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Sports Medicine

, Volume 33, Issue 5, pp 323–345 | Cite as

Glutamine Supplementation In Vitro and In Vivo, in Exercise and in Immunodepression

  • Linda M. CastellEmail author
Review Article

Abstract

In situations of stress, such as clinical trauma, starvation or prolonged, strenuous exercise, the concentration of glutamine in the blood is decreased, often substantially. In endurance athletes this decrease occurs concomitantly with relatively transient immunodepression. Glutamine is used as a fuel by some cells of the immune system. Provision of glutamine or a glutamine precursor, such as branched chain amino acids, has been seen to have a beneficial effect on gut function, on morbidity and mortality, and on some aspects of immune cell function in clinical studies. It has also been seen to decrease the self-reported incidence of illness in endurance athletes. So far, there is no firm evidence as to precisely which aspect of the immune system is affected by glutamine feeding during the transient immunodepression that occurs after prolonged, strenuous exercise. However, there is increasing evidence that neutrophils may be implicated. Other aspects of glutamine and glutamine supplementation are also addressed.

Keywords

Glutamine Branch Chain Amino Acid Strenuous Exercise Marathon Runner Glutamine Concentration 
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.

Notes

Acknowledgements

There are no conflicts of interest in relation to this review, and the preparation of it was not funded. The author is grateful to Professor Philip Calder for reading the manuscript.

