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Life Extension Magazine

LE Magazine January 2006
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Glutamine

This Amino Acid Helps to Preserve Muscle Mass
While Bolstering Immune and Gastrointestinal Health
By Armond Scipione
Glutamine synthetase enzyme computer model. This ligase enzyme forms chemical bonds between molecules. The different colors show the different sub-units that comprise the protein.

Glutamine is an important amino acid that may help to maintain muscle, boost the immune system, support gastrointestinal health, and sustain healthy growth hormone levels.1-5 Of the 20 amino acids needed for protein synthesis, glutamine is the most abundant, making up 50% of all amino acids in the blood and 60% of those in the body.1 It is found in high concentrations in skeletal muscle, lung, liver, brain, and stomach tissue. The best dietary sources of glutamine include poultry, beef, fish, cabbage, beets, and dairy products.

Amino acids are generally divided into two categories: essential and non-essential. Essential amino acids cannot be synthesized in the body and must be obtained from dietary sources. By contrast, non-essential amino acids are formed in the body. Glutamine, however, is referred to as a “conditionally” essential amino acid because in certain circumstances, the body is unable to produce enough glutamine to meet its needs.6 Studies have shown that prolonged exercise, surgery, burns, and infectious disease can deplete glutamine levels by as much as 50%.2 Under these conditions, supplementation with glutamine becomes crucial.

Maintaining Muscle Mass

Maintaining skeletal muscle is essential to good health and weight management. An increase in muscle mass increases the basal metabolic rate, or amount of calories the body burns while at rest. Glutamine may help to maintain healthy muscle tissue in people who are susceptible to a loss of muscle mass. One study found that patients who had major surgery and were given glutamine did not lose muscle mass during the recuperative period, even though they were inactive.7 The researchers concluded that glutamine supplementation counteracts the decline in muscle protein synthesis that occurs after surgery, while improving nitrogen retention. This research may prove especially useful to those on calorie-restricted diets, who often have difficulty maintaining muscle mass.

Increasing Growth Hormone

Produced by the pituitary gland, growth hormone supports health in a variety of ways. According to researchers, growth hormone levels begin falling around the age of 30 and continue to diminish over time, contributing to weight gain, reduced energy, and muscle loss.

Unfortunately, growth hormone injections require a prescription and are seldom covered by health insurance. The cost of supplementing with this revitalizing hormone can exceed $1,000 a month. However, in a study published in the American Journal of Clinical Nutrition, a relatively small amount of glutamine significantly increased growth hormone levels.4 The study subjects were given either a placebo or 2 grams of glutamine to drink. At 30 and 60 minutes after supplementation, their blood samples were analyzed for plasma growth hormone levels. Those who consumed glutamine had markedly increased growth hormone levels, while the placebo group exhibited no change in growth hormone levels.

Another study adds to the evidence that that glutamine boosts growth hormone levels. In a randomized, double-blind, placebo-controlled trial of 42 healthy middle-aged and elderly adults, the subjects consumed either a placebo or 5 grams of a nutritional supplement composed mainly of glutamine, glycine, and niacin. The supplement was ingested twice daily for three weeks. At baseline and at the study’s end, the investigators analyzed the participants’ blood. Ingesting the supplement led to a 70% increase in serum growth hormone levels compared to placebo, leading the researchers to conclude that an oral mixture of glutamine, glycine, and niacin can enhance growth hormone secretion in healthy adults.8

Boosting Immunity, Antioxidant Status

Because glutamine fuels white blood cells, it is essential in supporting the body’s immune system and immune response. Trauma, surgery, viral infections, and chemotherapy have all been shown to deplete glutamine levels.2 It has been suggested that diminished plasma glutamine levels may lead to suppressed immune function.5

