A systematic review of randomized, double-blind, placebo-controlled trials examining the clinical efficacy of vitamin D in multiple sclerosis

Neuroepidemiology. 2013;40(3):147-53. doi: 10.1159/000345122. Epub 2012 Dec 18.


Background: An association between multiple sclerosis (MS) prevalence as well as MS mortality and vitamin D nutrition has led to the hypothesis that high levels of vitamin D could be beneficial for MS. The purpose of this systematic review is to establish whether there is evidence for or against vitamin D in the treatment of MS.

Methods: Systematic literature searches were performed to locate randomized, placebo-controlled, double-blind trials measuring the clinical effect of vitamin D on MS in human participants. Data were extracted in a standardized manner, and methodological quality was assessed by the Jadad score.

Results: Five trials were located that met the selection criteria. Of the 5 trials, 4 showed no effect of vitamin D on any outcome, and 1 showed a significant effect, namely by a reduction in the number of T1 enhancing lesions on brain magnetic resonance imaging. Three studies commented on adverse effects of vitamin D, with gastrointestinal adverse effects being the most frequently reported. The literature is limited by small study sizes (ranging from 23 to 68 patients), heterogeneity of dosing, form of vitamin D tested (vitamin D3 in 4 trials and vitamin D2 in 1) and clinical outcome measures. Therefore, a meta-analysis was not performed.

Conclusions: The evidence for vitamin D as a treatment for MS is inconclusive. Larger studies are warranted to assess the effect of vitamin D on clinical outcomes in patients with MS. We further encourage researchers to also test the effect of vitamin D on the health-related quality of life experienced by patients and their families.

Publication types

  • Research Support, N.I.H., Extramural
  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Double-Blind Method
  • Humans
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / epidemiology
  • Randomized Controlled Trials as Topic / methods
  • Treatment Outcome
  • Vitamin D / blood
  • Vitamin D / therapeutic use*


  • Vitamin D