Vitamin D Supplementation May Reduce Annualized Relapse Rate in Multiple Sclerosis: Meta-Analysis Findings
China: Vitamin D supplementation may play a selective role in reducing relapse risk in multiple sclerosis (MS), particularly when used at low to moderate doses, a new meta-analysis published in Frontiers in Neurology has found.
The study, led by Yujing Zhang from the Department of Neurology, Beijing Fengtai You’anmen Hospital, Beijing, China, evaluated the relationship between vitamin D status, supplementation dose, and clinical outcomes in patients with MS.
Vitamin D deficiency has long been associated with increased susceptibility to MS and higher disease activity, prompting interest in supplementation as a potential disease-modifying strategy. However, uncertainty remains regarding the optimal dosage and its impact on relapses and disability progression. To address this, the researchers conducted a systematic review and meta-analysis focusing on the dose–response relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and the annualized relapse rate (ARR) in MS.
The analysis included nine randomized controlled trials comprising a total of 1,078 participants. Studies published up to April 2025 were identified from major databases, including PubMed, Medline, Web of Science, Cochrane Library, and EMBASE. Study quality was assessed using the Cochrane risk-of-bias tool, and pooled analyses were performed using standard meta-analytic methods. The primary outcome was ARR, while secondary outcomes included changes in Expanded Disability Status Scale (EDSS) scores and serum 25(OH)D concentrations.
The meta—analysis revealed the following findings:
- Vitamin D supplementation consistently produced a significant increase in serum 25(OH)D levels compared with control groups, irrespective of the dose used.
- Pooled analysis confirmed a marked rise in circulating vitamin D levels, demonstrating the effectiveness of supplementation in correcting biochemical deficiency.
- The overall impact of vitamin D supplementation on relapse frequency was modest when all doses were analyzed together.
- No statistically significant difference in annualized relapse rate was observed between the vitamin D and control groups in the overall analysis.
- Subgroup analysis revealed a dose-dependent effect, with low to medium doses of vitamin D significantly reducing the annualized relapse rate.
- High-dose vitamin D supplementation did not provide additional benefit and showed no meaningful effect on relapse rates.
- Disability outcomes were not significantly influenced by vitamin D supplementation.
- No significant difference in Expanded Disability Status Scale scores was found between the vitamin D and control groups, suggesting limited impact on disability progression over the short to medium term.
The authors noted that these findings help clarify inconsistencies in previous studies and underscore the importance of dosing strategies. While raising vitamin D levels appears achievable across dosing regimens, higher doses do not necessarily translate into superior clinical outcomes and may offer no added advantage in relapse prevention.
In conclusion, the meta-analysis supports the use of vitamin D supplementation to correct deficiency in patients with MS and suggests that low to moderate doses may help reduce relapse frequency. However, the lack of significant effects on overall ARR and disability highlights the need for individualized treatment approaches, longer follow-up periods, and further research to better define optimal dosing and underlying mechanisms.
Reference:
Zhang, Y., Yu, S., Zu, Y., Lv, J., Chen, J., & Feng, X. (2026). Vitamin D deficiency and multiple sclerosis relapse: A meta-analysis. Frontiers in Neurology, 16, 1727615. https://doi.org/10.3389/fneur.2025.1727615
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