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News Briefs

Glutamine and Arginine: Immunonutrients and Metabolic Modulators?

Joyner, Michael J.

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Exercise and Sport Sciences Reviews: July 2005 - Volume 33 - Issue 3 - p 105-106
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Throughout history there has been an interest in using various nutritional strategies to improve athletic performance, to help athletes, and to recover from strenuous exercise. Early work in this area before World War II laid the ground work for ideas about optimal regimens for carbohydrate feeding before, during, and after exercise, as well as optimal fluid replacement during exercise. These general topics were explored extensively beginning in the 1960s, and interest in them remains high. More recently there has been interest in the possibility that specific amino acids might be used as part of the advanced nutritional strategies in athletes and in selected patient groups. There are four specific potential “targets” for this general strategy: 1) improved immune function; 2) modulation of the hormonal responses to exercise; 3) modification of postexercise recovery; and 4) modification of cardiac or skeletal muscle metabolism during exercise.

Modification of Immune Function by Glutamine

Glutamine supplementation has been postulated to be an important immuno-modulating amino acid in a variety of disease states, during critical illness in the intensive care unit, and as an adjunct to maintain health in athletes undergoing prolonged intense endurance exercise training. A recent review by Castell (1) provides an overview on this topic. Parallels between endurance training and other stressful situations including trauma and starvation are made. The general idea is that during stressful situations, the concentration of glutamine in the blood can be reduced substantially, and that glutamine is a key fuel for several cell types in the immune system. In a variety of clinical situations, glutamine supplementation has been shown to have a variety of positive effects on morbidity and mortality, and these improved outcomes have been linked to altered immune cell function in some studies. There is also a decrease in the incidence of self-reported illness in athletes undergoing prolonged intense endurance training. This review concludes that there is a lack of firm evidence on this topic, but that positive evidence is generally emerging.

In a second paper, Hiscock et al. (2) used a strategy of glutamine supplementation before and during exercise and demonstrated that the normal decline in plasma glutamine concentrations associated with 2 h of cycle ergometry at 75% O2max was blunted. Additionally, associated with the enhanced plasma levels of glutamine were enhanced exercise-associated IL-6 levels. The authors postulate that the glutamine supplementation may have augmented IL-6 production from the exercising skeletal muscle. The extent to which changes in IL-6 may enhance or modulate immune function after exercise remains to be determined.

Effects of Amino Acid Supplementation on Hormonal and Recovery Responses to Acute Exercise

There is emerging evidence that addition of protein or amino acids to glucose containing beverages might enhance postexercise glycogen repletion in endurance athletes. Williams et al. (5) report that after 2-h rides at 65–75% max, ingestion of the carbohydrate/protein-containing beverage after exercise resulted in a greater plasma glucose response, a greater insulin response, and a 128% greater storage of muscle glycogen. The authors interpret these findings to suggest that there might be an additive effect between carbohydrate ingestion, insulin, and glycogen storage when amino acids are added to glucose containing drinks. One possible mechanism is that arginine (and perhaps glutamine) can augment insulin secretion in the postexercise period. In a previous study, Yaspelkis and Ivy (6) presented evidence that arginine supplementation can improve postexercise glycogen storage after 2-h rides at approximately 65–75% O2max. Evidence was also presented that the arginine supplementation blunted postexercise carbohydrate oxidation, and this reduced carbohydrate oxidation might also have contributed to increased carbohydrate availability for postexercise glycogen resynthesis. Though it is well known that addition of small amounts of protein to glucose-containing beverages can enhance postexercise skeletal muscle protein synthesis and suppress postexercise skeletal muscle protein breakdown, it also appears as if this strategy can enhance postexercise muscle glycogen synthesis. Thus, postexercise protein consumption can have two potential positive effects on skeletal muscle recovery after exercise. One key mechanism in this response might be the effects of arginine or other amino acids on insulin secretion and/or carbohydrate metabolism.

Effects of Arginine and Glutamine on Muscle Metabolism

There is also evidence that amino acid supplementation can alter cardiac and skeletal muscle metabolism during exercise. Schaefer et al. (4) investigated the effects of L-arginine supplementation on cardiovascular, respiratory, and metabolic response to maximal exercise. They used intravenous L-arginine supplementation and compared it to a saline control experiment. The arginine supplementation did not affect exercise-induced increases in heart rate, O2, or CO2, but peak plasma ammonia and lactate values were lower during the maximal exercise trial with arginine. In further analysis, the authors point out that the L-arginine caused an increase in L-citrulline during exercise, and that there was an inverse relationship between changes in lactate and L-citrulline concentrations after the arginine load. The results suggest that perhaps the arginine supplementation affected metabolism via changes in nitric oxide. It is also possible that either the arginine or the citrulline had some direct effects on metabolism, or some secondary effects through modulation of hormonal responses to exercise. Whereas these data do not report performance, they suggest that well-designed trials of arginine supplementation on endurance performance at relatively high workloads might be warranted.

In a patient study, Khogali et al. (3) performed a combined study in isolated working hearts and in patients with stable myocardial ischemia. They demonstrated that addition of glutamine during ischemia reperfusion studies in isolated hearts improved recovery in the reperfusion period in their model. Additionally, a single dose of glutamine (80 mg·kg−1) delayed the time of onset to 1 mm of ST segment depression in their patients. The authors conclude that glutamine may be cardioprotective in patients with coronary heart disease. They speculate on its effects on cardiac metabolism. It is reasonable to raise the question about whether similar effects would be seen in skeletal muscle during prolonged intense exercise in humans.


The review article and experimental papers summarized in this News Briefs suggest that in addition to their effects on postexercise skeletal muscle recovery via alterations in protein degradation and supplementation of specific amino acids before, during, and after exercise, amino acids might have beneficial effects on immune function and skeletal muscle metabolism during and after exercise. Additional mechanistic and applied studies in this area are clearly warranted. This line of investigation might be fruitful for individuals interested in applied sports nutrition, ergogenic aids, and the basic biology of skeletal muscle metabolism during exercise. It might also be of interest to those who seek to optimize nutritional support for patients with diseases that cause inadequate blood flow to cardiac or skeletal muscle.


1. Castell, L. Glutamine supplementation in vitro and in vivo, in exercise and immunodepression. Sports Med. 33:323–345, 2003.
2. Hiscock, N., E.W. Petersen, K. Krzywkowski, J. Boza, J. Halkjaer-Kristensen, and B.K. Pedersen. Glutamine supplementation further enhances exercise-induced plasma IL-6. J. Appl. Physiol. 95:145–148, 2003.
3. Khogali, S.E.O., S.D. Pringle, B.V. Weryk, and M.J. Rennie. Is glutamine beneficial in ischemic heart disease? Nutrition 18:123–126, 2002.
4. Schaefer, A., F. Piquard, B. Geny, S. Doutreleau, E. Lampert, B. Mettauer, and J. Lonsdorfer. L-arginine reduces exercise-induced increase in plasma lactate and ammonia. Int. J. Sports Med. 23:403–407, 2002.
5. Williams, M.B., P.B. Raven, D.L. Fogt, and J.L. Ivy. Effects of recovery beverages on glycogen restoration and endurance exercise performance. J. Strength Cond. Res. 17:12–19, 2003.
6. Yaspelkis, B.B. III, and J.L. Ivy. The effect of a carbohydrate-arginine supplement on postexercise carbohydrate metabolism. Int. J. Sport Nutr. 9:241–250, 1999.
©2005 The American College of Sports Medicine