation of Lewis-Lung-Carcinoma cells. RESULTS Hepatic and circulating but not adipose tissue FGF21 levels were profoundly increased by protein starvation and independent of the state of ketosis. We demonstrate that endogenous FGF21 is not essential for the maintenance of normoglycemia upon protein and carbohydrate starvation and is dispensable for the effects of KDs on energy expenditure. Furthermore, the tumor-suppressing effects of KDs were independent from FGF21, and rather driven by concomitant protein and carbohydrate starvation. CONCLUSION/INTERPRETATION Our data indicate that multiple systemic effects of KDs exposure in mice that were previously ascribed towards increased FGF21 secretion are rather a consequence of protein malnutrition. PMID:26099854

  15. Ketogenic diet exposure during the juvenile period increases social behaviors and forebrain neural activation in adult Engrailed 2 null mice.

    Science.gov (United States)

    Verpeut, Jessica L; DiCicco-Bloom, Emanuel; Bello, Nicholas T

    2016-07-01

    Prolonged consumption of ketogenic diets (KD) has reported neuroprotective benefits. Several studies suggest KD interventions could be useful in the management of neurological and developmental disorders. Alterations in the Engrailed (En) genes, specifically Engrailed 2 (En2), have neurodevelopmental consequences and produce autism-related behaviors. The following studies used En2 knockout (KO; En2(-/-)), and wild-type (WT; En2(+/+)), male mice fed either KD (80% fat, 0.1% carbohydrates) or control diet (CD; 10% fat, 70% carbohydrates). The objective was to determine whether a KD fed from weaning at postnatal day (PND) 21 to adulthood (PND 60) would alter brain monoamines concentrations, previously found dysregulated, and improve social outcomes. In WT animals, there was an increase in hypothalamic norepinephrine content in the KD-fed group. However, regional monoamines were not altered in KO mice in KD-fed compared with CD-fed group. In order to determine the effects of juvenile exposure to KD in mice with normal blood ketone levels, separate experiments were conducted in mice removed from the KD or CD and fed standard chow for 2days (PND 62). In a three-chamber social test with a novel mouse, KO mice previously exposed to the KD displayed similar social and self-grooming behaviors compared with the WT group. Groups previously exposed to a KD, regardless of genotype, had more c-Fos-positive cells in the cingulate cortex, lateral septal nuclei, and anterior bed nucleus of the stria terminalis. In the novel object condition, KO mice previously exposed to KD had similar behavioral responses and pattern of c-Fos immunoreactivity compared with the WT group. Thus, juvenile exposure to KD resulted in short-term consequences of improving social interactions and appropriate exploratory behaviors in a mouse model that displays autism-related behaviors. Such findings further our understanding of metabolic-based therapies for neurological and developmental disorders

  16. Genetic modifications associated with ketogenic diet treatment in the BTBRT+Tf/J mouse model of autism spectrum disorder.

    Science.gov (United States)

    Mychasiuk, Richelle; Rho, Jong M

    2017-03-01

    Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder characterized by hallmark behavioral features. The spectrum of disorders that fall within the ASD umbrella encompass a distinct but overlapping symptom complex that likely results from an array of molecular and genetic aberrations rather than a single genetic mutation. The ketogenic diet (KD) is a high-fat low-carbohydrate anti-seizure and neuroprotective diet that has demonstrated efficacy in the treatment of ASD-like behaviors in animal and human studies. We investigated changes in mRNA and gene expression in the BTBR mouse model of ASD that may contribute to the behavioral phenotype. In addition, we sought to examine changes in gene expression following KD treatment in BTBR mice. Despite significant behavioral abnormalities, expression changes in BTBR mice did not differ substantially from controls; only 33 genes were differentially expressed in the temporal cortex, and 48 in the hippocampus. Examination of these differentially expressed genes suggested deficits in the stress response and in neuronal signaling/communication. After treatment with the KD, both brain regions demonstrated improvements in ASD deficits associated with myelin formation and white matter development. Although our study supports many of the previously known impairments associated with ASD, such as excessive myelin formation and impaired GABAergic transmission, the RNAseq data and pathway analysis utilized here identified new therapeutic targets for analysis, such as Vitamin D pathways and cAMP signaling. Autism Res 2017, 10: 456-471. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

  17. Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model

    Science.gov (United States)

    Brunetti, Dario; Dusi, Sabrina; Giordano, Carla; Lamperti, Costanza; Morbin, Michela; Fugnanesi, Valeria; Marchet, Silvia; Fagiolari, Gigliola; Sibon, Ody; Moggio, Maurizio; d’Amati, Giulia

    2014-01-01

    Pantothenate kinase-associated neurodegeneration, caused by mutations in the PANK2 gene, is an autosomal recessive disorder characterized by dystonia, dysarthria, rigidity, pigmentary retinal degeneration and brain iron accumulation. PANK2 encodes the mitochondrial enzyme pantothenate kinase type 2, responsible for the phosphorylation of pantothenate or vitamin B5 in the biosynthesis of co-enzyme A. A Pank2 knockout (Pank2−/−) mouse model did not recapitulate the human disease but showed azoospermia and mitochondrial dysfunctions. We challenged this mouse model with a low glucose and high lipid content diet (ketogenic diet) to stimulate lipid use by mitochondrial beta-oxidation. In the presence of a shortage of co-enzyme A, this diet could evoke a general impairment of bioenergetic metabolism. Only Pank2−/− mice fed with a ketogenic diet developed a pantothenate kinase-associated neurodegeneration-like syndrome characterized by severe motor dysfunction, neurodegeneration and severely altered mitochondria in the central and peripheral nervous systems. These mice also showed structural alteration of muscle morphology, which was comparable with that observed in a patient with pantothenate kinase-associated neurodegeneration. We here demonstrate that pantethine administration can prevent the onset of the neuromuscular phenotype in mice suggesting the possibility of experimental treatment in patients with pantothenate kinase-associated neurodegeneration. PMID:24316510

  18. A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease

    OpenAIRE

    Van Leuven Fred; Wera Stefaan; Van der Auwera Ingrid; Henderson Samuel T

    2005-01-01

    Abstract Background Alzheimer's disease (AD) is a progressive neurodegenerative disorder that primarily strikes the elderly. Studies in both humans and animal models have linked the consumption of cholesterol and saturated fats with amyloid-β (Aβ) deposition and development of AD. Yet, these studies did not examine high fat diets in combination with reduced carbohydrate intake. Here we tested the effect of a high saturated fat/low carbohydrate diet on a transgenic mouse model of AD. Results S...

  19. Effectiveness of ketogenic diet in pentylenetetrazol-induced and kindling rats as well as its potential mechanisms.

    Science.gov (United States)

    Wang, Shan; Ding, Yao; Ding, Xiao-Yan; Liu, Zhi-Rong; Shen, Chun-Hong; Jin, Bo; Guo, Yi; Wang, Shuang; Ding, Mei-Ping

    2016-02-12

    The effects and mechanisms of ketogenic diets (KD) are unclear. In this study, we aimed to reveal electrographic and behavioral thresholds in responses to the KD in pentylenetetrazol (PTZ)-induced seizures, as well as its antiepileptogenic effects on PTZ-kindling rats. Additionally, we investigated the potential link between KD and expression levels of two cation chloride co-transporters: K(+)-Cl(-) co-transporter 2 (KCC2) and Na(+)-K(+)-Cl(-) co-transporter 1 (NKCC1). The KD group had significantly higher electrographic thresholds than the control (ND) group for the first spike-and-wave, subcontinuous spike-and-wave, high amplitude spike-and-wave, and polyspikes both in the cortex and hippocampus. Compared to the ND group, the KD group had higher behavioral thresholds for behavioral absence, first jerk, first overt myoclonia, and generalized seizures. In the PTZ-kindling model, KD not only prolonged the latency of myoclonic and clonic convulsions, but shortened clonic and generalized duration. In addition, KD rats had higher KCC2 protein expression before kindling, during myoclonic jerks, and GTCS compared with ND rats. There were no significant differences in NKCC1 protein levels between both groups following the four-week dietary intervention without PTZ exposure (before kindling). Moreover, KD inhibited the upregulation of NKCC1 expression induced by kindling in myoclonic jerks and GTCS. Therefore, our findings demonstrated that KD had antiepileptic features in elevating thresholds to most electrographic and behavioral seizure patterns in PTZ-induced rats, as well as delaying the progression and alleviating the severity of seizure in PTZ-kindling model. The antiepileptogenic effects of KD may be attributed to its regulatory properties on KCC2 and NKCC1 protein expression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Ketogenic Diet Impairs FGF21 Signaling and Promotes Differential Inflammatory Responses in the Liver and White Adipose Tissue.

    Directory of Open Access Journals (Sweden)

    Mohamed Asrih

    Full Text Available Beside its beneficial effects on weight loss, ketogenic diet (KD causes dyslipidemia, a pro-inflammatory state involved in the development of hepatic steatosis, glucose intolerance and insulin resistance, although the latter is still being debated. Additionally, KD is known to increase fibroblast growth factor 21 (FGF21 plasma levels. However, FGF21 cannot initiate its beneficial actions on metabolism in these conditions. We therefore hypothesized and tested in the present study that KD may impair FGF21 signaling.Using indirect calorimetry, we found that KD-fed mice exhibited higher energy expenditure than regular chow (RC-fed mice associated with increased Ucp1 levels in white adipose tissue (WAT, along with increased plasma FGF21 levels. We then assessed the effect of KD on FGF21 signaling in both the liver and WAT. We found that Fgfr4 and Klb (β-klotho were downregulated in the liver, while Fgfr1 was downregulated in WAT of KD-fed mice. Because inflammation could be one of the mechanisms linking KD to impaired FGF21 signaling, we measured the expression levels of inflammatory markers and macrophage accumulation in WAT and liver and found an increased inflammation and macrophage accumulation in the liver, but surprisingly, a reduction of inflammation in WAT.We also showed that KD enhances lipid accumulation in the liver, which may explain hepatic inflammation and impaired Fgfr4 and Klb expression. In contrast, import of lipids from the circulation was significantly reduced in WAT of KD-fed mice, as suggested by a downregulation of Lpl and Cd36. This was further associated with reduced inflammation in WAT.Altogether, these results indicate that KD could be beneficial for a given tissue but deleterious for another.

  1. Improvement in age-related cognitive functions and life expectancy by ketogenic diets

    DEFF Research Database (Denmark)

    Astrup, Arne; Hjorth, Mads Fiil

    2017-01-01

    Rodent studies have indicated that low-carbohydrate diets prevent age-related cognitive decline and extend lifespan due to increased circulating levels of ketone bodies. A possible physiological mechanism for how ketone bodies exert this effect might be by improving central nervous system insulin...

  2. Ketogenic diet benefits body composition and well-being but not performance in a pilot case study of New Zealand endurance athletes.

    Science.gov (United States)

    Zinn, Caryn; Wood, Matthew; Williden, Mikki; Chatterton, Simon; Maunder, Ed

    2017-01-01

    Low-carbohydrate, high-fat and ketogenic diets are increasingly adopted by athletes for body composition and sports performance enhancements. However, as yet, there is no consensus on their efficacy in improving performance. There is also no comprehensive literature on athletes' experiences while undertaking this diet. The purpose of this pilot work was two-fold: i. to examine the effects of a non-calorie controlled ketogenic diet on body composition and performance outcomes of endurance athletes, and ii. to evaluate the athletes' experiences of the ketogenic diet during the 10-week intervention. Using a case study design, five New Zealand endurance athletes (4 females, 1 male) underwent a 10-week ketogenic dietary intervention. Body composition (sum of 8 skinfolds), performance indicators (time to exhaustion, VO 2 max, peak power and ventilatory threshold), and gas exchange thresholds were measured at baseline and at 10 weeks. Mean change scores were calculated, and analysed using t-tests; Cohen's effect sizes and 90% confidence limits were applied to quantify change. Individual interviews conducted at 5 weeks and a focus group at 10 weeks assessed athletes' ketogenic diet experiences. Data was transcribed and analysed using thematic analysis. All athletes increased their ability to utilise fat as a fuel source, including at higher exercise intensities. Mean body weight was reduced by 4 kg ± SD 3.1 ( p  = 0.046; effect size (ES):0.62), and sum of 8 skinfolds by 25.9 mm ± SD 6.9; ES: 1.27; p  = 0.001). Mean time to exhaustion dropped by ~2 min (±SD 0.7; p  = 0.004; ES: 0.53). Other performance outcomes showed mean reductions, with some increases or unchanged results in two individuals (VO2 Max: -1.69 ml.kg.min ± SD 3.4 ( p  = 0.63); peak power: -18 W ± SD 16.4 ( p  = 0.07), and VT2: -6 W ± SD 44.5 ( p  = 0.77). Athletes reported experiencing reduced energy levels initially, followed by a return of high levels thereafter

  3. The Three-Month Effects of a Ketogenic Diet on Body Composition, Blood Parameters, and Performance Metrics in CrossFit Trainees: A Pilot Study

    Science.gov (United States)

    Kephart, Wesley C.; Pledge, Coree D.; Roberson, Paul A.; Mumford, Petey W.; Romero, Matthew A.; Mobley, Christopher B.; Young, Kaelin C.; Lowery, Ryan P.; Wilson, Jacob M.; Huggins, Kevin W.; Roberts, Michael D.

    2018-01-01

    Adopting low carbohydrate, ketogenic diets remains a controversial issue for individuals who resistance train given that this form of dieting has been speculated to reduce skeletal muscle glycogen levels and stifle muscle anabolism. We sought to characterize the effects of a 12-week ketogenic diet (KD) on body composition, metabolic, and performance parameters in participants who trained recreationally at a local CrossFit facility. Twelve participants (nine males and three females, 31 ± 2 years of age, 80.3 ± 5.1 kg body mass, 22.9 ± 2.3% body fat, 1.37 back squat: body mass ratio) were divided into a control group (CTL; n = 5) and a KD group (n = 7). KD participants were given dietary guidelines to follow over 12 weeks while CTL participants were instructed to continue their normal diet throughout the study, and all participants continued their CrossFit training routine for 12 weeks. Pre, 2.5-week, and 12-week anaerobic performance tests were conducted, and pre- and 12-week tests were performed for body composition using dual X-ray absorptiometry (DXA) and ultrasound, resting energy expenditure (REE), blood-serum health markers, and aerobic capacity. Additionally, blood beta hydroxybutyrate (BHB) levels were measured weekly. Blood BHB levels were 2.8- to 9.5-fold higher in KD versus CTL throughout confirming a state of nutritional ketosis. DXA fat mass decreased by 12.4% in KD (p = 0.053). DXA total lean body mass changes were not different between groups, although DXA dual-leg lean mass decreased in the KD group by 1.4% (p = 0.068), and vastus lateralis thickness values decreased in the KD group by ~8% (p = 0.065). Changes in fasting glucose, HDL cholesterol, and triglycerides were similar between groups, although LDL cholesterol increased ~35% in KD (p = 0.048). Between-group changes in REE, one-repetition maximum (1-RM) back squat, 400 m run times, and VO2peak were similar between groups. While our n-sizes were limited, these preliminary data suggest that

  4. The Three-Month Effects of a Ketogenic Diet on Body Composition, Blood Parameters, and Performance Metrics in CrossFit Trainees: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Wesley C. Kephart

    2018-01-01

    Full Text Available Adopting low carbohydrate, ketogenic diets remains a controversial issue for individuals who resistance train given that this form of dieting has been speculated to reduce skeletal muscle glycogen levels and stifle muscle anabolism. We sought to characterize the effects of a 12-week ketogenic diet (KD on body composition, metabolic, and performance parameters in participants who trained recreationally at a local CrossFit facility. Twelve participants (nine males and three females, 31 ± 2 years of age, 80.3 ± 5.1 kg body mass, 22.9 ± 2.3% body fat, 1.37 back squat: body mass ratio were divided into a control group (CTL; n = 5 and a KD group (n = 7. KD participants were given dietary guidelines to follow over 12 weeks while CTL participants were instructed to continue their normal diet throughout the study, and all participants continued their CrossFit training routine for 12 weeks. Pre, 2.5-week, and 12-week anaerobic performance tests were conducted, and pre- and 12-week tests were performed for body composition using dual X-ray absorptiometry (DXA and ultrasound, resting energy expenditure (REE, blood-serum health markers, and aerobic capacity. Additionally, blood beta hydroxybutyrate (BHB levels were measured weekly. Blood BHB levels were 2.8- to 9.5-fold higher in KD versus CTL throughout confirming a state of nutritional ketosis. DXA fat mass decreased by 12.4% in KD (p = 0.053. DXA total lean body mass changes were not different between groups, although DXA dual-leg lean mass decreased in the KD group by 1.4% (p = 0.068, and vastus lateralis thickness values decreased in the KD group by ~8% (p = 0.065. Changes in fasting glucose, HDL cholesterol, and triglycerides were similar between groups, although LDL cholesterol increased ~35% in KD (p = 0.048. Between-group changes in REE, one-repetition maximum (1-RM back squat, 400 m run times, and VO2peak were similar between groups. While our n-sizes were limited, these preliminary data suggest

  5. Changes in quality of life as a result of ketogenic diet therapy: A new approach to assessment with the potential for positive therapeutic effects.

    Science.gov (United States)

    Bruce, Susan; Devlin, Anita; Air, Linda; Cook, Lucy

    2017-01-01

    There are difficulties inherent in measuring Quality of life (QoL) in patients with chronic illness, including agreement on definitions of quality of life and the type of measure used, disease specific or generic. Well validated QoL instruments for epilepsy exist but focus on capturing common themes pertinent to children and families as a group instead of focusing on themes important to individual patients and their families/carers. In addition, it is common for numerous items on these inventories to be left incomplete or responded to with "not applicable" since many of the items are not suitable for children with disabilities and their families. This led us to devise a way to capture individual quality-of-life measures that are linked to parental/carer expectations in families of children undergoing ketogenic diet therapy for epilepsy. As part of our routine clinical assessment, parents/carers were asked to describe what they would like to see happen or change as a result of their child being on ketogenic diet therapy. A simple unstructured form was designed to facilitate the assessment process. Parents were then asked to rate their own QoL against these criteria on a Likert scale of 0-10 prior to commencement of the diet. This assessment was repeated at subsequent visits with parents/carers initially blinded to their original responses. Our assessments indicated that ketogenic diet therapy improves quality of life over a twelve-month period when measured against parental expectations. This ideographic approach has demonstrated changes in parental Qol and parental perceptions of their child's quality of life that would not have been captured by other validated measures. A lengthy questionnaire is avoided and is replaced by a skilled supportive conversation that identifies goals for treatment that are important to parents. This helps parents to reflect on the progress their child makes on the diet by revisiting their previously stated aspirations, and assessing

  6. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials.

    Science.gov (United States)

    Bueno, Nassib Bezerra; de Melo, Ingrid Sofia Vieira; de Oliveira, Suzana Lima; da Rocha Ataide, Terezinha

    2013-10-01

    The role of very-low-carbohydrate ketogenic diets (VLCKD) in the long-term management of obesity is not well established. The present meta-analysis aimed to investigate whether individuals assigned to a VLCKD (i.e. a diet with no more than 50 g carbohydrates/d) achieve better long-term body weight and cardiovascular risk factor management when compared with individuals assigned to a conventional low-fat diet (LFD; i.e. a restricted-energy diet with less than 30% of energy from fat). Through August 2012, MEDLINE, CENTRAL, ScienceDirect,Scopus, LILACS, SciELO, ClinicalTrials.gov and grey literature databases were searched, using no date or language restrictions, for randomised controlled trials that assigned adults to a VLCKD or a LFD, with 12 months or more of follow-up. The primary outcome was bodyweight. The secondary outcomes were TAG, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), systolic and diastolic blood pressure,glucose, insulin, HbA1c and C-reactive protein levels. A total of thirteen studies met the inclusion/exclusion criteria. In the overall analysis,five outcomes revealed significant results. Individuals assigned to a VLCKD showed decreased body weight (weighted mean difference 20·91 (95% CI 21·65, 20·17) kg, 1415 patients), TAG (weighted mean difference 20·18 (95% CI 20·27, 20·08) mmol/l, 1258 patients)and diastolic blood pressure (weighted mean difference 21·43 (95% CI 22·49, 20·37) mmHg, 1298 patients) while increased HDL-C(weighted mean difference 0·09 (95% CI 0·06, 0·12) mmol/l, 1257 patients) and LDL-C (weighted mean difference 0·12 (95% CI 0·04,0·2) mmol/l, 1255 patients). Individuals assigned to a VLCKD achieve a greater weight loss than those assigned to a LFD in the longterm; hence, a VLCKD may be an alternative tool against obesity.

  7. Short-term impact of a classical ketogenic diet on gut microbiota in GLUT1 Deficiency Syndrome: A 3-month prospective observational study.

    Science.gov (United States)

    Tagliabue, Anna; Ferraris, Cinzia; Uggeri, Francesca; Trentani, Claudia; Bertoli, Simona; de Giorgis, Valentina; Veggiotti, Pierangelo; Elli, Marina

    2017-02-01

    The classical ketogenic diet (KD) is a high-fat, very low-carbohydrate normocaloric diet used for drug-resistant epilepsy and Glucose Transporter 1 Deficiency Syndrome (GLUT1 DS). In animal models, high fat diet induces large alterations in microbiota producing deleterious effects on gut health. We carried out a pilot study on patients treated with KD comparing their microbiota composition before and after three months on the diet. Six patients affected by GLUT1 DS were asked to collect fecal samples before and after three months on the diet. RT - PCR analysis was performed in order to quantify Firmicutes, Bacteroidetes, Bifidobacterium spp., Lactobacillus spp., Clostridium perfringens, Enterobacteriaceae, Clostridium cluster XIV, Desulfovibrio spp. and Faecalibacterium prausnitzii. Compared with baseline, there were no statistically significant differences at 3 months in Firmicutes and Bacteroidetes. However fecal microbial profiles revealed a statistically significant increase in Desulfovibrio spp. (p = 0.025), a bacterial group supposed to be involved in the exacerbation of the inflammatory condition of the gut mucosa associated to the consumption of fats of animal origin. A future prospective study on the changes in gut microbiota of all children with epilepsy started on a KD is warranted. In patients with dysbiosis demonstrated by fecal samples, it my be reasonable to consider an empiric trial of pre or probiotics to potentially restore the «ecological balance» of intestinal microbiota. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  8. Long-term ketogenic diet contributes to glycemic control but promotes lipid accumulation and hepatic steatosis in type 2 diabetic mice.

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    Zhang, Xiaoyu; Qin, Juliang; Zhao, Yihan; Shi, Jueping; Lan, Rong; Gan, Yunqiu; Ren, Hua; Zhu, Bing; Qian, Min; Du, Bing

    2016-04-01

    The ketogenic diet (KD) has been widely used in weight and glycemic control, although potential side effects of long-term KD treatment have caused persistent concern. In this study, we hypothesized that the KD would ameliorate the progression of diabetes but lead to disruptions in lipid metabolism and hepatic steatosis in a mouse model of diabetes. In type 2 diabetic mouse model, mice were fed a high-fat diet and administered streptozotocin treatment before given the test diets for 8 weeks. Subsequently, ameliorated glucose and insulin tolerance in KD-fed diabetic mice was found, although the body weight of high-fat diet- and KD-fed mice was similar. Interestingly, the weight of adipose tissue in KD mice was greater than in the other groups. The KD diet resulted in higher serum triacylglycerol and cholesterol levels in diabetic mice. Moreover, the KD-fed mice showed greater hepatic lipid accumulation. Mice fed the KD showed significant changes in several key genes such as sterol regulatory element-binding protein, fibroblast growth factor 21, and peroxisome proliferator-activated receptor α, which are all important in metabolism. In summary, KD ameliorates glucose and insulin tolerance in a mouse model of diabetes, but severe hepatic lipid accumulation and hepatic steatosis were observed, which should be considered carefully in the long-term application of KD. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Long-Term Effects of Ketogenic Diet on Subsequent Seizure-Induced Brain Injury During Early Adulthood: Relationship of Seizure Thresholds to Zinc Transporter-Related Gene Expressions.

