occur. First, there is a limitation in the rate of fatty
acid oxidation so that a high rate of ATP genera-
tion cannot be supported by fatty acid oxidation
alone so that, once fat becomes the dominant
fuel, the pace must slow. Secondly, and these are
not mutually exclusive, fatty acids must be mobi-
lized from adipose tissue to be oxidized and
mobilization of fatty acids can result in central
fatigue. A mechanism for this is described below.
Plasma levels of tryptophan, branched-chain
amino acids and the 5-HT hypothesis for
central fatigue
The branched-chain amino acids (leucine,
isoleucine and valine), unlike other amino acids,
are taken up largely by muscle and adipose
tissue. Like most amino acids, tryptophan is
taken up and metabolized by the liver. However,
a small amount of tryptophan is taken up by the
brain, where it is converted to the neurotransmit-
ter 5-hydroxytryptamine (5-HT). Once this neu-
rotransmitter is released in the synapses of some
neurones, it can influence a variety of behav-
iours, including tiredness, sleep, mood and pos-
sibly mental fatigue. It is suggested that an
increase in 5-HT level in these neurones makes it
harder mentally to maintain the same pace of
running, cycling, etc.
The basic tenets of the hypothesis are as
follows.
1 Both branched-chain amino acids and trypto-
phan (and other aromatic amino acids) enter the
brain upon the same amino acid carrier so that
there is competition between the two groups of
amino acids for entry (for review, see Fernstrom
1990).
2 Tryptophan is converted via two enzymes in
the brain to 5-HT. However, an increased level of
brain tryptophan can increase the rate of forma-
tion and hence the level of 5-HT in some areas of
the brain (Blomstrand et al.1989).
3 A high 5-HT level could result in increased
amount of this neurotransmitter being released
into the synaptic cleft during neuronal firing,
therefore leading to a greater postsynaptic stimu-
lation in some 5-HT neurones.
156 nutrition and exercise
4 It is proposed that some of these neurones are
involved in fatigue.
5 Tryptophan is unique amongst the amino
acids in that it is bound to albumin, so that
it exists in the plasma and interstitial space
in bound and free forms, which are in equi-
librium. This equilibrium changes in favour
of free tryptophan as the plasma fatty acid
level increases, since the latter also binds to
albumin and this decreases the affinity for
tryptophan.
6 It is considered that the plasma concentration
of free tryptophan governs, in competition with
branched chain amino acids, the rate of entry of
tryptophan into the brain, the level of tryptophan
in the brain and hence that of 5-HT (Fernstrom
1990).
As a consequence of these basic tenets, it is
proposed that either an increase in the plasma
fatty acid level and/or a decrease in that of
branched-chain amino acids would increase the
plasma concentration ratio of free tryptophan to
branched chain amino acids. This would then
favour the entry of tryptophan into the brain,
and increase the level of 5-HT which would lead
to a decrease in motor drive and a fall in power
output. Hence a marked increase in the plasma
fatty acid level could lead, via changes in the
plasma level of free tryptophan, to fatigue.
This could occur in both the middle-distance or
marathon runner as the muscle and liver glyco-
gen stores are depleted and the fatty acid is mobi-
lized from adipose tissue.Importance of precision in the mobilization
and oxidation of fatty acids
The precise balance between the use of the
two fuels, glycogen and fatty acids, may be
extremely important for the athlete, since too
high or too low a rate of fatty acid mobi-
lization/oxidation could cause problems
(Newsholmeet al.1994). After 20–30 min of exer-
cise, mobilization of fatty acids from adipose
tissue increases, probably as a result of sympa-
thetic stimulation. However, despite increased
rates of mobilization, the plasma concentration