Intravenous vitamin C has attracted significant clinical interest as a low-cost, seemingly safe intervention capable of reducing fluid resuscitation volumes and oxidative stress in critically ill patients — burn victims in particular. The hypothesis rested on decades of smaller studies suggesting massive ascorbate doses could blunt capillary leak, a leading driver of multi-organ failure after severe burns. This international randomized clinical trial from JAMA now puts that hypothesis to a rigorous test, and the results are sobering.
The trial evaluated high-dose intravenous vitamin C against placebo in patients with severe burn injury, measuring a composite primary endpoint: 28-day mortality combined with persistent organ dysfunction — defined as continued dependence on mechanical ventilation, kidney replacement therapy, or vasopressor/inotropic support at day 28. Across the enrolled international cohort, high-dose IV vitamin C did not produce a statistically significant reduction in either mortality or persistent organ dysfunction compared to standard care. The intervention, despite its biological plausibility, failed to translate mechanistic promise into measurable patient benefit on these hard clinical endpoints.
This finding carries real weight in the landscape of critical care supplementation. High-dose vitamin C has had a turbulent evidence trail — early enthusiasm from Fowler and colleagues' sepsis trials gave way to neutral or negative results in larger follow-up work, and this burn-specific trial continues that pattern. The study's international, randomized design substantially strengthens confidence in the null result compared to earlier single-center or observational data. Key limitations worth noting: composite endpoints can obscure differential effects on mortality versus organ support, and subgroup heterogeneity across burn severity and resuscitation protocols may matter. Still, for clinicians and health-conscious observers watching the IV vitamin C space, this is not an incremental finding — it is a meaningful signal that high-dose ascorbate is unlikely to be the adjunct therapy burn medicine has sought. The burden of proof for future trials in this population has risen considerably.