High-Dose Vitamin C Results in Negative Outcome in Severe Burn Injury
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on July 3rd, 2026
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Severe burn injuries trigger a profound inflammatory response characterized by the release of large amounts of reactive oxygen species. Because of its antioxidant properties, vitamin C has been proposed as a potential therapy for severe burns. Previous studies have also suggested that vitamin C may help preserve endothelial function, enhance host defense against infection, and support wound healing. To evaluate these potential benefits, a recent study investigated the use of high-dose vitamin C in patients with severe burn injuries.
Publication: Journal of the American Medical Association
Funding Source(s): US Department of Defense Military Burn Research Program
The phase 3 clinical trial enrolled 238 participants with a mean age of 49 years. All patients had sustained second- or third-degree burns involving an average of 37% of total body surface area. Inhalation injury was present in 29% of participants, and 57% required mechanical ventilation. Patients were randomly assigned to receive either placebo or intravenous vitamin C. The vitamin C regimen consisted of 50 mg per kilogram of body weight administered every six hours for 96 hours following hospital admission.
After 28 days of follow-up, the researchers found that high-dose vitamin C was associated with a 96% increase in mortality compared with placebo. This increased risk was observed across different care settings, including both intensive care unit patients and those receiving standard hospital care. In addition, vitamin C treatment was associated with a modest increase in organ dysfunction, although this difference did not reach statistical significance. The investigators suggested several possible explanations for these findings. In the setting of critical illness, redox biology is highly complex, and high doses of vitamin C may paradoxically promote oxidative stress rather than reduce it. Furthermore, the acidic nature of vitamin C may contribute to disturbances in acid-base balance and impair the body's buffering capacity.
Publication: Journal of the American Medical Association
Funding Source(s): US Department of Defense Military Burn Research Program
The phase 3 clinical trial enrolled 238 participants with a mean age of 49 years. All patients had sustained second- or third-degree burns involving an average of 37% of total body surface area. Inhalation injury was present in 29% of participants, and 57% required mechanical ventilation. Patients were randomly assigned to receive either placebo or intravenous vitamin C. The vitamin C regimen consisted of 50 mg per kilogram of body weight administered every six hours for 96 hours following hospital admission.
After 28 days of follow-up, the researchers found that high-dose vitamin C was associated with a 96% increase in mortality compared with placebo. This increased risk was observed across different care settings, including both intensive care unit patients and those receiving standard hospital care. In addition, vitamin C treatment was associated with a modest increase in organ dysfunction, although this difference did not reach statistical significance. The investigators suggested several possible explanations for these findings. In the setting of critical illness, redox biology is highly complex, and high doses of vitamin C may paradoxically promote oxidative stress rather than reduce it. Furthermore, the acidic nature of vitamin C may contribute to disturbances in acid-base balance and impair the body's buffering capacity.