bic energy provision from glycogen breakdown
and the glycolytic pathway may contribute to the
improvement in performance during repeated
bouts of intense exercise (100% V
.
o2max.) lasting
2–5 min (Jackman et al. 1996). If this occurred, it
would likely be the result of a direct effect of caf-
feine or a caffeine metabolite.
A few additional metabolic mechanisms have
been suggested to contribute to the ergogenic
effects of caffeine. It is commonly stated that caf-
feine inhibits phosphodiesterase, leading to an
increase in cyclic AMP concentration and
muscle glycogen PHOS activation. However, the
support for these conclusions is from in vitroor
‘test tube’ studies that used pharmacological caf-
feine levels and it is now generally accepted that
these effects would not be present at physiolog-
ical caffeine concentrations (for review, see
Tarnopolsky 1994; Spriet 1995). Vergauwen et al.
(1994) recently reported that adenosine receptors
mediate the stimulation of glucose uptake and
transport by insulin and contractions in rat skele-
tal muscle. Caffeine, as an adenosine receptor
antagonist and at a physiological level (77mm),
decreased glucose uptake during contractions.
This may be an additional mechanism whereby
CHO use is spared following caffeine inges-
tion and replaced by increased fat oxidation.
However, there have been no definitive reports
demonstrating that adenosine receptors exist in
human skeletal muscle.
Ion handling in skeletal muscle
Caffeine may alter the handling of ions in skele-
tal muscle and contribute to an ergogenic effect
during exercise. Most of the supporting evidence
has come from in vitroexperiments using phar-
macological doses of methylxanthines. The can-
didates that have been suggested to contribute to
an ergogenic effect in a physiological environ-
ment are increased Ca^2 +release during the latter
stages of exercise and increased Na+–K+-ATPase
activity, which may help maintain the membrane
potential during exercise. These are the most
likely candidates since the lowest methylxan-
thine concentration used to show these effects in
thein vitroexperiments approached the actual
methylxanthine concentrations that have been
shown to be ergogenic in vivo(Lindingeret al.
1993; Tarnopolsky 1994).
It has been demonstrated in vitrothat pharma-
cological levels of methylxanthine affect several
steps in skeletal muscle excitation–contraction
coupling:
1 increasing the release of Ca^2 +from the sar-
coplasmic reticulum;
2 enhancing troponin/myosin Ca^2 +sensitivity;
and
3 decreasing the reuptake of Ca^2 +by the sar-
coplasmic reticulum (Tarnopolsky 1994).
Methylxanthines also stimulate Na+–K+-
ATPase activity in inactive skeletal muscle
leading to increased rates of K+uptake and Na+
efflux. This attenuates the rise in plasma [K+]
with exercise, which may help maintain the
membrane potential in contracting muscle and
contribute to caffeine’s ergogenic effect during
exercise (Lindinger et al. 1993, 1996). Any of these
changes could produce increases in skeletal
muscle force production. However, at the present
time, it is not clear if these potential ion-handling
effects of caffeine contribute to an ergogenic
effect, given the physiological or in vivo
methylxanthine concentration normally found in
humans.Central effects of caffeine
While it is almost universally accepted that some
of the ergogenic effects of caffeine are manifested
through effects on the CNS, it is almost impossi-
ble to quantify how much of caffeine’s ability
to delay fatigue is due to central or peripheral
effects. Complicating the problem is the fact that
it is not clear how caffeine exerts its actions on
the CNS. Caffeine is certainly a CNS stimulant,
causing increased wakefulness and vigilance
(Van Handel 1983; Nehlig et al. 1992; Daly 1993).
Some have attributed the increased performance
derived from caffeine simply to this increased
alertness or improved mood (Nehlig & Debry
1994). However, the ability of caffeine to delay
fatigue points to more complex mechanisms than