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Executive Summary The goal of any employer, regardless of the field of endeavor, is optimal job performance without compromising the health and well-being of the worker. Intermittent or prolonged physiological and psychological stressors that employ- ees bring to the workplace have an impact not only on their own performance but also on those with whom they work and interact. These stressors are com- pounded by the physical and mental stressors of the job itself. Military personnel in combat settings endure highly unpredictable timing and types of stressors, both personal and job-related, as well as situations that require continuing vigi- lance for extended periods of time. Changes in military operations over the last 50 years have required contin- ued assessment and adoption of technologies that will sustain or enhance physi- cal and cognitive performance of the individual service member. This urgency in maintaining and enhancing performance is fostered by increased reliance on the individual's cognitive skills in the operation and maintenance of complex mili- tary equipment in an increasing variety of environmental conditions. Today's military relies heavily on the use of computer-controlled systems that require highly trained and alert individuals. There is also greater reliance on rapid mo- bility to enable deployment at any time to achieve the nation's military objec- tives. The urgency to maintain and enhance performance is driven by personnel reductions and shortfalls in recruitment goals resulting in the need to have the individual perform for longer periods of time with less sleep, shorter transition times, less recovery time between missions, and less reliance on traditional logistical support. 1
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2 CAFFEINE FOR MENTAL TASK PERFORMANCE These scenarios can have severe impacts on the individual's level of fatigue, alertness, response time, mood, judgment, reliability in decision making, and other cognitive skills. Increased likelihood of decrements in cognitive function coincides with greater dependence on the individual's performance, and both have a profound impact on the success or failure of a mission. BACKGROUND At the request of the U.S. Army Medical Research and Materiel Command (USAMRMC) in 1992, the Committee on Military Nutrition Research (CMNR) of the Institute of Medicine's Food and Nutrition Board reviewed the scientific literature, held a workshop, and produced a report on Food Components to En- hance Performance (IOM, 1994~. In that report the CMNR recommended that the military pursue additional research on the mechanisms of effects of caffeine on cognitive performance, mood, and alertness, focusing on maximizing positive effects when performance is already degraded. Specifically, the committee recommended: Caffeine definitely should be considered in developing perform- ance-enhancing rations or ration components. Caffeine is safe as a component of food at doses required to overcome sleep deprivation and has been included in diets in coffee and many soft drinks. Since many soldiers may not normally drink coffee, a mechanism for including caf- feine in another ration component—that can be selectively used when the situation requires—should be evaluated. It appears that doses of 300~00 mg/70 kg person will achieve the desired stimulus in those not habituated to caffeine; additional research needs to be conducted to determine the effects of this level of caffeine in those with higher ha- bitual intakes. (IOM, 1994, p. 50) THE COMMITTEE'S TASK Recent surveys indicate that more than 90 percent of the military population consumes caffeine at some level on a daily basis. Typically, older personnel consume more caffeine than younger ones, and males consume slightly more than females. The majority of caffeine (approximately 70 percent) is consumed as coffee, 23 percent as soda, 5 percent as tea, and slightly less than 2 percent as chocolate, with the remainder coming from medications. The variety of amounts and sources of caffeine consumed confounds the ability to determine risk and to make risk management decisions on the use of caffeine for maintenance and enhancement of cognitive performance in military operations. Thus, the military requested the CMNR's assistance in the decision-making process. The request for this review of caffeine's effects on mental performance and its application to
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EXECUTIVE SUMMARY 3 military operations originated with Army scientists from the U.S. Army Re- search Institute of Environmental Medicine and USAMRMC. In October 1998, a subgroup of the CMNR participated in a series of conference calls with USAMRMC and CMNR staff to identify the key areas that should be reviewed and to solicit suggestions for the names of scientists who were active in the research fields of interest. On February 2-3, 1999, the CMNR convened a workshop in response to a request from Army representatives to provide information on the safety, effi- cacy, and appropriate doses and formulations of caffeine for transition to field application during military operations. The purpose of the workshop was two- fold: first, to evaluate the relevant caffeine research completed since the 1992 CMNR workshop "Food Components to Enhance Performance", particularly research conducted by the military on the ability of caffeine to counteract mental task performance deficits engendered by sleep deprivation, and, second, to re- view military research on the pharmacokinetics and effectiveness of caffeine- supplemented food bars versus caffeinated chewing gum, and assist the Depart- ment of Defense (DOD) in the transition of this research to military application. The USAMRMC provided specific information and questions for the com- mittee's response. These are included in the later section, Response to Military Questions. METHODS One purpose of the study was to organize a workshop to review the scientific data on the efficacy of caffeine in maintaining physical and cognitive perform- ance in military operations, caffeine safety, appropriate formulations for admini- stration during military operations, and to identify any ethical or other considera- tions. Another purpose was to review the effectiveness of caffeine compared to other compounds that have central nervous system-stimulating effects. The research presented in this report addresses these issues. Information from the speaker presentations and the published scientific literature, as well as the deliberations of the CMNR, were used in the preparation of this report.
