... body does not produce enough parathyroid hormone), refractory rickets (softening and weakening of bones that does not respond to treatment), and familial hypophosphatemia (rickets or osteomalacia caused by an inherited condition with ...
Full Text Available Introduction: Vitamin D has become an area of intensive scrutiny, both in medical and lay literature. However, there are limited data to suggest proper repletion regimens for those patients who have hypovitaminosis D. Consequently, various methods are used in clinical practice. The aim of this study was to assess the efficacy of various treatment strategies for hypovitaminosis D in an ambulatory internal medicine practice. Methods: A retrospective chart review between October 2005 and June 2010 of a suburban internal medicine practice was performed via query of the electronic medical record (Centricity, General Electric Healthcare, UK. Patients with a 25-hydroxyvitamin D concentration less than 32 mg/dl were identified and treated. Treatment success was defined as 25-hydroxyvitamin D concentrations greater than 32 mg/dl. Statistical analysis to assess changes in vitamin D level controlling for season, comorbidities, and demographics were used. Results: A total of 607 treatment episodes were identified, with 395 excluded due to lack of follow-up vitamin D level within 16 weeks, no treatment documented, topical treatment, doxercalciferol treatment, or non-compliance. Of the remaining patients, there were 212 treatment instances on 178 patients. Ergocalciferol 50,000 international units (IU was used most frequently (71.4% of the time.. A higher initial vitamin D level was positively associated with treatment success (adjusted odds ratio = 1.11, p=0.002. Increased doses of ergocalciferol increased the likelihood of treatment success (p=0.0011. Seasonal variation was related to posttreatment 25-hydroxyvitamin D concentration as was body mass index (BMI (p=0.003 and p=0.044. Conclusion: Pretreatment levels of 25-hydroxyvitamin D, BMI, season, and vitamin D dose are predictors of successful hypovitaminosis D treatment. Our data suggest that patients with initial 25-hydroxyvitamin D concentrations of <20 should be treated with a higher total dose of
Gravesen, Eva; Hofman-Bang, Jacob; Lewin, Ewa
Focus on non-classical effects and possible less side effects of treatment with nutritional vitamin D, raises the expectation of possible benefits from treating chronic kidney disease (CKD) patients with ergocalciferol (vitamin D2). Treatment with 1,25(OH)2 vitamin D (calcitriol) induces elevated...... of treatment with high doses of ergocalciferol on parameters of mineral homeostasis in predialysis CKD patients....
Quinones, Javier Perez; Gothelf, Kurt Vesterager; Kjems, Jørgen
Glycol chitosan was linked to vitamin D2 hemisuccinate (ergocalciferol hemisuccinate) for controlled release through water-soluble carbodiimide activation. The resulting conjugate formed self-assembled nanoparticles in aqueous solution with particle size of 279 nm and ergocalciferol hemisuccinate...... content of 8.4% (w/w). Almost spherical 50–90 nm nanoparticles were observed by scanning and transmission electron microscopy upon drying. Drug linking to glycol chitosan was confirmed by FTIR spectroscopy and proton NMR. Particles were also characterized by differential scanning calorimetry and wide...
Full Text Available An accurate, sensitive and selective method is developed for determination of ergocalciferol (vitamin D2 in human plasma using LCâMS/MS. After liquid-liquid extraction with n-hexane, ergocalciferol was derivatized by reacting with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD, a strong dienophile based on Diels-Alder reaction. Ergocalciferol and its deuterated internal standard, ergocalciferol-d6, were analyzed on X Select CSH C18 (100Â mmÃ4.6Â mm, 2.5Â Âµm column using acetonitrile and 0.1% (v/v formic acid in water containing 0.14% methylamine within 6.0Â min under gradient elution mode. Tandem mass spectrometry in positive ionization mode was used to quantify ergocalciferol by multiple reaction monitoring (MRM. Entire data processing was done using Watson LIMSâ¢ software which provided excellent data integrity and high throughput with improved operational efficiency. The major advantage of this method includes higher sensitivity (0.10Â ng/mL, superior extraction efficiency (â¥83% and small sample volume (100Â ÂµL for processing. The method was linear in the concentration range of 0.10â100Â ng/mL for ergocalciferol. The intra-batch and inter-batch accuracy and precision (% CV values varied from 97.3% to 109.0% and 1.01% to 5.16%, respectively. The method was successfully applied to support a bioequivalence study of 1.25Â mg ergocalciferol capsules in 12 healthy subjects. Keywords: Ergocalciferol, Diels-Alder reaction, 4-phenyl-1,2,4-triazoline-3,5-dione, LCâMS/MS, Human plasma
Knudsen, Mikkel Malham; Jørgensen, S. P.; Lauridsen, A. L.
Objective: The goal of this study was to examine the effects of a single oral dose of 300 000 international units of either ergocalciferol (D2) or cholecalciferol (D3) on the plasma levels of 25-hydroxyvitamin D in patients with alcoholic liver cirrhosis. Methods: Inclusion criteria for this stud...
Hymøller, Lone; Jensen, Søren Krogh
treatments: D2, housed indoor and fed 625-μg/d (25.000 IU) ERG; D3, housed indoor and fed 625-μg/d CHO; D2+D3, housed indoor and fed 625-μg/d ERG and 625-μg/d CHO; SUN, let out for daily pasture to facilitate CHO synthesis from sunlight; and D2+SUN, fed 625-μg/d ERG and let out for daily pasture. Blood....../mL 25CHO in pasture or CHO-treated cows with the highest concentration in SUN (P ≤ 0.01). In plasma fractions, CHO was mainly found in the HLP fraction, whereas 25CHO was almost exclusively found in the protein fraction, probably due to its reported high binding affinity to vitamin D-binding protein...
Full Text Available ne hydrochloride - cyanocobalamin - ascorbic acid - ergocalciferol - tocopherol acetate - calcium pantothena...[DR:D00166], Ascorbic acid [DR:D00018], Ergocalciferol [DR:D00187], Tocopherol acetate [DR:D01735], Calcium
Conclusions. Short ergocalciferol treatment can be a valuable and reliable clinical method to differentiate isolated vitamin D deficiency and asymptomatic primary hyperparathyroidism combined with a lack of vitamin D.
Vestergaard, Peter; Eiken, Pia A
This review discusses the mineral bone disorders in patients with chronic kidney disease. We focus on the management of these conditions by administration of calcium, vitamin D (ergocalciferol and cholecalciferol), vitamin D receptor activators (calcitriol, alphacalcidiol), phosphate binders and ...... and calcimimetics (cinacalcet)....
... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Vitamin D. 184.1950 Section 184.1950 Food and Drugs... Substances Affirmed as GRAS § 184.1950 Vitamin D. (a) Vitamin D is added to food as the following food ingredients: (1) Crystalline vitamin D2 (C28H44O, CAS Reg. No. 50-14-6), also known as ergocalciferol, is the...
... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Vitamin D2. 172.379 Section 172.379 Food and Drugs... Dietary and Nutritional Additives § 172.379 Vitamin D2. Vitamin D2 may be used safely in foods as a... prescribed conditions: (a) Vitamin D2, also known as ergocalciferol, is the chemical 9,10-seco(5Z,7E,22E)-5,7...
