Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis.

• Main Authors: Joost Smolders, Evelyn Peelen, Mariëlle Thewissen, Jan Willem Cohen Tervaert, Paul Menheere, Raymond Hupperts, Jan Damoiseaux
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2010-12-01
• Series: PLoS ONE
• Online Access: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21179201/?tool=EBI

<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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).<h4>Conclusion/significance</h4>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.<h4>Trial registration</h4>Clinicaltrials.gov NCT00940719.