Sports Medicine

, Volume 26, Issue 3, pp 177–191 | Cite as

Glutamine, Exercise and Immune Function

Links and Possible Mechanisms
  • Neil P. Walsh
  • Andrew K. Blannin
  • Paula J. Robson
  • Michael GleesonEmail author
Review Article


Glutamine is the most abundant free amino acid in human muscle and plasma and is utilised at high rates by rapidly dividing cells, including leucocytes, to provide energy and optimal conditions for nucleotide biosynthesis. As such, it is considered to be essential for proper immune function.

During various catabolic states including surgical trauma, infection, starvation and prolonged exercise, glutamine homeostasis is placed under stress. Falls in the plasma glutamine level (normal range 500 to 750 μmol/L after an overnight fast) have been reported following endurance events and prolonged exercise. These levels remain unchanged or temporarily elevated after short term, high intensity exercise. Plasma glutamine has also been reported to fall in patients with untreated diabetes mellitus, in diet-induced metabolic acidosis and in the recovery period following high intensity intermittent exercise. Common factors among all these stress states are rises in the plasma concentrations of cortisol and glucagon and an increased tissue requirement for glutamine for gluconeogenesis. It is suggested that increased gluconeogenesis and associated increases in hepatic, gut and renal glutamine uptake account for the depletion of plasma glutamine in catabolic stress states, including prolonged exercise.

The short term effects of exercise on the plasma glutamine level may be cumulative, since heavy training has been shown to result in low plasma glutamine levels (<500 μmol/L) requiring long periods of recovery. Furthermore, athletes experiencing discomfort from the overtraining syndrome exhibit lower resting levels of plasma glutamine than active healthy controls. Therefore, physical activity directly affects the availability of glutamine to the leucocytes and thus may influence immune function. The utility of plasma glutamine level as a marker of overtraining has recently been highlighted, but a consensus has not yet been reached concerning the best method of determining the level.

Since injury, infection, nutritional status and acute exercise can all influence plasma glutamine level, these factors must be controlled and/or taken into consideration if plasma glutamine is to prove a useful marker of impending overtraining.


