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OCR for page 33
Efficacy of Caffeine
Caffeine has been shown clinically to induce a variety of positive effects
that have contributed to its extensive use worldwide. Caffeine use has been
associated with increased alertness and enhanced physical performance, and as a
countermeasure to the effects of sleep deprivation. Extensive research has been
done on each of these effects of caffeine. A brief summary of research findings
on the efficacy of caffeine is presented here.
PHYSICAL PERFORMANCE
Caffeine has been proposed as an ergogenic aid in physical performance. Its
use is associated with a reproducible increase in endurance time in activities of
moderate intensity and long duration. Caffeine consumed both at rest and during
exercise increases a variety of physiological processes (heart rate, respiratory
rate, blood pressure), probably through the secretion of epinephrine. Recent
research indicates that caffeine may also act by altering pain perception since it
has been reported to increase plasma p-endorph~ns during endurance exercise
(Laurent et al., 2000~. Typically, the magnitude of the exercise response far
exceeds and masks the resting effects of caffeine intake. However, if the inten-
sity of the exercise is low and the caffeine dose is high, the effect of the caffeine
may be obvious even during exercise. Caffeine also shifts cellular metabolism,
possibly through antagonism of adenosine receptors (Graham et al., 1994~. Spe-
cifically, caffeine increases lipolysis via activation of hormone-sensitive lipase,
decreases glycogenolysis via direct inhibition of glycogen phosphorylase, and
33
OCR for page 34
34
CAFFEINE FOR MENTAL TASK PENANCE
increases blood glucose and oxygen consumption (Spriet, 1999~. Earlier work
indicated this increase in lipolysis may actually be stimulated by the caffeine
metabolite, paraxanthine, rather than by caffeine itself (Hetzler et al., 1990~.
Energy derived from fat during exercise is increased with caffeine ingestion,
while the energy derived from carbohydrate is somewhat reduced at the same
intensity of exercise (Sasaki et al., 1987~. Glycogen utilization is, at least ini-
tially, depressed (Erickson et al., 1987; Essig et al., 1980; Spriet et al., 1992~.
Blood lactate, which usually increases in exercise above 7~75 percent of
VOW,, is not affected by caffeine at rest, and may (Flinn et al., 1990;
McNaughton, 1986) or may not (Dodd et al., 1991; Gastin et al., 1990) be af-
fected by caffeine during exercise, depending on the intensity of the exercise
and the level of caffeine ingested.
Although in today's military there is an increasing reliance on sophisticated
computer-controlled systems, special operations and infantry missions will al-
ways rely on the physical fitness of the soldier. These operations consist of either
prolonged endurance or brief, high-intensity activity. The efficacy of caffeine in
promoting physical performance is different for these two kinds of activity.
Four separate reviews (Dodd et al., 1993; Graham et al., 1994; Spriet, 1995;
Tarnopolsky, 1994) have concluded consistently that caffeine enhances endurance
performance in a variety of activities (i.e., naming, cross-country skiing, cycling),
with doses from 2 to 9 mg/kg, in naive and habituated, trained and untrained test
subjects. The performance effects are seen at intakes that result in urinary caffeine
levels below the legal limits stipulated by the International Olympic Committee
and are more pronounced in well-trained athletes (Spriet, 1999~.
These same reviews concluded that there was little effect of caffeine on ac-
tivities requiring high power outputs over a short time, such as lifting, carrying,
and sprinting. Such activities utilize primarily anaerobic generation of adenosine
triphosphate, a process that is probably not affected by caffeine. In contrast,
other studies have shown slightly increased power output due to caffeine intake
(Anselme et al., 1992; Collomp et al., 1992; Wiles et al., 1992), or increased
time to exhaustion in brief (2-minute) supramaximal exercise (Jackman et al.,
1996~. This suggests a possible direct effect of caffeine on muscle tissue (Green
et al., 1990; Lopes et al., 1983; Tarnopolsky et al., 1992~.
Response to caffeine ingestion may vary among studies as a consequence of
the caffeine habits of participants. As mentioned elsewhere in this report,
chronic use of caffeine results in habituation to some of its effects, possibly by
up-regulation of adenosine receptors. The epinephrine response to circulating
caffeine or methylxanthine by-products may be attenuated as a result (Tarnopol-
sky et al., 1989; van Soeren et al., 1993~. If the epinephrine response is required
for the performance-enhancing effects of caffeine to be realized, habitual users
may require a higher dose of caffeine to garner the positive results (Spriet et al.,
1992~. The dose of caffeine required for significant improvements in physical
performance ranges from 3 to 9 mg/kg (Graham and Spriet, 1995~. It should be
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EFFICA CY OF CAFFEINE
35
noted, as well, that exercise has been shown to counteract the anxiety that may
accompany high doses of caffeine. Youngstedt et al. (1998) showed that after
ingestion of 800 mg of caffeine, cycling for 60 minutes at 60 percent of Wax
significantly reduced anxiety compared with consumption of this amount of
caffeine while at rest.
