Vitamin D status, supplementation, and multiple sclerosis: a systematic review and meta-analysis

Area of Science:

• Neuroimmunology
• Endocrinology
• Epidemiology

Background:

• Multiple sclerosis (MS) is a chronic, immune-mediated neurodegenerative disease.
• Vitamin D deficiency is a potential environmental risk factor for MS.
• The role of vitamin D in MS progression and treatment remains debated.

Purpose of the Study:

• To meta-analyze the association between serum 25-hydroxyvitamin D (25(OH)D) levels and MS.
• To evaluate the impact of vitamin D3 supplementation on MS relapse rates and disability.

Main Methods:

• Systematic literature review of PubMed, Cochrane Library, Web of Science, and EMBASE up to November 17, 2025.
• Inclusion of 40 studies on 25(OH)D levels and MS, and 22 studies on vitamin D3 supplementation.
• Meta-analysis and multivariable-adjusted analyses were performed.

Main Results:

• MS patients had significantly lower 25(OH)D levels than controls, with lower levels during relapse.
• Higher 25(OH)D levels correlated with lower MS risk and disability scores (EDSS).
• High-dose vitamin D3 supplementation significantly reduced annualized relapse rate (ARR), unlike low-dose or overall supplementation.

Conclusions:

• MS patients exhibit lower serum 25(OH)D levels, inversely correlating with disease risk and severity.
• High-dose vitamin D3 supplementation shows potential in reducing MS relapse rates.
• Vitamin D's role in MS is complex and dose-dependent, impacting relapse risk more than short-term disability.