Introduction and Background
THE COMMITTEE’S TASK
The Committee on Military Nutrition Research (CMNR) of the Food and Nutrition Board (FNB), Institute of Medicine (IOM), National Academy of Sciences (NAS), was asked by the Division of Military Nutrition, U.S. Army Research Institute of Environmental Medicine (USARIEM), U.S. Army Medical Research and Development Command (USARMRDC), to review the potential for specific food components to enhance the performance of military personnel under the stress of field settings. The committee was thus charged with providing a thorough review of the literature in this area and with interpreting these diverse data in terms of military applications.
The committee was also asked to address six general questions that dealt with enhancement of performance.
Is enhancement of physical and mental performance in “normal,” healthy, young adult soldiers by diet or supplements a potentially fruitful approach or are there other methods of enhancing performance that have greater potential?
The Army Science and Technology Objective (STO) states: By FY98 demonstrate a 10–15 percent enhancement of soldier performance in selected combat situations through the use of rations/nutrients that enhance caloric utilization and/or optimize the physiological levels of neurotransmitters. (Army Science Board, 1991).
Is the level of enhancement identified in this STO reasonable with the current scientific knowledge?
Which food components, if any, would be the best candidates to enhance military physical and mental performance?
Should the mode of administration be via fortification of the food in rations, supplemented via a separate food bar or beverage component, or administered in a “vitamin pill mode”? Is palatability a significant issue in this type of supplementation?
Are there specific ethical issues that need to be considered with this type of research?
What regulatory issues must be considered with the types of food components that are being evaluated by the Army?
Within this context the CMNR was charged with specifically evaluating the potential of selected amino acids, carbohydrates, structured lipids, choline, carnitine, and caffeine to enhance performance. The committee was also asked to provide its recommendations regarding which, if any, of these compounds should be developed further within the current “Soldier as a System” initiative (Army Science Board, 1991).
The CMNR realized that there was a large amount of research—of variable quality—devoted to enhancement of performance. In addition, questions about dose levels, informed consent, time span, and timing of administration were raised with regard to the application and desired outcome within a combat setting. To help focus the objects of its report, the committee requested that the Army develop several scenarios that illustrated the hypothetical application of these food components. Seven scenarios written by Drs. Harris Lieberman and Mary Mays, USARIEM, are included in Appendix A.
To assist the CMNR in responding to these questions and developing their recommendations, a workshop was convened on November 16–17, 1992. This workshop included presentations from individuals familiar with or having expertise in cognition, endocrinology, exercise physiology, food engineering,
food science, immunology, metabolism, neuropsychology, nutrition, nutritional biochemistry, performance psychology, and sports medicine. The invited speakers discussed their presentations with committee members at the workshop and submitted the contents of their verbal presentations as written reports. The committee met after the workshop to discuss the issues raised and the information provided. The CMNR later reviewed the written reports and drew on its collective expertise and the scientific literature to develop the summary, conclusions, and recommendations that appear in Chapters 1 and 2.
Terms Used in This Report
For the purposes of this report, the Committee on Military Nutrition Research defines the term enhancement to include both an avoidance of reduction in performance decrement during stress and improvement of performance above the baseline. Both physical and mental performances measured by a wide variety of tests are explored. Improvements over baseline performance and prevention of performance decrements during stress are admittedly widely different problems, but ones with similar overall military objectives. Possible approaches to each of these problems are also explored. Ergogenic aid, (“work-producing”) is used to refer to any substance, whether in a food or not, that enhances physical performance.
This summary begins with an overview of the specific military issues and research that led to interest in performance enhancement. The committee then provides a summary of information related to nutrition and stress. This is followed by a review and interpretation of the available data on the food components proposed for consideration by the Army. Chapter 1 concludes with a discussion of the safety and regulatory aspects of performance-enhancing food components.
MILITARY RESEARCH ON NUTRITIONAL ENHANCEMENT OF SOLDIER PERFORMANCE
History and Current Research
The introductory chapter by COL Eldon W.Askew summarizes the interest of the Army in enhancing soldier performance (see Chapter 3). In the
past, the focus for maximizing soldier performance has largely been on efforts to improve training, doctrine, and equipment, with little research emphasis on how the physical and cognitive abilities of individual soldiers may be enhanced through nutritional supplementation or design of rations. Military rations are designed in accordance with the nutritional standards established by the Military Recommended Dietary Allowances (MRDAs) (AR 40–25, 1985), which are intended to ensure that soldiers are receiving nutritionally adequate rations.
There has been a concern that the development of sophisticated equipment and the increasing demands that are made on the soldier, both physically in load carrying and in the cognitive abilities required to use the more sophisticated weaponry, place additional burdens on the nutritional needs of the individual. This has raised the question of whether soldier performance can be improved through design of special rations. USARIEM and the U.S. Army Natick Research, Development and Engineering Center (NRDEC), located at Natick, Massachusetts, share responsibility for implementing the new Science and Technology Objective (STO) that is principally directed at the sustainment or enhancement of soldier performance through the use of performance-enhancing food components (see description of this STO in question 2 on page 4). In this context, if soldier performance that may be reduced under the stress of sustained field operations could be sustained at preoperational levels, it would be considered an enhancement of performance.
COL Eldon W.Askew (Chapter 3) briefly summarizes the research that USARIEM has conducted in the past few years in three areas, dietary macronutrients (carbohydrates), nutritional pharmacology (caffeine), and nutritional neuroscience (tyrosine). These areas are reviewed in more depth in the chapters that follow (Chapters 15–17 and 20). Although some responses have been measured under carefully controlled laboratory conditions, the results have not always been transferable to field operations. The difficulty in obtaining precise measures in the field, the considerable variations frequently experienced among subjects, and the difficulty of actually duplicating conditions imposed either in the laboratory or in the field affect the outcome of this research.
The issues considered in the workshop and this report center around the identification of potential performance-enhancing nutrients or food components that may be used to supplement or improve the operational rations that already provide liberal allowances of nutrients as established by the MRDAs.1 Soldiers who consume these military rations are thus presumed to be in a state of good nutrition.
The Military Recommended Dietary Allowances (MRDAs) are being revised. The current edition is included in its entirety in Appendix B.
Design Issues for Rations
There are two primary tasks in meeting the objective of enhancing performance by using rations. The first requires the identification of food components that may, through prior research or consideration of metabolic pathways, appear to be candidates for evaluation. This task is further complicated by the need to design the appropriate environmental stresses and identify the physical and cognitive measures that may be sufficiently sensitive to evaluate their influence on performance.
The second requires the development of the appropriate delivery system to supply the components to the soldier in the proper amount and at the appropriate time.
Two introductory chapters (Chapters 4 and 5) by Irwin A.Taub and C. Patrick Dunne, of the Food Engineering Directorate, Natick Research, Development and Engineering Command (NRDEC), provide an excellent review of the complexity of developing operational rations for the military. These rations must meet special nutritional needs, be acceptable to the soldier, have sufficient shelf-lives under the storage time and conditions imposed for the ration system, and meet the safety and performance criteria established for the ration when used possibly 3 to 4 years after manufacture. The capability of NRDEC and the extent of the challenge this task presents are eloquently discussed in Taub and Dunne’s chapters.
Biochemical Strategies and Issues
Biochemists may identify nutrients or food components that are important sources of energy or that function as metabolic regulators at the cellular level for which changes in the supply or concentration may affect metabolism at that site. However, in the complex functioning of the various tissues and organs and metabolic regulation, these cellular observations may not be transferable to performance enhancement of the individual. Therefore, it is important in selecting potential performance-enhancing components for study to carefully evaluate (1) the physiological basis for the potential performance enhancement at the functional site(s); (2) the potential for being able to deliver such a component through the physiological processes of digestion, absorption, and circulation; and (3) the delivery of the food component to the functional site at a concentration that will be effective and not adversely affect the complex interactions in the overall metabolism. With all of the complexities of human metabolism, it is important to carefully evaluate food components or nutrients as potential performance enhancers (physical and/or cognitive) on the basis of their demonstrated potential in studies on the functioning tissue or organ.
As discussed in the chapters by Drs. Dunne and Taub, the ration developers are acutely aware of these problems and are looking to the CMNR for guidance on the selection of components for evaluation in the appropriate food delivery systems.
PERFORMANCE ISSUES AND MEASUREMENT APPROPRIATE TO THE MILITARY
The performance of physical tasks in any job setting requires the confluence of physiological and psychological processes. As discussed by James A.Vogel (Chapter 6), many of these processes and related factors can be viewed as potential targets for performance enhancement through ergogenic aids. Although experimental studies can focus on measurement of physical performance at levels ranging from the isolated muscle cell to the whole organism, the issue for the military is the performance of the soldier in physically demanding tasks, often under stressful conditions. Review of food components that may enhance physical performance through psychological factors that contribute to performance of all tasks, such as arousal, concentration, and motivation (see Dishman, 1989, for a review), will be reviewed in the following sections. In Chapter 6, Vogel focuses on the four categories of physiological factors that are involved in physical task performance: metabolic capacity, neuromotor control, energy substrates, and tissue homeostasis. The various physical performance tasks in the military involve several or all of these physiological categories,
The physical task of firing a rifle is predominantly determined by neuromotor control factors, while that of running for long distances is predominantly determined by the other three groupings of factors (Chapter 6, p. 114).
