Effects of high-dose vitamin D supplementation in patients with multiple sclerosis: A systematic review of efficacy and safety.

BACKGROUND

Multiple sclerosis (MS), a chronic autoimmune disease, is the leading cause of non-traumatic neurological disability in young adults. Vitamin D plays a vital immunomodulatory role, and deficiency has been linked to increased MS risk and activity. High-dose vitamin D supplementation has been proposed as a therapeutic approach. However, safety concerns and inconsistent evidence on efficacy highlights the need for systematic evaluation.

OBJECTIVES

To evaluate the efficacy and safety of high-dose vitamin D supplementation in patients with MS, with emphasis on immune markers, disability progression, magnetic resonance imaging (MRI) findings, and reported adverse-events.

METHODS

This systematic review follows the PRISMA 2020 guidelines. The protocol was registered on PROSPERO (CRD420251128444). Relevant studies were systematically retrieved and searched in public databases. Randomized controlled trials were included that evaluates high-dose vitamin D supplementation (≥10,000 IU/day) in adults with multiple sclerosis, reporting efficacy and/or safety. Data extraction was performed independently by two reviewers. Risk of bias was assessed using RoB-2 for randomized trials. Outcomes of interest are safety, MRI findings, clinical measures, and immunological biomarkers.

RESULTS

Eleven randomized controlled trials were included. High-dose vitamin D increased serum 25‑hydroxy vitamin D levels and was surprisingly safe, with rare and transient disturbances in calcium serum levels. MRI and clinical outcomes showed variable effects. Several trials demonstrated immunomodulatory effects, particularly reductions in interleukin-17-related pro-inflammatory activity.

CONCLUSION

High-dose vitamin D is safe under appropriate monitoring. While clinical and radiological benefits remain inconsistent, evidence of immune modulation suggests a promising adjunctive role requiring further investigation in larger, long-term trials.