Vitamin D levels and risk of multiple sclerosis in patients with clinically isolated syndromes

Mult Scler. 2014 Feb;20(2):147-55. doi: 10.1177/1352458513494959. Epub 2013 Jul 8.


Background: Growing evidence suggests that vitamin D deficiency may be one of the most important environmental factors for the development of multiple sclerosis (MS).

Objectives: The objectives of this paper are to evaluate serum 25-hydroxyvitamin D (25(OH)D) levels in patients with clinically isolated syndromes (CIS) and to examine whether they are related to MS risk.

Methods: This is a retrospective study of 100 CIS patients hospitalized from 2000 to 2009 at San Raffaele Hospital, Milan, Italy. We evaluated baseline 25(OH)D level as well as clinical, brain magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) data.

Results: A total of 52% of CIS patients had vitamin D deficiency (25(OH)D < 50 nmol/l). During follow-up (median: 7.17 years), 55 patients developed clinically definite MS (CDMS). Patients with very low (< 10th percentile) and low (< 25th percentile) 25(OH)D levels were particularly at risk of CDMS (HRs (95% CIs): 2.12 (0.91-4.96) and 1.61 (0.85-3.03), respectively), while no further reduction in the HRs of disease was observed at high levels of 25(OH)D. This association was even stronger after adjustment for additional risk factors for CDMS development (HRs (95% CIs) for 25(OH)D levels < 10th and 25th percentiles: 3.34 (1.32-8.45) and 2.04 (0.96-4.36), respectively).

Conclusion: Low serum vitamin D is associated with increased MS risk in patients with CIS.

Keywords: Multiple sclerosis; natural history studies; risk factors in epidemiology; vitamin D.

MeSH terms

  • Adolescent
  • Adult
  • Demyelinating Diseases / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / etiology
  • Retrospective Studies
  • Risk Factors
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / epidemiology*
  • Vitamins / blood*
  • Young Adult


  • Vitamins
  • Vitamin D
  • 25-hydroxyvitamin D