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4 CAFFEINE FOR MENTAL TASK PENANCE CAFFEINE USE Caffeine (1,3,7-trimethylxanthine) and the related methylxanthines theo- bromine (3,7-dimethylxanthine) and theophylline (1,3-dimethylxanthine) are alkaloid compounds widely distributed in plants throughout the world. More than 60 different plant species containing caffeine have been identified. The primary sources of these compounds are coffee (Canada arabica), kola nuts (Cola acuminata), tea (Thea sinensis), and chocolate (Cocoa bean). Caffeine is the most widely consumed psychoactive or central nervous sys- tem stimulant in the world. In addition to its natural occurrence in some foods, caffeine is used as a food additive and as a drug or a component of many phar- maceutical preparations. When administered in the amounts commonly found in foods, beverages, and drugs, it has measurable effects on certain types of human performance. As a food additive, caffeine is generally considered safe based on a long history of use and on extensive research conducted over more than a century throughout the world. However, despite this long history of use, modern epide- miological techniques have raised concerns about associations between contin- ued use of high levels of caffeine and long-term health. Amounts of caffeine in commonly used beverages and other products vary a great deal (Table S-1) from as low as 2 mg/8 oz of chocolate milk, to as much as 300 mg/6 oz of strong espresso coffee. Caffeine intakes in the United States have been estimated based on the available product usage and food consumption data. Mean per capita caffeine intake for all U.S. adults was approximately 3 mg/kg body weight (BOO) (equivalent to 180-210 mg for a 6~70-kg person). Mean daily intake for adult consumers of caffeine products was 4 mg/kg BW, and for the ninetieth percen- tile of caffeine users, intakes approximated 5-7 mg/kg BW. CAFFEINE METABOLISM Pharmacology Caffeine is rapidly and completely absorbed in humans, with 99 percent be- ing absorbed within 45 minutes of ingestion. Peak plasma concentrations occur between 15 and 120 minutes after oral ingestion, and may be influenced by route of administration, the for of administration, or other components of the diet. Once caffeine is absorbed, it is distributed rapidly throughout body water. How- ever, caffeine is also sufficiently lipophilic to pass through all biological mem- branes and readily crosses the blood-brain barrier. The mean half-life of caffeine in plasma of healthy individuals is about 5 hours, although its half-life may range between 1.5 and 9.5 hours. This wide variation in reported half-life may
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EXECUTIVE SUMMARY TABLE S-1 Caffeine Content of Some Common U.S. Food Products Item Average (mg) Rarlge (mg) Coffee (5-oz cup)a Brewed, drip method 120 9~150 Percolated 90 6~124 Instant 75 3~120 Decaffeinated 3 1-5 Espresso (6-oz cup) 240 18~300 Teas (loose or bags, 5-oz cupja 1-m~nute brew 21 9-33 3-m~nute brew 33 20~6 Tea products Instant (5-oz cup) 20 12-28 Iced (12-oz glass) 29 22-36 Carbonated beverages 24 20~0 Colas and pepper drinks (12 oz) National brands, packaged 42 36~8 National brands, fountain 39 32~8 Store brands, packaged 18 5-29 Citrus drinks (12 oz) National brands, packaged 52 43-56 Store brands, packaged 38 2~52 Chocolate products Cocoa beverage (8 oz) 6 3-32 Chocolate m~lkbeverage(8 oz) 5 2-7 Milk chocolate (1 oz) 6 1-15 Dark chocolate, sem~sweet(1 oz) 20 5-35 Baker's chocolate (1 oz) 35 35 Chocolate-flavored syrup (1 oz) 4 4 a Note these caffeine amounts are based on a 5-oz cup of beverage. Servings today are more likely to be 8 or 12 oz arid caffeine intake should be calculated accordingly. SOURCE: Adapted from FDA (1980a); Grand and Bell (1997~; IFT (19834; Lieberman (1992~. 5 be due to individual variation in excretion rates, or whether the individual smokes (decreases half-life) or uses oral contraceptives (increases half-life). The pharmacological effects of caffeine (similar to those of other methyl- xanthines) include mild stimulation and wakefulness, ability to sustain intellec- tual activity, and decreased reaction times. The fatal acute oral dose of caffeine in humans is estimated to be between 10 and 14 g (15~200 mg/kg). Ingestion of caffeine in doses up to 10 g has caused convulsions and vomiting, with com- plete recovery in 6 hours. Side effects have also been observed in humans at caffeine intakes of 1 g (15 mg/kg), progressing from mild effects including
