INTRODUCTION

The demands and pace of continuous military operations produce sleep fragmentation and varying degrees of sleep deprivation in soldiers. The observable effects of this sleep disruption include decreased alertness, slowed thinking, lapses in attention, decreased motivation, and a performance phenomenon called the speed-accuracy-tradeoff. Several studies have documented performance and mood changes during periods of sleep deprivation (Babkoff et al., 1989a,b; Mikulincer et al., 1989; Thorne et al., 1983). There is a decline in the performance of accuracy tasks involving attention, reasoning abilities, and reaction time. Alertness decreases, and there are changes in self-reported fatigue (increases) and vigor (decreases). Sustaining optimum soldier performance relates to the prevention or amelioration of these changes. Three categories of solutions include the following: (1) Doctrinal solutions involve the overtraining of soldiers to perform their tasks with a minimum of cognitive effort; ensuring that soldiers are cross-trained so that crew members can substitute for each other when necessary; developing and adhering to appropriate work-rest cycles, including rotating crews as the mission permits; developing efficient leadership tactics so that unnecessary demands are not placed on subordinates; and modifying equipment and systems so that the likelihood of making errors is as small as possible. (2) Behavioral solutions make sure that soldiers sleep as much as they can, whenever they can (sleep discipline), while paying attention to where and how they sleep (sleep hygiene), that is, in as comfortable a position as possible, away from the noise and bustle of other soldiers and equipment. (3) Pharmacological solutions may be warranted in special circumstances, when adherence to doctrinal and behavioral solutions is not possible or breaks down. This last category of solutions for preventing or ameliorating sleep deprivation effects is the topic of the research reported in this chapter.

The characteristics of stimulant drugs useful in specific military situations are not only effectiveness but low therapeutic toxicity and low abuse potential, d-Amphetamine was tested for its ability to reverse changes in mood, alertness, and cognitive performance after an extended period of sleep deprivation (Newhouse et al., 1989). Although effective, its restricted legal status and the psychological side effects associated with long-term use, coupled with its abuse potential, almost certainly prohibit large-scale use. Caffeine is a universally available, legal, and socially accepted and used stimulant with low toxicity and low abuse potential. It is believed to reverse the performance and mood effects seen during sleep deprivation, although it has not been tested systematically.

Caffeine has a long history of use and can be found in many common foods, drinks, and medications. Although caffeine has been the subject of pharmacological studies for several decades, the mechanism of action of its effects on the central nervous system have only recently been defined as a blockade of adenosine receptors (Choi et al., 1988; Fredholm, 1985; Snyder, 1984). Extensive reviews of caffeine (Dews, 1984; Weiss and Laties, 1962) conclude that its stimulant properties are weak in comparison with those of other drugs (e.g., amphetamine) and that its effects are modest, making detection of these effects difficult and generalizations cumbersome. Dews (1984), however, states that the following three effects are clear: (1) it has the tendency to postpone sleep; (2) it reduces the degradation of performance because of fatigue and boredom; and (3) it decreases hand steadiness. The interpretation distilled from these and other reviews is that caffeine's effects are significant primarily when performance of repetitive, nonintellectual tasks is partially degraded. What is lacking in the literature and of importance to military operations is a systematic study of caffeine's effects on sleep-deprived individuals and the assessment of caffeine's effectiveness in reversing the changes caused by sleep deprivation.

EFFECTS OF CAFFEINE ON PERFORMANCE

A common method of assessing the effects of stimulant drugs is to measure individuals' reaction times on laboratory tasks. Older reviews and several recent articles failed to find that caffeine has significant effects on the reaction times of various tasks (Bruce et al., 1986; Kuznicki and Turner, 1986; Rapoport et al., 1981; Swift and Tiplady, 1988). Recently, however, caffeine has been found to significantly decrease reaction times in auditory and visual choice tasks when it was used at doses of as little as 32 mg and as great as 600 mg (Jacobson and Edgley, 1987; Lieberman et al., 1987a,b; Roache and Griffiths, 1987). Other cognitive and psychomotor skills measured by the digit-symbol substitution task, serial subtraction of numbers, addition, symbol cancellation, card sorting, signal detection, symbol copying, and number cancellation have not been found to be affected by caffeine (Bruce et al., 1986; Childs, 1978; Ghoneim et al., 1986; Lieberman et al., 1987b; Loke et al., 1985; Roache and Griffiths, 1987; Swift and Tiplady, 1988), although Battig et al. (1984) report that 300 mg of caffeine had a positive effect on a letter cancellation test.