Carbohydrat - Caffeine Mixtures
The most important theoretical mechanism of action of caffeine in the con-
text of physical performance of the whole organism is a shift in the primary fuel
used for exercise. In adipocytes, caffeine promotes lipolysis by increasing cyclic
adenosine monophosphate levels, which in turn increase stimulation of hor-
mone-sensitive lipase. The resulting increase in circulating free fatty acids hy-
pothetically spares muscle glycogen. An independent effect of caffeine on mus-
cle glycogenolysis has also been postulated (as discussed in previous section). In
addition, carbohydrate has been shown to enhance performance during continu-
ous exercise lasting at least 5~60 minutes (Armstrong and Maresh, 1996~. The
hypothesis has been put forward that incorporating the lipolytic qualities of
caffeine with the carbohydrate utilization-promoting qualities of carbohydrate
ingestion might augment the performance effects of both, suggesting that caf-
feine delivered in a carbohydrate-containing medium may further enhance per-
formance. The following three studies have tested the efficacy of such a mixture.
Wemple et al. (1997), using a carbohydrate and electrolyte drink (3 mL/kg)
with and without caffeine (60 mg per dose), evaluated time to exhaustion at 85
percent VO2~aX after 3 hours of continuous cycling exercise in six trained subjects.
Cycling performance was not affected by including caffeine in the carbohydrate-
containing fluid. However, caffeine intake in this experiment was extremely low.
Kovacs et al. (1998) added different doses of caffeine (2~.5 mg/kg) to a
carbohydrate-electrolyte solution and examined the effects on substrate me-
tabolism and endurance performance time in 15 trained subjects during a 1-hour
time trial. The addition of caffeine to the carbohydrate-electrolyte drink resulted
in a significant improvement in the performance times as compared to placebo
or carbohydrate-electrolyte drink alone, with a maximum effect at an intake of
about 3 mg of caffeine per kilogram There was no apparent change in metabolic
fuel used during the cycling exercise, thus ruling out fuel shifts as the mecha-
nism by which caffeine augmented the carbohydrate effect. No caffeine-only
treatment was included in this experiment, leaving the question open as to how
much of the effect was due to caffeine alone and how much to the interaction of
caffeine and carbohydrate.
Sasaki and colleagues (1987) looked at the effect of placebo, sucrose, caf-
feine (approximately 6 mg/kg of body weight), and a sucrose plus caffeine
mixture on time to fatigue in five trained males running at 80 percent VO2maX.
There was no additive effect of caffeine on time to exhaustion when it was given
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36
CAFFEINE FOR MENTAL TASK PERFORMANCE
with sucrose, although the mean distance covered was greater in the two trials
where the subjects consumed sucrose compared to placebo. Caffeine alone re-
sulted in a distance intermediate between the two sucrose trials, but it was not
significantly different from either. Caffeine alone was associated with an in-
crease in energy derived from fat, whereas sucrose alone was associated with an
increased utilization of carbohydrate. Sucrose in combination with caffeine
maintained the higher carbohydrate utilization equivalent to sucrose alone. The
small number of subjects in this experiment makes it difficult to project these
findings to all other populations, including military personnel.
Other Effects on Physical Performance
It has been postulated that caffeine might impinge on physical performance
via changes in body temperature and fluid balance. Caffeine apparently has no
effect on rectal temperature, plasma volume change, or sweat rate during endur-
ance exercise in warm (25-29°C) environments (Fain et al., 1990; Gordon et al.,
1982~. No similar studies have been conducted in hotter conditions; however, if
an effect is not seen at 25-29°C, it is unlikely that there would be a differential
response due to caffeine at temperatures greater than 29°C. Further, a study by
Cohen et al. (1996) on performance in a hot and humid environment showed no
effect of consuming 5 or 9 mg of caffeine per kilogram on time to exhaustion,
body temperature, or blood levels of glucose and lactate during multiple 21-krn
runs in trained men and women.
High-altitude exposure may augment the positive effects of caffeine on en-
durance performance. Exercise performance is dramatically reduced by altitude
exposure, and maximal effort may be diminished by as much as 25 percent.
