Efeitos da ingestão dos aminoácidos de cadeia ramificada na fadiga central

 

Paulo Armada-da-Silva*

Francisco Alves

Universidade Técnica de Lisboa

Faculdade de Motricidade Humana

Portugal

 

RESUMO

A descoberta de alterações na actividade e concentração intracefálica de alguns neurotransmissores, nomeadamente a serotonina (5-hidroxitriptamina, 5-HT), durante e após o exercício intenso de longa duração, colocou a questão da relação entre o conhecido efeito depressor destes compostos e o controlo metabólico em esforço de dominante aeróbia. A perturbação do funcionamento dos sistemas monoaminérgicos encefálicos induzida pelo exercício pode estar na base do impedimento à continuação da activação central do sistema neuromuscular em situações próximas do limite, tão habituais no atleta de fundo quando em competição. Ora, sabe-se que a taxa de síntese da 5-HT é sensível à concentração plasmática do triptofano (TRP) livre, dos aminoácidos de cadeia ramificada (AACR) e dos ácidos gordos, o que permitirá a manipulação da função serotoninérgica indirectamente através da suplementação de AACR e de hidratos de carbono. A exploração da intervenção dietética ganhou importância devido à probabilidade da suplementação em AACR induzir uma redução da taxa de passagem dos percursores da 5-HT pela barreira hemato-encefálica. É nosso objectivo neste trabalho discutir a eficácia da intervenção dietética sobre os mecanismos subjacentes ao fenómeno da fadiga central a partir da apreciação do quadro actual de conhecimentos sobre estes complexos mecanismos de regulação metabólica e neuro-humoral.

Palavras-chave: fadiga central, aminoácidos de cadeia ramificada, serotonina.

 

ABSTRACT

The role of branched chain amino acids supplementation on central fatigue.

Evidence of changes in the concentration of certain neurotransmitters in the brain during and after long distance high-intensity exercise, especially serotonin (5-hydroxytryptamine, 5-HT), raised the question of the relationship between the well known depressor effect of these compounds and the metabolic and neuro-hormonal regulation present in the acute response to this type of physical exertion. Functional disturbance of the brain monoaminergic systems induced may be the reason for the inability to maintain central activation of muscle in near the limit situations as happens so often to long distance athletes in competition. Since it is well known that the rate of synthesis of 5-HT is sensitive to the plasma content in free triptophan (TRP), branched-chain amino acids (BCAA) and free fatty acids, it has been postulated that an increase in free fatty acids during and after endurance exercise mediates an increment of free TRP which, in combination with a decline of circulating BCAA, facilitates the entry of TRP into the brain, there by increasing cerebral serotonergic tone. This way, supplementation with BCAAs and/or carbohydrates during exercise becomes an interesting procedure to explore, since it may reduce the rate of penetration of 5-HT precursors through the blood-brain barrier. The aim of this review is to discuss the efficacy of nutritional strategies on the mechanisms underlying central fatigue from present knowledge on the complex metabolic and neurohumoral regulation mechanisms.

Key Words: central fatigue, branched-chain amino acids, serotonin.

 

 

Texto completo disponível apenas em PDF.

Full text only available in PDF format.

 

 

BIBLIOGRAFIA

1. Abbate F, De Ruiter C J, Offringa C, Sargeant A J, De Haan A (2002). In situ rat fast skeletal muscle is more efficient at submaximal than at maximal activation levels. J Appl Physiol 92: 2089-96.        [ Links ]

2. Acworth I, Nicholass J, Morgan B, Newsholme E A (1986). Effect of sustained exercise on concentrations of plasma aromatic and branched-chain amino acids and brain amines. Biochem Biophys Res Commun 137: 149-53.        [ Links ]

3. Aftring R P, Block K P, Buse M G (1986). Leucine and isoleucine activate skeletal muscle branched-chain alpha-keto acid dehydrogenase in vivo. Am J Physiol 250: E599-604.        [ Links ]

4. Ahlenius S, Kaur P, Salmi P (1997). Biphasic effects of 8-OH-DPAT on endurance of treadmill performance in the male rat. Eur Neuropsychopharmacol 7: 89-94.        [ Links ]