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    Tian, Tian; Li, Li-Li; Zhang, Shu-Qi; Ni, Hong

    2016-12-01

    The divalent cation zinc is associated with cortical plasticity. However, the mechanism of zinc in the pathophysiology of cortical injury-associated neurobehavioral damage following neonatal seizures is uncertain. We have previously shown upregulated expression of ZnT-3; MT-3 in hippocampus of neonatal rats submitted to flurothyl-induced recurrent seizures, which was restored by pretreatment with ketogenic diet (KD). In this study, utilizing a novel "twist" seizure model by coupling early-life flurothyl-induced seizures with later exposure to penicillin, we further investigated the long-term effects of KD on cortical expression of zinc homeostasis-related genes in a systemic scale. Ten Sprague-Dawley rats were assigned each averagely into the non-seizure plus normal diet (NS + ND), non-seizure plus KD (NS + KD), recurrent seizures plus normal diet (RS + ND) and recurrent seizures plus KD (RS + KD) group. Recurrent seizures were induced by volatile flurothyl during P9-P21. During P23-P53, rats in NS + KD and RS + KD groups were dieted with KD. Neurological behavioral parameters of brain damage (plane righting reflex, cliff avoidance reflex, and open field test) were observed at P43. At P63, we examined seizure threshold using penicillin, then the cerebral cortex were evaluated for real-time RT-PCR and western blot study. The RS + ND group showed worse performances in neurological reflex tests and reduced latencies to myoclonic seizures induced by penicillin compared with the control, which was concomitant with altered expressions of ZnT-7, MT-1, MT-2, and ZIP7. Specifically, there was long-term elevated expression of ZIP7 in RS + ND group compared with that in NS + ND that was restored by chronic ketogenic diet (KD) treatment in RS + KD group, which was quite in parallel with the above neurobehavioral changes. Taken together, these findings indicate that the long-term altered expression of the metal transporter ZIP7 in adult cerebral cortex might

  10. Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus.

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    Goday, A; Bellido, D; Sajoux, I; Crujeiras, A B; Burguera, B; García-Luna, P P; Oleaga, A; Moreno, B; Casanueva, F F

    2016-09-19

    Brackground:The safety and tolerability of very low-calorie-ketogenic (VLCK) diets are a current concern in the treatment of obese type 2 diabetes mellitus (T2DM) patients. Evaluating the short-term safety and tolerability of a VLCK diet (diet), and 44 to the standard low-calorie diet. No significant differences in the laboratory safety parameters were found between the two study groups. Changes in the urine albumin-to-creatinine ratio in VLCK diet were not significant and were comparable to control group. Creatinine and blood urea nitrogen did not change significantly relative to baseline nor between groups. Weight loss and reduction in waist circumference in the VLCK diet group were significantly larger than in control subjects (both Pdiet group (Pdiet group declined at last follow-up. The interventional weight loss program based on a VLCK diet is most effective in reducing body weight and improvement of glycemic control than a standard hypocaloric diet with safety and good tolerance for T2DM patients.

  11. Effects of a ketogenic diet on adipose tissue, liver, and serum biomarkers in sedentary rats and rats that exercised via resisted voluntary wheel running.

    Science.gov (United States)

    Holland, Angelia Maleah; Kephart, Wesley C; Mumford, Petey W; Mobley, Christopher Brooks; Lowery, Ryan P; Shake, Joshua J; Patel, Romil K; Healy, James C; McCullough, Danielle J; Kluess, Heidi A; Huggins, Kevin W; Kavazis, Andreas N; Wilson, Jacob M; Roberts, Michael D

    2016-08-01

    We investigated the effects of different diets on adipose tissue, liver, serum morphology, and biomarkers in rats that voluntarily exercised. Male Sprague-Dawley rats (∼9-10 wk of age) exercised with resistance-loaded voluntary running wheels (EX; wheels loaded with 20-60% body mass) or remained sedentary (SED) over 6 wk. EX and SED rats were provided isocaloric amounts of either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), a Western diet (WD; 15.2%-42.7-42.0%), or standard chow (SC; 24.0%-58.0%-18.0%); n = 8-10 in each diet for SED and EX rats. Following the intervention, body mass and feed efficiency were lowest in KD rats, independent of exercise (P diets [total acetyl coA carboxylase (ACC), CD36, and CEBPα or phosphorylated NF-κB/p65, AMPKα, and hormone-sensitive lipase (HSL)], although EX unexpectedly altered some OMAT markers (i.e., higher ACC and phosphorylated NF-κB/p65, and lower phosphorylated AMPKα and phosphorylated HSL). Liver triglycerides were greatest in WD rats (P < 0.05), and liver phosphorylated NF-κB/p65 was lowest in KD rats (P < 0.05). Serum insulin, glucose, triglycerides, and total cholesterol were greater in WD and/or SC rats compared with KD rats (P < 0.05), and serum β-hydroxybutyrate was greater in KD vs. SC rats (P < 0.05). In conclusion, KD rats presented a healthier metabolic profile, albeit the employed exercise protocol minimally impacts any potentiating effects that KD has on fat loss. Copyright © 2016 the American Physiological Society.

  12. Organisation of Dietary Control for Nutrition-Training Intervention Involving Periodized Carbohydrate (CHO) Availability and Ketogenic Low CHO High Fat (LCHF) Diet.

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    Mirtschin, Joanne G; Forbes, Sara F; Cato, Louise E; Heikura, Ida A; Strobel, Nicki; Hall, Rebecca; Burke, Louise M

    2018-02-12

    We describe the implementation of a 3-week dietary intervention in elite race walkers at the Australian Institute of Sport, with a focus on the resources and strategies needed to accomplish a complex study of this scale. Interventions involved: traditional guidelines of high carbohydrate (CHO) availability for all training sessions (HCHO); a periodized CHO diet which integrated sessions with low CHO and high CHO availability within the same total CHO intake, and a ketogenic low-CHO high-fat diet (LCHF). 7-day menus and recipes were constructed for a communal eating setting to meet nutritional goals as well as individualized food preferences and special needs. Menus also included nutrition support pre, during and post-exercise. Daily monitoring, via observation and food checklists, showed that energy and macronutrient targets were achieved: diets were matched for energy (~14.8 MJ/d) and protein (~2.1 g.kg/d), and achieved desired differences for fat and CHO: HCHO and PCHO: CHO = 8.5 g/kg/d, 60% energy; fat = 20% of energy; LCHF: 0.5 g/kg/d CHO, fat = 78% energy. There were no differences in micronutrient intakes or density between HCHO and PCHO diets; however, the micronutrient density of LCHF was significantly lower. Daily food costs per athlete were similar for each diet (~AUDS$27 ± 10). Successful implementation and monitoring of dietary interventions in sports nutrition research of the scale of the present study require meticulous planning and the expertise of chefs and sports dietitians. Different approaches to sports nutrition support raise practical challenges around cost, micronutrient density, accommodation of special needs and sustainability.

  13. Beneficial effect of feeding a ketogenic diet to mothers on brain development in their progeny with a murine model of pyruvate dehydrogenase complex deficiency.

    Science.gov (United States)

    Pliss, Lioudmila; Jatania, Urvi; Patel, Mulchand S

    2016-06-01

    Pyruvate dehydrogenase complex (PDC) deficiency is a major inborn error of oxidative metabolism of pyruvate in the mitochondria causing congenital lactic acidosis and primarily structural and functional abnormalities of the central nervous system. To provide an alternate source of acetyl-CoA derived from ketone bodies to the developing brain, a formula high in fat content is widely employed as a treatment. In the present study we investigated efficacy of a high-fat diet given to mothers during pregnancy and lactation on lessening of the impact of PDC deficiency on brain development in PDC-deficient female progeny. A murine model of systemic PDC deficiency by interrupting the X-linked Pdha1 gene was employed in this study. Maternal consumption of a high-fat diet during pregnancy and lactation had no effect on number of live-birth, body growth, tissue PDC activity levels, as well as the in vitro rates of glucose oxidation and fatty acid biosynthesis by the developing brain of PDC-deficient female offspring during the postnatal age 35 days, as compared to the PDC-deficient progeny born to dams on a chow diet. Interestingly, brain weight was normalized in PDC-deficient progeny of high fat-fed mothers with improvement in impairment in brain structure deficit whereas brain weight was significantly decreased and was associated with greater cerebral structural defects in progeny of chow-fed mothers as compared to control progeny of mothers fed either a chow or high fat diet. The findings provide for the first time experimental support for beneficial effects of a ketogenic diet during the prenatal and early postnatal periods on the brain development of PDC-deficient mammalian progeny.

  14. The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma

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    Stafford Phillip

    2010-09-01

    Full Text Available Abstract Background Malignant brain tumors affect people of all ages and are the second leading cause of cancer deaths in children. While current treatments are effective and improve survival, there remains a substantial need for more efficacious therapeutic modalities. The ketogenic diet (KD - a high-fat, low-carbohydrate treatment for medically refractory epilepsy - has been suggested as an alternative strategy to inhibit tumor growth by altering intrinsic metabolism, especially by inducing glycopenia. Methods Here, we examined the effects of an experimental KD on a mouse model of glioma, and compared patterns of gene expression in tumors vs. normal brain from animals fed either a KD or a standard diet. Results Animals received intracranial injections of bioluminescent GL261-luc cells and tumor growth was followed in vivo. KD treatment significantly reduced the rate of tumor growth and prolonged survival. Further, the KD reduced reactive oxygen species (ROS production in tumor cells. Gene expression profiling demonstrated that the KD induces an overall reversion to expression patterns seen in non-tumor specimens. Notably, genes involved in modulating ROS levels and oxidative stress were altered, including those encoding cyclooxygenase 2, glutathione peroxidases 3 and 7, and periredoxin 4. Conclusions Our data demonstrate that the KD improves survivability in our mouse model of glioma, and suggests that the mechanisms accounting for this protective effect likely involve complex alterations in cellular metabolism beyond simply a reduction in glucose.

  15. Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodies

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    Mantis John G

    2004-10-01

    Full Text Available Abstract Background The high fat, low carbohydrate ketogenic diet (KD was developed as an alternative to fasting for seizure management. While the mechanisms by which fasting and the KD inhibit seizures remain speculative, alterations in brain energy metabolism are likely involved. We previously showed that caloric restriction (CR inhibits seizure susceptibility by reducing blood glucose in the epileptic EL mouse, a natural model for human multifactorial idiopathic epilepsy. In this study, we compared the antiepileptic and anticonvulsant efficacy of the KD with that of CR in adult EL mice with active epilepsy. EL mice that experienced at least 15 recurrent complex partial seizures were fed either a standard diet unrestricted (SD-UR or restricted (SD-R, and either a KD unrestricted (KD-UR or restricted (KD-R. All mice were fasted for 14 hrs prior to diet initiation. A new experimental design was used where each mouse in the diet-restricted groups served as its own control to achieve a 20–23% body weight reduction. Seizure susceptibility, body weights, and the levels of plasma glucose and β-hydroxybutyrate were measured once/week over a nine-week treatment period. Results Body weights and blood glucose levels remained high over the testing period in the SD-UR and the KD-UR groups, but were significantly (p Conclusions The results indicate that seizure susceptibility in EL mice is dependent on plasma glucose levels and that seizure control is more associated with the amount than with the origin of dietary calories. Also, CR underlies the antiepileptic and anticonvulsant action of the KD in EL mice. A transition from glucose to ketone bodies for energy is predicted to manage EL epileptic seizures through multiple integrated changes of inhibitory and excitatory neural systems.

  16. An Online Intervention Comparing a Very Low-Carbohydrate Ketogenic Diet and Lifestyle Recommendations Versus a Plate Method Diet in Overweight Individuals With Type 2 Diabetes: A Randomized Controlled Trial.

    Science.gov (United States)

    Saslow, Laura R; Mason, Ashley E; Kim, Sarah; Goldman, Veronica; Ploutz-Snyder, Robert; Bayandorian, Hovig; Daubenmier, Jennifer; Hecht, Frederick M; Moskowitz, Judith T

    2017-02-13

    Type 2 diabetes is a prevalent, chronic disease for which diet is an integral aspect of treatment. In our previous trial, we found that recommendations to follow a very low-carbohydrate ketogenic diet and to change lifestyle factors (physical activity, sleep, positive affect, mindfulness) helped overweight people with type 2 diabetes or prediabetes improve glycemic control and lose weight. This was an in-person intervention, which could be a barrier for people without the time, flexibility, transportation, social support, and/or financial resources to attend. The aim was to determine whether an online intervention based on our previous recommendations (an ad libitum very low-carbohydrate ketogenic diet with lifestyle factors; "intervention") or an online diet program based on the American Diabetes Associations' "Create Your Plate" diet ("control") would improve glycemic control and other health outcomes among overweight individuals with type 2 diabetes. In this pilot feasibility study, we randomized overweight adults (body mass index ≥25) with type 2 diabetes (glycated hemoglobin [HbA 1c ] 6.5%-9.0%) to a 32-week online intervention based on our previous recommendations (n=12) or an online diet program based around a plate method diet (n=13) to assess the impact of each intervention on glycemic control and other health outcomes. Primary and secondary outcomes were analyzed by mixed-effects linear regression to compare outcomes by group. At 32 weeks, participants in the intervention group reduced their HbA 1c levels more (estimated marginal mean [EMM] -0.8%, 95% CI -1.1% to -0.6%) than participants in the control group (EMM -0.3%, 95% CI -0.6% to 0.0%; P=.002). More than half of the participants in the intervention group (6/11, 55%) lowered their HbA 1c to less than 6.5% versus 0% (0/8) in the control group (P=.02). Participants in the intervention group lost more weight (EMM -12.7 kg, 95% CI -16.1 to -9.2 kg) than participants in the control group (EMM -3.0 kg

  17. Ketogenic Diet Improves Brain Ischemic Tolerance and Inhibits NLRP3 Inflammasome Activation by Preventing Drp1-Mediated Mitochondrial Fission and Endoplasmic Reticulum Stress

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    Min Guo

    2018-03-01

    Full Text Available Background: Neuroprotective effects of ketogenic diets (KD have been reported in stroke models, and nucleotide-binding domain (NOD-like receptor protein 3 (NLRP3 inflammasome has also been implicated in the pathogenesis of stroke. This study aimed to investigate the effects of KD on NLRP3 inflammasome and explore the potential molecular mechanisms.Methods: In in vivo study, mice were fed with KD for 3 weeks and then subjected to middle cerebral artery occlusion/reperfusion (MCAO/R-injury. In in vitro study, SH-SY-5Y cells were treated with β-hydroxybutyrate (BHB followed by oxygen–glucose deprivation/reoxygenation (OGD/R. NLRP3 inflammasome activation and related regulatory mechanisms were evaluated.Results: Mice fed with KD had increased tolerance to MCAO/R. KD inhibited endoplasmic reticulum (ER stress and suppressed TXNIP/NLRP3 inflammasome activation in the brain. The in vitro study showed BHB (10 mM prevented the mitochondrial translocation of dynamin-related protein 1 (Drp1 to inhibit mitochondrial fission. Furthermore, BHB decreased reactive oxygen species (ROS generation, inhibited ROS-NLRP3 pathway in OGD/R-treated cells, and suppressed ER stress-induced NLRP3 inflammasome activation.Conclusions: KD may suppress ER stress and protect mitochondrial integrity by suppressing the mitochondrial translocation of Drp1 to inhibit NLRP3 inflammasome activation, thus exerting neuroprotective effects. Our findings provide evidence for the potential application of KD in the prevention of ischemic stroke.

  18. Non-Toxic Metabolic Management of Metastatic Cancer in VM Mice: Novel Combination of Ketogenic Diet, Ketone Supplementation, and Hyperbaric Oxygen Therapy.

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    A M Poff

    Full Text Available The Warburg effect and tumor hypoxia underlie a unique cancer metabolic phenotype characterized by glucose dependency and aerobic fermentation. We previously showed that two non-toxic metabolic therapies - the ketogenic diet with concurrent hyperbaric oxygen (KD+HBOT and dietary ketone supplementation - could increase survival time in the VM-M3 mouse model of metastatic cancer. We hypothesized that combining these therapies could provide an even greater therapeutic benefit in this model. Mice receiving the combination therapy demonstrated a marked reduction in tumor growth rate and metastatic spread, and lived twice as long as control animals. To further understand the effects of these metabolic therapies, we characterized the effects of high glucose (control, low glucose (LG, ketone supplementation (βHB, hyperbaric oxygen (HBOT, or combination therapy (LG+βHB+HBOT on VM-M3 cells. Individually and combined, these metabolic therapies significantly decreased VM-M3 cell proliferation and viability. HBOT, alone or in combination with LG and βHB, increased ROS production in VM-M3 cells. This study strongly supports further investigation into this metabolic therapy as a potential non-toxic treatment for late-stage metastatic cancers.

  19. Retrospective evaluation of low long-term efficacy of antiepileptic drugs and ketogenic diet in 39 patients with CDKL5-related epilepsy.

    Science.gov (United States)

    Müller, A; Helbig, I; Jansen, C; Bast, T; Guerrini, R; Jähn, J; Muhle, H; Auvin, S; Korenke, G C; Philip, S; Keimer, R; Striano, P; Wolf, N I; Püst, B; Thiels, Ch; Fogarasi, A; Waltz, S; Kurlemann, G; Kovacevic-Preradovic, T; Ceulemans, B; Schmitt, B; Philippi, H; Tarquinio, D; Buerki, S; von Stülpnagel, C; Kluger, G

    2016-01-01

    Mutations in the CDKL5 gene cause an early-onset epileptic encephalopathy. To date, little is known about effective antiepileptic treatment in this disorder. Accordingly, the aim of this retrospective study was to explore the role of different antiepileptic drugs (AEDs) and the ketogenic diet (KD) in the treatment of this rare genetic disorder. We evaluated the efficacy in 39 patients with CDKL5 mutations at 3, 6 and 12 months after the introduction of each treatment. One patient was lost to follow-up after 6 and 12 months. The responder rate (>50% reduction in seizure frequency) to at least one AED or KD was 69% (27/39) after 3 months, 45% (17/38) after 6 months and 24% (9/38) after 12 months. The highest rate of seizure reduction after 3 months was reported for FBM (3/3), VGB (8/25), CLB (4/17), VPA (7/34), steroids (5/26), LTG (5/23) and ZNS (2/11). Twelve patients (31%) experienced a seizure aggravation to at least one AED. Most patients showed some but only initial response to various AEDs with different modes of actions. Considering both age-related and spontaneous fluctuation in seizure frequency and the unknown impact of many AEDs or KD on cognition, our data may help defining realistic treatment goals and avoiding overtreatment in patients with CDKL5 mutations. There is a strong need to develop new treatment strategies for patients with this rare mutation. Copyright © 2015. Published by Elsevier Ltd.

  20. An economic evaluation of the ketogenic diet versus care as usual in children and adolescents with intractable epilepsy: An interim analysis.

    Science.gov (United States)

    de Kinderen, Reina J A; Lambrechts, Danielle A J E; Wijnen, Ben F M; Postulart, Debby; Aldenkamp, Albert P; Majoie, Marian H J M; Evers, Silvia M A A

    2016-01-01

    To gain insight into the cost-effectiveness of the ketogenic (KD) diet compared with care as usual (CAU) in children and adolescents with intractable epilepsy, we conducted an economic evaluation from a societal perspective, alongside a randomized controlled trial. Participants from a tertiary epilepsy center were randomized into KD (intervention) group or CAU (control) group. Seizure frequency, quality adjusted life years (QALYs), health care costs, production losses of parents and patient, and family costs were assessed at baseline and during a 4-month study period and compared between the intervention and control groups. The incremental cost-effectiveness ratios (ICERs) (i.e., cost per QALY and cost per responder), and cost-effectiveness acceptability curves (CEACs) were calculated and presented. In total, 48 children were included in the analyses of this study (26 KD group). At 4 months, 50% of the participants in the KD group had a seizure reduction ≥50% from baseline, compared with 18.2 of the participants in the CAU group. The mean costs per patient in the CAU group were €15,245 compared to €20,986 per patient in the KD group, resulting in an ICER of €18,044 per responder. We failed, however, to measure any benefits in terms of QALYs and therefore, the cost per QALY rise high above any acceptable ceiling ratio. It might be that the quality of life instruments used in this study were not sufficiently sensitive to detect changes, or it might be that being a clinical responder is not sufficient to improve a patient's quality of life. Univariate and multivariate sensitivity analyses and nonparametric bootstrapping were performed and demonstrated the robustness of our results. The results show that the KD reduces seizure frequency. The study did not find any improvements in quality of life and, therefore, unfavorable cost per QALY ratio's resulted. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  1. The 1-Week and 8-Month Effects of a Ketogenic Diet or Ketone Salt Supplementation on Multi-Organ Markers of Oxidative Stress and Mitochondrial Function in Rats

    Science.gov (United States)

    Kephart, Wesley C.; Mumford, Petey W.; Mao, Xuansong; Romero, Matthew A.; Hyatt, Hayden W.; Zhang, Yufeng; Mobley, Christopher B.; Quindry, John C.; Young, Kaelin C.; Beck, Darren T.; McCullough, Danielle J.; D’Agostino, Dominic P.; Lowery, Ryan P.; Wilson, Jacob M.; Kavazis, Andreas N.; Roberts, Michael D.

    2017-01-01

    We determined the short- and long-term effects of a ketogenic diet (KD) or ketone salt (KS) supplementation on multi-organ oxidative stress and mitochondrial markers. For short-term feedings, 4 month-old male rats were provided isocaloric amounts of KD (n = 10), standard chow (SC) (n = 10) or SC + KS (~1.2 g/day, n = 10). For long-term feedings, 4 month-old male rats were provided KD (n = 8), SC (n = 7) or SC + KS (n = 7) for 8 months and rotarod tested every 2 months. Blood, brain (whole cortex), liver and gastrocnemius muscle were harvested from all rats for biochemical analyses. Additionally, mitochondria from the brain, muscle and liver tissue of long-term-fed rats were analyzed for mitochondrial quantity (maximal citrate synthase activity), quality (state 3 and 4 respiration) and reactive oxygen species (ROS) assays. Liver antioxidant capacity trended higher in short-term KD- and SC + KS-fed versus SC-fed rats, and short-term KD-fed rats exhibited significantly greater serum ketones compared to SC + KS-fed rats indicating that the diet (not KS supplementation) induced ketonemia. In long term-fed rats: (a) serum ketones were significantly greater in KD- versus SC- and SC + KS-fed rats; (b) liver antioxidant capacity and glutathione peroxidase protein was significantly greater in KD- versus SC-fed rats, respectively, while liver protein carbonyls were lowest in KD-fed rats; and (c) gastrocnemius mitochondrial ROS production was significantly greater in KD-fed rats versus other groups, and this paralleled lower mitochondrial glutathione levels. Additionally, the gastrocnemius pyruvate-malate mitochondrial respiratory control ratio was significantly impaired in long-term KD-fed rats, and gastrocnemius mitochondrial quantity was lowest in these animals. Rotarod performance was greatest in KD-fed rats versus all other groups at 2, 4 and 8 months, although there was a significant age-related decline in performance existed in KD-fed rats which was not evident in the

  2. Ketogenic food pyramid for patients with refractory epilepsy: From theory to clinical practice

    OpenAIRE

    PRUDENCIO, Mariana Baldini; LIMA, Patricia de Azevedo; FREITAS, Maria Camila Pruper de; CARTOLANO, Flávia de Conti; MURAKAMI, Daniela Kawamoto; DAMASCENO, Nágila Raquel Teixeira

    2017-01-01

    ABSTRACT Objective: To develop a graphical representation in the form of a food pyramid for a ketogenic diet for dietary treatment in children and adolescents with refractory epilepsy. Methods: The pyramid was constructed based on: the estimation of energy requirements for different age groups, macronutrient distribution, food groups, and the number of servings and respective amounts of food according to the ketogenic diet. Serving sizes were based on the calculation of energy and macronutr...