Vogel contends that to evaluate the effectiveness of ergogenic aids, the specific target of action among these categories must be identified and then appropriately measured using well-validated techniques. A careful review of the most appropriate methodologies for each category is provided by James A.Vogel in Chapter 6. Evaluation of the effectiveness of any food component on performance would then optimally be tested in experiments that isolated the target categories in several stages: in a controlled laboratory setting, in a single field task, and as part of an operational scenario. Appendix A provides several
scenarios that depict militarily relevant physical performance tasks in which ergogenic aids might prove effective.
The issues of mental performance that are of concern to military personnel in a combat setting do not differ from those in a regular workplace, with the exception of the severity of the levels and types of stress superimposed on the situation. The ability to perceive, attend to, and respond appropriately to cues, as well as make appropriate decisions, and to remain vigilant are critical in military combat settings. These areas of cognitive performance also form the basis for many physical performance tasks, such as positioning and loading artillery shells or moving through a mine field. Laboratory studies in many settings have shown that well-trained personnel will typically sacrifice speed for accuracy in cognitive performance tests in stressful situations. Although in the workplace this may reduce monetary cost-effectiveness, in a field combat situation a significant decrease in speed of performance could be life-threatening.
Sleep deprivation is a major overlying factor that can further lead to performance degradation in the workplace (Commission on Sleep Disorders Research, 1993). This problem has long been recognized by the Army and thus has been the focus of laboratory and field research in military settings. In Chapter 7, Belenky et al. present a review of recent research on sleep deprivation and its effects on performance during continuous combat operations. Belenky et al. state that the “The ability to do useful mental work declines by 25 percent for every successive 24 hours awake” (p. 128). In laboratory and field studies, although psychomotor performance, physical strength, and endurance do not appear to be less affected by sleep deprivation, complex mental functions such as the ability to perceive and understand changing situations, adapt to changes, and plan alternative strategies are significantly degraded. For example, soldiers were able to maintain accuracy at fixed targets after 90 hours without sleep, but they exhibited poor performance with targets that appeared at random time intervals and in changing locations (Haslam and Abraham, 1987, see Belenky et al.; Chapter 7).
An extended, uninterrupted sleep (7-plus hours) appears to provide the best means of restoring cognitive performance. Sleep that is fragmented, however, has been shown to provide little recuperative value in terms of cognitive performance (Bonnet, 1987). Unfortunately, fragmented sleep—interrupted by noise, lights, and nearby movements—is more typical of combat settings than an uninterrupted rest. The trade-offs for commanders in allowing more sleep for their troops or making increased forward progress in an operation were
addressed by McNally et al. (1989) through integration of experimental data from Thorne et al. (1983) into models of military performance under different conditions of sleep deprivation. The results indicate that restricting a unit’s sleep is unproductive. The total output on any given task of units with mild to moderate sleep deprivation would be expected to drop as the days pass. During this time, the more complex reasoning and decision-based tasks would be expected to suffer the greatest decline in performance. In Chapter 7, Belenky et al. illustrate these types of problems with accounts of experiments using simulated artillery fire (Banderet et al., 1981) and after-action debriefings from Operation Desert Storm.
Preliminary data indicate that decrements in cognition-based performance are paralleled by decreases in glucose metabolism in specific areas of the brain (Thomas et al., 1988). The effects of dietary glucose supplements on performance enhancement under conditions of sleep deprivation have not been fully examined.
The scenarios in Appendix A provide additional direct examples of the types of cognitive performance changes that are of concern in military settings. Reduction in performance degradation through ingestion of food components that may affect neurotransmitters, more general neuronal excitability, or the specific brain regions involved in cognitive activities will be discussed in the sections that follow.
PROVIDING FOOD IN THE CONTEXT OF MILITARY COMBAT SETTINGS
Many contextual factors are influential in the amount and type of food that individuals consume. An individual’s expectations (Cardello and Sawyer, 1992), the time of day (Kramer et al., 1992), the effort needed to obtain food (Collier, 1989; Engell et al., 1990), the amount and diversity of available food (Engell, 1992; Rolls et al., 1992), the appropriateness of the meal to the time of day (Birch et al., 1984; Kramer et al., 1992), food acceptability (Meiselman et al., 1988), food presentation (Cardello and Sawyer, 1992), and the dynamics of the social situation while eating (de Castro and Brewer, 1992; Goldman et al., 1991) all affect the amount eaten and what is selected. Since appropriate food intake is essential for performance, these contextual factors are recognized by the Army as important; however, the manner of food delivery in combat settings is necessarily constrained by the food engineering concerns that were previously described. As Meiselman and Kramer mention in Chapter 8, the long-term storage requirements for rations contribute to difficult demands for production as well as for the consumer. In addition, soldiers typically eat considerably less than the total ration that is provided for them (of the 3,900
kcal per day for moderate activity in a temperate climate, soldiers eat 2,000–3,000 kcal, on average). This reduction in intake does not appear to be related to food acceptance, since soldiers consistently give good ratings to military rations (see Chapter 8 for review). The stress of the training or combat situation is another mediating factor for consideration. Although a hungry individual may not eat if fearful, once eating does occur the level of intake will most likely be enhanced (Gray, 1987). Individual responses differ greatly, however, and although the “typical” response may be to reduce food intake under stressful conditions, some subgroups of the population increase food intake under the same conditions (see discussion in Chapter 8).
In Chapter 8 Meiselman and Kramer review the history, methodological approaches, and methodological issues related to research in food intake, contextual factors, and performance enhancement. In the military setting these authors point out that performance science has yet to resolve many methodological questions. Provision of food in a military setting and its impact on soldier performance are presented as complex multifactorial problems that require an initial resolution of the definition of performance. The authors refer to the military initiative that calls for soldier performance enhancement in the following five capabilities: lethality, mobility, command and control, survivability, and sustainment. Translating these capabilities into reliably measurable components of cognitive and physical performance that can be enhanced by food component intake in the context of military rations is no easy task. As discussed by these authors, not only will the contextual issues of food component provision require careful examination but new methodologies will most likely require development or refinement. In addition, physical and cognitive performance measurement need to be well-integrated—an area where there is little previous research.
In summary, although an individual’s food intake in the military is influenced by the same set of factors that influence food intake in nonmilitary settings, the stress of military training or combat settings, the shelf life requirements, the packaging and delivery constraints of military rations, and the added performance capability demands result in a highly complex set of problems for performance enhancement. Research in this area will not only require careful attention to the issue of context in food item delivery—similar to standard military rations—but also to the integration of physical and cognitive performance measurement and most likely the development of new methodologies that would test the performance capabilities valued in soldier field settings.
STRESS AND NUTRIENT INTERACTIONS
The Central Nervous System
Primary neurotransmitters in the central nervous system include the monoamines dopamine, norepinephrine (NE), and serotonin (also called 5-hydroxytryptamine or 5HT). The catecholamine norepinephrine is believed to be an important neurotransmitter involved in the sleep-wake cycle, pain, anxiety, and arousal, whereas the indoleamine serotonin is thought to be important in many central processes, including pain perception, memory, appetite, thermoregulation, blood pressure control, heart rate, and respiration.
Tyrosine hydroxylation is the rate-limiting step in the synthesis of all major catecholamines including NE and dopamine, while serotonin is synthesized from tryptophan. Several lines of investigation have examined the effects of administration or manipulation of these or other precursors on various physiological functions and behaviors. Protocols have included acute (short-term, i.e, minutes to hours) manipulations as well as chronic (usually long-term -days to months- diet-related) administration.
Studies using acute paradigms have examined the behavioral consequences of altered neurotransmitter precursor availability and, hence, neurotransmitter synthesis. Alterations in brain amino acids and neurotransmitter levels are seen within 15–20 minutes after administration of amino acids such as L-tyrosine (TYR), or after feeding diets high in carbohydrates (CHOs) or protein to experimental animals (see Chapter 9 by John D.Fernstrom).
In addition, both serotonin and NE have been examined for their effects on macronutrient selection (see Chapter 13 by Richard J.Wurtman). In experimental animals pharmacological doses of NE (either central or peripheral administration) have been reported to enhance CHO consumption relative to protein or fat consumption, whereas central or peripheral administration of 5HT appears to inhibit CHO consumption while sparing protein and fat intake (see Blundell, 1986 for a review). In one example, with a two-diet choice (protein-rich versus CHO-rich), a small dose of 5HT introduced into the parventricular nucleus of experimental animals selectively suppressed the CHO-rich diet (Shor-Posner et al., 1986).
In Chapter 9, John D.Fernstrom reviews the biochemical basis underlying L-tyrosine (TYR) administration to counter stress. Results from several studies suggest that TYR administration enhances dopamine (DA) and NE synthesis in the brain and reverses deficient performance in rats and humans (Lehnert et al., 1984; Banderet and Lieberman, 1989). However, the author cautions that while TYR administration may increase transmitter (DA and NE) synthesis and release and may potentially affect brain functions, the exact consequences of TYR administration are unknown. Further study would be essential to
understanding the usefulness of TYR or other pharmacological or nutritional agents that stimulate DA or NE release.
