THE EFFECT OF BCAA SUPPLEMENTATION UPON THE IMMUNE RESPONSE OF TRIATHLETES.

 

Reinaldo Abunasser BASSIT

Mara Assis MALVERDI

Bassit, R.A.2,4; Sawada, L.A.3; Bacurau, R.F.P.1,4; Navarro, F.2,4 & Costa Rosa, L.F.B.P.2,4

1Department of Physiology and Biophysics and 2Department of Histology and Embryology, Institute of Biomedical Sciences, University of Sao Paulo, Brazil.

3Department of Biodynamic of the Movement of the Human Body, School of Sport and Physical Education, University of Sao Paulo, Brazil.

4Laboratory of Human Nutrition for Athletes - CEPEUSP, University of São Paulo, Brazil

Short tittle: BCAA supplementation and immune response

Key words: triathlon, immune system, glutamine, immunossupression, cytokines, lymphocyte proliferation

Correspondence to:

  • Dr. Luís F. B. P. Costa Rosa, Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas I, Universidade de São Paulo, Av. Lineu Prestes, 1524, 05508-900, Butantã, São Paulo, SP, Brasil.
  • Phone/fax: 55-011-818.7227

Discussion

Participation in triathlon is continuously growing. This sport, which began in the mid-seventies, includes three sequentially performed endurance events: swimming, cycling and running. The distance of each segment varies substantially, so that the total time of competition ranges from 30 min to several hours (25). The physiological effects of a triathlon have been extensively studied (5, 7, 8, 12, 14, 19, 24, 26, 35, 41). It is interesting to note that the physiological and energetic demands, of such a sequence of exercise are unique and require the triathletes to develop a blend of characteristics seen in endurance swimming, cycling and running (33). As a consequence of these elevated demands triathletes presented some side-effects such as glomerular damage (41) and the presence of oxidised DNA bases in urine (12) as well as cellular dehydration and a decrease in serum amino acids, reflecting a catabolic state (19).

The imbalance in plasma amino acids concentration could be related to the increased risk of upper respiratory tract infections that follows intense long-duration exercise (13, 23, 29), by inducing, in the host, a suppression of natural killer and lymphokine activated cells activity and lymphocyte proliferation (36, 37). Glutamine decrease seems to be the main factor causing immunessuppresion, since this amino acid is essential for lymphocyte and macrophage metabolism (2, 27, 30) and its concentration is reduced in the plasma of athletes after long-term, strenuous exercise (17, 28). Rhodes and colleagues (30) showed that after a long term intense exercise (a triathlon consisting of 2.5km swimming, 81km cycling and 19km running) there was a reduction in NK and LAK cell activities paralleled by a decrease in serum glutamine concentrations.

In this study we have evaluated the effect of branched chain amino acid supplementation (BG) upon peripheral blood lymphocyte proliferation, serum glutamine concentration and the production of IL-1, IL-2, TNF-a and INF-g , as well as in the incidence of infections by a questionnaire.

As previously reported (30) the athletes presented reduced serum glutamine concentration (22.8%) after the triathlon, what is very similar to the observed by Parry-Billings and colleagues (28) after a marathon (a reduction of 16%) and by Rhode and colleagues (30), after another triathlon - 2.5km swimming, 81km cycling and 19km running (reduction of 32%). The supplementation of the athletes with BCAA restored serum glutamine concentration to values similar to those found before the competition. In fact, it is known that supplementation with BCAA is able to increase the circulating levels of these amino acids and their metabolisation to glutamine in the skeletal muscle (21) leading to a greater muscle NH3 production (21). NH3, in such model, is derived from the transamination with 2-oxoglutarate which forms glutamate and branched-chain oxo acids, a reaction catalysed by BCAA aminotransferase. Glutamate can then be oxidatively deaminated by glutamate dehydrogenase, releasing the NH3 and reforming 2-oxoglutarate (22). The NH3 produced in such pathway, during exercise, is released in the form of glutamine (21) . This mechanism is reinforced by the fact that the rate limiting step in BCAAs catabolism involves the non-reversible decarboxylation of the BCOAs by branched-chain oxo acid dehydrogenase, which is activated during exercise (11, 16, 38) and is responsive to an increase in the intracellular concentration of BCOAs (21).

