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Vitamin D for the treatment of multiple sclerosis: a meta-analysis

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Abstract

Objective

There is an association between latitude, relative vitamin D deficiency and risk of multiple sclerosis (MS), and an association between vitamin D and disease progression. We have performed a meta-analysis with the aim of investigating the role of therapeutic vitamin D in MS.

Methods

A systematic search of databases was performed to identify clinical trials assessing vitamin D in patients with relapsing–remitting MS. Studies were selected based on inclusion and exclusion criteria. Analysis was performed using RevMan 5.3 software.

Results

Twelve studies involving 950 patients were included in the final analysis. Studies were divided into four groups because of heterogeneity in study design. Studies were judged to be at low or unclear risk of bias, except in three studies, and this was confirmed by funnel plots. No statistically significant difference was seen for any of the outcome measures. There were non-significant trends in favour of vitamin D for all outcome measures, particularly when only placebo-controlled studies were included. Dose comparison studies showed a significant increase in annualised relapse rate (mean difference 0.15 [95%CI 0.01–0.30]) and non-significant trends of increased Expanded Disability Status Scale and gadolinium-enhancing lesions for the higher-dose arms.

Conclusion

These findings suggest that vitamin D supplementation may have a therapeutic role in the treatment of MS. However, there is uncertainty with regard to the most appropriate dose, with high doses potentially being associated with worse outcomes. There remains the need for further well-performed randomised, dose-ranging, placebo-controlled trials of vitamin D in MS.

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Abbreviations

ARR:

Annualised relapse rate

CI:

Confidence interval

EDSS:

Expanded Disability Status Scale

MRI:

Magnetic resonance imaging

MS:

Multiple sclerosis

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Acknowledgements

We are grateful to Dr Karen O’Connell and Prof Michael Hutchinson for providing mean (SD) data for change in EDSS in their study. We are grateful to Prof Ariel Miller and Dr Daniel Golan for providing mean (SD) data for change in EDSS from their study. We are also grateful to Prof Peter Calabresi, Prof Samia Khoury, Dr Jan-Markus Dörr, and Prof Masoud Etemadifar and Prof William Camu for clarifying the status of their studies. We are extremely grateful to Dr Mark Stein for reviewing and providing invaluable comments on drafts of this manuscript.

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Authors and Affiliations

  1. School of Medicine, Gold Coast Campus, Griffith University, Gold Coast, QLD, 4222, Australia

    Laurie McLaughlin, Laura Clarke, Elham Khalilidehkordi & Simon A. Broadley

  2. Department of Neurology, Gold Coast University, Hospital, Southport, QLD, Australia

    Laurie McLaughlin, Laura Clarke, Elham Khalilidehkordi & Simon A. Broadley

  3. MS and Neuroimmunology Service, Dept of Neuroscience, Central Clinical School, Alfred Health, Monash University, Melbourne, VIC, Australia

    Helmut Butzkueven

  4. Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS, Australia

    Bruce Taylor

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  1. Laurie McLaughlin
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Correspondence to Simon A. Broadley.

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Conflicts of interest

HB, BVT and SAB are currently principal investigators on a phase II clinical trial of vitamin D in MS sponsored by Multiple Sclerosis Research Australia. Otherwise, the authors have no conflicts of interest.

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McLaughlin, L., Clarke, L., Khalilidehkordi, E. et al. Vitamin D for the treatment of multiple sclerosis: a meta-analysis. J Neurol 265, 2893–2905 (2018). https://doi.org/10.1007/s00415-018-9074-6

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  • DOI: https://doi.org/10.1007/s00415-018-9074-6

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