Neuroprotective Effects of Vitamin D Supplementation on Outcomes in Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Background: Traumatic brain injury (TBI) remains a leading cause of morbidity and mortality worldwide, with secondary brain damage driven by inflammation and oxidative stress. Vitamin D is increasingly recognized for potential neuroprotective effects in TBI, while data regarding vitamin E remain limited. Objective: To systematically review and meta-analyze the effects of vitamin D supplementation, and qualitatively review evidence for vitamin E, on clinical and functional outcomes after moderate to severe TBI. Methods: A comprehensive search was carried out in PubMed, Scopus, Embase, Web of Science, and Google Scholar up to January 2025. Studies reporting on vitamin D or E supplementation in clinical TBI were eligible. Risk of bias was assessed using JBI checklists. A meta-analysis of randomized controlled trials reporting pre- and post-treatment GCS scores following vitamin D supplementation was performed with a fixed-effect model. Results: From 4,546 records, nine clinical studies met criteria; three RCTs on vitamin D (n=151 patients) were included in the meta-analysis, which found that vitamin D supplementation significantly improved GCS scores versus controls (SMD = 1.02, 95% CI: 0.68-1.36, p < 0.0001; I2 = 0%). Narrative analysis suggested that vitamin D may improve functional outcomes, reduce inflammatory biomarkers, and lower mortality in select studies. Evidence for vitamin E in TBI is currently limited to a small number of heterogeneous studies, with early data suggesting possible benefits for acute recovery and oxidative stress reduction, but insufficient for quantitative synthesis. Conclusion: Vitamin D supplementation may confer short-term improvement in neurological and functional outcomes following moderate to severe TBI. Existing evidence for vitamin E is insufficient to support robust conclusions. Larger, rigorously designed RCTs particularly for vitamin E are required to clarify effectiveness, optimal dosing, and long-term outcomes.