Glutamine Adis International Limited Prolonged Exercise High Intensity Exercise Glutamine Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Brenner IKM, Shek PN, Shephard RJ. Infection in athletes. Sports Med 1994; 17: 86–107PubMedCrossRefGoogle Scholar
  2. 2.
    Nieman DC, Johanssen LM, Lee JW, et al. Risk of infectious episodes in runners before and after the Los Angeles Marathon. J Sports Med Phys Fitness 1990; 30: 316–28PubMedGoogle Scholar
  3. 3.
    Noakes T. Lore of running. Cape Town: Oxford University Press, 1986Google Scholar
  4. 4.
    Nieman DC, Nehlsen-Cannarella, Markoff PA, et al. The effects of moderate exercise training on natural killer cells and acute upper respiratory tract infections. Int J Sports Med 1990; 11: 467–73PubMedCrossRefGoogle Scholar
  5. 5.
    Nehlsen-Cannarella SL, Nieman DC, Balk-Lamberton AJ, et al. The effects of moderate exercise training on immune response. Med Sci Sports Exerc 1991; 23: 64–70PubMedGoogle Scholar
  6. 6.
    Oshida Y, Yamanouchi K, Hayamizu S, et al. Effect of acute physical exercise on lymphocyte subpopulations in trained and untrained subjects. Int J Sports Med 1988; 9: 137–40PubMedCrossRefGoogle Scholar
  7. 7.
    McCarthy DA, Dale MM. The leucocytosis of exercise: a review and a model. Sports Med 1988; 6: 333–63PubMedCrossRefGoogle Scholar
  8. 8.
    Field CJ, Gougeon R, Marliss EB. Circulating mononuclear cell numbers and function during intense exercise and recovery. J Appl Physiol 1991; 71: 1089–97PubMedGoogle Scholar
  9. 9.
    Nieman D. Effect of long-term training on the immune system and on resistance to infectious diseases. In. Maughan RJ, Shirreffs SM, editors. Biochemistry of exercise IX. Champaign (IL): Human Kinetics, 1997: 383–99Google Scholar
  10. 10.
    Blannin AK, Gleeson M, Cave R. Changes in the human blood leucocyte count during and following brief exercise: influence of exercise intensity and duration [abstract]. J Physiol 1994; 474: 18PGoogle Scholar
  11. 11.
    Nieman DC, Nehlsen-Cannerella SL. Exercise and infection. In. Watson RR, Eisinger M, editors. Exercise and disease. Boca Raton (FL): CRC Press, 1992: 121–48Google Scholar
  12. 12.
    Pedersen BK. Influence of physical activity on the cellular immune system: mechanisms of action. Int J Sports Med 1991; 12 Suppl. 1: S23–9PubMedCrossRefGoogle Scholar
  13. 13.
    Shephard RJ, Shek PN. Infection and the athlete. Clin J Sports Med 1993; 3: 57–77Google Scholar
  14. 14.
    Keast D, Cameron K, Morton AR. Exercise and the immune response. Sports Med 1988; 5: 248–67PubMedCrossRefGoogle Scholar
  15. 15.
    Lewicki R, Tchorzewski H, Majewska E, et al. Effect of maximal physical exercise on T-lymphocyte subpopulations and on interleukin 1 (IL1) and interleukin 2 (IL2) production in vitro. Int J Sports Med 1988; 9: 114–7PubMedCrossRefGoogle Scholar
  16. 16.
    Eskola J, Ruuskanen O, Soppi E, et al. Effect of sport stress on lymphocyte transformation and antibody formation. Clin Exp Immunol 1978; 32: 339–45PubMedGoogle Scholar
  17. 17.
    Ryan AJ, Brown RL, Frederick EC, et al. Overtraining of athletes. Phys Sportsmed 1983; 11: 93–110Google Scholar
  18. 18.
    Bosenberg AT, Brock-Utne JG, Gaffin SL, et al. Strenuous exercise causes endotoxemia. J Appl Physiol 1988; 65: 106–8PubMedGoogle Scholar
  19. 19.
    Israel S, Buhl B, Krause M, et al. Die Konzentration der Immunoglobuline A,G and M im Serum bie trainierten und sowie nach verschiedenen sportlicken Ausdauerleistungen. Med Sport 1982; 22: 225–31Google Scholar
  20. 20.
    Blannin AK, Gleeson M, Brooks S, et al. Acute effect of exercise on human neutrophil degranulation [abstract]. J Physiol 1996; 495: 140PGoogle Scholar