Pavlovic, Drasko; Katicic, Dajana; Gulin, Tonko; Josipovic, Josipa
Alteration in vitamin D metabolism has a central role in the pathogenesis of secondary hyperparathyroidism (SHPT) and is also associated with increased cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). For more than sixty years, vitamin D, nutritional vitamin D (ergocalciferol, cholecalciferol or calcifediol) and nonselective vitamin D receptor (VDR) activators (calcitriol, alfacalcidol) have been used in the prevention and treatment of SHPT. In the last tw...
including diabetes mellitus type 1, rheumatoid arthritis , experimental autoimmune encephalomyelitis, inflammatory bowel disease, and systemic lupus...the safety and effectiveness of monthly ergocalciferol in hemodialysis patients . Nephron Clin Pract 2007;105(3):132-8 91. Goldzieher JW, Zerwekh...D in patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc 2003;78:1463-1470. 31. Glerup H, Mikkelsen K, Poulsen L, et al
Full Text Available Previously, we demonstrated i that ergocalciferol (vitamin D2 increases axon diameter and potentiates nerve regeneration in a rat model of transected peripheral nerve and ii that cholecalciferol (vitamin D3 improves breathing and hyper-reflexia in a rat model of paraplegia. However, before bringing this molecule to the clinic, it was of prime importance i to assess which form - ergocalciferol versus cholecalciferol - and which dose were the most efficient and ii to identify the molecular pathways activated by this pleiotropic molecule. The rat left peroneal nerve was cut out on a length of 10 mm and autografted in an inverted position. Animals were treated with either cholecalciferol or ergocalciferol, at the dose of 100 or 500 IU/kg/day, or excipient (Vehicle, and compared to unlesioned rats (Control. Functional recovery of hindlimb was measured weekly, during 12 weeks, using the peroneal functional index. Ventilatory, motor and sensitive responses of the regenerated axons were recorded and histological analysis was performed. In parallel, to identify the genes regulated by vitamin D in dorsal root ganglia and/or Schwann cells, we performed an in vitro transcriptome study. We observed that cholecalciferol is more efficient than ergocalciferol and, when delivered at a high dose (500 IU/kg/day, cholecalciferol induces a significant locomotor and electrophysiological recovery. We also demonstrated that cholecalciferol increases i the number of preserved or newly formed axons in the proximal end, ii the mean axon diameter in the distal end, and iii neurite myelination in both distal and proximal ends. Finally, we found a modified expression of several genes involved in axogenesis and myelination, after 24 hours of vitamin supplementation. Our study is the first to demonstrate that vitamin D acts on myelination via the activation of several myelin-associated genes. It paves the way for future randomised controlled clinical trials for peripheral
Miranda C, Daisy; Leiva B, Laura; León S, José Pablo; de la Maza C, Ma Pía
El estado nutrícional de vitamina D ha cobrado importancia en los últimos años debido a que su deficiencia es altamente prevalente, y además por sus conocidos efectos en el metabolismo óseo, participa en la diferenciación y proliferación celular, función muscular y equilibrio, entre otros. La molécula activa es la 1,25(OH)2D, pero se recomienda medir niveles séricos de 25 OH vitamina D total (es decir la suma de ergocalciferol o vitamina D2 y colecalciferol o vitamina D3), como reflejo del st...
John A. A. Geddes
Full Text Available Introduction. Vitamin D is common treatment for osteoporosis. Both age >70 years and living in residential care are associated with increased fracture risk. Community dwelling elderly are a heterogeneous group who may have more similatiry with residential care groups than younger community dwelling counterparts. Aims. To review the evidence for cholecalciferol or ergocalciferol tretment of osteoporosis in either community dwelling patients aged ≥70 years of age, or redidential care patients. Secondly endpoints were changes in bone mineral denisty, and in bone turnover markers. Methods. We performed a literature search using search terms for osteoporosis and vitamin D. Treatment for at least one year was required. Results. Only one residential care study using cholecalciferol, showed non-vertebral and hip fracture reduction in vitamin D deficient subjects. In the community setting one quasi randomised study using ergocalciferol showed reduction in total but not hip or non-vertebral fracture, and a second randomised study showed increased hip fracture risk. Three studies reported increases in hip bone mineral denisty. Discussion. A minority of studies demonstrated a fracture benefit form vitamin D and one suggested possible harm in a community setting. Current practice should be to only offer this treatment to subjects identified as deficient.
Galassi, Andrea; Bellasi, Antonio; Ciceri, Paola; Pivari, Francesca; Conte, Ferruccio; Cozzolino, Mario
Deranged vitamin D metabolism represents an active trigger of secondary hyperparathyroidism (SHPT) in CKD. Correction of 25(OH)D deficiency by nutritional Vitamin D administration is suggested by KDIGO guidelines, to prevent and treat SHPT in CKD stage G3-G5 and G1T-G5T patients, although with a still inconsistent background. Nutritional vitamin D is available as cholecalciferol, ergocalciferol, or calcifediol. Superiority of calcifediol in increasing 25(OH)D levels has been suggested due to its better bioavailability. The safer pharmacokinetic of the recent modified-release (MR) formulation of calcifediol was effective in replenishing 25(OH)D levels with minimal impact on vitamin D catabolism and fibroblast-growth factor-23 (FGF-23) activation. Areas covered: the review discusses utility of calcifediol for treating SHPT in different CKD stages under physiology driven approach, focusing on vitamin D metabolism, guidelines suggestions and comparison between clinical effects on SHPT elicited by calcifediol, cholecalciferol and ergocalciferol. Expert commentary: although optimal targets of 25(OH)D and parathormone remain uncertain, calcifediol, especially in its newer MR formulation, may represent an intriguing option to combine an efficacious correction of 25(OH)D deficit and SHPT, with a limited impact on vitamin D catabolism and FGF-23 activation. Newer data are required to better explore the role of MR calcifediol in treating SHPT.
Duffy, Sarah K.; O'Doherty, John V.; Rajauria, Gaurav
This study investigates dietary fortification of heifer feeds with cholecalciferol and ergocalciferol sources and effects on beef total vitamin D activity, vitamer, respective 25-hydroxymetabolite contents, and meat quality. Thirty heifers were allocated to one of three dietary treatments [(1......) basal diet + 4000 IU of vitamin D3 (Vit D3); (2) basal diet + 4000 IU of vitamin D2 (Vit D2); and (3) basal diet + 4000 IU of vitamin D2-enriched mushrooms (Mushroom D2)] for a 30 day pre-slaughter period. Supplementation of heifer diets with Vit D3 yielded higher (p ...) total vitamin D activity (by 38–56%; p vitamin D source, carcass characteristics, sensory and meat quality parameter were unaffected (p > 0.05) by the dietary...
Bjelakovic, Goran; Nikolova, Dimitrinka; Bjelakovic, Marko
BACKGROUND: Vitamin D deficiency is often reported in people with chronic liver diseases. Therefore, improving vitamin D status could have a beneficial effect on people with chronic liver diseases. OBJECTIVES: To assess the beneficial and harmful effects of vitamin D supplementation in people...... with chronic liver diseases. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science. We also searched databases...... that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults with chronic liver diseases. Vitamin D could have been administered as supplemental vitamin D (vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol)), or an active form of vitamin D (1α...
Við Streym, Susanna; Højskov, Carsten S; Møller, Ulla Kristine
BACKGROUND: Parents are advised to avoid the direct sun exposure of their newborns. Therefore, the vitamin D status of exclusively breastfed newborns is entirely dependent on the supply of vitamin D from breast milk. OBJECTIVES: We explored concentrations of ergocalciferol (vitamin D2......) and cholecalciferol (vitamin D3) (vitamin D) and 25-hydroxivitamin D2 plus D3 (25-hydroxyvitamin D [25(OH)D]) in foremilk and hindmilk during the first 9 mo of lactation and identified indexes of importance to the concentrations. DESIGN: We collected blood and breast-milk samples from mothers at 2 wk (n = 107), 4 mo......, (n = 90), and 9 mo (n = 48) postpartum. Blood samples from infants were collected 4 and 9 mo after birth. We measured concentrations of vitamin D metabolites in blood and milk samples with the use of liquid chromatography-tandem mass spectrometry. RESULTS: Concentrations of vitamin D and 25(OH)D...