  3. Dieta cetogênica no tratamento das epilepsias graves da infância: percepção das mães Ketogenic diet in the treatment of intractable epilepsy in children: mothers view

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    Alexsandra Tomé

    2003-06-01

    Full Text Available Este estudo teve como propósito perceber os sentimentos e dificuldades de mães de crianças com epilepsia resistente ao tratamento medicamentoso em relação à adoção e ao seguimento da dieta cetogênica, bem como auxiliar a influência dessa dietoterapia na rotina familiar. A metodologia utilizada foi a da pesquisa qualitativa, tendo como técnica de coleta de dados a entrevista semi-estruturada, realizada com três mães atendidas pelo Centro de Neuropediatria do Hospital de Clínicas da Universidade Federal do Paraná. Em virtude das características da dieta cetogênica, os resultados mostram que o período inicial, o da sua adoção, é bastante difícil, tanto para a criança como para toda a sua família. Entretanto, com a diminuição das crises epilépticas e a adaptação ao tratamento, uma mudança de sentimentos é observada. O estudo revela também a importância da atuação de profissionais, não apenas com competência técnica mas também com sensibilidade e empatia, no apoio às famílias das crianças em tratamento.The purpose of this study was to identify the feelings and difficulties experienced by mothers of children with drug-resistant epilepsy concerning the adoption of the ketogenic diet and its follow-up, as well as to evaluate the influence of this dietotherapy on the family routine. The qualitative research methodology was used, and data were collected through semi-structured interview, carried out with three mothers who attended the Neuropediatrics Center of the Clinical Hospital of the Federal University of Paraná, Brazil. Because of the characteristics of the ketogenic diet, the results show that the initial period, corresponding to the phase of adoption, is very difficult, for both the child and all the family. However, with the decrease in the epileptic crises and the adaptation to the treatment, a change in the feelings is observed. The study also reveals the importance of the performance of the

  4. Principios bioéticos en el proyecto de dieta cetogénica para niños epilépticos cubanos Bioethical principles of the ketogenic diet project aimed at Cuban epileptic children

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    Ileana Valdivia Álvarez

    2007-06-01

    Full Text Available Se realiza un análisis de los 4 principales principios de la Bioética: beneficencia, no maleficencia, autonomía y justicia, y se aplican al proyecto de dieta cetogénica para niños epilépticos. Se plantean las preguntas de Bradford y se les da respuesta, considerando el beneficio que este proyecto representa para la calidad de vida del niño y la precaución de no dañarlo con nuestro tratamiento. Con este fin se plantean criterios de inclusión y de exclusión, y la necesidad de solicitar, en todos los casos, el consentimiento informado por escrito, después de conocer todos los elementos concernientes al tratamiento.The four principles of Bioethics, that is, welfare, no harm, autonomy and justice were analyzed and then applied to a ketogenic diet for epileptic children. Bradford questions were posed and answered, taking into consideration the benefits that this project may bring to the quality of life of the child and the caution of not damaging him/her with our treatment. Several inclusion and exclusion criteria and the need of requesting in all cases a written informed consent after knowing all the treatment elements were set forth.

  5. Presentación de un caso de aplicación de la dieta cetogénica en la epilepsia refractaria Presentation of a case of ketogenic diet application to refractory epilepsy

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    Ligia M Marcos Plasencia

    2007-12-01

    Full Text Available Se presenta el caso de un paciente del sexo masculino, de 2 años de edad, que padece síndrome de West y que ha recibido tratamiento con múltiples drogas antiepilépticas sin obtener resultados alentadores ni en las crisis ni en su desarrollo psicomotor, seriamente afectado. Se establece el régimen de alimentación cetogénico de instalación progresiva, sin período de ayuno inicial, y se observa un cambio clínico en el paciente a partir de que se logran niveles de cetosis, constatados por la aparición de cuerpos cetónicos en la orina. Los cambios clínicos consisten en la disminución del número de crisis diarias y de su intensidad, en la posibilidad de suspender una de las drogas antiepilépticas que usaba, y en el aumento del nivel de vigilia del paciente. Se concluye que no se debe renunciar a esta alternativa de tratamiento en los casos de epilepsia refractaria.The case of a 2-year-old male patient suffering from West syndrome that had been treated with multiple antiepileptic drugs without encouraging results, neither in the seizures, nor in his psychomotor development, which was seriously affected, was reported. A progressive ketogenic diet was established without initial fasting, and it was observed a clinical change in the patient, since ketosis levels were attained and confirmed by the appearance of ketone bodies in urine. The clinical changes consisted in the reduction of the number of daily seizures and their intensity, in the possibility of stopping the use of one of the antiepileptic drugs, and in the increase of the level of sleeplessness of the patient. It was concluded that this treatment alternative should not be rejected in the cases of refractory epilepsy.

  6. Ketogenic dietary therapy for epilepsy and other disorders: current perspectives

    OpenAIRE

    Neal, Elizabeth

    2014-01-01

    Elizabeth G Neal 1Matthew's Friends Clinics, Lingfield, UK, 2UCL Institute of Child Health, London, UK Abstract: The ketogenic diet (KD) is a high-fat, restricted-carbohydrate regime, originally designed to mimic metabolic responses to fasting and has been used since the 1920s as a treatment for epilepsy. Modified variants of the KD include the addition of medium-chain triglyceride and less-restrictive modified Atkins and low glycemic index protocols. Scientifically proven as treatme...

  7. A putative low-carbohydrate ketogenic diet elicits mild nutritional ketosis but does not impair the acute or chronic hypertrophic responses to resistance exercise in rodents.

    Science.gov (United States)

    Roberts, Michael D; Holland, A Maleah; Kephart, Wesley C; Mobley, C Brooks; Mumford, Petey W; Lowery, Ryan P; Fox, Carlton D; McCloskey, Anna E; Shake, Joshua J; Mesquita, Paulo; Patel, Romil K; Martin, Jeffrey S; Young, Kaelin C; Kavazis, Andreas N; Wilson, Jacob M

    2016-05-15

    We examined whether acute and/or chronic skeletal muscle anabolism is impaired with a low-carbohydrate diet formulated to elicit ketosis (LCKD) vs. a mixed macronutrient Western diet (WD). Male Sprague-Dawley rats (9-10 wk of age, 300-325 g) were provided isoenergetic amounts of a LCKD or a WD for 6 wk. In AIM 1, basal serum and gastrocnemius assessments were performed. In AIM 2, rats were resistance exercised for one bout and were euthanized 90-270 min following exercise for gastrocnemius analyses. In AIM 3, rats voluntarily exercised daily with resistance-loaded running wheels, and hind limb muscles were analyzed for hypertrophy markers at the end of the 6-wk protocol. In AIM 1, basal levels of gastrocnemius phosphorylated (p)-rps6, p-4EBP1, and p-AMPKα were similar between diets, although serum insulin (P ketosis, as the LCKD-fed rats in AIM 2 exhibited ∼1.5-fold greater serum β-hydroxybutyrate levels relative to WD-fed rats (diet effect P = 0.003). This study demonstrates that the tested LCKD in rodents, while only eliciting mild nutritional ketosis, does not impair the acute or chronic skeletal muscle hypertrophic responses to resistance exercise. Copyright © 2016 the American Physiological Society.

  8. Nutritional Ketosis Condition and Specific Ketogenic Diet, May Benefit Cancer Patients as an Alternative Treatment by Sudden Change in the Metabolic State of Cancer Cells

    OpenAIRE

    Somayeh Zaminpira; Somayeh Zaminpira

    2017-01-01

    Cancer disease is the second cause of death in the United States and world-wide. Most Researchers estimate that 595,690 of American people will die from cancer at the end of the year 2017. That means 1,600 deaths/day approximately [1]. Cancer in modern societies is commonly treated with the combination of organ surgery, chemotherapy and radiotherapy. Many kinds of diet strategies have been experimented. However, none of them have been particularly effective. Interestingly, the...

  9. Factors Affecting Diet Variation in the Pyrenean Rock Ptarmigan (Lagopus muta pyrenaica: Conservation Implications.

    Directory of Open Access Journals (Sweden)

    Ricardo García-González

    Full Text Available The Pyrenean rock ptarmigan (Lagopus muta pyrenaica lives at one of the southernmost limits of the ptarmigan range. Their small population sizes and the impacts of global changes are limiting factors in the conservation of this threatened subspecies. An effective conservation policy requires precise basic knowledge of a species' food and habitat requirements, information that is practically non-existent for this Pyrenean population. Here, we describe the diet of a ptarmigan population in the Eastern Pyrenees, the environmental factors influencing its variability and the relationship between diet floristic composition and quality. Diet composition was determined by microhistological analysis of faeces and diet quality was estimated from free-urate faecal N content. Our results show that grouse diet is based mainly on arctic-alpine shrubs of the Ericaceae family, as well as dwarf willows (Salix spp. and Dryas octopetala. The most frequently consumed plant species was Rhododendron ferrugineum, but its abundance in the diet was negatively related to the diet nitrogen content. Conversely, the abundance of Salix spp., grass leaves and arthropods increased the nitrogen content of the diet. Seasonality associated with snow-melting contributed the most to variability in the Pyrenean ptarmigan diet, differentiating winter from spring/summer diets. The latter was characterised by a high consumption of dwarf willows, flowers, arthropods and tender forb leaves. Geographic area and sex-age class influenced diet variability to a lesser extent. Current temperature increases in the Pyrenees due to global warming may reduce the persistence and surface area of snow-packs where preferred plants for rock ptarmigan usually grow, thus reducing food availability. The high consumption of Rh. ferrugineum characterised the diet of the Pyrenean population. Given the toxicity of this plant for most herbivores, its potential negative effect on Pyrenean ptarmigan populations

  10. Avaliação do perfil metabólico, nutricional e efeitos adversos de crianças com epilepsia refratária em uso da dieta cetogênica Assessment of serum biochemistry, nutritional status and adverse effects of children with refractory epilepsy using the ketogenic diet

    Directory of Open Access Journals (Sweden)

    Sueli Rizzutti

    2006-10-01

    Full Text Available OBJETIVO: Avaliar os efeitos adversos, o perfil metabólico e o crescimento pôndero-estatural de crianças com crises epilépticas de difícil controle, as quais foram submetidas a dieta cetogênica. MÉTODOS: Selecionaram-se 23 pacientes na faixa etária de 2 até 17 anos com epilepsia de difícil controle medicamentoso, sendo 43,5% (n=10 do sexo masculino e 56,5% (n=13 do sexo feminino, provenientes do Setor de Neuropediatria da Disciplina de Neurologia da Universidade Federal de São Paulo. Foram submetidos a dieta cetogênica e acompanhados por um período mínimo de um ano. Dois pacientes não conseguiram manter a cetose por falta de adesão dos pais à dieta. RESULTADOS: Os efeitos adversos encontrados foram reversíveis, incluindo hiperlipidemia, obstipação (17,4%, náuseas e vômitos (43,4%, sonolência (47,8%, infecções intercorrentes (3,0%, recusa da dieta (13,0% e epistaxe (4,3%. O crescimento pôndero-estatural não foi afetado, tendo o peso e a estatura seguido o percentil adequado. CONCLUSÃO: A dieta cetogênica pode constituir-se em uma alternativa segura e efetiva para o tratamento de crianças com epilepsia refratária.OBJECTIVE: The purpose of this research was to evaluate adverse events, serum biochemistry, growth and nutritional status of children with difficult-to-control seizures who were submitted to ketogenic diet. METHODS: Twenty-three patients aging from 2 to 17 years with refractory epilepsies, where 43.5% (n=10 were males and 56.5% (n=13 females from the Sector of Neuropediatrics, Discipline of Neurology of the Universidade Federal de São Paulo, were treated with the ketogenic diet and followed up for at least 1 year. Two patients were not able to achieve persistent ketosis either because they rejected the diets or their parents did not comply. RESULTS: Adverse events were all reversible and included hyperlipidemia, constipation (17.4%, nausea and vomiting (43.4%, drowsiness (47.8%, intercurrent infections (3

  11. The use of diet in the treatment of epilepsy.

    Science.gov (United States)

    Bailey, Elizabeth E; Pfeifer, Heidi H; Thiele, Elizabeth A

    2005-02-01

    Fasting and other dietary regimens have been used to treat epilepsy since biblical times. The ketogenic diet, which mimics the metabolism of fasting, was used by modern physicians to treat intractable epilepsy beginning in the 1920s. With the rising popularity of drug treatments however, the ketogenic diet lost its previous status and was used in only a handful of clinics for most of the 20th century. The diet regained widespread recognition as a viable treatment option beginning in 1992 due to the efforts of parent advocate groups. Despite challenges to implementation of the treatment, the ketogenic diet has significant potential as a powerful tool for fighting epilepsy.

  12. Effects of glucogenic and ketogenic feeding strategies on splanchnic glucose and amino acid metabolism in postpartum transition Holstein cows

    DEFF Research Database (Denmark)

    Larsen, Mogens; Kristensen, Niels Bastian

    2012-01-01

    assigned to 1 of 3 feeding strategies: a glucogenic diet (GLCG) based on sodium hydroxide treated wheat grain (56.5% of diet dry matter); a ketogenic diet (KETO) based on fodder beets (40.5% of diet dry matter); or an alfalfa-glucogenic strategy (ALF-GLCG) supplying 100% alfalfa (Medicago sativa L......Nine periparturient Holstein cows catheterized in major splanchnic vessels were used in a complete randomized design with repeated measurements to investigate effects of glucogenic and ketogenic feeding strategies on splanchnic metabolism of glucose and amino acids. At parturition, cows were.......) haylage at the day of parturition, followed by a 6-d linear shift to the GLCG diet. Samples were obtained 14 d before expected parturition as well as at 4, 15, and 29 d in milk (DIM). The net portal release of glucose was greatest with GLCG, reflecting the higher intake of ruminal escape starch with GLCG...

  13. A Ketogenic Formula Prevents Tumor Progression and Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice

    Directory of Open Access Journals (Sweden)

    Kentaro Nakamura

    2018-02-01

    Full Text Available Low-carbohydrate, high-fat diets (ketogenic diets might prevent tumor progression and could be used as supportive therapy; however, few studies have addressed the effect of such diets on colorectal cancer. An infant formula with a ketogenic composition (ketogenic formula; KF is used to treat patients with refractory epilepsy. We investigated the effect of KF on cancer and cancer cachexia in colon tumor-bearing mice. Mice were randomized into normal (NR, tumor-bearing (TB, and ketogenic formula (KF groups. Colon 26 cells were inoculated subcutaneously into TB and KF mice. The NR and TB groups received a standard diet, and the KF mice received KF ad libitum. KF mice preserved their body, muscle, and carcass weights. Tumor weight and plasma IL-6 levels were significantly lower in KF mice than in TB mice. In the KF group, energy intake was significantly higher than that in the other two groups. Blood ketone body concentrations in KF mice were significantly elevated, and there was a significant negative correlation between blood ketone body concentration and tumor weight. Therefore, KF may suppress the progression of cancer and the accompanying systemic inflammation without adverse effects on weight gain, or muscle mass, which might help to prevent cancer cachexia.

  14. Spatial and temporal patterns in golden eagle diets in the western United States, with implications for conservation planning

    Science.gov (United States)

    Bedrosian, Geoffrey; Watson, James W.; Steenhof, Karen; Kochert, Michael N.; Preston, Charles R.; Woodbridge, Brian; Williams, Gary E.; Keller, Kent R.; Crandall, Ross H.

    2017-01-01

    Detailed information on diets and predatory ecology of Golden Eagles (Aquila chrysaetos) is essential to prioritize prey species management and to develop landscape-specific conservation strategies, including mitigation of the effects of energy development across the western United States. We compiled published and unpublished data on Golden Eagle diets to (1) summarize available information on Golden Eagle diets in the western U.S., (2) compare diets among biogeographic provinces, and (3) discuss implications for conservation planning and future research. We analyzed 35 studies conducted during the breeding season at 45 locations from 1940–2015. Golden Eagle diet differed among western ecosystems. Lower dietary breadth was associated with desert and shrub-steppe ecosystems and higher breadth with mountain ranges and the Columbia Plateau. Correlations suggest that percentage of leporids in the diet is the factor driving overall diversity of prey and percentage of other prey groups in the diet of Golden Eagles. Leporids were the primary prey of breeding Golden Eagles in 78% of study areas, with sciurids reported as primary prey in 18% of study areas. During the nonbreeding season, Golden Eagles were most frequently recorded feeding on leporids and carrion. Golden Eagles can be described as both generalist and opportunistic predators; they can feed on a wide range of prey species but most frequently feed on abundant medium-sized prey species in a given habitat. Spatial variations in Golden Eagle diet likely reflect regional differences in prey community, whereas temporal trends likely reflect responses to long-term change in prey populations. Evidence suggests dietary shifts from traditional (leporid) prey can have adverse effects on Golden Eagle reproductive rates. Land management practices that support or restore shrub-steppe ecosystem diversity should benefit Golden Eagles. More information is needed on nonbreeding-season diet to determine what food resources

  15. Prey preferences of the snow leopard (Panthera uncia: regional diet specificity holds global significance for conservation.

    Directory of Open Access Journals (Sweden)

    Salvador Lyngdoh

    Full Text Available The endangered snow leopard is a large felid that is distributed over 1.83 million km(2 globally. Throughout its range it relies on a limited number of prey species in some of the most inhospitable landscapes on the planet where high rates of human persecution exist for both predator and prey. We reviewed 14 published and 11 unpublished studies pertaining to snow leopard diet throughout its range. We calculated prey consumption in terms of frequency of occurrence and biomass consumed based on 1696 analysed scats from throughout the snow leopard's range. Prey biomass consumed was calculated based on the Ackerman's linear correction factor. We identified four distinct physiographic and snow leopard prey type zones, using cluster analysis that had unique prey assemblages and had key prey characteristics which supported snow leopard occurrence there. Levin's index showed the snow leopard had a specialized dietary niche breadth. The main prey of the snow leopard were Siberian ibex (Capra sibrica, blue sheep (Pseudois nayaur, Himalayan tahr (Hemitragus jemlahicus, argali (Ovis ammon and marmots (Marmota spp. The significantly preferred prey species of snow leopard weighed 55±5 kg, while the preferred prey weight range of snow leopard was 36-76 kg with a significant preference for Siberian ibex and blue sheep. Our meta-analysis identified critical dietary resources for snow leopards throughout their distribution and illustrates the importance of understanding regional variation in species ecology; particularly prey species that have global implications for conservation.

  16. Prey preferences of the snow leopard (Panthera uncia): regional diet specificity holds global significance for conservation.

    Science.gov (United States)

    Lyngdoh, Salvador; Shrotriya, Shivam; Goyal, Surendra P; Clements, Hayley; Hayward, Matthew W; Habib, Bilal

    2014-01-01

    The endangered snow leopard is a large felid that is distributed over 1.83 million km(2) globally. Throughout its range it relies on a limited number of prey species in some of the most inhospitable landscapes on the planet where high rates of human persecution exist for both predator and prey. We reviewed 14 published and 11 unpublished studies pertaining to snow leopard diet throughout its range. We calculated prey consumption in terms of frequency of occurrence and biomass consumed based on 1696 analysed scats from throughout the snow leopard's range. Prey biomass consumed was calculated based on the Ackerman's linear correction factor. We identified four distinct physiographic and snow leopard prey type zones, using cluster analysis that had unique prey assemblages and had key prey characteristics which supported snow leopard occurrence there. Levin's index showed the snow leopard had a specialized dietary niche breadth. The main prey of the snow leopard were Siberian ibex (Capra sibrica), blue sheep (Pseudois nayaur), Himalayan tahr (Hemitragus jemlahicus), argali (Ovis ammon) and marmots (Marmota spp). The significantly preferred prey species of snow leopard weighed 55±5 kg, while the preferred prey weight range of snow leopard was 36-76 kg with a significant preference for Siberian ibex and blue sheep. Our meta-analysis identified critical dietary resources for snow leopards throughout their distribution and illustrates the importance of understanding regional variation in species ecology; particularly prey species that have global implications for conservation.

  17. Ketogenic dietary therapy for epilepsy and other disorders: current perspectives

    Directory of Open Access Journals (Sweden)

    Neal EG

    2014-04-01

    Full Text Available Elizabeth G Neal 1Matthew's Friends Clinics, Lingfield, UK, 2UCL Institute of Child Health, London, UK Abstract: The ketogenic diet (KD is a high-fat, restricted-carbohydrate regime, originally designed to mimic metabolic responses to fasting and has been used since the 1920s as a treatment for epilepsy. Modified variants of the KD include the addition of medium-chain triglyceride and less-restrictive modified Atkins and low glycemic index protocols. Scientifically proven as treatment for intractable seizures in children, these ketone-generating diets are increasingly also being used in adults. They are the treatment of choice in glucose transporter type 1 deficiency syndrome and pyruvate dehydrogenase deficiency. Evidence for the potential of KD therapy to be included within the treatment options for cancer and neurodegenerative disorders is more limited, albeit an exciting area of research with future clinical potential. This review discusses the key aspects of KD therapy, including the efficacy of treatments and clinical implementation. The importance of appropriate initiation, adequate clinical supervision, regular monitoring, and assessment of nutritional needs is highlighted. Keywords: diet, seizures, ketosis

  18. Low-carbohydrate diet induces metabolic depression: a possible mechanism to conserve glycogen.

    Science.gov (United States)

    Winwood-Smith, Hugh S; Franklin, Craig E; White, Craig R

    2017-10-01

    Long-term studies have found that low-carbohydrate diets are more effective for weight loss than calorie-restricted diets in the short term but equally or only marginally more effective in the long term. Low-carbohydrate diets have been linked to reduced glycogen stores and increased feelings of fatigue. We propose that reduced physical activity in response to lowered glycogen explains the diminishing weight loss advantage of low-carbohydrate compared with low-calorie diets over longer time periods. We explored this possibility by feeding adult Drosophila melanogaster a standard or a low-carbohydrate diet for 9 days and measured changes in metabolic rate, glycogen stores, activity, and body mass. We hypothesized that a low-carbohydrate diet would cause a reduction in glycogen stores, which recover over time, a reduction in physical activity, and an increase in resting metabolic rate. The low-carbohydrate diet reduced glycogen stores, which recovered over time. Activity was unaffected by diet, but metabolic rate was reduced, in the low-carbohydrate group. We conclude that metabolic depression could explain the decreased effectiveness of low-carbohydrate diets over time and recommend further investigation of long-term metabolic effects of dietary interventions and a greater focus on physiological plasticity within the study of human nutrition. Copyright © 2017 the American Physiological Society.

  19. Conservation

    NARCIS (Netherlands)

    Noteboom, H.P.

    1985-01-01

    The IUCN/WWF Plants Conservation Programme 1984 — 1985. World Wildlife Fund chose plants to be the subject of their fund-raising campaign in the period 1984 — 1985. The objectives were to: 1. Use information techniques to achieve the conservation objectives of the Plants Programme – to save plants;

  20. Conservation.

    Science.gov (United States)

    National Audubon Society, New York, NY.

    This set of teaching aids consists of seven Audubon Nature Bulletins, providing the teacher and student with informational reading on various topics in conservation. The bulletins have these titles: Plants as Makers of Soil, Water Pollution Control, The Ground Water Table, Conservation--To Keep This Earth Habitable, Our Threatened Air Supply,…

  1. Diets

    Science.gov (United States)

    ... beef and pork, and sweets is limited. Drinking wine in moderation is encouraged. Studies have shown that ... levels and improve cholesterol levels. This diet can benefit people with high blood pressure and may benefit ...

  2. DNA Metabarcoding Reveals Diet Overlap between the Endangered Walia Ibex and Domestic Goats - Implications for Conservation

    Science.gov (United States)

    Gebremedhin, Berihun; Flagstad, Øystein; Bekele, Afework; Chala, Desalegn; Bakkestuen, Vegar; Boessenkool, Sanne; Popp, Magnus; Gussarova, Galina; Schrøder-Nielsen, Audun; Nemomissa, Sileshi; Brochmann, Christian; Stenseth, Nils Chr.

