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The Role of Some Amino Acids in Post-Operative Fatigue and in Chronic Fatigue Syndrome

L. M. Castell1, J. Phoenix2, T. Yamamoto3, J. McGuire1 and E.A. Newsholme.1   1Cellular Nutrition Research Group, Univ. Dept of Biochemistry, Oxford OX1 3QU, U.K.; 2Univ. Dept of Medicine, P.O. Box 147, Liverpool L69 3BX, U.K;  3Health  Sci. Lab., Tezukayama Univ.,  Nara, Japan.

The neurotransmitter 5-hydroxytryptamine (5-HT) is involved in fatigue and sleep.  Its precursor, tryptophan, binds to albumin in the blood.  Increased mobilisation of plasma free fatty acids (FFA), which also bind to albumin, leads to more free tryptophan (FT) and thus to an increased rate of brain 5-HT synthesis, which may cause central fatigue.  The branched chain amino acids (BCAA) compete with tryptophan for entry into the brain across the blood-brain barrier, thus an elevated plasma free tryptophan concentration results in an increased plasma concentration ratio of these amino acids (p[FT:BCAA]).   Central fatigue is implicated in chronic fatigue syndrome (CFS) and post-operative fatigue. 

Plasma albumin, free tryptophan, total tryptophan and BCAA were measured before and after major surgery;  and in CFS patients before, during and after maximal exercise on a bicycle ergometer compared with sedentary controls.  Ethical permission was obtained for all studies. 

During post-operative recovery in both elderly and coronary artery bypass graft patients (CABG), plasma FT concentrations were significantly increased compared with baseline levels;  the p[FT:BCAA] was also increased (Yamamoto et al., 1997).  Plasma albumin concentrations were significantly decreased after surgery in both elderly and CABG patients.  More recently both fatigue (as measured by the Profile of Mood States questionnaire)and plasma amino acid concentrations have been measured in patients after major surgery.  An increase in post-operative fatigue has shown a trend towards a correlation with increased plasma free tryptophan. 

In CFS patients, plasma free tryptophan was higher pre-exercise than in controls (p<0.05) but did not change during or after exercise.   Plasma free tryptophan increased in the controls at maximal exercise (p<0.02), peaking at 5 min post-exercise (p<0.001), returning to baseline at 60 min.  The baseline p[FT:BCAA] appeared 31% higher (p<0.1) in the CFS patients than in the controls and remained at similar levels during and after exercise.  The apparent failure of these patients to change the p[FT/BCAA] during exercise may indicate increased sensitivity of brain 5-HT receptors as demonstrated in other studies (Cleare et al., 1995).

Provision of BCAA has improved mental performance in endurance athletes (Blomstrand et al., 1997).  BCAA supplementation might help to counteract the effects of an increase in plasma free tryptophan, and thus improve the symptoms associated with post-operative or chronic fatigue.


Blomstrand, E., Hassmen, P. et al. (1997).  Acta physiol. scand.  159:  41-49.

Cleare, A.J., Bearne, J. et al.  (1995).  J. Affect. Disord.  35:  283-289.

Yamamoto, T., Castell, L.M. et al. (1997).  Brain Res. Bull.  43:  43-46.

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