The studies of Levine and colleagues (Levine et al., 1990) further illustrate the effects of different types of stressful stimuli on increasing the activity of NE-containing neurons in the brain. Acute stress appears to have little effect on NE receptors in the brain. Chronic stress, however, is associated with increased NE synthesis and turnover (Stanford et al., 1984; Thierry et al., 1968). Chronic stress may also be associated with marked decrements in the number of activated beta receptors, in that a stress-induced increase in NE release by brain neurons via stimulation of beta receptors on target neurons and the production of second-messenger-mediated effects leads to beta receptor down regulation (Torda et al., 1981). The available evidence thus suggests that NE receptor responsiveness is changed following chronic stress and that these changes are different from those accompanying acute stress. Data also suggest that such changes are not uniform; i.e., NE receptors and subtypes as well as activity in different brain regions may differ. Therefore, agents such as TYR that enhance NE synthesis and release following acute stress may have different effects under chronic stress.
Stress also affects brain DA neurons, although there is some controversy whether all DA neurons or only some are activated by stress. Again, further research is needed to determine whether administration of TYR in animal models under acute stress stimulates DA synthesis and release and improves functioning. Stress also reportedly increases the brain levels of the major DA metabolite dihydroxyphenylacetic acid (DOPAC) (Dunn, 1988). There are few available studies on brain DA neuronal activity under chronic stress, but several suggest increased levels of DOPAC. Although one cannot determine at present whether DA receptor sensitivity is influenced by chronic stress, administration of TYR should stimulate DA receptor synthesis and release; this is again suggestive of enhanced performance.
Although stress does not influence the activity of the serotonin precursor neurons, stress does increase brain concentrations of the essential amino acid tryptophan (TRP)—possibly as a consequence of increased serotonin (5HT) synthesis and turnover. The mechanism responsible for the stress-induced increase in 5HT synthesis and turnover differs from those in DA and NE (see Fernstrom, 1990). In animals, with 5HT administration through a large dose of valine (or TYR), the stress-induced rise in brain TRP levels or the rise in brain 5HT may be blocked, with unknown consequences to brain function.
In summary, there are few studies that clearly define the catecholamine receptor responses to stress. In addition, there is marked diversity among the various catecholamines suggesting the need for additional animal studies to examine differences in acute and chronic stress on catecholamine receptors in particular brain regions, and their correlations with function.
Endocrine System Responses to Stress
A broad overview of endocrine system responses to military-type stresses is given by William R.Beisel (Chapter 10). Multiple endocrine responses are but one component of a complex of interacting responses that include close communications and coordination among the central nervous system (CNS), the endocrine system, and the immune system. Thus, molecular participants in these broad responses to stress include traditional hormones, neuropeptide mediators, and immunologically generated cytokines, all of which combine to induce the formation of secondary and tertiary molecular messengers within responding body cells.
Endocrine responses show different patterns, depending on the nature of the stress. Sudden or frightening forms of stress are likely to generate a typical “fight or flight” response, or “alarm reaction,” manifested endocrinologically by the release of norepinephrine from CNS neurons and of epinephrine from the adrenal medulla and sympathetic nerve terminals. These two hormones, plus other neurotransmitters, initiate the well-known immediate responses to stress, including tachycardia, hyperventilation, sweating, and other sympathetic responses.
Typical military stresses generate endocrine responses that tend to be remarkably stereotyped in pattern, although they may vary with the form, duration, and severity of the inciting stress. Hormonal responses may also evolve longitudinally, over time, if stress is protracted. These hormonal responses are not simply “all out” but are carefully controlled by a variety of feedback loops.
Although Selye (1946) had theorized that an adrenocorticotropic hormone (ACTH)-induced production of adrenal glucocorticosteroids was the principal endocrine response to stress, subsequent findings revealed that the adrenals contributed only relatively small, brief portions of the overall panoply of endocrine responses. In fact, the adrenocorticoid component may consist of only a loss of the normal circadian rhythm of cortisol production, with the highest normal values which occur in the morning, being sustained throughout both day and night.
Pituitary responses to stress are initiated by the CNS action of neurotransmitters and immunologically generated cytokines, which lead to the CNS production of corticotropin releasing factor and other neurohormones. These, in turn, regulate the anterior pituitary gland production of ACTH, thyroid-stimulating hormone (TSH), growth hormone, and the gonadotropins. Pancreatic islet cell production of insulin and glucagon during stress may be stimulated by acute-phase cytokines (the interleukins IL-1 and IL-6 and tumor necrosis factor [TNF]).
As detailed in Chapter 10, comprehensive endocrine studies of military-type stresses have been performed in Ranger trainees of the Norwegian (see Opstad and colleagues 1980, 1981, 1982, 1983, 1984, 1985, 1990, 1992) and U.S. armies (Moore et al., 1992)1. These studies have documented a small adrenocorticoid response (with loss of circadian rhythm), an increased secretion of aldosterone and renin, and consistent large increases in plasma growth hormone values. In contrast, the production of thyroid and gonadal hormones was suppressed in these soldiers. The declines in prolactin and follicle-stimulating hormone were accompanied by sharp and sustained declines in levels of plasma testosterone and other gonadal androgens. These data are quite complete, with the exception of possible responses by neuroendocrine and intestinal hormones.
Although dietary factors certainly influence the endocrine system, there is no evidence that individual dietary components (other than carbohydrate) serve to alter the response patterns of the endocrine system to stress. Current evidence does not suggest that research initiatives along this line would be worthwhile. On the other hand, severe reductions in total dietary intake should be avoided during military stress, for starvation can initiate its own pattern of endocrine responses.
Attempts have been made by athletes to improve their strength, performance, and muscle mass by the prolonged use of androgenic steroids in pharmacological doses. But the adverse long-term medical consequences of such attempts far outweigh any short-term performance gains; this practice has now been outlawed by all major athletic groups.
In summary, despite the occurrence of stress-induced endocrine responses in military personnel, these responses are transient in nature. No hormonal manipulation of the endocrine system during military-type stress can be recommended.
Immune System Responses to Stress
A review of immune system responses to stress is also provided by William R.Beisel (see Chapter 10). Despite the paucity of data generated by sophisticated modern immunological methodologies, the available evidence indicates that military-type stresses do initiate a variety of responses in both innate (i.e., inborn, generalized, antigen-nonspecific) and adaptive (i.e., acquired, antigen-specific) immunity. Further, both arms of the adaptive
immune system (i.e., humoral immunity provided by specific antibodies generated by B lymphocytes, and cell-mediated immunity provided primarily by T lymphocytes) appear to be affected adversely by stress.
A large body of inadequately controlled data suggests that mental and emotional stresses may reduce cell-mediated immune system competence. Substantial data attest to the impairment of cell-mediated immunity, humoral immunity, and generalized innate immunity caused by generalized malnutrition or by isolated deficiencies of single essential micronutrients. A diet adequate in protein and energy and with adequate quantities of all essential nutrients provides the immune system with optimum protection.
In a study conducted at the Walter Reed Army Institute for Research (WRAIR), the month-long stress of Ranger training was accompanied by diminished humoral immunity (depressed antibody responses to standard vaccine antigens) (Moore et al., 1992). This finding confirmed in soldiers the substantial body of data showing impaired antibody production in animals subjected to various types of stress.
As detailed in Chapter 10, recent studies of cell-mediated immunity showed transient impairments of function during the course of Ranger training. Again, this result appeared to confirm, in humans, a large body of experimental data obtained in animals. These studies, however, contained no data on natural killer (NK) lymphocyte activities. Impairments of NK cell activities are caused by many forms of experimentally induced stress.
An important aspect of both innate and acquired immunity is the production (by lymphocytes, monocytes/macrophages, and many other body cell types) of cytokines with a wide range of actions. Cytokines include the various interleukins, interferons, colony-stimulating factors, cell growth factors, as well as tumor necrosis factor (TNF) and lymphotoxin. Many cytokines play an important role in stress responses, being responsible for initiating hormonal responses as well as acute-phase reactions, which in turn causes large nutrient losses (Beisel, 1991).
Acute phase reactions are important in military-type stresses such as infection, injury, or severe muscular exertion. These reactions include headaches, myalgia, arthralgia, fever, sleepiness, loss of appetite, loss of muscle protein, and an accelerated metabolism of stored body nutrients, all of which serve to reduce both physical and mental performance. Biochemical components of these cytokine-generated acute-phase reactions include the cellular production of prostaglandins, prostacyclines, leukotrienes, and nitric oxide, which, in turn, generate many of the accompanying symptoms. However, it is not known whether stress causes human cells to generate protective “stress proteins” in vivo; such information should be gathered initially in animals.
Decrements in military performance associated with cytokine-induced acute-phase reactions can by reduced, in part, by the prophylactic or therapeutic administration of common over-the-counter drugs (such as aspirin or ibuprofen) that block the formation of prostaglandins. In addition to reducing performance-impairing symptoms, such therapy appears to serve to reduce the destruction of muscle protein and the accelerated metabolism of stored body nutrients (see Beisel et al., 1968, 1974; Beisel, 1991).
In summary, impairments in humoral and cell-mediated immunity need to be defined more completely and more precisely, by using modern technologies, and their poststress duration must be delineated. Measurements of levels of key cytokines (IL-1, IL-6, and TNF) in plasma are needed during military-type stress to help define the potential usefulness of prostaglandin-blocking agents in the prophylaxis and therapy of stress-induced symptoms that interfere with optimal military performance.
Metabolic Responses to Stress and Activity
After abroad introductory analysis of the many complex factors implicated in metabolic responses to stress and physical activity, Edward S.Horton and William R.Beisel (see Chapter 11) focus the remainder of their chapter on the nutritional, endocrinologic, and physiological aspects of fuel metabolism needed to sustain physical and mental performance under a variety of stressful conditions.
