Fatigue pp 315-320 | Cite as

Tryptophan, 5-Hydroxytryptamine and a Possible Explanation for Central Fatigue

  • E. A. Newsholme
  • E. Blomstrand
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 384)


In prolonged exercise the plasma level of branched-chain amino acids (BCAA) may fall and that of fatty acid increases: the latter increases the free tryptophan level, so that the plasma concentration ratio, free tryptophan/BCAA may increase leading to higher levels of tryptophan and therefore of 5-hydroxytryptamine (5-HT) in brain. The latter increases the activity of some 5-HT neurons in the brain which can cause sleep and which could, therefore, increase the mental effort necessary to maintain athletic activity. Drinks containing branched-chain amino acids should restore vigor to athletes whose performance is depressed by an excess of cerebral 5-HT. Recent work suggests that intake of branched-chain amino acids may improve performance in slower runners in the marathon and decrease perceived physical and mental exertion in laboratory experiments. This suggestion is supported by pharmacological manipulations that result in either increased or decreased physical performance.


Muscle Glycogen Apply Physiology Prolonged Exercise Mental Fatigue Central Fatigue 
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. Bailey SP, Davis JM & Ahlborn EA (1992). Effect of increased brain serotonergic activity on endurance performance in the rat. Acta Physiologica Scandinavica 145, 75–76.PubMedCrossRefGoogle Scholar
  2. Bailey SP, Davis JM & Ahlborn EA (1993). Neuroendocrine and substrate responses to altered brain 5-HT activity during prolonged exercise to fatigue. Journal of Applied Physiology 74, 3006–3012.PubMedGoogle Scholar
  3. Blomstrand E, Celsing F & Newsholme EA (1988). Changes in plasma concentrations of aromatic and branched-chain amino acids during sustained exercise in man and their possible role in fatigue. Acta Physiologica Scandinavica 133, 115–121.PubMedCrossRefGoogle Scholar
  4. Blomstrand E, Hassmén P, Ekblom B & Newsholme EA (1991a). Administration of branched-chain amino acids during sustained exercise—effects on performance and on plasma concentration of some amino acids. European Journal of Applied Physiology 63, 83–88.CrossRefGoogle Scholar
  5. Blomstrand E, Hassmén P & Newsholme EA (1991b). Effect of branched-chain amino acid supplementation on mental performance. Acta Physiologica Scandinavica 143, 225–226.PubMedCrossRefGoogle Scholar
  6. Blomstrand E, Perrett D, Parry-Billings M & Newsholme EA (1989). Effect of sustained exercise on plasma amino acid concentrations and on 5-hydroxytryptamine metabolism in six different brain regions of the rat. Acta Physiologica Scandinavica 136, 473–481.PubMedCrossRefGoogle Scholar
  7. Cowen PJ, Anderson IM & Grahame-Smith DG (1990). Neuroendocrine effects of azapirones. Journal of Clinical Psychopharmacology 10, 215–255.CrossRefGoogle Scholar
  8. Davis JM, Bailey SP, Woods JA, Galiano FJ, Hamilton MT & Bartoli WP (1992). Effects of carbohydrate feedings on plasma free tryptophan and branched-chain amino acids during prolonged cycling. European Journal of Applied Physiology 65, 513–519CrossRefGoogle Scholar
  9. Fernstrom JD (1990). Aromatic amino acids and monamine synthesis in the CNS: influence of diet. Journal of Nutritional Biochemistry 10, 508–517.CrossRefGoogle Scholar
  10. Jakeman PM, Hawthorne JE, Maxwell SRJ, Kendall MJ & Holder G (1994). Evidence for down regulation of hypothalamic 5-hydroxytryptamine receptor function in endurance-trained athletes. Experimental Physiology 79, 461–464.PubMedGoogle Scholar
  11. Newsholme EA (1986). Application of knowledge of metabolic integration to the problem of metabolic limitations in middle distance and marathon running. Acta Physiologica Scandinavica 128 (suppl. 556), 93–97.Google Scholar
  12. Newsholme EA, Blomstrand E, Hassmén P & Ekblom B (1991). Physical and mental fatigue: do changes in plasma amino acids play a role? Biochemical Society Transactions 19, 358–362PubMedGoogle Scholar
  13. Newsholme EA, & Leech AR (1983). Biochemistry for the Medical Sciences. Chichester, England: John Wiley & Sons.Google Scholar
  14. Okamura K, Matsubara F, Yoshioka Y, Kikuchi N, Kikuchi Y & Kohri H (1987). Exercise-induced changes in branched chain amino acid/aromatic amino acid ratio in the rat brain and plasma. Japanese Journal of Pharmacology 45, 243–248.PubMedCrossRefGoogle Scholar
  15. Wilson WM & Maughan RJ (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. Experimental Physiology 77, 921–924.PubMedGoogle Scholar
  16. Wright DA, Sherman WM & Dernbach AR (1991). Carbohydrate feedings before, during or in combination improve cycling endurance performance. Journal of Applied Physiology 71, 1082–1088.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • E. A. Newsholme
    • 1
  • E. Blomstrand
    • 2
  1. 1.Cellular Nutrition Research Group, Department of BiochemistryUniversity of OxfordOxfordUK
  2. 2.Pripps Research LaboratoryPripps BryggeriBrommaSweden

Personalised recommendations