Submaximal performance may be improved with acclimatization, but maximal
effort does not normally recover (IOM, 1996~. However, Fulco et al. (1994)
showed that ingestion of caffeine (4 mg/kg) could increase the time to exhaus-
tion in eight trained men riding a cycle ergometer at 80 percent of high-altitude
VO2maX (65 percent of sea-level VO2~aX) at 4,300 m, but not at sea level. This
positive effect was present after 1 hour of altitude exposure (54 percent increase
in time to exhaustion with caffeine ingestion 1 hour before exercise) and tended
to remain after 2 weeks of acclimatization (24 percent increase). Because Fulco
et al. did not find any differences in substrate metabolism between the two con-
ditions, they hypothesized that the mechanism of improvement involved an
increase in residual lung capacity (tidal volume) or an improvement in muscle
strength. Similarly, Berglund and Hemmingsson (1982) showed that caffeine
significantly decreased the race time (by 101 seconds after one lap, 152 seconds
after two) of trained cross-country skiers in a 21-km race at 2,900 m. No change
in race time occurred in a test at an altitude of 300 m.
A combination of caffeine and ephedrine enhances running performance
(Bell and Jacobs, 1999), but also raises metabolic heat production and thus poses
OCR for page 37
EFFICA CY OF CAFFEINE
37
a theoretical risk of hyperthermia during exercise-heat stress. However, during 2
hours of brisk treadmill walking in a 40°C hot, dry environment, Bell et al.
(1999) observed that this increased metabolic heat production was offset by
increased heat dissipation and that the internal body temperature change was no
greater than during a control trial. However, recent information on adverse car-
diovascular and central nervous system events resulting from the use of ephedra-
containing supplements (Hailer and Benowitz, 2000) makes the use of a caf-
feine-ephedra combination less than desirable. Although hyperthermia is more
likely when prolonged, strenuous exercise and intense environmental stress are
concurrent, the effects of caffeine in this situation have not been examined.
COGNITIVE FUNCTION AND ALERTNESS
Both common experience and the results of scientific investigations support
the belief that caffeine enhances performance on a variety of cognitive tasks.
However, a review of the experimental literature reveals inconsistencies in the
amount of caffeine that is required to produce positive effects on cognitive be-
havior. These discrepant findings can be explained by differences among experi-
ments in a number of variables including whether or not subjects were tested fol-
lowing a period in which they had abstained from using caffeine, the tasks used to
assess cognitive behavior, the age and gender of the subjects, the subjects' history
of caffeine use, and whether the subjects were rested or sleep deprived.
There has been some debate whether caffeine enhances cognitive perform-
ance or simply restores degraded performance following caffeine withdrawal in
rested individuals. James (1994, 1995, 1998) argued that the majority of studies
reporting the effects of caffeine in rested subjects studied moderate caffeine
consumers (200-300 mg/d) who were required to abstain from caffeine for some
period of time prior to cognitive testing (2-24 fur). Abstinence for regular caf-
feine users could have resulted in symptoms of withdrawal which include head-
aches, fatigue, and irritability (Griffiths and Mumford, 1995; Griffiths et al.,
1990~. James (1994, 1995, 1998), hypothesized that comparisons between caf-
feine and placebo conditions in experiments assessing the effects of caffeine on
cognitive behavior could represent a reversal of deteriorated performance. This
may be due to caffeine withdrawal in the placebo condition compared to base-
line performance in the presence of caffeine.
A clearer picture of caffeine's effects on cognitive function and behavior
has begun to emerge, however. Caffeine can enhance performance on some
types of cognitive tasks, and some aspects of mood in rested individuals inde-
pendent of its ability to reverse symptoms of withdrawal and regardless of the
background consumption of caffeine. Warburton (1995) demonstrated that caf-
feine administered in doses of 0, 75, and 150 mg to adult male, nonsmoking,
regular caffeine users, without abstinence from caffeine prior to treatment, im-
proved attention, problem solving, and delayed recall and significantly improved
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38
CAFFEINE FOR MENTAL TASKPE~O~ANCE
mood ratings. Rogers et al. (1995), using caffeine doses of 0, 70, and 250
mg/day in caffeine users (> 200 mg/d) and nonusers (< 15 mg/d), demonstrated
that although caffeine withdrawal had a negative effect on mood, it did not ap-
pear to affect psychomotor performance. Jarvis (1993) reported results of a large
survey study on coffee and tea consumption showing a highly significant dose-
response relationship between habitual caffeine intake and psychomotor per-
formance (simple reaction time, choice reaction time, incidental verbal memory,
and vi-quo-spatial reasoning). This report also clearly demonstrates that tolerance
to the performance-enhancing effects of caffeine, if it occurs at all, is incomplete
with the result that higher daily caffeine consumers tend to perform better than
do low consumers (Jarvis, 1993~.
