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Caffeine and exercise: metabolism, endurance and performance


Abstract and Figures

Caffeine is a common substance in the diets of most athletes and it is now appearing in many new products, including energy drinks, sport gels, alcoholic beverages and diet aids. It can be a powerful ergogenic aid at levels that are considerably lower than the acceptable limit of the International Olympic Committee and could be beneficial in training and in competition. Caffeine does not improve maximal oxygen capacity directly, but could permit the athlete to train at a greater power output and/or to train longer. It has also been shown to increase speed and/or power output in simulated race conditions. These effects have been found in activities that last as little as 60 seconds or as long as 2 hours. There is less information about the effects of caffeine on strength; however, recent work suggests no effect on maximal ability, but enhanced endurance or resistance to fatigue. There is no evidence that caffeine ingestion before exercise leads to dehydration, ion imbalance, or any other adverse effects. The ingestion of caffeine as coffee appears to be ineffective compared to doping with pure caffeine. Related compounds such as theophylline are also potent ergogenic aids. Caffeine may act synergistically with other drugs including ephedrine and anti-inflammatory agents. It appears that male and female athletes have similar caffeine pharmacokinetics, i.e., for a given dose of caffeine, the time course and absolute plasma concentrations of caffeine and its metabolites are the same. In addition, exercise or dehydration does not affect caffeine pharmacokinetics. The limited information available suggests that caffeine non-users and users respond similarly and that withdrawal from caffeine may not be important. The mechanism(s) by which caffeine elicits its ergogenic effects are unknown, but the popular theory that it enhances fat oxidation and spares muscle glycogen has very little support and is an incomplete explanation at best. Caffeine may work, in part, by creating a more favourable intracellular ionic environment in active muscle. This could facilitate force production by each motor unit.
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Caffeine and Exercise
Metabolism, Endurance and Performance
Terry E. Graham
Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 785
1. Mode of Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 787
2. Forms of Caffeine and Related Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 787
2.1 Coffee Versus Caffeine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 788
2.2 Dimethylxanthines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 789
2.3 Caffeine Taken in Combination with Other Compounds . . . . . . . . . . . . . . . . . . . . . 789
3. Optimal ‘Prescription’ of Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 791
3.1 Timing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 791
3.2 Dose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 791
3.3 Urinary Excretion of Caffeine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 793
4. Caffeine Habits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 793
4.1 Caffeine Habituation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 793
4.2 Caffeine Withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 794
5. Participant Characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 794
6. Caffeine Ingestion and Exercise Performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 795
6.1 Endurance for Long Term Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 795
6.2 Speed/Power in Long Term Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 796
6.3 Endurance in Short Term, Intense Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 796
6.4 Power in Short Term, Intense Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 797
6.5 Strength Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 797
7. Possible Adverse Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 797
7.1 Fluid and Electrolyte Balance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 798
7.2 Caffeine Dependency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 798
8. Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 798
8.1 Fat Oxidation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 799
8.2 Muscle Glycogen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 799
8.3 Blood Glucose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 800
8.4 Lactate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 800
8.5 Energy Status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 801
8.6 Catecholamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 801
8.7 Blood Flow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 802
8.8 Ion Balance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 802
8.9 Central Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 803
9. Ethical Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 803
10.Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 803
Caffeine is a common substance in the diets of most athletes and it is now
appearing in many new products, including energy drinks, sport gels, alcoholic
Sports Med 2001; 31 (11): 785-807
© Adis International Limited. All rights reserved.
beverages and diet aids. It can be a powerful ergogenic aid at levels that are
considerably lower than the acceptable limit of the International Olympic Com-
mittee and could be beneficial in training and in competition. Caffeine does not
improve maximal oxygen capacity directly, but could permit the athlete to train
at a greater power output and/or to train longer. It has also ben shown to increase
speed and/or power output in simulated race conditions. These effects have been
found in activities that last as little as 60 seconds or as long as 2 hours. There is
less information about the effects of caffeine on strength; however, recent work
suggests no effect on maximal ability, but enhanced endurance or resistance to
fatigue. There is no evidence that caffeine ingestion before exercise leads to
dehydration, ion imbalance, or any other adverse effects.
The ingestion of caffeine as coffee appears to be ineffective compared to
doping with pure caffeine. Related compounds such as theophylline are also
potentergogenicaids.Caffeinemayact synergisticallywithotherdrugsincluding
ephedrine and anti-inflammatory agents. It appears that male and female athletes
have similar caffeinepharmacokinetics, i.e., for a given doseof caffeine,the time
course and absolute plasma concentrations of caffeine and its metabolites are the
same. In addition, exercise or dehydration does not affect caffeine pharmaco-
kinetics. The limited information available suggests that caffeine non-users and
users respond similarly and that withdrawal from caffeine may not be important.
The mechanism(s) by which caffeine elicits its ergogenic effects are unknown,
but the popular theory that it enhances fat oxidation and spares muscle glycogen
has very little support and is an incomplete explanation at best. Caffeine may
work, in part, by creating a more favourable intracellular ionic environment in
active muscle. This could facilitate force production by each motor unit.
Numerous review articles
have addressed
caffeine and its influence on exercise capacity. To
avoid repeating material covered in these articles,
this review generally considers recent (i.e the last
5 years) findings only. In addition, possible under-
lying mechanisms of caffeine action are examined,
how characteristics of individual athletes could al-
ter responses to caffeine are discussed, and areas
where further studies are required have been iden-
tified. Caffeine use by the general population has
not been considered.
Humans have a very long history of consuming
it is the most commonly consumed
drug in the world and the health risks are minimal.
Perkins and Williams
provided an excellent, brief
overview of the research history of caffeine in the
exercise sciences. They pointed out that, over a cen-
tury ago, there were formal, scientific reports re-
garding the ergogenic properties of caffeine. Dur-
ing the ensuing decades, renowned workers such
as Meyerhof and Hill examined the effects of caf-
feine on muscle in vitro, and leading scientists in-
effects in exercising humans.
Perkins and Wil-
also documented that the current issues
regarding caffeine use in competitive sport are not
new: in 1939, Boje recommended that caffeine be
banned from use in athletic competition, and caf-
feine has been forbidden or controlled at various
times by various sports’organisations over the last
40 years. In their review in 1962, Weiss and Lat-
madeinsightful comments, which wouldnot
be out of place today, regarding concerns about the
use of drugs for enhancing performance. They cred-
ited Rivers and Webber for publishing the first well-
controlled study with suitable controls and placebo
administration in 1907. As with so many investiga-
tors at that time, Rivers and Webber participated in
786 Graham
Adis International Limited. All rights reserved. Sports Med. 2001; 31 (11)
their own study. They used a ‘Mosso ergometerto
quantify the work done in pulling a weight with a
finger and found that caffeine 500mg increased work
Today, with so many high profile drugs avail-
able, why should one address caffeine? It can be a
very powerful ergogenic aid and it could be useful
to athletes in a wide range of activities involving
aerobic endurance, strength and/or reaction time.
It may be highly beneficial, not only during com-
petition, but also for increasing endurance in train-
ing sessions. Caffeine is readily available both in
foods and as an inexpensive, over-the-counter drug.
It is a legal, socially acceptabledrug. Insome com-
petitive sports it is not banned, and in others it is
controlled or tolerated to a very high level. As with
most other drugs, it is impossible to obtain statis-
tics documenting the frequency of caffeine use in
sports. However, in 1993, a large survey of Cana-
dian teenagers reported that 27% of respondents
had used caffeine in the last year for the specific
purpose of enhancing athletic performance.
1. Mode of Action
Physiological concentrations of caffeine are nor-
mally less than 70
µmol/L; plasma concentrations
µmol/Lare common. However,the con-
centrations employed in most in vitro investiga-
tions ranged from 500 to 5000
µmol/L. The phys-
iological significance of such studies is not clear.
While several modes of action for caffeine have
been identified, the only one that is important, within
the physiological concentration range of caffeine,
is inhibition of adenosine receptors. Caffeine is very
similar in structure to adenosine and can bind to
ing their action. Adenosine receptors are found in
most tissues, including the brain, heart, smooth mus-
cle, adipocytes and skeletal muscle (although the
natureof these receptorsin skeletalmuscle ispoor-
ly understood). The ubiquitous nature and varied
types of adenosine receptor facilitates caffeine si-
multaneously affecting a variety of tissues, result-
ing in a wide range of often interacting responses.
This issue is not discussed in detail here, since it has
received much attention in other publications.
Nonetheless, such interacting responses complicate
the ability to establish which tissues are affected
(and which responses occur) first, and which are
critical to the ergogenic nature of caffeine.
Caffeine may also have intracellular actions, but
it is not clear whether these are direct effects on
enzymes or due to post-receptor events. In addi-
tion, caffeine is known to stimulate the secretion
of adrenaline (epinephrine). This response could
produce a number of secondary metabolic changes
that could promote an ergogenic action. It also cre-
ates a situation in which it is difficult to attribute
any one response to an action of caffeine on a spe-
cific tissue. For example, an apparently straight-
forward response, such as increasing adrenaline
levels, could be due to stimulation of various brain
areas, direct stimulation of the adrenal medulla, or
a reaction to cardiovascular changes induced by
caffeine. One can study animal models and indi-
vidual tissues in isolation, but the responses one
observes in an integrated organism could be very
different. In this review, attempts are made to con-
of humans to physiological doses of caffeine.