These authors emphasize the fact that many different kinds of stress are involved in military performance and that the body’s responses to these stresses are extremely complex, involving many separate systems. Acute and chronic stresses may call for widely different responses. Although adaptations to stress seem designed to aid in survival, some may be deleterious, a point to be considered when considering nutritional methods of enhancing performance.
Despite whatever stresses they face, soldiers must be able to think and act. Optimal performance requires optimal fuel metabolism—primarily glucose for the CNS and a mixture of glucose and fatty acids for muscle. Multiple levels of integration are involved in maintaining homeostasis of glucose and other fuels throughout periods of stress.
Under resting conditions, glucose uptake is mainly by noninsulin-dependent pathways in the CNS, blood cells, and kidneys, whereas only about one-third is used by insulin-dependent pathways, chiefly in skeletal muscles (which primarily burn fatty acids and some amino acids as their source of metabolic fuels). The blood glucose level remains quite constant, being supplied by hepatic glycogen and, to a smaller extent, by hepatic gluconeogenesis from
glycerol, pyruvate, lactate, and amino acids. Fatty acids generated by lipolysis of body fat stores are the predominant source of energy.
Dramatic changes occur when exercise begins. Rapid increases in energy demands activate the sympathetic nervous system, which in turn stimulates both glycogenolysis within muscle itself and additional lipolysis in fatty tissues. Soon, blood flow to muscles is increased, and as more blood glucose is delivered, uptake of glucose by muscle is also increased.
These dramatic changes, however, are carefully regulated through at least five different mechanistic levels: hormone secretion, hormone integration, substrate availability, blood flow controls, and management of glucose uptake by cells. All of these controls are further influenced by the intensity of exercise, the duration of exercise, the antecedent diet, and the modifying effects of prior physical conditioning.
Leg muscle exercise on a cycle ergometer is accompanied by a progressive increase in glucose uptake, which is associated with increased blood flow and increased cellular uptake. Hepatic glucose production parallels demands, initially by glycogenolysis, and then by gluconeogenesis. Blood glucose will actually increase initially during brief high-intensity exercise. As exercise continues, however, fatty acid dependency is increased, and after several hours, fatty acids become the predominant fuel. With prolonged, exhaustive exercise, the liver cannot keep up with glucose needs.
Activation of the sympathetic nervous system is the key initiating factor, which leads in turn to stimulation of muscle cell glycogenolysis, fat cell lipolysis, and activation of both the adrenal cortex and medulla. The adrenal response gives rise to both cortisol and epinephrine and, thus, secondarily to an increase in hepatic glucose output. The epinephrine also stimulates glucagon secretion while inhibiting that of insulin.
Norepinephrine concentrations rise proportionally to the intensity of exercise, once it is above half of maximum. Insulin values actually fall during exercise, whereas the glucagon values increase slowly, responding both to the intensity and the duration of exercise and to the rising catecholamine concentrations.
Animal studies have shown that the falling insulin-to-glucagon ratio stimulates hepatic glucose production. On the other hand, a falling insulin-to-norepinephrine ratio activates lipolysis and mobilizes fatty acids. Pancreatic clamp techniques have demonstrated the effects of individual hormones, with others held constant. Glucagon increases cause prompt increases in arterial blood glucose, primarily because of enhanced hepatic glycogenolysis. Epinephrine also increases arterial blood glucose, but more slowly, acting to stimulate both glycogenolysis and gluconeogenesis in the liver and lipolysis in the periphery. On the other hand, the effects of norepinephrine are primarily in the periphery, releasing substrates that slowly
lead to enhanced hepatic gluconeogenesis. Cortisol alone seems to play little role in acute hepatic glucose production.
This increase in glucose turnover during stress is generally related to increased hepatic production, but factors such as blood flow to skeletal muscle and changes in the cellular uptake of glucose are also involved. Certain neurotransmitters, when injected into the third ventricle of dogs, cause responses that mimic many of the initiating and counterregulatory hormonal responses and glucostimulatory effects of stress. Similar experimental studies in dogs with alloxan-induced diabetes demonstrate the need for permissive amounts of insulin to obtain a stress-related increase in peripheral glucose utilization.
Studies of glucose utilization in skeletal muscle during stress have also involved the carrier-mediated pathways of glucose transport across cell walls, producing evidence that insulin and the contraction stimulus of exercise exert independent effects for increasing glucose transport into muscle cells. Additional research is needed in the areas of peripheral glucose uptake.
More research is also needed to understand the initiating CNS and sympathetic nervous system role, and the actions of various neurotransmitters and their receptors in stimulating and maintaining the hepatic production of glucose during exercise-related military stresses.
POTENTIAL PERFORMANCE-ENHANCING FOOD COMPONENTS
Physical Performance Enhancement
A broad overview of food components that may optimize physical performance is provided by John L.Ivy (Chapter 12). Ivy divides such ergogenic aids into five categories: (1) mechanical, (2) psychological, (3) physiological, (4) pharmacological, and (5) nutritional. The line between the last two categories is difficult to draw, especially from a regulatory point of view, since foods and drugs are regulated quite differently. This difficulty is of particular relevance to the subject of this report, since food components will fall into classifications either as nutritional or pharmacological ergogenic aids. The general rule is that a nutrient consumed at a level reasonably comparable to a dietary level and acting via the known mechanism for that nutrient would be considered a nutritional aid. In contrast, when nutrients are consumed at levels much greater than dietary levels and have physiological effects clearly different from their known nutritional roles, they are usually considered to be acting via a pharmacological route. However, from a legal or regulatory perspective, the distinction between the “foods” and “drugs” may be less clear, as described by John E.Vanderveen (Chapter 23). In addition, food compo-
nents that are not nutrients but that have pharmacological effects may pose complications, for example, the inhibition of insulin secretion caused by mannoheptulose found in avocados (Simon et al., 1972). Ivy, in his review, considers five mechanisms by which a variety of foods and derivatives of food products may act as ergogenic aids. These are (1) acting as central or peripheral stimulants, (2) increasing the storage or availability of limiting substrates, (3) acting as a supplemental fuel source, (4) reducing or neutralizing metabolic by-products, and (5) enhancing recovery.
The prime example of a central stimulant found in food beverages is caffeine, as discussed elsewhere in this report (Chapter 20). Another example is branched-chain amino acids (BCAAs). It has been hypothesized that supplementation with BCAAs might delay the fatigue associated with endurance exercise by preventing a rise in brain serotonin levels. However, data are not available to confirm this hypothesis. Still another possibility is the facilitation of excitation-contraction at the neuromuscular junction by choline. The utility of choline supplementation is considered in more depth in Chapter 19.
The ergogenic aid most used to increase the storage and subsequent availability of a limiting substrate is carbohydrate. The well-known procedure to accomplish this is by exercise-stimulated glycogen depletion and then feeding a high-carbohydrate diet. Storage of increased levels of muscle glycogen results. Another possibility is phosphate loading, which has been reported to increase maximal oxygen uptake, possibly via an increase in the blood concentration of 2,3-diphosphoglycerate. This has the effect of increasing tissue oxygen extraction.
Carbohydrate also can act as a supplemental fuel source during exercise. This topic was considered extensively in an earlier CMNR report (Marriott and Rosemont, 1991). Other possible approaches to increasing aerobic endurance via a supplemental fuel source considered by Ivy include elevating plasma-free fatty acid levels via either consumption of a high-fat meal or secondary to the lipolytic effect of caffeine, consumption of a combination of pyruvate and dihydroxyacetone, or consumption of medium-chain triglycerides (see also Chapter 18).
A decrease in muscle pH during exercise is believed to limit physical performance; thus, buffering this pH change makes physiological sense. Consumption of sodium bicarbonate has been demonstrated to increase cycling duration at 90 percent by reducing acidosis (Sutton et al., 1976). Dichloroacetate has been reported to lower blood lactate concentrations in animals and humans (Carraro et al., 1989; Schneider et al., 1981). Ivy also emphasizes that body heat during exercise limits physical performance, and hence, water can be considered one of the most important ergogenic aids. To enhance recovery after physical activity, water and carbohydrate are both
needed, as emphasized also in the previous CMNR workshop proceedings on fluid replacement and heat stress (Marriott and Rosemont, 1991).
In summary, data from a wide range of studies on the effects of ergogenic aids indicate that there are a variety of foods and food products that act through one of five known mechanisms to improve athletic performance. Acting to increase both storage and availability of a limiting substrate and as a supplemental fuel source, data on the athletic performance enhancement of carbohydrates are most compelling. Physical tasks performed in the military occasionally mirror the short-term intensive bursts of activity studied in athletic competitors. However, most research with carbohydrate supplementation has been conducted in prolonged continuous moderate exercise such as marathon running or situations that do not readily compare to the exercise demands of military combat.
Food Components that May Enhance Mental Performance
Various foods and food components have been evaluated for their behavioral effects in animals and humans, including protein and carbohydrate (CHO), caffeine, and several amino acids such as tryptophan, tyrosine, and phenylalanine. Since the dosages of these cognitive enhancers are far greater than those available in foods, many investigators believe that these substances should be classified as pharmacological agents rather than nutritional supplements and that their safety as well as their efficacy in these separate formulations have not been demonstrated.
