Vitamin D3

Cholecalciferol is a naturally occuring form of vitamin D. Reported that upon metabolic activation, Cholecalciferol induces cell differentiation and prevents proliferation of cancer cells.

Effects of calcium and vitamin D3 on transforming growth factors in rectal mucosa of sporadic colorectal adenoma patients: a randomized controlled trial.[Pubmed:24166893]

Mol Carcinog. 2015 Apr;54(4):270-80.

Transforming growth factor alpha (TGFalpha) and TGFbeta1 are growth-promoting and -inhibiting autocrine/paracrine growth factors, respectively, that may (1) affect risk for colorectal cancer and (2) be modifiable by anti-proliferative exposures. The effects of supplemental calcium and Vitamin D3 on these two markers in the normal-appearing colorectal mucosa in humans are unknown. We conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial (n = 92; 23/treatment group) of calcium 2 g and/or Vitamin D3 800 IU/d versus placebo over 6 mo. TGFalpha and TGFbeta1 expression was measured in biopsies of normal-appearing rectal mucosa using automated immunohistochemistry and quantitative image analysis at baseline and 6-mo follow-up. In the calcium, Vitamin D3 , and calcium plus Vitamin D3 groups relative to the placebo group (1) the mean overall expression of TGFbeta1 increased by 14% (P= 0.25), 19% (P = 0.17), and 22% (P = 0.09); (2) the ratio of TGFalpha expression in the upper 40% (differentiation zone) to that in the lower 60 (proliferation zone) of the crypts decreased by 34% (P = 0.11), 31% (P = 0.22), and 26% (P = 0.33); and (3) the TGFalpha/TGFbeta1 ratio in the upper 40% of the crypts decreased by 28% (P = 0.09), 14% (P = 0.41), and 22% (P = 0.24), respectively. These preliminary results, although not statistically significant, suggest that supplemental calcium and Vitamin D3 may increase TGFbeta1 expression and shift TGFalpha expression downward from the differentiation to the proliferation zone in the crypts in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, and support further investigation in a larger clinical trial.

Dissecting high from low responders in a vitamin D3 intervention study.[Pubmed:25448738]

J Steroid Biochem Mol Biol. 2015 Apr;148:275-82.

Vitamin D3 is a pleiotropic signaling molecule that has via activation of the transcription factor vitamin D receptor (VDR) a direct effect on the expression of more than 100 genes. The aim of this study was to find transcriptomic and clinical biomarkers that are most suited to identify Vitamin D3 responders within 71 pre-diabetic subjects during a 5-month intervention study (VitDmet). In hematopoietic cells, the genes ASAP2, CAMP, CD14, CD97, DUSP10, G0S2, IL8, LRRC8A, NINJ1, NRIP1, SLC37A2 and THBD are known as primary vitamin D targets. We demonstrate that each of these 12 genes carries a conserved VDR binding site within its genomic region and is expressed in human peripheral blood mononuclear cells (PBMCs). The changes in the expression of these genes in human PBMCs at the start and the end of the vitamin D-intervention were systematically correlated with the alteration in the circulating form of Vitamin D3, 25-hydroxyVitamin D3 (25(OH)D3). Only 39-44 (55-62%) of the study subjects showed a highly significant response to Vitamin D3, i.e., we considered them as "responders". In comparison, we found for 37-53 (52-75%) of the participants that only 12 biochemical and clinical parameters, such as concentrations of parathyroid hormone (PTH) and insulin, or computed values, such as homeostatic model assessment and insulin sensitivity index, show a correlation with serum 25(OH)D3 levels that is as high as that of the selected VDR target genes. All 24 parameters together described the pleiotropic vitamin D response of the VitDmet study subjects. Interestingly, they demonstrated a number of additional correlations that define a network, in which PTH plays the central role. In conclusion, Vitamin D3-induced changes in human PBMCs can be described by transcriptomic and serum biomarkers and allow a segregation into high and low responders. This article is part of a Special Issue entitled '17th Vitamin D Workshop' .

Vitamin D3 increases in abdominal subcutaneous fat tissue after supplementation with vitamin D3.[Pubmed:25661743]

Eur J Endocrinol. 2015 Mar;172(3):235-41.

OBJECTIVE: The objective was to assess the amount of Vitamin D3 stored in adipose tissue after long-term supplementation with high dose Vitamin D3. DESIGN: A cross-sectional study on 29 subjects with impaired glucose tolerance who had participated in a randomized controlled trial with Vitamin D3 20 000 IU (500 mug) per week vs placebo for 3-5 years. METHODS: Abdominal subcutaneous fat tissue was obtained by needle biopsy for the measurements of Vitamin D3 and 25-hydroxyVitamin D3 (25(OH)D3). Body fat was measured with dual-energy X-ray absorptiometry, and serum 25(OH)D3 level was quantified. RESULTS: In the subjects given Vitamin D3, the median concentrations of serum 25(OH)D3, fat Vitamin D3, and fat 25(OH)D3 were 99 nmol/l, 209 ng/g, and 3.8 ng/g, respectively; and correspondingly in the placebo group 62 nmol/l, 32 ng/g, and 2.5 ng/g. If assuming an equal amount of Vitamin D3 stored in all adipose tissue in the body, the median body store was 6.6 mg Vitamin D3 and 0.12 mg 25(OH)D3 in those given Vitamin D3. CONCLUSIONS: Subcutaneous adipose tissue may store large amounts of Vitamin D3. The clinical importance of this storage needs to be determined.