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6 CAFFEINE FOR MENTAL TASK PERFORMANCE restlessness, nervousness, and irritability, to more serious effects such as delir- ium, emesis, neuromuscular tremors, and convulsions. Physiology Physiological effects of caffeine include cardiovascular, respiratory, renal, and smooth muscle effects, as well as effects on mood, memory, alertness, and physical and cognitive performance. Caffeine's effect on cognitive function appears to be mediated via several mechanisms: the antagonism of adenosine receptors, the inhibition of phosphodiesterases, the release of calcium from intracellular stores, and antagonism of benzodiazepine receptors. Caffeine's action in blocking adenosine receptors and inhibiting phosphodiesterase appears to be the most important mechanism of action with respect to physiological and behavioral effects. RESPONSE TO MILITARY QUESTIONS 1. Efficacy: Does CMNR stand by its earlier recommendation that there are sufficient data to recommend a caffeine product to enhance per- formance? What are the specific indications for use and contraindications for use? Military personnel face many situations in which extended wakefulness may be required including sentry duty, deployment-related activities, air trans- portation during emergencies, radar and sonar monitoring, submarine duty, and combat. As part of their duties in these situations, individuals may have to per- form complex cognitive tasks. The performance of these tasks is compromised during periods of extended wakefulness. Caffeine has been shown to induce a variety of positive effects that have contributed to its extensive use worldwide. Caffeine use has been associated with enhanced physical performance, increased alertness, and a countermeasure to the effects of sleep deprivation. Extensive research has been done on each of these effects. Caffeine use is associated with a reproducible increase in endurance time in physical activities of moderate intensity and long duration with doses of 2-9 mg/kg, in both naive and habituated, trained and untrained test subjects. High- altitude exposure may augment the positive effects of caffeine on endurance performance. Exercise performance is dramatically reduced by altitude expo- sure, and maximal effort may be diminished by as much as 25 percent. Ingestion of caffeine (4 mg/kg) increased the time to exhaustion at 4,300 m, but not at sea level. This effect was present even after 2 weeks of acclimatization. Although there is some debate about whether caffeine enhances cognitive performance or simply restores degraded psychomotor performance in rested
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EXECUTIVE SUMMARY individuals, a number of studies have demonstrated that caffeine enhances cog- nitive performance independent of its ability to reverse symptoms of withdrawal and sleep deprivation. Caffeine enhanced accuracy and reduced reaction time on auditory and visual vigilance tasks in a dose-related manner. Moreover, caffeine significantly increased self-reports of vigor and decreased reports of fatigue, depression, and hostility on the Profile of Moods Scale. 