Branched-Chain Amino Acids and Central Fatigue: Implications for Diet and Behavior

  • Eva Blomstrand


The branched-chain amino acids (BCAA) leucine, isoleucine, and valine can influence metabolism in the brain in several ways, including an effect on the synthesis of the monoamines dopamine, norepinephrine, and 5-hydroxytryptamine (5-HT). These monoamines are synthesized from the aromatic amino acids tyrosine and tryptophan, the latter being the precursor for 5-HT. The rate-limiting step in the synthesis of 5-HT is the transport of tryptophan across the blood–brain barrier, a process that is influenced not only by the plasma concentration of tryptophan, but also by the plasma levels of the other large neutral amino acids, including the BCAA, which compete with tryptophan for entry into the brain. Changes in the release of 5-HT in the brain are known to be involved in the control of arousal, sleepiness, and changes in mood and have also been suggested to play a role in the fatigue that occurs during and after physical exercise. In agreement with this proposal, the synthesis and release of 5-HT in experimental animals is enhanced during sustained exercise. Moreover, studies on human subjects reveal that the ratio of free tryptophan (i.e., unbound to albumin)/BCAA in plasma increases during endurance exercise and, furthermore, that tryptophan is taken up by the brain in this situation. Ingestion of BCAA leads to elevation in their plasma concentrations and should consequently decrease uptake of tryptophan into the brain, thereby attenuating the rate of synthesis and release of 5-HT and reducing central fatigue. When this hypothesis was tested in human subjects in connection with different types of physical exertion, positive effects on mental performance and perceived effort were reported in both field studies and under controlled laboratory conditions. Under certain conditions, BCAA can also improve physical performance, but this is dependent on the type of exercise, the amount and composition of the supplement administered, and the physical condition of the subjects. Finally, although exercise also increases uptake of BCAA by the brain, the significance of this effect remains unclear. Perhaps BCAA play some additional role in connection with central neurotransmission during sustained exercise.


Amyotrophic Lateral Sclerosis Prolonged Exercise Central Fatigue Large Neutral Amino Acid Arterial 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.