    2016-01-01

    Human population expansion and associated degradation of the habitat of many wildlife species cause loss of biodiversity and species extinctions. The small Simen Mountains National Park in Ethiopia is one of the last strongholds for the preservation of a number of afro-alpine mammals, plants and birds, and it is home to the rare endemic Walia ibex, Capra walie. The narrow distribution range of this species as well as potential competition for resources with livestock, especially with domestic goat, Capra hircus, may compromise its future survival. Based on a curated afro-alpine taxonomic reference library constructed for plant taxon identification, we investigated the diet of the Walia ibex and addressed the dietary overlap with domestic goat using DNA metabarcoding of faecal samples. Faeces of both species were collected from different localities in the National Park. We show that both species are browsers, with forbs, shrubs and trees comprising the largest proportion of their diet, supplemented by grasses. There was a considerable overlap in dietary preferences. Several of the preferred diet items of the Walia ibex (Alchemilla sp., Hypericum revolutum, Erica arborea and Rumex sp.) were also among the most preferred diet items of the domestic goat. These results indicate that there is potential for competition between the two species, especially during the dry season, when resources are limited. Our findings, in combination with the expected increase in domestic herbivores, suggest that management plans should consider the potential threat posed by domestic goats to ensure future survival of the endangered Walia ibex. PMID:27416020

  3. Prey Preferences of the Snow Leopard (Panthera uncia): Regional Diet Specificity Holds Global Significance for Conservation

    OpenAIRE

    Lyngdoh, Salvador; Shrotriya, Shivam; Goyal, Surendra P.; Clements, Hayley; Hayward, Matthew W.; Habib, Bilal

    2014-01-01

    The endangered snow leopard is a large felid that is distributed over 1.83 million km(2) globally. Throughout its range it relies on a limited number of prey species in some of the most inhospitable landscapes on the planet where high rates of human persecution exist for both predator and prey. We reviewed 14 published and 11 unpublished studies pertaining to snow leopard diet throughout its range. We calculated prey consumption in terms of frequency of occurrence and biomass consumed based o...

  4. Diet and conservation implications of an invasive chameleon, Chamaeleo jacksonii (Squamata: Chamaeleonidae) in Hawaii

    Science.gov (United States)

    Kraus, Fred; Medeiros, Arthur; Preston, David; Jarnevich, Catherine S.; Rodda, Gordon H.

    2012-01-01

    We summarize information on current distribution of the invasive lizard Chamaeleo jacksonii and predict its potential distribution in the Hawaiian Islands. Potential distribution maps are based on climate models developed from known localities in its native range and its Hawaiian range. We also present results of analysis of stomach contents of a sample of 34 chameleons collected from native, predominantly dryland, forest on Maui. These data are the first summarizing prey range of this non-native species in an invaded native-forest setting. Potential distribution models predict that the species can occur throughout most of Hawaii from sea level to >2,100 m elevation. Important features of this data set are that approximately one-third of the diet of these lizards is native insects, and the lizards are consuming large numbers of arthropods each day. Prey sizes span virtually the entire gamut of native Hawaiian arthropod diversity, thereby placing a large number of native species at risk of predation. Our dietary results contrast with expectations for most iguanian lizards and support suggestions that chameleons comprise a third distinct foraging-mode category among saurians. The combination of expanding distribution, large potential range size, broad diet, high predation rates, and high densities of these chameleons imply that they may well become a serious threat to some of the Hawaiian fauna.

  5. Antiseizure Effects of Ketogenic Diet on Seizures Induced with ...

    African Journals Online (AJOL)

    olayemitoyin

    experimental data in Nigeria on the usefulness of KD in epilepsy models. This is ... Fasting glucose, ketosis level and serum chemistry were determined and seizure parameters recorded. ..... in animal occurs through the inhibition of GABA.

  6. [Not Quite] The Ketogenic Diet in a Pill

    Directory of Open Access Journals (Sweden)

    Andrew J Kim

    2015-04-01

    Full Text Available Researchers at Okayama University, Japan showed lactate dehydrogenase (LDH inhibition suppresses neuronal excitation in vitro, reduces EEG discharges and seizures in rodent models, and may provide a novel mechanism for anticonvulsant medications in human patients.

  7. Foods, macronutrients and fibre in the diet of blue sheep (Psuedois nayaur) in the Annapurna Conservation Area of Nepal.

    Science.gov (United States)

    Aryal, Achyut; Coogan, Sean C P; Ji, Weihong; Rothman, Jessica M; Raubenheimer, David

    2015-09-01

    Food resources are often critical regulating factors affecting individual fitness and population densities. In the Himalayan Mountains, Bharal "blue sheep" (Pseudois nayaur) are the main food resource for the endangered snow leopard (Panthera uncia), as well as being preyed upon by other predators. Blue sheep, however, may face a number of challenges including food resource competition with other wild and domestic ungulates, and hunting pressure. Here, we characterized the diet of blue sheep in the Annapurna Conservation Area (ACA) of Nepal and conducted proximate nutritional analysis on a limited number of plants identified as foods. Furthermore, we investigated the macronutrient and fiber balance of these plants using nutritional geometry which is a state-space approach to modeling multidimensional and interactive nutritional aspects of foraging. A total of 19 plant species/genera were identified in blue sheep pellets using microhistological analysis. On average, across seasons and regions of the study area, the two most frequently occurring plants in pellets were graminoids: Kobressia sp. and Carex spp. The macronutrient balance of Kobresia sp. was relatively high in carbohydrate and low in protein, while other plants in the diet were generally higher in protein and lipid content. Analysis of fiber balance showed that the two most consumed plants of blue sheep (i.e., Kobresia spp. and Carex spp.) contained the highest concentration of hemicellulose, which is likely digestible by blue sheep. The hemicellulose and lignin balance of plants ranged relatively widely, yet their cellulose contents showed less variation. Foraging by blue sheep may therefore be a balance between consuming highly digestible high-carbohydrate plants and plants less-digestible but higher in protein and/or lipid.

  8. Utilization of conserved Lucerne Hay as a Protein Supplement in the Diet of Calves on Smallholder Farms of Kenya

    International Nuclear Information System (INIS)

    Kiragu, J.W.; Tamminga, S.; Mitaru, B.N.

    1999-01-01

    The nutritive value and the conserved lucerne hay as a protein supplement in the diet of calves reared on the smallholder farms of Kenya was studied in relation to feed intake, growth rate and efficiency of feed utilization. Forty Friesian calves aged one week were allocate in a completely randomised design experiment to the following five dietary treatments: Napier Grass only (N) and supplemented with 33% lucerne (NL33), 50% lucerne (NL50), 67% lucerne (NL67) and 100% lucerne hay (L100) in the diet of calves. Results showed that increasing the level of lucerne supplementation in the ratio of dairy calves from 50 to 100% lucerne hay significantly (P <0.01) increased the crude protein content the mixed ration from 13.8 t o 16.88% CP which would meet the protein, requirement of the growing ruminants. The growth rate of calves increased linearly (P < 0.001) with the levels of lucerne supplements fro 50 to 100 % lucerne hay resulting in 0.02 kg gain more growth per day per kg additional feed supplement given. The cost of production per kg gain decreased with increase in the level of lucerne supplementation and cost of could further reduced by farmers growing lucerne on the smallholder farms for use in compounding home-made ration at the farm level. Result of these study further shows that lucerne as a leguminous forage has ability to fix Nitrogen in the soil which has significantly effect on soil fertility, increased crop yields and reduction in the cost of fertilisers. It is recommended that an acre of lucerne could yield five to seven tons of dry matter per year sufficient to rear a herd of 15 to 20 calves for a period of 1 year. This research has further shown that a pure stand of lucerne crop which is very deep rooted crop has a longevity of five to seven years in the same field and that pest and diseases are not of a serious problem to lucerne, thus making it excellent supplementary legume to the Napier grass in the diet of calves on smallholder farms of Kenya

  9. Evaluation of black bear (Ursus americanus) diet and consequences in its conservation in Sierra de Picachos, Nuevo León, Mexico

    OpenAIRE

    Juárez-Casillas, Luis Antonio; Varas, Cora

    2013-01-01

    Black bears (Ursus americanus) are considered endangered in Mexico. In northern Mexico, bears are considered responsible for preying on livestock, damaging private property, and crops; therefore they are killed to protect locals' livelihoods. There is a need to understand bears' ecological requirements in order to create conservation plans that include human-bear conflict resolution and that reduce the hunting of this endangered species. We studied the diet of black bears in the Sierra de Pic...

  10. Breath acetone concentration; biological variability and the influence of diet

    Czech Academy of Sciences Publication Activity Database

    Španěl, Patrik; Dryahina, Kseniya; Rejšková, A.; Chippendale, T. W. E.; Smith, D.

    2011-01-01

    Roč. 32, č. 8 (2011), N23-N31 ISSN 0967-3334 R&D Projects: GA ČR GP203/09/P172 Institutional research plan: CEZ:AV0Z40400503 Keywords : acetone * breath * ketogenic diet Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.677, year: 2011

  11. Low-protein diet for conservative management of chronic kidney disease: a systematic review and meta-analysis of controlled trials.

    Science.gov (United States)

    Rhee, Connie M; Ahmadi, Seyed-Foad; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

    2018-04-01

    Recent data pose the question whether conservative management of chronic kidney disease (CKD) by means of a low-protein diet can be a safe and effective means to avoid or defer transition to dialysis therapy without causing protein-energy wasting or cachexia. We aimed to systematically review and meta-analyse the controlled clinical trials with adequate participants in each trial, providing rigorous contemporary evidence of the impact of a low-protein diet in the management of uraemia and its complications in patients with CKD. We searched MEDLINE (PubMed) and other sources for controlled trials on CKD to compare clinical management of CKD patients under various levels of dietary protein intake or to compare restricted protein intake with other interventions. Studies with similar patients, interventions, and outcomes were included in the meta-analyses. We identified 16 controlled trials of low-protein diet in CKD that met the stringent qualification criteria including having 30 or more participants. Compared with diets with protein intake of >0.8 g/kg/day, diets with restricted protein intake (disease, and a trend towards lower rates of all-cause death. In addition, very-low-protein diets (protein intake kidney function and reduction in the rate of progression to end-stage renal disease. Safety and adherence to a low-protein diet was not inferior to a normal protein diet, and there was no difference in the rate of malnutrition or protein-energy wasting. In this pooled analysis of moderate-size controlled trials, a low-protein diet appears to enhance the conservative management of non-dialysis-dependent CKD and may be considered as a potential option for CKD patients who wish to avoid or defer dialysis initiation and to slow down the progression of CKD, while the risk of protein-energy wasting and cachexia remains minimal. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia

  12. Macronutrients and energy content of oral hospital diet prescribed to chronic kidney disease patients on conservative treatment.

    Science.gov (United States)

    David Silva, Janiara; Louvera Silva, Karine A; Baggio, Sueli R; Morgano, Marcelo A; Aguiar Nemer, Aline S; Quintaes, Késia D

    2014-11-01

    The contribution of diet and treatment planning in the treatment of Chronic Kidney Disease (CKD) has been recognized as having a significant clinical impact if introduced early. determine the levels of carbohydrates, proteins, lipids, energy and energy density (ED) in an oral hospital diet prescribed to CKD patients, and to evaluate the adequacy of this diet with respect to dietary recommendations. Diets were collected in a Brazilian public hospital on two non-consecutive days of six different weeks. The carbohydrate, protein, and lipid (total, saturated, monounsaturated, polyunsaturated, linoleic, linolenic and trans fatty acids) contents were determined in a laboratory. The amount of energy and the ED of the diets were calculated using the correction factor Atware and by dividing the total energy of the diet by weight, respectively. About 14.3% of the diets produced for patients with CKD were analyzed. The average density of the diets was low (0.7 kcal/g). In terms of nutritional adequacy, the average lipid content (15%) and linolenic fatty acid content (0.4%) were below the recommendation, as was energy (23.4 kcal / kg / day). The average carbohydrate content (63.5%) and protein content (1.0 g/kg/day) exceeded the recommendations levels. The oral hospital diet prepared for patients with CKD were considered unbalanced, and an unfavorable clinical treatment for these patients. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  13. Keto analogue and amino acid supplementation affects the ammonaemia response during exercise under ketogenic conditions.

    Science.gov (United States)

    Prado, Eduardo Seixas; de Rezende Neto, José Melquiades; de Almeida, Rosemeire Dantas; Dória de Melo, Marcelia Garcez; Cameron, Luiz-Claudio

    2011-06-28

    Hyperammonaemia is related to both central and peripheral fatigue during exercise. Hyperammonaemia in response to exercise can be reduced through supplementation with either amino acids or combined keto analogues and amino acids (KAAA). In the present study, we determined the effect of short-term KAAA supplementation on ammonia production in subjects eating a low-carbohydrate diet who exercise. A total of thirteen male cyclists eating a ketogenic diet for 3 d were divided into two groups receiving either KAAA (KEx) or lactose (control group; LEx) supplements. Athletes cycled indoors for 2 h, and blood samples were obtained at rest, during exercise and over the course of 1 h during the recovery period. Exercise-induced ammonaemia increased to a maximum of 35 % in the control group, but no significant increase was observed in the supplemented group. Both groups had a significant increase (approximately 35 %) in uraemia in response to exercise. The resting urate levels of the two groups were equivalent and remained statistically unchanged in the KEx group after 90 min of exercise; an earlier increase was observed in the LEx group. Glucose levels did not change, either during the trial time or between the groups. An increase in lactate levels was observed during the first 30 min of exercise in both groups, but there was no difference between the groups. The present results suggest that the acute use of KAAA diminishes exercise-induced hyperammonaemia.

  14. Blood ketones are directly related to fatigue and perceived effort during exercise in overweight adults adhering to low-carbohydrate diets for weight loss: a pilot study.

    Science.gov (United States)

    White, Andrea M; Johnston, Carol S; Swan, Pamela D; Tjonn, Sherrie L; Sears, Barry

    2007-10-01

    Ketogenic diets have been associated with reductions in free-living physical activity, a response that can be counterproductive in individuals trying to lose weight. To explore whether popular low-carbohydrate diets might impact the desire to exercise by raising blood ketone concentrations, fatigue and perceived effort during exercise were compared in untrained, overweight adults adhering to a ketogenic low-carbohydrate diet or to a control diet low in carbohydrate, but not ketogenic (5%, 65%, and 30% or 40%, 30%, and 30% of energy from carbohydrate, fat, and protein, respectively). In this prospective, randomized, 2-week pilot study, all meals and snacks were provided to subjects, and energy intake was strictly controlled to provide approximately 70% of that needed for weight maintenance. At baseline and at the end of week 2, exercise testing was conducted in fasting participants. Weight loss and the reductions in fat mass did not differ by group during the trial. At week 2, blood beta-hydroxybutyrate concentrations were 3.6-fold greater for the ketogenic vs nonketogenic group (P=0.018) and correlated significantly with perceived exercise effort (r2=0.22, P=0.049). Blood beta-hydroxybutyrate was also significantly correlated to feelings of "fatigue" (r=0.458, P=0.049) and to "total mood disturbance" (r=0.551, P=0.015) while exercising. These pilot data indicate that ketogenic, low-carbohydrate diets enhance fatigability and can reduce the desire to exercise in free-living individuals.

  15. Effects of glucogenic and ketogenic feeding strategies on splanchnic glucose and amino acid metabolism in postpartum transition Holstein cows.

    Science.gov (United States)

    Larsen, M; Kristensen, N B

    2012-10-01

    Nine periparturient Holstein cows catheterized in major splanchnic vessels were used in a complete randomized design with repeated measurements to investigate effects of glucogenic and ketogenic feeding strategies on splanchnic metabolism of glucose and amino acids. At parturition, cows were assigned to 1 of 3 feeding strategies: a glucogenic diet (GLCG) based on sodium hydroxide treated wheat grain (56.5% of diet dry matter); a ketogenic diet (KETO) based on fodder beets (40.5% of diet dry matter); or an alfalfa-glucogenic strategy (ALF-GLCG) supplying 100% alfalfa (Medicago sativa L.) haylage at the day of parturition, followed by a 6-d linear shift to the GLCG diet. Samples were obtained 14 d before expected parturition as well as at 4, 15, and 29 d in milk (DIM). The net portal release of glucose was greatest with GLCG, reflecting the higher intake of ruminal escape starch with GLCG, as compared with a lower starch intake with KETO. Postpartum, the portal recovery of feed starch was greater (28 ± 3%, mean ± SEM) with KETO as compared with GLCG (15 ± 4%). At 4 DIM, the net hepatic release of glucose was greatest with KETO and least with ALF-GLCG, whereafter it increased as lactation progressed with ALF-GLCG and GLCG, but not with KETO. The high alfalfa haylage allowance at 4 DIM with the ALF-GLCG treatment induced the lowest net release of nutrients from the splanchnic tissues at 4 DIM. The hepatic removal of lactate as percent of total influx (mean ± SEM) increased from 27 ± 3% prepartum to 56 ± 3% at 4 DIM. The hepatic removal of lactate as percent of net portal release increased from 144 ± 10% prepartum to 329 ± 17% at 4 DIM with ALF-GLCG and KETO as compared with 242 ± 20% in GLCG. No clear evidence for an amino acid sparing effect in splanchnic tissues from increasing small intestinal glucose absorption was observed. In conclusion, the glucogenic feeding strategy induced the highest glucogenic status among the tested feeding strategies due to

  16. Variants in KCNJ11 and BAD do not predict response to ketogenic dietary therapies for epilepsy.

    Science.gov (United States)

    Schoeler, Natasha E; Leu, Costin; White, Jon; Plagnol, Vincent; Ellard, Sian; Matarin, Mar; Yellen, Gary; Thiele, Elizabeth A; Mackay, Mark; McMahon, Jacinta M; Scheffer, Ingrid E; Sander, Josemir W; Cross, J Helen; Sisodiya, Sanjay M

    2015-12-01

    In the absence of specific metabolic disorders, predictors of response to ketogenic dietary therapies (KDT) are unknown. We aimed to determine whether variants in established candidate genes KCNJ11 and BAD influence response to KDT. We sequenced KCNJ11 and BAD in individuals without previously-known glucose transporter type 1 deficiency syndrome or other metabolic disorders, who received KDT for epilepsy. Hospital records were used to obtain demographic and clinical data. Two response phenotypes were used: ≥ 50% seizure reduction and seizure-freedom at 3-month follow-up. Case/control association tests were conducted with KCNJ11 and BAD variants with minor allele frequency (MAF)>0.01, using PLINK. Response to KDT in individuals with variants with MAFBAD sequencing data and diet response data. Six SNPs in KCNJ11 and two in BAD had MAF>0.01. Eight variants in KCNJ11 and seven in BAD (of which three were previously-unreported) had MAFBAD do not predict response to KDT for epilepsy. We can exclude, with 80% power, association from variants with a MAF of >0.05 and effect size >3. A larger sample size is needed to detect associations from rare variants or those with smaller effect sizes. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Effect of forage conservation method on ruminal lipid metabolism and microbial ecology in lactating cows fed diets containing a 60:40 forage-to-concentrate ratio.

    Science.gov (United States)

    Halmemies-Beauchet-Filleau, A; Kairenius, P; Ahvenjärvi, S; Crosley, L K; Muetzel, S; Huhtanen, P; Vanhatalo, A; Toivonen, V; Wallace, R J; Shingfield, K J

    2013-04-01

    The effect of forage conservation method on ruminal lipid metabolism and microbial ecology was examined in 2 complementary experiments in cows. Treatments comprised fresh chopped grass, barn-dried hay, or untreated (UTS) or formic acid-treated silage (FAS) prepared from the same grass sward. Preparation of conserved forages coincided with the collection of samples from cows offered fresh grass. In the first experiment, 5 multiparous Finnish Ayrshire cows (229 d in milk) were used to compare the effects of feeding diets based on grass followed by hay during 2 consecutive 14-d periods separated by a 5-d transition during which extensively wilted grass was fed. In the second experiment, 5 multiparous Finnish Ayrshire cows (53 d in milk) were assigned to 1 of 2 blocks and allocated treatments according to a replicated 3×3 Latin square design with 14-d periods to compare the effects of hay, UTS, and FAS. Cows received 7 or 9 kg/d of the same concentrate in experiments 1 and 2, respectively. Conservation of grass by drying, but not ensiling, decreased forage fatty acid content primarily due to losses of 18:2n-6 and 18:3n-3. Compared with grass, feeding hay had no effect on dry matter intake (DMI), rumen pH, or fermentation characteristics, other than increasing ammonia content, but lowered whole-tract organic matter and fiber digestibility (experiment 1). Relative to hay, silage increased DMI, rumen volatile fatty acid (VFA) concentrations, and molar proportions of butyrate, and decreased molar acetate proportions (experiment 2). Compared with UTS, FAS increased DMI, had no effect on rumen ammonia or VFA concentrations, but tended to lower rumen pH and the molar ratio of lipogenic to glucogenic VFA. Conservation method had no substantial effect on ruminal or whole-tract digestibility coefficients. Compared with fresh grass and silages, hay decreased lipolysis and biohydrogenation (BH) of dietary unsaturates in the rumen, resulting in similar flows of 18:2n-6 and 18:3n-3

  18. 21 CFR 862.1385 - 17-Hydroxycorticosteroids (17-ketogenic steroids) test system.

    Science.gov (United States)

    2010-04-01

    ... the adrenal gland. Measurements of 17-hydroxycorticosteroids (17-ketogenic steroids) are used in the diagnosis and treatment of various diseases of the adrenal or pituitary glands and gonadal disorders. (b...

  19. Food safety in scavenger conservation: Diet-associated exposure to livestock pharmaceuticals and opportunist mycoses in threatened Cinereous and Egyptian vultures.

    Science.gov (United States)

    Blanco, Guillermo; Junza, Alexandra; Barrón, Dolores

    2017-01-01

    Pharmaceuticals from veterinary treatments may enter terrestrial food webs when medicated livestock are available to wildlife in supplementary feeding stations aimed at the conservation of endangered scavengers. Here, we hypothesized that the exposure risk to livestock fluoroquinolones, as indicators of pharmaceutical burden in food, is related to the variable reliance of scavengers on domestic versus wild animal carcasses. Since the misuse of broad-spectrum antibiotics is a major predisposing factor for opportunistic mycoses, we evaluated disease signs potentially associated with diet-dependent drug exposure in nestlings of two threatened vultures. A greater occurrence (100%, n=14) and concentration of fluoroquinolones (mean±SD=73.0±27.5µgL -1 , range=33.2-132.7), mostly enrofloxacin, were found in Cinereous vultures, Aegypius monachus, due to their greater dependence on livestock carcasses than Egyptian vultures, Neophron percnopterus (fluoroquinolones occurrence: 44%, n=16, concentration: 37.9±16.6µgL -1 , range=11.5-55.9), which rely much more on carcasses of wild animals (42% of remains vs. 23% in the cinereous vulture). The chaotic, chronic and pulsed ingestion of these drugs throughout nestling development is proposed as one of the most plausible explanations for the high occurrence and intensity of oral Candida-like lesions in nestling vultures. The high occurrence of fluoroquinolone residues and disease hindered the probing of a cause-effect relationship between both factors in individual vultures. This relationship could be evaluated through a population-based approach by sampling vultures not exposed to these drugs. The high dependence of vultures on domestic animals today compared to past decades and the growing intensification of livestock farming, imply an expected increase in the impact of pharmaceuticals on scavenger populations. This requires further evaluation due to potential consequences in biodiversity conservation and environmental health

  20. Weight loss and body composition changes following three sequential cycles of ketogenic enteral nutrition

    Directory of Open Access Journals (Sweden)

    Gianfranco Cappello

    2012-01-01

    Full Text Available Background: Ketogenic enteral nutrition (KEN is a modification of the protein sparing modified fast in which a protein solution is introduced with a continuous infusion through a nasogastric tube over 10-days cycles. The aim of the study was to perform a retrospective analysis of the safety, compliance, weight loss and body composition changes after 3 sequential 10-days cycles of KEN therapy. Materials and Methods: From a large number of patients who underwent KEN therapy in our department over a 5-year period, we selected 188 patients who participated in 3 KEN cycles with 10-13 days of break between them. Before and after the treatment cycles, body composition was analyzed by bioelectric impedance; a final assessment was made 10 days after the end of last cycle. During each rest period all the patients were on a low-carbohydrate, normal caloric diet. Results: Most patients (97% successfully tolerated the nasogastric treatment and lost an average of 14.4 kg of body weight, 10.6 kg of fat mass and 3.4 kg of body cell mass. Adverse effects were recorded as mild gastric hypersecretion (2% and constipation (5%. Patients continued to lose fat during the 10-day follow up period after the end of each KEN Cycle. This effect may be explained by abnormality of water distribution during the rapid weight loss inducing the observed change in fat mass. Conclusion: Ten-days KEN treatment cycles can induce rapid weight loss and reduction of fat mass in obese patients. Furthermore, preservation of lean mass can be achieved by infusing 1.9 g of protein/kg of BCM.