It is interesting to note that in the athletes of the PG, who showed a reduction in serum glutamine concentration after the triathlon, an increased proliferative response of peripheral blood lymphocytes, harvested before and after the exercise session, cultivated without mitogens was also observed. These cells, however, showed a reduced response to ConA and LPS, mitogens for T and B cells, respectively, when compared to those obtained from BG athletes, who presented a normal serum glutamine concentration after the triathlon.

An important aspect of immune response concerns the production of cytokines by immune cells. This group of intercellular signalling proteins regulates local and systemic immune and inflammatory responses, as well as other biologic processes. Their effect often overlap considerably and one cytokine may induce the secretion of others, producing a cascade of biological effects. We have evaluated the effect of BCAA supplementation upon cultivated blood mononuclear cells capacity to produce IL-1 and -2, TNF and INF. IL-1 is expressed during infections, particularly with Gram-negative bacteria, and activates B and T cells besides stimulating haemopoiesis (3). IL-1 and TNF share most of their activities, except for the toxic effect of TNF against tumour cells (9). INF is synthesised by T and NK cells in response to mitogens, antigens and IL-2 and enhances macrophage tumoricidal, anti-microbial and antigen presenting activities as well as presents anti-viral properties (34). IL-2 is produced by activated T lymphocytes and is essential for clonal T cell proliferation and for NK cytolytic activity. It also induces the production of IFN, TNF, IL-3, -4, -5 and -6 by activated lymphocytes.

BCAA supplementation increased IL-1, IL-2, TNF and INF production in cells cultivated for 48h in the presence of LPS or PHA. Cells obtained from the PG showed a reduction in cytokine production after the competition, except for IL-2, whose synthesis was not changed after exercise. BCAA supplementation increased the production of all cytokines before the competition, but only that of IL-1 and IL-2 after the test (20% and 41%, respectively). The production of IFN and TNF by the BG athletes was the same before and after the triathlon. Considering the importance of these cytokines in the establishment and control of immune response, the supplementation of the athletes with BCAA seems to be important to keep this signalling and effector mechanism working properly, leading to a reduced incidence of infections in those athletes.

The data show that BCAA supplementation can reverse the reduction in serum glutamine concentration observed after prolonged intense exercise such as an Olympic triathlon. This change in plasma glutamine concentration is paralleled by an increased incidence of infections that results in augmented proliferative response of lymphocytes cultivated in the absence of mitogens. The prevention of the lowering of plasma glutamine concentration allows an increased response of lymphocytes to ConA and LPS, as well as an increased production of IL-1 and 2, TNF and IFN, possibly linked to the lower incidence of infection, reported by the supplemented athletes.

Acknowledgements - We gratefully acknowledge Twinlabâ for kindly provide the amino acids for this project. The work was supported by FAPESP 98/07141-7.

