Why Does Caffeine Delay Exercise-Induced Fatigue?
March. 19, 2003
Consuming caffeine, whether in coffee of soft drinks, has been shown
to delay fatigue during prolonged exercise. Studies have shown, for example,
that ingesting three to nine mg/kg of caffeine can increase the amount of
exercise time to achieve by as much as 50 percent. How caffeine achieves
this effect has not been fully determined.
No previous research effort has examined the possible direct central
nervous system (CNS) effects of caffeine on fatigue during prolonged
exercise. Now, a team of researchers from the University of South Carolina
has hypothesized that the blockade of adenosine receptors by caffeine may be
the most likely mechanism of CNS stimulation and delayed fatigue.
Their theory is based on the fact that adenosine is produced within the
body and inhibits neuronal excitability and synapse transmission. Adenosine
also inhibits the release of most brain excitatory neurotransmitters,
particularly dopamine (DA), and may reduce DA synthesis. Decreases in
dopamine (DA), along with increases in 5-HT (serotonin, which is generally
associated with behavioral suppression), have been linked to central fatigue
during exercise. In addition, adenosine has been shown to reduce arousal,
induce sleep, and suppress spontaneous activity, which are all behaviors
associated with increases in 5-HT.
The researchersÿ hypothesis is the foundation of a new study to determine
the effects of intracerebroventricular injection of caffeine and the
adenosine A1 and A2 receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA)
on treadmill run time to fatigue in rats. NECA was chosen for the study
because caffeine is a nonselective adenosine receptor antagonist, and it is
not known which of the four subtypes of adenosine receptors may be involved
in an effect of caffeine on fatigue. However, A2b and A3 receptors are
relatively less active than A1 and A2a receptors under normal physiological
conditions. If the researchers were correct, the CNS administration of
caffeine will increase run time to fatigue, whereas NECA will reduce run
time to fatigue. Furthermore, pretreatment with caffeine before NECA will
weaken the fatigue-inducing effects of NECA.
The authors of "Central Nervous System Effects of Caffeine and Adenosine
on Fatigue," are J. Mark Davis, Zuowei Zhao, Howard S. Stock, Kristen A.
Mehl, James Buggy, and Gregory A. Hand, all from the Schools of Public
Health and Medicine, University of South Carolina, Columbia, SC. Their
findings appear in the February 2003 edition of the American Journal of
Physiology -Regulatory, Integrative and Comparative Physiology. The journal
is one of 14 peer-reviewed publications produced monthly by the American
Physiological Society (APS).
Methodology
Male Wistar rats, five weeks old and weighing 200-250 grams, were used in
this study, and randomly assigned to intracerebroventricular or
intraperitoneal injection groups. Rats were given two weeks of treadmill
acclimation of running for 15 minutes a day. The treadmill speed was slowly
increased from eight meters a minute, 7.5 percent grade at the beginning,
progressing to 20 meters a minute at the end of the acclimation period.
Gentle hand prodding and mild electric shock were combined to encourage the
animals to run throughout the study.
After the first two weeks of acclimation, rats assigned to the
intracerebroventricular group were anesthetized with pentobarbital sodium,
and tubes were implanted bilaterally into the lateral ventricles. After
seven days of recovery from surgery, the rats were again acclimated to
treadmill running for another one to two weeks, until they were able to run
easily for at least 15 minutes per day for 5 consecutive days at a speed of
20 meters a minute at a 7.5 percent grade. Animals that were unable to run
at that pace were excluded.
Four drug treatments were used in the study: NECA, caffeine, caffeine
plus NECA, and a vehicle solution (Normosol-R). The vehicle solution has
been used as a control solution in other studies involving
intracerebroventricular infusions of drugs and tissue microdialysis. In the
CNS groups (n = 10), each rat was injected intracerebroventricularly with
one of the four drugs (NECA, caffeine, caffeine plus NECA, or vehicle) in
one testing session. The other drugs were then given in successive testing
sessions at one-week intervals to allow full recovery from the exercise bout
and washout of the drugs. On two days during the recovery period, all rats
were exercised for 15 minutes to maintain acclimation to the treadmill
protocol. All rats received all four-drug treatments in a randomized and
counterbalanced design to minimize possible order effects.
Results
The major findings of this study revealed that:
- CNS administration of caffeine at a dose of 200 µg/rat (0.6 mg/kg),
which is much less than the effective dose given peripherally (6 mg/kg),
does increase treadmill run time to fatigue in rats by approximately 60
percent;
- the same dose of caffeine given peripherally (intraperitoneally) is
ineffective.
- the results supported the researchersÿ hypothesis that
intracerebroventricular CNS administration of the selective adenosine A1
and A2 receptor agonist NECA significantly reduced run time to fatigue,
whereas intracerebroventricular caffeine increased run time to fatigue.
- inhibitory effects of NECA on run time to fatigue were also reversed
by intracerebroventricular pretreatment with caffeine, suggesting that the
ergogenic effects of intracerebroventricular caffeine are mediated through
blockade of the adenosine receptors.
- CNS administration of the adenosine receptor agonist NECA inhibited
treadmill run time to fatigue and spontaneous locomotor activity in rats.
- pretreatment with caffeine blocked the inhibitory effects of NECA on
exercise performance, although not on spontaneous behavioral activity.
- peripheral (intraperitoneal) administration of the same drugs at the
same doses had no effect on treadmill run time to fatigue.
Conclusions
These results indicate that caffeine can act specifically within the CNS
to delay fatigue, at least in part by blocking adenosine receptors. Because
caffeine easily crosses the BBB, these results also suggest that the CNS
also plays an important role in the ergogenic effect of caffeine ingestion.
The precise independent contribution of caffeine at the central
(behavioral) and peripheral (metabolic) levels awaits further research. The
researchers argue that some interaction at both levels is likely.
Source: February 2003 edition of the American Journal of Physiology³
Regulatory, Integrative and Comparative Physiology - The American
Physiological Society
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