ArticlePDF AvailableLiterature Review

Caffeine and exercise: metabolism, endurance and performance

February 2001
Sports Medicine 31(11):785-807

Source
PubMed

Authors:

University of Guelph

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.

A summary of net free fatty acid (FFA) exchange across the leg (data from Graham et al. [97] ). 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.

…

A summary of net glucose exchange across the leg (data from Graham et al. [97] ). 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.

…

A summary of net lactate exchange across the leg (data from Graham et al. [97] ). 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.

…

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Content uploaded by Terry Graham

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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

Contents

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

Abstract

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

REVIEW ARTICLE

Sports Med 2001; 31 (11): 785-807

0112-1642/01/0011-0785/$22.00/0

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

[1-7]

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

caffeine;

[5,8-10]

it is the most commonly consumed

drug in the world and the health risks are minimal.

Perkins and Williams

[11]

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-

cludingBoje,AsmussenandMargariaexaminedits

effects in exercising humans.

[11]

Perkins and Wil-

liams

[11]

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-

ies

[12]

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

their own study. They used a ‘Mosso ergometer’to

quantify the work done in pulling a weight with a

finger and found that caffeine 500mg increased work

output.

[12]

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.

[13]

1. Mode of Action

Physiological concentrations of caffeine are nor-

mally less than 70

µmol/L; plasma concentrations

of20to50

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

cellmembranereceptorsforadenosine,thusblock-

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.

[14-18]

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-

centrate,inanintegratedfashion,ontheresponses

of humans to physiological doses of caffeine.

2. Forms of Caffeine and

Related Compounds

Coffee, tea and other caffeine-containing bever-

ages

[9,10]

areconsumedbymost adultsintheworld.

In some countries, children

[9,10]

and even infants

[19]

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

At what point should caffeine be classified as a

drug?Tomovefurtherintothistransitionfromacom-

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,

[5,8-10]

and

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.

[9,10,20]

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-

ercise

[21-25]

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

[26]

compared

these different regimens in high quality runners who

ran to voluntary exhaustion at a pace similar to their

besttimefor10km.Asexpected,caffeineenhanced

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

Protocol

Key results

Costill et al.

[22]

7 M, 2 F Decaf ± caf 300mg; (M

4.4, F 5.8)

80% max to exh Endurance (min): decaf 75.5; caf

90.2

Butts & Crowell

[25]

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

[24]

9 M Decaf ± caf 400mg; (6.0) 75% for 45 min FFAs, RER not different

Wiles et al.

[23]

Protocol (a) 18 M;

protocol (b) 10 M

Decaf; reg cof ≈200mg;

(2-2.5)

Simulated 1500m run Total time (sec): decaf 290; reg cof

286

; last min (km/h): decaf 22.9;

reg cof 23.5

Trice & Haymes

[21]

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

77.5

Graham et al.

[26]

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,

[23]

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,

[23]

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.

[22]

data for men and women were not tested separately; in Butts & Crowell,

[25]

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

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

[26]

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

‘arms’of 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

[21-23]

and

can increase FFAlevels.

[22]

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

catabolised.Inhumans,themajorproductisparaxan-

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-

merciallyasapharmacologicalproduct.Theophyl-

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.

[27]

Marsh et al.

[28]

reported an ergogenic effect of theophylline in a

study involving only 3 participants and, recently,

theophylline was found to increase endurance to a

similarextentascaffeine.

[29]

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

regulated.

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

[30-34]

have assessed the effects of caffeine in solution

with carbohydrates and/or electrolytes, whereas one

study

[35]

evaluatedcaffeineas acalorie-free, decaf-

feinated cola (see table II).

Unfortunately, 3 of the 6 investigations in table

[33-35]

did not evaluate performance or endurance,

and Wemple et al.

[30]

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,

[32]

or with

carbohydrate plus electrolytes,

[31]

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

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-

mercialbeverage,thesefindingsshouldnotbeused

to endorse any particular product.

Vandenberghe et al.

[36]

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

[37]

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

theeffectsofnonsteroidalanti-inflammatorydrugs

including aspirin and ibuprofen.

[37]

In the area of bodyweight loss, the combination

of caffeine, ephedrine and aspirin (‘stacking’) has

been found

[38,39]

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

investigation

[40]

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

Caffeine

dose

Protocol Key results

Gaesser & Rich

[35]

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.

[33]

10 M glu/ele ± caf 5 mg/kg Ran 32.2km No difference in plasma ele, FFA or

RER

Erickson et al.

[34]

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.

[32]

5 M (a) con; (b) suc; (c)

caf; (d) b

420mg;

(≈7.2

mg/kg)

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.

