Review

Exercise, Heat, Hydration and the Brain

R.J. Maughan, S.M. Shirreffs, and P. Watson

School of Sport and Exercise Sciences, Loughborough University, Leicestershire, UNITED KINGDOM
Key words: exercise, heat, hydration, fatigue

The performance of both physical and mental tasks can be adversely affected by heat and by dehydration. There
are well-recognized effects of heat and hydration status on the cardiovascular and thermoregulatory systems that can
account for the decreased performance and increased sensation of effort that are experienced in the heat. Provision of
fluids of appropriate composition in appropriate amounts can prevent dehydration and can greatly reduce the adverse
effects of heat stress. There is growing evidence that the effects of high ambient temperature and dehydration on
exercise performance may be mediated by effects on the central nervous system. This seems to involve serotonergic
and dopaminergic functions. Recent evidence suggests that the integrity of the blood brain barrier may be compro-
mised by combined heat stress and dehydration, and this may play a role in limiting performance in the heat.

Key teaching points:

• Endurance exercise performance is impaired in the heat. Performance in most physical and cognitive tasks is impaired by
dehydration. Peripheral factors, e.g. muscle glycogen depletion, can account for fatigue in endurance exercise in cool or
temperature environments, but not in the heat.
• Fluid ingestion during exercise can decrease the subjective sensation of fatigue and enhance performance when exercise lasts more
than about 40 minutes.
• A high core temperature, and especially a high brain temperature, seems to be associated with the onset of fatigue in endurance
exercise in warm environments.
• Changes in brain neurotransmission, in particular dopamine, appear to be responsible for fatigue when exercising in the heat. Alterations
to cerebral blood flow and/or metabolism may also be important mediators of fatigue during exercise in a warm environment.

INTRODUCTION death. The signs and symptoms can be remarkably similar whether
body temperature is high (hyperthermia) or low (hypothermia).
Humans have evolved to tolerate a wide range of environ- Numerous strategies are available to limit the loss of function and
mental temperatures while keeping the body’s core temperature to protect health in individuals exposed to high environmental
within rather narrow limits. By adopting a combination of temperatures or exercise stress; among the most effective of these
physiological and behavioral mechanisms, humans cope well strategies is maintenance of hydration status [1].
with environmental extremes and successfully maintain core
temperature at about 36 to 38°C in a wide range of environ-
ments and activity states. Excursions of deep body temperature EXERCISE IN THE HEAT: EFFECT
above or below these limits demand greater involvement of the ON THERMOREGULATION AND
body’s homeostatic mechanisms and a point may be reached PERFORMANCE
where temperature must be allowed to drift. Loss of control of
body temperature can result in impairments of physiological It is an everyday experience for athletes and those with
function and, if sufficiently severe, loss of consciousness and physically demanding occupations that exercise feels harder

Address correspondence to: Professor RJ Maughan, School of Sport and Exercise Sciences, Loughborough University, Leicestershire LE11 3TU, UNITED KINGDOM.
E-mail: r.maughan@lboro.ac.uk
Presented at the ILSI North America Conference on Hydration and Health Promotion, November 29-30, 2006 in Washington, DC.
Conflict of Interest Disclosure: RJ Maughan is a member of the Gatorade Sports Science Institute Sports Medicine Advisory Board but does not believe this to be a conflict
of interest. The other authors have no conflicts of interest to declare in relation to this work.

Journal of the American College of Nutrition, Vol. 26, No. 5, 604S–612S (2007)
Published by the American College of Nutrition

