Special Formulations

Glutamine and arginine Glutamine is the most abundant amino acid in the human body, comprising nearly two-thirds of the free intracellular amino acid pool, of which 75% is found within the skeletal muscles. In healthy individuals, glutamine is considered a nonessential amino acid because it is synthesized within the skeletal muscles and the lungs. Glutamine is a necessary substrate for nucleotide synthesis in most dividing cells and hence provides a major fuel source for enterocytes. It also serves as an important fuel source for immunocytes, such as lymphocytes and macrophages, as well as a precursor for glutathione, a major intracellular antioxi-dant. During stress states such as sepsis or in tumor-bearing hosts, peripheral glutamine stores are rapidly depleted and the amino acid is preferentially shunted as a fuel source toward the visceral organs and tumors, respectively. These situations create, at least experimentally, a glutamine-depleted environment of which the consequences include enterocyte and immunocyte starvation.

The beneficial effects of glutamine supplementation demonstrated experimentally are multifaceted (Table 6). However, glutamine metabolism during stress in humans may be more complex than in previously reported animal data. More advanced methods of detecting glutamine traffic in patients with gastrointestinal cancer have not demonstrated more tumor sequestration of glutamine than in normal intestine. There are data demonstrating decreased dependency on total parenteral nutrition in severe cases of short bowel syndrome when glutamine therapy with modified diets and growth hormones are used. However, in patients with milder forms of short bowel syndrome and better nutritional status, glutamine supplementation did not demonstrate appreciable enhancement in intestinal absorption. In healthy subjects, glutamine-supplemented total parenteral nutrition did not attenuate endotoxin-induced symptoms or proinflammatory cytokine release compared to standard total parenteral nutrition. Although it is hypothesized that provision of glutamine may preserve immune cell and enterocyte function and enhance nitrogen balance during injury or sepsis, the pool of clinical evidence in support of this phenomenon in human subjects remains inconclusive.

Arginine, also a nonessential amino acid in healthy subjects, first attracted attention for its immunoen-hancing properties, wound-healing benefits, and improved survival in animal models of sepsis and injury. As with glutamine, the benefits of experimental arginine supplementation during stress states are diverse. Clinical studies in which arginine was administered enterally have demonstrated net nitrogen

Table 6 Experimental benefits of glutamine and arginine supplementation

Glutamine

Enhances bowel absorptive capacity after intestinal resection Decreases intestinal permeability Early resolution of experimental pancreatitis Maintains nitrogen balance Promotes liver regeneration after hepatectomy Restores mucosal IgA function Enhances bacterial clearance in peritonitis Protects postradiation enterocyte viability Restores intracellular glutathione levels Facilitates tumor sensitivity to chemotherapy and radiation therapy

Enhances natural killer (NK) and lymphocyte-activated killer (LAK) cell function

Arginine

Minimizes hepatic ischemia-reperfusion injury Reduces intestinal bacterial translocation Enhances NK and LAK cell function Increases nitrogen retention and protein synthesis retention and protein synthesis compared to isonitro-genous diets in critically ill and injured patients and following surgery for certain malignancies. Some of these studies are also associated with in vitro evidence of enhanced immunocyte function. The clinical utility of arginine in improving overall patient outcome remains an area of investigation.

Omega-3 fatty acids The provision of omega-3 polyunsaturated fatty acids (canola oil or fish oil) displaces omega-6 fatty acids in cell membranes, which theoretically reduce the proinflammatory response from prostaglandin production.

Nucleotides RNA supplementation in solutions is purported, at least experimentally, to increase cell proliferation, provide building blocks for DNA synthesis, and improve T-helper cell function.

Patient monitoring In the first month of home nutrition support, nutrition and metabolic assessments should be performed weekly. In the stable patient, the frequency of these assessments can be reduced to monthly and then quarterly. Hepatic stea-tosis, cholestasis, and cholelithiasis are all known sequelae of long-term parenteral nutrition. Regular assessments are necessary because specific nutrient deficiencies, such as selenium, vitamin C, iron, and thiamin, are known in patients on long-term parent-eral nutrition support. Patients on a fat-free diet or who receive infrequent lipid infusions are at risk of developing essential fatty acid deficiencies that manifest as dermatitis, scaling, and sparse hair growth. These can be circumvented by the provision of long-chain fatty acids in the diet on a regular basis. Zinc and copper deficiencies are particularly prevalent in patients who have short bowel syndrome or malab-sorptive states. In many instances, routine biochemical screening may not adequately reflect the functional level of a particular nutrient but, rather, the concentration in a body compartment such as the intravascular space. In these instances, treatment for any nutrient deficiencies should be initiated based on anticipation or clinical suspicion.

See also: Colon: Disorders; Nutritional Management of Disorders. Energy: Requirements. Fatty Acids: Omega-3 Polyunsaturated. Gall Bladder Disorders. Liver Disorders. Nutritional Support: In the Home Setting; Adults, Enteral; Adults, Parenteral. Small

Intestine: Disorders. Stomach: Disorders. Supplementation: Role of Micronutrient Supplementation. Surgery: Long-term Nutritional Management.

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