Glutamine

Purported Benefits, Side Effects & More
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Glutamine

Purported Benefits, Side Effects & More
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Glutamine

Common Names

  • L-Glutamine
  • GLN

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For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.

What is it?

Glutamine is a chemical that your body makes to build protein.  It’s also found in foods such as wheat, corn, barley, peanuts, soybeans, egg whites, and milk.

You can also take glutamine supplements as a pill or powder (which can be made into a drink by dissolving it in water).

What are the potential uses and benefits?

Glutamine is used to:

  • Treat weakness and loss of muscle mass caused by cancer treatment
  • Treat neuropathy (numbness or tingling hands and feet) caused by chemotherapy
  • Treat nausea (feeling like you’re going to throw up), vomiting (throwing up), and diarrhea (loose, watery bowel movements) due to cancer treatments
  • Help recovery after surgery by reducing your risk for infection

Glutamine also has other uses that haven’t been studied by doctors to see if they work.

Glutamine that you get from food is safe. Talk with your healthcare provider before taking glutamine supplements because they have higher amounts of glutamine.

Supplements can also interact with some medications and affect how they work. For more information, read the “What else do I need to know?” section below.

What are the side effects?

Side effects of using glutamine may include:

  • Swelling
  • Headache
  • Fever
  • Nausea (feeling like you’re going to throw up)
  • Vomiting (throwing up)
  • Infections
What else do I need to know?

Do not confuse glutamine with another chemical known as glutamate, which is important for normal brain function. Taking too much glutamate can cause seizures and kill brain cells.

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For Healthcare Professionals

Clinical Summary

Glutamine is an amino acid that can be absorbed from food and synthesized and stored, mainly in the muscles and lungs. It is the building block of proteins and a major source of cellular fuel. Although abundant in the body, patients with cancer and AIDS-related cachexia or those recovering from catabolic states such as surgery, sepsis, and intense exercise may need to increase intake. Parenteral supplementation is used in hospitals and oral formulations are available as medical food products. Glutamine is also marketed as a dietary supplement to enhance muscle building, wound healing, and for intestinal and immune system health.

Despite its popularity, evidence is lacking to support the use of glutamine supplements for increasing muscle mass and strength (42).

In post-surgical or critically ill patients, glutamine may improve nitrogen balance, preserve intestinal integrity, maintain intracellular glutamine levels, and reduce hospital stay (3) (4) (12) (13) (40), but data on whether it can prevent infections are mixed (5) (40) and it did not reduce the time to discharge alive from hospital in patients with severe burns (52). In patients with irritable bowel syndrome, supplementation reduced related symptoms (36). Among patients with sickle cell anemia, treatment with glutamine resulted in significantly fewer pain crises (35).

In oncology settings, studies suggest glutamine or its derivatives are useful against peripheral neuropathy (14) (15), mucositis (16) (17) (18) (19) (46), fluorouracil-induced GI toxicity (20) and FOLFOX-induced diarrhea (48). Intravenous glutamine also reduced chemotherapy-induced nausea, vomiting, and diarrhea in patients with gastric or colorectal cancer (21), and enteral nutrition that includes arginine, glutamine, and omega-3 fatty acids may improve short-term survival in stage IV gastric cancer patients (22). Preliminary data on a supplement containing HMB, L-arginine and glutamine suggest it may help prevent sorafenib-associated hand-foot skin reactions in patients with advanced hepatocellular carcinoma (39). In addition, perioperative diet containing arginine, glutamine, and fish oil led to reductions in mucocutaneous fistula and length of hospital stay in clean-contaminated head and neck cancer surgery patients (49). Glutamine alone also reduced length of hospital stay in patients with colorectal cancer (53). But findings from cachexia trials are mixed (11) (50).

Other studies suggest glutamine may reduce radiation morbidity in breast cancer patients (23) and treatment-induced mucositis and dysphagia in patients with oropharynx and larynx carcinoma (37), and delay esophagitis onset in non-small cell lung cancer patients (38). However, meta-analyses report lack of strong evidence with glutamine for oral mucositis (43), for radiation dermatitis (54) or for radiation-associated gastrointestinal toxicity (47), a systematic review cited the need for well-designed trials (44), and conflicting data indicate no impact on postsurgical complications or infections in cancer patients (25) (55), nor on acute radiation-induced esophagitis in patients with advanced thoracic malignancies (51). Furthermore, findings also suggest a role for glutamine in tumor cell growth and maintenance (26) (27). More research is needed to resolve these ambiguities.