Using objective measures of alertness (multiple sleep latency test, visual
and auditory vigilance tasks), Zwyghuizen-Doorenbos et al. (1990) demon-
strated in rested, moderate (< 250 mg/d) caffeine users that caffeine adminis-
tered in 250-mg doses twice a day compared to placebo improved daytime alert-
ness and reaction time on auditory vigilance tasks. Kenemans and Lorist (1995),
using male and female undergraduate students with an average coffee consump-
tion of 5.9 cups/day, demonstrated that caffeine given in a single dose of 3
mg/kg body weight (a 250 mg/day) increased cortical activation, increased sen-
sitivity (rate at which information on stimuli is accumulated), and increased both
speed and accuracy of target selection.
Amendola et al. (1998) reported caffeine at doses of 0, 64, 128, and 256
mg/day enhanced accuracy and reduced reaction time on auditory and visual
vigilance tasks in a dose-related manner. Moreover, caffeine significantly in-
creased self-reports of vigor and decreased reports of fatigue, depression, and
hostility on the Profile of Moods Scale (POMS). Self-assessments of energy
levels were also improved by caffeine (Lieberman et al., 1987; Sicard et al.,
1996~. However, caffeine did not improve long-term memory (list learning),
false alarms in an auditory vigilance task, commission of errors in a four-choice
reaction time, or motor coordination. In a simulated military situation involving
a tedious task that required sustained attention for proficient performance (i.e.,
sentry duty), caffeine eliminated the vigilance decrement that occurred with
increasing time on duty, reduced subjective reports of tiredness, and did not
impair rifle firing accuracy (Johnson, 1999~. Additionally, in this situation, caf-
feine increased the number of correct target identifications in both males and
females. However, the reason for this differed with gender. With prolonged
sentry duty and no caffeine, men were more likely to fire at friendly targets and
women were less likely to fire at foes. Caffeine returned both of these deficits to
baseline levels (Johnson, 1999~.
Thus, caffeine's effects on cognitive function and mood can be detected in
rested individuals, both users and nonusers of caffeine, using a variety of stan-
dardized tests. Only certain behavioral functions appear to be susceptible to the
influence of moderate doses of caffeine (32-256 lug). In particular, it appears
OCR for page 39
EFFICA CY OF CAFFEINE
39
that in well-rested individuals, low and moderate doses of caffeine preferentially
affect functions related to vigilance (i.e., the ability of the individual to maintain
alertness and appropriate responsiveness to the external environment for sus-
tained periods of time), but have limited effects on memory and problem-solving
abilities. At high doses caffeine can interfere with performance of tasks requir-
ing fine motor control (Durlach, 1998; Rogers and Dernoncourt, 1998~.
The effects of caffeine on cognitive behavior vary according to dose, the
subject's experience with caffeine, and gender. In general, low to intermediate
doses (10~600 ma) of caffeine are associated with increased alertness, energy,
and concentration, while higher doses can lead to anxiety, restlessness, insom-
nia, and tachycardia (Heishman and Henningfield, 1992, 1994~. Individuals who
do not consume caffeine on a regular basis appear to be more susceptible to the
negative consequences of caffeine than regular consumers. With respect to gen-
der, because of their smaller lean body mass, women may be more affected by a
given dose of caffeine than men.
A number of studies have reported on the effect of age on physiological and
cognitive responses to caffeine. Arciero et al. (1995) reported that caffeine in-
gestion (5 mg/kg fat-free mass) increased free fatty acids and tended to increase
rate of appearance of fatty acids in younger men (19-26 years old), but not in
older men (65-80 years old); while norepinephrine kinetics and fat oxidation
were not affected by caffeine in either age group. Arciero et al. (1998) reported
on effects of caffeine ingestion (5 mg/kg fat-free mass) on blood pressure, heart
rate, norepinephrine kinetics, and behavioral mood in younger and older men.
Resting baseline blood pressure was significantly lower for younger men than
for older men. Following caffeine ingestion, blood pressure increased signifi-
cantly above baseline for older men whereas it remained statistically unchanged
in younger men. Heart rates in both groups were unaffected by caffeine inges-
tion. Norepinephrine kinetics (appearance and clearance rates) were not affected
by caffeine in either group, although older men had higher norepinephrine con-
centrations with caffeine. Older men reported declines in feelings of tension and
anger following caffeine ingestion, while younger men reported increased feel-
. ~
ngs OI anger.