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. Caffeine also increased the number of correct target identifications in both males and females. Conclusions Although there is considerable variation in both the doses tested and sub- jects' responses to the effects of caffeine on cognitive function, overall research shows that caffeine in the range of 100 to 600 mg is effective in increasing the speed of reaction time without affecting accuracy and in improving performance on visual and audio vigilance tasks. A number of studies have also reported improved performance on long-term memory recall, but not short-term word recall. These enhancing effects of caffeine on cognitive performance are most pronounced when functions are impaired or suboptimal (e.g., as a result of sleep deprivation). Furthermore, caffeine in amounts ranging from 200 to 600 mg/d enhances endurance performance in a variety of activities. Limited research has shown caffeine to be especially useful in restoring decrements in physical performance that occur at high altitudes. Food and fluid intake must be monitored carefully when caffeine is used for this purpose, since they are frequently suboptimal in operational situations, especially in extremes of hot and cold environments and at altitude. Recommendations Caffeine in doses of 100-600 mg may be used to maintain cognitive per- formance, particularly in situations of sleep deprivation. Specifically it can be used in maintaining speed of reactions and visual and auditory vigilance, which in military operations could be a life or death situation. A similar dose range (200-600 ma) of caffeine is also effective in enhanc- ing physical endurance and may be especially useful in restoring some of the physical endurance lost at high altitude.
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8 CAFFEINE FOR MENTAL TASK PERFORMANCE 2. Safety: What are the medical risks to individuals associated with ready availability of caffeine, including acute health risks, long-term health risks, potential interaction with other drugs or factors specific to military operations, and potential problems of habituation of use? The effect of caffeine on various aspects of health has been and continues to be an active area of scientific research, in spite of the fact that caffeine has been used by people around the world for more than 1,000 years without apparent ill effects. Extensive research has been done to evaluate the impact of caffeine consumption on the incidence of cardiovascular disease, reproduction and preg- nancy outcomes, fluid homeostasis, and osteoporosis. It has been shown that ingestion of very high doses of caffeine can produce undesirable effects on mental function. Additionally, caffeine use has been associated with physical dependence, which may be reflected in performance decrements during with- drawal under some circumstances. Potential Health Risks Hypertension Results summarized in recent reviews suggest that caffeine-naive individu- als experience a small increase in blood pressure after acute dosing with caf- feine. During chronic administration of caffeine, tolerance appears to develop, and chronic, long-lasting changes in blood pressure are usually not seen in indi- viduals who consume caffeine routinely. A recent critical review of 30 years of research on the blood pressure effects of coffee and caffeine concluded that the acute presser effects of caffeine are well documented, but that at present there is no clear epidemiological evidence that caffeine consumption is causally related to hypertension. One potential risk should be noted, however. A number of studies have demonstrated that caffeine consumption produces a transient elevation in blood pressure and that this occurs regardless of whether or not the individual is a habitual user of caffeine. Thus, high caffeine intake may be an additional risk factor for hypertension at the indi- vidual level due to long-lasting stress or genetic susceptibility to hypertension. Heart Disease In general, controlled clinical attempts to demonstrate effects of caffeine on increasing heart rate or inducing arrhythmia have been unsuccessful. A meta- analysis of 11 prospective, longitudinal cohort studies showed no increased risk of coronary heart disease associated with consumption of up to 6 cups of coffee per day. Thus, increased risk of cardiovascular problems resulting from the use of caffeine supplements by the military would not appear to be of major concern.