In pediatric patients with acute lymphoblastic leukemia, glutamine may have benefits against oral mucositis and chemo-induced peripheral neuropathy (56).

Food Sources

Wheat, corn, barley, peanuts, soybeans, egg whites, and milk

Purported Uses and Benefits
  • Cachexia
  • Neuropathy
  • Gastrointestinal toxicity
  • Infections
Mechanism of Action

Glutamine is essential for the maintenance of intestinal mucosal integrity and function (1). It maintains immune function by serving as the principle metabolic fuel for cells, acts as a precursor for protein synthesis, and along with cysteine and glycine, is involved in glutathione (GSH) synthesis. Intravenous glutamine preserves liver and intestinal glutathione stores in animal models of oxidant damage. Glutamine is also involved in nitrogen exchange, as it neutralizes and eliminates excess ammonia formed during protein catabolism. As a nitrogen donor, it contributes to the synthesis of other non-essential amino acids, including the purines and pyrimidines, and is therefore essential for the proliferation of most cells (29). It also plays a supportive role during biochemical stress and sepsis. Reduced oxidative stress and sickle cell-related pain with l-glutamine is attributed to increased proportions of the reduced form of nicotinamide adenine dinucleotides in sickle cell erythrocytes (35).

Although the mechanism underlying benefits against cachexia is unclear, it is thought that glutamine, a modulator of protein turnover, enhances net protein synthesis (11). Clinical evidence suggests that total parenteral nutrition supplemented with glutamine improves nitrogen balance, maintains the intracellular glutamine pool, enhances protein synthesis, and prevents deterioration of gut permeability in post-surgery patients (12).

Glutamine prevented genotoxic and clastogenic damages caused by cisplatin in mice (30). It may also potentiate the tumoricidal effect of methotrexate (MTX) since polyglutamation of MTX impairs its efflux from tumor cells and reduces its accumulation in the gut (31). The supplemental intravenous form leads to increases of GSH in the gut, but not in tumors, in a sarcoma-bearing rat model.

However, other findings show that glutamine transporters are upregulated in tumor cells and that glutamine acts as a mitochondrial substrate and promotes protein translation. This indicates tumor cell dependence for growth and maintenance (26). In addition, glutamine helps cancer cells survive acidic stress through enzymatic deamidation rather than provide nutrition (27).

Adverse Reactions
  • Some studies in cancer patients suggest oral glutamine is well tolerated (14) (17) (18) (19). However, others using specific oral preparations reported peripheral edema, gastrointestinal symptoms, headache, fever, and infections (32) (33).

Case report

  • Severe abdominal pain and scleral icterus: In a 35-year-old female athlete following consumption of glutamine powder for three weeks. Testing suggested hepatoxicity, but the patient recovered successfully after discontinuing glutamine (45).
Herb-Drug Interactions

Lactulose: Glutamine may reduce the ammonia-lowering effect of lactulose (34). This interaction does not apply when lactulose is used as a laxative.
Methotrexate: Glutamine may preferentially increase tumor retention of MTX, thereby increasing its therapeutic efficacy (31).