Dispersive liquid-liquid microextraction for the determination of vitamins D and K in foods by liquid chromatography with diode-array and atmospheric pressure chemical ionization-mass spectrometry detection.
Viñas, Pilar; Bravo-Bravo, María; López-García, Ignacio; Hernández-Córdoba, Manuel
A simple and rapid method was developed using reversed-phase liquid chromatography (LC) with both diode array (DAD) and atmospheric pressure chemical ionization mass spectrometric (APCI-MS) detection, for the simultaneous analysis of the vitamins ergocalciferol (D2), cholecalciferol (D3), phylloquinone (K1), menaquinone-4 (K2) and a synthetic form of vitamin K, menadione (K3). The Taguchi experimental method, an orthogonal array design (OAD), was used to optimize an efficient and clean preconcentration step based on dispersive liquid-liquid microextraction (DLLME). A factorial design was applied with six factors and three levels for each factor, namely, carbon tetrachloride volume, methanol volume, aqueous sample volume, pH of sample, sodium chloride concentration and time of the centrifugation step. The DLLME optimized procedure consisted of rapidly injecting 3 mL of acetonitrile (disperser solvent) containing 150 µL carbon tetrachloride (extraction solvent) into the aqueous sample, thereby forming a cloudy solution. Phase separation was performed by centrifugation, and the sedimented phase was evaporated with nitrogen, reconstituted with 50 µL of acetonitrile, and injected. The LC analyses were carried out using a mobile phase composed of acetonitrile, 2-propanol and water, under gradient elution. Quantification was carried out by the standard additions method. The APCI-MS spectra, in combination with UV spectra, permitted the correct identification of compounds in the food samples. The method was validated according to international guidelines and using a certified reference material. The validated method was applied for the analysis of vitamins D and K in infant foods and several green vegetables. There was little variability in the forms of vitamin K present in vegetables, with the most abundant vitamer in all the samples being phylloquinone, while menadione could not be detected. Conversely, cholecalciferol, which is present in food of animal origin, was
Full Text Available Tanto la equivalencia entre colecalciferol (D3 y ergocalciferol (D2, como las dosis y forma de administración de ambos, son actualmente un tema controvertido. El objetivo de este estudio fue comparar la efectividad de 800 UI/día de D2 (gotas y D3 (comprimidos para alcanzar niveles adecuados de 25 hidroxivitamina D (25OHD (= 30 ng/ml. Veintiún mujeres posmenopáusicas que vivían en la Ciudad de Buenos Aires, edad promedio ( ± DS 77.1 ± 6.8 años fueron incluidas y asignadas en forma aleatoria a uno de los siguientes grupos: GD2 (n = 13: 800 UI (gotas y GD3 (n = 8: 800 UI (comprimidos. Se midió 25OHD sérica (RIA-DIASORIN basal y a los 7, 28 y 45 días del estudio. Basalmente, 19 de las 21 mujeres presentaron niveles de deficiencia de 25(OHD (The equivalence of cholecalciferol (D3 and ergocalciferol (D2 as well as their corresponding doses and administration route remain controversial to date. The aim of this study was to compare the effectiveness of daily supplementation with 800 IU of D2 (drops and D3 (pills on 25-hydroxivitamin D (25OHD levels (= 30 ng/ml. Twenty-one ambulatory postmenopausal women from Buenos Aires City with a mean ( ± SD age of 77.1 ± 6.8 years were included. The participants were randomly assigned to one of the following groups: GD2 (n = 13: 800 IU (drops and GD3 (n = 8: 800 IU (pills. Serum 25OHD levels were measured (RIA-DIASORIN at baseline, and at 7, 28 and 45 days. Nineteen out of twenty one women showed deficient levels of 25OHD at baseline (< 20 ng/ml: GD2: 14.0 ± 4.8 ng/ml and GD3: 13.2 ± 4.9 ng/ml (NS. Whereas only GD3 exhibited an increase (~25% at 7 days, both groups showed a significant increase at the end of the study. However, neither attained adequate 25OHD levels (GD2: 17.4 ± 5.5 vs. GD3:22.9 ± 4.6 ng/ml; p < 0.001. Administration of 800 IU of vitamin D3 during 45 days was more effective than D2 in increasing 25OHD, but both failed to achieve adequate levels of 25OHD (= 30 ng/ml. but neither
Wyskida, Magdalena; Wieczorowska-Tobis, Katarzyna; Chudek, Jerzy
Vitamin D deficiency affects a large part of the population of elderly people, especially women, who live in moderate climate countries due to a reduced amount of vitamin D in the diet (small sea fish consumption) and reduced content of 7-dehydrocholesterol, which causes decreased skin synthesis. The lowest seasonal concentration of 25(OH)D3 is usually observed during winter and spring. Sun exposure influences 25(OH)D3 concentration more strongly in men than in women. Sociodemographic factors that increase the risk of vitamin D deficiency in the elderly include poor environmental conditions, low economic status, lower educational level, drug exposure (smoking), reduced physical activity, overall poor health and obesity, which causes reduced skin exposure to sunlight. The use of medications or supplements that contain vitamin D and staying in a nursing home that employ such supplementation are factors that prevent deficiency. Significant prevalence of diseases of the gastrointestinal tract may contribute to cholecalciferol and ergocalciferol malabsorption or impair their liver transformation. In addition, the high incidence of chronic kidney disease in old age reduces processing hydroxylation of vitamin D and the formation of active metabolites. Vitamin D deficiency can not only cause bone mineralization disorders, but also increase incidence of cardiovascular diseases, cancers, type 2 diabetes and depression. The aim of this study was to summarize current knowledge about the risk factors of vitamin D deficiency development in the elderly population.
Slawinska, Aneta; Fornal, Emilia; Radzki, Wojciech; Jablonska-Rys, Ewa; Parfieniuk, Ewa
The effects of ultraviolet B (UVB) irradiation on the synthesis of vitamin D2 and its stability during refrigerated storage was determined in fresh cultivated culinary-medicinal mushrooms (Agaricus bisporus, Pleurotus ostreatus, and Lentinus edodes) after harvest. The irradiated mushrooms were stored at 4°C for up to 10 days. The concentrations of vitamin D2 and ergosterol were determined using ultrahigh-performance liquid chromatography/tandem mass spectrometry. The cultivated mushrooms not treated with UVB were devoid of vitamin D2. After UVB irradiation, we obtained mushrooms with a large amount of ergocalciferol. A. bisporus showed the lowest vitamin D2 content (3.55 ± 0.11 μg D2/g dry weight); P. ostreatus contained 58.96 ± 1.15 μg D2/g dry weight, and L. edodes contained 29.46 ± 2.21 μg/g dry weight. During storage at 4°C, the amount of vitamin D2 was gradually decreased in P. ostreatus and L. edodes, whereas in A. bisporus vitamin D2 gradually increased until the sixth day, then decreased. Mushrooms exposed to UVB radiation contain a significant amount of vitamin D2 and are therefore an excellent food source of vitamin D.
