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Comment on the article by Allen et al. ‘A pilot study of the immunological effects of high-dose vitamin D in healthy volunteers’

There is increasing awareness that vitamin D might be beneficial in autoimmune diseases, like multiple sclerosis (MS), and that the effects are mediated via the immune system. In line with this theory Allan et al. recently performed a small vitamin D3 supplementation study to further support the potentially ameliorating immune modulating effects of vitamin D in MS.1 They report an increase in IL-10 production by peripheral blood mononuclear cells (PBMC), probably caused mainly by non T cells, and a decreased Thelper (Th)17 response. This study, however, included only four healthy controls, two males and two females. Obviously, these results might be used for identifying study endpoints and concomitant power calculations, both essential in the design of trials, but statistically this approach will be error prone. Interestingly, in recent years several small and uncontrolled vitamin D supplementation studies, which took into account state of the art immunological parameters, have been performed in MS.2–4 All of these studies are supplementation studies administering 10,000–20,000 IU vitamin D3 per day for 12 to 52 weeks. In agreement with Allan et al.1, Mosayebi et al.3 also reported an increase in IL-10 production by PBMC, while Smolders et al.4 even demonstrated higher percentages of IL-10 producing CD4+ T cells. Kimball et al.2 could not detect differences in IL-10 production after in vivo vitamin D supplementation in sera nor in supernatant after additional in vitro T cell activation. Th17 responses have only been investigated by Smolders et al. and here no effect on the proportion of IL-17+ CD4+ T cells could be shown. A second point of concern, which is shared by some of the previously mentioned vitamin D supplementation studies in MS, is the relatively short duration of the supplementation. Although a steady state in the vitamin D metabolism might be reached within 12 to 15 weeks,1,4 there is no evidence that a new equilibrium in immune homeostasis has been established by then. Currently at least two well powered placebo-controlled supplementation trials in MS patients are ongoing.5,6 Both trials share a long-term duration of supplementation of at least 18 months and have multiple clinical but also immunological outcome parameters. These studies will give us more reliable data with respect to the effects of vitamin D on the immune system. Furthermore, they will give us more information with regard to safety concerns of high dose vitamin D3 supplementation in autoimmune disease.