Oral ingestion of glutamine is useful for treating mucositis, an inflammatory condition of the mucous membranes that often results from chemotherapy or radiation therapy. Glutamine treatment can reduce the development and severity of mucositis and can shorten the duration of mouth pain in patients undergoing the aforementioned therapies.3 Glutamine supplementation is a highly cost-effective treatment for patients who undergo cancer treatments. In addition to chemotherapy-induced anorexia, painful sores in the oral mucosa can make eating an unpleasant or even intolerable experience for these patients who desperately need good nutrition during the course of therapy. Providing glutamine for such patients, and healing their mucositis, can improve their quality of life at a time when such support is much needed. GI cells are some of the most rapidly dividing cells in the body, and chemotherapy (as aside effect) targets these rapidly dividing cells, thus patients are at an increased risk of developing GI problems.
Glutamine supplementation can help prevent GI toxicity induced by chemotherapy and radiation, thereby assisting normal GI function.4 In animal models, glutamine supplementation reduced whole-body protein breakdown rate during chemotherapy in tumor-bearing rats. In addition, glutamine supplementation in patients with esophageal cancer demonstrated enhanced lymphocyte mitogenic function and reduced permeability of the intestines during radiochemotherapy.5 Glutamine is a preferential metabolic substrate for the enterocytes and is thought to play a regulatory role in the intestinal tissue by influencing cellular proliferation and differentiation.6 As a result, the GI tract is the largest consumer of glutamine in the body7; suboptimal dietary amounts of glutamine can lead to atrophic changes, including ulceration and necrosis of the intestinal tissue.
Similar to the cells of the GI system, certain cells of the immune system utilize glutamine preferentially during times of unusual stress. Even at times of relative physiologic normalcy, lymphocytes and macrophages consume glutamine at high rates.8 The intricate relationship between skeletal muscle glutamine stores and plasma levels of this amino acid is thought to influence immune function directly. Muscular overuse can lead to reduced levels of glutamine in the plasma and, thereby, may have a negative effect on lymphocyte function. The "glutamine hypothesis'' suggests that, at times when muscular cells are under intense and prolonged physical stress, the demand for glutamine in the muscle itself and in other organs may leave the lymphoid system in a state of relative glutamine scarcity. This is supported by studies that demonstrate a sharp decline in plasma glutamine concentration following long-term physical stress.9 Low plasma levels of glutamine are associated with overtraining as well.10 Given this evidence, however, some studies11,12 have demonstrated that, even though glutamine supplementation was able to offset postexercise drops in glutamine levels, postexercise immunodeficiency was not significantly altered. Researchers are still not certain if the quantitative decline in plasma glutamine is actually great enough to compromise immune-cell function or if intracellular glutamine concentrations are reduced because of declining plasma levels postexercise.
Because of this uncertainty, some researchers speculate that the glutamine hypothesis explains immune function decline in relation to stressful conditions adequately, but low plasma levels following exercise do not entirely explain postexercise immunodeficiency.13 Despite these findings, the literature is full of evidence that supports the need for exogenous glutamine supplementation in maintaining immune function in very ill patients and the utility of this amino acid in supporting muscle protein mass. When given to endurance athletes, glutamine was able to reduce the incidence of self-reported illness significantly.14 Immune function itself is a very broad term and, thus, simply stating that glutamine benefits the immune system is a very nonspecific claim. More research points to neutrophils as possible immune-system beneficiaries specific to glutamine supplementation.15 The majority of studies using glutamine for immunodeficient conditions used doses ranging from 3 to 6 g per day at a minimum. Other studies have used amounts ranging from 500 mg=kg per day in patients with radiation mucositis16 to 40 g per day in patients17 with HIV.
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