5. Anderson I M, Parry-Billings M, Newsholme E A, Fairburn C G, Cowen P J (1990). Dieting reduces plasma tryptophan and alters brain 5-HT function in women. Psychol Med 20: 785-91.        [ Links ]

6. Angus D J, Hargreaves M, Dancey J, Febbraio M A (2000). Effect of carbohydrate or carbohydrate plus medium-chain triglyceride ingestion on cycling time trial performance. J Appl Physiol 88: 113-9.        [ Links ]

7. Azmitia E C, Gannon P J (1986). The primate serotonergic system: a review of human and animal studies and a report on Macaca fascicularis. Adv Neurol 43: 407-68.        [ Links ]

8. Bailey S P, Davis J M, Ahlborn E N (1992). Effect of increased brain serotonergic activity on endurance performance in the rat. Acta Physiol Scand 145: 75-6.        [ Links ]

9. Bailey S P, Davis J M, Ahlborn E N (1993). Serotonergic agonists and antagonists affect endurance performance in the rat [see comments]. Int J Sports Med 14: 330-3.        [ Links ]

10. Bailey S P, Davis J M, Ahlborn E N (1993). Neuroendocrine and substrate responses to altered brain 5-HT activity during prolonged exercise to fatigue. J Appl Physiol 74: 3006-12.        [ Links ]

11. Baldwin J, Snow R J, Gibala M J, Garnham A, Howarth K, Febbraio M A (2003). Glycogen availability does not affect the TCA cycle or TAN pools during prolonged, fatiguing exercise. J Appl Physiol 94: 2181-7.        [ Links ]

12. Banister E W, Cameron B J (1990). Exercise-induced hyperammonemia: peripheral and central effects. Int J Sports Med 11 Suppl 2: S129-42.        [ Links ]

13. Bassit R A, Sawada L A, Bacurau R F, Navarro F, Martins E, Jr., Santos R V, Caperuto E C, Rogeri P, Costa Rosa L F (2002). Branched-chain amino acid supplementation and the immune response of long-distance athletes. Nutrition 18: 376-9.        [ Links ]

14. Becquet D, Faudon M, Hery F (1990). The role of serotonin release and autoreceptors in the dorsalis raphe nucleus in the control of serotonin release in the cat caudate nucleus. Neuroscience 39: 639-47.        [ Links ]

15. Bergstrom J, Hermansen L, Hultman E, Saltin B (1967). Diet, muscle glycogen and physical performance. Acta Physiol Scand 71: 140-50.        [ Links ]

16. Bergstrom J, Hultman E (1967). Synthesis of muscle glycogen in man after glucose and fructose infusion. Acta Med Scand 182: 93-107.        [ Links ]

17. Blomstrand E, Celsing F, Newsholme E A (1988). Changes in plasma concentrations of aromatic and branched-chain amino acids during sustained exercise in man and their possible role in fatigue. Acta Physiol Scand 133: 115-21.        [ Links ]

18. Blomstrand E, Hassmen P, Ekblom B, Newsholme E A (1991). Administration of branched-chain amino acids during sustained exercise- effects on performance and on plasma concentration of some amino acids. Eur J Appl Physiol 63: 83-8.        [ Links ]

19. Blomstrand E, Hassmen P, Newsholme E A (1991). Effect of branched-chain amino acid supplementation on mental performance. Acta Physiol Scand 143: 225-6.        [ Links ]

20. Blomstrand E, Newsholme E A (1992). Effect of branched-chain amino acid supplementation on the exercise-induced change in aromatic amino acid concentration in human muscle. Acta Physiol Scand 146: 293-8.        [ Links ]

21. Blomstrand E, Andersson S, Hassmen P, Ekblom B, Newsholme E A (1995). Effect of branched-chain amino acid and carbohydrate supplementation on the exercise-induced change in plasma and muscle concentration of amino acids in human subjects. Acta Physiol Scand 153: 87-96.        [ Links ]

22. Blomstrand E, Hassmen P, Ek S, Ekblom B, Newsholme E A (1997). Influence of ingesting a solution of branched-chain amino acids on perceived exertion during exercise. Acta Physiol Scand 159: 41-9.        [ Links ]

