Cholecalciferol plus calcium suppresses abnormal PBMC reactivity in patients with multiple sclerosis

J Clin Endocrinol Metab. 2011 Sep;96(9):2826-34. doi: 10.1210/jc.2011-0325. Epub 2011 Jun 22.


Context: 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).

Design: This was an open-label, 12-month, randomized controlled trial.

Setting: Patients with MS were recruited from the MS Clinic at St. Michael's Hospital, Toronto.

Patients: 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).

Intervention: 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.

Main outcome measures: 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.

Interpretation: MS-associated, abnormal T cell reactivities were suppressed in vivo by cholecalciferol at serum 25(OH)D concentrations higher than 100 nmol/liter.

Trial registration: NCT00644904.

Publication types

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

MeSH terms

  • Adult
  • Calcium / administration & dosage
  • Calcium / blood
  • Calcium / therapeutic use*
  • Cholecalciferol / administration & dosage
  • Cholecalciferol / therapeutic use*
  • Cytokines / blood
  • Drug Administration Schedule
  • Female
  • Humans
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Lost to Follow-Up
  • Male
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Treatment Outcome
  • Vitamin D / blood
  • Vitamins / administration & dosage
  • Vitamins / therapeutic use*


  • Cytokines
  • Vitamins
  • Vitamin D
  • Cholecalciferol
  • Calcium

Associated data