TY - JOUR
T1 - Safety and immunologic effects of high-vs low-dose cholecalciferol in multiple sclerosis
AU - Sotirchos, Elias S.
AU - Bhargava, Pavan
AU - Eckstein, Christopher
AU - Van Haren, Keith
AU - Baynes, Moira
AU - Ntranos, Achilles
AU - Gocke, Anne
AU - Steinman, Lawrence
AU - Mowry, Ellen M.
AU - Calabresi, Peter A.
N1 - Funding Information:
The Kenneth and Claudia Silverman Family Foundation and Montel Williams Foundation (P.A.C.); National Multiple Sclerosis Society Sylvia Lawry Physician Fellowship (FP-1787-A-1) (P.B.).
Publisher Copyright:
© 2015 American Academy of Neurology.
PY - 2016/1/26
Y1 - 2016/1/26
N2 - 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.
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.
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U2 - 10.1212/WNL.0000000000002316
DO - 10.1212/WNL.0000000000002316
M3 - Article
C2 - 26718578
AN - SCOPUS:84956835255
SN - 0028-3878
VL - 86
SP - 382
EP - 390
JO - Neurology
JF - Neurology
IS - 4
ER -