References

  1. 1.
    Ardawi MSM, Newsholme EA. Glutamine metabolism in lymphocytes of the rat. Biochem J 1983; 212: 835–42PubMedGoogle Scholar
  2. 2.
    Hume DA, Weidemann MJ. Mitogenic lymphocyte transformation. Amsterdam: Elsevier, 1980Google Scholar
  3. 3.
    Ardawi MSM, Newsholme EA. Metabolism in lymphocytes and its importance in the immune response. Essays Biochem 1985: 21: 1–44PubMedGoogle Scholar
  4. 4.
    Newsholme EA, Newsholme P, Curi R, et al. A role for muscle in the immune system and its importance in surgery, trauma, sepsis and burns. Nutrition 1988; 4: 261–8Google Scholar
  5. 5.
    Newsholme EA, Castell LM. Amino acids, fatigue and immunodepression in exercise. In: Maughan RJ, editor. Nutrition in sport IOC encyclopaedia of sport. Oxford: Blackwell Science. 2000Google Scholar
  6. 6.
    Newsholme EA, Crabtree B, Ardawi M. Glutamine metabolism in lymphocytes: its biochemical, physiological and clinical importance. Q J Exp Physiol 1985; 70: 473–89PubMedGoogle Scholar
  7. 7.
    Parry-Billings M, Evans J, Calder PC, et al. Does glutamine contribute to immunosuppression? Lancet 1990; 336: 523–5PubMedCrossRefGoogle Scholar
  8. 8.
    Rose WC. The nutritive significance of the amino acids. Physiol Rev 1938; 18: 109–36Google Scholar
  9. 9.
    Lacey JM, Wilmore D. Is glutamine a conditionally essential amino acid? Nutr Rev 1990; 48: 297–309PubMedCrossRefGoogle Scholar
  10. 10.
    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
  11. 11.
    Powell H, Castell LM, Parry-Billings M, et al. Growth hormone suppression and glutamine flux associated with cardiac surgery. Clin Physiol 1994; 14: 569–80PubMedCrossRefGoogle Scholar
  12. 12.
    Eagle H, Oyama VL, Levy M, et al. The growth response of mammalian cells in tissue culture to L-glutamine and L-glutamic acid. J Biol Chem 1955; 218: 607–17Google Scholar
  13. 13.
    Yaqoob P, Calder PC. Glutamine requirement of proliferating T-lymphocytes. Nutrition 1997; 13: 646–51PubMedCrossRefGoogle Scholar
  14. 14.
    Castell LM. The role of some amino acids in exercise, fatigue and immunodepression. Oxford: University of Oxford, 1996Google Scholar
  15. 15.
    Yaqoob P, Calder PC. Cytokine production by human peripheral blood mononuclear cells: differential sensitivity to glutamine availaibility. Cytokine 1998; 10: 790–4PubMedCrossRefGoogle Scholar
  16. 16.
    Liu CT, Chen KM, Chang PL, et al. Glutamine utilization in activated lymphocytes from rats receiving endotoxin. J Surg Res 2001; 96: 246–54PubMedCrossRefGoogle Scholar
  17. 17.
    Ogle CK, Ogle JD, Mao J-X, et al. Effect of glutamine on phagocytosis and bacterial killing by normal and pediatric burn patient neutrophils. JPEN J Parenter Enterai Nutr 1994; 18: 128–33CrossRefGoogle Scholar
  18. 18.
    Furukawa S, Saito H, Fukatsu K, et al. Glutamine-enhanced bacterial killing by neutrophils from postoperative patients. Nutrition 1997; 13: 863–9PubMedCrossRefGoogle Scholar
  19. 19.
    Vance CA, Eggleton P, Castell LM. The effects of in vitro and in vivo supplementation of glutamine upon human neutrophils [abstract]. Amino Acids 2001; 21: 62Google Scholar
  20. 20.
    Bergstrom J, Furst P, Noree LO, et al. Intracellular free amino acid concentration in human muscle tissue. J Appl Physiol 1974; 36: 693–7PubMedGoogle Scholar
  21. 21.
    Roth E, Funovics J, Muhlbacher F, et al. Metabolic disorders in severe abdominal sepsis: glutamine deficiency in skeletal muscle. Clin Nutr 1982; 1: 25–41PubMedCrossRefGoogle Scholar
  22. 22.
    Elia M, Wood S, Khan K, et al. Ketone body metabolism in lean male adults during short-term starvation, with particular reference to forearm muscle metabolism. Clin Sci (Lond) 1990; 78: 579–84Google Scholar
  23. 23.
    Newsholme EA, Parry-Billings M. Properties of glutamine release from muscle and its importance for the immune system. J Parenter Enterai Nutr 1990; 14: 63–67SCrossRefGoogle Scholar
  24. 24.
    Horig H, Spagnoli GC, Filgueira L, et al. Exogenous glutamine requirement is confined to late events of T cell activation. J Cell Biochem 1993; 53: 343–51PubMedCrossRefGoogle Scholar
  25. 25.
    Askanazi J, Carpentier YA, Michelsen CB, et al. Muscle and plasma amino acids following injury: influence of intercurrent infection. Ann Surg 1980; 192: 78–85PubMedCrossRefGoogle Scholar
  26. 26.
    Stinnett JD, Alexander JW, Watanabe C, et al. Plasma and skeletal muscle amino acids following severe burn injury in patients and experimental animals. Ann Surg 1982; 195: 75–89PubMedCrossRefGoogle Scholar
  27. 27.
    Parry-Billings M, Baigrie R, Lamont P, et al. Effects of major and minor surgery on plasma glutamine and cytokine levels. Arch Surg 1992; 127: 1237–40PubMedCrossRefGoogle Scholar
  28. 28.
    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: S122–8PubMedCrossRefGoogle Scholar
  29. 29.
    Baker CC, Oppenheimer L, Stephens B, et al. Epidemiology of trauma deaths. Am J Surg 1980; 140: 144–50PubMedCrossRefGoogle Scholar
  30. 30.
    Green DR, Faist E. Trauma and the immune response. Immunol Today 1988; 9: 253–5PubMedCrossRefGoogle Scholar
  31. 31.
