of fatty acids may be only slightly increased: this
is because the rates of fatty acid uptake and oxi-
dation by the active muscle are increased
(Winder 1996).
It is possible that the plasma fatty acid concen-
tration and therefore the free tryptophan level
increases markedly in exercise only in some
conditions:
- when the muscle (and liver) glycogen store are
totally depleted; - in unfit subjects, when control of fatty acid
mobilization may not be precisely regulated in
relation to demand and control of oxidation
within the muscle; - when the rate of fatty acid oxidation by muscle
is somewhat restricted by the intermittent nature
of the exercise that occurs, in games such as
soccer, rugby, tennis, or squash; - in obese individuals, in whom precision of
release may be restricted by the amount of
adipose tissue.
If the rate of fatty acid mobilization from
adipose tissue is higher than that of oxidation by
muscle, the plasma concentration of fatty acids
will increase, increasing the free tryptophan level
in the plasma, which will result in central fatigue
as described above. If the rate of fatty acid oxida-
tion is too low (e.g. if the rate of mobilization
is too low), the rate of glycogen oxidation will
be high, and the athlete may deplete glycogen
stores before the end of the race, resulting in a
very poor performance. Thus, the endurance
athlete appears to have to run on a metabolic
tightrope of fatty acid mobilization/oxidation
during the race, and the precise rate of mobiliza-
tion/oxidation for each athlete must be learnt by
training.
A summary of experimental findings which
support the hypothesis is as follows.
1 The plasma concentration ratio of free trypto-
phan/branched-chain amino acids is increased
in humans after prolonged exhaustive exercise
and, in the rat, the brain levels of tryptophan and
5-HT are increased (Blomstrand et al. 1989,
1991a).
2 Administration of a 5-HT agonist impairs
running performance, whereas a 5-HT antago-
nist improved running performance in rats
(Baileyet al.1992).
3 Administration of a 5-HT re-uptake blocker
to human subjects decreased physical perfor-
mance—exercise time to exhaustion during stan-
dardized exercise was decreased in comparison
with a control condition (Wilson & Maughan
1992).
4 The secretion of prolactin from the hypothala-
mus is controlled, in part, by 5-HT neurones, and
5-HT stimulates the rate of secretion. During
exercise, there is a correlation between the
plasma levels of prolactin and free tryptophan,
supporting the view that increased free trypto-
phan level in the blood can influence the 5-HT
level in the hypothalamus (Fischer et al.1991).
5 The blood prolactin level increased to a much
smaller extent in well-trained endurance ath-
letes, compared with controls, in response to an
agent that increased 5-HT levels in the hypotha-
lamus (e.g. fenfluramine). This could be caused
by down-regulation of 5-HT receptors as a result
of chronic elevation of the 5-HT level in this part
of the brain (Jakeman et al.1994).
In the past few years, supplementary feeding
with branched-chain amino acids has produced
some results supporting the hypothesis and
some which show no effect. The latter are
described in more detail by Davis in Chapter 12.
Table 11.2 gives a brief comparison of the results
from supplementation studies in exercise of
which the authors are aware. In one of the most
recent studies, a laboratory-based, cross-over
study, seven endurance cyclists were monitored
for perceived effort and mental fatigue (using the
Borg scale), with and without branched-chain
amino acid supplementation. When subjects
received the branched-chain amino acids, com-
pared with the placebo, there was a lower per-
ception of effort required to sustain the level
of exercise required (Blomstrand et al. 1997).
Mittlemanet al.(1998) have reported a positive
effect of branched-chain amino acids on perfor-
mance in moderate exercise during heat stress in
men and women.
In rats, injection of branched-chain amino
acids not only increased the time to fatigue of