Gentili, Alessandra; Caretti, Fulvia; Bellante, Simona; Ventura, Salvatore; Canepari, Silvia; Curini, Roberta
This paper describes a novel and efficient analytical method to define the profile of fat-soluble micronutrients in milk from different animal species. Overnight cold saponification was optimized as a simultaneous extraction procedure. Analytes were separated by nonaqueous reversed-phase (NARP) chromatography: carotenoids on a C(30) column and fat-soluble vitamins on a tandem C(18) column system. Besides 12 target analytes for which standards are available (all-trans-lutein, all-trans-zeaxanthin, all-trans-β-cryptoxanthin, all-trans-β-carotene, all-trans-retinol, α-tocopherol, γ-tocopherol, δ-tocopherol, ergocalciferol, cholecalciferol, phylloquinone, and menaquinone-4), the DAD-MS combined detection allowed the provisional identification of other carotenoids on the basis of the expected retention times, the absorbance spectra, and the mass spectrometric data. Retinol and α-tocopherol were the most abundant fat-soluble micronutrients and the only ones found in donkey's milk along with γ-tocopherol. Ewe's milk also proved to be a good source of vitamin K vitamers. Bovine milk showed a large variety of carotenoids that were absent in milk samples from other species with the only exception of all-trans-lutein and all-trans-zeaxanthin.
Heaney, Robert P
Vitamin D functions in the body through both an endocrine mechanism (regulation of calcium absorption) and an autocrine mechanism (facilitation of gene expression). The former acts through circulating calcitriol, whereas the latter, which accounts for more than 80% of the metabolic utilization of the vitamin each day, produces, uses, and degrades calcitriol exclusively intracellularly. In patients with end-stage kidney disease, the endocrine mechanism is effectively disabled; however, the autocrine mechanism is able to function normally so long as the patient has adequate serum levels of 25(OH)D, on which its function is absolutely dependent. For this reason, calcitriol and its analogs do not constitute adequate replacement in managing vitamin D needs of such patients. Optimal serum 25(OH)D levels are greater than 32 ng/mL (80 nmol/L). The consequences of low 25(OH)D status include increased risk of various chronic diseases, ranging from hypertension to diabetes to cancer. The safest and most economical way to ensure adequate vitamin D status is to use oral dosing of native vitamin D. (Both daily and intermittent regimens work well.) Serum 25(OH)D can be expected to rise by about 1 ng/mL (2.5 nmol/L) for every 100 IU of additional vitamin D each day. Recent data indicate that cholecalciferol (vitamin D(3)) is substantially more potent than ergocalciferol (vitamin D(2)) and that the safe upper intake level for vitamin D(3) is 10,000 IU/d.
Full Text Available Fractures are uncommon in young, nonambulatory infants. The differential diagnosis includes nonaccidental injury (NAI and metabolic bone disease, including rickets. While rickets typically present after six months of age, multiple cases have been reported in younger infants. We report a case of an 11-week-old male infant who presented with a spiral fracture of the humerus and no radiologic evidence of rickets. A detailed psychosocial assessment failed to reveal any risk factors for NAI. The patient had elevated alkaline phosphatase and PTH with low 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D levels. Additionally, the mother was noncompliant with prenatal vitamins, exclusively breastfeeding without vitamin D supplementation, and had markedly low vitamin D levels 15 weeks postpartum. The biochemical data and history were consistent with rickets. Given the diagnostic dilemma, the working diagnosis was rickets and the patient was started on ergocalciferol with subsequent normalization of his laboratory values and healing of the fracture. These findings are consistent with nutritional rickets largely due to maternal-fetal hypovitaminosis D. This case highlights that in young infants rickets should be considered even in the absence of positive radiologic findings. Additionally, it illustrates the importance of maintaining adequate vitamin D supplementation during pregnancy and early infancy.
Maria Morales Suárez-Varela
Full Text Available Vitamin D has important immunomodulatory effects on psoriasis in the Mediterranean region. To measure vitamin D intake in subjects with and without psoriasis, and to find an association with relevant clinical features, a case-control study was performed using cases (n = 50, 50% participation rate clinically diagnosed with psoriasis and 200 healthy subjects (39.5% participation rate, leaving a final sample of 104 people. A survey was conducted using a food frequency questionnaire and clinical histories. Cases and controls were compared using univariate and multivariate analyses. We observed insufficient intake of cholecalciferol (vitamin D3 or ergocalciferol (vitamin D2 for both cases and controls. Patients with psoriasis were at greater risk of associated pathologies: dyslipidaemia (OR: 3.6, 95% CI: 0.8–15.2; metabolic syndrome (OR: 3.3, 95% CI: 0.2–53.9; hypertension (OR: 1.7, 95% CI: 0.4–7.2. Insufficient vitamin D intake in both psoriasis patients and controls in the Mediterranean population, and cardiovascular comorbility is more frequent in patients with psoriasis.
Oberson, Jean-Marie; Campos-Giménez, Esther; Rivière, Johann; Martin, Frédéric
In the present manuscript, we describe a fully optimized and validated method suitable to analyse nine compounds (retinyl acetate, retinyl palmitate, retinol, α-tocopherol, α-tocopheryl acetate, cholecalciferol, ergocalciferol, phylloquinone, menaquinone-4) representing the major contributors to the fat-soluble vitamin activity of selected food products (infant formulas, adult nutritionals, infant cereals and mixed meals). Sample preparation involves direct solvent extraction using enzyme-assisted matrix disintegration and methanolic protein precipitation. Direct injection of the extract allows quantification of vitamins A, E and K in only 7 min, while vitamin D is determined after fast derivatization of the extract. Separation is achieved by supercritical fluid chromatography and detection performed by tandem mass spectrometry in positive Atmospheric Pressure Chemical Ionization mode. Results on a Standard Reference Material (SRM 1849a Infant/Adult Nutritional) were not statistically different from reference values. Full validation of the method showed excellent overall performance. Average recovery rate was between 90 and 110% for all vitamins and matrixes. The methodology shows enhanced safety and reduced cost as compared with previously published methods, together with potential for application to more complex matrixes. The full procedure can be easily applied in control laboratories dramatically increasing sample throughput and reducing solvent consumption. Copyright © 2018 Elsevier B.V. All rights reserved.
Full Text Available In the presented study for the first time a new, optimized, fast SFC (supercritical fluid chromatography method was applied to separate in one run fat-soluble vitamins from waste fish oil, including cis-and trans-retinyl palmitate, cis- and trans-retinyl acetate, retinol, α-tocopherol, β-tocopherol, γ‑tocopherol, δ-tocopherol, ergocalciferol (D2, cholecalciferol (D3, cis- and trans-phylloquinone (K1 and menaquinone-4 (K2-MK4. Vitamins were baseline separated on an Acquity UPC2 (ultra performance convergence chromatography HSS C18 SB (highly strength chemically modified silica column within 13 min. The influence of the stationary phase, such as Torus 1-AA (1-aminoanthracene, Torus Diol (high density diol, Torus DEA (diethylamine, BEH (silica with no bonding, BEH-2EP (2-ethylpirydine, CSH Fluoro-Phenyl (silica with fluoro-phenyl groups, column temperature, flow rate and back pressure on the separation of the compounds was described. The application of the modified saponification procedure allowed us to increase concentration in the sample prepared for the analysis of γ‑tocopherol from less than 1% (wt % to 14% for the first time. In addition, α‑tocopherol, γ‑tocopherol, δ‑tocopherol and retinol were identified in waste fish oil. Vitamin purification and analysis in waste fish oil are reported for the first time here. Due to the short time and effectiveness of the proposed method, it can be easily applied in industrial processes.
