Glutamine is a conditionally essential amino acid in the body because it falls into a shortage of supply during the catabolic state. Glutamine plays a key role in the gut function, immune system, and other essential processes in the body. A number of small randomized controlled trials have demonstrated positive clinical outcomes of a glutamine treatment, such as the ICU length of stay, and hospital mortality with glutamine supplementation. On the other hand, recent reports of large scale randomized controlled trials assessing the efficacy of glutamine supplementation demonstrated some negative effects and the main conclusions were a trend toward an increased 28-day mortality and significantly increased hospital stay and 6-month mortality in those who received glutamine. With such results, many academic societies have recommended that IV and enteral glutamine should not be used in a critical care setting based on the moderate quality of evidence available. The indiscriminate use of glutamine supplementation in critically ill patients with any type of organ failure can have deleterious effects. Nevertheless, more sophisticated and well-controlled larger studies will be needed to confirm how these moderate quality results are corrected and suggest the optimal usage of glutamine. More recent clinical trials have focused on specific populations and demonstrated benefits in burn and elective surgery patients with glutamine supplementation. The poor correlation between the plasma glutamine concentration and tissue concentration evoke scattered knowledge about glutamine treatments. A better understanding of the glutamine metabolism and proper guidelines for supplementation are expected.

Loss of body protein?mostly from skeletal muscles?is the most characteristic sign of critical illness. The most common immune-enhancing nutrients for favorable Compensatory Anti-inflammatory Response Syndrome (CARS) are glutamine, arginine, poly-unsaturated fatty acid, some trace elements and probiotics. Glutamine is an essential amino acid with an important role it fuels the proliferation of cells and acts as a precursor to antioxidant glutathione. The conflicting results of glutamine trials are largely related to its dosage and duration of treatment. However, its overall effects, when parenterally or enterally supplied, are thought to be helpful in immune-enhancing and decreasing infectious complications. Arginine is also conditionally essential and has an important role in the synthesis of anabolic hormones and in the activation of T lymphocytes. It also is converted to citrulline and nitric oxide, the latter is a potent intracellular signaling molecule. Leucine and citrulline are common in the mechanism of action and are mediated by the mTOR signaling pathway. Both leucine- and citrulline-enriched diets have been proven to increase nutritional status in various experimental models of injury. However, there are conflicting data about when they were supplied to the critically ill patients. The role of the most immune-modulating nutrients have not been fully discovered thus far. For critically ill patients, basic support with macro-nutrients should come first, followed by other specially provided nutrients, such as immunonutrients.

Glutamine is the most abundant amino acid, composed of more than 50 percent of free amino acid in the human body. It had been regarded as a conditional essential amino acid and its concentration is markedly reduced in critically ill patients with trauma, burn, or sepsis. From the early 1990s, many parenteral glutamine studies on critical illness have reported the benefits in mortality, infection, and length of stay. However, its clinical efficacy was based on out-of-date, smaller, single-center studies. Clinical effects of parenteral glutamine have shown no benefits or even harms in recent clinical trials and meta-analysis. Furthermore, it has challenged the hypothesis that low plasma glutamine concentration was associated with poor outcomes in critically ill patients. Although many studies showing the efficacy of glutamine have been reported, parenteral glutamine supplementation may be harmful in patients with multiorgan failure or baseline kidney dysfunction. Further studies should be conducted to identify the use of glutamine supplementation in combination with parenteral and enteral nutrition or enteral/oral nutrition alone, specific adult or pediatric patients, the appropriate time and doses for administration of glutamine, cost-benefit analysis, and the exact mechanisms of action.