EFFECTS OF CAFFEINE ON MOOD AND ALERTNESS

Several questionnaires and methods have been used to assess caffeine's effects on mood. Studies have shown that doses of 200 to 250 mg of caffeine elevate mood (Lieberman et al., 1987b; Swift and Tiplady, 1988) and that these effects can last for up to 3 h. Higher doses (600 mg) can produce increases in subjects self-ratings of tension or anxiety and increases in caffeine-related physical symptoms (Roache and Griffiths, 1987). Caffeine significantly affects measures of alertness and sleepiness. Doses of 100 mg and more postpone the onset of sleep (Dews, 1982; Goldstein et al., 1965), and a dose of approximately 300 mg significantly improves daytime alertness in both partially sleep-deprived and fully rested individuals, as measured by the multiple sleep latency test (Lumley et al., 1987). Walsh et al. (1990) report that 4 mg of caffeine per kg of body weight (approximately 300 mg) significantly increases latency to sleep onset at test periods throughout the night (0100 to 0500 h). This effect was seen in light and moderate caffeine users. Multiple sleep latency test results by Rosenthal et al., (1991) showed that caffeine at doses of 75 and 150 mg increases alertness whether an individual is fully rested or partially sleep deprived. Zwyghuizen-Doorenbos et al. (1990) showed that 250 mg of caffeine improved daytime alertness for at least 3 h in moderately sleepy subjects.

PHYSIOLOGICAL EFFECTS OF CAFFEINE

The literature supports the fact that caffeine has low toxicity and produces no serious physiological side effects in adults (Rall, 1985; Stavric, 1988). Caffeine's physiological effects are dependent on whether the subject is caffeine-naive or a regular user. In caffeine-naive subjects, a 250-mg oral dose increased the systolic blood pressure by 11 mm Hg (Robertson and Curatolo, 1984). The heart rate declined during the first hour after drug administration and then increased above the baseline during the second hour. Regular users who were deprived of caffeine showed a significant increase in their systolic blood pressure (4 mm Hg), whereas regular users who were not deprived of caffeine showed no significant increases. Other researchers have found no significant changes in blood pressure or heart rate even after a 500-mg oral dose (Bruce et al., 1986; Myers 1988). Newcombe et al. (1988) showed that doses of 300 to 350 mg do not affect the prevailing cardiac rhythm or rate and do not cause clinically significant ventricular or supraventricular dysrhythmias. Specific studies concerning the cardiovascular effects of caffeine at doses above 500 mg are lacking. In several studies, however, higher doses (up to 800 mg) were administered in other contexts (Chait and Griffiths, 1983; Griffiths and Woodson, 1988). Chait and Griffiths (1983) reported that one subject experienced shakiness and an upset stomach after receiving 200 mg of caffeine, and higher doses were not tested in that subject. All other subjects tolerated doses up to 800 mg well. Other clinically relevant physiological effects include the relaxation of smooth muscles (especially the bronchii) and diuresis. Respiration rate is increased by 250-mg doses in caffeine-naive users (Curatolo and Robertson, 1983). Caffeine has the ability to increase metabolic rate, but its effect on body temperature in humans has not been reported in the literature.

In summary, studies indicate that caffeine can have significant effects on mood and performance, even at relatively low doses, in non-sleep-deprived individuals and has effects on alertness in moderately sleep-deprived individuals. The following section reports the effectiveness of caffeine in reversing the alterations seen in performance, mood, and alertness following a prolonged period of sleep deprivation.

MATERIALS AND METHODS

RESULTS

Performance Tests

For each of the tasks, three measures of performance were analyzed: accuracy (percent correct), speed (responses per unit of time), and throughput (number of correct responses per unit of time). The throughput measure takes both accuracy and speed of performance into account and was subjected to statistical testing. Significant effects of caffeine were observed on the throughput measure for the choice reaction time, serial addition/subtraction, and logical reasoning tasks (Figure 20–1 and Table 20–1).

FIGURE 20–1

Mean throughput measures for three performance tasks: choice reaction time (Choice RT), serial addition/subtraction, and logical reasoning. Predrug means include data for all subjects; there were no differences between the groups prior to drug administration. (more...)

TABLE 20–1

Performance, Mood, and Physiology Analysis of Variance Summary.