Development of a validated UPLC method for simultaneous estimation of both free and entrapped (in solid lipid nanoparticles) all-trans retinoic acid and cholecalciferol (vitamin D3) and its pharmacokinetic applicability in rats.[Pubmed:24440824]

J Pharm Biomed Anal. 2014 Mar;91:73-80.

A sensitive ultra-performance liquid chromatography (UPLC) method was developed for simultaneous estimation of all-trans retinoic acid (ATRA) and cholecalciferol (Vitamin D3) in rat plasma. The method was validated over the linear range of 1.0-5000ng/ml (r(2)=0.999) for both vitamins with a limit of detection of 0.5ng/ml. Chromatographic separation was achieved using liquid-liquid extraction (LLE) on an Acquity BEH RP 18 column (2.1mmx50mm, I.D. 1.7mum), with mobile phase comprising of acetonitrile:methanol:water (90:8:2, v/v/v), at a flow rate of 0.20ml/min and a total run time of 5min. Intra and inter-day variability (RSD) was Vitamin D3. High recovery of >/=96.0% for ATRA and >/=87.80% for Vitamin D3 was achieved. ATRA and Vitamin D3 were stable in plasma under different storage and processing conditions. The method was applied to estimate the total drug content and entrapment efficiency of ATRA and Vitamin D3 loaded solid lipid nanoparticles (SLNs). Concentration of these two agents was determined in rat plasma after simultaneous subcutaneous administration in free form or when loaded into SLNs thus establishing pharmacokinetic application of the developed procedure. Results indicated an improvement in AUC0-infinity by 5.4 times and 29.4 times for ATRA and Vitamin D3, respectively, upon their incorporation into SLNs. Simultaneous administration of these two vitamins and their improved and prolonged bioavailability has scope for their use in treatment and control of tuberculosis.

Vitamin D and systemic lupus erythematosus: bones, muscles, and joints.[Pubmed:20429045]

Curr Rheumatol Rep. 2010 Aug;12(4):259-63.

Vitamin D3, or cholecalciferol, is the naturally occurring form of vitamin D that is converted in the skin and hydroxylated in the liver and kidney to the active form found in humans. The main role for vitamin D is calcium homeostasis, and low levels of vitamin D result in lower gastrointestinal absorption of calcium. Vitamin D is also critical for mineralization of bone tissue, muscle function, and coordination. Recent studies have found prevention of bone mass loss and reduction in falls and fractures in patients supplemented with vitamin D. A high percentage of systemic lupus erythematosus patients are reported to have insufficient or deficient levels of vitamin D. This paper reviews the biology of vitamin D, its role in calcium homeostasis, and how it contributes to the maintenance of bone, muscle, and joint function in older adults and individuals with systemic lupus erythematosus.

Vitamin D-3 receptor as a target for breast cancer prevention.[Pubmed:12840219]

J Nutr. 2003 Jul;133(7 Suppl):2425S-2433S.

The vitamin D-3 receptor (VDR) is a nuclear receptor that modulates gene expression when complexed with its ligand 1-alpha,25-dihydroxycholecalciferol [1,25(OH)(2)-D(3)], which is the biologically active form of vitamin D-3. The cellular effects of VDR signaling include growth arrest, differentiation and/or induction of apoptosis, which indicate that the vitamin D pathway participates in negative-growth regulation. Although much attention has been directed in recent years toward the development of synthetic vitamin D analogs as therapeutic agents for a variety of human cancers including those derived from the mammary gland, studies on vitamin D as a chemopreventive agent for breast cancer have been quite limited. The VDR is expressed in normal mammary gland, where it functions to oppose estrogen-driven proliferation and maintain differentiation; this suggests that 1,25(OH)(2)-D(3) participates in negative-growth regulation of mammary epithelial cells. Furthermore, preclinical studies show that vitamin D compounds can reduce breast cancer development in animals, and human data indicate that both vitamin D status and genetic variations in the VDR may affect breast cancer risk. Collectively, findings from cellular, molecular and population studies suggest that the VDR is a nutritionally modulated growth-regulatory gene that may represent a molecular target for chemoprevention of breast cancer.

Cholecalciferol(Vitamin D3) is a naturally occuring form of vitamin D; Reported that upon metabolic activation, Cholecalciferol induces cell differentiation and prevents proliferation of cancer cells.

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