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

**Authors:** Yujing Zhang, Shasha Yu, Yu Zu, Jing Lv, Jianhua Chen, Xuedan Feng

PMC · DOI: 10.3389/fneur.2025.1727615 · Frontiers in Neurology · 2026-01-02

## TL;DR

This study finds that low/medium-dose vitamin D supplements may reduce MS relapses, while high doses do not, and all doses raise vitamin D levels.

## Contribution

A meta-analysis revealing the dose-dependent effect of vitamin D on MS relapse rates.

## Key findings

- Vitamin D supplementation significantly increased serum 25(OH)D levels in MS patients.
- Low/medium-dose vitamin D reduced annualized relapse rates, but high-dose did not.
- No significant change in disability scores (EDSS) was observed between groups.

## Abstract

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.

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.

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).

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.

## Linked entities

- **Diseases:** multiple sclerosis (MONDO:0005301)

## Full-text entities

- **Diseases:** MS (MESH:D009103), Vitamin D deficiency (MESH:D014808)
- **Chemicals:** 25-hydroxyvitamin D (MESH:C104450), vitamin D (MESH:D014807), 25(OH)D (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12807898/full.md

## References

28 references — full list in the complete paper: https://tomesphere.com/paper/PMC12807898/full.md

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Source: https://tomesphere.com/paper/PMC12807898