Dosage (OneMSK Only)
References
  1. Wilmore DW. Metabolic support of the gastrointestinal tract: potential gut protection during intensive cytotoxic therapy. Cancer. May 1 1997;79(9):1794-1803.
  2. van der Hulst RR, van Kreel BK, von Meyenfeldt MF, et al. Glutamine and the preservation of gut integrity. Lancet. May 29 1993;341(8857):1363-1365.
  3. Morlion BJ, Stehle P, Wachtler P, et al. Total parenteral nutrition with glutamine dipeptide after major abdominal surgery: a randomized, double-blind, controlled study. Ann Surg. Feb 1998;227(2):302-308.
  4. Melis GC, ter Wengel N, Boelens PG, et al. Glutamine: recent developments in research on the clinical significance of glutamine. Curr Opin Clin Nutr Metab Care. Jan 2004;7(1):59-70.
  5. Andrews PJ, Avenell A, Noble DW, et al. Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients. BMJ. Mar 17 2011;342:d1542.
  6. Brinkmann SJ, Buijs N, Vermeulen MA, et al. Perioperative glutamine supplementation restores disturbed renal arginine synthesis after open aortic surgery: a randomized controlled clinical trial. Am J Physiol Renal Physiol. Sep 1 2016;311(3):F567-575.
  7. Liu X, Sun XF, Ge QX. The role of glutamine supplemented total parenteral nutrition (TPN) in severe acute pancreatitis. Eur Rev Med Pharmacol Sci. Oct 2016;20(19):4176-4180.
  8. Asrani V, Chang WK, Dong Z, et al. Glutamine supplementation in acute pancreatitis: a meta-analysis of randomized controlled trials. Pancreatology. Sep-Oct 2013;13(5):468-474.
  9. Ong EG, Eaton S, Wade AM, et al. Randomized clinical trial of glutamine-supplemented versus standard parenteral nutrition in infants with surgical gastrointestinal disease. Br J Surg. Jul 2012;99(7):929-938.
  10. Wagner JV, Moe-Byrne T, Grover Z, et al. Glutamine supplementation for young infants with severe gastrointestinal disease. Cochrane Database Syst Rev. Jul 11 2012(7):Cd005947.
  11. May PE, Barber A, D’Olimpio JT, et al. Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine. Am J Surg. Apr 2002;183(4):471-479.
  12. Jones C, Palmer TE, Griffiths RD. Randomized clinical outcome study of critically ill patients given glutamine-supplemented enteral nutrition. Nutrition. Feb 1999;15(2):108-115.
  13. Griffiths RD, Jones C, Palmer TE. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition. Apr 1997;13(4):295-302.
  14. Sands S, Ladas EJ, Kelly KM, et al. Glutamine for the treatment of vincristine-induced neuropathy in children and adolescents with cancer. Support Care Cancer. Mar 2017;25(3):701-708.
  15. Wang WS, Lin JK, Lin TC, et al. Oral glutamine is effective for preventing oxaliplatin-induced neuropathy in colorectal cancer patients. Oncologist. Mar 2007;12(3):312-319.
  16. Choi K, Lee SS, Oh SJ, et al. The effect of oral glutamine on 5-fluorouracil/leucovorin-induced mucositis/stomatitis assessed by intestinal permeability test. Clin Nutr. Feb 2007;26(1):57-62.
  17. Aquino VM, Harvey AR, Garvin JH, et al. A double-blind randomized placebo-controlled study of oral glutamine in the prevention of mucositis in children undergoing hematopoietic stem cell transplantation: a pediatric blood and marrow transplant consortium study. Bone Marrow Transplant. Oct 2005;36(7):611-616.
  18. Sayles C, Hickerson SC, Bhat RR, et al. Oral Glutamine in Preventing Treatment-Related Mucositis in Adult Patients With Cancer: A Systematic Review. Nutr Clin Pract. Apr 2016;31(2):171-179.
  19. Leung HW, Chan AL. Glutamine in Alleviation of Radiation-Induced Severe Oral Mucositis: A Meta-Analysis. Nutr Cancer. Jul 2016;68(5):734-742.
  20. Daniele B, Perrone F, Gallo C, et al. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: A double blind, placebo controlled, randomised trial. Gut. Jan 2001;48(1):28-33.