23. Blomstrand E, Saltin B (2001). BCAA intake affects protein metabolism in muscle after but not during exercise in humans. Am J Physiol Endocrinol Metab 281: E365-74.        [ Links ]

24. Bridge M W, Marvin G, Thompson C E, Sharma A, Jones D A, Kendall M J (2001). Quantifying the 5-HT1A agonist action of buspirone in man. Psychopharmacology (Berl) 158: 224-9.        [ Links ]

25. Calders P, Matthys D, Derave W, Pannier J L (1999). Effect of branched-chain amino acids (BCAA), glucose, and glucose plus BCAA on endurance performance in rats. Med Sci Sports Exerc 31: 583-7.        [ Links ]

26. Castell L M, Yamamoto T, Phoenix J, Newsholme E A (1999). The role of tryptophan in fatigue in different conditions of stress. Adv Exp Med Biol 467: 697-704.        [ Links ]

27. Chaouloff F, Kennett G A, Serrurrier B, Merino D, Curzon G (1986). Amino acid analysis demonstrates that increased plasma free tryptophan causes the increase of brain tryptophan during exercise in the rat. J Neurochem 46: 1647-50.        [ Links ]

28. Chaouloff F, Laude D, Elghozi J L (1989). Physical exercise: evidence for differential consequences of tryptophan on 5-HT synthesis and metabolism in central serotonergic cell bodies and terminals. J Neural Transm 78: 121-30.        [ Links ]

29. Chaouloff F (1993). Physiopharmacological interactions between stress hormones and central serotonergic systems. Brain Res Brain Res Rev 18: 1-32.        [ Links ]

30. Chaouloff F (1997). Effects of acute physical exercise on central serotonergic systems. Med Sci Sports Exerc 29: 58-62.        [ Links ]

31. Colombani P C, Bitzi R, Frey-Rindova P, Frey W, Arnold M, Langhans W, Wenk C (1999). Chronic arginine aspartate supplementation in runners reduces total plasma amino acid level at rest and during a marathon run. Eur J Nutr 38: 263-70.        [ Links ]

32. Costill D L, Dalsky G P, Fink W J (1978). Effects of caffeine ingestion on metabolism and exercise performance. Med Sci Sports 10: 155-8.        [ Links ]

33. Coyle E F, Hagberg J M, Hurley B F, Martin W H, Ehsani A A, Holloszy J O (1983). Carbohydrate feeding during prolonged strenuous exercise can delay fatigue. J Appl Physiol 55: 230-5.        [ Links ]

34. Coyle E F,Coggan A R (1984). Effectiveness of carbohydrate feeding in delaying fatigue during prolonged exercise. Sports Med 1: 446-58.        [ Links ]

35. Cunningham V J, Hay L, Stoner H B (1975). The binding of L-tryptophan to serum albumins in the presence of non-esterified fatty acids. Biochem J 146: 653-8.        [ Links ]

36. Davis J M, Welsh R S, De Volve K L, Alderson N A (1999). Effects of branched-chain amino acids and carbohydrate on fatigue during intermittent, high-intensity running. Int J Sports Med 20: 309-14.        [ Links ]

37. De Palo E F, Gatti R, Cappellin E, Schiraldi C, De Palo C B, Spinella P (2001). Plasma lactate, GH and GH-binding protein levels in exercise following BCAA supplementation in athletes. Amino Acids 20: 1-11.        [ Links ]

38. Delgado P L, Charney D S, Price L H, Aghajanian G K, Landis H, Heninger G R (1990). Serotonin function and the mechanism of antidepressant action. Reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan [see comments]. Arch Gen Psychiatry 47: 411-8.        [ Links ]

39. Dwyer D, Flynn J (2002). Short term aerobic exercise training in young males does not alter sensitivity to a central serotonin agonist. Exp Physiol 87: 83-9.        [ Links ]

40. Emori T, Sugiyama K, Nagase S (1983). Tryptophan metabolism in analbuminemic rats. J Biochem (Tokyo) 94: 623-32.        [ Links ]

41. Farris J W, Hinchcliff K W, McKeever K H, Lamb D R, Thompson D L (1998). Effect of tryptophan and of glucose on exercise capacity of horses. J Appl Physiol 85: 807-16.        [ Links ]