  21. 21.
    Fry RW, Morton AR, Keast D. Overtraining in athletes: an update. Sports Med 1991; 12: 32–65PubMedCrossRefGoogle Scholar
  22. 22.
    Kuipers H, Keizer HA. Overtraining in elite athletes: review and directions for the future. Sports Med 1988; 6: 79–92PubMedCrossRefGoogle Scholar
  23. 23.
    Pedersen BK, Bruunsgaard H. How physical exercise influences the establishment of infections. Sports Med 1995; 19: 393–400PubMedCrossRefGoogle Scholar
  24. 24.
    Parry-Billings M, Blomstrand E, McAndrew N, et al. A communicational link between skeletal muscle, brain and cells of the immune system. Int J Sports Med 1990; 11 Suppl. 2: S122–8PubMedCrossRefGoogle Scholar
  25. 25.
    Parry-Billings M, Budgett R, Koutedakis Y, et al. Plasma amino acid concentrations in the overtraining syndrome: possible effects on the immune system. Med Sci Sports Exerc 1992; 24: 1353–8PubMedGoogle Scholar
  26. 26.
    Kingsbury KJ, Kay L, Hjelm M. Contrasting plasma amino acid patterns in elite athletes: association with fatigue and infection. Br J Sports Med 1998; 32: 25–33PubMedCrossRefGoogle Scholar
  27. 27.
    Mackinnon LT, Hooper S. Plasma glutamine and upper respiratory tract infection during intensified training in swimmers. Med Sci Sports Exerc 1996; 28: 285–90PubMedGoogle Scholar
  28. 28.
    Felig P. Amino acid metabolism in man. Ann Rev Biochem 1975; 44: 933–55PubMedCrossRefGoogle Scholar
  29. 29.
    Rowbottom DG, Keast D, Morton AR. The emerging role of glutamine as an indicator of exercise stress and overtraining. Sports Med 1996; 21: 80–97PubMedCrossRefGoogle Scholar
  30. 30.
    Newsholme EA, Leech AR. Biochemistry for the medical sciences. Chichester: John Wiley, 1983Google Scholar
  31. 31.
    Damian AC, Pitts RF. Rates of glutaminase I and glutamine synthetase reactions in rat kidney in vivo. Am J Physiol 1970; 218: 1249–55PubMedGoogle Scholar
  32. 32.
    Krebs HA. Glutamine metabolism in the animal body. In. Mora J, Palacios R, editors. Glutamine: metabolism, enzymology, and regulation. New York (NY): Academic Press, 1980: 319–29Google Scholar
  33. 33.
    Max S. Glucocorticoid-mediated induction of glutamine synthetase in skeletal muscle. Med Sci Sports Exerc 1990; 22: 325–30PubMedGoogle Scholar
  34. 34.
    Calder PC. Fuel utilization by cells of the immune system. Proc Nutr Soc 1995; 54 (1): 65–82CrossRefGoogle Scholar
  35. 35.
    Ardawi MSM, Newsholme EA. Glutamine metabolism in lymphoid tissues. In. Häussinger D, Sies H, editors. Glutamine metabolism in mammalian tissues. Berlin: Springer-Verlag, 1984: 235–46CrossRefGoogle Scholar
  36. 36.
    Wallace C, Keast D. Glutamine and macrophage function. Metabolism 1992; 41: 1016–20PubMedCrossRefGoogle Scholar
  37. 37.
    Parry-Billings M, Blomstrand E, Leighton B, et al. Does endurance exercise impair glutamine metabolism [abstract]?. Can J Sport Sci 1988; 13: 27PGoogle Scholar
  38. 38.
    Parry-Billings M, Leighton B, Dimitriadis GD, et al. Skeletal muscle glutamine metabolism during sepsis in the rat. Int J Biochem 1989; 21: 419–23PubMedCrossRefGoogle Scholar
  39. 39.
    Calder PC, Newsholme EA. Glutamine promotes interleukin-2 production by concanavalin A-stimulated lymphocytes [abstract]. Proc Nutr Soc 1992; 51: 105ACrossRefGoogle Scholar
  40. 40.
    Wagenmakers AJM. Discussion: overtraining, immunosuppression, exercise-induced muscle damage and anti-inflammatory drugs. In. Reilly T, Orme M, editors. The clinical pharmacology of sport and exercise. Amsterdam: Excerpta Medica/ Elsevier, 1997: 47–57Google Scholar
  41. 41.
