Glutamine

Overview

Glutamine is the most abundant amino acid in the body – comprising approximately half of the free amino acids in the blood and muscle. As a non-essential amino acid, glutamine can be produced in the body by conversion from another amino acid - glutamic acid (primarily by the skeletal muscle and liver). Glutamine’s main functions in the body include serving as a precursor in the synthesis of other amino acids and for conversion into glucose for energy. Cells of the immune system, the small intestine and the kidney are the major consumers of glutamine – making “immune boosting” and “immune maintenance” claims for glutamine supplements quite common. In addition, and peripherally related to the control of immune response and inflammation, are claims for glutamine supplements in maintaining muscle mass, reducing post-exercise catabolism (muscle tissue breakdown), and accelerating recovery from intense exercise.

Intense exercise training results in a well-described drop in plasma glutamine levels. Chronically low glutamine levels have been implicated as a possible contributing factor in athletic overtraining syndrome as well as the transient immunosuppression and increased risk of infections that typically affects competitive athletes during intense training and competition. Under conditions of metabolic stress, the body’s need for glutamine may become “conditionally essential” – exceeding its ability to produce adequate levels and meaning that a dietary source is required to prevent catabolism of skeletal muscle – the primary source of stored glutamine in the body.

Comments

Glutamine supplements are relatively inexpensive compared to other amino acid supplements. For anybody exposed to heightened levels of stress, such as those recovering from injury, surgery, or intense exercise, glutamine supplements represent an economical way to promote tissue repair, reduce muscle catabolism and help prevent infections.

Scientific Support

A significant body of scientific literature exists to support the beneficial effects of glutamine supplementation in maintaining muscle mass and immune system function in critically ill patients and in those recovering from extensive burns and major surgery. When plasma glutamine levels fall, skeletal muscles may enter a state of catabolism in which muscle protein is degraded to provide free glutamine for the rest of the body. Since skeletal muscle is the major source of glutamine (other than the diet), prolonged deficits in plasma glutamine can lead to a significant loss of skeletal muscle protein and muscle mass. Post-surgical deposition of collagen (a marker for “wound healing”) can be enhanced by amino acid supplementation containing 14 grams of glutamine (Williams et al. 2002), but a lower dose of mixed amino acids containing glutamine (2.9 grams) provided no change in athletic performance or on adaptations to cycling training (Vukovich et al. 1997).

In recent years, several studies have been conducted on glutamine supplementation in athletes and a strong rationale exists for the efficacy of glutamine supplements in athletic populations. For example, glutamine’s role in immune system support has been shown to prevent infections following intense bouts of physical activity (which tend to reduce plasma glutamine levels). Glutamine supplements have also been shown to play a role in counteracting the catabolic (muscle-wasting) effects of stress hormones such as cortisol, which are typically elevated by strenuous exercise. Under conditions of stress-induced protein wasting in adults and children, including burns, post-surgery, and some forms of cancer, glutamine supplementation is associated with reduced protein (muscle tissue) breakdown (des Robert et al. 2002), enhanced lymphocyte function (Yoshida et al. 2001), reduced gut permeability (Klimberg et al. 1992, van Acker et al. 2000, Yoshida et al. 1998, Yoshida et al. 2001), and reduced infections (Barbosa et al. 1999, Burke et al. 1989, O’Riordain et al. 1996). It is interesting to note that although glutamine supplementation has shown benefits in maintaining immune system function and enhancing tumoricidal effectiveness in rodents of during chemotherapy and radiotherapy in various types of cancer (Klimberg et al. 1992), glutamine is also described as an essential factor for tumor growth and as an especially avid consumer of glutamine (Medina 2001, Souba 1993).

The function of glutamine in stimulating glycogen synthase, the enzyme which controls the synthesis and storage of glycogen fuel storage in muscles and liver, may provide a mechanism by which glutamine supplements promote enhanced fuel stores. Glutamine is also thought to increase cell volume, where it may stimulate the activity of enzymes in the liver and muscles involved in glycogen storage as well as those involved in anabolic activities such as protein synthesis. Glutamine supplements have also been hypothesized to increase levels of growth hormone, which may be expected to help stimulate protein synthesis and encourage gains in muscle mass and strength, but reliable evidence for this effect of glutamine supplements has not been demonstrated by clinical studies.