2. Forms of Caffeine and
Related Compounds
Coffee, tea and other caffeine-containing bever-
areconsumedbymost adultsintheworld.
In some countries, children
and even infants
ingest caffeine-containing beverages and foods.In
general, society would not approve of a young ath-
lete using a steroid drug or a stimulant, but we do
not react negatively to anyone drinking coffee, tea
or a cola beverage. Despite caffeinated beverages
being a common element in our food, caffeine is
not a typical nutrient and is not essential for health.
Furthermore,the commercialworld israpidly chang-
ing and expanding the availability of caffeine to all
ages.Thereare now energydrinks and gels thatare
promoted for their caffeine content. Similarly, a
wide range of bottled waters and even alcoholic
beverages that contain caffeine are now sold.
Caffeine as an Ergogenic Aid 787
Adis International Limited. All rights reserved. Sports Med. 2001; 31 (11)
At what point should caffeine be classified as a
mon component of our food, to a drug being added
or taken for a particular purpose, there are several
over-the-counter medications containing from 30
to 100mg of caffeine. These include cold remedies,
diuretics, weight loss products, and preparations to
help people stay awake. Some of these are referred
to as nutraceuticals and/or natural health products.
But, how or where do we draw a line? Which are
drugs and which are normal components of an in-
dividual’s diet? Is there a difference between ob-
taining a potentially ergogenic dose of caffeine from
coffee, a cold remedy, a ‘wake up’tablet, or a sup-
pository? Are such commercially synthesised forms
of caffeine different from the same amount of caf-
feineingested intablets preparedfrom‘natural’ex-
tracts of coffee, tea, mate or guarana?
Many reviews provide lists of the caffeine con-
tents of beverages, foods and medications,
it is redundant to reproduce such a list here. The
mainsources ofcaffeinearecoffee, tea,mate,guar-
ana, and soft drinks. The amount of caffeine in prod-
ucts, foods and beverages varies from country to
country depending on factors such as marketing
regulations and preparation.
For example, the
caffeine content of coffee varies widely depending
on the type of bean, method of coffee preparation,
and social traditions of brewing techniques.
2.1 Coffee Versus Caffeine
Does the form in which caffeine is ingested in-
fluence the effects? Afew studies of enduranceex-
have used decaffeinated coffee or reg-
ular coffee (or decaffeinated coffee plus caffeine)
and then interpreted the results in terms of caffeine
administration (see table I). One study
these different regimens in high quality runners who
ran to voluntary exhaustion at a pace similar to their
their endurance from 32 minutes in the placebo con-
dition to41 minutes, butingestion ofregular coffee
had no impact. Differences in caffeine absorption
could not explain the findings, since times to peak
plasma caffeine concentrations and the actual caf-
Table I. Asummary of studies that generally compared the ergogenic effects of caffeine with those of decaffeinated coffee
Reference Participants Solution Caffeine dose
Key results
Costill et al.
7 M, 2 F Decaf ± caf 300mg; (M
4.4, F 5.8)
80% max to exh Endurance (min): decaf 75.5; caf
Butts & Crowell
13 M, 15 F Decaf ± caf 300mg; (M
4.0, F 5.1)
75% max to exh Endurance (min): decaf M 67.7; caf
M 68.5; decaf F 59.9; caf F 68.5
Casal & Leon
9 M Decaf ± caf 400mg; (6.0) 75% for 45 min FFAs, RER not different
Wiles et al.
Protocol (a) 18 M;
protocol (b) 10 M
Decaf; reg cof 200mg;
Simulated 1500m run Total time (sec): decaf 290; reg cof
; last min (km/h): decaf 22.9;
reg cof 23.5
Trice & Haymes
8 M Decaf ± caf 5 mg/kg Intermittent ex (1 min ex/1
min rest) at 85-90% max
Endurance (min): decaf 61.3; caf
Graham et al.
9 M Decaf; decaf
+ caf; reg cof;
caf; pl
4.45 mg/kg 85% max to exh Endurance (min): decaf 32; decaf
caf 32; reg cof 32; pl 31; caf 41;
caf > all others)
a The caffeine dose was often given as an absolute dose. In these cases, the approximate dose in mg/kg is estimated and presented in pa-
rentheses. In 2 studies, men and women received the same absolute dose, resulting in women receiving a substantially larger dose in
mg/kg. In 1 study,
the administered solution was 3g of instant coffee; the amount of caffeine administered was therefore estimated.
b The exercise was described as a percentage of maximal oxygen uptake and, in most studies, participants exercised to voluntary exhaus-
tion. In 1 study,
participants in protocol (a) ran a simulated 1500m race as fast as possible; in protocol (b), speed was controlled un-
til approximately the last min (400m), during which participants ran as hard as possible.
c In Costill et al.
data for men and women were not tested separately; in Butts & Crowell,
data for the 2 genders were not combined.
caf = purecaffeine; decaf = decaffeinated coffee; ex =exercise;exh = voluntary exhaustion; F = female; FFA = freefatty acid; M = male;
pl = placebo; reg cof = regular coffee; RER = respiratory exchange ratio; * indicates that the difference was significant.
788 Graham
Adis International Limited. All rights reserved. Sports Med. 2001; 31 (11)
feine concentrations achieved were identical for
both the caffeine and regular coffee groups.
Caffeine, a trimethylxanthine, is catabolised by
the cytochrome P450 system in the liver to dimethyl-
xanthines. The difference between caffeine and cof-
fee ingestion in the above study
could not be
explained by caffeine metabolism, since the pat-
tern of appearance of dimethylxanthines in the cir-
culation was similarin both the coffee and caffeine
‘armsof the trial. However, the expected increase
in circulating free fatty acid (FFA) and adrenaline
levels was noted only in the caffeine arm. It is un-
likely that either FFAs or adrenaline directly en-
hanced performance(see section 8),but the lackof
response of these parameters to regular coffee is
objective evidence that coffee does not have the
same pharmacodynamic actions as caffeine alone.
Does this mean that coffee is of no benefit? Within
thelimitsof thisstudy, yes;butotherinvestigations
have shown that coffee can be ergogenic
can increase FFAlevels.
Clearly, more compar-
ative studies are needed. Meanwhile, coffee is prob-
ably inferior to caffeine alone as an ergogenic aid.
Coffee contains hundreds, if not thousands, of com-
pounds. Some of these must be pharmacodynami-
cally active and may therefore counteract some of
the effects of caffeine.
2.2 Dimethylxanthines
Is caffeine a unique ergogenic substance? As
mentioned above, caffeine is an adenosine-receptor
antagonist. The liver demethylates this trimethyl-
xanthine to 3 dimethylxanthines: paraxanthine, theo-
phylline, and theobromine, which are then further
thine. It and theophylline are also potent adenosine-
receptor antagonists (theobromine is much less
effective). Normally, as caffeine is metabolised,
paraxanthine and theophylline do not increase in
the circulation to a concentration considered ac-
tive. They are therefore unlikely to be of major con-
sequence to the effects of caffeine. However, they
can be prepared and used as drugs. Paraxanthine is
not biologically available and is not prepared com-
line is a major component of tea and is a common
drug (but it is not regulated by sports’ governing
bodies). Theophylline has some of the same phar-
macodynamic actions as caffeine.
Marsh et al.
reported an ergogenic effect of theophylline in a
study involving only 3 participants and, recently,
theophylline was found to increase endurance to a
Because paraxanthine
is also likely to be an ergogenic aid, dimethylxan-
thines in general should be considered performance
enhancing drugs and should therefore probably be
2.3 Caffeine Taken in Combination with
Other Compounds
The most obvious example of caffeine interact-
ing with co-ingested compounds is the discussion
above of caffeine and coffee. In addition, many new
commercial drinksnow combinecaffeine withcar-
bohydrates and/or electrolytes. Afew studies
have assessed the effects of caffeine in solution
with carbohydrates and/or electrolytes, whereas one
evaluatedcaffeineas acalorie-free, decaf-
feinated cola (see table II).
Unfortunately, 3 of the 6 investigations in table
did not evaluate performance or endurance,
and Wemple et al.
simply appraised the effects
of a carbohydrate/electrolyte beverage, with and
without caffeine, and found no difference between
the 2 regimens on a brief, intensive performance
cycleafter3 hoursofexercise.Theythereforedem-
onstrated only that caffeine failed to confer benefit
beyond that provided by the carbohydrate/electro-
lyte beverage. However, the 2 remaining studies in
table II provide different information: they suggest
that caffeinecombined with carbohydrate,
or with
carbohydrate plus electrolytes,
may be superior
to both carbohydrate, and carbohydrate plus elec-
trolytes, for increasing endurance during prolonged
activity. Although both studies lacked all the treat-
ment and control ‘arms’needed to make this a de-
finitive statement, these limited findings permit con-
clusion that caffeine ingestion with carbohydrate
and electrolytes is not detrimental to the ergogenic
effects of either carbohydrate or electrolytes. To
Caffeine as an Ergogenic Aid 789
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determine whether the caffeine plus carbohydrate
(with or without electrolytes) combination has a truly
additive effect requires much detailed work. Fur-
thermore, because the proportion of caffeine/car-
bohydrate/electrolytes ingested in these studies is
probably not foundin any currently available com-
to endorse any particular product.