Performance on the choice reaction time task for 8 h after drug administration in subjects who received the 600-mg dose was significantly different from that in subjects who received the placebo. The 150-mg dose improved performance for 4 h. For subjects receiving the 300-mg dose, performance was not significantly different from that for subjects receiving the placebo at any point following administration. For the serial addition/subtraction task, all doses of caffeine significantly improved performance for 3 h. For subjects receiving the 600-mg dose, performance remained significantly better than that for subjects receiving placebo for 10 h after drug administration, with no significant differences observed among the dose groups at the final 12-h testing period. Performance on the logical reasoning task by subjects receiving the two highest doses of caffeine was significantly better than by subjects receiving placebo for the entire 12-h period. In addition, caffeine restored performance to the levels obtained after rest during this interval. Performance after administration of the 150-mg dose was significantly different from that after administration of placebo for 6 h after drug administration.

Alertness Measures

Multiple Sleep Latency Tests

For the rested condition (day 1), mean sleep latency periods were between 16.3 and 19.9 min. Sleep deprivation significantly [F(11,506)=202.39, P<0.001] decreased latency periods to a range of 5.6 to 7 min on day 2. Significant dose [F(3,46)=5.18, P<0.005], time [F(7,322)=5.61, P<0.001] and time×dose interactions [F(21,322)=1.99, P<0.05] were observed following caffeine administration. Latency periods for the highest dose (600 mg/70 kg) group increased significantly above placebo latency periods for the placebo group (10.2 min versus 5.0 min) (Figure 20–2) and remained at this level for 4.5 h after drug administration. The dose of 300 mg/70 kg appeared to have effects intermediate between those of the highest dose tested and the placebo; however, these effects were not significantly different from those for the other dose groups.

FIGURE 20–2

Latency to stage 2 sleep following caffeine administration. *, results for the 600-mg dose group were significantly different from those for the placebo group (P<0.05).

Stanford Sleepiness Scale

Average values of the Stanford Sleepiness Scale increased gradually from 1.6 at 0900 h on day 1 (subjects rested) to a maximum average of 4.8 at 0600 h on the morning of day 3, indicating a significant effect of sleep deprivation (Table 20–2). Caffeine's effects were significant for 2 h after drug administration and were not dose-related (i.e., all doses were equally effective).

TABLE 20–2

Stanford Sleepiness Scale Scores.

Vital Signs

Diastolic blood pressure and oral temperature were significantly affected by caffeine administration (Table 20–1 and Figure 20–3). At 1 h after admini stration, both the 300- and the 600-mg doses significantly increased diastolic blood pressure in comparison with the placebo; there were no significant differences at other time points. The 600-mg dose of caffeine significantly increased oral temperature in comparison with placebo at several measurement times after administration: 2, 2.5, 3, 4, 6, 8, and 12 h. Neither systolic blood pressure nor pulse was significantly affected.

FIGURE 20–3

Time course of caffeine effects on four vital signs. Caffeine was observed to have significant effects on diastolic blood pressure (at 1 h) and oral temperature from 2 to 12 h after drug administration. See text for details.

DISCUSSION

The study described here indicates that caffeine is effective in reversing the performance degradations and the alterations in mood and alertness produced by periods of prolonged sleep deprivation. The results indicate that these beneficial effects can be long-lasting and not at the expense of serious mood or physiological side effects.

Sleep deprivation degrades cognitive performance. The effects of caffeine on performance in non-sleep-deprived volunteers have been well documented, even at the low dose levels commonly found in food and drink products (see Lieberman [1992] for a review). The study described here extends the usefulness of caffeine, showing that large doses (up to 600 mg) are effective in improving a variety of cognitive performances in sleep-deprived individuals, and outlines the time course of its effects in these individuals. The tasks used in the present study were chosen to sample a variety of cognitive abilities with varying mental demands. Choice reaction time requires little thinking but does require great accuracy and speed. The serial addition/subtraction task is a machine-paced task but has a greater mental component, whereas the logical reasoning task is self-paced and requires the greatest amount of thought for accurate responses. Caffeine produced improved performances of all three tasks, with performance returning to those of rested subjects for up to 12 h after caffeine administration. Caffeine was not observed to affect recall or code substitution tasks. In toto, these results are in concert with those presented previously (Lieberman, 1992; Roache and Griffiths, 1987) and document for the first time the relatively long-lasting effects of this drug on cognitive performance. The study described here shows that caffeine compares favorably with amphetamine in reversing the effects of sleep deprivation on cognitive performance. Using an identical sleep deprivation paradigm, Newhouse et al. (1989) showed that 20 mg of amphetamine is required to produce sustained performance improvements.

