Strategies to improve efficacy of specialized nutrition support in adults

This dissertation investigated strategies to improve specialized enteral and parenteral nutrition support (EN/PN) in selected adult patient populations. Critically ill patients commonly exhibit glutamine depletion, which may increase risks for hospital infection and organ dysfunction. We investigated the metabolic and clinical effects of glutamine-supplemented PN and EN administered to critically ill patients in double blind, randomized clinical trials. We found that glutamine-supplemented PN improved plasma glutamine, heat-shock protein-70 and glutathione concentrations and decreased nosocomial infection rates in surgical ICU patients following cardiac, vascular or colonic surgery. In critically ill patients requiring enteral tube feeding, intravenous and enteral glutamine supplementation yielded similar metabolic outcomes with the exceptions that glutamine-EN was associated with higher plasma alpha-tocopherol levels over time while glutamine-PN resulted in higher plasma glutamine levels.;Current PN is associated with significant side-effects. Reducing PN dependency is a major goal in patients with short bowel syndrome (SBS) following massive bowel resection. We explored potential biomarkers for intestinal absorptive function and status of key vitamin compounds in PN-dependent SBS patients. Plasma citrulline and glutamine levels were not associated with intestinal absorptive function in a group of SBS patients, whose intestinal absorptive rates of fluid, nitrogen, sodium, and potassium were significantly improved with a modified diet +/- growth hormone administration. These SBS patients were deficient in carotenoids despite oral and intravenous multivitamin supplementation and diet adjustments. Serum alpha-tocopherol concentration was negatively associated with the administered PN lipid dose, indicating that current IV lipid emulsions may be a source of oxidative stress.;We also characterized human intestinal redox status by measuring small bowel and colonic mucosal GSH/GSSG and thioredoxin-1 and -2 redox. We defined significant proximal to distal redox gradients in the human intestine. Patients with intestinal abnormalities (SBS and IBD) appeared to exhibit more oxidized mucosal redox.;Findings from this dissertation research provide novel data to support the efficacy of glutamine supplementation in critically ill patients, use of modified oral diets in patients with SBS to facilitate PN weaning and set the stage for new therapeutic strategies to improve intestinal redox status to potentially improve intestinal function in SBS and IBD patients.