In one well-designed, well-controlled experiment, tyrosine was given to male volunteers exposed to an acutely stressful environment (Banderet et al., 1987). Behavioral, cardiovascular, and endocrine measures were taken using a double-blind, placebo-controlled crossover design with each subject participating twice in three experimental conditions, combinations of cold (15°C) and hypobaric hypoxia (4,200 or 4,700 m) and a control condition. Tyrosine ameliorated many of the adverse consequences of the environmental stress and improved vigilance while lessening anxiety.
In general, to demonstrate nutrient or neurotransmitter effects on mood and performance, it is critical to use well-designed, specific tests. Improved performance may best be demonstrated with monotonous vigilance tests of long duration (Lieberman, 1989). In addition, dose-response functions should be convincingly demonstrated. Mood tests should include a range of possible affective responses such as depression and anxiety as well as behaviors including estimates of sleepiness and vigor. Differences in functioning can also be examined under experimental conditions ranging from neutral to extremely stressful or painful.
Presently, there are many unresolved issues. It is critical to select appropriate methods to examine the somewhat subtle effects of these nutrients on behaviors. Whether these nutrients can be used as sedatives or stimulants, antidepressants, or antistress agents will have major practical consequences. Further research is thus desirable.
Nutrients on Neurotransmitter release
A discussion of issues relating nutrients and neurotransmitter release and behavioral consequences can be found in Wurtman (1988). Chapter 13 of this report, also by Richard Wurtman reviews the history of much of the research relating nutrients to brain function and the reverse (i.e. brain function to food/nutrient choices). The major hypothesis in this area of research is that metabolic events occurring outside the brain and primarily occurring as consequences of eating behavior (e.g., amount, frequency, and type of macronutrient) can affect the levels of neurotransmitter precursors and thus guide the selection of nutrients in the next meal(s). With “normal” feeding, brain tryptophan levels and serotonin synthesis undergo variation. This variation itself reportedly produces differences in food choices such as that following an overnight fast (e.g., CHO-rich breakfast versus protein-rich breakfast).
The theory that serotonin is part of a feedback loop in the control of diet selection has led to much scientific debate. Experimental data suggest that neither the control of macronutrient intake nor diet-induced changes in neurochemistry are easily demonstrable or robust (Holder and Huether, 1990). In contrast, supporters maintain that the diet-induced changes in brain neurochemistry (e.g., serotonin or 5-hydroxytryptamine [5HT]) are meaningful and are involved in the process of food/macronutrient selection (see Blundell, 1986; Booth 1987; Booth et al, 1986; Garattini et al., 1986).
In particular, concern has been voiced as to the mechanism whereby contextual and sensory differences in food components can be meaningfully separated from macronutrient content. Note is made of the absence of a metabolic/neurochemical mechanism: “Neurochemistry or indeed neuroanatomy, unconnected to any account of how sensory information could be used to direct behavior towards the diets in a manner that achieves nutrient-oriented selection, leaves the feedback idea as a magical incantation, not a scientific hypothesis” (Booth, 1987, pp. 195–196).
Fernstrom (1987) reported that although it appears possible to relate protein and CHO intake to effects on the serum tryptophan/large neutral amino acid ratio and, thus, to brain tryptophan levels and serotonin synthesis in fasting rats in a single-meal situation, such a relationship does not exist in
chronic stress studies. Additionally, the use of anorectic agents such as fenfluramine does not provide convincing data for a suppression of CHO intake rather than total food intake. Some investigators are hopeful that the dietary self-selection paradigm will help to untangle this area if proper controls are available to determine differences in taste, smell, and texture.
Another area of scientific controversy has been the role of brain serotonin in excessive CHO snacking. Consumption of CHO-rich foods has been related, in animals and humans, to increases in the synthesis and release of brain serotonin and a decrease in the CHO content of a subsequent meal. An increase in the central uptake of the precursor tryptophan is the mechanism that has been presented. This increase in central serotonin level and decrease in CHO intake are not seen with protein intake.
One aspect of this hypothesis that has been extensively discussed is the concept of CHO craving. Rats have been reported to modify food choice (thereby diminishing their CHO intake) as a consequence of pretreatment with CHO snacks or pharmacological agents, facilitating serotoninergic neurotransmission (Wurtman and Wurtman, 1979). A question has been how well CHO-rich versus fat-rich foods are characterized in these discussions. (Amounts in grams versus calories represent markedly different total percentages, and thus, CHO-rich foods are frequently rich in other nutrients, fat in particular.) It is also unclear whether CHO cravers prefer sweet CHOs primarily. According to the feedback loop theory, the response of serotoninergic neurons to food-induced changes in the relative concentration of plasma amino acids allows for a special “sensor” role in nutrient choice (Wurtman, 1983, 1988).
CHO cravers have been suggested to show enhanced mood and reduced depression following CHO consumption. This decreased depression has been interpreted as a consequence of the food-induced changes in central serotonin levels (Lieberman et al., 1986b). In addition, it has been suggested that obese CHO cravers treated with an anoretic agent, D-l fenfluramine (which increases serotonin activity) decrease CHO snacking. Such drugs have also been considered in the treatment of several “affective” disorders, for example, seasonal affective disorders [SADS] (O’Rourke, 1989), premenstrual syndrome (PMS) (Brzezinski et al., 1990), and smoking cessation (Spring et al., 1991). However, the general conclusion seems to argue for further specification of CHO cravings and cravers.
The animal data are most convincing for fasted single meal situations. Most experimental evidence from the food choices of free-living human subjects suggests high daily variability. Meals following extended fasts such as breakfast may be high in protein (eggs, fish) as well as CHO. Although subjects confined to the hospital (Wurtman and Wurtman, 1989) showed relatively less variability, the food intake records and food frequency data suggest greater variability in CHO and fat. Also unresolved is how this sensor
mechanism might work and the interrelationships between brain and plasma levels.
In summary, there are insufficient data at this time to determine whether the neurotransmitter effects discussed in this section can be utilized to improve performance in military settings. It is unclear whether CHO or protein bars would promote sleep or decrease hunger thereby improving concentration in high-stress conditions. It is also unclear whether the ingestion of CHO is regulated by animals or humans to produce or control such differences. The use of pharmacological agents at varying doses might allow examination of the interrelationship between CHO consumption and brain serotonin levels. However, regulation is difficult to demonstrate, especially with marked variations in food intakes dependent on time of day, choices available, amounts, etc.
SPECIFIC FOOD COMPONENTS
Tyrosine is a nonessential dietary amino acid because it can be synthesized in vivo from the essential amino acid phenylalanine and because protein synthesis continues normally even if tyrosine is absent from the diet. However, tyrosine is recognized to be a physiologically important precursor of the catecholamine neurotransmitters dopamine, norepinephrine, and epinephrine. The physiological consequences of changes in concentrations of these neurotransmitters raises intriguing possibilities that expanded intakes of tyrosine beyond that typically present in the diet may alter a host of reactions and biological responses.
In Chapter 15, Harris R.Lieberman describes the results of human and animal studies which evaluated the effects of tyrosine supplements on mental performance under stressful conditions was evaluated. This and other evidence demonstrate that catecholaminergic (CA) neurons play a key role in the regulation of arousal level and anxiety. The primary hypothesis for these studies is that the function of CA neurons is dependent on the concentrations of the catecholamine neurotransmitters, which in turn are dependent on the supply of the precursor tyrosine. Further, it is hypothesized that under stress, the concentration of tyrosine is limited by its supply, which can be enhanced by large dietary supplements. In studies conducted with rats, administration of single doses of tyrosine in amounts of 200–400 mg/kg of body weight reduced the adverse effects of acute stresses such as cold and hypobaric oxygen (Rauch and Lieberman, 1990). The decline of core body temperature due to cold stress was reduced, whereas normal behavioral responses were restored. Specifically,
swimming time in the cold was improved by tyrosine, as was spatial learning and memory in a water maze under conditions of hypobaric oxygen. Other beneficial effects of tyrosine in rats under stressful conditions also were described by Lieberman.
Only a few studies have been reported in which single supplements of tyrosine were given to human subjects. These also are described by Lieberman (Chapter 15). Using a double-blind crossover design (100 mg of tyrosine per kg of body weight given orally versus placebo, human subjects at USARIEM were exposed to a combination of 4 hours of hyperbaric oxygen (4,200 or 4,700 m) and cold (15°C) (Banderet and Lieberman, 1989). Mood and mental performance were assessed using a battery of standardized behavioral tests. These adverse environmental conditions resulted in impaired cognitive performance, headache, lightheadedness, nausea, and general malaise. Tyrosine significantly reduced the severity of these symptoms, and improved functioning believed to be regulated by catecholaminergic neurons such as vigilance, alertness, and anxiety. In other studies at the U.S. Air Force Armstrong Laboratory (Dollins et al., 1990), the subjects who were given 100 mg of tyrosine per kg and exposed to lower-body negative pressure simulating gravitational stress, exhibited reduced adverse cardiovascular symptoms in comparison with controls. In these Air Force studies, the total dose of tyrosine administered to a 70-kg man would be 7 g. This compares to estimated phenylalanine and tyrosine intakes from 100 g of protein per day of 4 and 3 g/day, respectively.
Additional studies on the effect of tyrosine in reducing cognitive deficits resulting from cold stress were reported by Stephen T.Ahlers and colleagues (Chapter 16). In studies carried out in an environmental chamber at the Naval Medical Research Institute, administration of 150 mg of tyrosine per kg of body weight completely reversed cold-induced memory loss using the delayed matching-to-sample (DMTS) test. This controlled study in the laboratory chamber was followed by a study under field conditions. After a day in which all the military personnel performed maneuvers in the cold (-20°C), half of the subjects were given 75 mg of tyrosine per kg, and the other half a placebo. Subjects given tyrosine also performed substantially better on the DMTS memory test under field conditions.
