title: Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis.
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.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Elias S
authors.initials: ES
authors.lastname: Sotirchos
authors.affiliation: 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.
authors.forename: Pavan
authors.initials: P
authors.lastname: Bhargava
authors.affiliation: 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.
authors.forename: Christopher
authors.initials: C
authors.lastname: Eckstein
authors.affiliation: 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.
authors.forename: Keith
authors.initials: K
authors.lastname: Van Haren
authors.affiliation: 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.
authors.forename: Moira
authors.initials: M
authors.lastname: Baynes
authors.affiliation: 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.
authors.forename: Achilles
authors.initials: A
authors.lastname: Ntranos
authors.affiliation: 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.
authors.forename: Anne
authors.initials: A
authors.lastname: Gocke
authors.affiliation: 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.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Steinman
authors.affiliation: 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.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Mowry
authors.affiliation: 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. calabresi@jhmi.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002762:Cholecalciferol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D020381:Interleukin-17 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology*; D010865:Pilot Projects; D016896:Treatment Outcome; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: C508717:IL17A protein, human; D007155:Immunologic Factors; D020381:Interleukin-17; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D