    Hiscock N, Mackinnon LT. A comparison of plasma glutamine concentration in athletes from different sports. Med Sci Sports Exerc 1998; 30: 1693–6PubMedCrossRefGoogle Scholar
  32. 32.
    Matthews DE, Campbell RG. The effect of dietary protein intake on glutamine and glutamate nitrogen metabolism in humans. Am J Clin Nutr 1992; 55: 963–70PubMedGoogle Scholar
  33. 33.
    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
  34. 34.
    Budgett R, Newsholme E, Lehmann M, et al. Redefining the overtraining sundrome as the unexplained underperformance syndrome. Br J Sports Med 2000; 34: 67–8PubMedCrossRefGoogle Scholar
  35. 35.
    Bailey DM, Davies B, Castell LM, et al. Do infections and altitude illness represent a common pathophysiology? Metabolic significance of free radical-mediated tissue damage and glutamine metabolism in man. J Physiol 2002; 539P: 30PGoogle Scholar
  36. 36.
    Poortmans JR, Siest G, Galteau MM, et al. Distribution of plasma amino acids in humans during submaximal prolonged exercise. Eur J Appl Physiol Occup Physiol 1974; 32: 143–7PubMedCrossRefGoogle Scholar
  37. 37.
    Maughan RJ, Gleeson M. Influence of a 36h fast followed by refeeding with glucose, glycerol or placebo on metabolism and performance during prolonged exercise. Eur J Appl Physiol Occup Physiol 1988; 57: 570–6PubMedCrossRefGoogle Scholar
  38. 38.
    Parry-Billings M. Studies of glutamine release from skeletal muscle. Oxford: University of Oxford, 1989Google Scholar
  39. 39.
    Decombaz J, Reinhardt P, Anantharaman K, et al. Biochemical changes in a 100km run: free amino acids, urea and creatinine. Eur J Appl Physiol Occup Physiol 1979; 41: 61–72PubMedCrossRefGoogle Scholar
  40. 40.
    Brodan V, Kuhn E, Pechar J, et al. Changes of free amino acids in plasma in healthy subjects induced by physical exercise. Eur J Appl Physiol Occup Physiol 1986; 35: 69–77CrossRefGoogle Scholar
  41. 41.
    Castell LM, Poortmans J, Newsholme EA. Does glutamine have a role in reducing infections in athletes? Eur J Appl Physiol Occup Physiol 1996; 73: 488–91PubMedCrossRefGoogle Scholar
  42. 42.
    Rennie MJ, Edwards RHT, Krywawych S, et al. Effect of exercise on protein turnover in man. Clin Sci (Lond) 1981; 61: 627–39Google Scholar
  43. 43.
    Walsh NP, Blannin AK, Clark AM, et al. The effects of high-intensity intermittent exercise on the plasma concentrations of glutamine and organic acids. Eur J Appl Physiol Occup Physiol 1998; 77: 434–8PubMedCrossRefGoogle Scholar
  44. 44.
    Rohde T, MacLean DA, Hartkopp A, et al. The immune system and serum glutamine during a triathlon. Eur J Appl Physiol Occup Physiol 1996; 74: 428–34PubMedCrossRefGoogle Scholar
  45. 45.
    Lehmann M, Huonker M, Dimeo F, et al. Serum amino acids in nine athletes before and after the 1993 Colmar ultra triathlon. Int J Sports Med 1995; 16: 155–9PubMedCrossRefGoogle Scholar
  46. 46.
    Maclntyre DL, Reid WD, Lyster DM, et al. Presence of WBC, decreased strength, and delayed soreness in muscle after eccentric exercise. J Appl Physiol 1996; 80: 1006–13CrossRefGoogle Scholar
  47. 47.
    Bassit RA, Sawada LA, Bacurau RFP, et al. The effect of BCAA supplementation upon the immune response of triathletes. Med Sci Sports Exerc 2000; 32: 1214–9PubMedCrossRefGoogle Scholar
  48. 48.
    Stein TP, Schluter MD, Leskiw MJ, et al. Attenutation of the protein wasting associated with bed rest by branched-chain amino acids. Nutrition 1999; 15: 656–60PubMedCrossRefGoogle Scholar
  49. 49.
    Windmueller HG, Spaeth AE. Uptake and metabolism of glutamine by the small intestine. J Biol Chem 1974; 249: 5070–9PubMedGoogle Scholar
  50. 50.
    Lund P. Determination with glutaminase and glutamate dehydrogenase. In: Bergmeyer HU, editor. Methods of enzymatic analysis. New York: Academic Press, 1974: 1719–22Google Scholar
  51. 51.
    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
  52. 52.
    Smith DJ, Norris SR. Changes in glutamine and glutamate concentrations for tracking training tolerance. Med Sci Sports Exerc 2000; 32: 684–9PubMedCrossRefGoogle Scholar
  53. 53.
    Beaton JR, McGanity WJ, McHenry EW. Plasma glutamic acid levels in malignancy. Can Med Assoc J 1951; 65: 21–4Google Scholar
  54. 54.
    Castro-Bello F, Ramos F, Vivanco F, et al. High serum glutamic acid levels in patients with carcinoma of the pancreas. Digestion 1976; 14: 360–3PubMedCrossRefGoogle Scholar
  55. 55.
    Droge W, Eck HP, Betzler M, et al. Elevated plasma glutamate levels in colorectal carcinoma patients and in patients with acquired immunodeficiency syndrome (AIDS). Immunobiology 1987; 174: 473–9PubMedCrossRefGoogle Scholar
  56. 56.
    Droge W, Eck HP, Betzler M, et al. Plasma glutamate concentration and lymphocyte activity. J Cancer Res Clin Oncol 1988; 113: 1–5Google Scholar
  57. 57.
    Ollenschlager G, Karner J, Karner-Hanusch J, et al. Plasma glutamate: a prognostic marker of cancer of of other immunodeficiency syndromes? Scand J Clin Lab Invest 1989; 49: 773–7PubMedCrossRefGoogle Scholar
  58. 58.
    Hack V, Weiss C, Friedmann B, et al. Decreased plasma glutamine level and CD4+ T cell number in response to 8 wk of anaerobic training. Am J Physiol 1997; 272: E788–95PubMedGoogle Scholar
