Vitamins D2 and D3 Have Overlapping but Different Effects on Human Gene Expression Revealed Through Analysis of Blood Transcriptomes in a Randomised Double-Blind Placebo-Controlled Food-Fortification Trial

For the first time, we report the influence of vitamin D2 and vitamin D3 on genome-wide gene expression in whole blood from healthy women representing two ethnic groups, white European and South Asian. In this randomised placebo-controlled trial, participants were given daily physiological doses (15 g) of either vitamin D2 or D3 for 12 weeks and changes in the transcriptome were compared relative to the transcriptome at baseline. While there was some overlap in the repertoire of differentially expressed genes after supplementation with each vitamin D source, most changes were specific to either vitamin D3 or vitamin D2, suggesting that each form of the vitamin may have different effects on human physiology. Notably, following vitamin D3 supplementation, the majority of changes in gene expression reflected a down-regulation in the activity of genes, many encoding components of the innate and adaptive immune systems. These are consistent with the emerging concept that vitamin D orchestrates a shift in the immune system towards a more tolerogenic status. The profound differences in gene expression after supplementation with vitamin D2 compared with vitamin D3 warrant a more intensive investigation of the biological effects of the two forms of vitamin D on human physiology.