Vitamin D in clinically isolated syndrome: evidence for possible neuroprotection

Eur J Neurol. 2016 Feb;23(2):327-32. doi: 10.1111/ene.12844. Epub 2015 Oct 31.


Background and purpose: Vitamin D status has been associated with inflammatory activity in multiple sclerosis (MS), but it is not known if it is associated with gray matter volume, the loss of which predicts long-term disability in MS. The association of vitamin D levels with brain volume measures and inflammatory activity in patients with clinically isolated syndrome (CIS) was investigated.

Methods: In the phase 2 CIS trial of atorvastatin, 25-hydroxyvitamin D levels were evaluated for their age-adjusted associations with normalized gray matter and brain parenchymal volumes on brain magnetic resonance imaging (MRI). The relationships between 25-hydroxyvitamin D levels and clinical and MRI measures of inflammatory activity were also assessed.

Results: In 65 patients in this substudy, each 25 nmol/l higher 25-hydroxyvitamin D level was associated with 7.8 ml higher gray matter volume (95% confidence interval 1.0, 14.6, P = 0.025). There was a tendency for an inverse association of average 25-hydroxyvitamin D levels and the composite end-point of ≥3 new brain T2 lesions or ≥1 relapse within a year (odds ratio per 25 nmol/l higher 25-hydroxyvitamin D level 0.66, 95% confidence interval 0.41, 1.08, P = 0.096).

Conclusions: Vitamin D status may impact neurodegeneration after CIS, although these results should be replicated in a second study. If confirmed in clinical trials, vitamin D supplementation may reduce long-term disability.

Keywords: demyelinating disease; epidemiology; magnetic resonance imaging; multiple sclerosis; neurodegenerative disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Clinical Trials, Phase II as Topic
  • Demyelinating Diseases / blood*
  • Demyelinating Diseases / pathology*
  • Female
  • Gray Matter / pathology*
  • Humans
  • Male
  • Middle Aged
  • Neuroprotection*
  • Randomized Controlled Trials as Topic
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood


  • Vitamin D
  • 25-hydroxyvitamin D