REFERENCES

    1. Ardawi, M.S.M., and E.A. Newsholme. Maximal activities of some enzymes of glycolysis, the tricarboxilic acid cycle ketone-body and glutamine utilisation pathways in lymphocytes of the rat. Biochem. J. 208, 743-748, 1982.
    2. Ardawi, M.S.M. and E.A. Newsholme. Intracellular localisation and properties of phosphate-dependent glutaminase in rat mesenteric lymph nodes. Biochem. J. 217:289-296, 1984.
    3. Beuscher, H.U., and M. Röllinghoff. Interleukin-1. In: Humoral factors. E. Sim (Ed), IRL PRESS, Oxford, 1993, 31-45.
    4. Steel, D.M., and A.S. Whitehead. In: Humoral factors. E. Sim (ED), IRL PRESS, Oxford, 1993, 1-29.
    5. De Vito, G., M. Bernardi, E. Sproviero, and F. Figura. Decrease of endurance performance during Olympic Triathlon. Int. J. Sports Med. 16:24-28, 1995.
    6. Dengel, D.R., M.G. Flynn, D.L. Costill, and J.P. Kirman. Determinants of success during triathlon competition. Res. Q. Exerc. Sports 60:234-238, 1989.
    7. Douglas, P., M. O’Toole, W. Hiller, R. Hackney, and N. Reichav. Cardiac fatigue after prolonged exercise. Circulation 76:1206-1213, 1987.
    8. Farber, H., E. Schaefer, R. Francey, R. Grinaldi, and . N. Hill. The endurance triathlon: metabolic changes after each event and during recovery. Med. Sci. Sports Exerc. 23:959-965, 1991.
    9. Fiers, W. tumour necrosis factor. In: Humoral factors. E. Sim (ED), IRL PRESS, Oxford, 1993, 65-119.
    10. Gastmann, U., F. Dimeo, M. Huonker, J. Böcker, J.M. Steinacker, K.G. Petersen, H. Wieland, J. Keul, and M. Lehmann. Ultra-triathlon-related blood-chemical and endocrinological responses in nine athletes. J. Sports Med. Phys. Fitness 38:18-23, 1998.
    11. Hall, van G., D.A. McLean, B. Saltin, and A.J.M. Wagenmakers. Mechanisms of activation of muscle branched-chain a-keto acid dehydrogenase during exercise in man. J. Physiol. 494:899-905, 1996.
    12. Hartman, A., S. Pfuhler, C. Demong, D. Germadnik, A. Pilger, and G. Speit. Exercise-induced DNA effects in human leukocytes are not accompanied by increased formation of 8-hydroxy-2’-deoxyguanosine or induction of micronuclei. Free Radic. Biol. Med. 24:245-251, 1998.
    13. Heath, G.W., E.S. Ford, T.E. Craven, C.A. Macera, K.L. Jackson, and R.R. Pate. Exercise and the incidence of upper respiratory tract infections. Med. Sci. Sports Exerc. 23:152-157, 1991.
    14. Hill, N., C. Jacoby, and H. Farber. Effect of an endurance triathlon on pulmonary function. Med. Sci. Sports Exerc. 23:1260-1264, 1991.
    15. Holly, R., R. Barnard, M. Rosenthal, E. Applegate, and N. Pritikin. Triathlete characterisation and response to prolonged strenuous competition. Med. Sci. Sports Exerc. 18:123-127, 1986.
    16. Kasperek, G.J., G.L. Dohn, and R.D. Snider. Activation of branched-chain keto acid dehydrogenase by exercise. Am. J. Physiol. 248:R166-R171, 1985.
    17. Keast, D., D. Arstein, W. Harper, R.W. Fry, and A.R. Morton. Depression of plasma glutamine concentration after exercise stress and its possible influence on the immune system. Med. J. Aust. 162:15-18, 1995.
    18. Lakka, T. KIHD 12-Month leisure-time physical activity history. Med. Sci. Sports Exerc. 29:S50-S52, 1997.
    19. Lehmann, M., M. Huonker, F. Dimeo, N. Heinz, U. Gastmann, N. Treis, J.M. Steinacker, J. Keul, R. Kajewski, and D. Häussinger. Serum amino acid concentrations in nine athletes before and after the 1993 Colmar Ultra Triathlon. Int. J. Sports Med. 16:155-159, 1995.
    20. Lehmann, M., H. Mann, U. Gastmann, J. Keul, D. Vetter, J.M. Steinacker, and D. Häussinger. Unaccustomed high-mileage vs intensity training-related changes in performance and serum amino acid levels. Int. J. Sports Med. 17:187-192, 1996.