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EXECUTIVE SUMMARY Reproduction 9 Caffeine consumption has been suggested as the cause of numerous nega- tive reproductive outcomes, from shortened menstrual cycles to reduced con- ception, delayed implantation, spontaneous abortion, premature birth, low infant birthweight, and congenital malformations. As with most other aspects of caf- feine consumption, there is a paucity of reliable data concerning the effects of caffeine on reproductive processes. Recent reviews of human studies suggest that some of the initial reported associations between caffeine and reduced fertility, teratogenicity, and other fetal and maternal effects in humans may be explained by confounding factors such as associated cigarette smoking, alcohol consumption, reporting inaccura- cies, and other methodological errors. A recent, well-controlled study using serum paraxanthine levels to quantitate caffeine exposure demonstrated that women who had spontaneous abortions also had significantly higher serum paraxanthine. However, the odds ratio for spontaneous abortion was not signifi- cantly increased except in subjects with extremely high paraxanthine levels (> 1,845 ng/rnL). The authors concluded that moderate consumption of caffeine was not likely to increase the risk of spontaneous abortion. Osteoporosis Caffeine consumption has also been proposed as a risk factor for osteoporo- sis. In the large number of studies that have been conducted, there appears to be no consistent trend linking caffeine consumption and negative effects on bone mineral density or incidence of fracture. Early studies also indicated a signifi- cant effect on acute calcium diuresis; however, subsequent work indicated that this acute phase of excretion was accompanied by a later decrease in excretion of calcium in the urine. Later studies found either no significant effect of caf- feine on calcium balance or negative balance only in subjects consuming less than half of the currently recommended intake of calcium. Fluid Homeostasis Caffeine is a diuretic and has been found to increase urinary excretion within 1 hour of treatment. Significant increases have been observed in 3-hour urine output as well as in 24-hour urine output as a result of caffeine consump- tion in amounts of 250 to 642 ma. Currently, data are inconsistent with respect to whether caffeine creates a total body water deficit. The deficit may depend on the amount of caffeine consumed, the individual's history of caffeine use, and the total solute load of any accompanying food or beverage. However, the risk of water deficit may be increased when caffeine is used in situations already known to put personnel at risk of dehydration such as in hot or desert environ- ments (IOM, 1993) or in cold environments (IOM, 1996~.
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10 Behavioral Elects CAFFEINE FOR MENTAL TASK PERFORMANCE One potential risk of high doses of caffeine, which needs further substantia- tion, is a dose-related decrement in mental functioning. A number of researchers have found that high doses of caffeine can adversely affect mental performance. Although a relatively low dose of caffeine (250 ma) produced favorable subjec- tive effects (e.g., elation and pleasantness) and enhanced performance on cogni- tive tasks in healthy volunteers, higher doses (500 ma) led to less favorable subjective reports (e.g., tension, nervousness, anxiety, restlessness) and less improvement in cognitive performance than placebo. Negative effects may be more pronounced in nonusers than in regular users of caffeine. Excessive intake of caffeine (caffeinism) may be mistaken for anxiety disorder. Physical Dependence and Withdrawal The use of caffeine by humans is generally not associated with abuse or ad- diction. Tolerance develops to some of the effects of caffeine when caffeine- containing beverages are consumed regularly. Withdrawal symptoms often occur with the abrupt removal of caffeine from the diet. The frequency of occur- rence of withdrawal varies anywhere from 4 to 100 percent. The symptoms of cessation, when they do occur, are not long-lasting and are generally mild. These include headaches, drowsiness, irritability, fatigue, low vigor, and flu-like symptoms. This withdrawal phenomenon could conceivably lead to decrements in performance during military operations. Caffeine and Stress Among the variables that may contribute to differences in caffeine sensitiv- ~ty are baseline levels of stressor exposure and genetically mediated stress reac- tivity. Stress may include physical stressors (e.g., exercise) physiological stres- sors (e.g., heat stress, infection, sleep deprivation), or psychological stressors. After stressor exposures, stress-responsive neurohormonal and neurotransmitter systems are activated. Caffeine alters the degree of responsiveness of these stress-responsive systems to stressful stimuli. The degree to which responsive- ness is altered varies according to previous caffeine consumption (habitual users versus nonusers). Conclusions The acute presser effects of caffeine are well documented, but at present there is no clear epidemiological evidence that caffeine consumption is causally related to hypertension. However, high caffeine intake may be an additional risk factor for hypertension at the individual level. In borderline-hypertensive men,
