Glutamine for Preventing URI in Athletes

June 2001; Volume 4; 65-67

By Dónal P. O’Mathúna, PhD

Athletes have become very interested in glutamine supplementation to intensify their training regimens and improve performances. Glutamine is involved in numerous metabolic functions and currently is used in the alimentation of some critically ill patients under severe metabolic stress. Intense, endurance exercise elicits some of the same metabolic reactions that occur in critically ill patients.

In theory, glutamine supplementation would be expected to benefit athletes by preventing immunosuppression, reducing muscle breakdown, and providing additional fuel for gluconeogenesis. Good data suggest that glutamine supplementation may reduce the incidence of upper respiratory tract infection (URI), especially after exercise.

Athletes’ URI Incidence

People who exercise moderately and regularly have fewer URIs than sedentary people.1 However, athletes who engage in intense, prolonged exercise, such as marathons or triathlons, or who train excessively and become overtrained, have a much higher incidence of infections.2 For example, 13% of athletes who completed the 1987 Los Angeles marathon had infectious illnesses the week after the race compared to 2.2% of athletes with similar training regimens who did not compete that day.3 The risk of infection increases when runners exceed 60 miles/wk, and also has been observed in dancers and military personnel after intensive training.4 Some studies have found that about half of those who participated in prolonged endurance events had a URI in the following week.5

Hypothesis

Several studies on athletes’ blood collected immediately after intense endurance events have shown impaired immune activity, lowered immune cell counts, and lowered plasma glutamine concentration.6 Because glutamine acts as substrate for lymphocytes and macrophages,1 and because glutamine supplementation in critically ill patients has been shown to reduce infections and speed recovery,7 the "glutamine hypothesis" has been generated. The hypothesis proposes that the documented higher incidence of URIs after intense, prolonged exercise in athletes is the result of impaired immune function caused by lower than normal plasma glutamine levels.

Pharmacology

Glutamine is a nonessential amino acid, readily synthesized in the human body. It is the most abundant amino acid in humans, and its largest stores are found in skeletal muscle. Some describe glutamine as a "conditionally essential" amino acid. That is, under certain conditions of metabolic stress, the human body is unable to synthesize sufficient glutamine endogenously, requiring the provision of supplemental glutamine.8

The cells of the intestinal tract utilize large proportions of orally ingested glutamine; most of the glutamine required by other cells is synthesized in skeletal muscle.2 Adequate glutamine levels are important to maintain skeletal muscle mass and promote protein synthesis during healing. When broken down, protein in skeletal muscle releases glutamine.8 Glutamine also provides a number of metabolites, which are active during the immune response and are needed during DNA and RNA synthesis.4

Pathophysiology and Mechanism of Action

Plasma glutamine levels change rapidly, declining when the body enters catabolic conditions such as after major surgery, trauma, sepsis, and burns.2 Glutamine often is included in the total parenteral nutrition (TPN) that patients with these conditions may require.7

Glutamine must be available in the bloodstream at a fairly constant level for the cells of the immune system to respond adequately to stress or infections.4 Prolonged exercise and overtraining lead to lower plasma glutamine levels. Lower plasma glutamine levels stimulate further breakdown of skeletal muscle in an attempt to restore adequate plasma glutamine levels. Thus, for athletes, glutamine supplementation is believed to have muscle-sparing effects and to prevent suppression of the immune system.8

However, glutamine’s impact on athletic performance may be more complicated. Prolonged exercise can induce circulatory acidosis, and the kidneys use glutamine to buffer hydrogen ions. Glutamine also may be extracted from the plasma by the liver to make glucose (via gluconeogenesis). When athletes consume insufficient carbohydrate they enter acidosis more rapidly and their glutamine levels are reduced, perhaps contributing to their increased susceptibility to infections.9 Therefore, adequate intake of carbohydrate along with glutamine supplementation may also be significant in performance enhancement for endurance exercise.

Clinical Studies

All the studies found examined the impact of glutamine on immunosuppression in athletes. The results of eight separate, small studies, conducted by the same research team, have been summarized in two reports.1,5 Overall, 151 athletes consumed a drink containing either glutamine or placebo immediately after a marathon or ultra-marathon. They drank an equal volume of the same liquid two hours later, receiving a total dose of 5 g glutamine or placebo. The incidence of URIs in the week following the race was statistically different (P < 0.001) between the glutamine group (19.2%) and the placebo group (51.2 %).

The same research team conducted a study of 18 male runners in the 1993 Brussels Marathon.10 The runners were randomly assigned to consume a glutamine or placebo drink one and two hours after the race. Each test drink contained 5 g glutamine in 330 mL of water. Immune cell counts (natural killer cells, T-helper cells, and T-suppressor cells) were determined from blood drawn prior to the marathon and 15 minutes, 1 hour, and 16 hours after the race. No statistically significant differences in immune cell counts were observed between the glutamine and placebo groups. Incidence of URIs was not measured.

A study of 24 elite swimmers examined plasma glutamine levels during four weeks of intensive exercise during which eight swimmers exhibited symptoms of overtraining syndrome.11 The overtrained swimmers had significantly lower plasma glutamine levels than the other swimmers (P < 0.025), but only at the midpoint of the study period. Ten swimmers developed URIs during the study, but their plasma glutamine levels were not significantly different from those who did not develop URIs.

