James Meschino DC, MS, ROHP
L-Glutamine is the most abundant amino acid in the bloodstream and in the body. It is involved in more metabolic processes than any other amino acid, fulfilling a number of biochemical needs. It operates as a nitrogen shuttle, taking up excess ammonia and forming urea. Ammonia, a by-product of certain normal biochemical reactions in the body (including the brain) is toxic to the human body and thus glutamine serves an important function in helping to convert ammonia into urea, a non toxic end product, which the body can easily eliminate. L-Glutamine can contribute to the production of other amino acids, glucose, nucleotides, protein and glutathione. It is the principal metabolic fuel for the epithelial cells that line the small intestine (enterocytes), and for certain immune cells, namely lymphocytes, macrophages, and fibroblasts.1
Glutamine intake has been shown to enhance glutathione stores in conjunction with N-acetylcysteine, which may forestall the progression of HIV infection to AIDS in afflicted patients.2 Glutamine supplementation has been shown to help protect the gastrointestinal tract from damage by certain chemotherapy drugs (i.e. fluorouracil) and also prevents diarrhea that these drugs are known to produce.1,3
Glutamine supplementation has been shown to enhance immune system function and result in a lower level of infection and a shorter stay in hospital following surgery, radiation treatment, bone marrow transplantation, and in patients suffering from injury, compared with patients receiving Glutamine-free parenteral nutrition.4,5,6
Glutamine is a non-essential amino acid in that the body can synthesize it from the amino acid glutamic acid via the Glutamine synthase enzyme.7
However, during periods of fasting, starvation, critical illness, cancer, AIDS and following trauma, radiation treatment, surgery, bone marrow transplantation or in patients with a weakened immune system or catabolic stress, extra Glutamine replenishment has been shown to be beneficial to re-establish homeostatis.7
Glutamine is also a main anti-catabolic agent in muscle, which when supplemented, may help preserve muscle tissue (preventing its breakdown), during and after exercise. The heavier one trains, the greater the stress on the muscle and the greater is the use of Glutamine.8
During and following exercise or trauma, large amounts of alanine and Glutamine are released from muscle. They then travel through the blood stream to the liver where they can be used to form glucose and glycogen. The total loss of alanine and Glutamine induced by exercise is above the amount available in muscle and represents more than 50 percent of the total loss of muscle amino acids and nitrogen loss from muscle tissue during exercise. Studies show that during exercise other muscle amino acids (branched-chain amino acids) are used to donate their carbon skeletons to make alanine and certain alpha ketoacids and amino acids, such as alpha ketogluturate and glutamic acid are converted within the muscle to glutamine. Most notably, the branched-chain amino acid, leucine, isoleucine and valine serve as a substrate for alanine synthesis, but higher levels of intramuscular glutamine (via supplementation) may help to stop the catabolism of branched chain-amino acids, as glutamine can diffuse from the muscle and become a source of glucose in the liver to help maintain blood glucose and liver glycogen levels during periods of stress (i.e. exercise)8,9,10 This is also the role played by alanine, and thus, higher glutamine concentrations may reduce the requirement for alanine synthesis in the muscle, and thereby spare the breakdown of muscle tissue (branched-chain amino acid catabolism) during exercise and under other periods of catabolic stress (burn victims, infection, post surgery etc). 8,9,10
Supplementation Studies and Clinical Applications
Glutamine supplementation plus N-acetylcysteine supplementation enhances glutathione levels in HIV patients. Higher glutathione status correlates with a slowing of the progression of HIV to AIDS. Glutathione depletion is common in these patients due to increased free radical production. Glutathione is a first line antioxidant in the quenching of free radicals and participates in Phase I and Phase II liver detoxification functions.2
- Post-Trauma, Radiation Therapy, Post Bone Marrow Transplant, Certain Chemotherapy Agents
These patients have been shown to benefit from additional Glutamine, although it may be required as part of parenteral nutrition requiring medical prescription and supervision.4
- Anti-Catabolic Effect with Exercise
Oral Glutamine has been shown to maintain muscle mass in catabolic patients.11 However, Glutamine supplementation may increase ammonia levels and add to the ammonia burden of certain patients and athletes, jeopardizing recovery and performance respectively.8 To overcome this burden the use of alpha-ketogluturate has been shown to act as a Glutamine precursor, without contributing to ammonia build up. However, L-glutamine at a dose of up to 2,000-5,000 mg per day appears to be safe.
Oral ornithine alpha-ketogluturate reduces muscle catabolism in burn and surgery patients and is known to increase muscle Glutamine levels. Ornithine alpha-ketogluturate also stimulates the release of growth hormone and may thereby further provide an anti-catabolic and indirect anabolic effect on muscle tissue and lean mass, in general. A daily dosage of 2-4 mg per day of ornithine alpha-ketogluturate is required to increase growth hormone levels. 12,13,14
- Prevention of Infections in Athletes
Glutamine supplementation in endurance athletes has been shown to reduce the incidence of infections in this population, who are known to have their immune system suppressed by excess training of this nature. A double-blind, placebo-controlled study showed that Glutamine supplementation at a dose of 5 gm, taken after the end of exercise, in 151 endurance athletes resulted in a significantly lower incidence of infections (19%) compared to the placebo group (51%), during the study period.24 It has been suggested that the immune system suppression associated with endurance exercise, may be in part, due to reduction in Glutamine that results from intensive training.25 Another study, using the same protocol, demonstrated that 81% of athletes taking Glutamine had no subsequent infection during the study period compared to 49% in the placebo group.24
N.B. As oral Glutamine supplementation can potentially produce undesirable levels of ammonia in the body, it is unclear as to what levels of intake are safe (as a supplement). As an alternative oral ornithine alpha-ketogluturate has been used to elevate Glutamine status without ammonia build up when taken orally.
