Rationale for and Efficacy of Glutamine Supplementation in Critical Illness

Glutamine, the most abundant free amino acid in the human body, is present in the highest concentration in both plasma and skeletal muscle, and contributes more than 50% of the free amino acid pool in the body. The majority of glutamine entering the plasma is derived from skeletal muscle and approximately one-third of all nitrogen derived from protein metabolism is transported in the form of glutamine. In critical illness, the depletion of both intramuscular and circulating glutamine concentrations points toward an inability to increase intramuscular glutamine synthesis to match its rate of uptake. In support of this, stable isotope studies have found that in critical illness, glutamine rate of appearance in plasma is unchanged despite increased protein breakdown, indicating a potential defect in de novo glutamine synthesis. The Reducing Deaths due to Oxidative Stress trial unexpectedly demonstrated potential harm from glutamine supplementation in critically ill patients.