Goldring, Stephen T; Griffiths, Chris J; Martineau, Adrian R; Robinson, Stephen; Yu, Christina; Poulton, Sheree; Kirkby, Jane C; Stocks, Janet; Hooper, Richard; Shaheen, Seif O; Warner, John O; Boyle, Robert J
Observational studies suggest high prenatal vitamin D intake may be associated with reduced childhood wheezing. We examined the effect of prenatal vitamin D on childhood wheezing in an interventional study. We randomised 180 pregnant women at 27 weeks gestation to either no vitamin D, 800 IU ergocalciferol daily until delivery or single oral bolus of 200,000 IU cholecalciferol, in an ethnically stratified, randomised controlled trial. Supplementation improved but did not optimise vitamin D status. Researchers blind to allocation assessed offspring at 3 years. Primary outcome was any history of wheeze assessed by validated questionnaire. Secondary outcomes included atopy, respiratory infection, impulse oscillometry and exhaled nitric oxide. Primary analyses used logistic and linear regression. We evaluated 158 of 180 (88%) offspring at age 3 years for the primary outcome. Atopy was assessed by skin test for 95 children (53%), serum IgE for 86 (48%), exhaled nitric oxide for 62 (34%) and impulse oscillometry of acceptable quality for 51 (28%). We found no difference between supplemented and control groups in risk of wheeze [no vitamin D: 14/50 (28%); any vitamin D: 26/108 (24%) (risk ratio 0.86; 95% confidence interval 0.49, 1.50; P = 0.69)]. There was no significant difference in atopy, eczema risk, lung function or exhaled nitric oxide between supplemented groups and controls. Prenatal vitamin D supplementation in late pregnancy that had a modest effect on cord blood vitamin D level, was not associated with decreased wheezing in offspring at age three years. Controlled-Trials.com ISRCTN68645785.
Roddam Andrew W
Full Text Available Abstract Background Vitamin D supplementation for fracture prevention is widespread despite conflicting interpretation of relevant randomised controlled trial (RCT evidence. This study summarises quantitatively the current evidence from RCTs and observational studies regarding vitamin D, parathyroid hormone (PTH and hip fracture risk. Methods We undertook separate meta-analyses of RCTs examining vitamin D supplementation and hip fracture, and observational studies of serum vitamin D status (25-hydroxyvitamin D (25(OHD level, PTH and hip fracture. Results from RCTs were combined using the reported hazard ratios/relative risks (RR. Results from case-control studies were combined using the ratio of 25(OHD and PTH measurements of hip fracture cases compared with controls. Original published studies of vitamin D, PTH and hip fracture were identified through PubMed and Web of Science databases, searches of reference lists and forward citations of key papers. Results The seven eligible RCTs identified showed no significant difference in hip fracture risk in those randomised to cholecalciferol or ergocalciferol supplementation versus placebo/control (RR = 1.13[95%CI 0.98-1.29]; 801 cases, with no significant difference between trials of 21 (heterogeneity = 51.02, p 216 (heterogeneity = 137.9, p 29 (heterogeneity = 149.68, p Conclusions Neither higher nor lower dose vitamin D supplementation prevented hip fracture. Randomised and observational data on vitamin D and hip fracture appear to differ. The reason for this is unclear; one possible explanation is uncontrolled confounding in observational studies. Post-fracture PTH levels are unrelated to hip fracture risk.
Yorleny Araya Quesada
Full Text Available El ergocalciferol y el colecalciferol, vitamina D2 y vitamina D3, respectivamente, se conocen comúnmente con el nombre de vitamina D. La vitamina D3 se sintetiza en la piel a partir de 7-dehidrocolesterol a causa de la irradiación de los rayos ultravioleta. La bioactivación de la vitamina D3 como hormona posteriormente se lleva a cabo por 1 α,25-dihidroxivitamina D3 (calcitriol en el riñón. La concentración de la vitamina D3, 25-(OHD3 se ha usado como indicador del estatus de vitamina D. Se han detectado deficiencias en la población, debido al aumento en un estilo de vida sedentario y a la protección solar que utilizan los individuos o a causa de ciertas enfermedades, y se considera un problema emergente de salud mundial. El riesgo de insuficiencia de vitamina D se relaciona con la raza (color de la piel, latitud geográfica, exposición solar (estilo de vida, género y la salud del individuo en general. Es mayor la deficiencia en zonas del sur del continente que del norte y más en mujeres que en hombres, así como en invierno. Se hizo una recopilación del impacto de la vitamina D en suero sanguíneo sobre la salud, como lo es la osteoporosis, efecto sobre la tiroides y el cerebro, enfermedades cardiovasculares, artritis enfermedades autoinmunes, cáncer y diabetes, y las dosis recomendadas de vitamina D para mantener los niveles suficientes, así como la fortificación de alimentos para lograr llenar esas recomendaciones.
Full Text Available Tanto la equivalencia entre colecalciferol (D3 y ergocalciferol (D2, como las dosis y forma de administración de ambos, son actualmente un tema controvertido. El objetivo de este estudio fue comparar la efectividad de 800 UI/día de D2 (gotas y D3 (comprimidos para alcanzar niveles adecuados de 25 hidroxivitamina D (25OHD (= 30 ng/ml. Veintiún mujeres posmenopáusicas que vivían en la Ciudad de Buenos Aires, edad promedio ( ± DS 77.1 ± 6.8 años fueron incluidas y asignadas en forma aleatoria a uno de los siguientes grupos: GD2 (n = 13: 800 UI (gotas y GD3 (n = 8: 800 UI (comprimidos. Se midió 25OHD sérica (RIA-DIASORIN basal y a los 7, 28 y 45 días del estudio. Basalmente, 19 de las 21 mujeres presentaron niveles de deficiencia de 25(OHD (< 20 ng/ml: GD2: 14.0 ± 4.8 y GD3: 13.2 ± 4.9 (NS. Se observó en el día 7 un incremento del ~25% solo en GD3 y un aumento significativo al final del estudio en ambos grupos, sin alcanzar los valores adecuados de 25OHD (GD2: 17.4 ± 5.5 vs. GD3:22.9 ± 4.6 ng/ml p < 0.001. La administración por 45 días de 800 UI de vitamina D3 fue más efectiva que D2 para incrementar los niveles de 25OHD, aunque ambas fueron insuficientes para alcanzar niveles adecuados de 25OHD (= 30 ng/ml.
Richard G Moore
Full Text Available BACKGROUND: Numerous vitamin-D analogs exhibited poor response rates, high systemic toxicities and hypercalcemia in human trials to treat cancer. We identified the first non-hypercalcemic anti-cancer vitamin D analog MT19c by altering the A-ring of ergocalciferol. This study describes the therapeutic efficacy and mechanism of action of MT19c in both in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDING: Antitumor efficacy of MT19c was evaluated in ovarian cancer cell (SKOV-3 xenografts in nude mice and a syngenic rat ovarian cancer model. Serum calcium levels of MT19c or calcitriol treated animals were measured. In-silico molecular docking simulation and a cell based VDR reporter assay revealed MT19c-VDR interaction. Genomewide mRNA analysis of MT19c treated tumors identified drug targets which were verified by immunoblotting and microscopy. Quantification of cellular malonyl CoA was carried out by HPLC-MS. A binding study with PPAR-Y receptor was performed. MT19c reduced ovarian cancer growth in xenograft and syngeneic animal models without causing hypercalcemia or acute toxicity. MT19c is a weak vitamin-D receptor (VDR antagonist that disrupted the interaction between VDR and coactivator SRC2-3. Genome-wide mRNA analysis and western blot and microscopy of MT19c treated xenograft tumors showed inhibition of fatty acid synthase (FASN activity. MT19c reduced cellular levels of malonyl CoA in SKOV-3 cells and inhibited EGFR/phosphoinositol-3kinase (PI-3K activity independently of PPAR-gamma protein. SIGNIFICANCE: Antitumor effects of non-hypercalcemic agent MT19c provide a new approach to the design of vitamin-D based anticancer molecules and a rationale for developing MT19c as a therapeutic agent for malignant ovarian tumors by targeting oncogenic de novo lipogenesis.
