Vitamin D for multiple sclerosis as an adjuvant therapy: A network meta-analysis of randomized controlled trials

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system, with limited effective adjuvant therapies beyond immunomodulatory agents. Vitamin D supplementation has been proposed as a potential adjunct treatment due to its immunomodulatory properties. We aimed to evaluate the efficacy and safety of vitamin D supplementation as an adjuvant therapy for patients with MS.

We conducted a network meta-analysis of randomized controlled trials comparing vitamin D supplementation (any form or dose) plus standard care versus standard care alone or with placebo in adults with MS. We searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and clinical trial registries from inception to January 31, 2026. We performed frequentist random-effects network meta-analyses and used the GRADE framework to assess the certainty of evidence.

An analysis of 32 RCTs involving 2254 MS patients showed that compared with placebo, Long-term follow-up vitamin D intervention significantly reduced relapse risk (RR 0.80), improved EDSS scores (MD -0.22). Network meta-analysis revealed high-dose long-duration vitamin D supplementation was the most effective for EDSS scores (MD -0.28; 95% CI -0.54 to -0.03) and relapse (RR 0.76; 95% CI 0.59 to 0.98) compared with placebo. Mid-dose long-duration supplementation showed favorable effects on ARR. For safety, no significant difference in SAEs was observed (RR 1.49; 95% CI 0.94 to 2.37).

Vitamin D supplementation as an adjuvant therapy may reduce relapse and disability progression, with a favorable safety profile. These findings support the consideration of vitamin D supplementation in MS management, particularly in deficient populations.

PROSPERO CRD420251163641.