42. Fitts R H, Courtright J B, Kim D H, Witzmann F A (1982). Muscle fatigue with prolonged exercise: contractile and biochemical alterations. Am J Physiol 242: C65-73.        [ Links ]

43. Fitts R H (1994). Cellular mechanisms of muscle fatigue. Physiol Rev 74: 49-94.        [ Links ]

44.Ftaiti F, Grelot L, Coudreuse J M, Nicol C (2001). Combined effect of heat stress, dehydration and exercise on neuromuscular function in humans. Eur J Appl Physiol 84: 87-94.        [ Links ]

45. Gibala M, MacLean D, Graham T, Saltin B (1997). Anaplerotic processes in human skeletal muscle during brief dynamic exercise. J Physiol (Lond) 502: 703-713.        [ Links ]

46. Gibala M J, Gonzalez-Alonso J, Saltin B (2002). Dissociation between muscle tricarboxylic acid cycle pool size and aerobic energy provision during prolonged exercise in humans. J Physiol 545: 705-13.        [ Links ]

47. Gibala M J, Peirce N, Constantin-Teodosiu D, Greenhaff P L (2002). Exercise with low muscle glycogen augments TCA cycle anaplerosis but impairs oxidative energy provision in humans. J Physiol 540: 1079-86.        [ Links ]

48. Graham T E,MacLean D A (1992). Ammonia and amino acid metabolism in human skeletal muscle during exercise. Can J Physiol Pharmacol 70: 132-41.        [ Links ]

49. Graham T E, Turcotte L P, Kiens B, Richter E A (1995). Training and muscle ammonia and amino acid metabolism in humans during prolonged exercise. J Appl Physiol 78: 725-35.        [ Links ]

50. Graham T E,MacLean D A (1998). Ammonia and amino acid metabolism in skeletal muscle: human, rodent and canine models. Med Sci Sports Exerc 30: 34-46.        [ Links ]

51. Hermansen L, Hultman E, Saltin B (1967). Muscle glycogen during prolonged severe exercise. Acta Physiol Scand 71: 129-39.        [ Links ]

52. Hillegaart V, Wadenberg M L, Ahlenius S (1989). Effects of 8-OH-DPAT on motor activity in the rat. Pharmacol Biochem Behav 32: 797-800.        [ Links ]

53. Jacobs B L, Azmitia E C (1992). Structure and function of the brain serotonin system. Physiol Rev 72: 165-229.        [ Links ]

54. Jakeman P M, Hawthorne J E, Maxwell S R, Kendall M J, Holder G (1994). Evidence for downregulation of hypothalamic 5-hydroxytryptamine receptor function in endurance-trained athletes. Exp Physiol 79: 461-4.        [ Links ]

55. Kasperek G J (1989). Regulation of branched-chain 2-oxo acid dehydrogenase activity during exercise. Am J Physiol Endocrinol Metab 256: E186-190.        [ Links ]

56. Kay D, Marino F E, Cannon J, St Clair Gibson A, Lambert M I, Noakes T D (2001). Evidence for neuromuscular fatigue during high-intensity cycling in warm, humid conditions. Eur J Appl Physiol 84: 115-21.        [ Links ]

57. Knowles R G, Pogson C I (1984). Characteristics of tryptophan accumulation by i solated rat forebrain synaptosomes. J Neurochem 42: 663-9.        [ Links ]

58. Kreider R B, Miriel V, Bertun E (1993). Amino acid supplementation and exercise performance. Analysis of the proposed ergogenic value. Sports Med 16: 190-209.        [ Links ]

59. Lehmann M, Huonker M, Dimeo F, Heinz N, Gastmann U, Treis N, Steinacker J M, Keul J, Kajewski R, Haussinger D (1995). Serum amino acid concentrations in nine athletes before and after the 1993 Colmar ultra triathlon. Int J Sports Med 16: 155-9.        [ Links ]

60. MacLean D A,Graham T E (1993). Branched-chain amino acid supplementation augments plasma ammonia responses during exercise in humans. J Appl Physiol 74: 2711-7.        [ Links ]