Drori, Ariel; Shabat, Yehudit; Ben Ya'acov, Ami; Danay, Ofer; Levanon, Dan; Zolotarov, Lidya; Ilan, Yaron
Vitamin D has been known for its anti-inflammatory properties. Extracts derived from Lentinula edodes (Shiitake) edible mushroom exert an anti-inflammatory effect. These extracts contain high levels of ergosterol, which converts into ergocalciferol (vitamin D2) following exposure to ultraviolet light, followed by absorption and hydroxylation into the active form 25-hydroxyvitamin D [25(OH)D]. To determine the anti-inflammatory effect of overexpression of vitamin D in edible mushrooms, L. edodes mushrooms were exposed to ultraviolet-B light, freeze-dried, followed by measurement of vitamin D2 contents, in their dry weight. C57B1/6 mice were orally treated with vitamin D2-enriched or nonenriched mushroom extract prior and during concanavalin A-immune-mediated liver injury. Exposure to ultraviolet light increased vitamin D2 content in Shiitake edible mushrooms. Following feeding of vitamin D-enriched mushroom extracts to mice with immune-mediated hepatitis, a significant decrease in liver damage was noted. This was shown by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels, a decrease in proportion of mice with severe liver injury, and by improvement in liver histology. These effects were associated with a decrease in serum interferon gamma levels. A synergistic effect was noted between the anti-inflammatory effect of the mushroom extracts and that of vitamin D. Oral administration of vitamin D-enriched L. edodes edible mushroom exerts a synergistic anti-inflammatory effect in the immune-mediated hepatitis. The data support its potential use as safe immunomodulatory adjuvant for the treatment of HCV and nonalcoholic steatohepatitis.
Alshayeb, Hala M; Wall, Barry M; Showkat, Arif; Mangold, Therese; Quarles, L Darryl
25-Hydroxyvitamin D [25(OH)D] is a marker of nutritional status; however, chronic kidney disease (CKD) results in alterations in vitamin D metabolism, including the loss of vitamin D-binding proteins and alterations in CYP27B1 and CYP24 enzymes that metabolize 25(OH)D. This study was designed to determine the predictors of responsiveness to correction of vitamin D deficiency with oral vitamin D2 (ergocalciferol) in adults. A retrospective study of 183 veterans with 25(OH)D level vitamin D2, was performed. Logistic regression models were developed to determine the factors predicting the response to treatment, defined as either the change in serum 25(OH)D level/1000 IU of vitamin D2 or the number of vitamin D2 doses (50,000 IU per dose) administered. The mean age of the patients was 63 ± 12 years. About 87% were men and 51% diabetic, and 29% had an estimated glomerular filtration rate of vitamin D2 doses was 10.91 ± 5.95; the average increase in 25(OH)D level was 18 ± 10.80 ng/mL. 25(OH)D levels remained vitamin D2 treatment in logistic regression models. Patients with CKD required greater amounts of vitamin D2 to achieve similar increases in 25(OH)D levels, versus non-CKD patients. The presence of CKD and diabetes mellitus is associated with resistance to correction of 25(OH)D deficiency with vitamin D2 therapy. The underlying mechanism needs to be evaluated in prospective studies.
Burnett, Jason; Hochschild, Ann; Smith, Scott M.; Diamond, Pam; Stotts, Angela; Dyer, Carmel
Despite high mortality rates, elder self-neglect is characterized by refusal of medical and social interventions. To date there have been no tested clinical interventions in elders who self-neglect. Previous research from the TEAM Institute has shown significantly low vitamin D levels in this population. This study aimed to determine the feasibility of a clinical intervention. Replacement of vitamin D was chosen because of its ease of administration and favorable safety profile. Methods: A randomized clinical trial using directly observed therapy of vitamin D was conducted using 50 elders, >65 years of age, with Adult Protective Services (APS) validated self-neglect. A staggered intervention with waiting controls was used to maximize statistical power. One-third (n=17) of the group was administered 50,000 IU vitamin D2 (ergocalciferol) monthly and the remainder (n=33) were administered 400 IU monthly. Serum 25-OH vitamin D was assessed at baseline and 5-months. Results: 69% agreed to participate in the study and of those n=40 (80%) remained at 5-months. At baseline, 12% (n=7) were deficient in vitamin D (vitamin D levels (vitamin D level was 59 nmol/L +25 (mean SD), and increased significantly to 72nmol/L +21 nmol/L at 5-months. Conclusion: These data are the first to provide evidence that clinical interventions are feasible in elders who self-neglect. The increase in vitamin D levels confirmed that the study personnel were able to successfully intervene community-dwelling elders with self-neglect. This study sets the precedent for future intervention and prevention studies
Mykkanen, H.M.; Wasserman, R.H.
The uptake of selenite by purified brush border membrane vesicles isolated from duodena of rachitic or vitamin D-treated chicks was studied by using radioactive selenite and a rapid filtration technique. Cholecalciferol treatment (500 IU at 72 h) significantly enhanced selenite uptake, a response that decreased when the vesicles were stored at room temperature for 2.5 h prior to the uptake measurement. Preincubation of the vesicles in 1.0 mmol/L H2O2 reduced [75Se]selenite uptake, indicating the involvement of oxidizable groups in the uptake reaction. Iodoacetic acid (IAA), a sulfhydryl-blocking reagent, at 1-2 mmol/L concentration eliminated the difference in selenite uptake due to cholecalciferol and had no effect on vesicles from rachitic animals. A higher concentration of IAA (10 mmol/L) enhanced selenite uptake manyfold and increased the absolute difference due to cholecalciferol treatment. Single intravenous doses of 100 IU cholecalciferol, 100 IU ergocalciferol, or 0.1 micrograms 1,25-dihydroxycholecalciferol also stimulated selenite uptake, suggesting a general response to vitamin D compounds. Normal animals given a single dose of 1,25-dihydroxycholecalciferol 12 h prior to killing also responded. Treatments that enhanced the uptake of [75Se]selenite also increased the amount of membrane-bound sulfhydryl groups, suggesting the involvement of membrane-bound sulfhydryl groups in the vitamin D response. A significant increase in selenite uptake by intravenous 1,25-dihydroxycholecalciferol occurred within 10 min. This rapid effect provides a new tool to probe early biochemical effects of vitamin D on intestinal epithelium
Cashman, Kevin D; van den Heuvel, Ellen Ghm; Schoemaker, Ruud Jw; Prévéraud, Damien P; Macdonald, Helen M; Arcot, Jayashree
There is substantial evidence that the prevalence of vitamin D deficiency is unacceptably high in the population, and this requires action from a public health perspective. Circulating 25-hydroxyvitamin D [25(OH)D] is a robust and reliable marker of vitamin D status and has been used by numerous agencies in the establishment of vitamin D dietary requirements and for population surveillance of vitamin D deficiency or inadequacy. In a wider context, modeling of serum 25(OH)D data and its contributory sources, namely dietary vitamin D supply and UVB availability, can inform our understanding of population vitamin D status. The aim of this review is to provide the current status of knowledge in relation to modeling of such vitamin D-relevant data. We begin by highlighting the importance of the measurement of 25(OH)D and its standardization, both of which have led to new key data on the prevalence of vitamin D deficiency and inadequacy in North America and Europe. We then overview how state-of-the-art modeling can be used to inform our understanding of the potential effect of ergocalciferol and 25(OH)D on vitamin D intake estimates and how meteorological data on UVB availability, when coupled with other key data, can help predict population serum 25(OH)D concentration, even accounting for seasonal fluctuations, and lastly, how these in silico approaches can help inform policymakers on strategic options on addressing low vitamin D status through food-based approaches and supplementation. The potential of exemplar food-based solutions will be highlighted, as will the possibility of synergies between vitamin D and other dairy food-based micronutrients, in relation to vitamin D status and bone health. Lastly, we will briefly consider the interactions between season and vitamin D supplements on vitamin D status and health. © 2017 American Society for Nutrition.
