Uses of this Supplement
Crohn's Disease
Peptic Ulcer
Wounds
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Look Up > Supplements > Glutamine
Glutamine
Overview
Dietary Sources
Constituents/Composition
Commercial Preparations
Therapeutic Uses
Dosage Ranges and Duration of Administration
Side Effects/Toxicology
Warnings/Contraindications/Precautions
Interactions
References

Overview

Glutamine is an amino acid, one of the building blocks of protein that are linked together by peptide bonds in specific chemical arrangements to form proteins. It is found in both plant and animal proteins and is available in a variety of supplemental forms. Glutamine helps the body maintain the correct acid–alkaline balance and is a necessary part of the synthesis of RNA and DNA. Glutamine also helps promote a healthy digestive tract.

Unlike other amino acids that have a single nitrogen atom, glutamine contains two nitrogen atoms that enable it to transfer nitrogen and remove ammonia from body tissues. Glutamine readily passes the blood–brain barrier and, within the brain, is converted to glutamic acid, which the brain needs to function properly. It also increases gamma-aminobutyric acid (GABA) in the brain, which is also needed for proper mental activity.

Glutamine is the most plentiful free amino acid in muscles. Its ability to help build and maintain muscle makes glutamine especially attractive to dieters and muscle-builders, but that same ability also helps prevent muscle-wasting associated with prolonged inactivity, disease, and stress. With sufficient glutamine in the bloodstream, muscle loss that would otherwise be caused by injury, surgery, trauma, prolonged illness, or stress can be prevented. The body uses glutamine and glucose to make glucosamine, an amino sugar that plays a key role in the formation of nails, tendons, skin, eyes, bones, ligaments, heart valves, and mucous secretions throughout the body.

Conditions that have been treated with L-glutamine supplements include fibrosis, autoimmune diseases, arthritis, intestinal ailments, peptic ulcers, diseases of the connective tissues, tissue damage caused by radiation treatment, developmental disabilities, epilepsy, schizophrenia, fatigue, and impotence.

Because L-glutamine possibly reduces sugar and alcohol cravings, it could be considered for treating recovering alcoholics. Suggested dose: 1,000 mg tid with 50 mg of vitamin B6, on an empty stomach.


Dietary Sources

Glutamine is found in animal proteins and vegetable proteins. Natural sources of glutamine include soy proteins, milk, meats, raw spinach, raw parsley, and cabbage.

Nutrition experts recommend choosing supplements whose label describes the contents as USP pharmaceutical grade L-crystalline amino acids.

The purest form of amino acid supplements is called free-form and is available in powder or encapsulated powder. Free-form amino acids are readily absorbed and nonallergenic, and are stable at room temperature but destroyed by high temperatures (350 to 660 F) typical of cooking.


Constituents/Composition

Glutamine is available as an isolated amino acid or in combination amino acid and protein supplements.

L-forms of amino acid supplements such as L-glutamine are believed to be more compatible with human biochemistry than D-forms because the chemical structure spirals to the left.


Commercial Preparations

Glutamine is available in a variety of foods and food supplements, protein mixtures, amino acid formulas, and individual supplements in liquid, powder, tablets, and capsules. Supplemental forms of glutamine are sold in vitamin and mineral sections of most pharmacies and health food stores.


Therapeutic Uses
  • Glutamine is not one of the nine essential amino acids (which must be ingested because the body cannot manufacture them). However, extreme stress and prolonged illness may cause glutamine to become an essential amino acid, and hence a valuable dietary component.
  • Glutamine aids recovery after surgery, wounds or injury, hemorrhage, prolonged illness including AIDS and cancer, and chemotherapy.
  • In one recent study, glutamine reduced mouth pain by 4.5 days compared to placebo users in 24 methotrexate chemotherapy patients suffering from mouth sores and difficulty swallowing.
  • Glutamine speeds healing of peptic ulcers.
  • Because glutamine is one of the primary fuels used by intestinal lining cells, supplementation with glutamine helps restore gastric mucosa and improves mucosa metabolism. Glutamine also helps repair the gastrointestinal lining after damage caused by radiation or leaky gut syndrome, and benefits chronic GI diseases such as colitis, AIDS, cancer, and Crohn's disease. Large doses (more than 1,000 mg tid) helped protect chemotherapy patients' stomach linings, according to a 1996 study.
  • Glutamine helps suppress food cravings.