    Gleeson M, Bishop NC. Immunology. In: Maughan RJ, editor. Basic science for sports medicine. Oxford: Butterworth Heinemann. In pressGoogle Scholar
  42. 42.
    Herberer M, Babst R, Juretic A, et al. Role of glutamine in the immune response in critical illness. Nutrition 1996; 12 Suppl. 11-12: S71–2CrossRefGoogle Scholar
  43. 43.
    Rohde T, Ullum H, Rasmussen JP, et al. Effects of glutamine on the immune system: influence of muscular exercise and HIV infection. J Appl Physiol 1995; 79: 146–50PubMedGoogle Scholar
  44. 44.
    O’Riordain MG, DeBeaux A, Fearon KC. Effect of glutamine on immune function in the surgical patient. Nutrition 1996; 12 Suppl. 11-12: S82–4PubMedCrossRefGoogle Scholar
  45. 45.
    Brambilla G, Pardodi S, Cavanna M, et al. The immunodepressive activity of E. coli L-asparaginase in some transplant systems. Cancer Res 1970; 30: 2665–70Google Scholar
  46. 46.
    Wagenmakers AJM. Role of amino acids and ammonia in mechanisms of fatigue. In. Marconnet P, Komi P, Saltin B, editors. Muscle fatigue mechanisms in exercise and training. Karger Series on Med Sport Sci. Basel: Karger, 1992; 34: 69–86Google Scholar
  47. 47.
    Graham TE, Rush JWE, Maclean DA. Skeletal muscle amino acid metabolism and ammonia production during exercise. In. Hargreaves M, editor. Exercise metabolism. Champaign (IL): Human Kinetics, 1995: 131–77Google Scholar
  48. 48.
    Meyer RA, Terjung RL. Differences in ammonia and adenylate metabolism in contracting fast and slow muscle. Am J Physiol 1979; 237: C111–18PubMedGoogle Scholar
  49. 49.
    Goldberg AL, Chang TW. Regulation and significance of amino acid metabolism in skeletal muscle. Fed Proc 1978; 37: 2301–7PubMedGoogle Scholar
  50. 50.
    Rennie MJ, Edwards RHT, Krywawych S, et al. Effect of exercise on protein turnover in man. Clin Sci 1981; 61: 627–39PubMedGoogle Scholar
  51. 51.
    Max SR, Thomas JW, Banner C, et al. Glucocortiocoid receptor-mediated induction of glutamine synthetase in skeletal muscle cells in vitro. Endocrinology 1987; 120: 1179–83PubMedCrossRefGoogle Scholar
  52. 52.
    Ardawi MSM, Jamal YS. Glutamine metabolism in skeletal muscle of glucocorticoid-treated rats. Clin Sci 1990; 79: 139–47PubMedGoogle Scholar
  53. 53.
    Christophe J, Winand J, Kutzner R, et al. Amino acid levels in plasma, liver, muscle, and kidney during and after exercise in fasted and fed rats. Am J Physiol 1971; 221: 453–7PubMedGoogle Scholar
  54. 54.
    Babij P, Mattews SM, Rennie MJ. Changes in blood ammonia, lactate and amino acids in relation to workload during bicycle ergometer exercise in man. Eur J Appl Physiol 1983; 50: 405–11CrossRefGoogle Scholar
  55. 55.
    Eriksson LS, Broberg S, Björkman O, et al. Ammonia metabolism during exercise in man. Clin Physiol 1985; 5: 325–36PubMedCrossRefGoogle Scholar
  56. 56.
    Maughan RJ, Gleeson M. Influence of a 36h fast followed by refeeding with glucose, glycerol or placebo on metabolism and performance during prolonged exercise in man. Eur J Appl Physiol 1988; 57: 570–6CrossRefGoogle Scholar
  57. 57.
    Sahlin K, Katz A, Broberg S. Tricarboxylic acid cycle intermediates in human muscle during prolonged exercise. Am J Physiol 1990; 259: C834–41PubMedGoogle Scholar
  58. 58.
    Sewell DA, Gleeson M, Blannin AK. Hyperammonaemia in relation to high-intensity exercise duration in man. Eur J Appl Physiol 1994; 69: 350–4CrossRefGoogle Scholar
  59. 59.
    Robson PJ, Blannin AK, Walsh NP, et al. Effect of exercise intensity and duration on plasma glutamine responses following exercise and the time course of recovery in physically active men [abstract]. J Physiol 1998; 506: 118P–9PGoogle Scholar
