on portions of the CNS that alter the perception
of effort and/or motor unit recruitment.
Metabolic mechanisms for improved
exercise performance
Presently, it seems that metabolic mechanisms
are part of the explanation for the improvement
in endurance performance following caffeine
ingestion (5–13 mg · kg–1), except at low caffeine
doses (2–4 mg · kg–1) where this has not been fully
examined. The increased plasma FFA concentra-
tion at the onset of exercise, the glycogen sparing
in the initial 15 min of exercise and increased
intramuscular TG use during the first 30 min of
exercise suggest a greater role for fat metabolism
early in exercise following caffeine doses of at
least 5 mg · kg–1. However, there are currently no
definitive measurements of increased plasma
FFA use following caffeine ingestion. Also, these
metabolic findings do not preclude other factors
contributing to enhanced endurance perfor-
mance as discussed below.
It has been suggested that the increased fat oxi-
dation and decreased glycogen use in muscle fol-
lowing caffeine ingestion could be explained by
the classic glucose–fatty acid cycle proposed by
Randle and colleagues (Spriet & Dyck 1996). In
this scheme, elevated FFA availability to the
muscle produced increases in muscle citrate
and acetyl-coenzyme A, which were believed
to inhibit the enzymes phosphofructokinase
and pyruvate dehydrogenase. The subsequent
decrease in glycolytic activity increased glucose
6-phosphate content, leading to inhibition of
hexokinase and ultimately decreased muscle
glucose uptake and oxidation. However, these
mechanisms were not involved in the CHO
sparing during exercise at 85% V
.
o2max.with caf-
feine ingestion or increased fat availability
(Sprietet al. 1992; Dyck et al. 1993). Instead, the
mechanism for muscle glycogen sparing follow-
ing caffeine ingestion appeared related to the
regulation of glycogen PHOS activity via the
energy status of the cell (Chesley et al. 1998). Sub-
jects who spared muscle glycogen had smaller
decreases in muscle phosphocreatine and
384 nutrition and exercise
smaller increases in free AMP during exercise in
the caffeine vs. placebo trials. The resultant lower
free inorganic phosphate and AMP concentra-
tions decreased the flux through the more active
aform of PHOS. There were no differences in
these metabolites between trials in subjects who
did not spare muscle glycogen. It is not presently
clear how caffeine defends the energy state of the
cell at the onset of intense exercise, but it may be
related to the availability of fat (Chesley et al.
1998).
It also appears that adrenaline does not con-
tribute to the metabolic changes which lead to
enhanced endurance performance following
caffeine ingestion. First, performance was
enhanced with 3 mg caffeine · kg–1without signif-
icant increases in plasma adrenaline and FFA,
although FFA were increased twofold at rest
(Graham & Spriet 1995). Second, an infusion
of adrenaline, designed to produce resting and
exercise adrenaline concentrations similar to
those induced by caffeine had no effect on
plasma FFA concentration or muscle glycogenol-
ysis during exercise (Chesley et al. 1995). Third,
Van Soeren et al. (1996) gave caffeine to spinal-
cord injured subjects and reported an increased
plasma FFA concentration without changes in
adrenaline concentration. These findings suggest
that caffeine ingestion affects the mobilization of
fat by antagonizing the adenosine receptors in
adipose tissue.
Therefore, while it is clear that metabolic
changes contribute to the ergogenic effect of caf-
feine during endurance exercise, aspects of the
metabolic contribution have not been adequately
examined in all situations. Measurements of
muscle glycogen and TG use and plasma FFA
turnover are required to determine the magni-
tude of the metabolic link to improved perfor-
mance at all caffeine doses and endurance
exercise situations.
There is some evidence that caffeine has an
ergogenic effect on short-term intense exercise.
The mechanism will not be related to increased
fat oxidation and decreased CHO oxidation, as
CHO availability does not limit performance in
this situation. It is possible that increased anaero-