Safety / Dosage

Glutamine supplements are well tolerated at levels up to at least 20 grams per day and intakes of as much as 40 grams per day should induce no significant adverse effects outside of mild gastrointestinal discomfort. As with any isolated amino acid supplement, consumption in divided doses throughout the day should increase total body stores without posing significant absorption issues. For the immune system support and anti-catabolic actions that are of interest to most athletes, recommended doses range from 1-10 grams.

References

1.Alvestrand A, Bergstrom J, Furst P, Germanis G, Widstam U. Effect of essential amino acid supplementation on muscle and plasma free amino acids in chronic uremia. Kidney Int. 1978 Oct;14(4):323-9.

2.Barbosa E, Moreira EA, Goes JE, Faintuch J. Pilot study with a glutamine-supplemented enteral formula in critically ill infants. Rev Hosp Clin Fac Med Sao Paulo. 1999 Jan-Feb;54(1):21-4.

3.Burke DJ, Alverdy JC, Aoys E, Moss GS. Glutamine-supplemented total parenteral nutrition improves gut immune function. Arch Surg. 1989 Dec;124(12):1396-9.

4.Calder PC, Yaqoob P. Glutamine and the immune system. Amino Acids. 1999;17(3):227-41.

5.Carli F, Webster J, Ramachandra V, Pearson M, Read M, Ford GC, McArthur S, Preedy VR, Halliday D. Aspects of protein metabolism after elective surgery in patients receiving constant nutritional support. Clin Sci (Colch). 1990 Jun;78(6):621-8.

6.Castell LM, Newsholme EA. The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise. Nutrition. 1997 Jul-Aug;13(7-8):738-42.

7.des Robert C, Le Bacquer O, Piloquet H, Roze JC, Darmaun D. Acute effects of intravenous glutamine supplementation on protein metabolism in very low birth weight infants: a stable isotope study. Pediatr Res. 2002 Jan;51(1):87-93.

8.Klimberg VS, Nwokedi E, Hutchins LF, Pappas AA, Lang NP, Broadwater JR, Read RC, Westbrook KC. Glutamine facilitates chemotherapy while reducing toxicity. JPEN J Parenter Enteral Nutr. 1992 Nov-Dec;16(6 Suppl):83S-87S.

9.Medina MA. Glutamine and cancer. J Nutr. 2001 Sep;131(9 Suppl):2539S-42S.

10.Newsholme EA, Calder PC. The proposed role of glutamine in some cells of the immune system and speculative consequences for the whole animal. Nutrition. 1997 Jul-Aug;13(7-8):728-30.

11.O'Riordain MG, De Beaux A, Fearon KC. Effect of glutamine on immune function in the surgical patient. Nutrition. 1996 Nov-Dec;12(11-12 Suppl):S82-4.

12.Smith DJ, Norris SR. Changes in glutamine and glutamate concentrations for tracking training tolerance. Med Sci Sports Exerc. 2000 Mar;32(3):684-9.

13.Souba WW. Glutamine and cancer. Ann Surg. 1993 Dec;218(6):715-28.

14.van Acker BA, Hulsewe KW, Wagenmakers AJ, von Meyenfeldt MF, Soeters PB. Response of glutamine metabolism to glutamine-supplemented parenteral nutrition. Am J Clin Nutr. 2000 Sep;72(3):790-5.

15.Vukovich MD, Sharp RL, Kesl LD, Schaulis DL, King DS. Effects of a low-dose amino acid supplement on adaptations to cycling training in untrained individuals. Int J Sport Nutr. 1997 Dec;7(4):298-309.

16.Walsh NP, Blannin AK, Robson PJ, Gleeson M. Glutamine, exercise and immune function. Links and possible mechanisms. Sports Med. 1998 Sep;26(3):177-91.

17.Williams JZ, Abumrad N, Barbul A. Effect of a specialized amino acid mixture on human collagen deposition. Ann Surg. 2002 Sep;236(3):369-74.

18.Yoshida S, Kaibara A, Ishibashi N, Shirouzu K. Glutamine supplementation in cancer patients. Nutrition. 2001 Sep;17(9):766-8.

19.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 Apr;227(4):485-91.

20.Young LS, Bye R, Scheltinga M, Ziegler TR, Jacobs DO, Wilmore DW. Patients receiving glutamine-supplemented intravenous feedings report an improvement in mood. JPEN J Parenter Enteral Nutr. 1993 Sep-Oct;17(5):422-7.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.