Vandenberghe et al.
reported that, when cre-
atine was ingested with caffeine, the ergogenic ben-
efit of creatine loading was lost, even though total
muscle creatine increased.While this is an isolated
finding, it does point out that when drugs or sup-
plements are combined, the effects of each may be
altered. This could have implications for strength
athletes who could be attracted to using both cre-
atine and caffeine.
A second example of caffeine acting in combi-
nation with othercompounds is thatas ananalgesic
adjuvant. Sawynok and Yaksh
point out that, on
its own, caffeine may contribute to amelioration of
pain. This may be caused by peripheral actions at
the level of a local injury oractions within the CNS
by modifying nociceptive processing. These actions
could add to the ergogenic potential of caffeine.
Furthermore, even low doses of caffeine augment
including aspirin and ibuprofen.
In the area of bodyweight loss, the combination
of caffeine, ephedrine and aspirin (‘stacking’) has
been found
to be more effective than caffeine
alone and to be a potent metabolic stimulus. There
is limited information available about the ergoge-
nic properties of this ‘cocktail’, but a military based
suggests that the combination is
potent. The cocktail is not discussed in detail here,
as the information is limited and ephedrineis banned
from sports. However, while this mixture is well
within what most of us would term true drugs, it is
also readilyavailable in NorthAmericain ‘natural’
Table II. Asummary of studies that administered caffeine with carbohydrates and/or electrolytes to athletes before exercise
Reference Participants Solution
Protocol Key results
Gaesser & Rich
8 M Artificial sweetened
decaf cola
± caf
5 mg/kg Incremental ex No difference in RER, maximal work
rate; caf increased lactate*
Wells et al.
10 M glu/ele ± caf 5 mg/kg Ran 32.2km No difference in plasma ele, FFA or
Erickson et al.
4 M, 1 F (a) con; (b) fru; (c)
caf; (d) glu; (e) b
5 mg/kg 90 min at 75-70% max No differences in RER; con used more
glycogen (91 mmol/kg) than caf* or
glu*. Solutions b-e all resulted in 62-67
mmol/kg being used
Sasaki et al.
5 M (a) con; (b) suc; (c)
caf; (d) b
Drink 60 and 0 min
before, and after, 45 min
at 85% of max
Endurance (min): solution (a) 40; (b)
58;* (c) 53;* (d) 57*
Wemple et al.
4M,2F Glu/ele± caf Total of 8.7
60% of max for 3h, then
500 rpm at high
resistance as fast as
No difference in plasma ele,
thermoregulation, or in performance
(343 and 344 sec)
Kovacs et al.
15 M (a) con; (b) cho/ele;
(c) b
+ caf; (d) b +
caf; (e) b+ caf
(c) 2.1; (d)
3.2; (e) 4.5
Complete a work output
Work time (min): (a) 62.5; (b) 61.5; (c)
60.4;* (d) 58.9;** (e) 58.9**
a In Sasaki et al.,
60 min before exercise in every trial, 200ml of water ± 300mg of caf were consumed. Immediately before exercise
and after 45 min, 250ml of water (a), water with 45g of suc, 60mg of caf (c), or both (d), were consumed. In Wemple et al.,
of sport drink (glu/ele)
± caf were consumed 1h before exercise and 3 ml/kg at the beginning of, and every 20 min during, exercise. In
Kovacs et al.,
a 7% cho/ele drink ± caf was ingested as follows: 8 ml/kg before exercise and 3 ml/kg at 20 and 40 min of exercise.
The caf was 150, 225 and 320 mg/L in c, d, and e, respectively.
caf = pure caffeine; cho = carbohydrates; con = control (water); decaf = decaffeinated coffee; ele = electrolytes; ex =exercise;F = female;
FFA =free fatty acid;fru =fructose; glu = glucose; M = male; RER = respiratoryexchange ratio;suc =sucrose; * indicatesthat thedifference
was significant; ** indicates that the results from this treatment were significantly different from those without **.
790 Graham
Adis International Limited. All rights reserved. Sports Med. 2001; 31 (11)
products (‘herbal’ or ‘botanical’ supplements) in
health food stores and is often promoted as a weight
loss aid. Thus, use of the mixture should be an area
of concern and further research.
3. Optimal ‘Prescription’ of Use
Does the method of administration influence
the effects of caffeine? It is not possible to give a
complete answer to this question, as the necessary
comparisons have not been done. Caffeine and other
methylxanthines can be administered by supposi-
tory, intramuscular injection, venous infusion, or
oral ingestion. Most investigations have adminis-
tered caffeine as a pure anhydrous drug orally, ei-
ther in capsules or dissolved in water. In most stud-
ies, oral ingestion has involved a single dose, but,
in a few investigations, repeated doses have been
given. Which mode or pattern of administration is
optimal, and when a given dose of caffeine causes
the optimal performance conditions, remains un-
3.1 Timing
Most investigators have had the participants in-
gest a caffeinedose, restan hour, andthen exercise.
This protocol has been selected because caffeine is
rapidly absorbed and plasma concentrations approx-
imateamaximumlevelin 1hour.Whilethistiming
for administration and exercise may be optimal, it
is remarkable how rarely theinvestigators have mea-
sured the circulating concentration of the drug they
arestudying.Moststudiesofferno information about
the plasma concentration of caffeine or its varia-
tion among study participants. Caffeine is slowly
catabolised (half-life is 4 to 6 hours) and individu-
als maintain a circulating concentration close to
this levelfor 3 to 4 hours.Ithas been suggested
thatwaiting 3 hoursis optimalbecausethisis when
caffeine-induced lipolysis produces the highest FFA
level. However, this hypothesis has not been tested
andthe ergogenic roleof such lipolysis is verysus-
pect (see section 8). The author is unaware of any
systematic examination of lipolysis in relation to
the time between caffeine ingestion and exercise
3.2 Dose
Surprisingly, some scientists have given caffeine
in an absolute dose, rather than as one indexed for
body mass (tables I, II and III present several ex-
amples of this). This could create large variability
in responses. Afew studies have given caffeine per
unit lean mass. However, caffeine is both water-
and lipid-soluble and it is unlikely that body fat is
an important factor in caffeine distribution. As noted
above, most investigators have not measured plasma
caffeine concentrations of study participants and
this severely limits understanding of why some re-
sults are inconsistent with the literature. In the au-
thors laboratory, plasma caffeine concentration is
routinely measured: giving caffeine indexed to body
mass results in a very consistent plasma caffeine
concentration in both men and women.
istered an absolute dose of caffeine to both male
and female study participants (see tables I, II and
III). The smaller bodyweight of the women gener-
ally resulted in their average caffeine dose being
approximately 20% higher than that of the men. In
addition, most of these investigations did not ex-
amine the data for gender differences.
There have been only a few dose-response stud-
(see table IV). Perkins and Wil-
did not find any ergogenic benefit of any
caffeine dose, but their protocol led to a very rapid
fatigue. Cohen et al.
also failed to show any im-
provements with 2 different doses of caffeine, while
Cadarette et al.
did not find conclusive results.
The latter study reported that the middle dose of
4.4 mg/kg was effective, but suggested that this was
causedbythe resultsfrom1individual.Thesefind-
ings are difficult to interpret because the investiga-
tors also reported that participants in the placebo
condition had plasma caffeine concentrations equiv-
alent to a dose of about 3 mg/kg of caffeine.
As indicated in section 6, these studies are in the
minority in finding no ergogenic effect of caffeine.
Examination of doses of 3 to 9 mg/kg at the au-
thors laboratory revealed that even 3 mg/kg was
effective forincreasingenduranceinprolongedex-
ercise. Subsequently, Pasman et al.
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this finding. Bruce et al.
reported that doses of
6 and 9 mg/kg were equally effective in increasing
performance/power in a simulation of 2000m row-
ing. Similarly, Kovacs et al.
found that, when
ingesting caffeine with a sport drink, the lowest
dose used (
2.1 mg/kg) was ergogenic, but doses
of3.2 and4.5 mg/kghad a greater effect.It appears
that a dose of 3 to 6 mg/kg is optimal. It is not clear
what are the minimal and maximal doses.
Another aspect that has not been examined
methodically is comparison of single and repeated
doses of caffeine. Most studies have had partici-
then administered a single, oral dose. A few inves-
havegivensmaller doses at reg-
ular intervals, but have not compared these to a
single, pre-exercise dose. Only Kovacs et al.
reported the plasma caffeine concentrations for such
a procedure. Their data suggest that exercise does
not impair caffeine absorption and repeated doses
should prolong the elevation in plasma caffeine.
However, given that even a single dose elevates
vantage of repeated doses is not obvious. It might
Table III. Asummary of studies that examined the effects of caffeine on performance
Reference Participants Caffeine
dose (mg/kg)
Protocol Key results
Ivy et al.