  59. 59.
    Castell LM. Endurance exercise, immunodepression and glutamine. In: The Biochemist. London: Portland Press, 1998: 28–33Google Scholar
  60. 60.
    Castell LM, Poortmans JR, Leclercq R, 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, 53Google Scholar
  61. 61.
    Bernt E, Bergmeyer HU. L-glutamate uv-assay with GDH and NAD. In: Bergmeyer HU. Methods on enzymatic analysis. London: Academic Press, 1974: 1704–8CrossRefGoogle Scholar
  62. 62.
    Peters EM, Bateman ED. Ultramarathon running and upper respiratory tract infections. S Afr Med J 1983; 64: 582–4PubMedGoogle Scholar
  63. 63.
    Nieman D, Johanssen LM, Lee JW, et al. Infectious episodes before and after the Los Angeles marathon. J Sports Med Phys Fitness 1990; 30: 289–96Google Scholar
  64. 64.
    Weidner TG. Literature review: upper respiratory tract illness and sport and exercise. Int J Sports Med 1994; 15: 1–9PubMedCrossRefGoogle Scholar
  65. 65.
    Nieman D. Exercise, upper respiratory tract infection and the immune system. Med Sci Sports Exerc 1994; 26: 128–39PubMedCrossRefGoogle Scholar
  66. 66.
    Nieman D. Immune response to heavy exertion. J Appl Physiol 1997; 82: 1385–94PubMedGoogle Scholar
  67. 67.
    Brenner IKM, Shek PN, Shephard RJ. Infection in athletes. Sports Med 1994; 17: 86–107PubMedCrossRefGoogle Scholar
  68. 68.
    Nieman D, Pedersen BK. Exercise and immune function: recent developments. Sports Med 1999; 27: 73–80PubMedCrossRefGoogle Scholar
  69. 69.
    Nash HL. Can exercise make us immune to disease? Phys Sports Med 1986; 14: 251–3Google Scholar
  70. 70.
    Fitzgerald L. Overtraining increases the susceptibility to infection. Int J Sports Med 1991; 12: 55–8CrossRefGoogle Scholar
  71. 71.
    Noakes TD. The lore of running. 2nd ed. Oxford: Oxford University Press, 1995Google Scholar
  72. 72.
    Casey JM, Dick EC. Acute respiratory infections. In: Casey JM, Dick EC, editors. Winter sports medicine. Philadelphia (PA): FA Davis Co., 1990: 112–28Google Scholar
  73. 73.
    Dick EC, Jennings LC, Mink KA, et al. Aerosol transmission of rhinovirus colds. J Infect Dis 1987; 156: 442–8PubMedCrossRefGoogle Scholar
  74. 74.
    Gwaltney Jr JM, Moskalski P, Hendley JO. Hand-to-hand transmission of rhinovirus colds. Ann Intern Med 1978; 88: 463–7PubMedGoogle Scholar
  75. 75.
    Mast EE, Goodman RA. Prevention of infectious disease transmission in sports. Sports Med 1997; 24: 1–7PubMedCrossRefGoogle Scholar
  76. 76.
    Ryan MA, Christian RS, Wohlrabe J. Handwashing and respiratory illness among young adults in military training. Am J Prev Med 2001; 21: 79–83PubMedCrossRefGoogle Scholar
  77. 77.
    Heath GW, Ford ES, Craven TE, et al. Exercise and the incidence of upper respiratory tract infections. Med Sci Sports Exerc 1991; 23: 152–7PubMedGoogle Scholar
  78. 78.
    O’Connor SA, Jones DP, Collins JV, et al. Changes in pulmonary function after naturally acquired respiratory infection in normal persons. Am Rev Respir Dis 1979; 120: 1087–93PubMedGoogle Scholar
  79. 79.
    Niinimaa V, Cole P, Mintz S, et al. The switching point from nasal to oronasal breathing. Respir Physiol 1980; 42: 61–71PubMedCrossRefGoogle Scholar
  80. 80.
    Becquemin MH, Swift DL, Bouchikhi A, et al. Particle deposition and resistance in the noses of adults and children. Eur Respir J 1991; 4: 694–702PubMedGoogle Scholar
  81. 81.
    Latvala JJ, Reijula KE, Clifford PS, et al. Cold-induced responses in the upper respiratory tract. Arctic Med Res 1995; 54: 4–9PubMedGoogle Scholar
  82. 82.
    Brouns F. Etiology of gastrointestinal disturbances during endurance events. Scand J Med Sci Sports 1991; 1: 66–77CrossRefGoogle Scholar
  83. 83.
    Marshall JC. The gut as a potential trigger of exercise-induced inflammatory responses. Can J Physiol Pharmacol 1998; 76: 479–84PubMedCrossRefGoogle Scholar
  84. 84.
    Platell C, McCauley R, McCulloch R, et al. The influence of parenteral glutamine and branched-chain amino acids on total parenteral nutrition-induced atrophy of the gut. J Parenter Enterai Nutr 1993; 17: 348–54CrossRefGoogle Scholar
  85. 85.
    Tannuri U, Carrazza FR, Iriya K. The effects of glutamine-supplemented diet on the intestinal mucosa of the malnourished growing rat. Rev Hosp Clin Fac Med Sao Paolo 2000; 55: 87–92Google Scholar
  86. 86.
    Furukawa S, Saito H, Inaba T. Glutamine-enriched enterai diet enhances bacterial clearance in protected bacterial peritonitis, regardless of glutamine form. J Parenteral Enterai Nutr 1997; 21: 208–14CrossRefGoogle Scholar
  87. 87.
    Klimberg VS, Souba WW. The importance of intestinal glutamine metabolism in maintaining a healthy gastrointestinal tract and supporting the body’s response to injury and illness. Surg Annu 1990; 22: 61–76PubMedGoogle Scholar
  88. 88.
    O’Dwyer ST, Smith RJ, Hwang TL, et al. Maintenance of small bowel mucosa with glutamine enriched parenteral nutrition. J Parenter Enterai Nutr 1989; 13: 579–85CrossRefGoogle Scholar
  89. 89.
    Yoshida S, Matsui M, Shirouzu Y, et al. Effects of glutamine supplements and radiochemotherapy on systemic immune and gut barrier function in patients with advanced esophageal cancer. Ann Surg 1998; 227: 485–91PubMedCrossRefGoogle Scholar
