Glutamine Supplementation and Gut Function
Because glutamine is the major energy source for enterocytes, glutamine may be necessary to maintain gut barrier function, restrict translocation of bacteria, and consequently help to prevent the development of multisystem organ failure. In postsurgical patients receiving TPN, addition of Ala-Gln prevented a worsening of intestinal permeability and maintained duodenal villus height, indicating that glutamine helps to maintain the gut barrier and preserve mucosal integrity (van der Hulst et al. 1993). Similarly, in patients with severe burns who received enteral feeding, gut permeability as measured by the lactulose/mannitol ratio was less in those patients who received Ala-Gln supplementation as compared with those who did not (Zhou et al. 2003), again demonstrating that glutamine may help to maintain gut integrity.
Glutamine Supplementation and Heat Shock Proteins
The induction of HSPs is a key mechanism, which provides cellular protection against systemic inflammation and renders cells more resistant to extreme stress. Because glutamine upregulates the expression of HSP-70 in animal models (Wischmeyer et al. 2001), its effect on HSP in critically ill patients was studied in a small group of patients admitted to the surgical intensive care unit with an anticipated 7-day requirement for parenteral nutrition. Supplementation with parenteral glutamine compared with placebo led to a greater rise in serum HSP-70 concentrations over time, and the magnitude of increase in HSP-70 concentrations was associated with improved clinical outcomes, including decreased intensive care unit (ICU) and ventilator days (Ziegler et al. 2005).
Glutamine Supplementation and Glutathione
In critically ill patients, both reduced and total glutathione concentrations in the skeletal muscle are decreased, and the ratio of reduced to total glutathione is also decreased, demonstrating an environment of increased oxidative stress (Hammarqvist et al. 1997). Supplementation of TPN with parenteral glutamine prevented the depletion of muscle glutathione (Flaring et al. 2003) in patients undergoing abdominal surgery. Similarly, patients admitted to the surgical ICU after non-pancreatic surgery who received Ala-Gln-supplemented TPN had improvement in plasma-reduced glutathione after 7 days (Luo et al. 2008).