- HIV-infection: 7 gm, twice daily with 7 gm of L-Arginine twice daily.22
- Recovering from illness (elderly), surgery, burn or wound healing: 10-30 gms per day of ornithine alpha-ketogluturate, in divided doses.15,16
- Muscle anti-catabolic-anabolic effect with exercise training: 2-4 gms, three times daily with meals (ornithine alpha-ketogluturate) or 2,000 mg per day of L-Glutamine.17
- Prevention of Infections in Athletes: 5,000 mg per day of L-Glutamine post exercise session.24,25
Side Effects and Toxicity
- L-Glutamine supplementation may increase the ammonia load on the body. Thus, medical supervision should accompany high dose supplementation of L-Glutamine (above 2,000-5,000 mg per day).8
- Ornithine alpha-ketogluturate supplementation is not associated with any side effects to date.18,19
- Glutamine may trigger epileptic seizures in epileptic patients, two case reports exist to support this side effect.26
- Mania symptoms may develop at doses above 2,000 mg per day. These symptoms may develop in the absence of prior bipolar disease.26
Supplementation with L-Glutamine has been shown to reduce side effects associated with the use of methotrexate, paclitaxel and chemotherapy drugs. It may also improve the efficacy of some chemotherapy drugs.
Use of Glutamine in these applications should be implemented in collaboration with the attending medical physician.20,21
There are no well-known drug interactions with ornithine alpha-ketogluturate.2
- Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev 1999;4:239-48.
- Patrick L. Nutrients and HIV: part three N-acetylcysteine, alpha-lipoic acid, L-Lglutamine, and L-carnitine. Altern Med Rev 2000;4:290-305.
- Daniele B, Perrone F, Gallo C, Pignata S, De Martino S, De Vivo R, et al. Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial. Gut 2001;48:28-33.
- Griffiths RP. Outcome of critically ill patients after supplementation with glutamine. Nutrition 1997;13:752-4.
- Chang WK, Yang KD, Shaio MF. Effect of glutamine on TH1 and TH2 cytokine responses of human peripheral blood mononuclear cells. Clin Imunol 1999;3:294-301.
- Calder PC, Yaqoob P. Glutamine and the immune system. Amino Acids 1999;17;3:227-41.
- Buchman AL. Glutamine for the gut: mystical properties or an ordinary amino acid? Curr Gastroenterol Rep 1999;417-23.
- Roth E, et al. Glutamine: An anabolic effector. J Parent Ent Nutr 1990;14:1305-65.
- Felig P, Wahren J. Amino acid metabolism in exercising man. J Clin Invert 1971;50:2703-8.
- Felig P. The glucose-alanine cycle. Metabolism 1973;22:179-86.
- Lacey JM, Wilmore DW. Is glutamine a conditionally essential amino acid? Nutr Rev 1990;48:297-309.
- Cynobar L, et al. Action of ornithine alpha-ketoglutarate, ornithine hydrochloride and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects. J Amer Coll Nutr 1990;9:2-12.
- Cynobar L, et al. Action of ornithine alpha-ketoglutarate on protein metabolism in burn patients. Nutrition 1987;3:187-91.
- Leander U, et al. Nitrogen sparing effects Ornicetil in the immediate post operative state. Clin Nutr 1985;4:43-51.
- Cynobar L. Amino Acid Metabolism in thermal burns. JPEN 1989;13:196.
- De Bandt JP, Coudray-Lucas C, Lioret N, Soo-Kyung-Lim, Saizy R, Giboudeau J, et al. A randomized controlled trial of the influence of the mode of enteral ornithine alpha-ketoglutarate administration in burn patients. J Nutr 1998;128:563-9.
- Colgan M. Optimum Sports Nutrition, Your Competitive Edge. A Complete Nutritional Guide for Optimising Athletic Performance. New York, NY: Advanced Research Press: 1993. 379.
- Le Boucher J, Cynober LA. Ornithine alpha-ketoglutarate: the puzzle. Nutrition 1998;14:870-73 [review].
- Brocker P, Vellas B, Albarede JL, Poynard T. A two-centre, randomized, double-blind trial of ornithine oxoglutarate in 194 elderly, ambulatory, convalescent subjects. Age Aging 1994;23:303-6.
- Klimberg VS, Nwokedi E, Hutchins LF, Pappas AA, Lang NP, Broadwater JR, et al. Glutamine facilitates chemotherapy while reducing toxicity. J Parent Ent Nutr 1992;16(6Suppl):83S-7S.
- Klimberg VS, Nwokedi E, Hutchins LF, et al. Glutamine facilitates chemotherapy while reducing toxicity. JPEN J Parenter Enteral Nutr 1992;16(6Suppl):83S-7S.
- Healthnotes online. Healthnotes, Inc 2000.
- Klatz R. Grow Young with HGH. New York: Harper Perrenial Pub 1977. 206-7.
- Castell LM, Poortmans JR, Newsholme EA. Does glutamine have a role in reducing infections in athletes? Eur J Appl Physiol Occup Physiol 1996;23:488-90.
- Rowbottom DG, Keast D, Morton AR. The emerging role of glutamine as an indicator of exercise stress and overtraining. Sport Med 1996;21:80-90[review].
- Mebane AH. L-glutamine and mania. Am J Psychiatry 1984;141:1303[letter].