7 M; 2 F; trained
250mg +
250mg (M
6.9, F 8.8)
Cycle for 2h to produce greatest
amount of work possible
Caf resulted in 7.4% more work done;
31% more fat oxidised; glu polymer
ingestion had no effect on work done
Cohen et al.
5 M; 2 F; trained
(a) 0; (b) 5;
(c) 9
Run 21km in hot, humid
No differences in run times
Berglund &
8-10 M; 4-5 F;
trained skiers
6 n = 13 raced 23km at altitude; n
= 14 raced 20km at sea level.
Both were 2 lap courses
Race time 55 and 67 min for M and F.
All 1 and 2 lap times were faster* with caf
except for 2 laps at low altitude (p < 0.10)
Kovacs et al.
15 M; trained
(a) 0; (b) 0;
(c) 2.1; (d)
3.2; (e) 4.5
Complete a simulated time trial
estimated to last about 1h
Time (min): (a) 62.5; (b) 61.5; (c) 60.4;*
(d) 58.9;** (e) 58.9**
MacIntosh & Wright
7 M; 4 F; trained
6 Swim 1500m Split times caf faster by: 500m 7sec;*
8 sec;* 1500m 23 sec;* (20 :
58.8 vs 21 : 21.8 min)
Bruce et al.
8 M; trained
(a) 0; (b) 6;
(c) 9
Simulated rowing 2000m Time (sec): (a) 416; (b) 411;* (c) 412*
Wemple et al.
Glu + ele ±
8.7 caf
60% of max for 3h followed by
500 rpm at high resistance
Time (sec) for 500 rpm: pl 343; caf 344
Wiles et al.
18 M; 10 M;
trained runners
Decaf or reg
cof (
Simulated 1500m run; (a) run
1500m while controlling speed;
(b) run 1100m at ‘controlled’
speed and then ‘kick’ to finish
(a) total time (sec); pl 290.2; coffee
286.0;* (b) final 400m (km/h); pl 22.9;
coffee 23.5*
Collomp et al.
Trained: 3 M; 4 F;
untrained: 2 M; 5
250mg (4.3) Swim 2 × 100m freestyle with 20
min recovery
Trained: caf resulted in 1sec
improvement* in both swims. Untrained:
no change in speed
Collomp et al.
3 M; 3 F; ‘active’ 5 One Wingate test, i.e., 30 sec
‘all-out’ cycling
No difference in peak, average power or
in rate of fatigue
Greer et al.
9 M; ‘active’ 6 4 Wingate tests with 4 min rest No differences in peak, average power or
in rate of fatigue
Anselme et al.
10 M; 4 F; ‘active’ 250mg (3.6) Repeated 6 sec cycle sprints (5
min rest) with progressively
greater resistance
Caf: max power 964 vs 904W*
caf = pure caffeine; decaf = decaffeinated coffee; ele = electrolytes; F = female; glu = glucose; M = male; pl = placebo; reg cof = regular
coffee; * indicates that the difference was significant; ** indicates that the results from this treatment were significantly different from those
without **.
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be a mechanism forachieving a high concentration
in an individual who experiences gastric irritation
from largedoses,and it could have applications for
prolonged events and those that extend over days.
Atthistime,thereare verylimiteddata for drawing
3.3 Urinary Excretion of Caffeine
With regard to urinary caffeine, there are no
new developments. Many studies
demonstrated that the urinary concentration of caf-
feine is extremely variable and a poor reflection of
either dose or plasma concentration. Urinary caf-
feineconcentrations are notoriously inaccurate re-
flections of caffeine intake. In addition, the Interna-
tional Olympic Committee’s acceptable maximum
level of 12
µg of caffeine per ml of urine is very
generous. A caffeine dose of 3 mg/kg is ergoge-
and yet, an acute dose of 9 mg/kg results in
urinary levels that only approach 12
µg/ml. Fur-
thermore,some sportspresentopportunities forthe
competitorto urinateduring the activityand/orrest
periods. In these situations, the urine collected post-
activity would be even less reliable as an indicator
of caffeine dose. Thus, it would seem to be very
difficult to achieve a urinary caffeine concentra-
tion of 12
µg/ml through a normal dietary intake
of caffeine. It is very clear that this ‘safety zone’of
acceptance could very easily result in many ath-
letes doping with caffeineand not being identified.
4. Caffeine Habits
4.1 Caffeine Habituation
Does an athlete who regularly ingests caffeine
still benefit from an acute ingestion of caffeine?
Rarely have the caffeine habits of individuals been
considered within the context of applied physiol-
ogy. There is ample evidence from animal models
that some tissues adapt to long term exposure to
caffeine by up-regulating adenosine receptor num-
ber, whereas other tissues adapt by altering post-
receptor actions.
However, these studies also
found that some tissues do not appear to adapt to
habitual exposure.
When we do not know what tissues are critical
in mediating the ergogenic responses to caffeine,it
is difficult to speculate about the importance of ha-
bituation within specific tissues. In 1991, Dodd et
compared habitual caffeine users to caffeine-
naive individuals. At rest, the latter were more re-
sponsive in heart rate, ventilation and oxygen con-
Table IV. A summary of studies that compared the effects of ingesting different doses of caffeine in association with exercise
Reference Participants Caffeine dose
Protocol Plasma caffeine
Key results
Perkins & Williams
14 F (a) 0; (b) 4; (c) 7;
(d) 10
Incremental; 300
+ 100 every
Not measured Endurance (sec): (a) 299.5; (b)
312.1; (c) 299.8; (d) 303.2
Cadarette et al.
4 M; 4 F (a) 0; (b) 2.2; (c)
4.4; (d) 8.8
Run at 80%
to exh
(a) 21.8; (b) 34.4;
(c) 48.8; (d) 74.8
Endurance (min): (a) 53.4; (b)
67.8;* (c) 73.4; (d) 57.9
Graham & Spriet
8 M (a) 0; (b) 3; (c) 6;
(d) 9
Run at 85%
to exh
(a) 0; (b) 18; (c)
41; (d) 69
Endurance (min): (a) 49.4; (b)
60;* (c) 60;* (d) 55.6
Pasman et al.
9 M (a) 0; (b) 5; (c) 9;
(d) 13
Cycle at 80%
to exh
Not measured Endurance (min): (a) 47; (b) 58;*
(c) 59;* (d) 58*
Cohen et al.
5 M; 2 F (a) 0; (b) 5; (c) 9 Run 21km in heat Not measured Endurance (min): (a) 88; (b)
87; (c) 88
Kovacs et al.
15 M (a) 0; (b) 0; (c) 2.1;
(d) 3.2; (e) 4.5
Complete a work
output estimated to
(a) 0; (b) 0; (c) 10;
(d) 15; (e) 24
Time (min): (a) 62.5; (b) 61.5; (c)
60.4;* (d) 58.9;** (e) 58.9**
Bruce et al.
8 M (a) 0; (b) 6; (c) 9 Simulated rowing
Not measured Time (sec): (a) 416; (b) 411;* (c)
exh = exhaustion; F = female; M = male; * indicates that the difference was significant; ** indicates that the results from this treatment were
significantly different from those without **.
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sumption, but there were no differences during an
incremental exercise protocol. One study
pared caffeine-users and non-users and found that
they differed only in the degree of increase in plasma
adrenaline following caffeine ingestion. Similarly,
Bangsbo et al.
found that habitual caffeine us-
ers, after 6 weeks of increased caffeine ingestion,
had less increase of adrenaline in response to a stand-
ard dose of caffeine. Given the lack of evidence for
a major role for the caffeine-induced increase in
adrenaline (section 8.6), it is impossible to specu-
late about the importance of this alteration. Wiles
and degreeof performance response in 1500m run-
ners,nordidTarnopolsky andCupido
find a dif-
ference between caffeine users and non-users in
degree of caffeine-induced muscle force develop-
ment. Caffeine habituation needs further study, but
thus far the differences caused by caffeine habits
do not appear to be major.
4.2 Caffeine Withdrawal
Does an athlete who regularly ingests caffeine
need to withdraw from caffeine before using it in
competition? If so, what length of time is optimal?
Would the daysof experiencinglethargy andso on,
during the withdrawal, affect the athlete? Gener-
ally, scientistshave the participants withdraw from
caffeine substances for 48 hours before testing. This
procedure results in barely detectable levels of caf-
feine in the circulation. However, the author fre-
quently observes plasma paraxanthine concentra-
tions of 1 to 5
µmol/Lafter 48 hours of withdrawal.
Whether or not this is important remains unclear,
and there is no information regarding the impact of
caffeine withdrawal on adenosine receptor popula-
Hetzler et al.
reported that withdrawing from
caffeine 5 mg/kg did not alter metabolic responses
to steady-state exercise (endurance was not mea-
sured). In another study,
the investigators had
participants habituate to coffee drinking and then
withdraw for 0, 2 or 4 days before ingesting caf-
feine 6 mg/kg. The days of withdrawal had no ef-
fect on the magnitude of the ergogenic impact. At-
tempts were made to repeat this protocol (unpub-
lished observations) with a dose of 9 mg/kg. It ap-
peared that, when participants had not withdrawn,
theybecame ‘overdosed’.Theywerementallycon-
fused, could not concentrate (some felt intoxicated
they were very talkative, giddy, could not per-
form simple functions such as telling time accu-
rately, etc.), and often stopped exercise early be-
cause of these feelings. These symptoms are not
unlike those of caffeineintoxication.