604S
 Exercise, Heat, Hydration and the Brain

when the ambient temperature is high and there is a corre-

sponding reduction in exercise performance. This observation
has been confirmed many times by well-controlled studies in
laboratory conditions and by less well-controlled studies in the
field. In the laboratory, exercise time to fatigue at constant
power output (about 70% of VO2max) is longest at about 11°C,
and is less at either higher or lower temperatures [2]. Parkin et
al. also showed that exercise time to fatigue at an ambient
temperature of 3°C was longer than at 20°C or 40°C [3]. A
recent analysis of performance in marathon races taking place
in varying environments concluded that there is an optimum
temperature of about 10 –12°C for marathon running [4].
Given the high rates of heat production sustained by faster
marathon runners, it is not surprising that increasing the ambi-
ent temperature results in performance impairment. Any reduc-
tion in the rate of heat loss or addition of an external heat load,
which occurs as soon as the environmental temperature exceeds
the skin temperature, will clearly result in a more rapid rise in
core temperature. This means that there must either be a faster
rise in core temperature or a faster rate of sweat evaporation to
increase the rate of heat loss. In turn, a faster sweat evaporation
rate requires a faster sweat secretion rate and/or a higher skin
temperature to achieve a higher evaporation rate. Maintaining a
high skin temperature requires a high skin blood flow, diverting
blood from the working muscles and/or increasing cardiac
output that must be achieved [5].
Even at moderate ambient temperatures, the reduced skin-
to-environment temperature gradient results in performance
decrements. For instance, Galloway and Maughan showed that
performance is reduced when ambient temperature is increased
from 11°C to 21°C [2]. Nielsen calculated that this effect’s Fig. 1. Effects of ambient temperature on (a) endurance capacity and
(b) core temperature (adapted from [2]). Data in (b) are shown for all
magnitude was such that it would not be possible for a well-
time points for which data are available for all subjects.
trained marathon runner to complete the distance in less than
3 h 20 min in the hot and humid conditions predicted for the
Atlanta Olympic Games held in 1996 [6]. Although increasing water. Once environmental temperature exceeds skin tempera-
ambient temperature’s effect on performance in competitive ture, evaporation is the only mechanism by which the body can
situations is less than might be predicted from theoretical lose heat. Sweating is evoked when core temperature rises and
considerations or from laboratory studies, the decrement is increases in proportion to core temperature, but the sweating
nonetheless real. rate is also influenced by skin temperature. Sweat evaporation
A change in body temperature may be regarded as a failure will depend on the water vapor pressure gradient at the skin
of homeostasis or as a re-setting of the point around which surface: this in turn depends on skin and environmental tem-
regulation occurs. Small fluctuations are normal: over the perature and the relative humidity at the skin surface.
course of the day, core temperature varies by about 1°C [7]. Although a rise in body temperature is commonly perceived
During exercise, some degree of core temperature elevation is to indicate a failure of the body’s thermoregulatory function,
normal with the increase proportional to the absolute and there may well be a regulated increase in core temperature
relative (expressed as a fraction of VO2max) power output [8]. during exercise. Effective heat loss by evaporation of sweat
Rise in body temperature is also influenced by the environment. demands adequate rates of sweat secretion onto the skin surface
Core temperature rises faster in hot environments when power to maintain a wet skin and a high skin temperature to allow for
output is maintained at a constant rate, and a higher core evaporation before the sweat drips from the skin surface. Hu-
temperature is observed at the point of fatigue (Fig. 1). mans are provided with abundant sweat glands distributed over
When skin temperature exceeds environmental temperature, the body surface and have a high capacity for sweat secretion:
heat can be lost to the environment through radiation, convec- trained athletes can sustain sweating rates of more than 2 L/h
tion, and evaporation. Heat loss by conduction is negligible for over prolonged periods [9]. Evaporation of all this sweat from
exercise in air, but becomes significant when immersed in the body surface would remove heat at a rate of 2.4 MJ/h (1160

JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 605S

Exercise, Heat, Hydration and the Brain

kcal/h). This approximates the average rate of metabolic heat Table 1. Effects of Prior Immersion in Water at Different
production for a 70 kg runner who completes a marathon in Temperatures on Time to Fatigue in a Cycle Ergometer Test
about 2 h 30 min. If all this sweat could be evaporated from the at 60% of VO2max [13]
skin surface and the latent heat of vaporization was contributed
Condition Exercise Time (min)
from the body rather than from the environment, this runner
Cool 63⫾3
would be able to maintain body temperature rather well. A Neutral 46⫾3
faster runner, however, would require a greater rate of evapo- Warm 28⫾2
rative heat loss to prevent a rise in core temperature, unless he
or she has a better running economy that allows the faster pace
to sustained with a lower metabolic rate.
At these high rates of sweat secretion, it is possible that a
significant fraction will simply drip from the skin surface once
the evaporative capacity of the environment is exceeded. This
will increase loss of water and solutes without making any
contribution to body temperature maintenance. To prevent this
and ensure the sweat evaporates, a high skin temperature, and
therefore a high skin blood flow, is required; this is a major
limitation to exercise performance. Heat convection from the
active muscles to the skin surface requires a cutaneous blood
flow that is inversely proportional to the temperature gradient
from the core to the skin: the smaller that temperature gradient,
the greater the blood flow to be diverted to the skin to lose heat,
and this may lead to a fall in perfusion of skeletal muscle, brain,
and other tissues in the case of prolonged, strenuous exercise in
the heat [10]. If body temperature is allowed to rise, the
gradient from core to skin is increased and the cutaneous blood
flow necessary to maintain thermal balance is reduced. Some
increase in core temperature may therefore be beneficial, and
even necessary to maintain thermoregulatory function, when
the heat production rate is high and the environment does not
favor heat loss. This may account for the observation from field
studies that faster runners normally have the highest post-race
core temperatures [11].
Manipulation of body temperature prior to exercise can
have profound effects on performance. Lee and Haymes
showed clear effects on performance when subjects exercised
to exhaustion at 82% VO2max at an ambient temperature of Fig. 2. Effect of prior warming on (a) core temperature during subse-
24°C when this was preceded by 30 min rest at either 5°C or quent exercise and recovery and (b) the subjective rating of perceived
exertion (RPE) during exercise. Redrawn from Watson et al. [36].
24°C followed by 10 –16 min at 24°C [12]. Although core
temperature at the end of exercise was the same during both
idea that fatigue during prolonged exercise in a warm environ-
trials, exercise time to fatigue was greater (26.2 ⫾ 9.5 min)
ment may coincide with the attainment of a critical core tem-
after cold exposure than after resting in the warmer environ-
perature [13,14]. These data suggest there may be a thermal
ment (22.4 ⫾ 8.5 min). Similarly, Gonzalez-Alonso et al. limit to exercise performance that serves as a protective mech-
immersed seven subjects in water at 17, 36, or 40°C for 30 min anism to prevent potential damage to the body by limiting
prior to exercise [13]. Subjects then exercised to exhaustion at further heat production. Nonetheless, it is clear that many
60% of VO2max on a cycle ergometer at an ambient temperature individuals reach the point of fatigue during exercise in the heat
of 40°C. Exercise times to fatigue are shown in Table 1. long before attaining values of 39.5°C [15], and there are many
Similar results have been demonstrated in many other stud- studies where there is no consistency in the core temperature at
ies. Prior heating can also dramatically increase the subjective the point of fatigue.
sensation of effort during exercise (Fig. 2), potentially indicat- It is possible that the concept of a critical core temperature,
ing a role of body temperature in the development of fatigue where individuals fatigue upon attaining a particular core tem-
during hyperthermia. There is some evidence to support the perature, is not as straightforward as originally proposed, with