Rees et al. (1999) examined the interaction of caffeine and age and found
that 250 mg of caffeine significantly decreased reaction times in both 20- to 25-
year-olds and 50- to 65-year-olds with no effect on word recall. In contrast,
Hogervorst et al. (1998) evaluated the effects of 225 mg of caffeine on memory
and memory-related processes in three age groups: young (2~34 y), middle-
aged (4~54 y), and older (6~74 y). Short-term memory was negatively af-
fected by caffeine in the young group, positively affected in the middle-aged
group, and had no effect in the older group. Jarvis (1993), in a large survey
study on coffee and tea consumption, found that when results for reaction time
tests were categorized by age group (1~34 y, 35-54 y, 55+ y), caffeine intake
had a greater performance-enhancing effect for older people (35-54 y, 55+ y)
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40
CAFFEINE FOR MENTAL TASKPE~O~ANCE
than younger people (1~34 y). The author hypothesized that this greater sensi-
tivity to caffeine in older adults might be due to the fact that older people tend to
operate further below their ceiling than do the young. Alternatively, since the
survey only measured coffee and tea consumption, the caffeine intake in the
young group was more likely to be underestimated due to much heavier cola and
soft drink use in this age group (Jarvis, 1993~. Amendola et al. (1998), using
subjects in two age groups (18-30 y and ~ 60 y), tested oral caffeine doses of 0,
64, 128, and 256 mg and found a dose-dependent improvement in mood and
performance on the modified Wilkinson Auditory Vigilance Task that was not
affected by age.
Thus, it would appear that caffeine effects on performance of vigilance
types of tasks is independent of age, while caffeine effects on memory-related
tasks may be age-dependent.
COMPENSATION OF SLEEP DEPRIVATION
IMPAIRMENTS
Effects of Sleep Deprivation on Cognitive Behavior
Military personnel face many situations in which extended wakefulness
may be required, including sentry duty, deployment-related activities, air trans-
portation during emergencies, submarine duty, and combat. As part of their
duties in these situations, individuals may have to perform complex cognitive
tasks. The performance of these tasks is compromised during periods of ex-
tended wakefulness. Sleep deprivation leads to a sequence of impairments in
cognitive functioning. These impairments include decreases in alertness, decre-
ments in mental performance, reductions in self-reports of vigor, increases in
sleepiness and fatigue, and increases in response reaction time (Kautz, 1999;
Newhouse et al., 1989; Penetar et al., 1993, 1994; Wyatt, 1999~.
A variety of instruments have been used to quantify the effects of sleep dep-
rivation on behavior in controlled-experimental as well as simulated real-world
situations. Alertness has been assessed using objective measures such as ambu-
latory vigilance monitors, visual and auditory vigilance tasks, and subjective
measures such as self-reports and questionnaires. Studies using these measures
have found that sleep deprivation impairs performance on vigilance tasks and
decreases self-reports of alertness (Bonnet and Arand, 1994a,b; Bonnet et al.,
1995; Caldwell et al., 1995; Penetar et al., 1993~. A number of mental tasks,
such as a serial add-subtract test, logical reasoning, mental rotation, perceptual
cueing, and memory tests have been used to assess the effects of sleep depriva-
tion on higher cognitive processes. Using these tasks, mental performance dete-
riorates as a function of sleep deprivation (Bonnet, 1999; Caldwell et al., 1995;
Kautz, 1999; Newhouse et al., 1989; Penetar et al., 1993; Smith, 1999; Stick-
gold, 1999~. Of particular significance, sleep deprivation leads to impairments in
OCR for page 41
EFFICACY OF CAFFEINE
41
performance on cognitive tasks that would be encountered in military situations,
such as piloting helicopters, fixed-winged aircraft, submarines, or advance
warning aircraft; monitoring sonar or radar screens; and sentry duty. Sleep dep-
rivation also affects mood as measured by standard scales such as the POMS
and visual analogue scales. More specifically, as subjects become incrasingly
sleep-deprived, increases in fatigue, tension, and depression and decreases in
vigor are reported (Bonnet, 1999; Caldwell et al., 1995; Kautz, 1999; Newhouse
et al., 1989; Penetar et al., 1993; Smith, 1999; Stickgold, 1999~. Sleepiness, as
assessed by objective measures including latency to sleep, eyelid movements,
electroencephalograms, and muscle tone, and subjective measures such as self-
report sleepiness scales, increases directly as a function of the amount of sleep
deprivation incurred.
Recent advances in the understanding of sleep mechanisms have identified
adenosine as a moderator of the sleep-inducing effects of prolonged wakeful-
ness. Studies have shown that extracellular concentrations of adenosine in the
chol~nergic regions of the basal forebrain increased progressively during pro-
longed wakefulness and declined slowly during recovery sleep (Porkka-
Heiskanen, 1999; Porkka-Heiskanen et al., 1997~. Caffeine, as a known antago-
nist of adenosine, could thus be expected to promote wakefulness by preventing
neuronal uptake of the sleep-promoting adenosine.