The author
speculates, based on observations of hundreds of
participants, thatcaffeinenon-usersdonotrespond
qualitativelydifferently, but thattheyaremoresus-
ceptible to reacting negatively to high doses. The
hepatic P450 system saturates at a caffeine dose of
about 5 mg/kg. Higher doses therefore run the risk
of producing disproportionate increases in plasma
caffeine concentration. This could suggest that a
moderate (3 to 5 mg/kg) dose before exercise and
small (1 to 2 mg/kg), repeated doses of caffeine
given during prolonged exercise could be superior
to a single, large (
9 mg/kg) dose, as the former
regimens would not saturate the P450 system.
5. Participant Characteristics
There is very limited information concerning
whetherall athletesmetabolisecaffeinein a similar
fashion. Any factor that influences the hepatic P450
system should affect caffeine clearance.
would includecharbroiled meats,cruciferousvegeta-
bles, polycyclic hydrocarbons (smoking), and drugs
such as phenobarbital (phenobarbitone) and cimet-
idine. Theoretically, estrogen should also inhibit caf-
feine metabolism.
However, no differences in
caffeine pharmacokinetics were noted in women
between the follicular and luteal phases of the
menstrual cycle, despite the differences in estrogen
It is possible that oral contraceptives and
could impair the metabolism of caf-
feine, but this has not been investigated in an exer-
cise situation.
It has beenreportedthat exercise could altercaf-
feine metabolismand/or excretion.
Close exam-
ination of these data illustrates that they are not
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internallyconsistent. Thepharmacokineticsof caf-
feinewerecomparedin men andwomen(follicular
phase of contraceptive non-users), both at rest and
when exercising.
Therewere no differencescaused
by gender, between rest and exercise, or even be-
tween rest and exercise with additional dehydra-
tion induced. As noted above, some studies have
included both maleand female participants, but have
not tested for gender differences. The one excep-
tion is by Butts and Crowell
who examined large
groups of both sexes in a prolonged exercise pro-
tocol (see table I). While the effect of caffeine was
not significant for either group, the women on aver-
age had a much greater increase in endurance time
with caffeine (8.6 minutes compared with 0.8 min-
utes for the men). However, the investigators gave
caffeine in an absolute dose and, thus, the women
had a larger caffeine ingestion on a bodyweight
It is likely that caffeine has direct actions on
muscle (see section 8.8). There is verylittle known
about factorsthatmay influencemuscle sensitivity
to caffeine or whether this is alterable. Kalow
reported that isolated muscle biopsies of men had
a greater sensitivity to caffeine than did those from
women. Mitsumoto et al.
found that in skinned
fibres, slow twitch cells were more than twice as
sensitive to caffeine. However, both studies were
performed in vitro and with pharmacological con-
centrations of caffeine.
Training status may influence responses to caf-
feine. Carey and colleagues
found that exer-
cise training altered the effects of adenosine on ad-
ipose tissue. Similarly, Mauriege et al.
differences in adenosine sensitivity between adipo-
cytes from lean and obese women. These findings
were based on in vitro assays of isolated cells and
presumably the tissue sensitivity to caffeine would
be changed in a similar fashion. LeBlanc et al.
found that trained compared with untrained in-
dividuals had a greater response to caffeine while
at rest: they had a larger increase in adrenaline,
FFAs, and resting metabolism. Unfortunately, the
researchers did not investigate exercise responses.
Collomp et al.
found that caffeine increased the
swimming speed of trained swimmers, but not that
of recreational swimmers. To the author’s knowl-
edge, theseare the only direct comparisonsof trained
and untrained individuals. Subjectively, caffeine ap-
pears to have a more predictable impact on highly
trained individuals. For example, in one study,
an athlete who placed in the top 10 in an Olympic
marathon was able to run for
105 minutes com-
pared with about 75 minutes in the placebo trial. It
couldbethat inhighlytrained ratherthan untrained
individuals, muscle and other tissues are more re-
sponsive, or that athletes have the mental disci-
pline to exercise long or hard enough to benefit
more from the caffeine stimulus.
6. Caffeine Ingestion and
Exercise Performance
6.1 Endurance for Long Term Exercise
Most investigations haveexamined exercise en-
durance in situations where fatigue occurs in 30 to
60 minutes. There can be no doubt that caffeine is
ergogenic in these situations,
while only rarely has no effect been found.
Since the ergogenic nature of caffeine has been
frequently reported in such settings, it is not ad-
dressed in detail here. However, even in situations
where exhaustion occurs in
30 minutes, caffeine
is effective. Under these circumstances, it is un-
likely that muscle glycogen is depleted. In fact, in
a recent study,
over 50% of glycogen remained
at fatigue, which suggests that sparing of glycogen
may not be a limiting factor in this situation.
A number of researchers commonly measure
endurance because, in this situation, power is kept
constant and exercise time can be quantified. This
is easier than protocols in which individuals vary
speed or power as they would during a race. The ex-
tent to which findings of endurance capacity trans-
late to performance is debatable, but there can be
no doubt that caffeine would be a useful training
aid. Even in terms of true performance, the debate
would only be about how great is the effect, rather
than whether or not there is one.
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6.2 Speed/Power in Long Term Exercise
Rarely have studies been conducted to evaluate
an endurance event (seetable III).The author, hav-
ing failed in attempting this because of factors in-
cluding small sample sizes and changing environ-
mentalconditions, canappreciatethedifficulties in
conducting a quality study of this sort. Early stud-
frequently found improvements in ac-
tivities such as repeated jumping and bench step-
ping, as well as cycle and treadmill tests. These
studies were frequently conducted with small groups
and with protocol designs that are not acceptable
Cohen et al.
feine ingestion in a small group who ran 21km in
a hot, humid environment. In contrast, Berglund and
found that caffeine did increase
the speed of high quality, cross-country skiers in a
competitive setting. This study has been criticised
because the investigators normalised their data in
a complex way. However, any field test is difficult,
and skiing is a particularly thankless challenge given
is the only investigation of caffeine ingestiontouse
elite athletes and to simulate a competition. The re-
searchers studied elite skiers on a 20 to 23km course,
both atlowand high altitude. They foundthat,both
at the halfway mark and finish, caffeine ingestion
resulted in faster performance times. The total time
was about 55 to 67 minutes and caffeine resulted
in the halfway times being 33 and 101 seconds faster
for low and high altitude, respectively. Similarly,
finishing times were 59 and 152 seconds faster [all
results were significant except for the finish time
at low altitude (p < 0.10)].
Ivy et al.
had individuals perform 2 hours of
ticipants generated a 7.3% greater total power out-
put.Similarly, MacIntosh andWright
caffeine ingestion reduced the time for completion
of a 1500m swim by 23 seconds. In perhaps the
most controlled study, Kovacs et al.
a cycle time trial. Skilled cyclists were told they
had to perform, as quickly as possible, aset amount
of work that was estimated to be approximately
that of a 1-hour time trial. Ingestion of a carbohy-
drate/electrolyte solution during this activity tended
to be beneficial and, when the solution also con-
significantly greater (i.e., performance time was
6.3 Endurance in Short Term, Intense Exercise
This aspect of exercise has received less atten-
tion, probably because it is more difficult to quan-
tify. Also, the dominant dogma accounting for the
ergogenic properties of caffeine has involved mus-
cle glycogen sparing. Since there is no evidence
that glycogen is limiting in such activities, the an-
ticipatednegativeresults mayhave discouragedin-
vestigations. Collomp et al.
reported that when
caffeine was consumed short term or for a longer
period (250 mg/day for 1 or 5 days), the exercise
duration at maximal oxygen uptake (V
and 341 seconds, respectively] was not significant-
ly greater than for placebo (320 seconds). In con-
trast, a significant increase in endurance from 4.12
to 4.93 minuteswas found in another study.
author is aware of no other studies of this nature.
There have been several studies in which a pro-
gressive exercise protocol was used. In one study,
the exercise resulted in rapid exhaustion within 6
minutes and caffeine had no effect. In 2 other in-
participants exercised for 15 to
20 minutes and caffeine ingestion caused a small
(0.3 to 0.5 minutes) nonsignificant increase in en-
durance. In contrast, Flinn et al.
reported that
caffeine ingestion significantly increased endurance
from 14.9 to 17.5 minutes. Marsh et al.
had 3
individuals perform a progressive forearm test while
undergoing nuclear magnetic resonance spectros-
copy (NMRS) imaging. The researchers found that
when the participants had ingested theophylline,
the maximal power generated increased 19%. It is
estimated from their protocol that endurance in-
considerable variability in investigations that have
used progressive work tests, the findings are that
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caffeine either has positive effects or causes a non-
significant improvement in exercise time.
