A systematic review on the role of high-dose vitamin C in trauma patients

BACKGROUND: Major trauma and polytrauma are leading causes of mortality, driven by haemorrhagic shock and a dysregulated inflammatory response. Vitamin C, which has a role in vasopressor synthesis, endothelial function and antioxidant defence, is rapidly depleted in critical illness. Vitamin C has been highlighted as a promising therapeutic opportunity in trauma patients. This systematic review evaluates the evidence of vitamin C use in adult trauma patients. METHODS: The systematic review was registered on PROSPERO (International Prospective Register of Systematic Reviews) and is reported according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Embase, Medline, CINAHL, SCOPUS, ClinicalTrials.gov, and Cochrane Central were searched up to December 2025. Studies evaluating intravenous vitamin C in adult trauma patients were included, with studies screened and quality assessed in duplicate by two blinded authors. Meta-analysis was not possible due to heterogeneous outcome reporting. RESULTS: Six studies, including three randomised controlled trials (RCTs) and three cohort studies, met the inclusion criteria. The included studies suggest patients receiving high-dose vitamin C may have a significantly lower mortality with significantly reduced intensive care unit and hospital stays. There were also lower rates of sepsis and organ failure in the vitamin C cohorts. These findings derive from a small number of methodologically heterogeneous studies, resulting in a limited certainty of evidence. CONCLUSIONS: This review identifies the potential benefit of intravenous high-dose vitamin C in trauma patients, supported by a strong biological rationale. The studies included are heterogeneous, which limits their strength and results in low certainty of our presented evidence. High-quality, adequately powered RCTs with standardised protocols, including dosing regimen and timing, are needed before routine clinical use can be recommended.