Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis
Joost Smolders, Evelyn Peelen, Mariëlle Thewissen, Jan Willem Cohen Tervaert, Paul Menheere, Raymond Hupperts, Jan Damoiseaux, Joost Smolders, Evelyn Peelen, Mariëlle Thewissen, Jan Willem Cohen Tervaert, Paul Menheere, Raymond Hupperts, Jan Damoiseaux
Abstract
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 D3 supplementation on safety and T cell related outcome measures.
Methodology/principal findings: Fifteen RRMS patients were supplemented with 20,000 IU/d vitamin D3 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 (naïve 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-γ+ and IL-4+ CD4+ T cells was observed (P=0.035).
Conclusion/significance: Twelve week supplementation of high dose vitamin D3 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.
Trial registration: Clinicaltrials.gov NCT00940719.
Conflict of interest statement
Competing Interests: Joost Smolders received consultancy fee from Merck Serono, and received funding for travelling from Biogen Idec; Raymond Hupperts receives on a regular basis consultancy fees from Bayer Schering, Merck Serono, Biogen Idec and TEVA Aventis. This does not alter the authors' adherence to all the PLoS One policies on sharing data and materials.
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