6.4 Power in Short Term, Intense Exercise
The ability to perform at high intensity has been
examinedin several studies(see table III). Wileset
had participants simulate a 1500m run, and
coffee ingestion produced a significant 4.2-second
improvement in running speed. However, it should
be noted that these were not elite athletes (times
averaged 286 and 290secondsforcaffeineand pla-
cebo, respectively). There was no relationship be-
and the degree of improvement with caffeine. Col-
lomp et al.
studied swimmers who swam 100m
freestyle. Caffeine ingestion significantly improved
themeantimeof highlytrainedswimmersbyabout
1 second, while untrained athletes showed no im-
When activities of shorter duration are exam-
ined, the results are more inconsistent, probably
because the potential improvement is small and dif-
ficult to measure because of the brief, intense na-
ture of the exercise. Anselme and co-workers
reported that caffeine improved maximum power
in6-second sprints,butnotin a30-second Wingate
Similarly, no improvement in maximum
force or fatigue was noted in a series of 4 Wingate
These areas are not well studied but it appears
that,inexerciselasting at least 60seconds,caffeine
can be ergogenic. Whether caffeine has a positive
effect in more intense exercise is controversial, but,
once again, there are no studies showing negative
6.5 Strength Activity
It is anecdotally reported that many strength
athletes use caffeineto increase theirperformance.
It is not clear whether the perception of improve-
ment is related to maximum strength or power or
to the rate of fatigue. This is an area where there is
a distinct paucity of quality work. There have been
with humans that suggested that caf-
feine enhances myoneural function and contractil-
ity. Supinski et al.
reported that caffeine increased
diaphragm contractility by 48%. Lopes et al.,
who studied the adductor pollicis in a small group
(n = 5), stimulated the ulnar nerve at 10 to 100Hz
and found no difference in maximum tension fol-
lowing ingestion of caffeine 500mg. However, dur-
ing low frequency stimulation there was an increase
in submaximal tension the frequency-force curve
was shifted to the left. Kalmar and Cafarelli
formed a detailed study recently and found that
caffeine increased maximal voluntary activation:
maximal voluntary contraction (MVC) increased
3.5% and the time to fatigue at 50% MVC improved
by 26%. They proposed thatcaffeinealtered neural
function at supraspinal and/or excitation-contraction
sites, but not at the level of the spinal cord or neu-
romuscular junction. In1989, Tarnopolskyet al.
measured a number of neuromuscular factors in
endurance athletes before and after a 90-minute
treadmill run. When the athletes had consumed caf-
feine, there were no measurable effects on MVC,
peak twitch torque, motor unit activation, or half
relaxation time. However, the investigatorsrecent-
revisitedthe issuewith moresensitivemethods.
During 2 minutes of tetanic stimulation, caffeine
ingestion resulted in increased force development
during low, but not during high frequency stimula-
tion. The researchers concluded that the enhanced
contractility was caused by local actions on the
muscle itself and probably involved excitation-
contraction mechanisms (possibly calcium release
via the ryanodine receptor).
This aspect of study is in its infancy, but is
promising. It suggests that caffeine has direct ac-
tions on muscle and that these are independent of
metabolic issues. Such studies not only reveal in-
sight regarding possible beneficial effects of caf-
feine for strength athletes, but also give valuable
information regarding possible sites of fatigue and
mechanisms of caffeine action.
7. Possible Adverse Effects
Can caffeine ingestion result in an adverse ef-
fect on performance? It has been mentioned pre-
viously thata negativeeffect on work performance
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was observed when participants received a high dose
of caffeine. While a few studies
did not find caffeine to improve endurance, several
of these studies
employed exerciseproto-
cols that led to rapid exhaustion. The author knows
of no published study that has shown a negative
effect of caffeine on performance.
7.1 Fluid and Electrolyte Balance
A frequently suggested adverse effect is a caf-
feine-induced diuresis leading to fluid and electro-
lyte loss and a decrease in plasma volume. In a
study comparing caffeine to coffee,
urine vol-
ume was measured an hour after ingestion of the
selected compound and also after exercise. No dif-
ferences were noted in urine output, and the vol-
ume closely matched that of the fluid ingested, re-
gardless of the presence or absence of caffeine.
weight loss, sweat rates, plasma volume and elec-
trolytes, and core temperature,did not find anyim-
pact of caffeine ingestion. While caffeine is a mild
diuretic, it takes several hours for changes in renin
to occur.
In the studies involving exercise, ac-
tivity takes place before this time and presumably
overrides the potential for diuresis. There does not
appearto be anybasis for thecommonconcernthat
caffeine ingestion will dehydrate athletes. Wemple
et al.
clearly demonstrated that caffeine inges-
tion resulted in a mild diuresis (1843 vs 1411ml of
urine)over4hours, but ifexercisetookplace,there
was no diuretic effect. Furthermore, in either case,
the diuresis did not generate measurable effects on
plasma volume, sweat rate, or plasma or urine os-
7.2 Caffeine Dependency
There is no doubt that people can develop a tol-
erance and dependency for caffeine.
The tol-
erance is associated with an up-regulation of aden-
osine A1 or A2 receptors in at least some tissues,
as well as adaptations in post-receptor events (sec-
tion 4.1). However, most of this information is de-
rived from animal models and/or in vitro evalua-
tions of isolated cells. The tissues that are critical
in responses in the intact organism remain unclear,
and very little is known about the mechanisms in-
Physical dependency for caffeine is described
extensivelybyStrain etal.
substance dependency is characterised by tolerance,
withdrawal symptoms, taking the substance in larger
doses, and persistent desire for the substance, and
so on. Caffeine withdrawal is associated with head-
aches, moodshifts (irritability,anxiety,depression,
etc.), drowsiness and fatigue,
beginning in 12
to 24 hours, peaking in 24 to 48 hours, and lasting
about 7 days. As little as 3 days of caffeine exposure
is sufficient to produce withdrawal symptoms.
Not everyone will developdependency,and thede-
pendency is often mild. Nevertheless, the syndrome
is similar to substance dependency syndromes for
other psychoactive drugs. Furthermore, a few indi-
viduals can present a caffeine-induced anxiety dis-
8. Mechanisms
If we are to address the various issues surround-
ing caffeine as an ergogenic aid, it is essential to
understand how caffeine results in increased exer-
cise capacity. It has been consistently reported that
caffeine enhances endurance in prolonged activity
lasting more than 30 minutes. While there are fewer
studies of activities lasting 1 to 30 minutes, it ap-
pears that both endurance and performance (speed
or power) are enhanced in these situations as well.
Very often, the explanation for the actions of caf-
feine is that caffeine stimulates adrenaline secre-
tion and this results in mobilisation of FFAs. This
enhanced delivery of fuel to active muscle is thought
to result in a ‘Randle’ effect, increasing fat oxida-
tion and sparing limited and critical muscle glyco-
gen stores. In 1980, Essig et al.
offered this as a
possible explanation. It was insightful at the time,
but in the last 2 decades, many findings have not
been compatible with this theory.
The glycogen-sparing theory is frequently re-
lied on to explain the actions of caffeine. However,
thereis aseriouslack ofsupport and, morerecently,
there are studies that clearly illustrate that it is not
798 Graham
Adis International Limited. All rights reserved. Sports Med. 2001; 31 (11)
correct in many circumstances. Unfortunately, most
investigations have been very descriptive and lack
critical measures. Many studies referred to above
did not even measure plasma caffeine concentra-
tions, let alone catecholamines, both of which are
fundamental to the glycogen-sparing hypothesis.
There are very few reports of data from muscle
biopsies, and only 2 investigations
have quanti-
fied muscle metabolism.
It is becoming apparent that caffeine is a pow-
erful drug that affects most, if not all, tissues. As
mentioned in section 1, this is not surprising given
the ubiquitous distribution of adenosine receptors.
This also means that these investigations with caf-
feineshould be regardednot onlyas practical stud-
ies of athletic performance, but also as important
examinationsoffundamentalaspectsof physiolog-
ical regulatory roles for adenosine.
8.1 Fat Oxidation
Does caffeine enhance fat metabolism? Even if
it does, fat oxidation is trivial in some situations
when caffeine is ergogenic, such as in short term,
intense activity and in resistance activity. In addi-
tion, the studies showing that caffeine did not de-
crease respiratory exchange ratio (RER) and/or in-
crease plasma FFA levels probably outnumber those
that found the ‘expected’result. In 12 different stud-
ies in the authors laboratory, no decrease in RER
following caffeine ingestion was observed. In only
6 of these studies were circulating FFA levels in-
creased (mainly at rest before exercise). Yet, in the
9 studies in which endurance was measured, caf-
feine was ergogenic in 8 (only when Wingate tests
were examined was an ergogenic effect not found).
Furthermore, Raguso et al.
reported that theo-
phylline failed to alter either the rate of appearance
(Ra) or disappearance (Rd) for FFAs or glycerol. In
another study,
while caffeine ingestion increased
arterial FFA levels, net uptake of FFAs by the ex-
ercising leg was not enhanced (fig. 1) and whole
body RER was not altered. Thus, in a wide variety
of circumstances, there is little support for the the-
ory thatcaffeine increasesfat oxidation,even though
it may well promote adipose tissue lipogenesis at
There are considerable data demonstrating that
caffeine increases adrenaline levels (section 8.6),
and a recent study
showed that leg sympathetic
stimulation was increased by caffeine. However,
FFAmobilisation occurs even in tetraplegics when
there is no increase in catecholamine levels.