  1. Diet-Induced Ketosis Improves Cognitive Performance in Aged Rats

    Science.gov (United States)

    Xu, Kui; Sun, Xiaoyan; Eroku, Bernadette O.; Tsipis, Constantinos P.; Puchowicz, Michelle A.; LaManna, Joseph C.

    2010-01-01

    Aging is associated with increased susceptibility to hypoxic/ischemic insult and declines in behavioral function which may be due to attenuated adaptive/defense responses. We investigated if diet-induced ketosis would improve behavioral performance in the aged rats. Fischer 344 rats (3- and 22-month-old) were fed standard (STD) or ketogenic (KG) diet for 3 weeks and then exposed to hypobaric hypoxia. Cognitive function was measured using the T-maze and object recognition tests. Motor function was measured using the inclined-screen test. Results showed that KG diet significantly increased blood ketone levels in both young and old rats. In the aged rats, the KG diet improved cognitive performance under normoxic and hypoxic conditions; while motor performance remained unchanged. Capillary density and HIF-1α levels were elevated in the aged ketotic group independent of hypoxic challenge. These data suggest that diet-induced ketosis may be beneficial in the treatment of neurodegenerative conditions. PMID:20204773

  2. Role of METTL20 in regulating β-oxidation and heat production in mice under fasting or ketogenic conditions.

    Science.gov (United States)

    Shimazu, Tadahiro; Furuse, Tamio; Balan, Shabeesh; Yamada, Ikuko; Okuno, Shuzo; Iwanari, Hiroko; Suzuki, Takehiro; Hamakubo, Takao; Dohmae, Naoshi; Yoshikawa, Takeo; Wakana, Shigeharu; Shinkai, Yoichi

    2018-01-19

    METTL20 is a seven-β-strand methyltransferase that is localised to the mitochondria and tri-methylates the electron transfer flavoprotein (ETF) β subunit (ETFB) at lysines 200 and 203. It has been shown that METTL20 decreases the ability of ETF to extract electrons from medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) and glutaryl-CoA dehydrogenase in vitro. METTL20-mediated methylation of ETFB influences the oxygen consumption rate in permeabilised mitochondria, suggesting that METTL20-mediated ETFB methylation may also play a regulatory role in mitochondrial metabolism. In this study, we generated Mettl20 knockout (KO) mice to uncover the in vivo functions of METTL20. The KO mice were viable, and a loss of ETFB methylation was confirmed. In vitro enzymatic assays revealed that mitochondrial ETF activity was higher in the KO mice than in wild-type mice, suggesting that the KO mice had higher β-oxidation capacity. Calorimetric analysis showed that the KO mice fed a ketogenic diet had higher oxygen consumption and heat production. A subsequent cold tolerance test conducted after 24 h of fasting indicated that the KO mice had a better ability to maintain their body temperature in cold environments. Thus, METTL20 regulates ETF activity and heat production through lysine methylation when β-oxidation is highly activated.

  3. Bland diet

    Science.gov (United States)

    ... bland diet; Nausea - bland diet; Diarrhea - bland diet; Peptic ulcer - bland diet ... be used alongside lifestyle changes to help treat ulcers, heartburn, ... stomach or intestinal surgery. A bland diet includes foods ...

  4. Monocarboxylate transporters in temporal lobe epilepsy: roles of lactate and ketogenic diet.

    Science.gov (United States)

    Lauritzen, Fredrik; Eid, Tore; Bergersen, Linda H

    2015-01-01

    Epilepsy is a serious neurological disorder that affects approximately 1 % of the general population, making it one of the most common disorders of the central nervous system. Furthermore, up to 40 % of all patients with epilepsy cannot control their seizures with current medications. More efficacious treatments for medication refractory epilepsy are therefore needed. A better understanding of the mechanisms that cause this disorder is likely to facilitate the discovery of such treatments. Impairment in cerebral energy metabolism has been proposed as a possible causative factor in the pathogenesis of temporal lobe epilepsy (TLE), which is one of the most common types of medication-refractory epilepsies in adults. In this review, we will discuss some of the current hypotheses regarding the possible causal relationship between brain energy metabolism and TLE. Emphasis will be placed on the role of energy substrates (lactate and ketone bodies) and their transporter molecules, particularly monocarboxylate transporters 1 and 2 (MCT1 and MCT2). We recently reported that the cellular distribution of MCT1 and MCT2 is perturbed in the hippocampus in patients with TLE. The changes may be an adaptive response aimed at keeping high levels of lactate in the epileptic tissue, which may serve to counteract epileptic activity by downregulating cAMP levels through the lactate receptor GPR81, newly discovered in hippocampus. We propose that the perturbation of MCTs may be further involved in the pathophysiology of TLE by influencing brain energy homeostasis, mitochondrial function, GABA-ergic and glutamatergic neurotransmission, and flux of lactate through the brain.

  5. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer

    OpenAIRE

    Zhou Weihua; Mukherjee Purna; Kiebish Michael A; Markis William T; Mantis John G; Seyfried Thomas N

    2007-01-01

    Abstract Background Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the second leading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting the health and vitality of normal brain cells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growth and su...

  6. CONVULSIVE DISORDERS IN CHILDREN WITH REFERENCE TO TREATMENT WITH KETOGENIC DIET.

    Science.gov (United States)

    KEITH, HADDOW M.

    WRITTEN FOR THE MEDICAL PROFESSION, THIS BOOK PROVIDES INFORMATION ON CHILDHOOD CONVULSIONS (EPILEPSY) AND METHODS OF TREATMENT. VARIOUS CONVULSIVE DISORDERS, INCLUDING HYPSARHYTHMIA, AUTONOMIC SEIZURES, SYMPTOM COMPLEXES, FEBRILE CONVULSIONS, AND "PHOTOGENIC" DISORDERS, ARE DISCUSSED IN TERMS OF CAUSES, SYMPTOMS, AND TREATMENT.…

  7. Ketogenic Diet and Hormonal Therapy in Prevention of Evolution of West Syndrome to Lennox-Gastaut

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-08-01

    Full Text Available Medical records of 98 patients diagnosed with West syndrome and monitored at Sanggye Paik Hospital, Seoul, Korea, for at least 3 years were retrospectively reviewed to assess etiology, age at onset, value of various therapies, and the rate of evolution from West syndrome to Lennox-Gastaut syndrome.

  8. Embryonic Lethality of Mitochondrial Pyruvate Carrier 1 Deficient Mouse Can Be Rescued by a Ketogenic Diet

    OpenAIRE

    Vanderperre, Beno?t; Herzig, S?bastien; Krznar, Petra; H?rl, Manuel; Ammar, Zeinab; Montessuit, Sylvie; Pierredon, Sandra; Zamboni, Nicola; Martinou, Jean-Claude

    2016-01-01

    Mitochondrial import of pyruvate by the mitochondrial pyruvate carrier (MPC) is a central step which links cytosolic and mitochondrial intermediary metabolism. To investigate the role of the MPC in mammalian physiology and development, we generated a mouse strain with complete loss of MPC1 expression. This resulted in embryonic lethality at around E13.5. Mouse embryonic fibroblasts (MEFs) derived from mutant mice displayed defective pyruvate-driven respiration as well as perturbed metabolic p...

  9. Dietary Management of the Ketogenic Glycogen Storage Diseases

    Directory of Open Access Journals (Sweden)

    Kaustuv Bhattacharya MBBS, MRCPCH, FRACP, MD

    2016-08-01

    Full Text Available The glycogen storage diseases (GSDs comprise a group of rare inherited disorders of glycogen metabolism. The hepatic glycogenolytic forms of these disorders are typically associated with hypoglycemia and hepatomegaly. For GSD I, secondary metabolic disturbances include fasting hyperlactatemia, hyperuricemia, and hyperlipidemia. Glycogen storage disease III is caused by reduced activity of the debrancher enzyme, GSD VI by phosphorylase, and GSD IX by phosphorylase kinase. It has often been reported that the non-GSD I group of disorders have a benign course. However, myopathy, cardiomyopathy, and cirrhosis have been reported significant clinical morbidities associated with GSD III and IX in particular. There have been a range of reports indicating high-protein diets, high-fat diets, medium chain triglyceride (MCT, modified Atkins diet, and therapeutic ketones as rescuing severe phenotypes of GSD III in particular. The etiology of these severe phenotypes has not been defined. Cases presented in this report indicate potential harm from excessive simple sugar use in GSD IX C. Review of the literature indicates that most interventions have reduced the glycemic load and provide alternate substrates for energy in rescue situations. Prevention of complications is most likely to occur with a mixed balanced low glycemic index diet potentially with relative increases in protein.

  10. Paleo Diet

    OpenAIRE

    Kaucká, Petra

    2012-01-01

    Topic: Paleo Diet Objectives: The aim of bachelor thesis is to study available literature about Paleo Diet and evaluated it. Then determine whether there is awareness of Paleo Diet in Czech republic. In addition, find out whether there is any experience in dieting according to Paleo Diet and whether Paleo Diet coul be applied in our environment. Methods: As a source of information served a survey. The research group consists of respondents who should have any experience in dieting according t...

  11. Perissodactyla diet

    Science.gov (United States)

    Schoenecker, Kathryn A.

    2018-01-01

    Perissodactyla (Schoch 1989) includes tapirs, rhinoceros, wild asses, horses, and zebras. It is the order of hoofed mammals referred to as “odd-toed ungulates” because its members have one to three weight-bearing toes and walk on hoofs or “ungules.” They are herbivores that are specialized to exploit grasslands and brushy habitat (rhinos, horses, asses, zebras) or dense tropical forests (tapirs). All share a common digestive system called hindgut fermentation, or cecal digestion (in the cecum), and can consume relatively tough, coarse forage. Some perissodactyls are “browsers” that forage primarily on woody shrubs and trees, whereas others are “grazers” with a graminoid-dominated diet. They are all predominantly opportunistic feeders and select for quantity over quality of forage; that is, they consume more abundant low-quality forage instead of searching and selecting for higher-quality forage because it gives them the advantage of reducing search effort, which conserves energy.

  12. Mediterranean diet

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000110.htm Mediterranean diet To use the sharing features on this page, ... and other health problems. How to Follow the Diet The Mediterranean diet is based on: Plant-based ...

  13. Low-carbohydrate, high-fat diets have sex-specific effects on bone health in rats

    DEFF Research Database (Denmark)

    Zengin, Ayse; Kropp, Benedikt; Chevalier, Yan

    2016-01-01

    the effects in female rats remain unknown. Therefore, we investigated whether sex-specific effects of LC-HF diets on bone health exist. METHODS: Twelve-week-old male and female Wistar rats were isoenergetically pair-fed either a control diet (CD), "Atkins-style" protein-matched diet (LC-HF-1), or ketogenic......PURPOSE: Studies in humans suggest that consumption of low-carbohydrate, high-fat diets (LC-HF) could be detrimental for growth and bone health. In young male rats, LC-HF diets negatively affect bone health by impairing the growth hormone/insulin-like growth factor axis (GH/IGF axis), while...... low-protein diet (LC-HF-2) for 4 weeks. In females, microcomputed tomography and histomorphometry analyses were performed on the distal femur. Sex hormones were analysed with liquid chromatography-tandem mass spectrometry, and endocrine parameters including GH and IGF-I were measured by immunoassay...

  14. Ketogenic enteral nutrition as a treatment for obesity: short term and long term results from 19,000 patients

    Directory of Open Access Journals (Sweden)

    Cappello Gianfranco

    2012-10-01

    Full Text Available Abstract Background Only protein diet has been used successfully to prevent loss of lean body mass first in post-surgical and then in obese patients. We studied overweight and obese patients receiving short treatments of an exclusively protein-based nutritional solution as 24-hour enteral infusion. Methods 19,036 patients (age 44.3 ± 13, M:F = 2:5 with an initial body mass index of 36.5 ± 7.1 underwent 10-day cycles of enteral nutrition through a fine nasogastric tube. The nutritional solution consisted solely of 50–65 g of proteins, plus vitamins and electrolytes. The 24-hour infusion was controlled with a small portable pump. Before and after each 10-day cycle body composition was checked with a Handy 3000 impedance analyzer. At the onset of treatment, average fat mass was 40.9 ± 12.8 kg while body cell mass was 42.7 ± 7.2 kg in males and 27.4 ± 4.6 kg in females. Results After an average of 2.5 cycles the patients lost 10.2 ± 7.0 kg of body weight, 5.8 ± 5.5 kg of fat mass and 2.2 ± 3.3 kg of body cell mass. No significant adverse effects were recorded except asthenia and constipation which were easily controlled with therapy. Long-term results were obtained from 15,444 patients and after an average of 362 ± 296 days we found a mean weight regain of 15.4%. Conclusion Ketogenic Enteral Nutrition treatment of over 19,000 patients induced a rapid 10% weight loss, 57% of which was Fat Mass. No significant adverse effects were found. The treatment is safe, fast, inexpensive and has good one-year results for weight maintenance.

  15. Diet & Nutrition

    Science.gov (United States)

    ... Nutrition Share this page Facebook Twitter Email Diet & Nutrition Eating healthy to take charge of your health. Shelly Diagnosed in 2006 Diet & Nutrition Take Control of Your Weight Portion Control Low ...

  16. Vegetarian Diet

    Science.gov (United States)

    A vegetarian diet focuses on plants for food. These include fruits, vegetables, dried beans and peas, grains, seeds and nuts. There is no single type of vegetarian diet. Instead, vegetarian eating patterns usually fall into the ...

  17. Breath acetone concentration; biological variability and the influence of diet

    International Nuclear Information System (INIS)

    Španěl, Patrik; Dryahina, Kseniya; Rejšková, Alžběta; Chippendale, Thomas W E; Smith, David

    2011-01-01

    Previous measurements of acetone concentrations in the exhaled breath of healthy individuals and the small amount of comparable data for individuals suffering from diabetes are briefly reviewed as a prelude to the presentation of new data on the sporadic and wide variations of breath acetone that occur in ostensibly healthy individuals. Data are also presented which show that following a ketogenic diet taken by eight healthy individuals their breath acetone concentrations increased up to five times over the subsequent 6 h. Similarly, the breath acetone increased six and nine times when a low carbohydrate diet was taken by two volunteers and remained high for the several days for which the diet was continued. These new data, together with the previous data, clearly indicate that diet and natural intra-individual biological and diurnal variability result in wide variations in breath acetone concentration. This places an uncertainty in the use of breath acetone alone to monitor blood glucose and glycaemic control, except and unless the individual acts as their own control and is cognizant of the need for dietary control. (note)

  18. Diverticulitis Diet

    Science.gov (United States)

    ... Examples of items allowed on a clear liquid diet include: Broth Fruit juices without pulp, such as apple juice Ice chips ... and poultry Refined white bread Fruit and vegetable juice with no ... two or three days of starting the diet and antibiotics. If you haven't started feeling ...

  19. Low carbohydrate, high fat diet impairs exercise economy and negates the performance benefit from intensified training in elite race walkers

    Science.gov (United States)

    Ross, Megan L.; Garvican‐Lewis, Laura A.; Welvaert, Marijke; Heikura, Ida A.; Forbes, Sara G.; Mirtschin, Joanne G.; Cato, Louise E.; Strobel, Nicki; Sharma, Avish P.; Hawley, John A.

    2017-01-01

    Key points Three weeks of intensified training and mild energy deficit in elite race walkers increases peak aerobic capacity independent of dietary support.Adaptation to a ketogenic low carbohydrate, high fat (LCHF) diet markedly increases rates of whole‐body fat oxidation during exercise in race walkers over a range of exercise intensities.The increased rates of fat oxidation result in reduced economy (increased oxygen demand for a given speed) at velocities that translate to real‐life race performance in elite race walkers.In contrast to training with diets providing chronic or periodised high carbohydrate availability, adaptation to an LCHF diet impairs performance in elite endurance athletes despite a significant improvement in peak aerobic capacity. Abstract We investigated the effects of adaptation to a ketogenic low carbohydrate (CHO), high fat diet (LCHF) during 3 weeks of intensified training on metabolism and performance of world‐class endurance athletes. We controlled three isoenergetic diets in elite race walkers: high CHO availability (g kg−1 day−1: 8.6 CHO, 2.1 protein, 1.2 fat) consumed before, during and after training (HCHO, n = 9); identical macronutrient intake, periodised within or between days to alternate between low and high CHO availability (PCHO, n = 10); LCHF (diets providing chronic or periodised high‐CHO availability, and despite a significant improvement in V˙O2 peak , adaptation to the topical LCHF diet negated performance benefits in elite endurance athletes, in part due to reduced exercise economy. PMID:28012184

  20. Leigh syndrome associated with a deficiency of the pyruvate dehydrogenase complex: results of treatment with a ketogenic diet

    NARCIS (Netherlands)

    Wijburg, F. A.; Barth, P. G.; Bindoff, L. A.; Birch-Machin, M. A.; van der Blij, J. F.; Ruitenbeek, W.; TURNBULL, D. M.; Schutgens, R. B.

    1992-01-01

    A one-year-old boy suffering from intermittent lactic acidosis, muscular hypotonia, horizontal gaze paralysis and spasticity in both legs had low activity of the pyruvate dehydrogenase complex associated with low amounts of immunoreactive E 1 alpha and E 1 beta. Leigh syndrome was diagnosed on the

  1. Food production and nature conservation

    NARCIS (Netherlands)

    Gordon, Iain J.; Squire, Geoff R.; Prins, Herbert H.T.

    2016-01-01

    Feeding the world's growing human population is increasingly challenging, especially as more people adopt a western diet and lifestyle. Doing so without causing damage to nature poses an even greater challenge. This book argues that in order to create a sustainable food supply whilst conserving

  2. Conservation Value

    OpenAIRE

    Tisdell, Clement A.

    2010-01-01

    This paper outlines the significance of the concept of conservation value and discusses ways in which it is determined paying attention to views stemming from utilitarian ethics and from deontological ethics. The importance of user costs in relation to economic decisions about the conservation and use of natural resources is emphasised. Particular attention is given to competing views about the importance of conserving natural resources in order to achieve economic sustainability. This then l...

  3. IBS Diet

    Science.gov (United States)

    ... the most common questions IBS patients have is what food to avoid. This can drive a person to ... Global Treatments IBS Diet What to Do and What to Avoid Foods That Cause Cramping and Diarrhea Foods that Cause ...

  4. Heart disease and diet

    Science.gov (United States)

    Diet - heart disease; CAD - diet; Coronary artery disease - diet; Coronary heart disease - diet ... diet and lifestyle can reduce your risk of: Heart disease, heart attacks, and stroke Conditions that lead ...

  5. Brain and behavioral perturbations in rats following Western diet access.

    Science.gov (United States)

    Hargrave, Sara L; Davidson, Terry L; Lee, Tien-Jui; Kinzig, Kimberly P

    2015-10-01

    Energy dense "Western" diets (WD) are known to cause obesity as well as learning and memory impairments, blood-brain barrier damage, and psychological disturbances. Impaired glucose (GLUT1) and monocarboxylate (MCT1) transport may play a role in diet-induced dementia development. In contrast, ketogenic diets (KD) have been shown to be neuroprotective. We assessed the effect of 10, 40 and 90 days WD, KD and Chow maintenance on spontaneous alternation (SA) and vicarious trial and error (VTE) behaviors in male rats, then analyzed blood glucose, insulin, and ketone levels; and hippocampal GLUT1 and MCT1 mRNA. Compared to Chow and KD, rats fed WD had increased 90 day insulin levels. SA was decreased in WD rats at 10, but not 40 or 90 days. VTE was perturbed in WD-fed rats, particularly at 10 and 90 days, indicating hippocampal deficits. WD rats had lower hippocampal GLUT1 and MCT1 expression compared to Chow and KD, and KD rats had increased 90 day MCT1 expression compared to Chow and WD. These data suggest that WD reduces glucose and monocarboxylate transport at the hippocampus, which may result in learning and memory deficits. Further, KD consumption may be useful for MCT1 transporter recovery, which may benefit cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. High-fat diets and seizure control in myoclonic-astatic epilepsy: a single center's experience.

    Science.gov (United States)

    Simard-Tremblay, Elisabeth; Berry, Patricia; Owens, Aaron; Cook, William Byron; Sittner, Haley R; Mazzanti, Marta; Huber, Jennifer; Warner, Molly; Shurtleff, Hillary; Saneto, Russell P

    2015-02-01

    To determine the efficacy of the Modified Atkins Diet (MAD) and Ketogenic Diet (KD) in seizure control within a population of myoclonic-astatic epilepsy (MAE) patients. This was a retrospective, single center study evaluating the seizure control by high fat diets. Seizure diaries kept by the parents performed seizure counts. All patients met the clinical criteria for MAE. Nine patients met the clinical criteria. We found that both the MAD and KD were efficacious in complete seizure control and allowed other medications to be stopped in seven patients. Two patients had greater than 90% seizure control without medications, one on the KD and the other on the MAD. Seizure freedom has ranged from 13 to 36 months, and during this time four patients have been fully weaned off of diet management. One patient was found to have a mutation in SLC2A1. Our results suggest that strictly defined MAE patients respond to the MAD with prolonged seizure control. Some patients may require the KD for seizure freedom, suggesting a common pathway of increased requirement for fats. Once controlled, those fully responsive to the Diet(s) could be weaned off traditional seizure medications and in many, subsequently off the MAD or KD. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  7. Conservation endocrinology

    Science.gov (United States)

    McCormick, Stephen; Romero, L. Michael

    2017-01-01

    Endocrinologists can make significant contributions to conservation biology by helping to understand the mechanisms by which organisms cope with changing environments. Field endocrine techniques have advanced rapidly in recent years and can provide substantial information on the growth, stress, and reproductive status of individual animals, thereby providing insight into current and future responses of populations to changes in the environment. Environmental stressors and reproductive status can be detected nonlethally by measuring a number of endocrine-related endpoints, including steroids in plasma, living and nonliving tissue, urine, and feces. Information on the environmental or endocrine requirements of individual species for normal growth, development, and reproduction will provide critical information for species and ecosystem conservation. For many taxa, basic information on endocrinology is lacking, and advances in conservation endocrinology will require approaches that are both “basic” and “applied” and include integration of laboratory and field approaches.

  8. Low-fiber diet

    Science.gov (United States)

    ... residue; Low-fiber diet; Fiber restricted diet; Crohn disease - low fiber diet; Ulcerative colitis - low fiber diet; ... them if they do not contain seeds or pulp: Yellow squash (without seeds) Spinach Pumpkin Eggplant Potatoes, ...

  9. Beneficial effects of curcumin nano-emulsion on spermatogenesis and reproductive performance in male rats under protein deficient diet model: enhancement of sperm motility, conservancy of testicular tissue integrity, cell energy and seminal plasma amino acids content.

