was found to be increased in electrically stimu-
lated hemidiaphragm perfused with choline in
vitro(Bierkamper & Goldberg 1980).
Wurtman and colleagues hypothesized that
fatigue during prolonged exercise may be ini-
tiated by a reduction in ACh activity subsequent
to depletions in availability of choline (Conley et
al.1986; Sandage et al.1992). This group recently
showed that plasma choline levels were reduced
approximately 40% in runners following com-
pletion of the Boston Marathon (Conley et al.
1986). They also reported that performance of a
32-km run was improved when plasma choline
was maintained or elevated by consumption of a
beverage supplemented with choline citrate
(Sandageet al.1992). However, there is still no
evidence that decreased plasma choline is associ-
ated with ACh depletion at the neuromuscular
junction, or in the brain for that matter,
and that this leads to fatigue. In addition, as
described earlier in this chapter, relatively
uncontrolled field studies such as these are often
misleading because it is difficult to know for sure
whether the effect ascribed to choline was not
due to a number of other uncontrolled variables.
Results of the only well-controlled laboratory
study of the effects of choline supplementation
on exercise performance do not support a benefi-
cial effect of choline supplementation (Spector et
al.1995). Neither low- nor high-intensity exercise
performance was improved with choline supple-
mentation. Choline was given (2.43 g, 1 h before
exercise) prior to either a prolonged cycling bout
to fatigue at 70% V
.
o2max.(ª73 min) or a shorter
term, high-intensity cycling bout at 150% of
V
.
o2max. (ª2 min). In addition, serum choline
levels were not reduced by either of these exer-
cise conditions. The authors did suggest that the
duration of exercise protocols might have to be
extended to allow for the hypothesized benefit of
choline administration to be realized.
Conclusion
It is unfortunate that so little is known about the
mechanisms underlying a CNS effect on fatigue.
This area of investigation has largely been
180 nutrition and exercise
ignored due in large part to difficulty in studying
brain function in humans, a lack of good theories
to explain such an occurrence, and a lack of
good methodologies to directly measure central
fatigue. However, in recent years, new method-
ologies and viable theories have sparked
renewed interest in the development of hypothe-
ses, which can be tested in a systematic fashion,
that may help to explain the role of the CNS in
fatigue.
Nutritional interventions are a common aspect
of recent studies on CNS fatigue. Nutritional
strategies designed to alter brain 5-HT metabo-
lism have received the most attention in this
regard. While 5-HT is almost certainly not the
only neurotransmitter involved in central fatigue
during prolonged exercise, review of the mecha-
nisms involved in the control of brain serotonin
synthesis and turnover make it a particularly
attractive candidate. It is well known that in-
creases in brain 5-HT can have important effects
on arousal, lethargy, sleepiness and mood that
could be linked to altered perception of effort
and feelings of fatigue. Increases in 5-HT metab-
olism appear to increase in several brain regions
due to an increase in plasma f-TRP during pro-
longed exercise and reach a peak at fatigue.
Drugs that increase and decrease brain 5-HT
activity have predictable effects on run times to
fatigue in the absence of any apparent peripheral
markers of muscle fatigue.
The evidence for a benefit of nutrition on
central fatigue during exercise is more tenuous.
Studies involving BCAA supplementation
usually show no performance benefit even
though preliminary evidence in rats suggests
that it may suppress brain 5-HT metabolism
during exercise. Perhaps negative effects of
ammonia accumulation on muscle and brain
function offset the potentially beneficial effect of
BCAA on brain 5-HT. CHO supplementation, on
the other hand, is associated with a large sup-
pression of plasma f-TRP and f-TRP/BCAA and
decreased brain 5-HT metabolism, and fatigue is
delayed by this strategy. In this case, however, it
is not possible to distinguish with certainty the
effects of CHO feedings on CNS fatigue mecha-