In summary, the studies reviewed suggest strongly that single doses of tyrosine can ameliorate some of the adverse effects of stress on cognitive performance in both animals and humans. The results are consistent with the hypothesis that under stress, the substrate supply of tyrosine to the brain may limit the synthesis of the catecholamine neurotransmitters norepinephrine, dopamine, and epinephrine. Many more studies are needed to confirm these findings under a greater variety of stressful conditions. In addition, the safety of such large single doses of tyrosine has not yet been demonstrated. Further,
data are lacking concerning the beneficial (or harmful) effects in humans of long-term administration of tyrosine supplements, as might be needed in continuous combat operations.
As discussed by John L.Ivy (Chapter 12), an important role has been demonstrated for carbohydrates in sustaining or enhancing physical performance. The role or potential role of dietary carbohydrate in other aspects of performance is considered by Spring and colleagues in Chapter 17. Target behaviors of relevance to the military were defined as mood and performance, with emphasis placed on sensorimotor and cognitive performances.
Spring et al. rightly consider mood, even though it is difficult to measure and even more difficult to quantify, to be an underrated outcome. Mood changes, including the motivation to undertake difficult tasks, are particularly important under stressful conditions such as combat. Stressful situations can unmask performance deficits that are not apparent under nonstressful conditions. In contrast, motivation, interest, and effort can increase functional capacity and overcome performance deficits caused by physiological conditions such as undernutrition. In a study cited by the authors, Gambian road workers subjected to calorie deprivation sufficient to cause significant weight loss nonetheless produced as much work output as nondeprived workers (Diaz et al., 1991). The authors explained these results as being derived from a strong motivational effect based on a monetary reward.
The role of carbohydrates in fatigue also is considered by Spring et al. (Chapter 17). Fatigue is defined as
(1) weariness from bodily or mental exertion; (2) a cause of weariness, labor, exertion; (3) physiological, temporary diminution of the irritability or functioning of organs, tissues, or cells after excessive exertion or stimulation; and (4) mechanical, the weakening or breakdown of material subjected to stress. (Random House, 1982).
The ability of carbohydrate supplements to prolong endurance during exercise clearly is related to preventing fatigue in a physiological sense (definition 3 above). The sense in which the word fatigue is used by Spring et al. relates to definition (1) i.e., weariness from bodily or mental exertion. It might better be called perceived fatigue since it may or may not correlate with physiological indicators. Nevertheless, as emphasized by Spring and her colleagues, when fatigue is perceived to be present, whether for physiological or psychological reasons, performance can be reduced.
The experimental model discussed by the authors is the measurement of subjective mood feelings postprandially following high-carbohydrate or high-protein meals. Both breakfast and lunch are considered. High-carbohydrate, low-protein lunches increased reported fatigue more than did higher-protein lunches. Breakfast of any macronutrient composition reduced fatigue compared with that in the baseline state. Protein-rich breakfasts reduced fatigue to a greater extent than did protein-poor, carbohydrate-rich breakfasts. Whether for breakfast or lunch, on a weight-for-weight basis, protein is reported to be more satiating than carbohydrate, an effect of possible importance in military situations.
The well-described effect of carbohydrate in increasing the tryptophan (TRP)/large neutral amino acid (LNAA) ratio in plasma is considered to be a possible mechanism for postprandial effects of carbohydrate on perceived fatigue. It has been reported that as little as 4 percent protein in the diet can prevent the elevation in the TRP/LNAA ratio caused by carbohydrate (Teff et al., 1989). Consistent with these data is the fact that the fatiguing effect of carbohydrate is most reliably seen when the meals contain less than 4 percent protein. In addition, considerable individual variation is encountered in these types of experiments, and from a military standpoint any practical utility is difficult to discern. The third, or physiological, definition of fatigue can also be a factor of major importance in military stresses involving severe or prolonged muscular exertion. Muscle fatigue, typified, for example, by the performance declines during the last stages of prolonged sprints or marathons, is associated with the buildup of lactic acid and other metabolic products of carbohydrate, amino acid, and fatty acid substrates used by the exercising muscles.
Also considered by Spring et al. (Chapter 17) are effects of carbohydrate on cognitive performance, which is affected differently by carbohydrates at breakfast, at lunch, or in snacks. However the reported effects are variable and not very robust. For example, even skipping breakfast altogether has only weak and inconsistent effects on cognitive performance in young children, adolescents, and adults. When performance differences were observed following meals varying in macronutrient composition, cognitive performance was better after higher-protein breakfasts (Spring et al., 1992).
Typically, it is observed that tasks involving cognitive performance including vigilance, reaction time, sorting, and arithmetic show steady improvement during the day, although the pattern is interrupted temporarily by a postlunch slump (see discussion in Chapter 17). Cognitive performance declines after lunch with bigger declines associated with bigger lunches. In addition to the number of calories, protein-poor meals have been reported to elicit larger decreases in cognitive performance than protein-rich meals (Lieberman et al., 1986a). Negative effects of skipping lunch were reported to
be modest in a laboratory setting and somewhat more robust in a field setting involving prolonged highway driving. In another setting, Kanarek and Swinney (1990) reported that a late afternoon calorie-rich snack enhanced performance compared with performance after consuming a low-calorie diet soda. No differences were observed between a confectionery-type snack and yogurt when both contained at least 25 percent protein.
In summary, meals containing protein and carbohydrate have more beneficial effects than meals that are nearly protein-free. However, any behavioral effects seen are time and context dependent. Snacks have utility in enhancing performance between meals. Spring and colleagues emphasize that research on diet and behavior has tended to overemphasize simple cognitive/sensorimotor measures, and insufficient attention has been given to more subtle characteristics such as the motivation to undertake important activities and the ability to cope with stress and exhibit sociability.
Data suggesting that administration of glucose enhances working memory during cold stress are reviewed by Stephen T.Ahlers and colleagues (Chapter 16). Previous studies reported in the literature and cited by the authors suggest that glucose administration can improve both long-term and working memory. Ahlers et al. evaluated the effect of glucose administration on the cold-induced impairment of working memory in rats using the delayed matching-to-sample (DMTS) test. Doses of glucose between 10–100 mg/kg of body weight substantially blocked the impairment of accuracy in matching in the test caused by cold exposure. Initial data reported by Belenky et al. (Chapter 7) demonstrated a decrease in brain glucose metabolism accompanying sleep deprivation-induced decrements in cognitive performance (Thomas et al., 1988).
In summary, there are tantalizing hints that glucose administration during cold stress and after sleep deprivation, such as could be accomplished with a candy bar, has some potential to improve memory and performance on cognition-based tasks. Much more work is needed to explore this possibility.
An overview of the performance enhancement potential of structured lipids is provided by Ronald L.Jandacek (Chapter 18). Structured lipids are defined as fats that are synthesized from mixtures of long- and medium-chain fatty acids. Structured lipids are therefore differentiated from typical dietary fats by the presence of significant amounts of medium-chain fatty acids (i.e., fatty
acids containing 6 to 10 carbon atoms). Jandacek reviews the digestion, absorption, and metabolism of long- and medium-chain fatty acids because any possible performance enhancement potential for structured lipids depends on differences in the way long- and medium-chain fatty acids are handled by the body.
A major demonstrated advantage of structured lipids in enteral and parenteral nutrition is through the provision of essential fatty acids and a high caloric density with a small osmotic load. These nutritional advantages of structured lipids have been demonstrated most notably under conditions of stress such as trauma, burns, and infection. Although such nutritional support has clear military importance, it is not closely relevant to the subject of this report.
The possibility that structured lipids might have performance-enhancing potential is based on the hypothesis that glycogen utilization during exercise might be spared by the rapid oxidation of the medium-chain fatty acids present in structured lipids. Medium-chain fatty acids in the diet are delivered directly and rapidly to the liver via the portal circulation. They appear to be preferentially oxidized compared to long chain triglycerides. It is further postulated that following metabolism in the liver, the ketone bodies that are produced, acetoacetate and ß-hydroxybutyrate, would be delivered to the muscle, sparing glycogen utilization. Unfortunately the studies published to date, as reviewed by Jandacek, do not support the hypothesis.
In summary, although structured lipids have an important role to play in enteral and parenteral nutrition, their potential for enhancing physical and mental performance, especially in a military setting, is low.
Choline is an essential component of the human diet that is important for the normal functioning of all cells (Zeisel, 1988). Choline and choline-containing compounds are critical for a wide variety of metabolic processes within the body, including acting as a messenger within the cells and as neurotransmitters in the nervous system, controlling muscle contraction, providing methyl groups in a variety of intracellular reactions, as a component of triglyceride transport, and participating in the immune response.
Functions of Choline
Perhaps the best-known function of choline is as a component of acetylcholine, an important neurotransmitter. A small fraction of dietary
choline is acetylated to acetylcholine by the action of acetyltransferase, an enzyme present in the terminals of cholinergic neurons in the brain and periphery. Acetylcholine in the brain is intimately associated with memory. Acetylcholine acts as a signaling agent in muscle by transmitting the neural signal across the neuromuscular junction. The availability of acetylcholine in the peripheral nerves and muscles affects muscle function. Deficiency of choline in the diet decreases the conduction velocity of nerve transmission and produces earlier fatigue.