61. MacLean D A, Graham T E, Saltin B (1996). Stimulation of muscle ammonia production during exercise following branched-chain amino acid supplementation in humans. J Physiol 493: 909-22.        [ Links ]

62. Madsen K, MacLean D A, Kiens B, Christensen D (1996). Effects of glucose, glucose plus branched-chain amino acids, or placebo on bike performance over 100 km. J Appl Physiol 81: 2644-50.        [ Links ]

63. Marsden C A, Conti J, Strope E, Curzon G, Adams R N (1979). Monitoring 5-hydroxytryptamine release in the brain of the freely moving unanaesthetized rat using in vivo voltammetry. Brain Res 171: 85-99.        [ Links ]

64. Marvin G, Sharma A, Aston W, Field C, Kendall M J, Jones D A (1997). The effects of buspirone on perceived exertion and time to fatigue in man. Exp Physiol 82: 1057-60.        [ Links ]

65. McKenzie S, Phillips S M, Carter S L, Lowther S, Gibala M J, Tarnopolsky M A (2000). Endurance exercise training attenuates leucine oxidation and BCOAD activation during exercise in humans. Am J Physiol Endocrinol Metab 278: E580-7.        [ Links ]

66. Meeusen R, Thorre K, Chaouloff F, Sarre S, De Meirleir K, Ebinger G, Michotte Y (1996). Effects of tryptophan and/or acute running on extracellular 5-HT and 5- HIAA levels in the hippocampus of food-deprived rats. Brain Res 740: 245-52.        [ Links ]

67. Meeusen R, Roeykens J, Magnus L, Keizer H, De Meirleir K (1997). Endurance performance in humans: the effect of a dopamine precursor or a specific serotonin (5-HT2A/2C) antagonist. Int J Sports Med 18: 571-7.        [ Links ]

68. Meeusen R, Piacentini M F, Van Den Eynde S, Magnus L, De Meirleir K (2001). Exercise performance is not influenced by a 5-HT reuptake inhibitor. Int J Sports Med 22: 329-36.        [ Links ]

69. Mittleman K D, Ricci M R, Bailey S P (1998). Branched-chain amino acids prolong exercise during heat stress in men and women. Med Sci Sports Exerc 30: 83-91.        [ Links ]

70. Newsholme E A, Acworth I N, Blomstrand E (1987). Amino acids, brain neurotransmitters and a functional link between muscle and brain that is important in sustained exercise. In G. Benzi (Ed.) Advances in Myochemistry. London: John Libbey Eurotext Ltd, 127-133.        [ Links ]

71. Newsholme E A, Blomstrand E, Ekblom B (1992). Physical and mental fatigue: metabolic mechanisms and importance of plasma amino acids. Br Med Bull 48: 477-95.        [ Links ]

72. Nybo L, Nielsen B, Blomstrand E, Moller K, Secher N (2003). Neurohumoral responses during prolonged exercise in humans. J Appl Physiol 95: 1125-31.        [ Links ]

73. Pitsiladis Y P,Maughan R J (1999). The effects of exercise and diet manipulation on the capacity to perform prolonged exercise in the heat and in the cold in trained humans. J Physiol 517: 919-30.        [ Links ]

74. Pitsiladis Y P, Strachan A T, Davidson I, Maughan R J (2002). Hyperprolactinaemia during prolonged exercise in the heat: evidence for a centrally mediated component of fatigue in trained cyclists. Exp Physiol 87: 215-26.        [ Links ]

75. Sahlin K, Katz A, Broberg S (1990). Tricarboxylic acid cycle intermediates in human muscle during prolonged exercise. Am J Physiol 259: C834-41.        [ Links ]

76. Strachan A T, Maughan R J (1999). The hormonal response to a d-fenfluramine challenge in trained and sedentary men. Med Sci Sports Exerc 31: 547-53.        [ Links ]

77. Struder H K, Hollmann W, Duperly J, Weber K (1995). Amino acid metabolism in tennis and its possible influence on the neuroendocrine system. Br J Sports Med 29: 28-30.        [ Links ]

78. Struder H K, Hollmann W, Platen P, Duperly J, Fischer H G, Weber K (1996). Alterations in plasma free tryptophan and large neutral amino acids do not affect perceived exertion and prolactin during 90 min of treadmill exercise. Int J Sports Med 17: 73-9.        [ Links ]

