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Vitamins D2 and D3 exert differing effects on the human immune system.

Scientists have identified five forms of vitamin D, but the two primary forms relevant to human health are ergocalciferol, commonly referred to as vitamin D2 (produced by invertebrates), and cholecalciferol (produced by mammals), commonly referred to as vitamin D3. Prescription vitamin D supplements in the United States typically provide D2, but over-the-counter dietary supplements and fortified foods typically provide D3. Considerable controversy exists regarding the bioequivalence of D2 and D3. Findings from a recent study suggest that D2 and D3 exert differing effects on the human immune system.

Vitamin D modulates both innate and adaptive immune responses via its interactions with immune cells, including antigen presenting cells, B cells, and T cells. Evidence suggests that people with vitamin D deficiency are at greater risk of viral infection and autoimmune disorders. This is in keeping with the widely held belief that a principal role of vitamin D is to restrain, or balance, immune system activity.

The study was part of a previous randomized placebo-controlled trial involving healthy white European and South Asian females who received 15 micrograms (600 IU) of vitamin D2 or D3 every day for 12 weeks during the winter months, when sun exposure was limited. Participants also consumed vitamin D-fortified foods (orange juice and tea biscuits) daily. The investigators used microarray analysis to measure changes in 97 of the participants' blood transcriptome (the full range of RNA molecules an organism produces) and weighed the changes against any influence of ethnic background.

They found that while the effects of both D2 and D3 showed some overlap, the two forms of the vitamin showed distinct differences in terms of changes to gene expression. In particular, D3 switched off the activity of genes involved in the regulation of the innate and adaptive immune systems. The investigators posited that these changes could make the immune system more tolerant and therefore less likely to promote autoimmunity. They also noted that vitamin D3 (and not D2) had a dramatic effect on genes involved in activation of interferon, which plays important roles in providing protection against pathogens and cancer. The investigators' analysis revealed that some of the variation in overall gene expression was likely due to ethnic differences among the participants.

These findings suggest that vitamins D2 and D3 exert differing effects on the human immune system, with D3s effects modulating tolerance and immunoreactivity. They also may have relevant implications for supplementation with vitamin D.

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