The author speculates that the following scenario
occurs with fat metabolism: caffeine antagonises
A1receptors of adipocytesand thisenhanceslipol-
ysis (this may be supplemented with increased sym-
pathetic activity resulting in adrenergic
stimulation); the elevation of FFA levels results in
increased hepatic uptake of FFAs, some of which
are oxidised or esterified to triglycerides; the ex-
cess FFAs form ketone bodies, which are released
and cleared by several tissues, including skeletal
8.2 Muscle Glycogen
It is commonly stated that caffeine results in
glycogen sparing, and thereare many exercisepro-
tocols (exercise lasting <30 minutes) in which caf-
feine has been shown to be beneficial when glyco-
gen does not appear to be limiting. Furthermore,
10 20 30 40 50 60
FFA exchange (umol/min)
Time (min)
Fig. 1. Asummary of net free fatty acid (FFA) exchange across
cised at 70% maximal oxygen uptake for 1 hour. Negative val-
ues are net uptake. Data are means
± SEM.
Caffeine as an Ergogenic Aid 799
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the literature is far from consistent regarding the
impact of caffeine on muscle glycogen. The initial
demonstrated that caffeine
reduced glycogen use during prolonged exercise
that was not performed to exhaustion. This was con-
firmed by Erickson et al.
and by other investi-
who found that reduced net catabolism
occurred only in the first 15 minutes of exercise.
Subsequently, Jackman et al.
found no dif-
ference in muscle glycogen use during exercise at
, although caffeine enhanced endurancetime.
Similarly, Chesley et al.
found no difference in
glycogen after either 3 or 15 minutes of exercise at
85% of V
. Greer et al.
recently found that,
while both theophylline and caffeine enhanced en-
durance time in exercise normally lasting 32 min-
utes, there was no difference in muscle glycogen,
nor was glycogen depleted in the placebo trial. Thus,
even if glycogen had been spared, there is no evi-
dence that it was the limiting factor for endurance
time. Laurent et al.
reported no glycogen spar-
at 65% V
. Recently, another study
that, at 10 and 60 minutes of exercise at 70% of
, there were no differences in net glycogen
catabolism. It is difficult to explain why the first 3
investigationsconsistently reportedglycogen spar-
ingand themorerecentstudies didnot confirmthis
observation. The obvious possibilities of individ-
ual training, exercise intensity, and so on, do not
appear to be different between the studies.
It is interesting to note that Chesley et al.
served that muscle glycogen phosphorylase a (the
more active form of the phosphorylase) had a very
strong tendency to be increased at 3 minutes of
exercisein thecaffeinetrials.Suchaphosphorylase
activation should promote rather than spare glyco-
gen catabolism. Vergauwen et al.
actually found
that, when the rat hind-limb model was exposed to
caffeine during stimulation, glycogen breakdown
was enhanced by 40% in the fast-oxidative fibres.
However, the researchers also demonstrated that
phosphorylase activity was not affected, but that
glycogen synthase activity was depressed.
8.3 Blood Glucose
The other component of carbohydrate metabo-
lism, blood glucose, is rarelyconsidered. There are
a few reports that blood glucose is increased by
but generally it is not altered.
Raguso et al.
found that the Ra for glucose was
not influenced by theophylline at rest, or during an
hour of exercise at 70% V
creased. They concluded that this was because of
decreased uptake of glucose by active muscle. Di-
rectmeasurements of leg glucoseuptakehavebeen
made during very similar exercise. Caffeine resulted
in an increase in arterial glucose levels, but in no
difference in uptake by the active leg (fig. 2). Sub-
sequently, a decrease in glucose uptake was noted
in nonexercising muscle (unpublished results). This
could account for the reduced Rd for glucose.
8.4 Lactate
There is one further aspect to carbohydrate me-
tabolism that raises some intriguing issues. It is
remarkable how often
it has been observed that caffeine ingestion increases
blood lactate levels. This is paradoxical consider-
ing the dogma that carbohydrate sparing is sup-
10 20 30 40 50 60
Glucose exchange (mmol/min)
Time (min)
Fig.2. Asummary of net glucose exchange across the leg(data
from Graham et al.
). Participants ingested either placebo or
caffeine 6 mg/kg, rested for 1 hour, and then exercised at 70%
maximal oxygen uptake for 1 hour. Negative values are net
uptake. Data are means
± SEM.
800 Graham
Adis International Limited. All rights reserved. Sports Med. 2001; 31 (11)
probably been observed more consistently than an
increase in FFA levels, and certainly more often
than a decrease in RER, in association with caf-
feine ingestion. However, it is rarely raised in dis-
cussions of the metabolic consequences of caffeine.
When it has been discussed, the interpretation has
been that lactate production is greater than pyru-
vate oxidation, perhaps because of the latter being
suppressed by enhancedfatoxidation.Asreviewed
above, there is little evidence for increased fat oxida-
tion. Furthermore, measurements of muscle acetyl
CoA and citrate
generally do not support
such a mechanism. Muscle lactate measurements
in steady-state exercise
showed no differ-
encewhen caffeineor theophylline wasconsumed.
Recently, direct evidence was published
that caf-
feine elevated arterial lactate levels during exer-
cise, but muscle lactate levels and release from the
exercising leg were not altered (fig. 3). Similarly,
no change in lactate exchange was observed in the
nonexercising leg when caffeine was administered
(unpublished results), possibly because caffeine was
inhibiting lactate clearance, perhaps by the liver.
8.5 Energy Status
Chesley et al.
found that caffeine improved
energy status, as evident from lessphosphocreatine
(PCr) degradation and less accumulation of the pre-
dicted free levels of adenosine diphosphate (ADP)
and adenosine monophosphate (AMP). However,
these changes were found only in the subgroup of
participants who had less muscle glycogen use fol-
lowing caffeine ingestion. The significance of this
finding is questionable as the participants were di-
vided post hoc into subgroups based on glycogen
data, and then examined further for energy status,
etc. Marsh et al.
conducted what could be clas-
sified as a pilot study using NMRS. They studied
3 individuals who had ingested theophylline and
performed progressive forearm exercise. In agree-
ment with Chesley et al.,
Marsh et al.
ed that there was a trend for the inorganic phos-
phate (Pi)/Pcr ratio to shift in favour of more Pcr
with theophylline. Clearly, these findings should
be followed up with further investigations.
8.6 Catecholamines
The final aspect of the glycogen-sparing model
isthatof caffeine-inducedincreasesinsympathetic
activity. Clearly, caffeine can increase circulating
levels of adrenaline.
Only rare-
has this not been observed. However, the
increase is quite modest and it is debatable whether
thiswouldhavemetabolicsignificance.At thevery
least, the increase is probably not critical to caf-
feine actions. Tetraplegic humans have a very low
level of plasma catecholamines that is not elevated
by caffeine.
Nevertheless, caffeine caused a
‘normal’ rise in FFA levels in individuals at rest
and, when their muscles were electrically stimu-
fatigue was delayed.
In addition, Chesley et al.
infused adrena-
line to levels very similar to those observed during
exercisewhen caffeine hadbeen administered. The
elevated adrenaline level did not result in any dif-
ference in muscle glycogen degradation, or in the
calculated free levels of lactate, phosphocreatine
or adenosine triphosphate (ATP), ADP and AMP.
Furthermore, van Baak and Saris
studied the
effects of propranolol on exercise (70% V
responses to caffeine ingestion: endurance increased
10 20 30 40 50 60
Lactate exchange (mmol/min)
Time (min)
Fig. 3. Asummary of net lactate exchange across the leg (data
from Graham et al.
). Participants ingested either placebo or
caffeine 6 mg/kg, rested for 1 hour, and then exercised at 70%
maximal oxygen uptake for 1 hour. Negative values are net
uptake. Data are means
± SEM.
Caffeine as an Ergogenic Aid 801
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from 22.6 to 31.2 minutes (p = 0.056), while circu-
lating FFA levels were low and not different be-
tween propranolol versus propranolol plus caffeine.
In contrast to data for adrenaline, rarely have
studies found an increase in noradrenaline (norepi-
nephrine) levels. However, circulating noradrena-
lineresults fromthe ‘washout’oftissues, andtissue
exchange must be measured directly to determine
whether or not thesympatheticsystem isenhanced.
Previous data were from mixed venous blood sam-
ples, but recently, tissue exchange measurements
were made for the exercising leg.
Contrary to
previous results, leg noradrenaline release/wash-
out was markedly enhanced during exercise when
participants had ingested caffeine.
Forthelast 2decades,moststudiesfailed to find
a decreaseinRER following caffeineingestion and
this was dismissed as being only an indirect mea-
idation, and of glycogen and glucose metabolism,
also failed to support the theory that caffeine shifts
metabolism in favour of fat oxidation. Clearly, it is
time to consider alternative theories.