[30]

4M,2F Glu/ele± caf Total of 8.7

mg/kg

60% of max for 3h, then

500 rpm at high

resistance as fast as

possible

No difference in plasma ele,

thermoregulation, or in performance

(343 and 344 sec)

Kovacs et al.

[31]

15 M (a) con; (b) cho/ele;

+ caf; (d) b +

caf; (e) b+ caf

3.2; (e) 4.5

mg/kg

Complete a work output

estimatedtotake1h

Work time (min): (a) 62.5; (b) 61.5; (c)

60.4;* (d) 58.9;** (e) 58.9**

a In Sasaki et al.,

[32]

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.,

[30]

8ml/kg

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.,

[31]

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

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-

clear.

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

[3,41]

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

onset.

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-

thor’s 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.

[2]

However,

itissurprisinghowofteninvestigatorshaveadmin-

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-

ies

[11,31,43,51-53]

(see table IV). Perkins and Wil-

liams

[11]

did not find any ergogenic benefit of any

caffeine dose, but their protocol led to a very rapid

fatigue. Cohen et al.

[43]

also failed to show any im-

provements with 2 different doses of caffeine, while

Cadarette et al.

[51]

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.

[31,53]

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-

thor’s laboratory revealed that even 3 mg/kg was

effective forincreasingenduranceinprolongedex-

ercise. Subsequently, Pasman et al.

[52]

confirmed

Caffeine as an Ergogenic Aid 791

this finding. Bruce et al.

[46]

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.

[31]

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-

pantswithdrawfromcaffeinefor48hoursandhave

then administered a single, oral dose. A few inves-

tigations

[31,32,42,54]

havegivensmaller doses at reg-

ular intervals, but have not compared these to a

single, pre-exercise dose. Only Kovacs et al.

[31]

have

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

circulatingcaffeineconcentrationforhours,thead-

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.

[42]

7 M; 2 F; trained

cyclists

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.

[43]

5 M; 2 F; trained

runners

(a) 0; (b) 5;

Run 21km in hot, humid

environment

No differences in run times

Berglund &

Hemmingsson

[44]

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.

[31]

15 M; trained

cyclists

(a) 0; (b) 0;

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

[45]

7 M; 4 F; trained

swimmers

6 Swim 1500m Split times caf faster by: 500m ≈7sec;*

1000m

≈8 sec;* 1500m 23 sec;* (20 :

58.8 vs 21 : 21.8 min)

Bruce et al.

[46]

8 M; trained

rowers

(a) 0; (b) 6;

Simulated rowing 2000m Time (sec): (a) 416; (b) 411;* (c) 412*

Wemple et al.

[30]

4M;2F;active

individuals

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.

[23]

18 M; 10 M;

trained runners

Decaf or reg

cof (

≈2-2.5)

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.

[47]

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.

[48]

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.

[49]

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.

[50]

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 **.

792 Graham

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

conclusions.

3.3 Urinary Excretion of Caffeine

With regard to urinary caffeine, there are no

new developments. Many studies

[31,46,52,55]

have

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-

nic,

[53]

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.

[18,56,57]

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

al.

[58]

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

(mg/kg)

Protocol Plasma caffeine

(

µmol/L)

Key results

Perkins & Williams

[11]

14 F (a) 0; (b) 4; (c) 7;

(d) 10

Incremental; 300

kpm

+ 100 every

min

Not measured Endurance (sec): (a) 299.5; (b)

312.1; (c) 299.8; (d) 303.2

Cadarette et al.

[51]

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;

Endurance (min): (a) 53.4; (b)

67.8;* (c) 73.4; (d) 57.9

Graham & Spriet

[53]

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.

[52]

9 M (a) 0; (b) 5; (c) 9;

(d) 13

Cycle at 80%

to exh

Not measured Endurance (min): (a) 47; (b) 58;*

Cohen et al.

[43]

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.

[31]

15 M (a) 0; (b) 0; (c) 2.1;

(d) 3.2; (e) 4.5

Complete a work

output estimated to

take

≈1h

(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.

[46]

8 M (a) 0; (b) 6; (c) 9 Simulated rowing

2000m

Not measured Time (sec): (a) 416; (b) 411;* (c)

412*

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 **.

Caffeine as an Ergogenic Aid 793

sumption, but there were no differences during an

incremental exercise protocol. One study

[59]

com-

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.

[60]

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

etal.

[23]

foundnorelationshipbetweencaffeinehabits

and degreeof performance response in 1500m run-

ners,nordidTarnopolsky andCupido

[61]

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-

tions.

Hetzler et al.