    21. MacLean, D.A., T.E. Graham, and B. Saltin. Stimulation of muscle ammonia production during exercise following branched-chain amino acid supplementation in humans. J. Physiol. 493:909-922, 1996.
    22. Newsholme, E.A., and Leech, A.R. Biochemistry form the medical sciences. John Willey, New York, 1983, 382-441.
    23. Nieman, D.C., L.M. Johanssen, J.W. Lee, and K. Arabatzis. Infections episodes in runners before and after the Los Angeles Marathon. J. Sports Med. Phys. Fitness 30:316-328, 1990.
    24. O’Toole, M., D. Hiller, L. Crosby, and P. Douglas. The ultraendurance triathlete: a physiological profile. Med. Sci. Sports Exerc. 19:45-50, 1987.
    25. O’Toole, M.L., P.S. Douglas, and W.D.B. Hiller. Applied physiology of a triathlon. Sports Med 8:201-225, 1989.
    26. O’Toole, M., and P.S. Douglas. Applied Physiology of Triathlon. Sports Med. 19:251-267, 1995.
    27. Parry-Billings, M., J. Evans, P.C. Calder, and E.A. Newsholme. Does glutamine contribute to immunosuppression after major burns? Lancet 336:523-525, 1990.
    28. Parry-Billings, M., R. Budgett, Y. Koutedakis, E. Blomstrand, S. Brooks, C. Willians, P. Calder, S. Pilling, R. Baigrie, and E.A. Newsholme. Plasma amino acid concentrations in the overstraining syndrome: possible effects on the immune system. Med. Sci. Sports Exerc. 24:1353-1358, 1992.
    29. Peters, E.M., and E.D. Bateman. Ultramarathon running and upper respiratory tract infectious. An epidemiological survey. S. Afr. Med. J. 64:582-584, 1983.
    30. Rohde, T., H. Ullum, J. Palmo, J. Halkjaer Kristensen, E.A. Newsholme, and B.K. Pedersen. Effects of glutamine on the immune system – influence of muscular exercise and HIV infection. J. Appl. Physiol. 79:146-150, 1995.
    31. Rodhe, T., D.A. MacLean, A. Hartkopp, and B.k. Pedersen. The immune system and serum glutamine during a triathlon. Eur. J. Appl. Physiol. 74:428-434, 1996.
    32. Shinkai, S., Y. Kurokawa, S. Hino, M. Hirose, J. Toni, S. Watanabe, S. Shiraishi, K. Oka, and T. Watanabe. Triathlon competition induced a transient immunosuppressive change in the peripheral blood of athletes. J. Sports Med. Phys. Fitness 33:70-78, 1993.
    33. Sleivert, G.G., and Rowlands, D.S. Physical and physiological factors associated with success in the triathlon. Sports Med. 22:8-18, 1996.
    34. STEEL, D.M., AND WHITEHEAD. The acute phase response. In: Humoral factors. E. Sim (ED), IRL PRESS, Oxford, 1993, 1-29.
    35. Steerenberg, P.A., I.A. van Asperen, A.N. Amerongen, A. Biewenga, D. Mol, G.J. Medema. Salivary levels of immunoglobulin A in triathletes. Eur. J. Oral Sci. 105:305-309, 1997.
    36. Tvede, N., B.K. Pedersen, F.R. Hansen, T. Bendix, L.D. Christensen, H. Galbo, J., and Halkjaer Kristensen. Effect of physical exercise on blood mononuclear cell subpopulations and in vitro proliferative responses. Scand. J. Immunol. 29:383-389, 1989.
    37. Tvede, N., M. Kappel, J. Halkjaer Kristensen, H. Galbo, and B.K. Pedersen. The effect of light, moderate and severe bicycle exercise on lymphocyte subsets, natural and lymphokine activated killer cells, lymphocyte proliferative response and interleukin 2 production. Int. J. Sports Med. 14:275-282, 1993.
    38. Wagenmakers, A.J.M., J.H. Brookes, J.H. Coakley, T. Reilly, and R.H.T. Edwards. Exercise-induced activation of the branched-chain 2-oxo acid dehydrogenase in human muscle. Eur. J. Appl. Physiol. 59:159-167, 1989.
    39. Weicker, H. and E. Werle. Interaction between hormones and the immune system. Int. J. Sports Med. 12:S30-S37, 1991.
    40. Windmuller, H.G., and A.E. Spaeth. Uptake and metabolism of plasma glutamine by small intestine. J. Biol. Chem. 249:5070-5079, 1974.
    41. Yaguchi, H., M. Ishigooka, S. Hayami, T. Kobayashi, Y. Kubota, T. Nakada, and K. Mitobe. The effect of triathlon on urinary excretion of enzymes and proteins. Int. Urol. Nephrol. 30:107-112, 1998.