606S VOL. 26, NO. 5

 Exercise, Heat, Hydration and the Brain

feedback from other factors likely to play a role in developing the short time scale of the 1500 m run (about 4 min), it seems
fatigue under heat stress. It must, of course, be remembered that very unlikely that thermoregulation plays a significant role,
rectal temperature was the measure of core temperature used in though muscle temperature is likely to rise rapidly in the active
most of these studies, while some studies have also used muscle groups.
oesophageal temperature. This may be inappropriate as the Evidence for the effects of hydration status in prolonged
relationship between rectal temperature and brain temperature exercise performance comes from many different lines of in-
has not been clearly established in humans, unlike some of the vestigation. When exercise lasts more than about 40 – 60 min,
various animal models that have been used where rectal and performance can be improved by ingesting water or carbohy-
brain temperature can be measured simultaneously [16]. It is drate, and the effects of the two are independent and additive
easier to believe that important events related to fatigue may be [20]. Many other studies, often less well-controlled, have pro-
taking place in the brain than in the rectum. duced similar results. The evidence that ingesting plain water is
There is also some evidence that the beneficial effects of effective is, perhaps, less conclusive than the evidence for a
repeated exposures to exercise in a hot environment are due to beneficial effect of dilute carbohydrate-electrolyte drinks [21].
a lowering of the pre-exercise resting core temperature, with It is not easy to be sure, however, that the carbohydrate in this
the rate of rise of body temperature during exercise being little case is playing a metabolic role, though some of it is undoubt-
affected [14]. This is contrary to the commonly held view that edly oxidized [22]. An alternative explanation may be that
acclimation benefits exercise performance in the heat by pro- adding small amounts of carbohydrate can promote water ab-
moting heat loss through a greater evaporative heat loss that sorption in the small intestine, thus providing more effective
results from more profuse sweating and a more effective dis- rehydration. When the time scale is short, as in exercise lasting
tribution of sweat secretion over the body surface [17]. less than a couple of hours, ingested fluid will be effective only
if it is emptied rapidly from the stomach and absorbed rapidly
in the small intestine. For this reason, concentrated carbohy-
HYDRATION, THERMOREGULATORY drate solutions may be ineffective as they may promote tran-
FUNCTION AND EXERCISE sient net secretion in the small intestine, resulting in a tempo-
PERFORMANCE rary loss of body water into the small intestine [21].

