For decades, high-dose intravenous vitamin C has been administered to severe burn patients under the assumption that its antioxidant and anti-inflammatory properties would reduce fluid requirements, limit organ damage, and improve survival. This JAMA-published trial challenges that clinical practice with hard outcome data rather than mechanistic inference.
The randomized controlled trial investigated whether high-dose intravenous vitamin C meaningfully reduced a composite endpoint of 28-day mortality and persistent organ dysfunction in patients with severe burn injuries. Burn-injured patients represent a particularly high-stakes population: massive systemic inflammation, capillary leak, and multi-organ stress converge acutely, creating conditions where antioxidant interventions were theoretically most likely to demonstrate benefit. The trial measured clinically meaningful endpoints — death and organ failure — rather than surrogate markers like fluid balance or biomarker levels, lending the findings significant weight. The results indicated no significant improvement in the primary composite outcome for patients receiving high-dose IV vitamin C compared to controls.
This finding carries important implications beyond burn care. High-dose IV vitamin C has attracted sustained interest across critical care medicine — from sepsis to COVID-19 — often justified by plausible mechanisms and small early trials. This JAMA trial adds to a growing body of evidence suggesting that biological plausibility does not reliably translate into clinical benefit in critically ill populations. The CITRIS-ALI trial and the LOVIT trial in sepsis previously found similarly null or negative results for high-dose IV vitamin C in ICU settings, making this burn-specific result a confirmatory rather than isolated signal. Key limitations include the specific population studied — severe burn injury has distinct pathophysiology from sepsis — and questions about optimal dosing timing and duration. Nonetheless, this represents a well-powered, clinically rigorous contribution that should prompt reassessment of routine high-dose vitamin C protocols in burn units.