Background: An association between multiple sclerosis (MS) prevalence as well as MS mortality and vitamin D nutrition has led to the hypothesis that high levels of vitamin D could be beneficial for MS. The purpose of this systematic review is to establish whether there is evidence for or against vitamin D in the treatment of MS. Methods: Systematic literature searches were performed to locate randomized, placebo-controlled, double-blind trials measuring the clinical effect of vitamin D on MS in human participants. Data were extracted in a standardized manner, and methodological quality was assessed by the Jadad score. Results: Five trials were located that met the selection criteria. Of the 5 trials, 4 showed no effect of vitamin D on any outcome, and 1 showed a significant effect, namely by a reduction in the number of T1 enhancing lesions on brain magnetic resonance imaging. Three studies commented on adverse effects of vitamin D, with gastrointestinal adverse effects being the most frequently reported. The literature is limited by small study sizes (ranging from 23 to 68 patients), heterogeneity of dosing, form of vitamin D tested (vitamin D3 in 4 trials and vitamin D2 in 1) and clinical outcome measures. Therefore, a meta-analysis was not performed. Conclusions: The evidence for vitamin D as a treatment for MS is inconclusive. Larger studies are warranted to assess the effect of vitamin D on clinical outcomes in patients with MS. We further encourage researchers to also test the effect of vitamin D on the health-related quality of life experienced by patients and their families.

1.
Pugliatti M, Sotgiu S, Rosati G: The worldwide prevalence of multiple sclerosis. Clin Neurol Neurosurg 2002;104:182–191.
2.
Benito-Leon J, Martin E, Vela L, Villar ME, Felgueroso B, Marrero C, Guerrero A, Ruiz-Galiana J: Multiple sclerosis in Mostoles, central Spain. Acta Neurol Scand 1998;98:238–242.
3.
Benito-Leon J: Multiple sclerosis: is prevalence rising and if so why? Neuroepidemiology 2011;37:236–237.
4.
Poser CM, Brinar VV: The accuracy of prevalence rates of multiple sclerosis: a critical review. Neuroepidemiology 2007;29:150–155.
5.
Benito-Leon J, Morales JM, Rivera-Navarro J, Mitchell A: A review about the impact of multiple sclerosis on health-related quality of life. Disabil Rehabil 2003;25:1291–1303.
6.
Mitchell AJ, Benito-Leon J, Gonzalez JM, Rivera-Navarro J: Quality of life and its assessment in multiple sclerosis: integrating physical and psychological components of wellbeing. Lancet Neurol 2005;4:556–566.
7.
Rivera-Navarro J, Benito-Leon J, Oreja-Guevara C, Pardo J, Dib WB, Orts E, Bello M; Caregiver Quality of Life in Multiple Sclerosis (CAREQOL-MS) Study Group: Burden and health-related quality of life of Spanish caregivers of persons with multiple sclerosis. Mult Scler 2009;15:1347–1355.
8.
Benito-Leon J, Rivera-Navarro J, Guerrero AL, de Las Heras V, Balseiro J, Rodriguez E, Bello M, Martinez-Martin P; Caregiver Quality of Life in Multiple Sclerosis (CAREQOL-MS) Study Group: The CAREQOL-MS was a useful instrument to measure caregiver quality of life in multiple sclerosis. J Clin Epidemiol 2011;64:675–686.
9.
Benito-Leon J, Mitchell AJ, Rivera-Navarro J, Morales-Gonzalez JM: Impaired health-related quality of life predicts progression of disability in multiple sclerosis. Eur J Neurol 2012, DOI: 10.1111/j.1468-1331.2012.03792.x.
10.
Benito-Leon J, Martinez-Martin P: Health-related quality of life in multiple sclerosis (in Spanish). Neurologia 2003;18:210–217.
11.
Rivera-Navarro J, Benito-Leon J: The social dimension of the quality of life in multiple sclerosis (in Spanish). Rev Neurol 2011;52:127, author reply 127–128.
12.
Rivera-Navarro J, Benito-Leon J, Morales-Gonzalez JM: Searching for more specific dimensions for the measurement of quality of life in multiple sclerosis (in Spanish). Rev Neurol 2001;32:705–713.
13.
Rivera-Navarro J, Morales-Gonzalez JM, Benito-Leon J; Madrid Demyelinating Diseases Group (GEDMA): Informal caregiving in multiple sclerosis patients: data from the Madrid Demyelinating Disease Group study. Disabil Rehabil 2003;25:1057–1064.
14.
Benito-Leon J, Morales JM, Rivera-Navarro J: Health-related quality of life and its relationship to cognitive and emotional functioning in multiple sclerosis patients. Eur J Neurol 2002;9:497–502.
15.
Ascherio A, Munger KL: Epstein-Barr virus infection and multiple sclerosis: a review. J Neuroimmune Pharmacol 2010;5:271–277.