  90. 90.
    Van der Hulst RRWJ, van Kreel BK, von Meyenfeldt MF, et al. Glutamine and preservation of gut integrity. Lancet 1993; 341: 1363–5PubMedCrossRefGoogle Scholar
  91. 91.
    Jiang ZM, Cao JD, Zhu XG, et al. The impact of alanyl glutamine on clinical safety, nitrogen balance, intestinal permeability and clinical outcome in post-operative patients: a randomized, double-blind, controlled study of 120 patients. J Parenter Enterai Nutr 1999; 23: S62–6CrossRefGoogle Scholar
  92. 92.
    Stehle P, Furst P. Glutamine and the gut. In: Cynober L, Furst P, Lawin P, editors. Pharmacological nutrition: immune nutrition. Munich: W. Zuckschwerdt Verlag, 1995Google Scholar
  93. 93.
    Pabst R, Binns RM. Lymphocyte trafficking. In: Roitt I, Delves R, editors. Encyclopaedia of immunology. London: Academic Press, 1992: 1003–5Google Scholar
  94. 94.
    Weight LM, Alexander D, Jacobs P. Strenuous exercise: analogous to the acute phase response? Clin Sci 1991; 81: 677–83PubMedGoogle Scholar
  95. 95.
    Larrabee RC. Leucocytosis after violent exercise. J Med Res 1902; 2: 76–82Google Scholar
  96. 96.
    Garrey WE, Bryan WR. Variations in white blood cell counts. Physiol Rev 1935; 15: 597–638Google Scholar
  97. 97.
    Maron MB, Horvath SM, Wilkerson JE. Acute blood biochemical alterations in response to marathon running. Eur J Appl Physiol Occup Physiol 1975; 34: 173–81PubMedCrossRefGoogle Scholar
  98. 98.
    Davidson RJL, Robertson JD, Galea G, et al. Hematological changes associated with marathon running. Int J Sports Med 1987; 8: 19–25PubMedCrossRefGoogle Scholar
  99. 99.
    Gmunder FK, Lorenzi G, Bechler B, et al. Effect of long-term physical exercise on lymphocyte reactivity: similarity to spaceflight reactions. Aviat Space Environ Med 1988; 59: 146–51PubMedGoogle Scholar
  100. 100.
    McCarthy DA, Dale MM. The leucocytosis of exercise: a review and a model. Sports Med 1988; 6: 333–63PubMedCrossRefGoogle Scholar
  101. 101.
    Haq A, Al-Hussein K, Lee J, et al. Changes in peripheral blood lymphocyte subsets associated with marathon running. Med Sci Sports Exerc 1993; 25: 186–90PubMedGoogle Scholar
  102. 102.
    Castell LM, Newsholme EA. Glutamine and the effects of exhaustive exercise upon the immune response. Can J Physiol Pharmacol 1998; 76: 524–32PubMedCrossRefGoogle Scholar
  103. 103.
    Pedersen BK, Ullum H. NK cell response to physical activity: possible mechanisms of action. Med Sci Sport Exerc 1994; 26: 140–6CrossRefGoogle Scholar
  104. 104.
    Mars M, Govender S, Weston A, et al. High intensity exercise: a cause of lymphocyte apoptosis? Biochem Biophys Res Commun 1998; 249: 366–70PubMedCrossRefGoogle Scholar
  105. 105.
    Exner R, Weingartmann G, Eliasen MM, et al. Glutamine deficiency renders human monocytic cells more susceptible to specific apoptosis triggers. Surgery 2002; 131: 75–80PubMedCrossRefGoogle Scholar
  106. 106.
    Hansen J-B, Wilsgård L, Osterud B. Biphasic changes in leukocytes induced by strenuous exercise. J Appl Physiol 1991; 62: 157–61Google Scholar
  107. 107.
    Keast D, Cameron K, Morton AR. Exercise and immune response. Sports Med 1988; 5: 248–67PubMedCrossRefGoogle Scholar
  108. 108.
    Pedersen BK. Influence of physical activity on the cellular immune system: mechanisms of action. Int J Sports Med 1991; 12: S23–9PubMedCrossRefGoogle Scholar
  109. 109.
    Shepherd RJ, Rhind S, Shek P. Exercise and the immune system. Sports Med 1994; 18: 340–69CrossRefGoogle Scholar
  110. 110.
    Pedersen BK, Toft AD. Effects of exercise on lymphocytes and cytokines. Br J Sports Med 2000; 34: 246–51PubMedCrossRefGoogle Scholar
  111. 111.
    Tvede N, Pedersen BK, Hansen FR. Effect of physical exercise on blood mononuclear cell subpopulations and in vitro proliferation responses. Scand J Immunol 1989; 29: 383–9PubMedCrossRefGoogle Scholar
  112. 112.
    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
  113. 113.
    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
  114. 114.
    Fry RW, Morton AR, Garcia-Webb P, et al. Biological re sponses to overload training in endurance sports. Eur J Appl Physiol Occup Physiol 1992; 64: 335–44PubMedCrossRefGoogle Scholar
  115. 115.
    Berk LS, Tan SA, Nieman DC, et al. The suppressive effect of stress from acute exhaustive exercise on T lymphocyte helper/ suppressor cell ratio in athletes and non-athletes [abstract]. Med Sci Sports Exerc 1986; 18: 706ACrossRefGoogle Scholar
  116. 116.
    Lewicki R, Tahorzewski H, Majewska E, et al. Effect of maximal physical exercise on T-lymphocyte subpopulations and on interleukin-1 (IL-1) and interleukin (IL-2) production in vitro. Int J Sports Med 1988; 9: 114–7PubMedCrossRefGoogle Scholar
  117. 117.
    Shepherd RJ, Verde TJ, Thomas SG, et al. Physical activity and the immune system. Can J Sports Sci 1991; 16: 163–85Google Scholar
  118. 118.
    Koyama K, Kaya M, Tsujita J, et al. Effects of decreased plasma glutamine concentrations on peripheral lymphocyte proliferation in rats. Eur J Appl Physiol Occup Physiol 1998; 77: 25–31PubMedCrossRefGoogle Scholar
  119. 119.
