Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats

Nutrients. 2020 Mar 16;12(3):783. doi: 10.3390/nu12030783.


Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). In recent years, vitamin D has gained attention, as low serum levels are suspected to increase the risk for MS. Cholecalciferol supplementation has been tested in several clinical trials, since hypovitaminosis D was linked to higher disease activity and may even play a role in long-term outcome. Here, we review the current understanding of the molecular effects of vitamin D beyond calcium homeostasis, the potential beneficial action in MS and hazards including complications of chronic and high-dose therapy. In clinical trials, doses of up to 40,000 IU/day were tested and appeared safe as add-on therapy for short-term periods. A recent meta-analysis of a randomized, double-blind, placebo-controlled clinical trial investigating vitamin D as add-on therapy in MS, however, suggested that vitamin D had no therapeutic effect on disability or relapse rate. We recognize a knowledge gap for chronic and high-dose therapy, which can lead to life-threatening complications related to vitamin D toxicity including renal failure, cardiac arrythmia and status epilepticus. Moreover, vitamin D toxicity may manifest as fatigue, muscle weakness or urinary dysfunction, which may mimic the natural course of progressive MS. Given these limitations, vitamin D supplementation in MS is a sensitive task which needs to be supervised by physicians. While there is strong evidence for vitamin D deficiency and the development of MS, the risk-benefit profile of dosage and duration of add-on supplementation needs to be further clarified.

Keywords: clinical trials; intoxication; multiple sclerosis; renal failure; vitamin D.

Publication types

  • Review

MeSH terms

  • Dietary Supplements*
  • Humans
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / pathology
  • Randomized Controlled Trials as Topic
  • Vitamin D / adverse effects*
  • Vitamin D / therapeutic use*
  • Vitamin D Deficiency / drug therapy*
  • Vitamin D Deficiency / metabolism
  • Vitamin D Deficiency / pathology


  • Vitamin D