Dosage Ranges and Duration of Administration
  • Glutamine supplements, like all amino acid supplements, should be taken on an empty stomach, preferably in the morning or between meals.
  • For peptic ulcers, 500 mg daily, taken on an empty stomach, is recommended.
  • To curb food cravings, 1,000 mg daily is recommended.
  • To treat irritable bowel syndrome (IBS), eliminate foods that trigger symptoms and take glutamine (500 mg tid) and peppermint oil (1 capsule three to six times daily).
  • For stasis ulcers (open sores on the leg that are caused by poor blood flow), take each day: glutamine (500 mg) with a basic nutritional supplement program and vitamin C (2,000 mg in divided doses with meals and at bedtime), vitamin A (10,000 IU), zinc (22.5 to 50 mg), and vitamin E (400 IU orally and additional vitamin E oil squeezed from capsules onto the wound to aid healing and prevent recurrence).
  • To aid wound healing, take glutamine (500 mg) with a basic vitamin-mineral formula and vitamin C (2,000 mg divided at meals and bedtime), vitamin A (10,000 IU), zinc (22.5 to 50 mg), vitamin E (400 IU), and vitamin B3 (100 mg) daily.

Side Effects/Toxicology

Glutamine can worsen damage caused by any disease that allows ammonia to accumulate to excess in the blood. It is not recommended in patients who have Reye's syndrome, kidney disease, cirrhosis of the liver, or other illnesses that cause overload of ammonia in the body.

Proteins (taken as a source of amino acid glutamine) should not be overused. In healthy persons, protein is safely metabolized and broken down by the liver into glucose and ammonia, which is a toxin. If one consumes an excessive amount of protein or if digestion is poor or liver function is impaired, ammonia can accumulate in the body and cause damage. Strenuous exercise can also promote excess ammonia in the body. Too much ammonia can cause encephalopathy or hepatic coma, or it can pose serious health threats. As ammonia is broken down by the body into urea, the urea can cause kidney inflammation and back pain.


Warnings/Contraindications/Precautions
  • Glutamine supplements must be kept completely dry because moisture causes glutamine powder to break down into ammonia and pyroglutamic acid.
  • Glutamine in foods is readily destroyed by cooking.
  • Despite the similarity of their names, the following substances are different and are not interchangeable: glutamine; glutamic acid, also called glutamate; glutathione; gluten; and monosodium glutamate.

Interactions
Doxorubicin; Fluorouracil; Methotrexate

In vitro, glutamine reduced the frequency of doxorubicin-induced chromosomal aberrations (Tavares et al. 1998). In rats, treatment with glutamine before and during doxorubicin administration diminished the cardiotoxic effects of the drug by upregulating glutathione synthesis in the heart (Cao et al. 1999). Clinically, treatment with glutamine (4 g bid) and doxorubicin reduced the incidence and severity of mucositis relative to prior experience with chemotherapy (Skubitz and Anderson 1996).

Chemotoxic effects were absent in 9 breast cancer patients treated with glutamine (0.5 g/kg/day) during therapy with escalating doses of methotrexate followed by doxorubicin; the median survival of participants was 35 months (Rouse et al. 1995). Preclinical and clinical studies have demonstrated that glutamine enhances the activity and tumor-selectivity of methotrexate therapy, while actively protecting normal tissues. In rats, glutamine (1 gm/kg/day po) and an intraperitoneal dose of methotrexate (20 mg/kg) increased the concentration of the drug in tumors threefold (Rubio et al. 1998). Supplemental glutamine also increased the therapeutic index for methotrexate by enhancing glutathione synthesis systemically, thus improving drug tolerance while simultaneously depleting tumor glutathione in rats (Rouse et al. 1995). In addition, rats fed a glutamine-supplemented diet (3%) had decreased clearance and urinary excretion of methotrexate by 25% and 65%, respectively (Charland et al. 1995).

Whether glutamine supplementation is beneficial during treatment with 5-fluorouracil appears to be questionable. In two placebo-controlled trials involving several patients, oral glutamine supplementation did not have a significant effect on 5-FU-induced mucositis (Jebb et al. 1994; Okuno et al. 1999). However, in another trial, glutamine (glycyl-L-glutamine) did reduce indices of ulcerations in the gastric and duodenal mucosae significantly (Decker-Baumann and Buhl 1999).