There is a well-recognized interaction among hydration

status, thermoregulation and exercise tolerance, and some of HYDRATION STATUS AND
the consequences of hypohydration are shown in Table 2. COGNITIVE FUNCTION
In exercise of short duration there is not sufficient time for
sweat loss to cause significant reductions in body water con- The absence of specific reliable tests of different aspects of
tent. However, an individual who begins such exercise in a cognitive function aspects has contributed, in large part, to the
state of hypohydration may perform less well. This was clearly limited amount of information available. There are few reports
demonstrated by Armstrong et al. who showed that inducing on the effects of hypohydration on mental performance and
hypohydration by administering a diuretic agent prior to sim- cognitive function, but some negative effects have been re-
ulated races at distances of 1500 m, 5 km and 10 km reduced corded. Gopinathan et al. reported a reduction in a variety of
performance by 3.1%, 6.7%, and 6.3% respectively [18]. The tasks involving arithmetic ability, short-term memory, and vi-
theoretical advantage of a reduction in body mass that has to be sual tracking after dehydration (2– 4% of body mass) induced
carried does not therefore compensate for the negative effects by exercise in the heat and water restriction; the decrement in
of a reduced body water content. In a field situation, measures performance was roughly proportional to the extent of the
of cardiovascular function are not possible, but it seems likely water deficit, but there was no measurable loss of performance
that there may be no reduction in the maximum cardiac output with a 1% reduction in body mass [23]. This may reflect the
that can be achieved, despite the reduced blood volume [19]. In relative insensitivity of the tests used. The effects of hydration
status are discussed in detail by Lieberman [24].
Table 2. Effects of Hypohydration, Induced Either before or Much of the popular press on drinking and hydration status
during Exercise, by Failure to Replace Sweat Losses suggests that a conscious effort is required by individuals if
they are to drink sufficient fluid to maintain a state of body
Impaired thermoregulation water balance. While many physiological responses to hypo-
Reduced blood volume
hydration have been studied extensively, the perceived subjec-
Increased heart rate
Increased perception of effort tive responses to hypohydration have been largely ignored.
Reduced exercise performance This is particularly relevant if it is possible that it is “easy” for
Headache, nausea, insomnia people to inadvertently restrict their fluid intake over a number
Impaired mental function of days and thus become hypohydrated. One recent study
Increased risk of heat illness
described the physiological responses and subjective feelings

JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 607S

Exercise, Heat, Hydration and the Brain

resulting from 13, 24 and 37 h of fluid restriction and compared The above is a remarkably elegant description of a phenom-
these with a euhydration trial of the same duration [25]. Body enon that most would take for granted, but its failure lies in the
mass decreased by 2.7% after 37 h with fluid restriction. The absence of any reference to the physiological mechanisms
subjects reported that their thirst increased during the first 13 h involved. In that sense, the “central governor” described at
of fluid restriction and then did not significantly increase fur- length in recent publications remains a “black box” and has not
ther. They also reported headache with fluid restriction and that increased our understanding. The key role of the central ner-
their ability to concentrate and alertness were reduced. They vous system (CNS) in setting the limits to exercise performance
also indicated they felt more tired when restricting their fluid and in anticipating demands is taken for granted by those
intake. However, what was clear from these subjects was that involved in sport and is manifested in the pacing strategies
they all greatly desired something to drink during the later adopted by runners, cyclists, and other athletes.
stages of the study and had to make a conscious effort to The relationship between speed and distance in athletic
abstain from drinking and to continue eating dry foods. These events was well described by AV Hill in 1925 [29], and by
subjects therefore would not have become dehydrated to this many others before and since. Given that a fairly uniform pace
extent “by accident.” is maintained in most athletic events, the pace adopted at the
outset is based on experience of what the maximum tolerable
pace is likely to be. This is then subject to modulation by
signals arising in the peripheral tissues as described by Bain-
THE ROLE OF THE BRAIN bridge [28] and by a conscious decision based on environmen-
tal conditions, tactical considerations and other factors. Every
The thermoregulatory responses to exercise and heat stress elementary coaching manual published in the last century or
occur without conscious action by the brain, but this does not more has emphasized the need for the inexperienced athlete to
mean the brain is not aware of what is occurring or that it is not be cautious in the early stages of a race and set off at a pace
essential for conservation of function when exposed to these more modest than might feel appropriate. Every athlete also
stresses. All animals seek to escape environmental extremes to knows that there are “good days” and “bad days” when per-
more comfortable zones, except when there is a compelling formance is above or below what is expected, and that these
reason, such as a need for food, to risk the thermal stress. The appear to be unrelated to peripheral factors.
primary human response to thermal stress is to change the Marino et al. suggest the brain is able to calculate the rate of
environmental conditions, and where this is not possible to heat storage allowable under the prevailing environmental con-
adjust the amount of insulation or type of clothing. A further ditions and that this information, along with knowledge of the
option is to alter the rate of metabolic heat production: this exercise duration, will determine motor unit recruitment at
involves increasing activity levels when subjected to cold stress different times during the exercise [30]. This system is pro-
or reducing effort in warm weather. People are more inclined to posed to limit the rate of heat production during exercise, thus
walk briskly on cold days and to dawdle on hot ones. Only allowing a task to be completed prior to catastrophe (fatigue).
when these strategies are not successful in preventing a change Unless one subscribes to the belief that some higher being
in thermal comfort are the physiological mechanisms invoked. controls the destiny of the human race, there must be a physical
Noakes and colleagues have recently made much of the basis for the CNS limitations to performance that clearly exist.
possible role of the brain in maintaining thermal homeostasis in The physical mechanisms involved in the “central governor”
exercise and stressed the importance of a “central governor” are not well understood, but are likely to have a neurological
that prevents a failure of homeostasis by causing a voluntary basis which ultimately means there must be a neurochemical
cessation of effort (or a reduction in exercise intensity) when mechanism, or more likely, a number of mechanisms acting in
homeostasis is challenged [26,27]. The concept of a “governor” concert. Various pharmacological interventions have been ap-
that limits exercise performance to prevent a catastrophic fail- plied to test this hypothesis and the outcomes are generally
ure of physiological function has been ascribed by Noakes to consistent with a role for key central neurotransmitters, specif-
AV Hill [26]. The central nervous system’s role in the fatigue ically dopamine, serotonin and noradrenaline in the fatigue
that accompanies exercise was widely recognized much earlier process.
than the work of Hill, however. In 1919, Bainbridge [28] wrote, Perhaps the most convincing evidence for the brain’s role in
“It has long been recognized that the main seat of fatigue after the fatigue process comes from pharmacological interventions.
muscular exercise is the central nervous system. Mosso long Amphetamines, which act on central dopamine (DA) receptors,
ago stated that “nervous fatigue is the preponderating phenom- are well known to enhance exercise performance and are pro-
enon and muscular fatigue is also at bottom an exhaustion of hibited under the rules of the World Anti-Doping Agency [31].
the nervous system.’ There appear, however, to be two types of Various studies demonstrated a marked increase in exercise
fatigue, one arising entirely within the central nervous system, capacity following administration of amphetamines to both
the other in which fatigue of the muscles themselves is su- rodents [32] and humans [33, 34]. Amphetamines are thought
peradded to that of the nervous system.” to enhance exercise performance through the maintenance of

