Understanding the mechanisms of glutamine action in critically ill patients

Abstract

Glutamine (Gln) is an important energy source and has been used as a supplementary energy substrate. Furthermore, Gln is an essential component for numerous metabolic functions, including acid-base homeostasis, gluconeogenesis, nitrogen transport and synthesis of proteins and nucleic acids. Therefore, glutamine plays a significant role in cell homeostasis and organ metabolism. This article aims to review the mechanisms of glutamine action during severe illnesses. In critically ill patients, the increase in mortality was associated with a decreased plasma Gln concentration. During catabolic stress, Gln consumption rate exceeds the supply, and both plasma and skeletal muscle pools of free Gln are severely reduced. The dose and route of Gln administration clearly influence its effectiveness: high-dose parenteral appears to be more beneficial than low-dose enteral administration. Experimental studies reported that Gln may protect cells, tissues, and whole organisms from stress and injury through the following mechanisms: attenuation of NF (nuclear factor)-κB activation, a balance between pro-and anti-inflammatory cytokines, reduction in neutrophil accumulation, improvement in intestinal integrity and immune cell function, and enhanced of heat shock protein expression. In conclusion, high-doses of parenteral Gln (>0.50 g/kg/day) demonstrate a greater potential to benefit in critically ill patients, although Gln pathophysiological mechanisms requires elucidation.

Therapeutic benefits of glutamine: An umbrella review of meta-analyses

“…Finally, glutamine supplementation enhances cellular heat shock protein production (HSP70 and HSP72) and glutathione expression, which both protect cells and enhance cell survival. Heat shock proteins are involved in the repair and removal of damaged proteins, and glutathione reacts directly with reactive oxygen species in order to prevent oxidative damage (36). Collectively, both mechanisms of action reduce the likelihood of cellular apoptosis.…”

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

“…Since glutamine is of absolute requirement as a fuel substrate for the enterocyte, intestinal utilization of glutamine is important for maintaining the integrity of the intestinal barrier, with subsequent prevention of bacterial translocation and, through stimulation of the gut-associated immune system, prevention of gut barrier atrophy. It is assumed that a derangement of the gut mucosal barrier function, which occurs during aging and critical illnesses, results in an amplification of the general inflammatory response predisposing patients to multiple organ failure [305]. In fact, chronic glutamine supplementation reduces exerciseinduced intestinal permeability while inhibiting NF-κB pro-inflammatory pathways in human PBMC, in a mechanism associated with the activation of HSP70 expression [269].…”

“…Although clinical studies with aged people remain scarce, experimental studies reported that glutamine supplementations may protect cells, tissues, and whole organisms from stress and injury by blocking NF-κB downstream inflammatory signals, thus promoting a balance between proand anti-inflammatory cytokines, by improving intestinal integrity and immune cell function, and, finally, by enhancing HS response, so that parenteral glutamine (> 0.50 g kg −1 day −1 ) may be of potential benefit to elderly individuals [305]. When (and preferably) orally given, glutamine may be administered as free amino acid or in its dipeptide forms.…”

The effect of stress on sleep quality in teenagers, the analysis of metal contamination due to heaps of steel-slag accumulation in southern Madrid (Spain), and a review of the mechanisms of glutamine action during severe illnesses

“…Gisele Oliveira of the Instituto de Biofísica Carlos Chagas Filho of the Universidade Federal do Rio de Janeiro (UFRJ) and colleagues have critically reviewed the main studies done in the last 10 years regarding the benefits provided by glutamine in patients (Oliveira et al 2010). As pointed out in…”

“…In those cases, application of glutamine has improved the patient's condition, but as the present study shows, the results vary depending on the dose and route of glutamine administration. Oliveira et al (2010) point out that more research is needed to fully understand the causes of the benefits in order to improve this therapy.…”