Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis

Neurology. 2016 Jan 26;86(4):382-90. doi: 10.1212/WNL.0000000000002316. Epub 2015 Dec 30.

Abstract

Objective: To study the safety profile and characterize the immunologic effects of high- vs low-dose cholecalciferol supplementation in patients with multiple sclerosis (MS).

Methods: In this double-blind, single-center randomized pilot study, 40 patients with relapsing-remitting MS were randomized to receive 10,400 IU or 800 IU cholecalciferol daily for 6 months. Assessments were performed at baseline and 3 and 6 months.

Results: Mean increase of 25-hydroxyvitamin D levels from baseline to final visit was larger in the high-dose group (34.9 ng/mL; 95% confidence interval [CI] 25.0-44.7 ng/mL) than in the low-dose group (6.9 ng/mL; 95% CI 1.0-13.7 ng/mL). Adverse events were minor and did not differ between the 2 groups. Two relapses occurred, one in each treatment arm. In the high-dose group, we found a reduction in the proportion of interleukin-17(+)CD4(+) T cells (p = 0.016), CD161(+)CD4(+) T cells (p = 0.03), and effector memory CD4(+) T cells (p = 0.021) with a concomitant increase in the proportion of central memory CD4(+) T cells (p = 0.018) and naive CD4(+) T cells (p = 0.04). These effects were not observed in the low-dose group.

Conclusions: Cholecalciferol supplementation with 10,400 IU daily is safe and tolerable in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects in MS, which include reduction of interleukin-17 production by CD4(+) T cells and decreased proportion of effector memory CD4(+) T cells with concomitant increase in central memory CD4(+) T cells and naive CD4(+) T cells.

Classification of evidence: This study provides Class I evidence that cholecalciferol supplementation with 10,400 IU daily is safe and well-tolerated in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects.

Publication types

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

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cholecalciferol* / administration & dosage
  • Cholecalciferol* / adverse effects
  • Cholecalciferol* / pharmacology
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Humans
  • Immunologic Factors* / administration & dosage
  • Immunologic Factors* / adverse effects
  • Immunologic Factors* / pharmacology
  • Interleukin-17 / metabolism*
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Pilot Projects
  • Treatment Outcome
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood

Substances

  • IL17A protein, human
  • Immunologic Factors
  • Interleukin-17
  • Vitamin D
  • Cholecalciferol
  • 25-hydroxyvitamin D