Vitamin D deficiency and multiple sclerosis relapse: a meta-analysis

OBJECTIVE: This meta-analysis was conducted to systematically evaluate the dose-response relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and the annualized relapse rate (ARR) in multiple sclerosis (MS), and to investigate the effect of vitamin D supplementation on reducing relapse risk. METHODS: Randomized controlled trials (RCTs) published from inception to April 2025 were retrieved from PubMed, Medline, Web of Science, Cochrane Library, and EMBASE. Study quality was assessed using the Cochrane RoB-2 tool. Meta-analyses were performed using RevMan 5.3. The primary outcome was ARR. Secondary outcomes included the Expanded Disability Status Scale (EDSS) score and serum 25(OH)D levels. RESULTS: Nine studies comprising 1,078 participants were included. No significant difference in EDSS scores was observed between the intervention and control groups (mean difference (MD) = -0.11, 95%CI [-0.40, 0.18], Z = 0.73, p = 0.47). Serum 25(OH)D levels were significantly higher in the intervention group (pooled MD = 44.97, 95%CI [29.93, 60.01], Z = 5.86, p < 0.001). Subgroup analysis by vitamin D dosage showed that the low/medium-dose group significantly reduced ARR (pooled MD = -0.14, 95%CI [-0.26, -0.03], p = 0.01), while the high-dose group had no significant effect on ARR (pooled MD = 0.05, 95%CI [-0.08, 0.18], p = 0.42). No significant overall difference in ARR was found between the two groups (pooled MD = -0.07, 95%CI [-0.18,0.03], Z = -1.37, p = 0.17). CONCLUSION: The results of this meta-analysis showed that vitamin D supplementation, regardless of dosage, could significantly increase the serum 25(OH)D level in patients with multiple sclerosis. Subgroup analysis showed that low/medium-dose vitamin D supplementation could significantly reduce the ARR, while high-dose supplementation had no significant effect on ARR. There was no significant difference in EDSS scores between the experimental group and the control group.