Influence of Vitamin D Status and Vitamin D3 Supplementation on Genome Wide Expression of White Blood Cells: A Randomized Double-Blind Clinical Trial

Abstract

BackgroundAlthough there have been numerous observations of vitamin D deficiency and its links to chronic diseases, no studies have reported on how vitamin D status and vitamin D3 supplementation affects broad gene expression in humans. The objective of this study was to determine the effect of vitamin D status and subsequent vitamin D supplementation on broad gene expression in healthy adults. (Trial registration: ClinicalTrials.gov NCT01696409).Methods and FindingsA randomized, double-blind, single center pilot trial was conducted for comparing vitamin D supplementation with either 400 IUs (n = 3) or 2000 IUs (n = 5) vitamin D3 daily for 2 months on broad gene expression in the white blood cells collected from 8 healthy adults in the winter. Microarrays of the 16 buffy coats from eight subjects passed the quality control filters and normalized with the RMA method. Vitamin D3 supplementation that improved serum 25-hydroxyvitamin D concentrations was associated with at least a 1.5 fold alteration in the expression of 291 genes. There was a significant difference in the expression of 66 genes between subjects at baseline with vitamin D deficiency (25(OH)D<20 ng/ml) and subjects with a 25(OH)D>20 ng/ml. After vitamin D3 supplementation gene expression of these 66 genes was similar for both groups. Seventeen vitamin D-regulated genes with new candidate vitamin D response elements including TRIM27, CD83, COPB2, YRNA and CETN3 which have been shown to be important for transcriptional regulation, immune function, response to stress and DNA repair were identified.Conclusion/SignificanceOur data suggest that any improvement in vitamin D status will significantly affect expression of genes that have a wide variety of biologic functions of more than 160 pathways linked to cancer, autoimmune disorders and cardiovascular disease with have been associated with vitamin D deficiency. This study reveals for the first time molecular finger prints that help explain the nonskeletal health benefits of vitamin D.Trial RegistrationClinicalTrials.gov NCT01696409

Vitamin D supplementation guidelines

“…This ligand interacts with its receptor, RANK on monocytes lineage, inducing them to aggregate to form multinucleated osteoclasts (28)(29)(30). Mature osteoclasts, after binding on to bone surfaces, release collagenases and hydrochloric acid, leading to degradation of collagen and releasing calcium back into the micro-environment, and consequently release calcium and phosphorus into the bloodstream (28)(29)(30).…”

“…In evolutionary terms, vitamin D is one of the oldest hormones, that is also produced by some of the earliest phytoplankton life forms (33,34 It is known that the local production of 1,25(OH)2D followed by its binding to VDR is responsible for upregulation of approximately 2,000 genes that are involved in many metabolic pathways (29,33).…”

Vitamin D deficiency is an independent predictor of mortality in patients with chronic heart failure

“…Vitamin D, on the other hand, has multiple effects on the cardiovascular system [25] that might be especially pertinent to the heart failure syndrome [9,26,27].…”

Effect of a Randomised Controlled Vitamin D Trial on Insulin Resistance and Glucose Metabolism in Patients with Type 2 Diabetes Mellitus

“…Since β-cells express the VDR, some of their pathways involved in insulin secretion are subject to VD actions such as metabolic processing, stress response and DNA repair, as well as epigenetic regulations. These mechanisms have recently been elucidated by microarray analysis of buff y coat cells from a small randomised double-blind clinical trial using 2 000 IU VD/d [ 43 ] . Since vitamin D dosing appears to be safe in this population of preadipose and obese individuals higher VD doses are needed to optimise VD status in more than half of patients.…”