  60. 60.
    Katz A, Broberg S, Sahlin K, et al. Muscle ammonia and amino acid metabolism during dynamic exercise in man. Clin Physiol 1986; 6: 365–79PubMedCrossRefGoogle Scholar
  61. 61.
    van Hall G, Saris WH, Wagenmakers AJ. Effect of carbohydrate supplementation on plasma glutamine during exercise and recovery. Int J Sports Med 1998; 19: 82–6PubMedCrossRefGoogle Scholar
  62. 62.
    van der Schoor P, van Hall G, Saris WHM, et al. Ingestion of drinks containing protein hydrolysate prevents the postexercise reduction of plasma glutamine [abstract]. Int J Sports Med 1997; 18 Suppl. 1: S115Google Scholar
  63. 63.
    Keast D, Arstein D, Harper W, et al. Depression of plasma glutamine concentration after exercise stress and its possible influence on the immune system. Med J Aust 1995; 162: 15–8PubMedGoogle Scholar
  64. 64.
    Walsh NP, Blannin AK, Clark AM, et al. The effects of high intensity intermittent exercise on the plasma concentrations of glutamine and organic acids of severe exercise stress. Eur J Appl Physiol 1998; 77: 434–8CrossRefGoogle Scholar
  65. 65.
    Decombaz J, Reinhardt P, Anantharaman K, et al. Biochemical changes in a 100km run: free amino acids, urea, and creatine. Eur J Appl Physiol 1979; 41: 61–72CrossRefGoogle Scholar
  66. 66.
    Rohde T, MacLean DA, Hartkopp A, et al. The immune system and serum glutamine during a triathlon. Eur J Appl Physiol 1996; 74: 428–34CrossRefGoogle Scholar
  67. 67.
    Hood DA, Terjung RL. Amino acid metabolism during exercise and following endurance training. Sports Med 1990; 9: 23–35PubMedCrossRefGoogle Scholar
  68. 68.
    Dohm GL, Beecher GR, Warren RQ, et al. Influence of exercise on free amino acid concentrations in rat tissues. J Appl Physiol 1981; 50: 41–4PubMedGoogle Scholar
  69. 69.
    Bergström J, Furst P, Noree L-O, et al. Intracellular free amino acid concentration in human muscle tissue. J Appl Physiol 1974; 36: 471–4Google Scholar
  70. 70.
    Rennie MJ, Tadros L, Khogali, S. Glutamine transport and its metabolic effects. J Nutr 1994; 124 Suppl. 8: S1503–8Google Scholar
  71. 71.
    Ahmed A, Taylor PM, Rennie MJ. Characteristics of glutamine transport in sarcolemmal vesicles from rat skeletal muscle. Am J Physiol 1990; 259: 284–91Google Scholar
  72. 72.
    Kjaer M. Hepatic fuel metabolism during exercise. In. Hargreaves M, editor. Exercise metabolism. Champaign (IL): Human Kinetics, 1995: 73–99Google Scholar
  73. 73.
    Sellers TL, Jaussi AW, Yang HT, et al. Effect of the exerciseinduced increase in glucocorticoids on endurance in the rat. J Appl Physiol 1988; 65: 173–8PubMedGoogle Scholar
  74. 74.
    Nurjhan N, Bucci A, Perriello G, et al. Glutamine: a major gluconeogenic precursor and vehicle for interorgan carbon transport in man. J Clin Invest 1995; 95: 272–7PubMedCrossRefGoogle Scholar
  75. 75.
    Galbo H. Hormonal and metabolic adaptation to exercise. New York (NY): Thieme Stratton, 1983Google Scholar
  76. 76.
    Brosnan JT, Ewart HS, Squires SA. Hormonal control of hepatic glutaminase. Adv Enzyme Regul 1995; 35: 131–46PubMedCrossRefGoogle Scholar
  77. 77.
    Fischer CP, Bode BP, Abcouwer SF, et al. Hepatic uptake of glutamine and other amino acids during infection and inflammation. Shock 1995; 3: 315–22PubMedGoogle Scholar
  78. 78.
    Unneberg K, Mjaaland M, Balteskard L, et al. Both growth hormone and glutamine increase gastrointestinal glutamine uptake in trauma. Ann Surg 1997; 225: 97–102PubMedCrossRefGoogle Scholar
  79. 79.
    Fischer CP, Bode BP, Souba WW. Starvation and endotoxin act independently and synergistically to coordinate hepatic glutamine transport. J Trauma 1996; 40: 688–92PubMedCrossRefGoogle Scholar
