1: Adv Exp Med Biol 1999;467:697-704


The role of tryptophan in fatigue in different conditions of stress.

Castell LM, Yamamoto T, Phoenix J, Newsholme EA.

University Department of Biochemistry, Oxford, UK. [log in to unmask]

Tryptophan is the precursor for the neurotransmitter 5-hydroxytryptamine
(5-HT), which is involved in fatigue and sleep. It is present in bound and
free from in the blood, where the concentration is controlled by albumin
binding to tryptophan. An increase in plasma free tryptophan leads to an
increased rate of entry of tryptophan into the brain. This should lead to a
higher level of 5-HT which may cause central fatigue. Central fatigue is
implicated in clinical conditions such as chronic fatigue syndrome and
post-operative fatigue. Increased plasma free tryptophan leads to an
increase in the plasma concentration ratio of free tryptophan to the
branched chain amino acids (BCAA) which compete with tryptophan for entry
into the brain across the blood-brain barrier. The plasma concentrations of
these amino acids were measured in chronic fatigue syndrome patients (CFS)
before and after exercise (Castell et al., 1998), and in patients undergoing
major surgery (Yamamoto et al., 1997). In the CFS patients, the pre-exercise
concentration of plasma free tryptophan was higher than in controls (p <
0.05) but did not change during or after exercise. This might indicate an
abnormally high level of brain 5-HT in CFS patients leading to persistent
fatigue. In the control group, plasma free tryptophan was increased after
maximal exercise (p < 0.001), returning towards baseline levels 60 min
later. The apparent failure of the CFS patients to change the plasma free
tryptophan concentration or the free tryptophan/BCAA ratio during exercise
may indicate increased sensitivity of brain 5-HT receptors, as has been
demonstrated in other studies (Cleare et al., 1995). In post-operative
recovery after major surgery plasma free tryptophan concentrations were
markedly increased compared with baseline levels; the plasma free
tryptophan/BCAA concentration ratio was also increased after surgery. Plasma
albumin concentrations were decreased after surgery: this may account for
the increase in plasma free tryptophan levels. Provision of BCAA has
improved mental performance in athletes after endurance exercise (Blomstrand
et al., 1995, 1997). It is suggested that BCAA supplementation may help to
counteract the effects of an increase in plasma free tryptophan, and may
thus improve the status of patients during or after some clinically
stressful conditions.

Publication Types:
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  b.. Review, Tutorial

PMID: 10721121 [PubMed - indexed for MEDLINE]