[62]

reported that withdrawing from

caffeinefor0,2,12,24or48hoursbeforeingesting

caffeine 5 mg/kg did not alter metabolic responses

to steady-state exercise (endurance was not mea-

sured). In another study,

[63]

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.

[64]

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.

[65,66]

This

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.

[66,67]

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

level.

[2]

It is possible that oral contraceptives and

pregnancy

[66,67]

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.

[68]

Close exam-

ination of these data illustrates that they are not

794 Graham

internallyconsistent. Thepharmacokineticsof caf-

feinewerecomparedin men andwomen(follicular

phase of contraceptive non-users), both at rest and

when exercising.

[2]

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

[25]

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

basis.

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

[69]

reported that isolated muscle biopsies of men had

a greater sensitivity to caffeine than did those from

women. Mitsumoto et al.

[70]

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

[71,72]

found that exer-

cise training altered the effects of adenosine on ad-

ipose tissue. Similarly, Mauriege et al.

[73]

found

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.

[74]

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.

[47]

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,

[55]

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,

[21,22,29,32,51-53,55,63,75,76]

while only rarely has no effect been found.

[25,77]

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,

[29]

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.

Caffeine as an Ergogenic Aid 795

6.2 Speed/Power in Long Term Exercise

Rarely have studies been conducted to evaluate

theimpactofcaffeineonspeedorperformancein

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-

ies

[11,12,78-80]

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

today.

Cohen et al.

[43]

failedtoshowabenefitofcaf-

feine ingestion in a small group who ran 21km in

a hot, humid environment. In contrast, Berglund and

Hemmingsson

[44]

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

howsnowconditionscanchangemomenttomoment,

letalonedaytoday.Totheauthor’sknowledge,this

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.

[42]

had individuals perform 2 hours of

cycleexerciseand,aftercaffeineingestion,thepar-

ticipants generated a 7.3% greater total power out-

put.Similarly, MacIntosh andWright

[45]

foundthat

caffeine ingestion reduced the time for completion

of a 1500m swim by 23 seconds. In perhaps the

most controlled study, Kovacs et al.

[31]

approximated

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-

tainedcaffeine,thepoweroutputimprovementwas

significantly greater (i.e., performance time was

faster).

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.

[81]

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

2max

)[349

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.

[82]

The

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,

[11]

the exercise resulted in rapid exhaustion within 6

minutes and caffeine had no effect. In 2 other in-

vestigations,

[58,83]

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.

[84]

reported that

caffeine ingestion significantly increased endurance

from 14.9 to 17.5 minutes. Marsh et al.

[28]

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-

creasedfrom13.5to16.8minutes.Whilethereis

considerable variability in investigations that have

used progressive work tests, the findings are that

796 Graham

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

al.

[23]

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-

tweeneitherhabitualcaffeineintakeorrunningspeed

and the degree of improvement with caffeine. Col-

lomp et al.

[47]

studied swimmers who swam 100m

freestyle. Caffeine ingestion significantly improved

themeantimeof highlytrainedswimmersbyabout

1 second, while untrained athletes showed no im-

provement.

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

[50]

reported that caffeine improved maximum power

in6-second sprints,butnotin a30-second Wingate

test.

[48]

Similarly, no improvement in maximum

force or fatigue was noted in a series of 4 Wingate

tests.

[49]

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

effects.

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

studies

[85-87]

with humans that suggested that caf-

feine enhances myoneural function and contractil-

ity. Supinski et al.

[87]

reported that caffeine increased

diaphragm contractility by 48%. Lopes et al.,

[88]

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

[89]

per-

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.

[90]

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-

[61]

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

Caffeine as an Ergogenic Aid 797

was observed when participants received a high dose

of caffeine. While a few studies

[11,25,30,48,54,58,77,81,83]

did not find caffeine to improve endurance, several

of these studies

[11,30,48,81]

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,

[26]

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.

Similarly,studies

[30,31,33,45,77,91]

thatquantifiedbody-

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.

[92]

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.

[30]

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-

molality.

7.2 Caffeine Dependency

There is no doubt that people can develop a tol-

erance and dependency for caffeine.

[64,93-95]

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-

volved.

Physical dependency for caffeine is described

extensivelybyStrain etal.

[64]

Theypointedoutthat

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,

[64,93]

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.

[64]

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-

order.

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.

[96]

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

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

[27,97]

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 author’s 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.

[27]

reported that theo-

phylline failed to alter either the rate of appearance

(Ra) or disappearance (Rd) for FFAs or glycerol. In

another study,

[97]

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

rest.