  21. Li Y, Ping X, Yu B, et al. Clinical trial: prophylactic intravenous alanyl-glutamine reduces the severity of gastrointestinal toxicity induced by chemotherapy—a randomized crossover study. Aliment Pharmacol Ther. Sep 1 2009;30(5):452-458.
  22. Klek S, Scislo L, Walewska E, et al. Enriched enteral nutrition may improve short-term survival in stage IV gastric cancer patients: A randomized, controlled trial. Nutrition. Apr 2017;36:46-53.
  23. Rubio I, Suva LJ, Todorova V, et al. Oral glutamine reduces radiation morbidity in breast conservation surgery. JPEN J Parenter Enteral Nutr. Sep 2013;37(5):623-630.
  24. Sun J, Wang H, Hu H. Glutamine for chemotherapy induced diarrhea: a meta-analysis. Asia Pac J Clin Nutr. 2012;21(3):380-385.
  25. Gianotti L, Braga M, Biffi R, et al. Perioperative intravenous glutamine supplemetation in major abdominal surgery for cancer: a randomized multicenter trial. Ann Surg. Nov 2009;250(5):684-690.
  26. Wise DR, Thompson CB. Glutamine addiction: a new therapeutic target in cancer. Trends Biochem Sci. Aug 2010;35(8):427-433.
  27. Huang W, Choi W, Chen Y, et al. A proposed role for glutamine in cancer cell growth through acid resistance. Cell Res. May 2013;23(5):724-727.
  28. Samocha-Bonet D, Chisholm DJ, Gribble FM, et al. Glycemic effects and safety of L-Glutamine supplementation with or without sitagliptin in type 2 diabetes patients-a randomized study. PLoS One. 2014;9(11):e113366.
  29. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. Aug 1999;4(4):239-248.
  30. Oliveira RJ, Sassaki ES, Monreal AC, et al. Pre-treatment with glutamine reduces genetic damage due to cancer treatment with cisplatin. Genet Mol Res. Dec 2 2013;12(4):6040-6051.
  31. Rubio IT, Cao Y, Hutchins LF, et al. Effect of glutamine on methotrexate efficacy and toxicity. Ann Surg. May 1998;227(5):772-778; discussion 778-780.
  32. Prescribing information. ENDARI (L-glutamine oral powder). Revised: 7/2017. Accessed July 14, 2021.
  33. Prescribing information. NutreStore [L-glutamine powder for oral solution]. Revised: 01/2008.
  34. Wright G, Jalan R. Management of hepatic encephalopathy in patients with cirrhosis. Best Pract Res Clin Gastroenterol. 2007;21(1):95-110.
  35. Niihara Y, Miller ST, Kanter J, et al. A Phase 3 Trial of l-Glutamine in Sickle Cell Disease. N Engl J Med. Jul 19 2018;379(3):226-235.
  36. Zhou Q, Verne ML, Fields JZ, et al. Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome. Gut.2019 Jun;68(6):996-1002.
  37. Pathak S, Soni TP, Sharma LM, Patni N, Gupta AK. A Randomized Controlled Trial to Evaluate the Role and Efficacy of Oral Glutamine in the Treatment of Chemo-radiotherapy-induced Oral Mucositis and Dysphagia in Patients with Oropharynx and Larynx Carcinoma. Cureus. 2019 Jun 7;11(6):e4855.
  38. Chang SC, Lai YC, Hung JC, Chang CY. Oral glutamine supplements reduce concurrent chemoradiotherapy-induced esophagitis in patients with advanced non-small cell lung cancer. Medicine (Baltimore). 2019 Feb;98(8):e14463.
  39. Naganuma A, Hoshino T, Ohno N, et al. β-Hydroxy-β-methyl Butyrate/L-Arginine/L-Glutamine Supplementation for Preventing Hand-Foot Skin Reaction in Sorafenib for Advanced Hepatocellular Carcinoma. In Vivo. 2019 Jan-Feb;33(1):155-161.
  40. Pimentel RFW, Fernandes SL. Effects of parenteral glutamine in critically ill surgical patients: a systematic review and meta-analysis. Nutr Hosp. Jul 13 2020;34(3):616-621.
  41. Hortensius LM, van Elburg RM, Nijboer CH, et al. Postnatal Nutrition to Improve Brain Development in the Preterm Infant: A Systematic Review From Bench to Bedside. Front Physiol. 2019 Jul 26;10:961.