Choline is critical for signal conduction in a number of tissues. Choline-containing phospholipids act as vital elements in signaling across cellular and intracellular membranes. Agents from outside the cells stimulate hydrolysis of phosphatidylinositides, and the resulting protein phosphorylation cascades are a major mechanism for transmitting messages into the interior of cells. Phosphatidylcholine and sphingomyelin and their metabolites play a role in this by serving as mediators and modulators of transmembrane signaling. Hundreds of messengers have been identified as mediated by the hydrolysis of phospholipids (e.g., insulin, norepinephrine, serotonin, vasopressin, thrombin, growth factors, and cytokines).
Choline is critical for lipid metabolism because phosphatidylcholine is a component of very low density lipoproteins (VLDLs). VLDLs are the major vehicle for transporting the triglycerides synthesized in the liver. Adequate choline must be available for the liver to form VLDLs, or triglyceride accumulation in the liver occurs.
Choline’s role in methyl group metabolism is through its metabolite, betaine, which serves as a methyl donor in the formation of methionine from homocysteine. Choline metabolism is linked to folate and vitamin B6 metabolism, the other major mechanism for methyl group donation. Disturbances in folate or methionine metabolism result in changes in choline metabolism and vice versa.
Dietary Choline and Choline Deficiency
Free choline or choline-containing esters are present in a wide variety of foods in the diet, and the usual intake of such compounds by humans is probably about 700–1000 mg per day. There is no recommended dietary allowance for choline for humans, but intakes of 500 mg/day result in decreased plasma choline and phosphatidylcholine concentrations. The human body (reference 70-kg man) contains about 500 mg of free choline and 30 g of choline esters. Diets deficient in choline produce liver dysfunction within 3 weeks, resulting in massive triglyceride accumulation in the liver and increases in plasma concentrations of liver enzymes. Dietary deficiency of
choline also produces changes in muscle conduction velocity on electromyography, and choline-deficient animals are more sensitive to the effects of administered acetylcholine. Finally, choline is the only single nutrient for which dietary deficiency is associated with the development of cancer. Choline-deficient rats have an increased incidence of hepatocellular malignancy and are much more sensitive to the effects of administered carcinogens.
Potential Areas of Clinical and Military Interest
Choline should be of interest to the military for several reasons, relating to its diversity of functions in the body. Soldiers who are active in the field frequently are given high calorie meals. Although studies have shown that the average calorie intake actually decreases in the field, those soldiers who increase their caloric intakes may be at risk of developing liver abnormalities, particularly fatty liver. This phenomenon can be prevented by adding choline or choline-containing products to the diet. Likewise, injured individuals who require total parenteral nutrition (TPN) may develop liver function abnormalities, since choline in TPN formulas is present only as phosphatidylcholine in the lipid emulsion. Malnourished soldiers who are given high-calorie TPN formulations may require extra choline (such as lecithin supplements) to prevent hepatic steatosis and liver function abnormalities.
Choline deficiency reduces muscle performance, and there is evidence that choline supplements may enhance performance. Supplementation (2.8 g) with dietary choline during a 20-mile (32-km) run prevented the drop in plasma choline concentrations usually seen and improved run time by 5 minutes (Sandage et al., 1992). Additional placebo-controlled, randomized, double-blind trials are needed to determine whether choline supplementation will enhance the performance of military personnel in the field.
Choline supplementation enhances memory and reaction time in animals, particularly aging animals, and enhances memory in humans (Bartus et al., 1980; Meck et al., 1989). The mechanisms of this are unclear, but increases in dendritic spines in the cerebral cortexes of aging mice suggest that choline may alter the anatomy of brain cells (Bertoni-Freddari et al., 1985; Mervis et al., 1985). An increase in muscarinic receptor density in the brain also has been suggested, as has acetylcholine content. Alterations in brain function may occur via changes in phospholipid biosynthesis that alter brain membrane composition and structure. These observations suggest that research should be done to determine whether choline supplementation enhances intellectual performance in the field.
Since choline and vitamin B6 are critical for methyl group metabolism and folate metabolism and acts as a messenger for some growth factors, protein
synthesis is dependent on adequate choline status. Wound healing is delayed in choline-deficient animals. Additional research is indicated to determine whether choline supplementation enhances wound healing in injured soldiers, particularly in injured individuals who are malnourished. Also, since choline deficiency alters the immune response, this may affect wound healing and recovery from injury or illness in the field.
In summary, basic studies to evaluate the mechanisms of action of choline in altering signal transduction may point the way to future clinical studies on improvement of both muscle and intellectual performance. Some studies of injury and injury in malnourished individuals would better be done in animals initially.
The literature on the effects of cafeine on behavior, performance, and health is extensive and somewhat contradictory (for reviews see for example Bergman and Dews, 1987; Graham, 1987; Hughes et al., 1988; Jarvis, 1993; Smith et al., 1994a,b). David Penetar and colleagues (Chapter 20) present a new study on the effects of caffeine on cognitive performance, mood, and alertness in human subjects who had been sleep deprived, and summarize current knowledge about the use of such supplements. Caffeine is known to exert its central nervous system-mediated effects by blockade of adenosine receptors. Its stimulant effects when compared with those of other drugs such as amphetamines are weak, but most studies to date suggest that it tends to delay sleep, reduce the deterioration of performance associated with fatigue and boredom, and decrease steadiness of the hands, particularly when performance is already partially degraded on repetitive, nonintellectual tasks.
Less well understood are the effects of caffeine in reversing changes caused by sleep deprivation. To clarify these issues, three doses of caffeine (150, 300, and 600 mg/70 kg of body weight) were assessed among normal healthy males after 2 days of sleep deprivation. Cognitive performance, mood, alertness, vital signs, serum caffeine concentrations, and plasma catecholamine levels were also assessed.
Cognitive performance was measured using a computerized assessment battery. Choice reaction time (for 8 hours), sustained attention (for 10 hours), and logical reasoning (for 12 hours) significantly improved after caffeine administration, although tests of code substitution and immediate and delayed recall were unaffected.
Mood was assessed by ratings on a profile of mood states questionnaire. Significant increases in vigor were reported for 2 hours after taking the dose, with decreases in fatigue and confusion. Also, significant improvements in
mood for 2 hours postdose were reported on visual analog scales for increased alertness, confidence, energy level, and talkativeness and decreased sleepiness. However, anxiety and jitteryness/nervousness also increased. At 12 hours postadministration, ratings for increased energy levels, decreased sleepiness, and jitteryness/nervousness remained elevated.
Alertness, assessed by the modified multiple sleep latency test, also improved for 4.5 hours after caffeine administration, with alertness returning to 50 percent of rested levels when the highest doses were used. Oral body temperature remained elevated for 12 hours and blood pressure (diastolic) for one hour, but neither heart rate nor systolic blood pressure were elevated.
It was concluded that large doses of caffeine reversed sleep deprivation-induced degradation in cognitive performance, mood, and alertness without serious side effects. These data were consistent with those represented in most other studies reviewed. Therefore, Penetar et al. (Chapter 20) recommended that caffeine be included in rations at 250 mg per tablet and that it be made available to soldiers for maintaining performance during specific military operations. The authors did not study individuals with habitually high levels of caffeine ingestion; it would be useful to determine whether the effects of the doses of 300–600 mg noted in this study were as pronounced in individuals with markedly higher levels of typical intakes.
Sustaining optimal soldier performance is recognized to depend on other measures as well. The first is training, so that tasks can be performed with a minimal level of cognitive effort, cross-training so that individuals can substitute for each other, developing and adhering to appropriate work and rest cycles, exerting wise leadership so that unnecessary demands are not placed on subordinates, and modification of systems to minimize errors. Second, enforcing sleep discipline so that the sleep-deprived individual sleeps as much as he or she can and in as a hygienic manner as possible.
The relationship between caffeine intake and health outcomes particularly cancer incidence, cardiovascular disease (CVD), and effects on fertility, and pregnancy and child outcome, has been the focus of many studies. While data from individual studies has been contradictory, reviews tend to conclude that there is no significant association or negligible/transient effects relating moderate caffeine consumption and cancer, CVD, fertility, and osteoporosis (see for example AMAC, 1984; Cooper et al., 1992; Gordis, 1990; Joesoef et al., 1990; Johansson et al., 1992; Lubin and Ron, 1990; Olsen, 1991; Rosenberg, 1990; Schairer et al., 1986; Wilson et al., 1989). However, reports continue to demonstate that caffeine intake causes an elevation in blood pressure (Smith et al., 1994a,b). Although the blood pressure elevation produced by caffeine has been interpreted as transient and within the range produced by typical activities (HHS, 1988; Myers, 1988), blood pressure bears monitoring in any future studies of performance enhancement with caffeine
supplementation. Recent reports that assessed the safety of caffeine consumption during pregnancy have continued to produce conflicting information (Eskenazi, 1993; Infante-Rivard et al., 1993; Mills et al., 1993). These data indicate that high levels of caffeine intake (>300 mdg/d) potentially increases the risk of spontaneous abortion and intrauterine growth retardation during pregnancy (Mills et al., 1993). The risk to pregnant women of low levels of caffeine intake is uncertain. Further, women often do not realize they are pregnant and/or do not receive prenatal care until after the time period when most spontaneous abortions occur. Should the Army pursue further research in performance enhancement using caffeine products, these health issues must be carefully considered.