There are considerable data demonstrating that

caffeine increases adrenaline levels (section 8.6),

and a recent study

[97]

showed that leg sympathetic

stimulation was increased by caffeine. However,

FFAmobilisation occurs even in tetraplegics when

there is no increase in catecholamine levels.

[76,98]

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

β-receptor

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

muscle.

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,

−200

10 20 30 40 50 60

−150

−100

−50

FFA exchange (umol/min)

Time (min)

Placebo

Caffeine

Fig. 1. Asummary of net free fatty acid (FFA) exchange across

theleg(datafromGrahametal.

[97]

).Participantsingestedeither

placeboorcaffeine6mg/kg,restedfor1hour,andthenexer-

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

the literature is far from consistent regarding the

impact of caffeine on muscle glycogen. The initial

studybyIvyetal.

[42]

demonstrated that caffeine

reduced glycogen use during prolonged exercise

that was not performed to exhaustion. This was con-

firmed by Erickson et al.

[34]

and by other investi-

gators,

[55]

who found that reduced net catabolism

occurred only in the first 15 minutes of exercise.

Subsequently, Jackman et al.

[82]

found no dif-

ference in muscle glycogen use during exercise at

2max

, although caffeine enhanced endurancetime.

Similarly, Chesley et al.

[99]

found no difference in

glycogen after either 3 or 15 minutes of exercise at

85% of V

2max

. Greer et al.

[29]

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.

[100]

reported no glycogen spar-

ingcausedbycaffeineduring2hoursofexercise

at 65% V

2max

. Recently, another study

[97]

found

that, at 10 and 60 minutes of exercise at 70% of

2max

, 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.

[99]

ob-

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.

[101]

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

caffeine,

[21,27,53,75,91,97]

but generally it is not altered.

Raguso et al.

[27]

found that the Ra for glucose was

not influenced by theophylline at rest, or during an

hour of exercise at 70% V

2max

,butRdwasde-

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

[27,48,51,53,55,62,75,81,91,97,99,102]

it has been observed that caffeine ingestion increases

blood lactate levels. This is paradoxical consider-

ing the dogma that carbohydrate sparing is sup-

posedtooccur.Itisalsointerestingthatthishas

−3

10 20 30 40 50 60

−2

−1

Glucose exchange (mmol/min)

Time (min)

Placebo

Caffeine

Fig.2. Asummary of net glucose exchange across the leg(data

from Graham et al.

[97]

). 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

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

[29,75,97]

generally do not support

such a mechanism. Muscle lactate measurements

in steady-state exercise

[29,97,99]

showed no differ-

encewhen caffeineor theophylline wasconsumed.

Recently, direct evidence was published

[97]

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.

[99]

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.

[28]

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.,

[99]

Marsh et al.

[28]

report-

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.

[29,49,53,55,59,63,75,82,97]

Only rare-

[30,90]

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.

[76,98]

Nevertheless, caffeine caused a

‘normal’ rise in FFA levels in individuals at rest

and, when their muscles were electrically stimu-

lated,

[98]

fatigue was delayed.

In addition, Chesley et al.

[103]

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

[104]

studied the

effects of propranolol on exercise (70% V

2max

)

responses to caffeine ingestion: endurance increased

−2

10 20 30 40 50 60

−1

Lactate exchange (mmol/min)

Time (min)

Placebo

Caffeine

Fig. 3. Asummary of net lactate exchange across the leg (data

from Graham et al.

[97]

). 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

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.

[97]

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-

sure.Morerecently,directdeterminationsoffatox-

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.

[105]

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,

[97]

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-

cruitment.

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

[106-108]

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.

[45,109]

Thiscouldbecausedbyless

washoutofpotassiumfromtheactivemuscleora

faster plasma clearance. Lindinger et al.

[109]

specu-

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.

[110]

have shown that

caffeine (in nonphysiological doses) directly stim-

ulates resting muscle potassium uptake. A recent

study

[97]

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

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.,

[98]

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

[104]

found that, during exercise, plas-

ma potassium levels were elevated with

β-block-

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

[61,88,89]

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

asthosebyFredholm

[17]

andBenowitz

[111]

and oth-

ers

[3,112,113]

demonstrate that such statements are

grossoversimplifications.TheCNSconsistsofmany

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,

[76]

and

other investigators

[61,88]

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

ofcaffeinecanbetakenwithoutcausinganergoge-

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

body are wide ranging, probably because of the

presence of various adenosine receptors in many

tissues.

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.

Acknowledgements

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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E-mail: terrygra@uoguelph.ca

Caffeine as an Ergogenic Aid 807

Ergogenic Aids and the Female Athlete

Chapter

Feb 2023

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.

Caffeine and exercise: metabolism, endurance and performance

Abstract and Figures