Branched-chain amino acids


The Borg CR10 scale®




Free fatty acids


Large neutral amino acids






5-Hydroxyindole acetic acid


Maximal pulmonary oxygen uptake


  1. Ahlborg G, Felig P, Hagenfeldt L, Hendler R, Wahren J J Clin Invest. 1974;53:1080–90.PubMedCrossRefGoogle Scholar
  2. Bailey SP, Davis JM, Ahlborn EN Acta Physiol Scand. 1992;145:75–6.PubMedCrossRefGoogle Scholar
  3. Bailey SP, Davis JM, Ahlborn EN Int J Sports Med. 1993;14:330–33.PubMedCrossRefGoogle Scholar
  4. Barchas JD, Freedman DX Biochem Pharmacol. 1963;12:1232–5.PubMedCrossRefGoogle Scholar
  5. Blomstrand E. J Nutr. 2006;136:544S–7S.PubMedGoogle Scholar
  6. Blomstrand E, Saltin B Am J Physiol Endocrinol Metab. 2001;281:E365–74.PubMedGoogle Scholar
  7. Blomstrand E, Perrett D, Parry-Billings M, Newsholme EA Acta Physiol Scand. 1989;136:473–81.PubMedCrossRefGoogle Scholar
  8. Blomstrand E, Hassmén P, Newsholme EA Acta Physiol Scand. 1991a;143:225–6.PubMedCrossRefGoogle Scholar
  9. Blomstrand E, Hassmén P, Ekblom B, Newsholme EA Eur J Appl Physiol Occup Physiol. 1991b;63:83–8.PubMedCrossRefGoogle Scholar
  10. Blomstrand E, Andersson S, Hassmén P, Ekblom B, Newsholme EA Acta Physiol Scand. 1995;153:87–96.PubMedCrossRefGoogle Scholar
  11. Blomstrand E, Hassmén P, Ek S, Ekblom B, Newsholme EA Acta Physiol Scand. 1997;159:41–9.PubMedCrossRefGoogle Scholar
  12. Blomstrand E, Møller K, Secher NH, Nybo L Acta Physiol Scand. 2005;185:203–9.PubMedCrossRefGoogle Scholar
  13. Borg G. The Borg CR Scales® Folder. Methods for measuring intensity of experience. Hasselby, Sweden: Borg Perception; 2004, 2008.Google Scholar
  14. Broocks A, Meyer T, George A, Hillmer-Vogel U, Meyer D, Bandelow B, Hajak G, Bartmann U, Gleiter C, Rüther E Neuropsychopharmacology. 1999;20:150–61.PubMedCrossRefGoogle Scholar
  15. Calders P, Pannier J-L, Matthys DM, Lacroix EM Med Sci Sports Exerc. 1997;29:1182–6.PubMedCrossRefGoogle Scholar
  16. Calders P, Matthys D, Derave W, Pannier J-L Med Sci Sports Exerc. 1999;31:583–7.PubMedCrossRefGoogle Scholar
  17. Caperuto EC, dos Santos RVT, Mello MT, Costa Rosa LFBP Clin Exp Pharmacol Physiol. 2009;36:189–91.PubMedCrossRefGoogle Scholar
  18. Chaouloff F. Med Sci Sports Exerc. 1997;29:58–62.PubMedGoogle Scholar
  19. Chaouloff F, Elghozi JL, Guezennec Y, Laude D Br J Pharmacol. 1985;86:33–41.PubMedGoogle Scholar
  20. Chaouloff F, Kennett GA, Serrurrier B, Merino D, Curzon G J Neurochem. 1986a;46:1647–50.PubMedCrossRefGoogle Scholar
  21. Cheuvront SN, Carter R 3rd, Kolka MA, Lieberman HR, Kellogg MD, Sawka MN J Appl Physiol. 2004;97:1275–82.PubMedCrossRefGoogle Scholar
  22. Choi S, DiSilvio B, Fernstrom MH, Fernstrom JD Physiol Behav. 2009;98:156–62.PubMedCrossRefGoogle Scholar
  23. Curzon G, Friedel J, Knott PJ Nature. 1973;242:198–200.PubMedCrossRefGoogle Scholar
  24. Davis JM, Bailey SP, Woods JA, Galiano FJ, Hamilton MT, Bartoli WP Eur J Appl Physiol Occup Physiol. 1992;65: 513–19.PubMedCrossRefGoogle Scholar
  25. Davis JM, Welsh RS, De Volve KL, Alderson NA Int J Sports Med. 1999;20:309–14.PubMedCrossRefGoogle Scholar
  26. Dwyer D, Browning JActa Physiol Scand. 2000;170:211–16.PubMedCrossRefGoogle Scholar
  27. Dwyer D, Flynn J Exp Physiol. 2002;87:83–9.PubMedCrossRefGoogle Scholar
  28. Eriksson T, Carlsson A Life Sci. 1988;42:1583–9.PubMedCrossRefGoogle Scholar
  29. Fernstrom JD. J Nutr. 2005;135:1539S–46S.PubMedGoogle Scholar
  30. Fernstrom JD, Fernstrom MH J Nutr. 2006;136:553S–9S.PubMedGoogle Scholar
  31. Gijsman HJ, Scarna A, Harmer CJ, McTavish SFB, Odontiadis J, Cowen PJ, Goodwin GM Psychopharmacology. 2002;160:192–7.PubMedCrossRefGoogle Scholar
  32. Gomez-Merino D, Béquet F, Berthelot M, Riverain S, Chennaoui M, Guezennec CY Int J Sports Med. 2001;22: 317–22.PubMedCrossRefGoogle Scholar