608S VOL. 26, NO. 5

 Exercise, Heat, Hydration and the Brain

DA release late in exercise, as an elevation in catecholaminer-

gic neurotransmission is typically linked to arousal, motivation,
and reward. Changes in regional dopamine metabolism have
also been implicated in the control of locomotion and posture in
moving animals, which may also be an important aspect of
DA’s role in fatigue [35].
Many different psychotropic drugs that act through changes
to central dopaminergic and noradrenergic neurotransmission
with varying degrees of receptor specificity to treat/manage
psychiatric disorders are now available. Bupropion, which acts
on central dopamine and noradrenaline receptors, was recently
shown to enhance endurance performance in the heat (Fig. 3),
but this effect was not seen when exercise was undertaken in
temperate conditions [36]. Even though a higher power output
was maintained during exercise in the heat after administration
of this drug, the subjects’ perception of effort and thermal
discomfort was the same on both the treatment and placebo
trials. Rectal temperature at the end of the trial was, however,
higher during the treatment trials than the placebo trials, which
is consistent with the higher mean power output. It is possible
that dopaminergic drugs may dampen or override inhibitory
signals arising from the CNS, to cease exercise due to hyper-
thermia and enable an individual to maintain a high power
output despite an elevated core temperature.
Traditional views of neurotransmission’s role in the devel-
opment of fatigue during prolonged exercise have centered on
the neurotransmitter serotonin (5-hydroxytrypamine; 5-HT).
Work by Newsholme and colleagues suggested that changes in
substrate mobilization occurring during prolonged exercise
Fig. 3. Effects of administration of an acute dose of Paroxetine (a
would result in an increased uptake of the amino acid trypto-
selective serotonin reuptake inhibitor); Figure 3A: and Bupropion (a
phan into the CNS [37]. As serotonin synthesis is largely
dopamine/noradrenaline reuptake inhibitor); Figure 3B: on subsequent
dependent on tryptophan’s availability, researchers postulated exercise (redrawn from [31] and [36] respectively). Note: Figure 3A
that central serotonergic synthesis, and therefore activity, shows a reduction in exercise capacity with Paroxetine, whereas Figure
would increase as a consequence of the metabolic changes 3B demonstrates an increase in time trial performance following
occurring as exercise continued. Serotonergic neurotransmis- Bupropion administration.
sion has been linked to feelings of lethargy and tiredness, and
Newsholme proposed that this response could contribute to the
[48]. Attempts to find a genetic basis for the success of specific
fatigue process. The evidence for drugs acting on serotonin
athletic populations, such as the East African distance runners,
receptors is perhaps less convincing than the work on dopa-
have generally been unsuccessful [49], perhaps because re-
mine, with some studies showing a reduction in exercise ca-
searchers have studied the wrong variables.
pacity following the administration of 5-HT agonists [38,39]
(Fig. 3) while others have shown no effect [40 – 42]. An attrac-
tion of this hypothesis was the possibility of altering central
5-HT activity via nutritional supplements, including branched- POTENTIAL MECHANISMS LINKING
chain amino acids, tryptophan, and carbohydrate. Attempts to HEAT, HYDRATION, AND
influence performance by nutritional interventions designed to PHYSIOLOGICAL FUNCTION
manipulate the availability of neurotransmitter precursors,
however, have generally been unsuccessful [43– 46], with only It is not easy to see an immediate mechanism that links fluid
a few exceptions [47]. balance, thermoregulatory function, and central serotonergic or
To further emphasize the potential involvement of dopami- dopaminergic function. However, it was recently shown that
nergic neurons in the fatigue process, there is some recent prolonged exercise performance in the heat may be associated
evidence that rats selectively bred for either high or low run- with an increased permeability of the blood brain barrier (BBB)
ning capacity show differences in the expression of genes [50]. This conclusion was based on an increased concentration
related to dopaminergic function in some regions of the brain of a brain specific protein (S-100␤) in the circulation after

JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 609S

Exercise, Heat, Hydration and the Brain

exercise in the heat, but not after a similar exercise bout maintain voluntary contractions, and an increase in perceived
performed in cool conditions. The BBB’s function is to protect exertion. While the precise role of the CNS in the development
the brain by preventing pathogens and small molecules that of fatigue is yet to be determined, preliminary evidence sup-
may disrupt CNS function from accessing it. It also acts to ports a neurotransmission role in the fatigue process. A number
prevent escape of valuable nutrients from the brain. The BBB of circulatory perturbations, including a reduction in cerebral
is normally impermeable to S-100␤, though it can escape from blood flow and increased permeability of the blood-brain bar-
the brain in various stress situations that disrupt barrier function rier, may also influence performance when exercise is under-
[51]. If S-100␤ can escape from the CNS during exercise, it taken in high ambient temperatures, particularly in the presence
seems likely that other compounds can leave or enter the brain. of significant levels of dehydration.
The fact that increased permeability is observed when core
temperature is elevated by exercise in the heat may not be
significant, but may be a factor in the early fatigue that occurs REFERENCES
in this situation.
Further circumstantial evidence to support this suggestion 1. Coyle EF, Montain S: Thermal and cardiovascular responses to
fluid replacement during exercise. In Gisolfi CV, Lamb DR, Nadel
comes from the observation that the rise in serum S-100␤ with
ER (eds): “Exercise, Heat and Thermoregulation.” Dubuque:
exercise in the heat is at least partially abolished by water
Brown & Benchmark, pp 179–223, (1993)
ingestion [52]. This may be associated with the better control of 2. Galloway SD, Maughan RJ: Effects of ambient temperature on the
osmotic equilibrium across the BBB, limiting the structural capacity to perform prolonged cycle exercise in man. Med Sci
changes responsible for the increased permeability that would Sports Exerc 29:1240–1249, 1997.
otherwise take place. While there is evidence that relatively 3. Parkin JM, Carey MF, Zhao S, Febbraio MA: Effect of ambient
mild dehydration can negatively influence cognitive perfor- temperature on human skeletal muscle metabolism during fatigu-
mance [23], little is known about the mechanisms affecting the ing submaximal exercise. J Appl Physiol 86:902–908, 1999.
brain. These data suggest that changes in whole body fluid 4. Montain S, Ely MR, Cheuvront SN: Marathon performance in
balance can directly influence the CNS, and this may poten- thermally stressing conditions. Sports Med, in press, 2007.
tially play a role in the mental and physical performance 5. Gonzalez-Alonso J: Hyperthermia impairs brain, heart and muscle
function in exercising humans. Sports Med, in press, 2007.
deterioration seen with dehydration.
6. Nielsen B: Olympics in Atlanta: a fight against physics. Med Sci
High cerebral temperature may lead to alterations in motor
Sports Exerc 28:665–668, 1996.
drive that affect the ability to recruit sufficient muscle fibers to 7. Redfern PH, Waterhouse JM, Minors DS: Circadian rhythms:
meet the demands of exercise [53]. This effect may be medi- principles and measurement. Pharmacol Ther 49:311–327, 1991.
ated, at least in part, by blood flow changes occurring in 8. Greenhaff PL, Clough PJ: Predictors of sweat loss in man during
response to redistribution of cardiac output due to exercise-heat prolonged exercise. Eur J Appl Physiol Occup Physiol 58:348–
stress. During exercise in temperate conditions, cerebral blood 352, 1989.
flow is markedly increased during exercise [54], but a decline 9. Costill DL: Sweating: its composition and effects on body fluids.
in blood flow to the brain has been reported during exercise Ann NY Acad Sci 301:160–174, 1977.
with hyperthermia [55]. It is clear that exercise, coupled with 10. Gonzalez-Alonso J, Mortensen SP, Dawson EA, Secher NH,
heat stress, results in a significant number of metabolic and Damsgaard R: Erythrocytes and the regulation of human skeletal
blood flow and oxygen delivery: role of erythrocyte count and
circulatory perturbations within the brain. At present, it is
oxygenation state of haemoglobin. J Physiol 572:295–305, 2006.
impossible to single out a key factor that is ultimately respon-
11. Maughan RJ, Leiper JB, Thompson J: Rectal temperature after
sible for development of central fatigue and reduction in exer- marathon running. Br J Sports Med 19:192–195, 1985.
cise performance in the heat, but this likely involves interplay 12. Lee DT, Haymes EM: Exercise duration and thermoregulatory
between these responses, to varying degrees. responses after whole body precooling. J Appl Physiol 79:1971–
1976, 1995.
13. Gonzalez-Alonso J, Teller C, Andersen SL: Influence of body
SUMMARY temperature on the development of fatigue during prolonged ex-
ercise in the heat. J Appl Physiol 86:1032–1039, 1999.
Performance of both physical and mental tasks is signifi- 14. Nielsen B, Hales JR, Strange S, Christensen NJ, Warberg J, Saltin
cantly reduced by heat and dehydration. The cardiovascular and B: Human circulatory and thermoregulatory adaptations with heat
acclimation and exercise in a hot, dry environment. J Physiol
thermoregulatory systems are particularly stressed under these
460:467–485, 1993.
conditions and provision of fluids can prevent dehydration and
15. Sawka MN, Young AJ, Latzka WA, Neufer PD, Quigley MD,
greatly reduce the adverse effects of heat stress. There is Pandolf KB. Human tolerance to heat strain during exercise: in-
growing evidence that the effects of high ambient temperature fluence of hydration. J Appl Physiol 73:368–375, 1992.
and dehydration on exercise performance may be mediated by 16. Walters TJ, Ryan KL, Tate LM, Mason PA: Exercise in the heat is
effects on the CNS. Hyperthermia results in changes in the limited by a critical internal temperature. J Appl Physiol 89:799–
brain’s electrical activity, a marked reduction in the ability to 806, 2000.