79. Struder H K, Hollmann W, Platen P, Donike M, Gotzmann A, Weber K (1998). Influence of paroxetine, branched-chain amino acids and tyrosine on neuroendocrine system responses and fatigue in humans. Horm Metab Res 30: 188-194.        [ Links ]

80. Struder H K,Weicker H (2001). Physiology and pathophysiology of the serotonergic system and its implications on mental and physical performance. Part II. Int J Sports Med 22: 482-97.        [ Links ]

81. Struder H K,Weicker H (2001). Physiology and pathophysiology of the serotonergic system and its implications on mental and physical performance. Part I. Int J Sports Med 22: 467-81.        [ Links ]

82. Tanaka H, West K A, Duncan G E, Bassett D R, Jr. (1997). Changes in plasma tryptophan/branched chain amino acid ratio in responses to training volume variation. Int J Sports Med 18: 270-5.        [ Links ]

83. van Hall G, Raaymakers J S, Saris W H, Wagenmakers A J (1995). Ingestion of branched-chain amino acids and tryptophan during sustained exercise in man: failure to affect performance. J Physiol (Lond) 486: 789-94.        [ Links ]

84. van Hall G, MacLean D A, Saltin B, Wagenmakers A J (1996). Mechanisms of activation of muscle branched-chain alpha-keto acid dehydrogenase during exercise in man. J Physiol 494: 899-905.        [ Links ]

85. van Hall G, Saltin B, Wagenmakers A J (1999). Muscle protein degradation and amino acid metabolism during prolonged knee-extensor exercise in humans. Clin Sci (Colch) 97: 557-67.        [ Links ]

86. Wagenmakers A J, Coakley J H, Edwards R H (1990). Metabolism of branched-chain amino acids and ammonia during exercise: clues from McArdle's disease. Int J Sports Med 11 Suppl 2: S101-13.        [ Links ]

87. Wagenmakers A J (1992). Amino acid metabolism, muscular fatigue and muscle wasting. Speculations on adaptations at high altitude. Int J Sports Med 13 Suppl 1: S110-3.        [ Links ]

88. Wagenmakers A J (1998). Muscle amino acid metabolism at rest and during exercise: role in human physiology and metabolism. Exerc Sport Sci Rev 26: 287-314.        [ Links ]

89. Weicker H,Struder H K (2001). Influence of exercise on serotonergic neuromodulation in the brain. Amino Acids 20: 35-47.        [ Links ]

90. Wilson W M,Maughan R J (1992). Evidence for a possible role of 5-hydroxytryptamine in the genesis of fatigue in man: administration of paroxetine, a 5-HT re-uptake inhibitor, reduces the capacity to perform prolonged exercise. Exp Physiol 77: 921-4.        [ Links ]

91. Yamamoto T, Castell L M, Botella J, Powell H, Hall G M, Young A, Newsholme E A (1997). Changes in the albumin binding of tryptophan during postoperative recovery: a possible link with central fatigue? [published erratum appears in Brain Res Bull 1997;44(6):735]. Brain Res Bull 43: 43-6.        [ Links ]

92. Yamamoto T, Newsholme E A (2000). Diminished central fatigue by inhibition of the L-system transporter for the uptake of tryptophan. Brain Res Bull 52: 35-8.        [ Links ]

93. Young S N,Gauthier S (1981). Tryptophan availability and the control of 5-hydroxytryptamine and tryptamine synthesis in human CNS. Adv Exp Med Biol 133: 221-30.        [ Links ]

94. Zanker C L, Swaine I L, Castell L M, Newsholme E A (1997). Responses of plasma glutamine, free tryptophan and branched-chain amino acids to prolonged exercise after a regime designed to reduce muscle glycogen. Eur J Appl Physiol 75: 543-8.        [ Links ]

 

CORRESPONDÊNCIA

Paulo A.S. Armada da Silva*

Faculdade de Motricidade Humana

Universidade Técnica de Lisboa

Estrada da Costa da Costa,

Cruz-Quebrada, Portugal

parmada@fmh.utl.pt