PT  - JOURNAL ARTICLE
AU  - Elias S. Sotirchos
AU  - Pavan Bhargava
AU  - Christopher Eckstein
AU  - Keith Van Haren
AU  - Moira Baynes
AU  - Achilles Ntranos
AU  - Anne Gocke
AU  - Lawrence Steinman
AU  - Ellen M. Mowry
AU  - Peter A. Calabresi
TI  - Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis
AID  - 10.1212/WNL.0000000000002316
DP  - 2016 Jan 26
TA  - Neurology
PG  - 382--390
VI  - 86
IP  - 4
4099  - http://n.neurology.org/content/86/4/382.short
4100  - http://n.neurology.org/content/86/4/382.full
SO  - Neurology2016 Jan 26; 86
AB  - 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.25(OH)D=25-hydroxyvitamin D; CI=confidence interval; EAE=experimental autoimmune encephalitis; IFN=interferon; IL=interleukin; IND=investigational new drug application; LOWESS=locally weighted scatterplot smoothing; MHC=major histocompatibility complex; MS=multiple sclerosis; PBMC=peripheral blood mononuclear cells