Safety and T Cell Modulating Effects of High Dose Vitamin D3 Supplementation in Multiple Sclerosis

Background: A poor vitamin D status has been associated with a high disease activity of multiple sclerosis (MS). Recently, we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS (RRMS) patients. In the present study, we studied the effects of high dose vitamin D-3 supplementation on safety and T cell related outcome measures. Methodology/Principal Findings: Fifteen RRMS patients were supplemented with 20 000 IU/d vitamin D-3 for 12 weeks. Vitamin D and calcium metabolism were carefully monitored, and T cell characteristics were studied by flowcytometry. All patients finished the protocol without side-effects, hypercalcaemia, or hypercalciuria. The median vitamin D status increased from 50 nmol/L (31-175) at week 0 to 380 nmol/L (151-535) at week 12 (P<0.001). During the study, 1 patient experienced an exacerbation of MS and was censored from the T cell analysis. The proportions of (naive and memory) CD4(+) Tregs remained unaffected. Although Treg suppressive function improved in several subjects, this effect was not significant in the total cohort (P=0.143). An increased proportion of IL-10(+) CD4(+) T cells was found after supplementation (P=0.021). Additionally, a decrease of the ratio between IFN-gamma(+) and IL-4(+) CD4(+) T cells was observed (P=0.035). Conclusion/Significance: Twelve week supplementation of high dose vitamin D-3 in RRMS patients was well tolerated and did not induce decompensation of calcium metabolism. The skewing towards an anti-inflammatory cytokine profile supports the evidence on vitamin D as an immune-modulator, and may be used as outcome measure for upcoming randomized placebo-controlled trials.