 

 

 

Reinaldo Abunasser BASSIT

 

 

CRN - 6845

Formação Profissional

  • Professor de Educação Física - Universidade de São Paulo - Escola de Educação Física. (EEFUSP) - 1988-1991.
  • Nutricionista - Universidade Anhembi Morumbi - 1993 - 1996
  • Mestrado - Universidade de São Paulo - Instituto de Ciências Biomédicas. (ICB- USP). Laboratório de Metabolismo
    • Ano de entrada: 1998
    • Previsão de Conclusão: 2000

Atividades Profissionais

  • Professor de Natação e Hidroginástica Período: 2º semestre de 1990
  • Preparação Física Individual (Personal Training) Período: 1989 a 1997
  • Professor de Musculação e Condicionamento Físico Período: 1992 a 1995
  • Coordenador de Natação e Hidroginástica Período: 1994
  • Avaliação e Orientação Nutricional dos Atletas Olímpicos
    • Roberto Scheidt
    • Aurélio Miguel
    • Daniele Zangrando
    • Cristiane Parmiggiane
    • Henrique Guimarães
    • Leandro Macedo
    • Mariana Ohata
  • Orientador Nutricional e Avaliador da Composição Corporal de Times Profissionais.
  • Olympikus Telesp (voleibol) 1995 e 1997
  • Sport Clube Banespa (voleibol) 1996 e 1997.
  • Sport Club Corinthians Paulista (Futebol) 1997
  • Portuguesa Futebol Clube 1997.
  • São Paulo Futebol Clube 1995 e 1996.
  • Preparador Físico das Equipes Masculina e Feminina de Handebol Profissional de Osasco. Período: 1997. (Campeão Brasileiro com a Equipe Feminina).
  • Nutricionista da Equipe Brasileira de Duplas na Travessia da Race Across América 98. Período: 1998. (O Brasil foi campeão pela primeira vez obtendo o record na categoria com o tempo de 7 dias e10 horas.)
  • Consultório particular (desde 1997)

 

Mara Assis MALVERDI

CRN - 6844

Formação Profissional

  • Professora de Educação Física - Universidade de São Paulo - Escola de Educação Física. (EEFUSP) - 1988-1991.
  • Nutricionista - Universidade Anhembi Morumbi - 1993 - 1996

Atividades Profissionais

Área de Educação Física

  • Professora de Ed. Física Escolar (1992-1994)
  • Professora de Natação e Hidroginástica (1992-1994)
  • Professora de Ginástica (1992-1994)
  • Coordenadora de atividades aquáticas (1994)

Área de Nutrição

  • Atendimento em clínicas médicas (1997-1998)
  • Atendimento em academias:
    • Master Academia (1997 - 1998)
    • Raia 4 Morumbi (1997-2000)
    • Raia 4 Moema (1997-2000)
    • Kainágua Fitness (desde 1998)
    • Aquademia Sports (1998-1999)
    • Consultório particular (desde 1997)

 

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