  42. Valenzuela PL, Morales JS, Emanuele E, Pareja-Galeano H, Lucia A. Supplements with purported effects on muscle mass and strength. Eur J Nutr. 2019 Dec;58(8):2983-3008.
  43. de Menêses AG, Normando AGC, Porto de Toledo I, Reis PED, Guerra ENS. Effects of oral supplementation in the management of oral mucositis in cancer patients: A meta-analysis of randomized clinical trials. J Oral Pathol Med. 2020 Feb;49(2):117-125.
  44. Bowen JM, Gibson RJ, Coller JK, et al. Systematic review of agents for the management of cancer treatment-related gastrointestinal mucositis and clinical practice guidelines. Support Care Cancer. 2019 Oct;27(10):4011-4022.
  45. Hatami B, Saffaei A, Jamali F, Abbasinazari M. Glutamine powder-induced hepatotoxicity: it is time to understand the side effects of sports nutritional supplements. Gastroenterol Hepatol Bed Bench. 2020 Winter;13(1):86-89.
  46. Widjaja NA, Pratama A, Prihaningtyas R, et al. Efficacy Oral Glutamine to Prevent Oral Mucositis and Reduce Hospital Costs During Chemotherapy in Children with Acute Lymphoblastic Leukemia. Asian Pac J Cancer Prev. Jul 1 2020;21(7):2117-2121.
  47. Bartsch B, Then CK, Harriss E, et al. The role of dietary supplements, including biotics, glutamine, polyunsaturated fatty acids and polyphenols, in reducing gastrointestinal side effects in patients undergoing pelvic radiotherapy: A systematic review and meta-analysis. Clin Transl Radiat Oncol. Jul 2021;29:11-19.
  48. Sabry NM, Naguib TM, Kabel AM, Khafagy ES, Arab HH, Almorsy WA. Ameliorative Potential of L-Alanyl L-Glutamine Dipeptide in Colon Cancer Patients Receiving Modified FOLFOX-6 Regarding the Incidence of Diarrhea, the Treatment Response, and Patients’ Survival: A Randomized Controlled Trial.  Medicina (Kaunas). 2022 Mar 7;58(3):394.
  49. Sittitrai P, Ruenmarkkaew D, Booyaprapa S, Kasempitakpong B. Effect of a perioperative immune-enhancing diet in clean-contaminated head and neck cancer surgery: A randomized controlled trial. Int J Surg. 2021 Sep;93:106051.
  50. Pascoe J, Jackson A, Gaskell C, et al. Beta-hydroxy beta-methylbutyrate/arginine/glutamine (HMB/Arg/Gln) supplementation to improve the management of cachexia in patients with advanced lung cancer: an open-label, multicentre, randomised, controlled phase II trial (NOURISH). BMC Cancer. 2021 Jul 12;21(1):800.
  51. Alshawa A, Cadena AP, Stephen B, et al. Effects of glutamine for prevention of radiation-induced esophagitis: a double-blind placebo-controlled trial. Invest New Drugs. 2021 Aug;39(4):1113-1122.
  52. Heyland DK, Wibbenmeyer L, Pollack JA, et al.  A Randomized Trial of Enteral Glutamine for Treatment of Burn Injuries.  N Engl J Med. 2022 Sep 15;387(11):1001-1010.
  53. Ye J, Hu Y, Chen X, Chang C, Li K. Comparative Effects of Different Nutritional Supplements on Inflammation, Nutritional Status, and Clinical Outcomes in Colorectal Cancer Patients: A Systematic Review and Network Meta-Analysis.  Nutrients. 2023 Jun 16;15(12):2772.
  54. E Vasconcelos SCCM, Guerra ENS, de Menêses AG, et al. Effects of oral supplementation to manage radiation dermatitis in cancer patients: a systematic review.  Support Care Cancer. 2023 Mar 28;31(4):240.
  55. Miller LJ, Douglas C, McCullough FS, Stanworth SJ, Calder PC. Impact of enteral immunonutrition on infectious complications and immune and inflammatory markers in cancer patients undergoing chemotherapy: A systematic review of randomised controlled trials.  Clin Nutr. 2022 Oct;41(10):2135-2146.
  56. Podpeskar A, Crazzolara R, Kropshofer G, et al. Recommendations for Nutritional Supplementation in Pediatric Oncology: A Compilation of the Facts.   Nutrients. 2023 Jul 21;15(14):3239.
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