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EXECUTIVE SUMMARY 11 the use of caffeine in situations of behavioral stress may elevate blood pressure to a clinically meaningful degree. Since military scenarios in which use of caffeine supplements might be de- sirable would frequently occur when personnel are also under acute mental and/or physical stress, this could be a concern to personnel with family histories of hypertension. Increased risk of cardiovascular problems resulting from the use of caffeine supplements by the military would not appear to be of major concern. Results of studies of the effects of caffeine on reproduction have been very mixed, and many studies showing increased reproductive problems have been confounded with other life-style factors, particularly smoking. The most convinc- ing evidence relates to caffeine and the small increased risk of spontaneous abor- tion. However, since this requires caffeine consumption during the first trimester of pregnancy, it is unlikely to be a major concern for sustained military operations. The preponderance of research on caffeine and osteoporosis has found no effect. Although caffeine can increase calcium diuresis, this is compensated by lower than normal calcium excretion later. The use of caffeine in this case is less of a concern than is low calcium intake. Caffeine may increase risk of dehydration which may be an issue for mili- tary personnel in operational environments where dehydration may already be a concern, such as desert environments, or where thirst mechanisms are inade- quate such as in cold or high-altitude environments. High doses of caffeine (> 600 ma) can cause decrements in cognitive func- tion. Caffeine can also potentiate the effects of stress. Recommendations Use of caffeine under conditions of sustained military operations would not appear to pose any serious, irreversible acute or chronic health risks for military personnel in situations where increased doses might be recommended. Caffeine use in sustained operations in hot or cold environments or at high altitudes may increase the risk of dehydration, so fluid and food intake of per- sonnel should be closely monitored in these situations. Female military personnel should be advised of the potential for a small in- creased risk of spontaneous abortion in the first trimester of pregnancy. 3. Dose and Warning Labels: What dose level should be recom- mended to habituated caffeine users and to nonusers? What warnings should be provided on such a product in the context of ethical, religious, and potential caffeine habituation concerns? The effective dose of caffeine will vary from individual to individual, de- pending on a variety of factors including time of day, usual caffeine intake, and
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12 CAFFEINE FOR MENTAL TASK PENANCE whether the individual is rested or fatigued. Levels of caffeine in the range of 100 to 400 mg have consistently demonstrated reductions in reaction time and en- hanced performance on vigilance tests without adverse effects. In some studies with rested subjects, levels of caffeine in excess of 500 mg in a single dose have shown negative effects on mood and behavior (this may be more likely in those who do not normally consume caffeine). The levels of caffeine that have consis- tently enhanced physical endurance in humans range from about 200 to 600 ma. In sleep-deprived individuals, similar to those engaging in sustained opera- tions, a range of 100 to 600 mg of caffeine appears to improve performance (e.g., vigilance, mood, higher cognitive functions) with few acute adverse be- havioral effects. Important ethical considerations for requiring the use of caffeine during sustained operations include: providing personnel with adequate information on use of the product, development of a product that would allow individual control of the dosage, and provision of information on potential negative effects that may be experienced if higher than recommended amounts are consumed. Individuals who are regular moderate to heavy users of caffeine may expe- rience headaches, fatigue, and other adverse effects if denied access to caffeine in anticipation of the later need to use a supplement. Conclusions A caffeine dose of 100-600 mg can be expected to improve vigilance and enhance cognitive performance. A delivery mechanism that provides caffeine in 100-mg increments could be used to allow individuals of smaller body size, non- habituated caffeine users, and those with a heightened sensitivity to caffeine to use the product. The recommended dosing interval should take into consideration that too- frequent dosing might produce a build-up of caffeine and its metabolite para- xanthine sufficient to precipitate negative effects, or inhibit sleep onset in some individuals when sleep is desired. The committee concludes that there is no specific need to include warning or cautionary statements on the product labels, and the dosage recommended is well within the range of caffeine consumption in the general population. Recommendations A caffeine delivery vehicle that provides caffeine in 100-mg increments with a total content not exceeding approximately 600 mg would appear to be the most appropriate dose for use in sustained military operations. No differential dosing is recommended for habitual and first-time caffeine users. However, a single dose should not exceed 600 ma, and 400 mg may be adequate for rested individuals performing sustained vigilance tasks.