Two recently identified neuropeptides (orexins A and B. or hypocretins) are
produced exclusively by a well-defined group of neurons in the lateral hypothala-
mus. These unique orexin peptides act directly at axon terminals to stimulate the
release of the major inhibitory neurotransmitter, gamma-amino benzoic acid, and
the major excitatory neurotransmitter, glutamate. Together, these two neurotrans-
mitters are responsible for almost all fast synaptic activity in the hypothalamus.
Chemelli and colleagues (1999) reported the development of a strain of or-
exin knockout mice that developed symptoms virtually identical to narcolepsy in
humans. To further evaluate the role of orexin in stimulating wakefulness, the
antinarcoleptic drug, modafinil (see Chapter 6) or placebo was administered to
normal mice. Modaf~nil strongly activated the orexin neurons in the lateral hy-
pothalamus. No research has yet been reported that examines the effect of caf-
feine or paraxanthine on orexin neurons.
Restoration of Sleep Deprivation-Induced Cognitive
Deficits with Sleep
All of the above-listed decrements in cognitive behavior can best be re-
versed by reconstituting sleep. There is a dose effect for the restorative effects of
sleep duration on cognitive performance (Bonnet, 1999; Bonnet and Arand,
1994b; Bonnet et al., 1995~. Any amount of sleep from as little as a 15-minute
nap can restore some degree of function, although the longer the sleep episode,
the greater the amount of cognitive function restored (Bonnet et al., 19954. Since
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42
CAFFEINE FOR MENTAL TASK PERFORMANCE
the drive for sleep is governed by both a homeostatic and a circadian drive,
which are interactive (Wyatt, 1999), these factors must be taken into considera-
tion in determining the timing of naps and their effectiveness in reconstituting
mental functioning. Naps are effective both prior to (prophylactic naps) and
during (restorative naps) a period of sleep deprivation (Bonnet, 1999; Bonnet
end Arand, 1994a;Bonnetetal., 1995~.
However, in an earlier, well-designed study, Dinges et al. (1987) examined
the effects of temporal placement of naps for alertness during a 56-hour period
of sleep deprivation. A 2-hour nap was preceded by either 6, 18, 30, 42, or 54
hours of wakefulness. Naps were placed 12 hours apart near the circadian peak
or circadian trough. Performance was measured by a visual reaction time test,
and mood was assessed using the Stanford Sleepiness Scale (SSS). Results indi-
cated that a nap at any time during the period of sleep deprivation improved
reaction time performance but not SSS ratings. The earlier naps (6 and 18 hours
into the wakefulness period) yielded better, and longer-lasting reaction time
performance improvements which could be detected more than 24 hours after
the nap, despite the fact that these naps were comprised of lighter sleep than
later naps. Bonnet (1999) also found that quality of sleep differs between pro-
phylactic naps and naps taken during sleep deprivation. Prophylactic naps are
associated with longer sleep latencies and less deep sleep than post-deprivation
recovery sleep. Dinges et al. (1987) also found circadian placement of naps had
no effect on any parameter measured, and concluded that napping prior to a
night of sleep loss is more important in meeting subsequent performance de-
mands than is circadian placement of the nap. Napping appears to prevent
sleepiness more readily than it permits recovery from sleepiness. In addition, a
negative side effect of sleep during a period of sleep deprivation (restorative
sleep) is sleep inertia, a short period of mental confusion upon awakening from
such naps that can last as long as 30 minutes (Dinges, 1989; Stamph, 1989~.
Restoration of Sleep Deprivation-Induced Cognitive
Deficits with Caffeine
When sleep is not an option, caffeine can help to alleviate decrements in
cognitive functioning resulting from shift work (Walsh et al., 1990, 1995), per-
formance during circadian troughs (Gander et al., 1998; Reyner and Home,
2000), restricted or disrupted sleep (Belland and Bissell, 1994; Rosenthal et al.,
1991), and complete sleep deprivation (Bonnet, 1999; Jarvis, 1993; Johnson,
1999; Kautz, 1999; Lieberman, 1999; Loristet al., 1994a,b; Smith end Rubin,
1999~. The effectiveness of caffeine in reversing sleep deprivation-induced dec-
rements in performance varies among subjects, and its ability to restore mental
performance is influenced by a number of factors. These include prior caffeine
exposure, dosage schedule, formulation of caffeine, metabolic factors, concurrent
drug use, degree of sleep deprivation, and time of day of dose administration
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EFFICACY OF CAFFEINE
43
(Kaplan et al., 1997; Kuznicki and Turner, 1986; Linde, 1995; Lorist et al.,
1994a,b). From the limited data available, gender does not appear to play a role in
the effects of caffeine on mental abilities. However, this variable and other po-
tential factors, such as P450 enzyme polymorphism, age, body weight, stress
hormonal and other endocrine responses, concurrent illness, and drug interactions
(Kam~mori et al., 1999), which might potentially contribute to intra- or intersub-
ject variability to the effects of caffeine, should be assessed further.