610S VOL. 26, NO. 5

 Exercise, Heat, Hydration and the Brain

17. McArdle WD, Katch FI, Katch VL: “Sports & Exercise Nutrition.” enhances human exercise performance in warm, but not temperate
Philadelphia: Lippincott Williams & Wilkins, p 282, 1999. conditions. J Physiol 565:873–883, 2005.
18. Armstrong LE, Costill DL, Fink WJ: Influence of diuretic-induced 37. Newsholme EA, Acworth I, and Blomstrand E: Amino acids, brain
dehydration on competitive running performance. Med Sci Sports neurotransmitters and a function link between muscle and brain
Exerc 17:456–461, 1985. that is important in sustained exercise. In Benzi G (ed): “Advances
19. Saltin B: Circulatory response to submaximal and maximal exer- in Myochemistry.” London: John Libbey Eurotext, pp. 127–133,
cise after thermal dehydration. J Appl Physiol 19:1125–1132, 1987.
1964. 38. Struder HK, Hollmann W, Platen P, Donike M, Gotzmann A,
20. Below P, Mora-Rodriguez R, Gonzalez-Alonso J, Coyle EF: Fluid Weber K: Influence of paroxetine, branched-chain amino acids and
and carbohydrate ingestion independently improve performance tyrosine on neuroendocrine system responses and fatigue in hu-
during 1 h of intense exercise. Med Sci Sports Exerc 27:200–210, mans. Horm Metab Res 30:188–194, 1998.
1995. 39. Wilson WM, Maughan RJ: Evidence for a possible role of 5-hy-
21. Maughan RJ: Carbohydrate-electrolyte solution during prolonged droxytryptamine in the genesis of fatigue in man: administration of
exercise. In Lamb DR, Williams MH (eds): “Perspectives in Ex- paroxetine, a 5-HT re-uptake inhibitor, reduces the capacity to
ercise Science and Sports Medicine.” Carmel: Benchmark Press, perform prolonged exercise. Exp Physiol 77:921–924, 1992.
pp 35–85, 1991. 40. Meeusen R, Piacentini MF, Van Den Eynde S, Magnus L, De
22. Jeukendrup AE, Jentjens R: Oxidation of carbohydrate feedings Meirleir K: Exercise performance is not influenced by a 5-HT
during prolonged exercise: current thoughts, guidelines and direc- reuptake inhibitor. Int J Sports Med 22:329–336, 2001.
tions for future research. Sports Med 29:407–424, 2000. 41. Pannier JL, Bouckaert JJ, Lefebvre RA: The antiserotonin agent
23. Gopinathan PM, Pichan G, Sharma VM: Role of dehydration in pizotifen does not increase endurance performance in humans. Eur
J Appl Physiol Occup Physiol 72:175–178, 1995.
heat stress-induced variations in mental performance. Arch Envi-
42. Strachan A, Leiper J, Maughan RJ: Paroxetine administration
ron Health 43:15–17, 1988.
failed [corrected] to influence human exercise capacity, perceived
24. Lieberman H: Hydration and cognition. J Am Coll Nutr, in press,
effort or hormone responses during prolonged exercise in a warm
2007.
environment.. Exp Physiol 89:657–664, 2004.
25. Shirreffs SM, Merson SJ, Fraser SM, Archer DT: The effects of
43. Blomstrand E, Hassmen P, Ek S, Ekblom B, Newsholme EA:
fluid restriction on hydration status and subjective feelings in man.
Influence of ingesting a solution of branched-chain amino acids on
Br J Nutr 91:951–958, 2004.
perceived exertion during exercise. Acta Physiol Scand 159:41–49,
26. Noakes TD: Maximal oxygen uptake: “classical” versus “contem-
1997.
porary” viewpoints: a rebuttal. Med Sci Sports Exerc 30:1381–
44. Madsen K, MacLean DA, Kiens B, Christensen D: Effects of
1398, 1998.
glucose, glucose plus branched-chain amino acids, or placebo on
27. Noakes TD, St Clair Gibson A, Lambert EV: From catastrophe to
bike performance over 100 km. J Appl Physiol 81:2644–2650,
