Impact of vitamin D supplementation and status on seizure frequency and quality of life in drug‐resistant epilepsy: A systematic review and meta‐analysis

BACKGROUND: Drug-resistant epilepsy (DRE) affects approximately one-third of patients with epilepsy and is associated with significant morbidity and reduced quality of life. Emerging evidence suggests that vitamin D may influence neuronal excitability and neuroinflammatory pathways, potentially impacting seizure control. OBJECTIVE: To systematically evaluate the effect of vitamin D supplementation and baseline vitamin D status on seizure frequency, biochemical outcomes, and quality of life in patients with drug-resistant epilepsy. METHODS: PubMed, Scopus, and Web of Science were searched from inception through March 2026. Eligible studies assessed vitamin D supplementation or serum vitamin D levels in DRE patients. RESULTS: Eleven studies were included, with four studies (n = 183) contributing to the meta-analysis of supplementation outcomes. Vitamin D supplementation was associated with a significant reduction in seizure frequency (mean difference [MD] = -8.31 seizures/month, 95% CI [-13.38, -3.25], p = .001) and a significant increase in serum vitamin D levels (MD = 18.4 nmol/L, 95% CI [4.26, 32.54], p = .01). No significant difference in baseline vitamin D levels was observed between drug-resistant and drug-responsive epilepsy (MD = .79 nmol/L, 95% CI [-.31, 1.89], p = .16). Qualitative findings suggested potential improvements in quality of life and fatigue with long-term supplementation, although short-term effects and neuroinflammatory marker changes were inconsistent. CONCLUSION: Vitamin D supplementation is a safe adjunctive therapy that may reduce seizure frequency in drug-resistant epilepsy, though further large-scale trials are needed to confirm its efficacy and define optimal use.