  80. 80.
    Wagenmakers AJM, Beckers ED, Brouns F, et al. Carbohydrate supplementation, glycogen depletion, and amino acid metabolism during exercise. Am J Physiol 1991; 260: E883–90PubMedGoogle Scholar
  81. 81.
    Wagenmakers AJM. Branched-chain amino acids and endurance performance. In. Reilly T, Orme M, editors. The clinical pharmacology of sport and exercise. Amsterdam: Excerpta Medica/Elsevier, 1997: 213–9Google Scholar
  82. 82.
    Broberg S, Sahlin K. Adenine nucleotide degradation in human skeletal muscle during prolonged exercise. J Appl Physiol 1989; 67: 116–22PubMedGoogle Scholar
  83. 83.
    Felig P, Wahren J, Karl I, et al. Glutamine and glutamate metabolism in normal and diabetic subjects. Diabetes 1973; 22: 573–6PubMedGoogle Scholar
  84. 84.
    Fry RW, Morton AR, Keast D. Acute intensive interval training and T-lymphocyte function. Med Sci Sports Exerc 1992; 24: 339–45PubMedGoogle Scholar
  85. 85.
    Hems DA. Metabolism of glutamine and glutamic acid by isolated perfused kidneys of normal and acidotic rats. Biochem J 1972; 130: 671–80PubMedGoogle Scholar
  86. 86.
    Newsholme EA, Lang J, Relman AS. Control of rate of glutamine metabolism in the kidney. Contrib Nephrol 1982; 31: 1–4PubMedGoogle Scholar
  87. 87.
    Simpson DP. Control of hydrogen ion homeostasis and renal acidosis. Medicine 1971; 50: 503–41PubMedCrossRefGoogle Scholar
  88. 88.
    Greenhaff PL, Gleeson M, Maughan RJ. The influence of an alteration in diet composition on plasma and muscle glutamine levels in man [abstract]. Clin Sci 1988; 74: 20PGoogle Scholar
  89. 89.
    Lund P. Glutamine. UV-method with glutaminase and glutamate dehydrogenas. In: Bergmeyer HU, editor. Methods of enzymatic analysis. Vol. 8. Metabolites 3: lipids, amino acids and related compounds. Weinheim: VCF, 1985: 357–63Google Scholar
  90. 90.
    Rowbottom DG, Keast D, Goodman C, et al. The haematological, biochemical and immunological profile of athletes suffering from the Overtraining Syndrome. Eur J Appl Physiol 1995; 70: 502–9CrossRefGoogle Scholar
  91. 91.
    Castell LM, Poortmans JR, Newsholme EA. Does glutamine have a role in reducing infections in athletes?. Eur J Appl Physiol 1996; 73: 488–90CrossRefGoogle Scholar
  92. 92.
    Greig JE, Rowbottom DG, Keast D. The effect of a common (viral) stress on plasma glutamine concentration. Med J Aust 1995; 163: 385–8PubMedGoogle Scholar
  93. 93.
    Lemon PWR. Effect of exercise on protein requirements. In. Williams C, Devlin J, editors. Foods nutrition and sports performance. London: E & FN Spon, 1992: 65–86Google Scholar
  94. 94.
    Roitt IM. Essential immunology. London: Blackwell Science, 1994Google Scholar
  95. 95.
    Shewchuk LD, Baracos VE, Field CJ. Dietary L-glutamine does not improve lymphocyte metabolism or function in exercisetrained rats. Med Sci Sports Exerc 1997; 29: 474–81PubMedCrossRefGoogle Scholar
  96. 96.
    Moriguchi S, Miwa H, Kishoni Y. Glutamine supplementation prevents the decrease of mitogen response after a treadmill exercise in rats. J Nutr Sci Vitaminol 1995; 41: 115–25PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited. All rights reserved 1998

Authors and Affiliations

  • Neil P. Walsh
    • 1
  • Andrew K. Blannin
    • 2
  • Paula J. Robson
    • 2
  • Michael Gleeson
    • 2
    Email author
  1. 1.Sport Health and Leisure DepartmentTrinity and All Saints University CollegeLeedsEngland
  2. 2.School of Sport and Exercise SciencesUniversity of Birmingham, EdgbastonBirminghamEngland

Personalised recommendations