  33. Hassmén P, Blomstrand E, Ekblom B, Newsholme EA Nutrition. 1994;10:405–10.PubMedGoogle Scholar
  34. Hutson SM, Lieth E, LaNoue KF J Nutr. 2001;131:846S–50S.PubMedGoogle Scholar
  35. Jakeman PM, Hawthorne JE, Maxwell SRJ, Kendall MJ, Holder G Exp Physiol. 1994;79:461–64.PubMedGoogle Scholar
  36. Langfort J, Baranczuk E, Pawlak D, Chalimoniuk M, Lukacova N, Marsala J, Gorski J Cell Mol Neurobiol. 2006;26:1327–42.PubMedCrossRefGoogle Scholar
  37. Lehmann M, Huonker M, Dimeo F, Heinz N, Gastmann U, Treis N, Steinacker JM, Keul J, Kajewski R, Haussinger D Int J Sports Med. 1995;16:155–9.PubMedCrossRefGoogle Scholar
  38. McGuire J, Ross GL, Price H, Mortensen N, Evans J, Castell LM Brain Res. 2003;60:126–30.Google Scholar
  39. Marvin G, Sharma A, Aston W, Field C, Kendall MJ, Jones DA Exp Physiol. 1997;82:1057–60.PubMedGoogle Scholar
  40. Meeusen R, Roeykens J, Magnus L, Keizer H, De Meirleir K Int J Sports Med. 1997;18:571–7.PubMedCrossRefGoogle Scholar
  41. Meeusen R, Piacentini MF, Van Den Eynde S, Magnus L, De Meirleir K Int J Sports Med. 2001;22:329–36.PubMedCrossRefGoogle Scholar
  42. Meeusen R, Watson P, Hasegawa H, Roelands B, Piacentini MF Sports Med. 2006;36:881–909.PubMedCrossRefGoogle Scholar
  43. Mittleman KD, Ricci MR, Bailey SP Med Sci Sports Exerc. 1998;30:83–91.PubMedGoogle Scholar
  44. Newsholme EA, Leech AR Biochemistry for the medical sciences. Chichester: Wiley; 1983. pp. 784–6.Google Scholar
  45. Newsholme EA, Acworth IN, Blomstrand E In: Benzi G, editor. Advances in myochemistry. London: John Libbey; 1987. pp. 127–33.Google Scholar
  46. Pardridge WM. Neurochem Res. 1998;23:635–44.PubMedCrossRefGoogle Scholar
  47. Portier H, Chatard JC, Filaire E, Jaunet-Devienne MF, Robert A, Guezennec CY Eur J Appl Physiol. 2008;104: 787–94.PubMedCrossRefGoogle Scholar
  48. Pannier JL, Bouckaert JJ, Lefebvre RA Eur J Appl Physiol. 1995;72:175–8.CrossRefGoogle Scholar
  49. Pitsiladis YP, Strachan AT, Davidson I, Maughan RJ Exp Physiol. 2002;87:215–26.PubMedCrossRefGoogle Scholar
  50. Romanowski W, Grabiec S Acta Physiol Pol. 1974;25:127–34.PubMedGoogle Scholar
  51. Sahlin K. In: Hargreaves M, Spriet L., editors. Exercise metabolism, Champaign: Human Kinetics. 2006. pp. 163–86.Google Scholar
  52. Sato Y, Eriksson S, Hagenfeldt L, Wahren J Clin Physiol. 1981;1:151–65.CrossRefGoogle Scholar
  53. Scarna A, Gijsman HJ, McTavish SFB, Harmer CJ, Cowen PJ, Goodwin GM Br J Psychiatry. 2003;182:210–13.PubMedCrossRefGoogle Scholar
  54. Smriga M, Kameishi M, Torii K J Nutr. 2006;136:548S–52S.PubMedGoogle Scholar
  55. Strachan AT, Maughan RJ Med Sci Sports Exerc. 1999;31:547–53.PubMedCrossRefGoogle Scholar
  56. Strachan AT, Leiper JB, Maughan RJ Exp Physiol. 2004;89:657–64.PubMedCrossRefGoogle Scholar
  57. Strüder HK, Weicker H Int J Sports Med. 2001;22:482–97.PubMedCrossRefGoogle Scholar
  58. Strüder HK, Hollmann W, Platen P, Donike M, Gotzmann A, Weber K Horm Metab Res. 1998;30:188–94.PubMedCrossRefGoogle Scholar
  59. Takao Y, Kamisaki Y, Itoh T Eur J Pharmacol. 1992;215:245–51.PubMedCrossRefGoogle Scholar
  60. Van Hall G, Raaymakers JSH, Saris WHM J Physiol. 1995;486:789–94.PubMedGoogle Scholar
  61. Verger PH, Aymard P, Cynobert L, Anton G, Luigi R Physiol Behav. 1994;55:523–6.PubMedCrossRefGoogle Scholar
  62. Watson P, Shirreffs SM, Maughan RJ Eur J Appl Physiol. 2004;93:306–14.PubMedCrossRefGoogle Scholar
  63. Wilson WM, Maughan RJ Exp Physiol. 1992;77:921–4.PubMedGoogle Scholar
  64. Young SN. In: Wurtman RJ, Wurtman JJ., editors. Nutrition and the brain (vol 7). New York: Raven Press; 1986. pp. 49–88.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.The Åstrand LabaratoryThe Swedish School of Sport and Health SciencesStockholmSweden

Personalised recommendations