Eight healthy males rode an exercise bike for three bouts, resting for two hours between each exercise session.6 In the randomized, crossover study, all subjects repeated the protocol twice, one month apart. Each subject took nine doses of glutamine or placebo dissolved in carbohydrate-free lemonade (100 mg/kg body weight). The supplement was taken during each exercise bout, 30 minutes before the bout ended, at the end, and 30 minutes after it ended. The plasma glutamine levels declined from 508 micromolar before exercise to 402 micromolar two hours after exercise in the placebo group, while the levels in the glutamine group remained unchanged. However, the two groups showed no significant differences between the amount or activity of lymphokine-activated killer cells or lymphocytes.

Similar results were obtained with 16 competitors in the 1996 Copenhagen Marathon.12 At 0, 30, 60, and 90 minutes after the race, runners were given glutamine (100 mg/kg) or placebo. In the placebo group, plasma glutamine levels declined from 647 micromolar before the race to 470 micromolar afterward. Post-race levels in the glutamine group were the same as pre-race levels. The amount or activity of lymphokine-activated killer cells or lymphocytes did not differ between the two groups.

Adverse Effects

No adverse effects or drug interactions have been reported with trauma patients given more than 25 g/d glutamine.

Formulation

In most clinical studies, between 5 and 10 g L-glutamine was given either during and/or within two hours of prolonged exercise or an endurance competition. Glutamine is available as a powder, but in water is unstable and not very soluble. For consumption, each gram of glutamine is dissolved in at least 20 ml water or flavored drink. Several glutamine peptides were developed for TPN and are more soluble and stable in water.13 Both formulations are available for athletes in capsules and powders as dietary supplements.

Conclusion

Glutamine supplementation theoretically is justified to counteract the metabolic stresses of intense, endurance exercise. The evidence suggests that oral supplementation may decrease the incidence of URIs and therefore allow athletes to return to intense training more rapidly. Not all studies have confirmed this conclusion, although the studies finding no beneficial effects generally have been conducted after shorter bouts of exercise. Although other benefits of taking glutamine are possible, even less research is available in those areas than the small number of studies available regarding immunosuppression. No studies have examined whether supplementation improves athletic performance. No research has examined whether chronic supplementation with glutamine has any benefits or dangers.

Recommendation

Athletes and others who engage in prolonged strenuous exercise (such as hikers, marathon and ultra-marathon runners, triathletes, dancers, and those undergoing military exercises) may benefit from taking 5-10 g glutamine immediately after completing training to reduce the possibility of URIs. Endurance athletes who present with overtraining symptoms (excessive fatigue, unexpectedly poor performances) also may benefit from a trial period of glutamine to reduce the possibility of URIs, along with a reduced training load.14  

Dr. O’Mathúna is Professor of Bioethics and Chemistry at Mount Carmel College of Nursing in Columbus, OH.

References

1. Castell LM, et al. Does glutamine have a role in reducing infections in athletes? Eur J Appl Physiol Occup Physiol 1996;73:488-490.

2. Rohde T, et al. Glutamine, exercise, and the immune system—is there a link? Exerc Immunol Rev 1998;4: 49-63.

3. Nieman DC, et al. Infectious episodes in runners before and after the Los Angeles Marathon. J Sports Med Phys Fitness 1990;30:316-328.

4. Newsholme EA, Castell LM. Amino acids, fatigue and immunodepression in exercise. In: Maughan R, ed. Nutrition in Sport. Oxford, UK: Blackwell Science Inc.; 2000:153-170.

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

6. Rohde T, et al. Effect of glutamine supplementation on changes in the immune system induced by repeated exercise. Med Sci Sports Exerc 1998;30:856-862.

7. Jones C, et al. Randomized clinical outcome study of critically ill patients given glutamine-supplemented enteral nutrition. Nutrition 1999;15:108-115.

8. Antonio J, Street C. Glutamine: A potentially useful supplement for athletes. Can J Appl Physiol 1999; 24:1-14.

9. Blanchard MA, et al. The influence of diet and exercise on muscle and plasma glutamine concentrations. Med Sci Sports Exerc 2001;33:69-74.

10. Castell, LM, et al. Some aspects of the acute phase response after a marathon race, and the effects of glutamine supplementation. Eur J Appl Physiol Occup Physiol 1997;75:47-53.

11. Mackinnon LT, Hooper SL. Plasma glutamine and upper respiratory tract infection during intensified training in swimmers. Med Sci Sports Exerc 1996;28:285-290.

12. Rohde, T, et al. Competitive sustained exercise in humans, lymphokine activated killer cell activity, and glutamine—an intervention study. Eur J Appl Physiol Occup Physiol 1998;78:448-453.

13. Glutamine peptides. In: PDR for Nutritional Supplements. Montvale, NJ: Medical Economics Co.; 2001: 189-191.

14. Sharp NC, Koutedakis Y. Sport and the overtraining syndrome: Immunological aspects. Br Med Bull 1992;48:518-533.