A Randomized Trial of Enteral Glutamine for Treatment of Burn Injuries

N Engl J Med. 2022 Sep 15;387(11):1001-1010. doi: 10.1056/NEJMoa2203364. Epub 2022 Sep 9.


Background: Glutamine is thought to have beneficial effects on the metabolic and stress response to severe injury. Clinical trials involving patients with burns and other critically ill patients have shown conflicting results regarding the benefits and risks of glutamine supplementation.

Methods: In a double-blind, randomized, placebo-controlled trial, we assigned patients with deep second- or third-degree burns (affecting ≥10% to ≥20% of total body-surface area, depending on age) within 72 hours after hospital admission to receive 0.5 g per kilogram of body weight per day of enterally delivered glutamine or placebo. Trial agents were given every 4 hours through a feeding tube or three or four times a day by mouth until 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission, whichever came first. The primary outcome was the time to discharge alive from the hospital, with data censored at 90 days. We calculated subdistribution hazard ratios for discharge alive, which took into account death as a competing risk.

Results: A total of 1209 patients with severe burns (mean burn size, 33% of total body-surface area) underwent randomization, and 1200 were included in the analysis (596 patients in the glutamine group and 604 in the placebo group). The median time to discharge alive from the hospital was 40 days (interquartile range, 24 to 87) in the glutamine group and 38 days (interquartile range, 22 to 75) in the placebo group (subdistribution hazard ratio for discharge alive, 0.91; 95% confidence interval [CI], 0.80 to 1.04; P = 0.17). Mortality at 6 months was 17.2% in the glutamine group and 16.2% in the placebo group (hazard ratio for death, 1.06; 95% CI, 0.80 to 1.41). No substantial between-group differences in serious adverse events were observed.

Conclusions: In patients with severe burns, supplemental glutamine did not reduce the time to discharge alive from the hospital. (Funded by the U.S. Department of Defense and the Canadian Institutes of Health Research; RE-ENERGIZE ClinicalTrials.gov number, NCT00985205.).

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Burns* / drug therapy
  • Burns* / pathology
  • Canada
  • Critical Illness / therapy
  • Double-Blind Method
  • Enteral Nutrition* / adverse effects
  • Enteral Nutrition* / methods
  • Glutamine* / administration & dosage
  • Glutamine* / adverse effects
  • Glutamine* / therapeutic use
  • Humans


  • Glutamine

Associated data

  • ClinicalTrials.gov/NCT00985205