In sleep-deprived subjects, judicious use of caffeine can restore alertness,
performance on mental tasks, and positive mood states. For example, Smith and
Rubin (1999) found that caffeine had a similar profile to amphetamine and
phentermine in that it reversed the sleep deprivation-induced increased response
time and number of errors on a visual vigilance task, as well as the sleep depri-
vation-induced decrements in a running memory test. Similarly, Bonnet and
Arand (1994b) observed that caffeine increased alertness and performance on a
visual vigilance task, mental arithmetic tests, and logical reasoning in sleep-
deprived subjects. A number of researchers have shown that caffeine is also
effective in delaying sleep onset in sleep-deprived subjects (Bonnet, 1999;
Kautz, 1999; Penetar, 1999; Smith, 1999~. With respect to mood, caffeine ad-
ministration in sleep-deprived subjects decreased reports of confusion and fa-
tigue and increased reports of vigor, but had no effect on reports of tension,
anger, and depression using the POMS (Kautz, 1999~. Using visual analog
scales, caffeine intake led to reports of decreased sleepiness and increased alert-
ness, ability to concentrate, confidence, talkativeness, energy levels, anxiety,
jitteriness, and nervousness (Kautz, 1999~. One study suggested that some of the
effects of caffeine were associated with increased measures of hypothalamic-
pituitary-adrenal axis activity (plasma cortisol levels). However, further studies
utilizing more extensive sampling are needed to confirm this effect.
Research suggests that doses of caffeine between 150 and 600 mg are ef-
fective in alleviating sleep deprivation-induced decrements in cognitive per-
formance (Kelley et al., 1996; Penetar et al., 1993~. Immediately following ad-
ministration, doses in the range of 150 mg were just as effective as 300 or 600
mg in improving mental function in sleep-deprived subjects. However, the lower
dose (150 ma) did not sustain performance on complex mental operations for as
long as the higher doses (300 or 600 ma) (Kautz, 1999~. Penetar et al. (1993)
administered caffeine at levels of 0, 150, 300, and 600 mg following 49 hours of
sleep deprivation and found a dose-related improvement in both subjective and
objective measures of alertness and improvements in mood. Kelley et al. (1996)
evaluated repeated doses of caffeine during 64 hours of sleep deprivation and
measured effects on recovery sleep. Treatments were placebo, 300 mg of caf-
feine every 6 hours, or 400 mg of caffeine every 24 hours starting the evening of
the first day of sleep deprivation. Subjects given the 300 mg every 6 hours de-
veloped a steady-state concentration of salivary caffeine by the third dose, while
those receiving the 400 mg every 24 hours had salivary caffeine concentrations
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44
CAFFEINE FOR MENTAL TASK PENANCE
that peaked and then declined to near placebo level by 18 hours after admini-
stration. Caffeine had no effect on recovery sleep with respect to sleep latency,
total sleep time, or rapid eye movement sleep. There was actually a nonsignifi-
cant increase in slow wave sleep with caffeine compared to placebo.
In comparison to 20 mg of amphetamine however, caffeine's effects are
modest. Newhouse et al. (1989) found that 20 mg of amphetamine effectively
restored alertness to almost 100 percent of rested values for 2 hours and re-
mained significantly better than placebo for 7 hours after administration. In the
Penetar et al. (1993) study caffeine restored alertness to approximately 50 per-
cent of that seen in the rested condition with effects declining after 4.5 hours,
although subjective measures of sleepiness following caffeine administration
were restored to rested levels for 2 to 12 hours.
Restoration of Sleep Deprivation-Induced Cognitive
Deficits with a Combination of Caffeine and Naps
Bonnet and Arand (1994a) compared the effectiveness of a 4-hour prophy-
lactic nap alone to a 4-hour prophylactic nap followed by 200 mg of caffeine
during the sleep deprivation period. Results showed that subjects given a combi-
nation of a 4-hour prophylactic nap prior to 24 hours of sleep deprivation and
200 mg of caffeine administered at 0130 and 0730 (normal circadian trough)
during the sleep deprivation period maintained alertness and performance at
levels equal to or better than those demonstrated prior to sleep deprivation, and
was significantly better than the 4-hour prophylactic nap alone. In a subsequent
study, Bonnet et al. (1995) evaluated differing lengths of prophylactic naps and
differing doses of caffeine on performance during sustained operations and
found that an 8-hour nap prior to the period of sleep deprivation was most effec-
tive in maintaining performance during the first 24 hours without sleep, and that
repeated doses of caffeine at 150 or 300 mg every 6 hours were more effective
than a single dose of 400 ma. However, neither nap nor caffeine conditions
could maintain performance near rested levels beyond 24 hours.