    Perkins V. Properdin: cDNA and proteins across species, and analysis of immune effector status in properdin-deficient pa tients. Oxford: University of Oxford, 1998Google Scholar
  120. 120.
    Robson PJ, Blannin AK, Walsh NP, et al. Effects of exercise intensity, duration and recovery on in vitro neutrophil function in male athletes. Int J Sports Med 1999; 20: 128–35PubMedGoogle Scholar
  121. 121.
    Gabriel H, Muller HJ, Kettler K, et al. Increased phagocytic capacity of the blood, but decreased phagocytic activity per individual circulating neutrophil after an ultradistance run. Eur J Appl Physiol Occup Physiol 1995; 71: 281–4PubMedCrossRefGoogle Scholar
  122. 122.
    Fukatsu A, Sato N, Shimizu H. 50-mile walking race suppresses neutrophil bactericidal function by inducing increases in cor tisol and ketone bodies. Life Sci 1996; 58: 2337–43PubMedCrossRefGoogle Scholar
  123. 123.
    Ostrowski K, Rohde T, Zacho M, et al. Evidence that in-terleukin-6 is produced in human skeletal muscle during prolonged running. J Physiol 1998; 508: 949–53PubMedCrossRefGoogle Scholar
  124. 124.
    Steensberg A, van Hall G, Osada T, et al. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol 2000; 529: 237–42PubMedCrossRefGoogle Scholar
  125. 125.
    Hiscock N, Morgan R, Davison G, et al. Peripheral blood mononuclear cell glutamine concentration and in vitro proliferation in response to an acute, exercise-induced decrease in plasma glutamine concentration in man. J Physiol 2002; 539P: 54PGoogle Scholar
  126. 126.
    Welbourne T, Weber M, Bank N. The effect of glutamine administration on urinary ammonium excretion in normal subjects and patients with renal disease. J Clin Invest 1972; 51; 1852–60PubMedCrossRefGoogle Scholar
  127. 127.
    Neu J, Roig JC, Meetze WH, et al. Enterai glutamine supplementation for very low weight birth infants decreases morbidity. J Pediatr 1997; 131: 691–9PubMedCrossRefGoogle Scholar
  128. 128.
    Coeffier M, Miralles-Barachina O, Le Pessot F, et al. Influence of glutamine on cytokine production by human gut in vitro. Cytokine 2001; 13: 148–54PubMedCrossRefGoogle Scholar
  129. 129.
    Hiscock N, Crawford R, Castell LM. Supplementation of branched chain amino acids (BCAA) in marathon runners for one month prior to competition. Med Sci Sports Exerc 2001; 33(5): ISEI Suppl. [abstract 15]Google Scholar
  130. 130.
    Ziegler TR, Young LS, Benfell K, et al. Clinical and metabolic efficacy of glutamine supplemented parenteral nutrition after bone marrow transplantation. Ann Intern Med 1992; 116: 821–8PubMedGoogle Scholar
  131. 131.
    Griffiths RD, Jones C, Palmer TEA. Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition. Nutrition 1997; 13: 295–302PubMedGoogle Scholar
  132. 132.
    O’Riordain MG, De Beaux A, Fearon K. Effect of glutamine on immune function in the surgical patient. Nutrition 1996; 12: S82–4PubMedCrossRefGoogle Scholar
  133. 133.
    de Beaux AC, O’Riordain MG, Ross JA, et al. Glutamine-supplemented total parenteral nutrition reduces blood mononuclear cell interleukin-8 release in severe acute pancreatitis. Nutrition 1998; 14: 261–5PubMedCrossRefGoogle Scholar
  134. 134.
    Ziegler TR, Bye RL, Persinger RL, et al. Effects of glutamine supplementation on circulating lymphocytes after bone marrow transplantation: a pilot study. Am J Med Sci 1998; 315: 4–10PubMedCrossRefGoogle Scholar
  135. 135.
    O’Riordain MG, Fearon KC, Ross JA, et al. Glutamine-supplemented total parenteral nutrition enhances T-lymphocyte response in surgical patients undergoing colorectal resection. Ann Surg 1994; 220: 212–21PubMedCrossRefGoogle Scholar
  136. 136.
    Wischmeyer PE, Lynch J, Lidel J, et al. Glutamine administration reduces Gram-negative bacteraemia in severely burned patients: a prospective, randomised, double-blind trial versus isonitrogenous control. Crit Care Med 2001; 29: 2075–80PubMedCrossRefGoogle Scholar
  137. 137.
    Schloerb PR, Amare M. Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications (a randomised, double-blind study). J Parenter Enterai Nutr 1993; 17: 407–13CrossRefGoogle Scholar
  138. 138.
    Venhuizen AM, Bell L, Garrard CS, et al. Enterai glutamine feeding and some aspects of immune function in intensive care patients [abstract]. Proceedings of the 22nd International Symposium on Intensive Care Medicine: 2001 Mar 20–23; BrusselsGoogle Scholar
  139. 139.
    Young LS, Bye R, Scheltinga M, et al. Patients receiving glutamine-supplemented intravenous feedings report an improvement in mood. J Parenteral Enterai Nutr 1993; 17: 422–7CrossRefGoogle Scholar
  140. 140.
    Houdijk AP, Rijnsburger ER, Jansen J, et al. Randomised trial of glutamine-enriched nutrition on infectious morbidity in patients with multiple trauma. Lancet 1998; 352: 772–6PubMedCrossRefGoogle Scholar
  141. 141.
    Morlion BJ, Stehle P, Wachtier P, et al. Total parenteral nutrition with glutamine dipeptide after major abdominal surgery: a randomised, double-blind, controlled study. Ann Surg 1998; 227: 302–8PubMedCrossRefGoogle Scholar
  142. 142.
    Manhart N, Vierlinger K, Spittler A, et al. Oral feeding with glutamine prevents lymphocyte and glutathione depletion of Peyer’s patches in endotoxemic mice. Ann Surg 2001; 234: 92–7PubMedCrossRefGoogle Scholar