    Science.gov (United States)

    Ahmed-Farid, Omar A H; Nasr, Maha; Ahmed, Rania F; Bakeer, Rofanda M

    2017-09-02

    Malnutrition resulting from protein and calorie deficiency continues to be a major concern worldwide especially in developing countries. Specific deficiencies in the protein intake can adversely influence reproductive performance. The present study aimed to evaluate the effects of curcumin and curcumin nano-emulsion on protein deficient diet (PDD)-induced testicular atrophy, troubled spermatogenesis and decreased reproductive performance in male rats. Juvenile rats were fed the protein deficient diet (PDD) for 75 days. Starting from day 60 the rats were divided into 4 groups and given the corresponding treatments for the last 15 days orally and daily as follows: 1st group; curcumin group (C) received 50 mg/kg curcumin p.o. 2 nd group; curcumin nano-form low dose group (NCL) received 2.5 mg/kg nano-curcumin. 3rd group; curcumin nano-form high dose group (NCH) received 5 mg/kg nano-curcumin. 4th group served as malnutrition group (PDD group) receiving the protein deficient diet daily for 75 days and received distilled water ingestions (5 ml/kg p.o) daily for the last 15 days of the experiment. A normal control group was kept under the same conditions for the whole experiment and received normal diet according to nutrition requirement center daily for 75 days and received distilled water ingestions (5 ml/kg p.o) daily for the last 15 days of the experiment. PDD induced significant (P curcumin (50 mg/kg) and curcumin nano-emulsion (2.5 and 5 mg/kg) showed significant (Pcurcumin (50 mg/kg). The present study suggests that administration of curcumin nano-emulsion as a daily supplement would be beneficial in malnutrition- induced troubled male reproductive performance and spermatogenesis cases.

  10. [Conservation Units.

    Science.gov (United States)

    Texas Education Agency, Austin.

    Each of the six instructional units deals with one aspect of conservation: forests, water, rangeland, minerals (petroleum), and soil. The area of the elementary school curriculum with which each correlates is indicated. Lists of general and specific objectives are followed by suggested teaching procedures, including ideas for introducing the…

  11. Creative conservation

    NARCIS (Netherlands)

    Bentham, Roelof J.

    1968-01-01

    The increasing exploitation of our natural resources, the unlimited occupation of ever more new areas, and the intensification of land-use, make it necessary for us to expand the concept of conservation. But we also need to reconsider that concept itself. For the changing conditions in the

  12. Reshaping conservation

    DEFF Research Database (Denmark)

    Funder, Mikkel; Danielsen, Finn; Ngaga, Yonika

    2013-01-01

    members strengthen the monitoring practices to their advantage, and to some extent move them beyond the reach of government agencies and conservation and development practitioners. This has led to outcomes that are of greater social and strategic value to communities than the original 'planned' benefits...

  13. Conservation of Charge and Conservation of Current

    OpenAIRE

    Eisenberg, Bob

    2016-01-01

    Conservation of current and conservation of charge are nearly the same thing: when enough is known about charge movement, conservation of current can be derived from conservation of charge, in ideal dielectrics, for example. Conservation of current is enforced implicitly in ideal dielectrics by theories that conserve charge. But charge movement in real materials like semiconductors or ionic solutions is never ideal. We present an apparently universal derivation of conservation of current and ...

  14. Sodium in diet

    Science.gov (United States)

    Diet - sodium (salt); Hyponatremia - sodium in diet; Hypernatremia - sodium in diet; Heart failure - sodium in diet ... Too much sodium in the diet may lead to: High blood pressure in some people A serious buildup of fluid in people with heart failure , cirrhosis of ...

  15. Nutrition and Diet

    Science.gov (United States)

    ... Thai HbH:Vietnamese Relevant links Living with Thalassemia NUTRITION AND EXERCISE ▶ Nutrition and DietDiet for the ... Thalassemia (for providers) Exercise for Patients with Thalassemia Nutrition and Diet Nutritional deficiencies are common in thalassemia, ...

  16. Low Tyramine Headache Diet

    Science.gov (United States)

    ... Find A Provider Contact Membership Donate 25 Oct Low-Tyramine Diet for Migraine Posted at 17:16h ... and Diamond Headache Clinic Headache Diet Tags: headache , low tyramine diet , MAOI , tyramine No Comments Post A ...

  17. Low-salt diet

    Science.gov (United States)

    Low-sodium diet; Salt restriction ... control many functions. Too much sodium in your diet can be bad for you. For most people, ... you limit salt. Try to eat a balanced diet. Buy fresh vegetables and fruits whenever possible. They ...

  18. Iodine in diet

    Science.gov (United States)

    Diet - iodine ... Many months of iodine deficiency in a person's diet may cause goiter or hypothyroidism . Without enough iodine, ... and older children. Getting enough iodine in the diet may prevent a form of physical and intellectual ...

  19. Fluoride in diet

    Science.gov (United States)

    Diet - fluoride ... bones and teeth. Too much fluoride in the diet is very rare. Rarely, infants who get too ... of essential vitamins is to eat a balanced diet that contains a variety of foods from the ...

  20. Inter-relationships among diet, obesity and hippocampal-dependent cognitive function.

    Science.gov (United States)

    Davidson, T L; Hargrave, S L; Swithers, S E; Sample, C H; Fu, X; Kinzig, K P; Zheng, W

    2013-12-03

    Intake of a Western diet (WD), which is high in saturated fat and sugar, is associated with deficits in hippocampal-dependent learning and memory processes as well as with markers of hippocampal pathology. In the present study, rats were trained to asymptote on hippocampal-dependent serial feature negative (FN) and hippocampal-independent simple discrimination problems. Performance was then assessed following 7 days on ad libitum chow and after 10, 24, 40, 60, and 90 days of maintenance on WD, on ketogenic (KETO) diet, which is high in saturated fat and low in sugar and other carbohydrates, or continued maintenance on chow (CHOW). Confirming and extending previous findings, diet-induced obese (DIO) rats fed WD showed impaired FN performance, increased blood-brain barrier (BBB) permeability, and increased fasting blood glucose levels compared to CHOW controls and to diet-resistant (DR) rats that did not become obese when maintained on WD. For rats fed the KETO diet, FN performance and BBB integrity were more closely associated with level of circulating ketone bodies than with obesity phenotype (DR or DIO), with higher levels of ketones appearing to provide a protective effect. The evidence also indicated that FN deficits preceded and predicted increased body weight and adiposity. This research (a) further substantiates previous findings of WD-induced deficits in hippocampal-dependent FN discriminations, (b) suggests that ketones may be protective against diet-induced cognitive impairment, and (c) provides evidence that diet-induced cognitive impairment precedes weight gain and obesity. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Diet-Induced Ketosis Protects Against Focal Cerebral Ischemia in Mouse.

    Science.gov (United States)

    Xu, Kui; Ye, Lena; Sharma, Katyayini; Jin, Yongming; Harrison, Matthew M; Caldwell, Tylor; Berthiaume, Jessica M; Luo, Yu; LaManna, Joseph C; Puchowicz, Michelle A

    2017-01-01

    Over the past decade we have consistently shown that ketosis is neuroprotective against ischemic insults in rats. We reported that diet-induced ketotic rats had a significant reduction in infarct volume when subjected to middle cerebral artery occlusion (MCAO), and improved survival and recovery after cardiac arrest and resuscitation. The neuroprotective mechanisms of ketosis (via ketogenic diet; KG) include (i) ketones are alternate energy substrates that can restore energy balance when glucose metabolism is deficient and (ii) ketones modulate cell-signalling pathways that are cytoprotective. We investigated the effects of diet-induced ketosis following transient focal cerebral ischemia in mice. The correlation between levels of ketosis and hypoxic inducible factor-1alpha (HIF-1α), AKT (also known as protein kinase B or PKB) and 5' AMP-activated protein kinase (AMPK) were determined. Mice were fed with KG diet or standard lab-chow (STD) diet for 4 weeks. For the MCAO group, mice underwent 60 min of MCAO and total brain infarct volumes were evaluated 48 h after reperfusion. In a separate group of mice, brain tissue metabolites, levels of HIF-1α, phosphorylated AKT (pAKT), and AMPK were measured. After feeding a KG diet, levels of blood ketone bodies (beta-hydroxyburyrate, BHB) were increased. There was a proportional decrease in infarct volumes with increased blood BHB levels (KG vs STD; 4.2 ± 0.6 vs 7.8 ± 2.2 mm 3 , mean ± SEM). A positive correlation was also observed with HIF-1α and pAKT relative to blood BHB levels. Our results showed that chronic ketosis can be induced in mice by KG diet and was neuroprotective against focal cerebral ischemia in a concentration dependent manner. Potential mechanisms include upregulation of cytoprotective pathways such as those associated with HIF-1α, pAKT and AMPK.

  2. A randomized trial of a low-carbohydrate diet vs orlistat plus a low-fat diet for weight loss.

    Science.gov (United States)

    Yancy, William S; Westman, Eric C; McDuffie, Jennifer R; Grambow, Steven C; Jeffreys, Amy S; Bolton, Jamiyla; Chalecki, Allison; Oddone, Eugene Z

    2010-01-25

    Two potent weight loss therapies, a low-carbohydrate, ketogenic diet (LCKD) and orlistat therapy combined with a low-fat diet (O + LFD), are available to the public but, to our knowledge, have never been compared. Overweight or obese outpatients (n = 146) from the Department of Veterans Affairs primary care clinics in Durham, North Carolina, were randomized to either LCKD instruction (initially, carbohydrate daily) or orlistat therapy, 120 mg orally 3 times daily, plus low-fat diet instruction (fat, 500-1000 kcal/d deficit) delivered at group meetings over 48 weeks. Main outcome measures were body weight, blood pressure, fasting serum lipid, and glycemic parameters. The mean age was 52 years and mean body mass index was 39.3 (calculated as weight in kilograms divided by height in meters squared); 72% were men, 55% were black, and 32% had type 2 diabetes mellitus. Of the study participants, 57 of the LCKD group (79%) and 65 of the O + LFD group (88%) completed measurements at 48 weeks. Weight loss was similar for the LCKD (expected mean change, -9.5%) and the O + LFD (-8.5%) (P = .60 for comparison) groups. The LCKD had a more beneficial impact than O + LFD on systolic (-5.9 vs 1.5 mm Hg) and diastolic (-4.5 vs 0.4 mm Hg) blood pressures (P Low-density lipoprotein cholesterol levels improved within the O + LFD group only, whereas glucose, insulin, and hemoglobin A(1c) levels improved within the LCKD group only; comparisons between groups, however, were not statistically significant. In a sample of medical outpatients, an LCKD led to similar improvements as O + LFD for weight, serum lipid, and glycemic parameters and was more effective for lowering blood pressure. clinicaltrials.gov Identifier: NCT00108524.

  3. Fad diets, miracle diets, diet cult… but no results.

    Directory of Open Access Journals (Sweden)

    Ignacio Jáuregui-Lobera

    2017-03-01

    Full Text Available Fad diets, miracle diets (in sum, diet cult are diets that make promises of weight loss or other health advantages (e.g. longer life without backing by solid science, and usually they are characterized by highly restrictive or unusual food choices. These diets are often supported by celebrities and some health “professionals”, and they result attractive among people who want to lose weight quickly. By means of pseudoscientific arguments, designers of fad, miracle or magic diets usually describe them as healthy diets with unusual properties but always with undoubted benefits. After revising the history of these diets and exploring the scientific evidence, it must be noted that there is not a diet better than eating less, moving more and eating lots of fruits and vegetables. In addition, it is necessary to be aware of our general daily habits, remembering that eating is important but it is not everything. Getting active is also very relevant to improve (or recover our health. Summarizing, eating healthy and taking care of yourself are a duty but not a miracle.

  4. Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer's mouse brain: implication for bioenergetic intervention.

    Science.gov (United States)

    Ding, Fan; Yao, Jia; Rettberg, Jamaica R; Chen, Shuhua; Brinton, Roberta Diaz

    2013-01-01

    We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3-15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6-9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential

  5. Early Decline in Glucose Transport and Metabolism Precedes Shift to Ketogenic System in Female Aging and Alzheimer's Mouse Brain: Implication for Bioenergetic Intervention

    Science.gov (United States)

    Ding, Fan; Yao, Jia; Rettberg, Jamaica R.; Chen, Shuhua; Brinton, Roberta Diaz

    2013-01-01

    We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3–15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6–9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential

  6. Caffeine in the diet

    Science.gov (United States)

    Diet - caffeine ... Caffeine is absorbed and passes quickly into the brain. It does not collect in the bloodstream or ... been consumed. There is no nutritional need for caffeine. It can be avoided in the diet. Caffeine ...

  7. Protein in diet

    Science.gov (United States)

    Diet - protein ... Protein foods are broken down into parts called amino acids during digestion. The human body needs a ... to eat animal products to get all the protein you need in your diet. Amino acids are ...

  8. Diet-boosting foods

    Science.gov (United States)

    Obesity - diet-boosting foods; Overweight - diet-boosting foods ... Low-fat and nonfat milk, yogurt, and cottage cheese are healthy sources of calcium, vitamin D , and potassium. Unlike sweetened drinks with extra calories, milk ...

  9. Gastric Bypass Diet

    Science.gov (United States)

    ... the guidance of your doctor. A new healthy diet Three to four months after weight-loss surgery, ... as your stomach continues to heal. Throughout the diet To ensure that you get enough vitamins and ...

  10. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    Directory of Open Access Journals (Sweden)

    de Mello Maria

    2002-04-01

    Full Text Available Abstract Background It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. Methods To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein: pregnant (N, tumor-bearing (WN, pair-fed rats (Np. Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine: leucine (L, tumor-bearing (WL and pair-fed with leucine (Lp. Non pregnant rats (C, which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Results Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Conclusions Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones.

  11. Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

    International Nuclear Information System (INIS)

    Ventrucci, Gislaine; Mello, Maria Alice Roston de; Gomes-Marcondes, Maria Cristina Cintra

    2002-01-01

    It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein): pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine): leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones

  12. Diet induced thermogenesis

    OpenAIRE

    Westerterp KR

    2004-01-01

    Objective Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. Methods Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition. Resu...

  13. Induction of ketosis in rats fed low-carbohydrate, high-fat diets depends on the relative abundance of dietary fat and protein.

    Science.gov (United States)

    Bielohuby, Maximilian; Menhofer, Dominik; Kirchner, Henriette; Stoehr, Barbara J M; Müller, Timo D; Stock, Peggy; Hempel, Madlen; Stemmer, Kerstin; Pfluger, Paul T; Kienzle, Ellen; Christ, Bruno; Tschöp, Matthias H; Bidlingmaier, Martin

    2011-01-01

    Low-carbohydrate/high-fat diets (LC-HFDs) in rodent models have been implicated with both weight loss and as a therapeutic approach to treat neurological diseases. LC-HFDs are known to induce ketosis; however, systematic studies analyzing the impact of the macronutrient composition on ketosis induction and weight loss success are lacking. Male Wistar rats were pair-fed for 4 wk either a standard chow diet or one of three different LC-HFDs, which only differed in the relative abundance of fat and protein (percentages of fat/protein in dry matter: LC-75/10; LC-65/20; LC-55/30). We subsequently measured body composition by nuclear magnetic resonance (NMR), analyzed blood chemistry and urine acetone content, evaluated gene expression changes of key ketogenic and gluconeogenic genes, and measured energy expenditure (EE) and locomotor activity (LA) during the first 4 days and after 3 wk on the respective diets. Compared with chow, rats fed with LC-75/10, LC-65/20, and LC-55/30 gained significantly less body weight. Reductions in body weight were mainly due to lower lean body mass and paralleled by significantly increased fat mass. Levels of β-hydroxybutyate were significantly elevated feeding LC-75/10 and LC-65/20 but decreased in parallel to reductions in dietary fat. Acetone was about 16-fold higher with LC-75/10 only (P ketosis. LC-HFDs must be high in fat, but also low in protein contents to be clearly ketogenic. Independent of the macronutrient composition, LC-HFD-induced weight loss is not due to increased EE and LA.

  14. Diet quality in childhood

    NARCIS (Netherlands)

    Velde, van der Laura A.; Nguyen, Anh N.; Schoufour, Josje D.; Geelen, Anouk; Jaddoe, Vincent W.V.; Franco, Oscar H.; Voortman, Trudy

    2018-01-01

    Purpose: We aimed to evaluate diet quality of 8-year-old children in the Netherlands, to identify sociodemographic and lifestyle correlates of child diet quality, and to examine tracking of diet quality from early to mid-childhood. Methods: For 4733 children participating in a population-based

  15. Are Detox Diets Safe?

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Are Detox Diets Safe? KidsHealth / For Teens / Are Detox Diets ... seguras las dietas de desintoxicación? What Is a Detox Diet? The name sounds reassuring — everyone knows that ...

  16. Diet induced thermogenesis

    NARCIS (Netherlands)

    Westerterp, K.R.

    2004-01-01

    OBJECTIVE: Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. METHODS: Measuring

  17. Clinical investigations on the urinary 17-ketogenic steroids. Part IV. Studies on the changes of urinary 17-ketogenic steroids. Excretion by age during adolescence of the children exposed to the atomic bomb in utero

    Energy Technology Data Exchange (ETDEWEB)

    Arai, Y

    1963-01-01

    A biochemical study was carried out during a three-year period from 1958 as a joint investigation of Kyoto University and the Atomic Bomb Casualty Commission (ABCC) under a research project to study adolescents who were exposed in utero. Determination of urinary 17-ketogenic steroids (17-KGS) was performed in 275 adolescents drawn from a group of 874 children who were either exposed to the atomic bomb in utero in Nagasaki or who entered the city after the bombing (nonexposed controls). The measurements were done in the same subjects between the age of 13 and 15 at three-month intervals. In the unexposed control group the 17-KGS excretion showed a rapid increase around the age of 14 in males and a slight increase around the same age in females. The mean values in males seemed to become higher than in females around the age of 14. Changes of 17-KGS excretion showed no statistically significant difference between the groups proximally exposed (under 2000 m from the hypocenter) or distally exposed (between 3000 and 5000 m) and the unexposed control children of both sexes. However, the mean values of 17-KGS excretion of every group tended to decrease in the order of unexposed, distally exposed, and proximally exposed groups in males after the age of 14.5 and in females at the age of 15. Changes of 17-KGS excretion showed no statistically significant difference between the exposed and unexposed groups in terms of 1 to 3 month, 4 to 6 month, and 7 to 10 month of gestation at the time of bombing. From these results it appears that there was no effect of the atomic bomb radiation in the adolescents exposed in utero with regard to their adrenocortical function.

  18. Diet and eating after esophagectomy

    Science.gov (United States)

    Esophagectomy - diet; Post-esophagectomy diet ... weight. You will also be on a special diet when you first get home. ... will teach you how to prepare the liquid diet for the feeding tube and how much to ...

  19. Conservation potential of agricultural water conservation subsidies

    Science.gov (United States)

    Huffaker, Ray

    2008-07-01

    A current policy subsidizes farmers to invest in improved on-farm irrigation efficiency, expecting water to be conserved off farm. Contrary to expectation, water has been increasingly depleted in some regions after such improvements. This paper investigates the policy's failure to conserve water consistently by (1) formulating an economic model of irrigated crop production to determine a profit-maximizing irrigator's range of responses to a subsidy and (2) embedding these responses into hypothetical streamflow diagrams to ascertain their potential to conserve water under various hydrologic regimes. Testable hypotheses are developed to predict the conservation potential of a subsidy in real-world application.

  20. Diet induced thermogenesis

    Directory of Open Access Journals (Sweden)

    Westerterp KR

    2004-08-01

    Full Text Available Objective Daily energy expenditure consists of three components: basal metabolic rate, diet-induced thermogenesis and the energy cost of physical activity. Here, data on diet-induced thermogenesis are reviewed in relation to measuring conditions and characteristics of the diet. Methods Measuring conditions include nutritional status of the subject, physical activity and duration of the observation. Diet characteristics are energy content and macronutrient composition. Results Most studies measure diet-induced thermogenesis as the increase in energy expenditure above basal metabolic rate. Generally, the hierarchy in macronutrient oxidation in the postprandial state is reflected similarly in diet-induced thermogenesis, with the sequence alcohol, protein, carbohydrate, and fat. A mixed diet consumed at energy balance results in a diet induced energy expenditure of 5 to 15 % of daily energy expenditure. Values are higher at a relatively high protein and alcohol consumption and lower at a high fat consumption. Protein induced thermogenesis has an important effect on satiety. In conclusion, the main determinants of diet-induced thermogenesis are the energy content and the protein- and alcohol fraction of the diet. Protein plays a key role in body weight regulation through satiety related to diet-induced thermogenesis.

  1. Beta-adrenergic receptors are critical for weight loss but not for other metabolic adaptations to the consumption of a ketogenic diet in male mice

    Directory of Open Access Journals (Sweden)

    Nicholas Douris

    2017-08-01

    Conclusions: The response of β-less mice distinguishes at least two distinct categories of physiologic effects in mice consuming KD. In the liver, KD regulates peroxisome proliferator-activated receptor alpha (PPARα-dependent pathways through an action of FGF21 independent of the SNS and beta-adrenergic receptors. In sharp contrast, induction of interscapular brown adipose tissue (BAT and increased energy expenditure absolutely require SNS signals involving action on one or more β-adrenergic receptors. In this way, the key metabolic actions of FGF21 in response to KD have diverse effector mechanisms.

  2. Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model

    NARCIS (Netherlands)

    Brunetti, Dario; Dusi, Sabrina; Giordano, Carla; Lamperti, Costanza; Morbin, Michela; Fugnanesi, Valeria; Marchet, Silvia; Fagiolari, Gigliola; Sibon, Ody; Moggio, Maurizio; d'Amati, Giulia; Tiranti, Valeria

    Pantothenate kinase-associated neurodegeneration, caused by mutations in the PANK2 gene, is an autosomal recessive disorder characterized by dystonia, dysarthria, rigidity, pigmentary retinal degeneration and brain iron accumulation. PANK2 encodes the mitochondrial enzyme pantothenate kinase type 2,

  3. Acetone as biomarker for ketosis buildup capability--a study in healthy individuals under combined high fat and starvation diets.

    Science.gov (United States)

    Prabhakar, Amlendu; Quach, Ashley; Zhang, Haojiong; Terrera, Mirna; Jackemeyer, David; Xian, Xiaojun; Tsow, Francis; Tao, Nongjian; Forzani, Erica S

    2015-04-22

    Ketogenic diets are high fat and low carbohydrate or very low carbohydrate diets, which render high production of ketones upon consumption known as nutritional ketosis (NK). Ketosis is also produced during fasting periods, which is known as fasting ketosis (FK). Recently, the combinations of NK and FK, as well as NK alone, have been used as resources for weight loss management and treatment of epilepsy. A crossover study design was applied to 11 healthy individuals, who maintained moderately sedentary lifestyle, and consumed three types of diet randomly assigned over a three-week period. All participants completed the diets in a randomized and counterbalanced fashion. Each weekly diet protocol included three phases: Phase 1 - A mixed diet with ratio of fat: (carbohydrate + protein) by mass of 0.18 or the equivalence of 29% energy from fat from Day 1 to Day 5. Phase 2- A mixed or a high-fat diet with ratio of fat: (carbohydrate + protein) by mass of approximately 0.18, 1.63, or 3.80 on Day 6 or the equivalence of 29%, 79%, or 90% energy from fat, respectively. Phase 3 - A fasting diet with no calorie intake on Day 7. Caloric intake from diets on Day 1 to Day 6 was equal to each individual's energy expenditure. On Day 7, ketone buildup from FK was measured. A statistically significant effect of Phase 2 (Day 6) diet was found on FK of Day 7, as indicated by repeated analysis of variance (ANOVA), F(2,20) = 6.73, p fat content and 90% fat content vs. 29% fat content (with p = 0.00159**, and 0.04435**, respectively), with no significant difference between diets with 79% fat content and 90% fat content. In addition, independent of the diet, a significantly higher ketone buildup capability of subjects with higher resting energy expenditure (R(2) = 0.92), and lower body mass index (R(2) = 0.71) was observed during FK.