SUMMARY
Caffeine can significantly improve physical performance of an endurance
nature. It is unclear at this time whether this is a result of increased production
of free fatty acids to spare glycogen or an increase in release of endorphins that
permits athletes to exercise longer by altering pain perception. Caffeine may be
particularly beneficial in enhancing performance at high altitudes, with or with-
out acclimation. The role of caffeine-carbohydrate combinations in enhancing
physical performance still needs to be clarified.
Evidence is presented that caffeine can enhance certain types of cognitive
performance, most notably vigilance and reaction times, in rested individuals
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EFFICA CY OF CAFFEINE
45
regardless of whether or not they are regular caffeine users. The response to
caffeine in caffeine users has been shown to be over and above any alleviation
of withdrawal symptoms.
Sleep is the most effective means of reconstituting the decrements in cogni-
tive functioning brought on by sleep deprivation. Thus, in situations where it is
feasible, sleep should be promoted. When naps are not an option, caffeine alone
could be used to partially alleviate sleep deprivation-induced impairments in
cognitive behavior. Combining naps with judicious caffeine use may be the best
remedy for sleep deprivation-induced decrements in cognitive function in mili-
tary situations where adequate sleep cannot be obtained.
The doses of caffeine most likely to be effective without causing undesir-
able mood effects are within the range of 100 to 600 ma.
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CAFFEINE FOR MENTAL TASK PERFORMANCE
containing beverages are consumed regularly. Withdrawal symptoms often occur with the abrupt
removal of caffeine from the diet. The frequency of occurrence of withdrawal, as reported in
survey studies and clinical trials, varies anywhere from 4 to 100 percent (Goldstein et al., 1965;
Griff~ths and Woodson, 1988; Griff~ths et al., 1986; Naismith et al., 1970; Robertson et al., 1981;
Weber et al., 1993~. The symptoms of cessation, when they do occur, are not long-lasting.
The signs and symptoms of withdrawal vary widely and can range from mild to severe,
following withdrawal from both low and high doses of caffeine (Silverman et al., 1992~. These
include headaches, drowsiness, irritability, fatigue, low vigor, and flu-like symptoms including
myalgia, nausea, and vomiting.
Caffeine acts as a vasoconstrictor of the cerebral arteries, reducing regional blood flow
(Cameron et al., 1990; Mathew et al., 1983), including blood flow velocity in the medullar-
cerebral artery (Perod et al., 2000~. Caffeine withdrawal is associated with electroencephalogram
(EEG) changes (Reeves et al., 1995) and also causes changes in cerebral blood flow leading to
vasodilation in high caffeine users that is thought to be associated with a throbbing, vascular-
type headache, one of the most commonly observed caffeine withdrawal symptoms (Couturier et
al., 1997; Lader, 1999; Mathew and Wilson, 1985~.
This withdrawal phenomenon could lead to decrements in performance during military
operations and thus should be avoided. Consuming low doses of caffeine (25-50 ma) or slowly
tapering the dose of caffeine can prevent withdrawal symptoms (Griff~ths, 19 ).
SUMMARY
Caffeine is approved as a food additive with provisional status by the FDA, thus indicating
that the agency concludes there is no evidence of a human health hazard arising from
consumption of caffeine added to foods and cola beverages. However, controversy continues
with respect to caffeine's role in cardiovascular disease, negative reproductive outcomes,
physical dependency and withdrawal, and excessive intake. The preponderance of evidence
indicates that the use of caffeine by the military would not place personnel at increased risk of
cardiovascular disease. Evidence on the risk of large doses of caffeine for individuals who are
hypertensive or borderline hypertensive is inconclusive. For women there may be a small
increase in risk of spontaneous abortion in the first trimester of pregnancy. The effects of
caffeine on calcium metabolism may be of some concern only for those with very low calcium
intakes (less than 50 percent of the current recommended intake). Caffeine can significantly
increase 24 hr urine output, and may or may not alter total body water. Therefore, if caffeine
supplements are used, emphasis should be placed on adequate fluid consumption particularly in
hot or high altitude environments.
High doses of caffeine can have a negative effect on mood and cognitive performance, and
thus the maximum content of caffeine in the delivery form of choice should not exceed 600 ma.
In addition, caffeine potentiates the effects of physical, physiological, and psychological stress.
Military personnel who are habitual caffeine consumers should not be denied access to caffeine
in order to maximize effects of a caffeine supplement.
Representative terms from entire chapter:
physical performance
