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.