  4. Ecology and conservation of the maned wolf: introduction

    OpenAIRE

    Consorte-McCrea, A.; Santos, Eliana Ferraz

    2013-01-01

    Wolves are considered controversial figures worldwide: mythical creatures as well as troublemakers, their conservation can polarize extreme views and it often is riddled with conflicts. In recent years much effort has focussed on the discussion of how to conserve large carnivores, such as wolves, while addressing public concerns. The maned wolf, however, has mostly eluded the discussion stage. With its solitary habits and unusual fruit-eating diet, the endangered maned wolf roams the grasslan...

  5. The Civil War Diet

    OpenAIRE

    Brennan, Matthew Philip

    2005-01-01

    The soldierâ s diet in the Civil War has been known as poor, and a number of illnesses and disorders have been associated with it. However, a nutritional analysis placed within the context of mid-nineteenth century American nutrition has been lacking. Such an approach makes clear the connection between illness and diet during the war for the average soldier and defines the importance of nutritionâ s role in the war. It also provides a bridge from the American diet to the soldier diet, ou...

  6. Conservation: Toward firmer ground

    Science.gov (United States)

    1975-01-01

    The following aspects of energy conservation were reviewed in order to place the problems in proper perspective: history and goals, conservation accounting-criteria, and a method to overcome obstacles. The effect of changing prices and available supplies of energy sources and their causes on consumption levels during the last few decades were described. Some examples of attainable conservation goals were listed and justified. A number of specific criteria applicable to conservation accounting were given. Finally, a discussion was presented to relate together the following aspects of energy conservation: widespread impact, involvement of government, industry, politics, moral and ethical aspects, urgency and time element.

  7. Early metabolic adaptation in C57BL/6 mice resistant to high fat diet induced weight gain involves an activation of mitochondrial oxidative pathways.

    Science.gov (United States)

    Boulangé, Claire L; Claus, Sandrine P; Chou, Chieh J; Collino, Sebastiano; Montoliu, Ivan; Kochhar, Sunil; Holmes, Elaine; Rezzi, Serge; Nicholson, Jeremy K; Dumas, Marc E; Martin, François-Pierre J

    2013-04-05

    We investigated the short-term (7 days) and long-term (60 days) metabolic effect of high fat diet induced obesity (DIO) and weight gain in isogenic C57BL/6 mice and examined the specific metabolic differentiation between mice that were either strong-responders (SR), or non-responders (NR) to weight gain. Mice (n = 80) were fed a standard chow diet for 7 days prior to randomization into a high-fat (HF) (n = 56) or a low-fat (LF) (n = 24) diet group. The (1)H NMR urinary metabolic profiles of LF and HF mice were recorded 7 and 60 days after the diet switch. On the basis of the body weight gain (BWG) distribution of HF group, we identified NR mice (n = 10) and SR mice (n = 14) to DIO. Compared with LF, HF feeding increased urinary excretion of glycine conjugates of β-oxidation intermediate (hexanoylglycine), branched chain amino acid (BCAA) catabolism intermediates (isovalerylglycine, α-keto-β-methylvalerate and α-ketoisovalerate) and end-products of nicotinamide adenine dinucleotide (NAD) metabolism (N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-3-carboxamide) suggesting up-regulation of mitochondrial oxidative pathways. In the HF group, NR mice excreted relatively more hexanoylglycine, isovalerylglycine, and fewer tricarboxylic acid (TCA) cycle intermediate (succinate) in comparison to SR mice. Thus, subtle regulation of ketogenic pathways in DIO may alleviate the saturation of the TCA cycle and mitochondrial oxidative metabolism.

  8. Diet and Nutrition

    Science.gov (United States)

    ... Stories Español Eye Health / Tips & Prevention Food and Nutrition Sections Diet and Nutrition Can Fish Oil Help ... Cataract Prevention in the Produce Aisle Diet and Nutrition Leer en Español: Dieta y nutrición May. 24, ...

  9. Diet, Nutrition, and Aggression.

    Science.gov (United States)

    Fishbein, Diana H.; Pease, Susan E.

    1994-01-01

    Examines the theoretical and methodological issues related to diet and aggressive behavior. Clinical evidence indicates that, for some persons, diet may be associated with, or exacerbate, such conditions as learning disability, poor impulse control, intellectual deficits, a tendency toward violence, hyperactivity, and alcoholism and/or drug abuse,…

  10. Children's diets (image)

    Science.gov (United States)

    ... diet of children is the proper amount of fat. Children under two years of age should not be on a fat-restricted diet, because cholesterol and fat are thought to be important nutrients for brain development. Children over two can have lower fat foods added ...

  11. Road diet informational guide.

    Science.gov (United States)

    2014-11-01

    A classic Road Diet converts an existing four-lane undivided roadway segment to a three-lane segment consisting of two : through lanes and a center two-way left turn lane (TWLTL). A Road Diet improves safety by including a protected left-turn lane : ...

  12. Diet and Transplantation

    Science.gov (United States)

    ... meat, skinned poultry and fish nonfat dairy products sugar-free drinks like diet soda. Controlling your weight will lower your chance ... with your doctor and dietitian to keep your diet and blood sugar in good control. Where can I get more ...

  13. Understanding the DASH diet

    Science.gov (United States)

    ... has been widely studied and has many health benefits. Following this diet plan may help: Lower high blood pressure Reduce the ... more expensive than prepared foods. The diet is flexible enough to follow if you are vegetarian , vegan, or gluten-free .

  14. Stroke Prevention & Treatment: Diet & Nutrition

    Science.gov (United States)

    ... Prevention & Treatment: Diet & Nutrition Stroke Prevention & Treatment: Diet & Nutrition A healthy diet can reduce your risk for ... Treatment How does a stroke affect eating and nutrition? Stroke can devastate a person's nutritional health because ...

  15. Diet and Nutrition (Parkinson's Disease)

    Science.gov (United States)

    ... Living With Parkinson's › Managing Parkinson's › Diet & Nutrition Diet & Nutrition 1. Maintain Health 2. Ease PD Symptoms 3. ... your team Seek reliable information about diet and nutrition from your medical team and local resources. Please ...

  16. Ethics of conservation triage

    Directory of Open Access Journals (Sweden)

    Kerrie A Wilson

    2016-09-01

    Full Text Available Conservation triage seems to be at a stalemate between those who accept triage based on utilitarian rationalization, and those that reject it based on a number of ethical principles. We argue that without considered attention to the ethics of conservation triage we risk further polarization in the field of conservation. We draw lessons from the medical sector, where triage is more intuitive and acceptable, and also from disaster planning, to help navigate the challenges that triage entails for conservation science, practice, and policy. We clarify the consequentialist, deontological, and virtue ethical stances that influence the level of acceptance of triage. We emphasize the ethical dimensions of conservation triage in principle and in practice, particularly in the context of stakeholder diversity, a wide range of possible objectives and actions, broader institutions, and significant uncertainties. A focus on a more diverse set of ethics, more considered choice of triage as a conservation tool, open communication of triage objectives and protocols, greater consideration of risk preferences, and regular review and adaptation of triage protocols is required for conservation triage to become more acceptable among diverse conservation practitioners, institutions, and the general public. Accepting conservation triage as fundamentally an ethical problem would foster more open dialogue and constructive debate about the role of conservation triage in a wider system of care.

  17. Conservation: Toward firmer ground

    Science.gov (United States)

    1975-01-01

    The following aspects of energy conservation were discussed: conservation history and goals, conservation modes, conservation accounting-criteria, and a method to overcome obstacles. The conservation modes tested fall into one of the following categories: reduced energy consumption, increased efficiency of energy utilization, or substitution of one or more forms of energy for another which is in shorter supply or in some sense thought to be of more value. The conservation accounting criteria include net energy reduction, economic, and technical criteria. A method to overcome obstacles includes (approaches such as: direct personal impact (life style, income, security, aspiration), an element of crisis, large scale involvement of environmental, safety, and health issues, connections to big government, big business, big politics, involvement of known and speculative science and technology, appeal to moral and ethical standards, the transient nature of opportunities to correct the system.

  18. Econometric modelling of conservation

    International Nuclear Information System (INIS)

    Parker, J.C.; Seal, D.J.

    1990-01-01

    The issue of energy conservation in general, and conservation in the natural gas markets in particular, has recently had a much lower profile than in the past, when energy prices were significantly higher and energy costs composed a much larger proportion of industrial operating costs than today. The recent downward trend in energy prices has diverted attention away from this issue. In the face of expected significant real price increases, increasing pressure from environmental groups, and directives on the part of regulator authorities, conservation is once again becoming a topic of consideration in the energy industry. From the point of view of gas demand forecasting, conservation has received too little attention. The intentions of this paper are to establish the need for forecasting conservation in the natural gas utility sector, and to construct a model of industrial demand which incorporates conservation and is appropriate for use as a forecasting tool

  19. Handbook on energy conservation

    International Nuclear Information System (INIS)

    1989-12-01

    This book shows energy situation in recent years, which includes reserves of energy resource in the world, crude oil production records in OPEC and non OPEC, supply and demand of energy in important developed countries, prospect of supply and demand of energy and current situation of energy conservation in developed countries. It also deals with energy situation in Korea reporting natural resources status, energy conservation policy, measurement for alternative energy, energy management of Korea, investment in equipment and public education for energy conservation.

  20. [Breastfeeding and vegan diet].

    Science.gov (United States)

    Wagnon, J; Cagnard, B; Bridoux-Henno, L; Tourtelier, Y; Grall, J-Y; Dabadie, A

    2005-10-01

    Vegan diet in lactating women can induce vitamin B12 deficiency for their children with risk of an impaired neurological development. A 9.5-month-old girl presented with impaired growth and severe hypotonia. She had a macrocytic anemia secondary to vitamin B12 deficiency. MRI showed cerebral atrophy. She was exclusively breastfed. Her mother was also vitamin B12 deficient, secondary to a vegan diet. She had a macrocytic anemia when discharged from the maternity. Vegan diet is a totally inadequate regimen for pregnant and lactating women, especially for their children. Prevention is based on screening, information and vitamin supplementation.

  1. Biology and conservation of owls of the Northern Hemisphere: 2nd International symposium

    Science.gov (United States)

    James R. Duncan; David H. Johnson; Thomas H. Nicholls

    1997-01-01

    The proceeding contains 91 papers authored by 143 people from 13 countries covering biology, ecology, monitoring, habitat-use, status conservation, education, genetics, toxicology, diet, migration, mortality and related topics concerning owls of the Northern Hemisphere. Thirty-three owl species are discussed. Information presented will be useful in owl conservation,...

  2. Biodiversity Conservation and Conservation Biotechnology Tools

    Science.gov (United States)

    This special issue is dedicated to the in vitro tools and methods used to conserve the genetic diversity of rare and threatened species from around the world. Species that are on the brink of extinction, due to the rapid loss of genetic diversity and habitat, come mainly from resource poor areas the...

  3. Paradigms for parasite conservation.

    Science.gov (United States)

    Dougherty, Eric R; Carlson, Colin J; Bueno, Veronica M; Burgio, Kevin R; Cizauskas, Carrie A; Clements, Christopher F; Seidel, Dana P; Harris, Nyeema C

    2016-08-01

    Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of

  4. Diet and cancer

    Science.gov (United States)

    Fiber and cancer; Cancer and fiber; Nitrates and cancer; Cancer and nitrates ... DIET AND BREAST CANCER The link between nutrition and breast cancer has been well studied. To reduce risk of breast cancer the American ...

  5. Diet and Atherosclerosis

    African Journals Online (AJOL)

    1974-08-14

    Aug 14, 1974 ... Animal experiments have demonstrated the possibility of producing lesions ... countries. Mortality statistics, hospital records and necropsy ... opportunity to study possible associations between diet .... risk of American men.".

  6. Diet - clear liquid

    Science.gov (United States)

    ... Group. Clear liquid diet. In: Morrison. Manual of Clinical Nutrition Management. Updated 2013. bscn2k15.weebly.com/uploads/1/2/9/2/12924787/manual_of_clinical_nutrition2013.pdf . Accessed August 20, 2016. Schattner MA, ...

  7. Diets that Work

    Science.gov (United States)

    ... get all the nutrients they need. Most vegetarians eat fewer calories than non-vegetarians. A vegetarian diet can help fight heart disease and high blood pressure. Sample Dinner Menu Vegetarian Spaghetti with Mushroom-Tomato-Asiago Cheese ...

  8. Sea Lion Diet Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — California sea lions pup and breed at four of the nine Channel Islands in southern California. Since 1981, SWFSC MMTD has been conducting a diet study of sea lions...

  9. Chloride in diet

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002417.htm Chloride in diet To use the sharing features on this page, please enable JavaScript. Chloride is found in many chemicals and other substances ...

  10. Fine-scale spatio-temporal variation in tiger Panthera tigris diet: Effect of study duration and extent on estimates of tiger diet in Chitwan National Park, Nepal

    Science.gov (United States)

    Kapfer, Paul M.; Streby, Henry M.; Gurung, B.; Simcharoen, A.; McDougal, C.C.; Smith, J.L.D.

    2011-01-01

    Attempts to conserve declining tiger Panthera tigris populations and distributions have experienced limited success. The poaching of tiger prey is a key threat to tiger persistence; a clear understanding of tiger diet is a prerequisite to conserve dwindling populations. We used unpublished data on tiger diet in combination with two previously published studies to examine fine-scale spatio-temporal changes in tiger diet relative to prey abundance in Chitwan National Park, Nepal, and aggregated data from the three studies to examine the effect that study duration and the size of the study area have on estimates of tiger diet. Our results correspond with those of previous studies: in all three studies, tiger diet was dominated by members of Cervidae; small to medium-sized prey was important in one study. Tiger diet was unrelated to prey abundance, and the aggregation of studies indicates that increasing study duration and study area size both result in increased dietary diversity in terms of prey categories consumed, and increasing study duration changed which prey species contributed most to tiger diet. Based on our results, we suggest that managers focus their efforts on minimizing the poaching of all tiger prey, and that future studies of tiger diet be of long duration and large spatial extent to improve our understanding of spatio-temporal variation in estimates of tiger diet. ?? 2011 Wildlife Biology, NKV.

  11. Effect of maize starch concentration in the diet on starch and cell wall digestion in the dairy cow.

    Science.gov (United States)

    van Vuuren, A M; Hindle, V A; Klop, A; Cone, J W

    2010-06-01

    An in vivo experiment was performed to determine the effect of level of maize starch in the diet on digestion and site of digestion of organic matter, starch and neutral detergent fibre (NDF). In a repeated change-over design experiment, three cows fitted with a rumen cannula and T-piece cannulae in duodenum and ileum received a low-starch (12% of ration dry matter) and a high-starch (33% of ration dry matter) diet. Starch level was increased by exchanging dried sugar beet pulp by ground maize. After a 2-week adaptation period, feed intake, rumen fermentation parameters (in vivo and in situ), intestinal flows, faecal excretion of organic matter, starch and NDF were estimated. When the high-starch diet was fed, dry matter intake was higher (19.0 kg/day vs. 17.8 kg/day), and total tract digestibility of organic matter, starch and NDF was lower when the low-starch diet was fed. Maize starch concentration had no significant effect on rumen pH and volatile fatty acid concentration nor on the site of digestion of organic matter and starch and rate of passage of ytterbium-labelled forage. On the high-starch diet, an extra 1.3 kg of maize starch was supplied at the duodenum in relation to the low-starch diet, but only an extra 0.3 kg of starch was digested in the small intestine. Digestion of NDF was only apparent in the rumen and was lower on the high-starch diet than on the low-starch diet, mainly attributed to the reduction in sugar beet pulp in the high-starch diet. It was concluded that without the correction for the reduction in NDF digestion in the rumen, the extra supply of glucogenic (glucose and propionic acid) and ketogenic nutrients (acetic and butyric acid) by supplemented starch will be overestimated. The mechanisms responsible for these effects need to be addressed in feed evaluation.

  12. Diets: MedlinePlus Health Topic

    Science.gov (United States)

    ... Spanish Mediterranean diet (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Diets updates by ... foods Diet-busting foods Mediterranean diet Related Health Topics Child Nutrition DASH Eating Plan Diabetic Diet Nutrition ...

  13. Diet and lung cancer

    DEFF Research Database (Denmark)

    Fabricius, P; Lange, Peter

    2003-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews and l...... are only ameliorated to a minor degree by a healthy diet.......Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...... and large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation...

  14. Vegan diets and hypothyroidism.

    Science.gov (United States)

    Tonstad, Serena; Nathan, Edward; Oda, Keiji; Fraser, Gary

    2013-11-20

    Diets eliminating animal products have rarely been associated with hypothyroidism but may protect against autoimmune disease. Thus, we investigated whether risk of hypothyroidism was associated with vegetarian compared to omnivorous dietary patterns. The Adventist Health Study-2 was conducted among church members in North America who provided data in a self-administered questionnaire. Hypothyroidism was queried at baseline in 2002 and at follow-up to 2008. Diet was examined as a determinant of prevalent (n = 4237 of 65,981 [6.4%]) and incident cases (1184 of 41,212 [2.9%]) in multivariate logistic regression models, controlled for demographics and salt use. In the prevalence study, in addition to demographic characterstics, overweight and obesity increased the odds (OR 1.32, 95% CI: 1.22-1.42 and 1.78, 95% CI: 1.64-1.93, respectively). Vegan versus omnivorous diets tended to be associated with reduced risk (OR 0.89, 95% CI: 0.78-1.01, not statistically significant) while a lacto-ovo diet was associated with increased risk (OR 1.09, 95% CI: 1.01-1.18). In the incidence study, female gender, white ethnicity, higher education and BMI were predictors of hypothyroidism. Following a vegan diet tended to be protective (OR 0.78, 95% CI: 0.59-1.03, not statistically significant). In conclusion, a vegan diet tended to be associated with lower, not higher, risk of hypothyroid disease.

  15. Introducing Conservation of Momentum

    Science.gov (United States)

    Brunt, Marjorie; Brunt, Geoff

    2013-01-01

    The teaching of the principle of conservation of linear momentum is considered (ages 15 + ). From the principle, the momenta of two masses in an isolated system are considered. Sketch graphs of the momenta make Newton's laws appear obvious. Examples using different collision conditions are considered. Conservation of momentum is considered…

  16. Water Conservation Resource List.

    Science.gov (United States)

    NJEA Review, 1981

    1981-01-01

    Alarmed by the growing water shortage, the New Jersey State Office of Dissemination has prepared this annotated list of free or inexpensive instructional materials for teaching about water conservation, K-l2. A tipsheet for home water conservation is appended. (Editor/SJL)

  17. Controllability of conservative behaviours

    NARCIS (Netherlands)

    Rao, Shodhan

    2012-01-01

    In this article, we first define the class of J-conservative behaviours with observable storage functions, where J is a symmetric two-variable polynomial matrix. We then provide two main results. The first result states that if J(-xi,xi) is nonsingular, the input cardinality of a J-conservative

  18. Conservation Science Fair Projects.

    Science.gov (United States)

    Soil Conservation Society of America, Ankeny, IA.

    Included are ideas, suggestions, and examples for selecting and designing conservation science projects. Over 70 possible conservation subject areas are presented with suggested projects. References are cited with each of these subject areas, and a separate list of annotated references is included. The references pertain to general subject…

  19. Fixism and conservation science.

    Science.gov (United States)

    Robert, Alexandre; Fontaine, Colin; Veron, Simon; Monnet, Anne-Christine; Legrand, Marine; Clavel, Joanne; Chantepie, Stéphane; Couvet, Denis; Ducarme, Frédéric; Fontaine, Benoît; Jiguet, Frédéric; le Viol, Isabelle; Rolland, Jonathan; Sarrazin, François; Teplitsky, Céline; Mouchet, Maud

    2017-08-01

    The field of biodiversity conservation has recently been criticized as relying on a fixist view of the living world in which existing species constitute at the same time targets of conservation efforts and static states of reference, which is in apparent disagreement with evolutionary dynamics. We reviewed the prominent role of species as conservation units and the common benchmark approach to conservation that aims to use past biodiversity as a reference to conserve current biodiversity. We found that the species approach is justified by the discrepancy between the time scales of macroevolution and human influence and that biodiversity benchmarks are based on reference processes rather than fixed reference states. Overall, we argue that the ethical and theoretical frameworks underlying conservation research are based on macroevolutionary processes, such as extinction dynamics. Current species, phylogenetic, community, and functional conservation approaches constitute short-term responses to short-term human effects on these reference processes, and these approaches are consistent with evolutionary principles. © 2016 Society for Conservation Biology.

  20. Setting conservation priorities.

    Science.gov (United States)

    Wilson, Kerrie A; Carwardine, Josie; Possingham, Hugh P

    2009-04-01

    A generic framework for setting conservation priorities based on the principles of classic decision theory is provided. This framework encapsulates the key elements of any problem, including the objective, the constraints, and knowledge of the system. Within the context of this framework the broad array of approaches for setting conservation priorities are reviewed. While some approaches prioritize assets or locations for conservation investment, it is concluded here that prioritization is incomplete without consideration of the conservation actions required to conserve the assets at particular locations. The challenges associated with prioritizing investments through time in the face of threats (and also spatially and temporally heterogeneous costs) can be aided by proper problem definition. Using the authors' general framework for setting conservation priorities, multiple criteria can be rationally integrated and where, how, and when to invest conservation resources can be scheduled. Trade-offs are unavoidable in priority setting when there are multiple considerations, and budgets are almost always finite. The authors discuss how trade-offs, risks, uncertainty, feedbacks, and learning can be explicitly evaluated within their generic framework for setting conservation priorities. Finally, they suggest ways that current priority-setting approaches may be improved.

  1. Madagascar Conservation & Development

    African Journals Online (AJOL)

    Madagascar Conservation & Development welcomes the results of original research, field surveys, advances in field and laboratory techniques, book reviews, and informal status reports from research, conservation, development and management programs and in-field projects in Madagascar. In addition, notes on changes ...

  2. Resource Conservation Glossary.

    Science.gov (United States)

    Soil Conservation Society of America, Ankeny, IA.

    This glossary is a composite of terms selected from 13 technologies, and is the expanded revision of the original 1952 edition of "The Soil and Water Conservation Glossary." The terms were selected from these areas: agronomy, biology, conservation, ecology, economics, engineering, forestry, geology, hydrology, range, recreation, soils, and…

  3. Creative Soil Conservation

    Science.gov (United States)

    Smith, Martha

    2010-01-01

    Take plant lessons outdoors with this engaging and inquiry-based activity in which third-grade students learn how to apply soil conservation methods to growing plants. They also collect data and draw conclusions about the effectiveness of their method of soil conservation. An added benefit to this activity is that the third-grade students played…

  4. Japan's energy conservation policy

    International Nuclear Information System (INIS)

    Yoda, Kenichi

    1990-01-01

    This article reviews developments in Japanese energy conservation since the 1970s. The industrial sector has achieved the greatest success, due to industrial restructuring as well as improvements in energy efficiency. In the residential/commercial sector, the efficiency of appliances has been much improved. Although improvements have been made in the fuel efficiency of passenger cars, energy consumption in the transportation sector has risen slightly owing to increased transport of passengers and freight. The overall responsibility for energy conservation policy rests with the Ministry of International Trade and Industry. MITI is also responsible for implementing specific conservation policies in regard to the industrial and commercial sectors. In the residential sector, MITI works with the Ministry of Construction and in the transportation sector with the Ministry of Transport. To realize the goals of energy conservation policy through general research, dissemination of public information and other activities, MITI works with the Energy Conservation Center (ECC). (author). 2 figs, 3 tabs

  5. Tests of conservation laws

    International Nuclear Information System (INIS)

    Goldhaber, M.

    1988-01-01

    For quite a while it has been realized that some discrete quantum numbers are conserved in some interactions but not in others. The most conspicuous cases are parity P, charge conjugation C, and the product CP which are conserved in strong and electromagnetic interactions but not in weak interactions. The question arises whether for some of the other conserved quantities, which are conserved in strong, electromagnetic and weak interactions, there is an interaction intermediate in strength between weak and gravitational which violates these quantum numbers, e.g., baryon number B and lepton number L. The possibility exists that these conservation laws, if they are broken at all, are only broken by the gravitational force which would make the mass of an intermediate boson which induces the break-down equal to the Planck mass. (orig.)

