title: Cholecalciferol plus calcium suppresses abnormal PBMC reactivity in patients with multiple sclerosis.
abstract: BACKGROUND
  The active metabolite of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)(2)D], is a potent modulator of immune cells in vitro.
  
  
  OBJECTIVE
  Our objective was to determine whether the sun-dependent nutrient, cholecalciferol, can alter disease-associated cellular immune abnormalities in patients with multiple sclerosis (MS).
  
  
  METHODS
  This was an open-label, 12-month, randomized controlled trial.
  
  
  METHODS
  Patients with MS were recruited from the MS Clinic at St. Michael's Hospital, Toronto.
  
  
  METHODS
  Forty-nine patients were matched (for age, sex, disease duration, disease-modifying drug, and disability) and enrolled (treated n = 25; control n = 24). Four patients were lost to follow-up (n = 2 from each group).
  
  
  METHODS
  Treated patients received increasing doses of cholecalciferol (4,000-40,000 IU/d) plus calcium (1200 mg/d), followed by equilibration to a moderate, physiological intake (10,000 IU/d). Control patients did not receive supplements.
  
  
  METHODS
  At enrollment and at 12 months, peripheral blood mononuclear cell (PBMC) proliferative responses to disease-associated, MS-relevant, and control antigens were measured, along with selected serum biochemical markers.
  
  
  RESULTS
  At 12 months, mean serum 25-hydroxyvitamin D [25(OH)D] concentrations were 83 ± 35 nmol/liter and 179 ± 76 nmol/liter in control and treated participants, respectively (paired t, P < 0.001). Serum 1,25(OH)(2)D did not differ between baseline and 1 yr. In treated patients, 12-month PBMC proliferative responses to neuron antigens myelin basic protein and exon-2 were suppressed (P = 0.002). In controls, there were no significant changes in disease-associated PBMC responsiveness. There were no significant differences between groups in levels of selected biomarkers.
  
  
  CONCLUSIONS
  MS-associated, abnormal T cell reactivities were suppressed in vivo by cholecalciferol at serum 25(OH)D concentrations higher than 100 nmol/liter.
authors.affiliation: Departments of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada. samantha.kimball@utoronto.ca
authors.forename: Samantha
authors.initials: S
authors.lastname: Kimball
authors.forename: Reinhold
authors.initials: R
authors.lastname: Vieth
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Dosch
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.forename: Roy
authors.initials: R
authors.lastname: Cheung
authors.forename: Donald
authors.initials: D
authors.lastname: Gagne
authors.forename: Paul
authors.initials: P
authors.lastname: O'Connor
authors.forename: Cheryl
authors.initials: C
authors.lastname: D'Souza
authors.forename: Melanie
authors.initials: M
authors.lastname: Ursell
authors.forename: Jodie M
authors.initials: JM
authors.lastname: Burton
mesh_terms: D000328:Adult; D002118:Calcium / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D002762:Cholecalciferol / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D059012:Lost to Follow-Up; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome; D014807:Vitamin D / Q000097:blood; D014815:Vitamins / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D014815:Vitamins; D014807:Vitamin D; D002762:Cholecalciferol; D002118:Calcium