Intesar N. Khelkal
Full Text Available An attempt has been made to determine the antimicrobial activity of vitamin D; D3 & D2 against clinical bacterial isolates as well as perform a comparative analytical study between the effects of both forms of vitamin. The ability of vitamin D (both D2 ergocalciferol& D3 cholecalciferol to inhibit bacterial growth of some clinical isolates have been tested . Forty - three pathogenic bacterial isolates (Gr+ ,Gr- have been identified from fifty - five specimen was collected from different sources ; 24 urine, 17 sputum , 9 blood , 5 skin at Al-Kindey hospital for a period of two months . Antibiotic sensitivity was carried out towards 12 different antibiotic discs. The most resistant isolates have been chosen to be tested in the study. Two bacterial suspensions of the selected isolates have been prepared; the first was adjusted to McFarland standard No. 0.5 (1 ×10 8 CFU /mL; the second = 1×1010 CFU /mL. Three concentrations of both vitamins have been prepared; 50,000, 70,000 and 90,000 IU/mL as well as the control ( solvent only . Antibacterial activity has been examined by using agar diffusion (pore plating method to determine the most effective concentration among the three concentrations of the two forms of vitamin D. Results were suggesting the important role of vitamin D specially D3 as antibacterial agent .The third concentration (90,000 IU/mL was causing the largest inhibition zone with all tested isolates even with the high turbidity culture (1010CFU/mL ,followed by the second one (70,000 IU/mL, the lower inhibitor concentration was (50,000 IU/mL. Significant differences have been appeared among the measurements of the diameters of inhibition zones towards three vitamin concentrations when compared one to another and to control.
Garbossa, Stefania Giuliana; Folli, Franco
Vitamin D is a key hormone involved in the regulation of calcium/phosphorous balance and recently it has been implicated in the pathogenesis of sub-inflammation, insulin resistance and obesity. The two main forms of vitamin D are cholecalciferol (Vitamin D3) and ergocalciferol (Vitamin D2): the active form (1,25-dihydroxyvitamin D) is the result of two hydroxylations that take place in liver, kidney, pancreas and immune cells. Vitamin D increases the production of some anti-inflammatory cytokines and reduces the release of some pro-inflammatory cytokines. Low levels of Vitamin D are also associated with an up-regulation of TLRs expression and a pro-inflammatory state. Regardless of the effect on inflammation, Vitamin D seems to directly increase insulin sensitivity and secretion, through different mechanisms. Considering the importance of low grade chronic inflammation in metabolic syndrome, obesity and diabetes, many authors hypothesized the involvement of this nutrient/hormone in the pathogenesis of these diseases. Vitamin D status could alter the balance between pro and anti-inflammatory cytokines and thus affect insulin action, lipid metabolism and adipose tissue function and structure. Numerous studies have shown that Vitamin D concentrations are inversely associated with pro-inflammatory markers, insulin resistance, glucose intolerance and obesity. Interestingly, some longitudinal trials suggested also an inverse association between vitamin D status and incident type 2 diabetes mellitus. However, vitamin D supplementation in humans showed controversial effects: with some studies demonstrating improvements in insulin sensitivity, glucose and lipid metabolism while others showing no beneficial effect on glycemic control and on inflammation. In conclusion, although the evidences of a significant role of Vitamin D on inflammation, insulin resistance and insulin secretion in the pathogenesis of obesity, metabolic syndrome and type 2 diabetes, its potential
Stuckey, Ashley; Brodsky, Alexander S; Fischer, Andrew; Miller, Daniel H; Hillenmeyer, Sara; Kim, Kyu K; Ritz, Anna; Singh, Rakesh K; Raphael, Benjamin J; Brard, Laurent
Ovarian cancer is the most deadly gynecological cancer with a very poor prognosis. Xenograft mouse models have proven to be one very useful tool in testing candidate therapeutic agents and gene function in vivo. In this study we identify genes and gene networks important for the efficacy of a pre-clinical anti-tumor therapeutic, MT19c. In order to understand how ovarian xenograft tumors may be growing and responding to anti-tumor therapeutics, we used genome-wide mRNA expression and DNA copy number measurements to identify key genes and pathways that may be critical for SKOV-3 xenograft tumor progression. We compared SKOV-3 xenografts treated with the ergocalciferol derived, MT19c, to untreated tumors collected at multiple time points. Cell viability assays were used to test the function of the PPARγ agonist, Rosiglitazone, on SKOV-3 cell growth. These data indicate that a number of known survival and growth pathways including Notch signaling and general apoptosis factors are differentially expressed in treated vs. untreated xenografts. As tumors grow, cell cycle and DNA replication genes show increased expression, consistent with faster growth. The steroid nuclear receptor, PPARγ, was significantly up-regulated in MT19c treated xenografts. Surprisingly, stimulation of PPARγ with Rosiglitazone reduced the efficacy of MT19c and cisplatin suggesting that PPARγ is regulating a survival pathway in SKOV-3 cells. To identify which genes may be important for tumor growth and treatment response, we observed that MT19c down-regulates some high copy number genes and stimulates expression of some low copy number genes suggesting that these genes are particularly important for SKOV-3 xenograft growth and survival. We have characterized the time dependent responses of ovarian xenograft tumors to the vitamin D analog, MT19c. Our results suggest that PPARγ promotes survival for some ovarian tumor cells. We propose that a combination of regulated expression and copy number
Navarro Valverde, Cristina; Quesada Gómez, José Manuel
Vitamin D is obtained mainly from ultraviolet irradiation of 7-dehydrocholesterol in the skin to form cholecalciferol (vitamin D3), and minimally from diet, unless vitamin D fortified food is taken, mainly enriched milk. In some countries, vitamin D is added to diet as ergocalciferol (vitamin D2). In the liver, vitamin D3 is hydroxylated to form 25-hydroxyvitamin D3 (marker of body nutritional status of vitamin D). Subsequently, in the kidney, 25OHD3 is hydroxylated to form 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). By VDR stimulation, (1,25)OH)2D3 controls calcium homeostasis and bone health and, what is more, many other cells and tissues including skin, muscle, cardiovascular and immune systems as well as glucose homeostasis. Thus, about 3% of the human genome is regulated by this hormone. Association and recent intervention studies describe beneficial effects on bone, cardiovascular disease, hypertension, diabetes mellitus type 2,colorectal cancer, breast cancer, multiple sclerosis, immune function inflammation etc. A minimum target for public health should be to achieve serum 25OHD levels above 20 ng/ml to ensure optimum status for bone health. However, levels above 30 ng/ml should be reached to achieve other health goals. Paradoxically, inadequacy (or even deficiency) in vitamin D levels is highly prevalent in children and youth in Spain. This deficit persists in adults, as well as in postmenopausal women (osteoporotic or not) and the elderly (especially amongst those institutionalized). Seasonal variation barely normalizes serum 25OHD levels after summer-autumn. Treated postmenopausal osteoporotic women also show high prevalence of inadequate levels of vitamin D, a major contributor to antiresortive treatments failure. A normalization of serum vitamin D enables diet to provide the calcium necessary to achieve a good bone health and an adequate response to antiresortive drugs. Given the difficulty to get adequate levels of vitamin D by UV irradiation and diet, a
Rice, Barbara L.; Zwart, Sara R.; Smith, Scott M.