References

Balch J, Balch P. Prescription for Nutritional Healing. 2nd ed. Garden City Park, NY: Avery Publishing Group; 1997.

Cao Y, Kennedy R, Klimberg VS. Glutamine protects against doxorubicin-induced cardiotoxicity. J Surg Res. 1999;85:178-182.

Castell LM, Newsholme EA. The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise. Nutrition. 1997;13:738-742.

Charland SL, Bartlett DL, Torosian MH. A significant methotrexate-glutamine pharmacokinetic interaction. Nutr. 1995;11:154-158.

Decker-Baumann C, Buhl K. Reduction of chemotherapy-induced side-effects by parenteral glutamine supplementation in patients with metastatic colorectal cancer. Eur J Cancer. 1999;35:202-207.

Den Hond E, Hiele M, Peeters M, Ghoos Y, Rutgeerts P. Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn's disease. J Parenter Enteral Nutr. 1999;23:7-11.

Giller R, Matthews K. Natural Prescriptions. New York, NY: Carol Southern Books/Crown Publishers; 1994.

Gottlieb B. New Choices in Natural Healing. Emmaus, Pa.: Rodale Press, Inc.; 1995.

Haas R. Eat Smart, Think Smart. New York, NY: HarperCollins; 1994.

Jebb SA, Osborne RJ, Maughan TS. 5-fluorouracil and folinic acid-induced mucositis: no effect of oral glutamine supplementation. Br J Cancer. 1994;70: 732-735.

Kirschmann G, Kirschmann J. Nutrition Almanac. 4th ed. New York, NY: McGraw Hill; 1996.

LaValle J. Natural agents for a healthy GI tract. Drug Store News. January 12, 1998;20.

Li J, Langkamp-Henken B, Suzuki K, Stahlgren LH. Glutamine prevents parenteral nutrition-induced increases in intestinal permeability. J Parenter Enteral Nutr. 1994;18:303-307.

Napoli M. Chemo effect alleviated. Health Facts. October 1998;23:6.

Noyer CM, Simon D, Borczuk A, Brandt LJ, Lee MJ, Nehra V. A double-blind placebo-controlled pilot study of glutamine therapy for abnormal intestintal permeability in patients with AIDS. Am J Gastroenterol. 1998;93:972-975.

Okuno SH, Woodhouse CO, Loprinzi CL. Phase III controlled evaluation of glutamine for decreasing stomatitis in patients receiving fluorouracil (5-FU)-based chemotherapy. Am J Clin Oncol. 1999;22:258-261.

Rouse K, Nwokedi E, Woodliff JE, et al. Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism. Ann Surg. 1995;221: 420-426.

Rubio IT, Cao Y, Hutchins LF, et al. Effect of glutamine on methotrexate efficacy and toxicity. Ann Surg. 1998;227:772-780.

Shabert JK, Wilmore DW. Glutamine deficiency as a cause of human immunodeficiency virus wasting. Med Hypotheses. March 1996; 46:252-256.

Skubitz KM, Anderson PM. Oral glutamine to prevent chemotherapy induced stomatitis: a pilot study. J Lab Clin Med. 1996;127:223-228.

Tavares DC, Cecchi AO, Antunes LM, et al. Protective effects of the amino acid glutamine and of ascorbic acid against chromosomal damage induced by doxorubicin in mammalian cells. Teratog Carcinog Mutagen. 1998;18:153-161.

Yoshida S, Matsui M, Shirouzu Y, Fujita H, Yamana H, Shirouzu K. Effects of glutamine supplements and radiochemotherapy on systemic immune and gut barrier function in patients with advanced esophageal cancer. Ann Surg. 1998;227:485-491.


Copyright © 2000 Integrative Medicine Communications

This publication contains information relating to general principles of medical care that should not in any event be construed as specific instructions for individual patients. The publisher does not accept any responsibility for the accuracy of the information or the consequences arising from the application, use, or misuse of any of the information contained herein, including any injury and/or damage to any person or property as a matter of product liability, negligence, or otherwise. No warranty, expressed or implied, is made in regard to the contents of this material. No claims or endorsements are made for any drugs or compounds currently marketed or in investigative use. The reader is advised to check product information (including package inserts) for changes and new information regarding dosage, precautions, warnings, interactions, and contraindications before administering any drug, herb, or supplement discussed herein.