MS Speaks

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

Elias S. Sotirchos, MD*, Pavan Bhargava, MD*, Christopher Eckstein, MD, Keith Van Haren, MD, Moira Baynes, RN, Achilles Ntranos, MD, Anne Gocke, PhD, Lawrence Steinman, MD, Ellen M. Mowry, MD, MCR and Peter A. Calabresi, MD

AFFILIATIONS:

From the Department of Neurology (E.S.S., P.B., M.B., A.N., A.G., E.M.M., P.A.C.), Johns Hopkins University School of Medicine, Baltimore, MD; Department of Neurology (C.E.), Duke University School of Medicine, Durham, NC; and Department of Neurology (K.V.H., L.S.), Stanford University School of Medicine, Palo Alto, CA.

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.