Vitamin D supplementation and relapses

High-dose vitamin D supplementation has no impact on relapses. #MSBlog #MSResearch

EpubJames et al. The effect of vitamin D-related interventions on multiple sclerosis relapses: a meta-analysis. Mult Scler. 2013 May 22. 

Background: Observational studies have shown an association between lower vitamin D levels and higher risk of relapse among MSers. This has raised interest in potential clinical benefits of vitamin D supplementation in the management of MS. 

Objectives: The objectives were to examine the effect of vitamin D based interventions on the relative risk of relapse in MS. 

Methods: Any randomised controlled trial assessing the effect on the relative risk of relapse of any formulation or dose of vitamin D, in participants with MS, was eligible. The inverse variance with random effects model in Review Manager 5.1 was used to calculate the odds ratio of relapses in high dose vitamin D treated patients vs. controls. 

Results: Five studies were published as of September 2012, yielding a total of 129 high-dose vitamin D-treated patients and 125 controls. We found no significant association between high-dose vitamin D treatment and risk of MS relapse (OR 0.98, 95% CI 0.45-2.16). 

Conclusion: In conclusion, although no significant association between high-dose vitamin D treatment and risk of MS relapses was found, the studies were limited by several methodological limitations. Further larger, more prolonged studies are merited.

“There is little evidence from published trials that high-dose vitamin D prevents or reduces relapses. The studies are too small to be confident about this result is why we need bigger and properly powered trials to assess the impact of vD on clinical outcomes. I don’t use the possible disease-modifying effects of vD to promote high-dose supplementation in MS; I do so on the grounds of promoting bone health. MSers are more likely than controls have thin bones and fractures.”

CoI: this paper is from our group

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


  • I wish researchers would include what they consider a high dose. The word 'high' is meaningless without quantification.

    • High dose generally means thousands of IU. Studies have used different doses, which makes things a little more difficult, and hence is not specified in this abstract, which is looking at combining a number of other publications. I tend to think of high dose as 4000-5000 IU. The European Food Safety Authority have set the "no adverse event level", ie safe level of supplementation at 4000 IU, and they comment that no consistent adverse events were seen at doses up to 10,000 IU.
      In contrast to this the current UK RDA is 400 IU, which I would think of as "low dose" supplementation.
      hope that helps

    • the reason for saying 5000 IU rather than 4000 IU is that many supplements are available as 5000 IU, so a matter of practicality!

  • The EU paper that discusses the upper limit of 4000IU sets a "no observed adverse effect level (NOAEL) of 250 μg/day", which is 10,000IU a day. I would argue that 5000IU is not high it is that 400IU is low. The problem with calling 5000IU high is people think it is in the pharmaceutical range which requires medical supervision and great caution. It is the dose that is safe for almost everyone without supervision. For those with MS you may need much higher doses to have an effect, if there is one, and these may need monitoring of the calcium levels in the urine and blood to avoid problems.

    • Sorry – my error – getting confused between tolerable upper intake level (4000 IU) and no adverse effect level (10,000 IU). I agree with the reasoning that we need to reframe the phraseology!

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