  6. Improvement of Cardiomyopathy After High-Fat Diet in Two Siblings with Glycogen Storage Disease Type III.

    Science.gov (United States)

    Brambilla, Alessandra; Mannarino, Savina; Pretese, Roberta; Gasperini, Serena; Galimberti, Cinzia; Parini, Rossella

    2014-01-01

    Glycogenosis type III (GSD III) is an autosomal recessive disorder due to amylo-1,6-glucosidase deficiency. This disease causes limit dextrin storage in affected tissues: liver, skeletal muscles, and heart in GSD IIIa and only liver in GSD IIIb. Cardiomyopathy is quite frequent in GSD IIIa with variable severity and progression of manifestations. It is not clear if diet manipulation may interfere with cardiomyopathy's progression. Recent case reports showed improvement of cardiomyopathy following a ketogenic diet.Two siblings (girl and boy), 7- and 5-year-old, both affected with GSD IIIa, developed severe and rapidly worsening left ventricular hypertrophy in the first years of life, while treated with frequent diurnal and nocturnal hyperproteic meals followed by orally administered uncooked cornstarch. Subsequently they were treated with high-fat (60%) and high-protein (25%), low-carbohydrate (15%) diet. After 12 months exertion dyspnea disappeared in the girl and biochemical blood tests, cardiac enzymes, and congestive heart failure markers improved in both (CK 3439→324, 1304→581 U/L; NT-proBNP 2084→206, 782→135 pg/mL, respectively); ultrasound assessment in both patients showed a relevant reduction of the thickness of interventricular septum (30→16, 16→11 mm, respectively) and left ventricle posterior wall (18→7, 13→8 mm, respectively) and an improvement of the outflow obstruction. A diet rich in fats as well as proteins and poor in carbohydrates could be a beneficial therapeutic choice for GSD III with cardiomyopathy. Future research is needed to confirm the beneficial effect of this treatment and to design treatment strategies with the aim to provide alternative source of energy and prevent glycogen accumulation.

  7. New Nordic diet versus average Danish diet

    DEFF Research Database (Denmark)

    Khakimov, Bekzod; Poulsen, Sanne Kellebjerg; Savorani, Francesco

    2016-01-01

    and 3-hydroxybutanoic acid were related to a higher weight loss, while higher concentrations of salicylic, lactic and N-aspartic acids, and 1,5-anhydro-D-sorbitol were related to a lower weight loss. Specific gender- and seasonal differences were also observed. The study strongly indicates that healthy...... metabolites reflecting specific differences in the diets, especially intake of plant foods and seafood, and in energy metabolism related to ketone bodies and gluconeogenesis, formed the predominant metabolite pattern discriminating the intervention groups. Among NND subjects higher levels of vaccenic acid...

  8. A Resource Conservation Unit.

    Science.gov (United States)

    Porter, Philip D.

    1979-01-01

    Describes a variety of learning activities for teaching elementary and junior high students about air, water, and energy conservation techniques. Suggests community resources, social studies objectives, language skills, and 20 activities. (CK)

  9. Hearing Conservation Team

    Data.gov (United States)

    Federal Laboratory Consortium — The Hearing Conservation Team focuses on ways to identify the early stages of noise-induced damage to the human ear.Our current research involves the evaluation of...

  10. Madagascar Conservation & Development

    African Journals Online (AJOL)

    Madagascar Conservation & Development. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 9, No 1 (2014) >. Log in or Register to get access to full text downloads.

  11. Metro Conservation Corridors

    Data.gov (United States)

    Minnesota Department of Natural Resources — The Metro Conservation Corridors (MeCC) grow out of the natural resource analysis work done by the DNR in the late '90's, documented in the Metro Greenprint...

  12. Madagascar Conservation & Development

    African Journals Online (AJOL)

    www.journalmcd.com

    2012-02-19

    Feb 19, 2012 ... MADAGASCAR CONSERVATION & DEVELOPMENT. VOLUME 7 ... die within a short period of time (e.g., infanticide) (Erhart and. Overdorff 1998 .... been as deep or may have healed by the time of examination. Falls during ...

  13. Birds of Conservation Concern

    Data.gov (United States)

    Department of the Interior — The 1988 amendment to the Fish and Wildlife Conservation Act mandates the U.S. Fish and Wildlife Service (USFWS) to “identify species, subspecies, and populations of...

  14. The New Nordic Diet

    DEFF Research Database (Denmark)

    Salomo, Louise Havkrog; Poulsen, Sanne Kellebjerg; Rix, Marianne

    2016-01-01

    PURPOSE: High phosphorus content in the diet may have adverse effect on cardiovascular health. We investigated whether the New Nordic Diet (NND), based mainly on local, organic and less processed food and large amounts of fruit, vegetables, wholegrain and fish, versus an Average Danish Diet (ADD......) would reduce the phosphorus load due to less phosphorus-containing food additives, animal protein and more plant-based proteins. METHODS: Phosphorus and creatinine were measured in plasma and urine at baseline, week 12 and week 26 in 132 centrally obese subjects with normal renal function as part....../10 MJ in the ADD group and decreased less in the NND compared to the ADD (67 ± 36 mg/10 MJ and -266 ± 45 mg/day, respectively, p high phosphorus intake and did not decrease the fractional phosphorus excretion compared with ADD. Further...

  15. Diet and lung cancer

    DEFF Research Database (Denmark)

    Fabricius, P; Lange, Peter

    2003-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. While cigarette smoking is of key importance, factors such as diet also play a role in the development of lung cancer. MedLine and Embase were searched with diet and lung cancer as the key words. Recently published reviews...... and large well designed original articles were preferred to form the basis for the present article. A diet rich in fruit and vegetables reduces the incidence of lung cancer by approximately 25%. The reduction is of the same magnitude in current smokers, ex-smokers and never smokers. Supplementation...... with vitamins A, C and E and beta-carotene offers no protection against the development of lung cancer. On the contrary, beta-carotene supplementation has, in two major randomised intervention trials, resulted in an increased mortality. Smoking remains the leading cause of lung cancer. The adverse effects...

  16. Mesocycles in conserving plastics

    DEFF Research Database (Denmark)

    Shashoua, Yvonne

    2016-01-01

    driven by the need to balance the requirements for reversibility in conservation practices with the artist’s intent and significance. Developments within each of the three mesocycles from the 1990s to date are discussed in this article. Environmental science and toxicology of waste plastics offer a novel...... source of information about real time degradation in terrestrial and marine microenvironments that seems likely to contribute to the conservation of similar materials in contemporary artworks....

  17. Soil conservation measures: exercises

    OpenAIRE

    Figueiredo, Tomás de; Fonseca, Felícia

    2009-01-01

    Exercises proposed under the topic of Soil Conservation Measures addresses to the design of structural measure, namely waterways in the context of a soil conservation plan. However, to get a better insight on the actual meaning of soil loss as a resource loss, a prior exercise is proposed to students. It concerns calculations of soil loss due to sheet (interrill) erosion and to gully erosion, and allows the perception through realistic number of the impact of these mechanism...

  18. Vegan Diets and Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Serena Tonstad

    2013-11-01

    Full Text Available Diets eliminating animal products have rarely been associated with hypothyroidism but may protect against autoimmune disease. Thus, we investigated whether risk of hypothyroidism was associated with vegetarian compared to omnivorous dietary patterns. The Adventist Health Study-2 was conducted among church members in North America who provided data in a self-administered questionnaire. Hypothyroidism was queried at baseline in 2002 and at follow-up to 2008. Diet was examined as a determinant of prevalent (n = 4237 of 65,981 [6.4%] and incident cases (1184 of 41,212 [2.9%] in multivariate logistic regression models, controlled for demographics and salt use. In the prevalence study, in addition to demographic characterstics, overweight and obesity increased the odds (OR 1.32, 95% CI: 1.22–1.42 and 1.78, 95% CI: 1.64–1.93, respectively. Vegan versus omnivorous diets tended to be associated with reduced risk (OR 0.89, 95% CI: 0.78–1.01, not statistically significant while a lacto-ovo diet was associated with increased risk (OR 1.09, 95% CI: 1.01–1.18. In the incidence study, female gender, white ethnicity, higher education and BMI were predictors of hypothyroidism. Following a vegan diet tended to be protective (OR 0.78, 95% CI: 0.59–1.03, not statistically significant. In conclusion, a vegan diet tended to be associated with lower, not higher, risk of hypothyroid disease.

  19. Behavioral Nutraceuticals and Diets.

    Science.gov (United States)

    Orlando, Jillian M

    2018-05-01

    Behavioral problems of companion animals are becoming more widely recognized. As a result, there are a growing number of behavioral nutraceuticals and diets on the market. These products may be useful for the treatment of mild conditions, for clients who are hesitant to give their pet a psychopharmacologic agent, or sometimes in conjunction with psychopharmacologic agents. Veterinarians should critically review the research associated with nutraceuticals and diets, and have an understanding of the functional ingredients and their mechanisms of action before prescribing treatment. This article provides an overview of nutraceuticals, their mechanisms of action, and relevant research regarding their use. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. International society of sports nutrition position stand: diets and body composition.

    Science.gov (United States)

    Aragon, Alan A; Schoenfeld, Brad J; Wildman, Robert; Kleiner, Susan; VanDusseldorp, Trisha; Taylor, Lem; Earnest, Conrad P; Arciero, Paul J; Wilborn, Colin; Kalman, Douglas S; Stout, Jeffrey R; Willoughby, Darryn S; Campbell, Bill; Arent, Shawn M; Bannock, Laurent; Smith-Ryan, Abbie E; Antonio, Jose

    2017-01-01

    Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature regarding the effects of diet types (macronutrient composition; eating styles) and their influence on body composition. The ISSN has concluded the following. 1) There is a multitude of diet types and eating styles, whereby numerous subtypes fall under each major dietary archetype. 2) All body composition assessment methods have strengths and limitations. 3) Diets primarily focused on fat loss are driven by a sustained caloric deficit. The higher the baseline body fat level, the more aggressively the caloric deficit may be imposed. Slower rates of weight loss can better preserve lean mass (LM) in leaner subjects. 4) Diets focused primarily on accruing LM are driven by a sustained caloric surplus to facilitate anabolic processes and support increasing resistance-training demands. The composition and magnitude of the surplus, as well as training status of the subjects can influence the nature of the gains. 5) A wide range of dietary approaches (low-fat to low-carbohydrate/ketogenic, and all points between) can be similarly effective for improving body composition. 6) Increasing dietary protein to levels significantly beyond current recommendations for athletic populations may result in improved body composition. Higher protein intakes (2.3-3.1 g/kg FFM) may be required to maximize muscle retention in lean, resistance-trained subjects under hypocaloric conditions. Emerging research on very high protein intakes (>3 g/kg) has demonstrated that the known thermic, satiating, and LM-preserving effects of dietary protein might be amplified in resistance-training subjects. 7) The collective body of intermittent caloric restriction research demonstrates no significant advantage over daily caloric restriction for improving body composition. 8) The long-term success of a diet depends upon compliance and suppression or

  1. Mediterranean Diet: Choose This Heart-Healthy Diet Option

    Science.gov (United States)

    ... Lifestyle Nutrition and healthy eating The heart-healthy Mediterranean diet is a healthy eating plan based on typical ... Mediterranean-style cooking. Here's how to adopt the Mediterranean diet. By Mayo Clinic Staff If you're looking ...

  2. Cadmium contamination in cereal-based diets and diet ingredients

    International Nuclear Information System (INIS)

    Siitonen, P.H.; Thompson, H.C. Jr.

    1990-01-01

    Cereal-based diet and/or diet ingredient cadmium levels were determined by graphite furnace AAS. Cadmium contamination was 88.3 and 447 ppb in two cereal-based diets, 44.6 and 48.9 ppb in two purified diets, and ranged from less than 1.1 to 22,900 ppb in the ingredients of one cereal-based diet. The major source of cadmium contamination was attributed to the calcium supplement used for diet formulation. Comparative analyses of two purified diet samples and one cereal-based diet by the National Institute of Standards and Technology (NIST, formerly the National Bureau of Standards) and the National Center for Toxicological Research (NCTR) gave virtually identical results for Cd. A comparative study of Cd levels determined by flame and furnace AAS was also made by the NCTR and the NIST

  3. DASH Diet: Reducing Hypertension through Diet and Lifestyle

    Science.gov (United States)

    ... include soy beans, collard greens and calcium-fortified beverages such as almond milk. Limit Saturated Fat A DASH diet is low in saturated fats, sodium and total fat. Studies have shown that a diet low in saturated ...

  4. Ileostomy and your diet

    Science.gov (United States)

    ... that collects it. You will need to take care of the stoma and empty the pouch many times a day. People who have had an ileostomy can most often eat a normal diet. But some foods may cause problems. Foods that may ... Your pouch should be sealed well enough to ...

  5. Diet - chronic kidney disease

    Science.gov (United States)

    ... you will need to eat more protein. A high-protein diet with fish, poultry, pork, or eggs at every meal may be recommended. People on dialysis should eat 8 to 10 ounces (225 to 280 grams) of high-protein foods each day. Your provider or dietitian ...

  6. Diet History Questionnaire: Suggested Citations

    Science.gov (United States)

    Use of the Diet History Questionnaire and Diet*Calc Analysis Software for publication purposes should contain a citation which includes version information for the software, questionnaire, and nutrient database.

  7. Hepatitis C: Diet and Nutrition

    Science.gov (United States)

    ... with Hepatitis » Daily Living: Diet and Nutrition Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... have high cholesterol and have fatty liver. How hepatitis C affects diet If you have hepatitis, you ...

  8. High blood pressure and diet

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007483.htm High blood pressure and diet To use the sharing features on ... diet is a proven way to help control high blood pressure . These changes can also help you lose weight ...

  9. Diet for rapid weight loss

    Science.gov (United States)

    ... very-low-calorie-diets/Pages/very-low-calorie-diets.aspx . Accessed May 25, 2016. Review Date 4/24/2016 Updated by: Emily Wax, RD, The Brooklyn Hospital Center, Brooklyn, NY. Also reviewed by David Zieve, ...

  10. Hydrology and Conservation Ecology

    Science.gov (United States)

    Narayanan, M.

    2006-12-01

    Responses to change in the behavior of ecological systems are largely governed by interactions at different levels. Research is essential and is to be necessarily designed to gain insights into various interactions at the community level. Sustainable resource management is only possible if conservation of biodiversity can be accomplished by properly using the knowledge discovered. It is well known that the United States Department of Agriculture provides technical information, resources, and data necessary to assist the researchers in addressing their conservation needs. Conservation aims to protect, preserve and conserve the earth's natural resources. These include, but not limited to the conservation of soil, water, minerals, air, plants and all living beings. The United States Department of Agriculture also encourages farmers and ranchers to voluntarily address threats to soil and water. Protection of wetlands and wildlife habitat has been on the radar screen of conservation experts for a very long time. The main objective has always been to help farmers and landowners conform and comply with federal and state environmental laws. During the implementation phase, farmers should be encouraged to make beneficial, cost-effective changes to methods of irrigation systems. In some cases, the hydrologic regime of the project area can be thought of as principally an issue of river flow regimes for floodplain forests. In this presentation, the author tries to focus on the impact of hydrology and conservation ecology on global warming. He also discusses the impact of hydrology and conservation ecology global air concerns such as greenhouse gas concentrations in the atmosphere. References: Chow, V. T, D. R. Maidment, and L. W. Mays. 1988. Applied Hydrology. McGraw-Hill, Inc. U.S. Soil Conservation Service. Technical Release 55: Urban Hydrology for Small Watersheds. USDA (U.S. Department of Agriculture). June 1986. Lehner, B. and P. Döll (2004). Development and validation

  11. Is the Chilean Diet a Mediterranean-type Diet?

    Directory of Open Access Journals (Sweden)

    JAIME ROZOWSKI

    2004-01-01

    Full Text Available Food intake in Chile has changed markedly in the last decades, showing an increase in fat consumption and presently a small fruit and vegetables intake. A parallel is made between the Chilean and Mediterranean diet (mainly the one from Spain, Italy, and Greece, both currently and from 50 years ago. The main differences and similarities are based on food availability. Although Chilean diet seems to be approaching the traditional Mediterranean diet of the 60's, there is concern about changes that are moving away from Chilean traditional diet and towards a western one. A new food pyramid for Chile is proposed based on the traditional Mediterranean-type diet

  12. Tourism and Conservation

    DEFF Research Database (Denmark)

    Budeanu, Adriana

    2017-01-01

    Tourism is promoted by policy makers and international organizations as a tool for advancing conservation agendas, while contributing to poverty alleviation and human development, under the banner of ecotourism or sustainable tourism. However, the indiscriminating use of complex and ambiguous...... concepts such as “poverty” and “sustainability” hide important nuances with regards to the variety of processes and subsequent effects that are triggered when tourism and conservation are being adjoined. Experiences with tourism developments show that destinations that are weak economically find it harder...... to draw benefits from tourism developments or to decline participation in tourism with only little or no losses of sources of income and wealth. If tourism should fulfil sustainability goals related to conservation, poverty, and human development, it needs consistent governmental intervention...

  13. Conservation of Mangifera sylvatica

    DEFF Research Database (Denmark)

    Akhter, Sayma

    and conservation of these valuable species. The present study considers an underutilised and threatened species of Bangladesh, namely wild mango (Mangifera sylvatica Roxb.). Although this wild mango is one of the genetically closest species to the common mango (Mangifera indica L.) research is very limited...... and mostly focused on wood quality and phylogenetic relationships. Therefore, this study investigated the conservation potential of wild mango considering its contribution for food, nutrition and livelihoods. To do so, an assessment was made of the current and future distribution of the species, which...... explored. The study conveyed five key messages: 1. Wild mango may become extinct under future climate change scenarios so it is high time to start thinking about conservation initiatives. 2. Wild mango is a small sized mango with a large kernel in relation to other Mangifera species which provides...

  14. Resource conservation management

    International Nuclear Information System (INIS)

    Miller, W.

    1999-01-01

    Resource conservation management is a management program similar to financial management in that its success requires commitment by all levels of the organization to the process as well as an accounting procedure and auditing of critical components. Resource conservation management provides a framework for all elements of efficient building operations and maintenance. The savings connected with the program are principally connected with changes in the way buildings are operated and maintained. Given the reduction in rebates for the installation of energy-efficient equipment, this approach has considerable promise. This paper discusses the evolution of the resource conservation management service and the savings associated with a two-year pilot effort with seven school districts, as well as the critical components of a successful program

  15. Conservation reaches new heights.

    Science.gov (United States)

    Pepall, J; Khanal, P

    1992-10-01

    The conservation program with the management assistance of the Woodlands Mountain Institute in 2 contiguous parks, the Mount Everest National Park in Nepal and the Qomolangma Nature Reserve in China, in 2 countries is described. The focus is on conservation of the complex ecosystem with sustainable development by showing local people how to benefit from the park without environmental damage. Cultural diversity is as important as biological diversity. The area has been designated by UNESCO as a World Heritage Site with the "last pure ecological seed" of the Himalayas. The regional geography and culture are presented. Population growth has impacted natural resources through overgrazing, cultivation of marginal land, and deforestation; future plans to build a dam and road bordering the nature reserve pose other threats. Proposed management plans for the Makalu-Barun Nature Park (established in November 1991) and Conservation Area include a division of the park into nature reserve areas free of human activity, protected areas which permit traditional land use, and special sites and trail for tourists and religious pilgrims. The conservation area will act as a buffer for the park and provide economic opportunities; further subdivisions include land use for biodiversity protection, community forest and pasture, agroforestry, and agriculture and settlement. Efforts will be made to increase the welfare of women and local people; proposed projects include the introduction of higher milk-producing animals for stall feeding. Also proposed is a cultural and natural history museum. 70% of the project's resources will be directed to local community participation in consultation and park maintenance. The project is a model of how conservation and protection of natural resources can coexist with local economic development and participation; an integration of preservation of biological diversity, mountain wisdom, and the value of local people as resources for conservation.

  16. Is a healthy diet an environmentally sustainable diet?

    Science.gov (United States)

    Macdiarmid, Jennie I

    2013-02-01

    The concept of a healthy and environmentally sustainable diet is not new, but with increasing concern about future global food security and climate change there is a renewed interest in this topic. Dietary intakes in UK accounts for approximately 20-30% of total annual greenhouse gas emissions (GHGE), with the greatest contributions coming from high intakes of meat and dairy products. Dietary proposals to help mitigate climate change (i.e. reduce GHGE) have focused on reducing consumption of meat and dairy products, but this must be considered in the context of the whole diet, alongside any possible nutritional consequences for health. Bringing together health and environmental impact of the diet raises the question of whether a healthy diet can also be an environmentally sustainable diet. While recent research showed that it is possible to achieve a realistic diet that meets dietary requirement for health and has lower GHGE, it cannot be assumed that a healthy diet will always have lower GHGE. With different combinations of food it is possible to consume a diet that meets dietary requirements for health, but has high GHGE. It is important to understand what constitutes a sustainable diet, but this then needs to be communicated effectively to try and change well-established dietary intakes of the population. Studies show that understanding of sustainable diets is poor and there are many misconceptions (e.g. the overestimation of the protein requirements for a healthy diet), which could contribute to the barriers towards changing dietary intakes.

  17. Energy conservation in industry

    International Nuclear Information System (INIS)

    Pembleton, P.

    1992-01-01

    Energy Conservation in Industry is the first number in the Energy and Environmental Series of the Industrial and Technological Information Bank (INTIB). The Series supersedes the INECA Journal and reflects the broader information programme undertaken by INTIB. The present number of the Series contains contributions from three major international databases and five topic-specific sources, including three United Nations Organizations. The present publication consists of a recent technical report on a current topic: reducing energy loss in four industrial sectors and improving energy conservation through waste-heat recovery, followed by two sections containing abstracts of technical materials

  18. Local instant conservation equations

    International Nuclear Information System (INIS)

    Delaje, Dzh.

    1984-01-01

    Local instant conservation equations for two-phase flow are derived. Derivation of the equation starts from the recording of integral laws of conservation for a fixed reference volume, containing both phases. Transformation of the laws, using the Leibniz rule and Gauss theory permits to obtain the sum of two integrals as to the volume and integral as to the surface. Integrals as to the volume result in local instant differential equations, in particular derivatives for each phase, and integrals as to the surface reflect local instant conditions of a jump on interface surface

  19. Diesel conservation: GSRTC'S experience

    Energy Technology Data Exchange (ETDEWEB)

    Ramesh Kumar, I V

    1980-01-01

    The Gujarat State Road Transport Corporation (GSRTC) in India has a fleet of about 6000 buses. The increasing cost of fuel and lubricants added to uncertainty in supplies, has necessitated the need for conserving High Speed Diesel Oil (HSD). GSRTC had achieved an overall average Kilometre Per Litre (kmpl) of 4.44 in the year 1976-1977 due to a variety of measures. In the year 1978-1979 the average kmpl was 4.52 and it is expected to be 4.60 for 1979-1980. The case study outlined describes the measures taken by GSRTC in conserving high speed diesel oil by various methods.

  20. Information, conservation and retrieval

    Energy Technology Data Exchange (ETDEWEB)

    Eng, T [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Norberg, E [National Swedish Archives, Stockholm (Sweden); Torbacke, J [Stockholm Univ. (Sweden). Dept. of History; Jensen, M [Swedish Radiation Protection Inst., Stockholm (Sweden)

    1996-12-01

    The seminar took place on the Swedish ship for transportation of radioactive wastes, M/S Sigyn, which at summer time is used for exhibitions. The seminar treated items related to general information needs in society and questions related to radioactive waste, i.e. how knowledge about a waste repository should be passed on to future generations. Three contributions are contained in the report from the seminar and are indexed separately: `Active preservation - otherwise no achieves`; `The conservation and dissemination of information - A democratic issue`; and, `Conservation and retrieval of information - Elements of a strategy to inform future societies about nuclear waste repositories`.