Sleep deprivation also alters mood and degrades alertness. The present study documents the fact that caffeine can have significant beneficial effects in reversing these mood changes; sleepiness and confusion declined, whereas increases in energy and confidence levels were reported. Although there were increased ratings of anxiety and jitteriness or nervousness, these effects were not severe and did not elicit complaints from the subjects. Depending on the measure, alertness, which was severely degraded by 49 h of sleep deprivation, was improved for 2 to 4.5 h, whereas self-ratings of sleepiness in groups treated with caffeine remained significantly lower than those in the placebo group for 12 h. In this regard, caffeine was not as effective as amphetamine. The alertness of amphetamine treated subjects (20 mg), as measured by sleep latency tests, was nearly restored to the levels of rested subjects for 7 h (Newhouse et al., 1989). Caffeine's effects on alertness are therefore less potent and shorter acting than amphetamine's.

Caffeine's effects on physiological measures are important for assessing its usefulness as a stimulant. The study described here shows that relatively high doses of caffeine are well tolerated by sleep-deprived individuals and that its effects are similar to those found in other studies in non-sleep-deprived subjects given lower doses than those used in the present study (Myers, 1988; Newcombe et al., 1988). Additionally, there were no changes in self-reports of other side-effects (heart pounding, headache, sweatiness, upset stomach). Of note was caffeine's observed effect on oral temperature. Oral temperature normally rises during the day, from a low in the early morning hours to a peak in the early evening hours. The subjects in the present study showed this typical response. Caffeine increased temperatures above the normal rise throughout the observation period, again revealing an important aspect of its effects and duration of action. The significance of this effect awaits further experimentation, although this type of effect has been observed previously with another stimulant, d-amphetamine (Newhouse et al., 1989).

RECOMMENDATIONS

• The results of the present study would seem to indicate that caffeine can be an ideal stimulant for use during military operations when performance declines secondary to sleep disruption and sleep fragmentation. Doses of 600 mg are needed to reverse severely degraded performance as a result of long periods of sleep deprivation. Presumably, lower doses (200–400 mg) would be effective in ameliorating the changes caused by shorter periods of deprivation.
• Given the legal and social acceptance of caffeine, and its low abuse potential, caffeine tablets (200 mg/tablet) should be included in food rations.
• Use of caffeine should be restricted to special situations when sleep has been unusually disrupted and for the benefit of temporarily (10–12 h) restoring alertness and sustaining performance during critical periods of military operations.
• Finally, although caffeine can temporarily sustain performance during continuous operations, it should be emphasized that no drug can substitute for adequate sleep.

ACKNOWLEDGMENTS

The authors thank the staff of the Behavioral Biology, in particular Sharon Balwinski and Kevin Peyton, for assistance in the conduct of the experiment described here. Investigators adhered to AR 70–25 and USAMRDC Reg 70–25 on the use of volunteers in research. Use of trade names does not constitute endorsement of product. The views of the authors do not purport to reflect the position of the Department of the Army or the Department of Defense.

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DISCUSSION

HARRIS LIEBERMAN: We have some unpublished data from a couple of studies in which we did find significant effects of caffeine on mood swing. We did not use doses as low as 32 milligrams but used doses of 64 and 128 milligrams of caffeine. Effects on performance by doses lower than those are hard to detect, but over the long run, over a series of studies, my feeling is that there really are effects with low dosages, and those are the doses that we typically take in our background.

JOEL GRINKER: I was just curious whether in any of the caffeine studies or in any of the other supplement studies age has been looked at systematically as a factor. I have two thoughts, one, that in fact it might potentiate the ability of older individuals or that in fact it has less effectiveness, and I wonder if you have any comments.

DAVID PENETAR: I have here one study that related to age. Typically, these studies were done, with young, healthy males.

HARRIS LIEBERMAN: We did look at the age parameter in one of our caffeine studies, but we did not see any significant differences as a function of age or gender.

JOHN VANDERVEEN: I was curious as to the uniformity of the synthesis associated with sleep. Do you find much variation that would indicate that shortness of sleep time versus onset of sleep, etc. Are they uniform in your subjects or are they highly individualistic?

DAVID PENETAR: In terms of a rested individual?

JOHN VANDERVEEN: Yes.

DAVID PENETAR: What we do is we bring them into the study the night before and give them 9 hours of time in bed before we start the study, so at that time they are all pretty consistent in the amount of sleep that they have had.

JOHN VANDERVEEN: No, I meant the effects of caffeine on their subsequent sleep. Do you find a uniform effect in terms of delay of sleep or shortness of length of sleep, etc?

DAVID PENETAR: We did not specifically look at that because by the time they went to bed it was over 12 hours after they had received caffeine.

WILLIAM WATERS: A couple of questions. One pertaining to the onset of parameters. Did you have a look at whether or not you have any data or whether or not sleep can be induced prior to that?

DAVID PENETAR: No, I do not have any data on that. I am not sure that is reported.