16.
Benito-Leon J, Pisa D, Alonso R, Calleja P, Diaz-Sanchez M, Carrasco L: Association between multiple sclerosis and candida species: evidence from a case-control study. Eur J Clin Microbiol Infect Dis 2010;29:1139–1145.
17.
Ho SL, Alappat L, Awad AB: Vitamin D and multiple sclerosis. Crit Rev Food Sci Nutr 2012;52:980–987.
18.
Holick MF: Vitamin D deficiency. N Engl J Med 2007;357:266–281.
19.
Stroud ML, Stilgoe S, Stott VE, Alhabian O, Salman K: Vitamin D – a review. Aust Fam Physician 2008;37:1002–1005.
20.
Saltyte Benth J, Myhr KM, Loken-Amsrud KI, Beiske AG, Bjerve KS, Hovdal H, Midgard R, Holmoy T: Modelling and prediction of 25-hydroxyvitamin D levels in Norwegian relapsing-remitting multiple sclerosis patients. Neuroepidemiology 2012;39:84–93.
21.
Ascherio A, Munger KL, Simon KC: Vitamin D and multiple sclerosis. Lancet Neurol 2010;9:599–612.
22.
McDowell TY, Amr S, Culpepper WJ, Langenberg P, Royal W, Bever C, Bradham DD: Sun exposure, vitamin D and age at disease onset in relapsing multiple sclerosis. Neuroepidemiology 2011;36:39–45.
23.
Simpson S Jr, Taylor B, Blizzard L, Ponsonby AL, Pittas F, Tremlett H, Dwyer T, Gies P, van der Mei I: Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol 2010;68:193–203.
24.
Jagannath VA, Fedorowicz Z, Asokan GV, Robak EW, Whamond L: Vitamin D for the management of multiple sclerosis. Cochrane Database Syst Rev 2010;(12):CD008422.
25.
Burton JM, Kimball S, Vieth R, Bar-Or A, Dosch HM, Cheung R, Gagne D, D’Souza C, Ursell M, O’Connor P: A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology 2010;74:1852–1859.
26.
Wingerchuk DM, Noseworthy JH: Randomized controlled trials to assess therapies for multiple sclerosis. Neurology 2002;58:S40–S48.
27.
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ: Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996;17:1–12.
28.
Mosayebi G, Ghazavi A, Ghasami K, Jand Y, Kokhaei P: Therapeutic effect of vitamin D3 in multiple sclerosis patients. Immunol Invest 2011;40:627–639.
29.
Stein MS, Liu Y, Gray OM, Baker JE, Kolbe SC, Ditchfield MR, Egan GF, Mitchell PJ, Harrison LC, Butzkueven H, Kilpatrick TJ: A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. Neurology 2011;77:1611–1618.
30.
Kampman MT, Steffensen LH, Mellgren SI, Jorgensen L: Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial. Mult Scler 2012;18:1144–1151.
31.
Soilu-Hänninen M, Aivo J, Lindstrom BM, Elovaara I, Sumelahti ML, Farkkila M, Tienari P, Atula S, Sarasoja T, Herrala L, Keskinarkaus I, Kruger J, Kallio T, Rocca MA, Filippi M: A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon beta-1b in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2012;83:565–571.
32.
Shaygannejad V, Janghorbani M, Ashtari F, Dehghan H: Effects of adjunct low-dose vitamin D on relapsing-remitting multiple sclerosis progression: preliminary findings of a randomized placebo-controlled trial. Mult Scler Int 2012;2012:452541.
33.
Aivo J, Lindsrom BM, Soilu-Hanninen M: A randomised, double-blind, placebo-controlled trial with vitamin D3 in MS: subgroup analysis of patients with baseline disease activity despite interferon treatment. Mult Scler Int 2012;2012:802796.
34.
Steffensen LH, Jorgensen L, Straume B, Mellgren SI, Kampman MT: Can vitamin D supplementation prevent bone loss in persons with MS? A placebo-controlled trial. J Neurol 2011;258:1624–1631.
35.
Simon KC, Munger KL, Kraft P, Hunter DJ, De Jager PL, Ascherio A: Genetic predictors of 25-hydroxyvitamin D levels and risk of multiple sclerosis. J Neurol 2011;258:1676–1682.
36.
Smolders J, Hupperts R, Barkhof F, Grimaldi LM, Holmoy T, Killestein J, Rieckmann P, Schluep M, Vieth R, Hostalek U, Ghazi-Visser L, Beelke M; SOLAR study group: Efficacy of vitamin D(3) as add-on therapy in patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon beta-1a: a phase II, multicenter, double-blind, randomized, placebo-controlled trial. J Neurol Sci 2011;311:44–49.
37.
Dorr J, Ohlraun S, Skarabis H, Paul F: Efficacy of vitamin D supplementation in multiple sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial. Trials 2012;13:15.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.