complexity: a novel model of integrative central neural regulation
1996.
of effort and fatigue during exercise in humans: summary and
45. van Hall G, Raaymakers JS, Saris WH, Wagenmakers AJ: Inges-
conclusions. Br J Sports Med 39:120–124, 2005.
tion of branched-chain amino acids and tryptophan during sus-
28. Bainbridge FA: “The Physiology of Muscular Exercise.” London:
tained exercise in man: failure to affect performance. J Physiol
Longmans, Green, 1919.
486:789–794, 1995.
29. Hill AV: The physiological basis of athletic records. The Scientific 46. Watson P, Shirreffs SM, Maughan RJ: The effect of acute
Monthly 21:409–428, 1925. branched-chain amino acid supplementation on prolonged exercise
30. Marino FE: Anticipatory regulation and avoidance of catastrophe capacity in a warm environment. Eur J Appl Physiol 93:306–14,
during exercise-induced hyperthermia. Comp Biochem Physiol B 2004.
Biochem Mol Biol 139:561–569, 2004. 47. Mittleman KD, Ricci MR, Bailey SP: Branched-chain amino acids
31. World Anti-Doping Agency (WADA): The 2007 Prohibited List. prolong exercise during heat stress in men and women. Med Sci
Montreal (Quebec), Canada: WADA, 2006. Available from: www. Sports Exerc 30:83–91, 1998.
wada-ama.org/en/prohibitedlist.ch2 48. Foley TE, Greenwood BN, Day HE, Koch LG, Britton SL, Flesh-
32. Gerald MC: Effects of (⫹)-amphetamine on the treadmill endur- ner M: Elevated central monoamine receptor mRNA in rats bred
ance performance of rats. Neuropharmacology 17:703–704, 1978. for high endurance capacity; implications for central fatigue. Be-
33. Borg G, Edstrom CG, Linderholm H, Marklund G: Changes in hav Brain Res 174:132–142, 2006.
physical performance induced by amphetamine and amobarbital. 49. Scott, RA, Pitsiladis YP: Genotypes and distance running: clues
Psychopharmacologica 26:10–18, 1972. from Africa. Sports Med 37: 424–427, 2007.
34. Chandler JV, Blair SN: The effect of amphetamines on selected 50. Watson P, Shirreffs SM, Maughan RJ: Blood-brain barrier integ-
physiological components related to athletic success. Med Sci rity may be threatened by exercise in a warm environment. Am J
Sports Exerc 12:65–69, 1980. Physiol Regul Integr Comp Physiol 288:R1689–R1694, 2005.
35. Freed CR, Yamamoto BK: Regional brain dopamine metabolism: 51. Marchi N, Rasmussen P, Kapural M, Fazio V, Kight K, Mayberg
a marker for the speed, direction, and posture of moving animals. MR, Kanner A, Ayumar B, Albensi B, Cavaglia M, Janigro D:
Science 229:62–65, 1985. Peripheral markers of brain damage and blood-brain barrier dys-
36. Watson P, Hasegawa H, Roelands B, Piacentini MF, Looverie R, function. Restor Neurol Neurosci 21:109–121, 2003.
Meeusen R: Acute dopamine/noradrenaline reuptake inhibition 52. Watson P, Black KE, Clark SC, Maughan RJ: Exercise in the heat:

JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION 611S

Exercise, Heat, Hydration and the Brain

Effect of fluid ingestion on blood-brain barrier permeability. Med 55. Nybo L, Nielsen B: Middle cerebral artery blood velocity is
Sci Sports Exerc 38:2118–2124, 2006. reduced with hyperthermia during prolonged exercise in humans.
53. Nybo L, Nielsen B: Hyperthermia and central fatigue during pro- J Physiol 534:279–286, 2001.
longed exercise in humans. J Appl Physiol 91:1055–1060, 2001.
54. Ide K, Secher NH: Cerebral blood flow and metabolism during
exercise. Prog Neurobiol 61:397–414, 2000. Received July 16, 2007

612S VOL. 26, NO. 5