  143. 143.
    Aosasa S, Mochizuki H, Yamamoto T, et al. A clinical study of the effectiveness of oral glutamine during total parenteral nutrition: influence on mesenteric mononuclear cells. J Parenteral Enterai Nutr 1999; 23: 41–44SCrossRefGoogle Scholar
  144. 144.
    Burke DJ, Alverdy JA, Aoys E, et al. Glutamine-supplemented total parenteral nutrition improves gut immune function. Arch Surg 1989; 124: 1396–9PubMedCrossRefGoogle Scholar
  145. 145.
    Klimberg VS, Nwokedi E, Hutchins LF, et al. Glutamine facilitates chemotherapy while reducing toxicity. J Parenteral Enterai Nutr 1992; 16: 83–87SCrossRefGoogle Scholar
  146. 146.
    Kweon MN, Moriguchi S, Mukai K, et al. Effect of alanyl-glutamine-enriched infusion on tumor growth and cellular immune function in rats. Amino Acids 1991; 1: 7–16CrossRefGoogle Scholar
  147. 147.
    Shewchuk LD, Baracos VE, Field CJ. Dietary L-glutamine supplementation reduces the growth of the Morris Hepatoma 7777 in exercise-trained and sedentary rats. J Nutr 1997; 127: 158–66PubMedGoogle Scholar
  148. 148.
    Wells SM, Kew S, Yaqoob P, et al. Dietary glutamine enhances cytokine production by murine macrophages. Nutrition 1999; 15: 881–4PubMedCrossRefGoogle Scholar
  149. 149.
    Wischmeyer PE, Kahana M, Wolfson R, et al. Glutamine reduces cytokine release, organ damage, and mortality in a rat model of endotoxemia. Shock 2001; 16: 398–402PubMedCrossRefGoogle Scholar
  150. 150.
    Yoshida S, Hikida S, Tanaka Y. Effect of glutamine supplementation on lymphocyte function in septic rats [abstract]. J Parenteral Enterai Nutr 1992; 16Suppl. 1: 30Google Scholar
  151. 151.
    Niihara Y, Zerez CR, Akiyama DS, et al. Oral L-glutamine therapy for sickle cell anemia. Am J Hematol 1998; 58: 117–21PubMedCrossRefGoogle Scholar
  152. 152.
    Griffiths RD, Allen KD, Andrews FJ, et al. Infection, multiple organ failure and death in the ICU: influence of glutamine-supplemented parenteral nutrition on intensive care acquired infections and survival. Nutrition 2002; 18: 546–52PubMedCrossRefGoogle Scholar
  153. 153.
    Saito H, Furukawa S, Matsuda T. Glutamine as an immu-noenhancing nutrient. JPEN J Parenter Enterai Nutr 1999; 23: S59–61CrossRefGoogle Scholar
  154. 154.
    Curi TC, De Melo MP, De Azevedo RB, et al. Glutamine utilization by rat neutrophils: presence of phosphate-dependent glutaminase. Am J Physiol 1997; 273: C1124–9PubMedGoogle Scholar
  155. 155.
    Castell LM, Newsholme EA. The effects of oral glutamine supplementation upon athletes after prolonged, exhaustive exercise. Nutrition 1997; 13: 738–42PubMedCrossRefGoogle Scholar
  156. 156.
    Castell LM, Liu CT, Newsholme EA. Diurnal variation of plasma glutamine in normal and fasting humans [abstract]. Proc Nutr Soc 1995; 54: 118AGoogle Scholar
  157. 157.
    Bassit RA, Sawada LA, Bacurau RFP, et al. Branched-chain amino acid supplementation and the immune response of longdistance athletes. Nutrition 2002; 18: 376–9PubMedCrossRefGoogle Scholar
  158. 158.
    Bacurau R, Bassi R, Sawada L, et al. Carbohydrate supplementation during intense exercise and the immune response of cyclists. Clin Nutr 2002; 21: 423–9PubMedCrossRefGoogle Scholar
  159. 159.
    Castell LM. Food for thought. Br J Sports Med 1999; 33: 226PubMedGoogle Scholar
  160. 160.
    Garlick PJ. Assessment of the safety of glutamine and other amino acids. J Nutr 2001; 131: 2556S–61SPubMedGoogle Scholar
  161. 161.
    Welbourne TC. Increased plasma bicarbonate and growth hormone after an oral glutamine load. Am J Clin Nutr 1995; 61: 1058–61PubMedGoogle Scholar
  162. 162.
    Antonio J, Street C. Glutamine: a potentially useful supplement for athletes. Can J Appl Physiol 1999; 24: 1–14PubMedCrossRefGoogle Scholar
  163. 163.
    Kreider RB. Dietary supplements and the promotion of muscle growth with resistance exercise. Sports Med 1999; 27: 97–110PubMedCrossRefGoogle Scholar
  164. 164.
    Scolapio JS, McGreevy K, Tennyson GS, et al. Effect of glutamine in short-bowel syndrome. Clin Nutr 2001; 20: 319–23PubMedCrossRefGoogle Scholar
  165. 165.
    Colker CM, Swain MA, Fabrucini B, et al. Effects of supplemental protein on body composition and muscular strength in healthy athletic male adults. Curr Ther Res 2000; 61: 19–28CrossRefGoogle Scholar
  166. 166.
    Candow DG, Chilibeck PD, Burke DG, et al. Effect of glutamine supplementation combined with resistance training in young adults. Eur J Appl Physiol Occup Physiol 2001; 86: 142–9CrossRefGoogle Scholar
  167. 167.
    Stehle P, Zander J, Mertes N, et al. Effects of parenteralglutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet 1989; I: 231–3CrossRefGoogle Scholar
  168. 168.
    Hammarqvist F, Wernerman J, von der Decken A, et al. Alanyl-glutamine counteracts the depletion of free glutamine and the postoperative decline in protein synthesis in skeletal muscle. Ann Surg 1990; 212: 637–44PubMedCrossRefGoogle Scholar
  169. 169.
    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
  170. 170.
    Rohde T, Asp S, MacLean DA, 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: 448–53PubMedCrossRefGoogle Scholar
