title: Vitamin D in clinically isolated syndrome: evidence for possible neuroprotection.
abstract: OBJECTIVE
  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.
authors.affiliation: Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Mowry
authors.affiliation: Neurology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: D
authors.initials: D
authors.lastname: Pelletier
authors.affiliation: Immune Tolerance Network, Bethesda, MD, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Immune Tolerance Network, Bethesda, MD, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Howell
authors.affiliation: Neurology, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Zamvil
authors.affiliation: Neurology, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Waubant
mesh_terms: D000328:Adult; D017322:Clinical Trials, Phase II as Topic; D003711:Demyelinating Diseases / Q000097:blood* / Q000473:pathology*; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000066829:Neuroprotection; D016032:Randomized Controlled Trials as Topic; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: demyelinating disease; epidemiology; magnetic resonance imaging; multiple sclerosis; neurodegenerative disorders