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EXECUTIVE SUMMAR Y 13 Since the average half-life of caffeine in the blood of adult men given 280 mg (4 mg/kg BW) is between 2.5 and 4.5 hours, a dosing interval of no less than 3 - hours is suggested. Any product that is used as a vehicle for providing caffeine to military per- sonnel should be prominently labeled, including a statement on the principal display panel that the product contains added caffeine and should be used only to maintain performance when involved in sustained operations. The label should also indicate the amount of caffeine per unit of product (or per serving) and instructions for use. This information is vital for commanders to make decisions about directives for use and for personnel to adapt consump- tion to their individual needs. An in-depth training program on the benefits, directions for use, and potential side effects of caffeine should be designed for command personnel. Military personnel should be given adequate training to ensure the benefits of caffeine supplementation and avoid any potential side effects. Such training should include the use of caffeine during periods of sleep deprivation and altered work-rest cycles in nonoperational situations. Military personnel who are habitual consumers of caffeine should not be re- stricted from caffeine use in preparation for the need of a caffeine supplement. 4. Alternatives: Are there practical alternatives to caffeine that would better serve the intended purpose of enhancing or maintaining performance in fatigued service members? 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. There is a dose effect for the restorative effects of sleep duration on cognitive performance. 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. Alternatives Combination of Caffeine and Naps The most effective nonprescription alternative to caffeine administration alone is a combination of caffeine and naps. In a series of studies, the combina- tion of a short nap and caffeine significantly decreased driving impairment, subjective sleepiness, and drowsiness as measured by electroencephalogram activity. The combination of a nap and caffeine also increased alertness during long periods of sleep deprivation as compared to either caffeine or nap treat- ments independently.
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14 Amphetamine CAFFEINE FOR MENTAL TASK PERFORMANCE Amphetamine has been found to "improve subjective feelings of fatigue, confusion, and depression while increasing feelings of vigor". Amphetamine is, however, a controlled substance and its use would require an individual medical evaluation to determine risk factors and health status before a prescription could be issued. It is possible that with appropriate supervision and control, ampheta- mine could provide benefits to individuals with unique skills and whose per- formance is critical to the safety of complex military hardware and personnel. The potential for abuse of amphetamine is considerable. Appropriate monitoring of its dispensation and use may add unnecessary burdens to person- nel involved in the intense and demanding tasks that are directly related to the success of sustained operations (SUSOPS). Although amphetamine (20 ma) was more effective than caffeine at 300 mg in reversing the negative effects on alert- ness during sleep deprivation, it had deleterious effects on recovery sleep, which also may be important in the ultimate success of demanding and constantly changing SUSOPS. Therefore, considerable caution is warranted, and use of this stimulant should be restricted to circumstances when such measures are consid- ered essential to the success of highly sensitive operations. Modafinil Modafinil is a controlled wakefulness-promoting drug developed to counter- act excessive daytime sleepiness (ED S) in narcolepsy. This drug appears to be useful in reducing EDS without affecting voluntary naps or nocturnal sleep ini- tiation. These properties suggest that this compound may be useful in extending high levels of vigilance In SUSOPS. The limited research to date on the effects of modafanil in simulated military situations indicates potential for this drug. Conclusions Providing the opportunity and environment for adequate sleep would be ideal, but obviously impractical, for continuous military operations. Combining naps with judicious caffeine use may be the best remedy for sleep deprivation-induced decrements in cognitive function in military situations where adequate sleep can- not be obtained. When naps are not an option, caffeine alone could be used. The use of amphetamine is superior to caffeine in offsetting decrements in cognitive performance; however, the risks outweigh the benefits for most situa- tions. It is a controlled substance, has a high abuse potential, and interferes with recovery sleep. In addition, it is assumed that the majority of combat personnel would not have previous experience with the drug. The drug modafanil, developed as a treatment for narcolepsy, shows con- siderable promise. It appears to be as effective as amphetamine in offsetting
