A. Glutamine is the most abundant amino acid in the human body. It is a conditionally essential amino acid, meaning that it is required in increased amounts under certain conditions, e.g., of metabolic stress, to support healthy intestinal function. In many cell types, including enterocytes, glutamine acts as a primary fuel for mitochondria and is essential to the maintenance of mitochondrial membrane (1) and optimal intestinal motility.*(2) Glutamine supplementation has been extensively validated in numerous controlled clinical trials, and has been shown to be effective at supporting healthy blood and tissue levels of glutamine and optimizing intestinal and digestive health function in diverse groups of patients.* (3-8) Glutamate, a degradation product of glutamine, has been implicated in some adverse neurological effects. Glutamine can also be converted to glutamate in cells by mitochondrial glutaminase, an enzyme whose levels are often upregulated in tumors and tumor lines. (9, 10) Thus, concern has been raised that glutamine supplementation might theoretically elevate glutamate levels, particularly in cancer patients. However, studies of high intakes of glutamine have shown that concentrations of glutamate are not significantly increased.(11) The most comprehensive safety study of glutamine supplementation performed five separate experiments to examine safety under different circumstances, assessing blood glutamine, glutamate, other amino acids, glucose, insulin, glucagon and growth hormone; urinary creatinine, ammonia, urea and total nitrogen; standard clinical chemistry, complete blood counts, mental status, vital signs, temperature and clinical and subjective evidence of toxicity. These careful studies, including treatments of up to 30 days long and at doses of up to 40 grams per day of glutamine, in both healthy volunteers and sick patients, were not able to detect any sign of adverse effects. (12) Lacey and colleagues investigated the effects of glutamine-supplemented parenteral nutrition for 15 days in 44 preterm neonates, who might possibly be more sensitive to adverse effects than adults. Plasma glutamine level rose by 50%, but glutamate and ammonia remained within the normal range. On the basis of the measurements of plasma ammonia and glutamate and the absence of clinical signs of neurotoxicity, it was concluded that glutamine as dosed was safe in preterm infants.(13) Glutamine supplementation has been studied in diverse patient groups, including cancer patients. No studies were identified in which glutamine supplementation raised glutamate to levels outside the normal range. Therefore, the best available evidence suggests that conversion of glutamine to glutamate is not a significant concern in glutamine supplementation. REFERENCES 1. Wise DR, Thompson CB. Glutamine addiction: a new therapeutic target in cancer. Trends Biochem Sci. 2010 Aug;35(8):427–33. 2. Mochiki E, Ohno T, Yanai M, et al. Effects of glutamine on gastrointestinal motor activity in patients following gastric surgery. World J Surg. 2011 Apr;35(4):805–10. 3. Mok E, Hankard R. Glutamine supplementation in sick children: is it beneficial? J Nutr Metab. 2011;2011:617597. doi: 10.1155/2011/617597. Epub 2011 Nov 14. 4. Noé JE. L-glutamine use in the treatment and prevention of mucositis and cachexia: a naturopathic perspective. Integr Cancer Ther. 2009 Dec;8(4):409–15. 5. Stachowicz-Stencel T, Synakiewicz A. Glutamine as a supplemental treatment in pediatric and adult oncology patients. Expert Opin Investig Drugs. 2012 Dec;21(12):1861–71. 6. Haynes TE, Li P, Li X, et al. L-Glutamine or L-alanyl-L-glutamine prevents oxidant- or endotoxin-induced death of neonatal enterocytes. Amino Acids. 2009 May;37(1):131–42. 7. Li Y, Yu Z, Liu F, Tan L, Wu B, Li J. Oral glutamine ameliorates chemotherapy-induced changes of intestinal permeability and does not interfere with the antitumor effect of chemotherapy in patients with breast cancer: a prospective randomized trial. Tumori. 2006 Sep-Oct;92(5):396–401. 8. Das S, Kar Mahapatra S, Gautam N, Das A, Roy S. Oxidative stress in lymphocytes, neutrophils, and serum of oral cavity cancer patients: modulatory array of L-glutamine. Support Care Cancer. 2007 Dec;15(12):1399–405. 9. DeBerardinis RJ, Cheng T. Q’s next: The diverse functions of glutamine in metabolism, cell biology, and cancer. Oncogene 2010;29:313–24. 10. Levine AJ, Puzio-Kuter AM. The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science 2010;330:1340–4. 11. Garlick PJ. Assessment of the safety of glutamine and other amino acids. J Nutr. 2001 Sep;131(9 Suppl):2556S–61S. 12. Ziegler TR, Benfell K, Smith RJ, et al. Safety and metabolic effects of L-glutamine administration in humans. JPEN J Parenter Enteral Nutr. 1990 Jul-Aug;14(4 Suppl):137S–146S. 13. Lacey JM, Crouch JB, Benfell K, et al. The effects of glutamine-supplemented parenteral nutrition in premature infants. JPEN J Parenter Enteral Nutr. 1996 Jan-Feb;20(1):74–80.