  171. 171.
    Rohde T, MacLean DA, Pedersen BK. Effect of glutamine supplementation on changes in the immune system induced by repeated exercise. Med Sci Sports Exerc 1998; 30: 856–62PubMedCrossRefGoogle Scholar
  172. 172.
    Krzywkowski K, Petersen EW, Ostrowski K, et al. Effect of glutamine and protein supplementation on exercise-induced decreases in salivary IgA. J Appl Physiol 2001; 91: 832–8PubMedGoogle Scholar
  173. 173.
    Krzywkowski K, Petersen EW, Ostrowski K, et al. Effect of glutamine supplementation on exercise-induced changes in lymphocyte function. Am J Physiol Cell Physiol 2001; 281: C1259–65PubMedGoogle Scholar
  174. 174.
    Walsh NP, Blannin AK, Bishop NC, et al. Effect of oral glutamine supplementation on human neutrophil lipopolysaccharide-stimulated degranulation following prolonged exercise. Int J Sport Exerc Metab 2000; 10: 39–50Google Scholar
  175. 175.
    Gohil K, Viguie C, Stanley WC, et al. Blood glutathione oxidation during human exercise. J Appl Physiol 1988; 64: 115–9PubMedGoogle Scholar
  176. 176.
    Sen CK, Rankinen T, Vaisanen S, et al. Oxidative stress after human exercise: effect of N-acetylcysteine supplementation. J Appl Physiol 1994; 76: 2570–7PubMedGoogle Scholar
  177. 177.
    Sen CK, Packer L. Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr 2000; 72: 6536–6569SGoogle Scholar
  178. 178.
    Sastre J, Asensi M, Gasco E, et al. Exhaustive physical exercise causes oxidation of glutathione status in blood: prevention by antioxidant administration. Am J Physiol 1992; 263: R992–5PubMedGoogle Scholar
  179. 179.
    Vina J, Gomez-Cabrere MC, Lloret A, et al. Free radicals in exhaustive physical exercise: mechanism of production, and protection by antioxidants. IUBMB Life 2000; 50: 271–7PubMedCrossRefGoogle Scholar
  180. 180.
    Cao Y, Feng Z, Hoos A, et al. Glutamine enhances gut glutathione production. JPEN J Parenter Enterai Nutr 1998; 22: 224–7CrossRefGoogle Scholar
  181. 181.
    Gambelunghe C, Rossi R, Micheletti A, et al. Physical exercise intensity can be related to plasma glutathione levels. J Physiol Biochem 2001; 57: 9–14CrossRefGoogle Scholar
  182. 182.
    Valencia E, Hardy G. Glutathione, nitric oxide and sepsis. Br J Intensive Care 2001; Sep/Oct: 167–75Google Scholar
  183. 183.
    Hong RW, Rounds JD, Helton WS, et al. Glutamine preserves liver glutathione after lethal hepatic injury. Ann Surg 1992; 215: 114–9PubMedCrossRefGoogle Scholar
  184. 184.
    Klimberg VS, Kornbluth J, Cao Y, et al. Glutamine suppresses PGE2 synthesis and breast cancer growth. J Surg Res 1996; 63: 293–7PubMedCrossRefGoogle Scholar
  185. 185.
    Mates JM, Perez-Gomez C, Nunez de Castro I, et al. Glutamine and its relationship with intracellular redox status, oxidative stress and cell proliferation/death. Int J Biochem Cell Biol 2001; 1217: 1–20Google Scholar
  186. 186.
    Newsholme P. Why is L-glutamine metabolism important to cells of the immune system in health, postinjury, surgery or infection? J Nutr 2001; 131: 2515–2522SGoogle Scholar
  187. 187.
    Garcia C, Pithon Curi T, De Lourdes C, et al. Effect of adrenaline on glucose and glutamine metabolism and superoxide production by rat neutrophils. Clin Sci 1998; 96: 549–55CrossRefGoogle Scholar
  188. 188.
    Furukawa S, Saito H, Matsuda T, et al. Relative effects of glucose and glutamine on reactive oxygen intermediate production by neutrophils. Shock 2000; 13: 274–8PubMedCrossRefGoogle Scholar
  189. 189.
    DeMarco V, Dyess K, Strauss D, et al. Inhibition of glutamine synthetase decreases proliferation of cultured rat intestinal epithelial cells. J Nutr 1999; 129: 57–62PubMedGoogle Scholar
  190. 190.
    Weiss MD, DeMarco V, Strauss DM, et al. Glutamine synthetase: a key enzyme for intestinal epithelial differentiation? J Parenter Enterai Nutrition 1999; 23: 140–6CrossRefGoogle Scholar
  191. 191.
    Clarke EC, Patel SD, PR Chadwick, et al. Glutamine deprivation facilitates tumour necrosis induced bacterial translocation in Caco-2 cells by depletion of enterocyte fuel substrate. Gut 2003; 52: 224–30CrossRefGoogle Scholar
  192. 192.
    Castell LM, Bevan SJ, Calder P, et al. The role of glutamine in the immune system and in intestinal function in catabolic states. Amino Acids 1994; 7: 231–44CrossRefGoogle Scholar
  193. 193.
    Newsholme EA, Carrie AL. Quantitative aspects of glucose and glutamine metabolism by intestinal cells. Gut 1994; 35: S13–7PubMedCrossRefGoogle Scholar
  194. 194.
    Wischmeyer PE, Musch MW, Madonna MB, et al. Glutamine protects intestinal epithelial cells: role of inducible HSP70. Am J Physiol 1997; 272: G879–84PubMedGoogle Scholar
  195. 195.
    Christensen HN, Streicher JA, Elbinger RL. Effects of feeding individual amino acids upon the distribution of other amino acids between cells and extracellular fluid. J Biol Chem 1948; 172: 515–24PubMedGoogle Scholar

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© Adis Data Information BV 2003

Authors and Affiliations

  1. 1.Nuffield Department of AnaestheticsUniversity of OxfordOxfordEngland

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