Total parenteral nutrition is the intravenous administration of nutrients to critically ill patients. Until recently, however, commercial total parenteral nutrition solutions did not contain glutamine. This can result in atrophy of the gut mucosa and compromised integrity of the gastrointestinal tract.2 In one study, glutamine was added to the total parenteral nutrition of patients following bone marrow transplantation. The results indicated lower incidence of infection and shorter hospital stays compared to patients who received glutamine-free parenteral nutrition.9

Endurance athletes also have decreased plasma glutamine concentrations after prolonged, strenuous exercise.2,10 Post-exercise glutamine depletion and associated immunosuppression may render the athlete more susceptible to infection. In one study, a group of 151 elite runners and rowers were given two drinks containing either glutamine or a placebo immediately after and two hours after exercise. Over the following seven days, the percentage of infection-free patients was significantly higher in the glutamine group (81%) than in the placebo group (49%).10

Glutamine also plays an important role in the body’s antioxidant systems. In combination with L-cysteine and glycine, glutamine promotes glutathione synthesis in the liver. Glutathione neutralizes damaging free radicals and recharges oxidized vitamin C.11 Optimal amounts of glutathione are also necessary to support the immune system and liver function.12

Aiding Digestive Health

A healthy gastrointestinal tract is a vital component of overall well-being. In fact, the gastrointestinal tract lining serves as a first line of defense against disease-causing microorganisms. Enterocytes, which are epithelial cells lining the small intestine, use glutamine as their primary metabolic fuel.13 Glutamine is thus essential in maintaining the structural integrity of the intestinal lining. Insufficient glutamine may lead to a loss of gut mucosal integrity, which can allow toxins and infectious agents to be absorbed.14,15 This condition, known as increased intestinal permeability, may be associated with health problems such as allergies, skin disorders, and Crohn’s disease.2,16-18 By helping guard against increased intestinal permeability, glutamine may have applications in the management of these and other conditions.19

Insufficient levels of glutamine can also lead to atrophy of the villi in the small intestine. Resembling small fingers, the villi serve to increase the gastrointestinal tract’s absorptive surface area. Supplementing with glutamine can help increase villous height, thus helping to maximize the surface area available for nutrient absorption.2

Celiac disease, which is caused by the body’s abnormal immune response to gluten protein from wheat, barley, or rye, is associated with villous atrophy. While avoiding gluten protein is essential to managing celiac disease, glutamine’s ability to support the intestinal lining and increase villous height suggests that it may help speed the recovery of the mucosal lining.20,21

Crohn’s disease is a chronic inflammatory condition that can affect the small and large intestines, as well as other tissues of the body. A study comparing Crohn’s disease patients with healthy control subjects found that Crohn’s sufferers have an abnormally higher incidence of intestinal hyperpermeability. The investigators speculated that increased intestinal permeability could play a role in the genesis of Crohn’s disease. Further research is needed to clarify the relationship between Crohn’s and intestinal hyperpermeability, and whether glutamine may be an effective therapeutic tool in managing the condition.18

Altered intestinal permeability may also be involved in the causation of skin conditions and food allergies. In one study, individuals with intestinal hyperpermeability were more susceptible to experimentally induced chronic urticaria (an allergic skin condition marked by itching and hives) compared to healthy control subjects.16 Intestinal hyperpermeability has also been associated with multiple food intolerance and atopic dermatitis in infants and young children.17

By supporting the structural integrity of the gastrointestinal lining, glutamine may offer relief for a number of gastrointestinal conditions, as well as support for certain skin and allergic conditions.

Summary

Because glutamine can be synthesized in the human body, its use as a nutritional supplement has long been overlooked. However, factors as varied as viral infections, surgery, burns, infectious disease, and even prolonged exercise can significantly deplete levels of this multifunctional amino acid.2 In these instances in which the body is under marked stress, supplementation with glutamine becomes essential. An impressive body of research supports glutamine’s efficacy in helping to maintain muscle mass, revitalize the immune system, promote gastrointestinal health, and support healthy antioxidant levels.

References

1. 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;14(4 Suppl):137S-46S.

2. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999 Aug;4(4):239-48.

