(ii) subjects accomplished a greater amount of
work following caffeine ingestion than controls
when RPE was held constant (Ivy et al. 1979; Cole
et al. 1996). This significant decline in experimen-
tal RPE is certainly supported by anecdotal evi-
dence. It has been speculated that the lowered
RPE with caffeine is due to a decrease in the
firing threshold of motorneurones (Nehlig &
Debry 1994; Cole et al. 1996) or changes in muscle
contraction force (Tarnopolsky 1994). Both
mechanisms would result in lowered afferent
feedback from the working muscle and a
lowered RPE, the first mechanism because more
motor units would be recruited for a given task
and the second because the force for a given stim-
ulus would be greater. However, the ability of
physiological caffeine concentration to alter con-
tractile function is equivocal as discussed earlier
(Grahamet al. 1994; Tarnopolsky 1994). Another
hypothesis is that caffeine directly affects the
release of b-endorphins and other hormones that
modulate the feelings of discomfort and pain
associated with exhaustive exercise (Nehlig et al.
1992). A final explanation for the reduced RPE
may involve the central fatigue hypothesis
(Tarnopolsky 1994).
central fatigue hypothesis
Given that caffeine affects the CNS, it is appeal-
ing to link it to one proposed mechanism of
fatigue currently being investigated, the central
fatigue hypothesis (see Chapter 12). Briefly, this
hypothesis argues that the central component of
fatigue caused by exhaustive exercise is medi-
ated by elevated levels of serotonin (5-HT) in the
brain, caused by an increase in its precursor,
tryptophan (TRP) (Blomstrand & Newsholme
1996). Tryptophan is the only amino acid that is
transported in plasma bound to albumin and it
competes for transport into the brain with
branched-chain amino acids (BCAA). Evidence
for the central fatigue theory includes increased
levels of brain 5-HT at fatigue, increased plasma
free TRP at fatigue caused by high FFAs, and
decreased fatigue with BCAA supplementation
(Blomstrand & Newsholme 1996). If caffeine
delayed the onset of CNS fatigue via serotonin
levels, then it must lower 5-HT levels or inhibit
the rise in 5-HT. However, the effects of caffeine
on the CNS and peripheral metabolism appear to
counter this process for two reasons. First, acute
caffeine ingestion has been shown to signifi-
cantly increase brain 5-HT levels, most likely due
to increases in brain free TRP levels (Fernstrom &
Fernstrom 1984; Nehlig et al. 1992). Second, caf-
feine ingestion prior to exercise elevates plasma
FFA concentration at the onset of exercise, which
should increase free TRP, due to competition for
albumin binding, and hasten fatigue. It is possi-
ble that the rise in 5-HT at the onset of exercise
is overridden by other factors, such as
increased sympathetic drive, or favourable meta-
bolic factors. Similarly, since it has been postu-
lated that the ratio of 5-HT to dopamine is a
larger determinant in fatigue than the [5-HT]
alone (Davis & Bailey 1997), the caffeine-induced
rise in both neurotransmitters could offset each
other.
In summary, the caffeine-induced mecha-
nism(s) that may delay central fatigue are still
undiscovered, but the link between caffeine
and the central fatigue hypothesis remains
intriguing.Complications of studying caffeine,
exercise performance and metabolism
It is important to note in a discussion of the per-
formance, metabolic and central effects of caf-
feine ingestion that the mechanism(s) of action
may not be entirely due to the primary effects of
caffeine. Caffeine is a trimethylxanthine com-
pound, which is rapidly metabolized in the liver
to three dimethylxanthines, paraxanthine, theo-
phylline and theobromine. These are released
into the plasma as the caffeine concentration
declines and remain in the circulation longer.
While the plasma dimethylxanthine concen-
trations are not large, paraxanthine and theo-
phylline are potential adenosine antagonists and
metabolic stimuli. Therefore, as caffeine and its
metabolites are often present at the same time, it
is difficult to resolve which tissues are directly or