Vitamin D deficiency has reemerged as a public health concern in the United States. It is also a concern for astronauts because spacecraft are shielded from ultraviolet light, leaving diet as the sole source of vitamin D. We report here the findings from four studies: one evaluation of astronauts before and after 4- to 6-month missions to the International Space Station, and the other three from a ground-based analog for space flight, long-term bed rest. For the space flight study, blood samples were collected before the flight and within hours of landing after it. Crewmembers (n = 11) were provided vitamin D supplements (as cholecalciferol (10 g/d) throughout the mission. The average number of vitamin D supplements reported to be consumed per week was 5.7 plus or minus 4.0. The vitamin D status indicator serum 25-hydroxycholecalciferol was 25% less after landing (48 plus or minus 20) than before flight (63 plus or minus 16) (P less than 0.01). A series of three studies was undertaken to evaluate nutritional changes during and after 60 or 90 days of -6 deg. head-down-tilt bed rest. A total of 11 subjects (8 M, 3 F; age 26-55 y) participated in the studies. Blood and urine were collected twice before bed rest and once per month during bed rest. During bed rest the average dietary intake of vitamin D for the three studies was 4.84 plus or minus 0.16 (study 1), 6.24 plus or minus 0.81 (study 2), and 7.16 plus or minus 1.40 (study 3) micrograms/day. In study 1 only, subjects were given a daily supplement of 10 g vitamin D (as ergocalciferol). Data were analyzed using repeated-measures ANOVA. In the first study, 7 days after the end of the bed rest, serum 25-hydroxycholecalciferol was 30% less than it was before bed rest (p less than 0.05). In the second and third studies, during or after bed rest the serum 25-hydroxycholecalciferol concentration was not significantly different from its concentration before bed rest. These data demonstrate that vitamin D intake is
Rueda, Angélica Maria Barba
Full Text Available Objetivos: Evidências publicadas sugerem que a suplementação da vitamina D pode ter efeito protetor nas infecções do trato respiratório inferior. O objetivo desta revisão foi avaliar os efeitos da ingestão de vitamina D na prevenção da bronquiolite viral aguda em crianças. Métodos: Foram feitas buscas nas bases de dados Medline, EMBASE, Web of Science, LILACS e Cochrane Central Register of Controlled Trials, até dezembro de 2014, usando os descritores "Vitamin D" ou cholecalciferol ou ergocalciferol e "bronchiolitis, viral" ou "viral bronchiolitis" ou "bronchiolitides, viral" ou "viral bronchiolitides". Foram incluídos estudos que avaliaram o efeito da ingesta da vitamina D na prevenção da bronquiolite viral aguda em crianças. Estudos com intervenção menor que duas semanas e artigos de revisão foram excluídos. Resultados: A busca identificou 241 artigos, entre os quais 20 artigos foram selecionados para leitura na íntegra e dois artigos foram incluídos na revisão sistemática, incluindo 296 crianças. Nenhum estudo mediu os níveis séricos de vitamina D. Um dos estudos incluídos foi um ensaio clinico, no qual o número de episódios de bronquiolite foi significativamente menor nas crianças suplementadas com vitamina D (Grupo I: média 0, 6±0, 7 Grupo II: média 1, 4 ±0, 9; P =0, 001. No outro, um estudo de casos e controles, não se encontrou relação significativa entre casos de bronquiolite viral aguda e ingesta de vitamina D (odds ratio 1, 7 intervalo de confiança 95% 0, 7 - 4, 0. Conclusões: As evidências científicas atuais são insuficientes para comprovar os benefícios clínicos da vitamina D na prevenção da bronquiolite viral aguda
Annweiler, Cedric; Drouet, Morgane; Duval, Guillaume T; Paré, Pierre-Yves; Leruez, Stephanie; Dinomais, Mickael; Milea, Dan
Vitamin D may be involved in ocular function in older adults, but there is no current consensus on a possible association between circulating concentrations of 25-hydroxyvitamin D (25OHD) and the occurrence of age-related macular degeneration (AMD). Our objective was to systematically review and quantitatively assess the association of circulating 25OHD concentration with AMD. A Medline search was conducted in November 2015, with no date limit, using the MeSH terms "Vitamin D" OR "Vitamin D deficiency" OR "Ergocalciferols" OR 'Cholecalciferol' combined with "Age-related macular degeneration" OR "Macular degeneration" OR "Retinal degeneration" OR "Macula lutea" OR "Retina". Fixed and random-effects meta-analyses were performed to compute (i) standard mean difference in 25OHD concentration between AMD and non-AMD patients; (ii) AMD risk according to circulating 25OHD concentration. Of the 243 retrieved studies, 11 observational studies-10 cross-sectional studies and 1 cohort study-met the selection criteria. The number of participants ranged from 65 to 17,045 (52-100% women), and the number with AMD ranged from 31 to 1440. Circulating 25OHD concentration was 15% lower in AMD compared with non-AMD on average. AMD was inversely associated with the highest 25OHD quintile compared with the lowest (summary odds ratio (OR)=0.83 [95%CI:0.71-0.97]), notably late AMD (summary OR=0.47 [95%CI:0.28-0.79]). Circulating 25OHD<50nmol/L was also associated with late-stage AMD (summary OR=2.18 [95%CI:1.34-3.56]), an association that did not persist when all categories of AMD were considered (summary OR=1.26 [95%CI:0.90-1.76]). In conclusion, this meta-analysis provides evidence that high 25OHD concentrations may be protective against AMD, and that 25OHD concentrations below 50nmol/L are associated with late AMD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
been recent publication comparing the immunity of patients with open clinical forms tuberculosis and without clinical symptoms, but ESAT6 - test-positive. One of the rational ways for helps to MTB - infected macrophages is the simultaneous use of urease inhibitors and simultaneously use selective activators of antibacterial complete phagocytosis. For the latter group, some authors include also histone deacetylase inhibitors (HDAi. The use of such inhibitors in the latter case will mass increase number reading frames in the macrophages genome and leads to stormy expression phagocytosis activators, that blocked by MBT. These inhibitors include valproic acid and trichostatin. Research in this area only started, and the expectations are very high. Another activator phagocytosis with very similar action mechanisms is the vitamin D3 - ergocalciferol. In a variety experiments shows that the soluble derivatives of vitamin D3 inoculation to the culture of MBT - infected macrophages leads to the completion phagocytosis and complete digestion of the MBT. The disadvantage of this method is the need to maintain a concentration of vitamin D3, which is quite toxic to the human body as a whole. Accordingly, a new form vitamin D3 is to be administered directly to the places where many infected macrophages, i.e. as an aerosol through the lungs. Also pay attention to the fact that, earlier for purpose combating tuberculosis the urease inhibitors have not been used, although quite a lot of well-known non-toxic compounds anti -urease activity. Thus, the most promising way to prevent tuberculosis reactivation in humans with positive test specimens and humans in remission following chemotherapy is to provide an aerosol preparation containing both urease inhibitor, activator phagocytosis vitamin D3 and histone deacetylase inhibitor. The use of such aerosol once a week will greatly reduce the number of macrophages with incomplete phagocytosis and prevent the background to tuberculosis with