3. Rudman D, Kutner MH, Rogers CM, et al. Impaired growth hormone secretion in the adult population: relation to age and adiposity. J Clin Invest. 1981 May;67(5):1361-9.

4. Welbourne TC. Increased plasma bicarbonate and growth hormone after an oral glutamine load. Am J Clin Nutr. 1995 May;61(5):1058-61.

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

6. Lacey JM, Wilmore DW. Is glutamine a conditionally essential amino acid? Nutr Rev. 1990 Aug;48(8):297-309.

7. Hammarqvist F, Wernerman J, Ali R, von der DA, Vinnars E. Addition of glutamine to total parenteral nutrition after elective abdominal surgery spares free glutamine in muscle, counteracts the fall in muscle protein synthesis, and improves nitrogen balance. Ann Surg. 1989 Apr;209(4):455-61.

8. Arwert LI, Deijen JB, Drent ML. Effects of an oral mixture containing glycine, glutamine and niacin on memory, GH and IGF-I secretion in middle-aged and elderly subjects. Nutr Neurosci. 2003 Oct;6(5):269-75.

9. Ziegler TR, Young LS, Benfell K, et al. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study. Ann Intern Med. 1992 May 15;116(10):821-8.

10. Castell LM, Poortmans JR, Newsholme EA. Does glutamine have a role in reducing infections in athletes? Eur J Appl Physiol Occup Physiol. 1996;73(5):488-90.

11. Shang F, Lu M, Dudek E, Reddan J, Taylor A. Vitamin C and vitamin E restore the resistance of GSH-depleted lens cells to H2O2. Free Radic Biol Med. 2003 Mar 1;34(5):521-30.

12. Hultberg B, Hultberg M. High glutathione turnover in human cell lines revealed by acivicin inhibition of gamma-glutamyltranspeptidase and the effects of thiol-reactive metals during acivicin inhibition. Clin Chim Acta. 2004 Nov;349(1-2):45-52.

13. O’Dwyer ST, Smith RJ, Hwang TL, Wilmore DW. Maintenance of small bowel mucosa with glutamine-enriched parenteral nutrition. JPEN J Parenter Enteral Nutr. 1989 Nov;13(6):579-85.

14. Li J, Langkamp-Henken B, Suzuki K, Stahlgren LH. Glutamine prevents parenteral nutrition-induced increases in intestinal permeability. JPEN J Parenter Enteral Nutr. 1994 Jul;18(4):303-7.

15. Unno N, Fink MP. Intestinal epithelial hyperpermeability. Mechanisms and relevance to disease. Gastroenterol Clin North Am. 1998 Jun;27(2):289-307.

16. Kanny G, Moneret-Vautrin DA, Schohn H, et al. Abnormalities in histamine pharmacodynamics in chronic urticaria. Clin Exp Allergy. 1993 Dec;23(12):1015-20.

17. Moneret-Vautrin DA, Kanny G, Guerin L, Flabbee J, Lemerdy P. The multifood allergy syndrome. Allerg Immunol.(Paris). 2000 Jan;32(1):12-5.

18. Secondulfo M, de Magistris L, Fiandra R, et al. Intestinal permeability in Crohn’s disease patients and their first degree relatives. Dig Liver Dis. 2001 Nov;33(8):680-5.

19. Khan J, Iiboshi Y, Cui L, et al. Alanyl-glutamine-supplemented parenteral nutrition increases luminal mucus gel and decreases permeability in the rat small intestine. JPEN J Parenter Enteral Nutr. 1999 Jan;23(1):24-31.

20. Alaedini A, Green PH. Narrative review: celiac disease: understanding a complex autoimmune disorder. Ann Intern Med. 2005 Feb 15;142(4):289-98.

21. Messing B, Dutra SL, Thuillier F, Darmaun D, Desjeux JF. Whole-body protein metabolism assessed by leucine and glutamine kinetics in adult patients with active celiac disease. Metabolism. 1998 Dec;47(12):1429-33.