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EXECUTIVE SUMMARY 15 performance degradation, does not interfere with initiation of recovery sleep, is not an appetite suppressant, and appears to have a much lower abuse potential. Recommendations It is recommended that the military have in place a doctrine related to the importance of sleep prior to extended missions, the importance of naps whenever possible during operations, and the timing of naps for maximum effectiveness. Of the psychostimulant compounds that have been thoroughly tested, caf- feine would be the compound of choice. Many personnel would have personal experience with the compound, it is not a restricted substance, it does not inter- fere with recovery sleep following periods of sleep deprivation, and it has very low abuse potential. Additional research should be conducted on the drug modafinil to further ex- plore its potential for sustaining cognitive performance during military operations. 5. Formulation: (a) Does the inclusion of other components (e.g., glu- cose) improve the beneficial effects of caffeine in sustained operations, as previously suggested by the committee? (b) Is there a better approach to caffeine delivery than the nutrient bar (HOOAlI) currently produced for the military? The evidence of the utility of adding glucose or other components to caf- feine to further enhance performance is unclear. Caffeine enhances the avail- ability of free fatty acids and decreases glycogenolysis, whereas carbohydrate increases the availability, and presumably the use, of glucose. There may be nutritional reasons (e.g., provision of food energy, nutrients, or fluid) for including caffeine in a food or beverage form. Various approaches to caffeine delivery for SUSOPS were considered, including a food/energy bar, caffeinated chewing gum, tablets (both sustained release and regular), and bev- erages. There is good evidence that caffeine consumed as a liquid is absorbed rapidly and completely from the gut, with virtually all (99 percent) of the ad- ministered dose absorbed in about 45 minutes. However, evidence on absorption of caffeine from a food matrix, such as energy bars, was not available. A caffeine delivery vehicle that is most appropriate in one setting may not be so in another. Caffeine in a food matrix or beverage may be advantageous when it is important to deliver nutrients, fluid, or other food constituents simul- taneously. Chewing gums are more appropriate if rapid absorption and action are needed, or weight or bulk is a concern. Caffeine in a fluid matrix or gel may be more appropriate when dehydration is a concern.
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16 CAFFEINE FOR MENTAL TASKPE~O~ANCE Conclusions Although evidence of a potentiating effect of carbohydrates on caffeine ef- fectiveness is equivocal there are other reasons to consider providing supple- mental nutrients along with the caffeine. Inadequate food and fluid intake is a common problem during military operations. The use of a caffeinated chewing gum would: appear to provide the most rapid absorption. Environmental circumstances and individual characteristics may make one caffeine delivery vehicle appropriate in some circumstances and inappropriate in others. Recommendations Definitive research is needed regarding the combined effects of caffeine and carbohydrate on performance since data currently available are inconclusive. If a food bar or some other solid food matrix is used, the rapidity and extent of caffeine absorption and action must be evaluated. Under certain circumstances, such as heat stress or desert operations, chewing gums may offer practical operational advantages over a food/energy bar. Thus, two delivery vehicles should be considered. Based on the DOD pref- erence to provide needed supplements to personnel in food form rather than in pill form, a caffeinated chewing gum or a caffeine-supplemented food/energy bar would be suitable delivery vehicles.
Representative terms from entire chapter: