Influence of Vitamin D Status and Vitamin D<sub>3</sub> Supplementation on Genome Wide Expression of White Blood Cells: A Randomized Double-Blind Clinical Trial Hossein-nezhadArash SpiraAvrum F. HolickMichael 2013 <div><p>Background</p><p>Although 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 D<sub>3</sub> 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).</p> <p>Methods and Findings</p><p>A randomized, double-blind, single center pilot trial was conducted for comparing vitamin D supplementation with either 400 IUs (nā€Š=ā€Š3) or 2000 IUs (nā€Š=ā€Š5) vitamin D<sub>3</sub> 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 D<sub>3</sub> 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 D<sub>3</sub> 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.</p> <p>Conclusion/Significance</p><p>Our 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.</p> <p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT01696409" target="_blank">NCT01696409</a></p> </div>