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

PLoS One. 2010 Dec 13;5(12):e15235. doi: 10.1371/journal.pone.0015235.


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: NCT00940719.

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / cytology
  • Cholecalciferol / metabolism*
  • Cholecalciferol / therapeutic use
  • Dietary Supplements
  • Female
  • Flow Cytometry / methods
  • Humans
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / metabolism*
  • T-Lymphocytes / cytology*
  • Treatment Outcome
  • Vitamin D / metabolism


  • Interleukin-10
  • Vitamin D
  • Cholecalciferol
  • Interferon-gamma

Associated data