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

BackgroundTraumatic 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. ObjectiveTo 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. MethodsA 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. ResultsFrom 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{square}= {square}1.02, 95% CI: 0.68-1.36, p{square}< {square}0.0001; I2{square}= {square}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. ConclusionVitamin 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.