WILLIAM WATERS: It could be that what you had was a referral of something that might allow it to occur. The other thing was, under the influence of caffeine, did you notice any change in the number, the length, stage one, and arousals?

DAVID PENETAR: Again, by the time our subjects went to bed, it was over 12 hours after they had received the caffeine, and we did not see any changes; there were no differences between the groups. We did monitor them. We recorded them through their sleep, and we saw no differences in sleep architecture, time of sleep, time to bed, or sleep efficiency; we saw no differences for 12 hours.

JOHANNA DWYER: I worked with a neurologist who was interested by some observations years ago, when they did a lot more electroconvulsive shock than they do now. Apparently, they used to prime the patients with caffeine, and by doing this, they could use a lower level of shock and still get the same effect. The reason I bring it up here is not because I hope anyone here is heavily into this, but rather, are there other changes in the electroencephalograms in terms of caffeine's effects that may be in addition to what we have been talking about?

DAVID PENETAR: No, I do not know.

ALLISON YATES: Just one thing. I noticed in some of the graphs that it almost looked as if at 600 milligrams the subjects might have had even a little bit better performance than they had initially in their first 24 hours. This result is important in considering enhancement of performance with normal subjects.

DAVID PENETAR: Harris, your subjects could not sleep at night.

HARRIS LIEBERMAN: Yes, two slides that you showed with my studies, the vigilance and reaction times, were for subjects who had stayed up all night the night before and who were back in the morning after the administration. Their performances were similar to those with placebos under the same conditions. I consider that to be above normal, although since caffeine is such a common component of the diet, it is hard to untangle it all.

ALLISON YATES: That is why I was wondering yesterday what the baseline levels were.

HARRIS LIEBERMAN: We typically include that as a parameter in our studies and look to see whether there are differences between moderate, low, and heavy caffeine users in their responsiveness, and in the low and moderate range there is not much difference. When you get to the real high users, you see big differences in responsiveness. That depends on the timing of administration, whether they are in a deprivation stage, or whether they are already on a lot caffeine.

ROBERT NESHEIM: Were you defining it high?

HARRIS LIEBERMAN: Average caffeine consumption is about 200 milligrams per day, which is maybe three cups of not very strong coffee. I define high for the purpose of categorizing subjects as above 400 or 500 milligrams per day.

DAVID SCHNAKENBERG: Just a couple of observations. We used to always think that members of the Army must be heavy coffee drinkers because you get that perception, but looking out in field studies where soldiers are eating rations, we found out that even though you gave a meal ready-to-eat, 90 percent of the coffee packets were returned unused. The rest of the 10 percent probably went mostly to the senior sergeants, who had a chance to stay by the talking place and make some coffee for themselves. So young soldiers in the field today are not heavy coffee drinkers. I am sure they drink plenty of caffeine if they have carbonated beverages. But most of the time carbonated beverages are not available to them in the field, although maybe in Desert Storm cans of Coke manged to get inside of the tanks anyway.

My question is, has anybody done sleep studies on evaluating caffeine using the vehicle of delivering the caffeine in the form of a cola or in the form of a coffee beverage itself?

DAVID PENETAR: A number of studies look at coffee drinking when they give caffeine. In fact, in some of the studies reported here, they took decaffeinated coffee and added caffeine to it, and the subjects drank it that way. In other studies it was either caffeine pills or caffeine powder dissolved in some drink.

DAVID SCHNAKENBERG: Can subjects get a comparable effect with the caffeinated coffee versus decaffeinated coffee? For instance, I am sure your subjects knew when they were receiving a placebo.

DAVID PENETAR: Ours was powdered caffeine dissolved in a lemon juice drink, and the lemon juice drink was very bitter. As you know, caffeine powders are very bitter, so they could not tell what they were drinking other than lemon juice drink. If they talked among themselves, they just said “oh, it is not very good, it was bitter.”

WILLIAM BEISEL: So many of the emergency rations and so on seem to be candy bars with chocolate flavoring. How much of that is caffeine?

DAVID PENETAR: Milk chocolate has about 7 milligrams per ounce, whereas bakery chocolate or unsweetened chocolate has about 35 milligrams per ounce. They figure that, for example, a Hershey's candy bar has 25 to 35 milligrams per ounce, so it is not a lot, and it is less than most sodas.

Footnotes

1

David M.Penetar, Walter Reed Army Institute of Research, Washington, D.C. 20307–5100

1

Subjects were paid for their participation. The investigators adhered to AR 70–25 (U.S. Department of the Army, 1989) and U.S. Army Medical Research and Development Command Reg 70–25 (1989), on the use of volunteers in research.