8.7 Blood Flow
Rarely have the cardiovascular consequencesof
caffeine ingestion been considered, perhaps because
early studies showed very little change in blood
pressureand heartrateforrestingor exercisingpar-
ticipants. There are several factors associated with
caffeine that could be important in cardiovascular
regulation, including adenosine-receptor antagonism
and enhanced sympathetic activity. Within the car-
diovascular system, these factors could result in
either central or peripheral actions. Recently, Dan-
iels et al.
found that caffeine ingestion caused
an increase in peripheral resistance of the forearm
vasculature and a decrease in flow during leg exer-
cise. In another study,
a modest, but significant
increase in mean blood pressure (measured by di-
rect arterial catheterisation) was noted during rest
and exercise. Since blood flow to the leg was not
altered, leg vascular resistance was elevated. The
importance of these changes is unknown, but like
the responses described above, they suggest multi-
ple, regulatory roles for endogenous adenosine.
If the ergogenic mechanisms are not those of
metabolism, then what are the alternatives? Meta-
bolism does not control muscle function, it is reg-
ulated by it. In other words, metabolism occurs as
a result of demands for replenishment of ATP con-
sumed by muscle contractions, and so on. How these
demands are met may alter the amounts of critical
metabolicstores andlimit theiractivity, but to date,
there is minimal evidence that aspects of fat or car-
bohydrate metabolismare changed. Themechanisms
that appear to be critical are associated with con-
tractilemechanismsand mayinvolve aspectsofex-
citation-contraction coupling and/or motor unit re-
8.8 Ion Balance
It is likely that many aspects of fatigue involve
electrolyte homeostasis. This could involve a sup-
pression in resting membrane potential caused by
a loss of potassium or be caused by reduced cal-
cium release from the sarcoplasmic reticulum. Ei-
ther of these actions would result in less motor unit
activation and/or less force production per motor
unit.It is clearthat potassium ionsare lostfromthe
muscle with every depolarisation
and that
plasma potassium levels subsequently increase. This
could result in a reduced resting membrane poten-
tial. It has been observed that caffeine ingestion
results in less of an increase in plasma potassium
during exercise.
faster plasma clearance. Lindinger et al.
lated that either caffeine,or the associated increase in
adrenaline, stimulated resting muscle sodium/po-
tassium ATPase to take up more potassium.
There are several lines of evidence to support
this hypothesis. Lindinger et al.
have shown that
caffeine (in nonphysiological doses) directly stim-
ulates resting muscle potassium uptake. A recent
demonstrated that, following caffeine in-
gestion, participants had less increase in arterial
potassium, but potassium release from the active
leg wasnot altered.No discrimination couldbe made
802 Graham
Adis International Limited. All rights reserved. Sports Med. 2001; 31 (11)
between the possible effects of caffeine and those
of adrenaline. The possibility that the signal is caf-
feine rather than adrenaline is supported by the work
of van Soeren et al.,
who found that caffeine
ingestion resulted in tetraplegic participants hav-
ing less of an increase in circulating potassium,
while adrenaline was not altered. In contrast, van
Baak and Saris
found that, during exercise, plas-
ma potassium levels were elevated with
ade, but were no different between caffeine and
placebo groups. These studies support the theory
that potassium clearance is enhanced. However, crit-
ical studies addressing whether or not lower arte-
rial (and hence interstitial) potassium levels mod-
erate fatigue have not been performed.
As reviewed earlier, studies
suggest that
excitation-contraction coupling is enhanced with
caffeine.It is wellknownthat pharmacological doses
of caffeine can alter calcium exchange by the sar-
coplasmic reticulum in isolated muscle preparations,
but studying this in vivo under physiological con-
ditions will prove to be a great challenge.
8.9 Central Nervous System
As every coffeedrinker knows, caffeinecan stim-
ulate the CNS. Adenosine receptors are plentiful in
manyareasofthebrain.Often,authorssuggest that
caffeine ‘stimulates the brain’. Clearly, reviews such
and oth-
demonstrate that such statements are
areas with different adenosine-receptor populations.
It is not merely that caffeine will bind to one spe-
cific set of receptors in one isolated area resulting
in asingle neuralevent.The CNS effectsarevaried
and far reaching, probably including altered sym-
pathetic activity, motor recruitment, and percep-
tion of fatigue and pain (see section 2.3). The topic
of the CNS is vast, and there are many reviews on
caffeine and the CNS, but rarely have these been
examinedwithregard to exercise. Furthermore,stud-
ies involving humans are normally conducted in
carefullycontrolled environmentsandthereforehave
limited application to athletes in competition, who
are usually highly aroused and, perhaps, anxious.
Any or all of these factors could be important, but
they are not vital. Caffeine increased muscle en-
durance in tetraplegicpatients in one study,
other investigators
found caffeine-induced ef-
fects when muscles were electrically stimulated.
Thus, the ergogenic effects of caffeine must involve
direct actions on peripheral tissues.
9. Ethical Considerations
Is there any reason to be concerned about caf-
feine as an ergogenic aid? It is difficult to resolve
what advice to give athletes. In competition, caf-
feine is allowed up to a critical limit: it is not ‘ille-
gal’. It is a powerful tool to increase exercise ca-
pacity in training, and probably also in competition.
There are very few adverse effects or health risks.
In addition, caffeineis a common part of most peo-
ple’s diets. One could draw parallels to carbohydrate
loading,creatineloading, andvitamin, mineraland
antioxidant supplementation. However, unlike these
examples, caffeine is not a traditional nutrient. Ath-
letes who ingest caffeine are using a drug for the
express purpose of gaining an advantage. As such,
the author considers it to be doping and unethical.
If an athlete has made a conscious decision to take
caffeine for the purpose of gaining an advantage
and enhancing performance, this could be the first
of a series of similar decisions for other drugs. It is
not possible at this time to demonstrate what dose
nic effect. However, even if this was known, uri-
nary excretion is too variable to accurately predict
the dose ingested (see section 3.3). Given this, the
only solutions at this time to create a fair opportu-
nity for all athletes are to recommend either blood
analysis or a ban on caffeine in sport.
10. Conclusion
Caffeine is a complex substance that is found in
many organic compounds and is consumed by hu-
mans in coffee, teas and chocolate. In addition, the
food industry is now adding caffeine to a wide as-
sortment of foods and drinks. Caffeine is also found
in various ‘natural health products’ and in many
over-the-counter drugs. The effects it has on the
Caffeine as an Ergogenic Aid 803
Adis International Limited. All rights reserved. Sports Med. 2001; 31 (11)
body are wide ranging, probably because of the
presence of various adenosine receptors in many
Caffeine, and probably dimethylxanthines, are
ergogenic in most if not all exercise situations. To
the author’s knowledge, no study has shown that
administration of these substances produces nega-
tive effects during exercise. The mechanisms in-
volved in actions of these compounds are varied
and complex and extend well beyond the traditional
explanation of sparing of muscle glycogen to prob-
ably involve fundamental aspects of muscle con-
tractility. Many scientists have conducted very de-
scriptive investigations. They should recognise that
the effects of caffeine are also demonstrating the
consequences of antagonising normal biological
function and, as such, may revealimportantaspects
of physiological regulation. Such results may well
have wider implications and apply to both basic
and medical sciences.
The author gratefully acknowledges the vital support of
his co-authors in the various publications cited from his
work, and the outstanding technical support of Ms Premila
Sathasivam. Hiswork hasbeen supportedbyNaturalScience
and Engineering Research Council (NSERC) of Canada, by
Sport Canada, and by Gatorade Sport Science Institute.
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... One question asked by athletes is how does caffeine tablet ingestion differ from drinking coffee [1]. While coffee does contain caffeine, it also contains many other compounds which form more metabolites in the body [134,135]. Coffee has also shown some ergogenic effects, just not to the same magnitude as ingesting caffeine alone [134]. Coffee would have to be consumed in large amounts to equal the caffeine typically found in tablets. ...
... Its effect is seen mainly at rest. Studies have found no effects of caffeine and dehydration after prolonged exercise so long as athletes are replacing fluids adequately [135,136]. During prolonged exercise, epinephrine-induced renal vasoconstriction causes blood flow to be diverted from the kidneys to the exercising muscle [136]. ...
... Other side effects of caffeine include tachycardia with exercise, increased blood pressure, gastrointestinal distress, and habituation/addiction to caffeine [135,136]. There are also side effects associated with discontinuing caffeine usage. ...
Female athletes tend to choose their supplements for different reasons than their male counterparts. Collegiate female athletes report taking supplements “for their health,” to make up for an inadequate diet, or to have more energy. Multivitamins, herbal substances, protein supplements, amino acids, creatine, fat burners/weight-loss products, caffeine, iron, and calcium are the most frequently used products reported by female athletes. Many female athletes are unclear on when to use a protein supplement, how to use it, and different sources of protein (animal vs. plant-based). This chapter addresses protein supplementation, amino acid supplementation, and creatine. In this chapter we also address the reported performance benefits, if any, of Echinacea, ginseng, caffeine, energy drinks, pre-workouts, and iron. The chapter concludes with a discussion on contamination of supplements and banned substances for competition. Competitive athletes should be aware of the banned substance list for their governing body and that over the counter (OTC) nutritional supplement products are not currently regulated by the food and drug administration (FDA). This lack of regulation may lead to supplements that are contaminated with banned substances.