In summary, continued research on the mechanisms for the evident effects of caffeine on cognitive performance, mood, and alertness and how these may be enhanced in combination with other dietary measures is warranted. Of particular interest is how to maximize positive effects when performance is already degraded. Individual differences, expectancy, and placebo effects need further elucidation. In the meantime, practical applications of demonstrated effects in ration planning may be in order.
In Chapter 21 Peggy R.Borum reviews the current evidence on whether administration of carnitine enhances physical performance. Carnitine, (ß-hydroxy-t-trimethylammonium butyrate) is a minor nitrogenous compound in muscle that plays a critical role in energy metabolism. Carnitine functions as a transportable high-energy compound that can be reformed without the use of ATP. It acts as a storehouse of high energy compounds, stimulates fatty acid oxidation, transports acyloenzyme A (acyl-COA) across membranes, prevents the accumulation of lactate, and stimulates carbohydrate and amino acid utilization. These functions have led to the hypothesis that supplementation of free carnitine, acetylcarnitine, or propionylcarnitine theoretically might enhance the oxidation of fatty acids during exercise, thus sparing the use of muscle glycogen, delaying the onset of fatigue, and enhancing exercise performance. Today, research is hindered by the lack of a simple method that permits measurement of the various acylcarnitines in large numbers of samples.
Originally, carnitine was called vitamin B-T because it was essential for a mealworm; present evidence is that it is not a vitamin for healthy humans, and there is no Recommended Dietary Allowance for it (National Research Council, 1989). In humans, a rare inborn error of carnitine metabolism is associated with muscle fatigue. Carnitine deficiency may also occur secondary to other pathologies. Most Americans consume 50–100 mg of carnitine per day
in their diets, with some eating three times that amount. Carnitine appears to be safe, but there is little evidence that more is better in normal individuals.
Clearly, carnitine is important metabolically in the exercising muscle. However, existing studies of carnitine supplementation differ in their reported effects, depending on the training or conditioning of the subject; the intensity of exercise; and the type, dose, timing, and route of supplement administration employed. The forms of carnitine used in supplementation studies vary. Most investigations have used free carnitine, but the uptake of the various acylcarnitines as opposed to free carnitine may differ from organ to organ. In studies of carnitine supplements on exercise performance, the amounts used are several times higher than usual dietary intakes of the substance. The absorption of pharmacological doses of carnitine may differ from that of lower doses. The time between carnitine supplementation and exercise has also varied in studies to date. The intensity of exercise also alters muscle metabolism, and it appears to affect carnitine metabolism in muscles. In addition, physical training alters many aspects of muscle metabolism, including that of carnitine.
Few changes are observed with low-intensity exercise, but with high-intensity exercise after the point at which elevated plasma lactate concentrations are first observed and below the individual’s maximal work capacity, the free carnitine concentration decreases and the short-chain acylcarnitine concentration increases (Hiatt et al., 1989). These changes persist into recovery after exercise. In contrast to muscle, changes in the type and amount of carnitine in plasma are relatively slight during or after exercise (Hiatt et al., 1989). Training affects nutrient utilization in muscle during exercise, and these changes include increased free fatty acid oxidation during prolonged exercise. There is evidence in isolated intact mitochondria in human muscle preparations that pyruvate oxidation increases when L-carnitine is present in the medium and that it decreases when either inhibitors of pyruvate or carnitine are added (Uziel et al., 1988). Human subjects performing maximal exercise tests on bicycle ergometers have been studied with 2g supplements of L-carnitine or placebos, and increases in both plasma lactate and pyruvate levels with maximal exercise were lower after carnitine administration throughout the trial, with greater or equal work accomplished, although returns to baseline concentrations of lactate were the same in both groups (Siliprandi et al., 1990).
Other evidence in humans suggests that carnitine supplementation may modestly increase the use of fatty acids during exercise. Carnitine supplementation may preserve the available coenzyme A pool. Carnitine supplementation prior to exercise increases work output in maximal exercise tests in some, but not all, studies (Oyono-Enguelle et al., 1988; Vecchiet et al., 1990). Exercise may also alter metabolic compartmentalization of carnitine and acylcarnitine in muscle during and after exercise, with free carnitine falling and short-chain carnitine rising (Decombaz et al., 1992). However, in the same study, which
did not employ carnitine supplementation, there was little evidence that endurance conditioning had an effect on skeletal muscle carnitine concentrations, nor were there correlations between total carnitine concentration in muscle at rest and finishing time or between muscle carnitine and maximal aerobic power or duration of training. In another study, following carnitine supplementation for 5 days, the ratio of acylated to free carnitine increased from preexercise values during exercise and remained elevated for 40 minutes postexercise (Soop et al., 1988).
In summary, while carnitine functions as a transportable high energy compound that can be reformed without the use of ATP, carnitine supplementation has not been demonstrated to improve physical or mental performance in well-nourished individuals. Basic research on the effects of various forms of carnitine in exercise may be in order. These will be facilitated by the development of simple methods that permit measurement of various acylcarnitines in large numbers of samples. There is no conclusive evidence to date that carnitine supplementation is helpful in enhancing physical performance during exercise. The status of carnitine research is such that, at present, no recommendation to increase levels of carnitine in rations are called for.
SAFETY AND REGULATORY ASPECTS OF POTENTIAL PERFORMANCE-ENHANCING FOOD COMPONENTS
Safety of Amino Acids
Military rations exceed the RDAs for protein and the protein source provides an adequate intake of the essential amino acids. Therefore, the supplementation of military rations with amino acids at the usual range of dietary intakes would not be expected to improve performance. Amino acid intakes at several times the usual dietary intakes must be evaluated for safety as well as effects on performance. Several of the chapters address the use of tyrosine supplements to enhance performance. Such use is pharmacological rather than nutritional and therefore presents different concerns with regard to safety. In Chapter 22, Timothy J.Maher discusses the recent issue associated with supplements of L-tryptophan. In this incident, the occurrence of eosinophilia-myalgia syndrome (EMS) was associated with the use of L-tryptophan supplements. It was subsequently shown that the induction of EMS was associated with one or more impurities in one particular product and was not the result of L-tryptophan ingestion per se. Nonetheless, this experience raised safety concerns about the use of amino acid supplements specifically and more generally the use of all nutrients as supplements at physiological levels. It is clear that these types of supplements must be highly
purified before they can be considered safe for use. The safety of amino acid supplements has been the subject of a recent review by the Life Sciences Research Office (LSRO) of the Federation of American Societies of Experimental Biology (Anderson and Raiten, 1992).
Much research has been published on the important nutritional roles of amino acids as the essential building blocks for proteins and as precursors of other physiologically important compounds such as hormones and neuroactive peptides. These needs are normally met by the quantities of amino acids supplied by ingested foods and are presented to the body as a mixture of many amino acids. These levels of exposure are generally recognized as presenting no safety concerns. However, amino acid supplements, particularly methionine and lysine, can provide much greater quantities of single amino acids, which raises the potential of direct toxic effects or the possibility of creating “imbalances” of amino acids that could have deleterious consequences.
Amino acid supplements proved to be a boon in poultry and swine production by permitting the upgrading of low-quality plant proteins to allow for maximal growth rates. In these circumstances the exposure levels were of the same order of magnitude as expected from normal diets, and the likelihood of toxicities or imbalances was nil. More recently, over-the-counter (OTC) availability of amino acid supplements and their potential use in pharmacological quantities have created concern. The LSRO report (Anderson and Raiten, 1992) reviews in detail the literature on animal and human studies that can shed light on the safety of supplements. It is clear from the LSRO report that many amino acids can have toxicological effects, that there is a paucity of information to establish safe use levels for individual amino acid supplements, and that there is adequate evidence to raise concern about certain vulnerable population groups.
One of the amino acids that was discussed at length during this workshop and that forms the basis for this report is tyrosine, which was reported to have beneficial effects in response to stress by virtue of its role as a precursor for catecholamines. Tyrosine appears to be well tolerated by rats consuming a high-protein diet, but in animals fed low-protein diets, a distinct syndrome is observed involving cataracts, skin lesions, and histopathological changes (Anderson and Raiten, 1992).
In summary, the available evidence, while inadequate to establish safety, does raise concerns about the indiscriminate use of amino acid supplements. These data make it clear that before advocating any use of supplements, appropriate safety studies should be conducted. The LSRO, in its report (Anderson and Raiten, 1992), has proposed a two-tiered approach to animal testing for individual amino acids or mixtures of amino acids. Human clinical studies were also recommended by LSRO, again involving a two-tiered
approach (see Anderson and Raiten, 1992). These recommendations represent a sound starting point for establishing the safe use of amino acid supplements.
Regulation of Food Components by the U.S. Food and Drug Administration1
The considerations for the approval of food additives are well developed by John E.Vanderveen in Chapter 23. The most important consideration is the demonstrated safety of the material in question. The general approach to demonstrating safety is delineated in the U.S. Food and Drug Administration’s (FDA) Red Book2. A further consideration is the matter of whether the uses considered during the CMNR workshop in November, 1992 represent usage as a “food” or as a “drug.” Different regulations control each class of materials. Further, if a substance is classified as a “drug,” then not only must safety be demonstrated but data showing efficacy must also be presented.
It would seem critical for the military to follow the same requirements that the FDA would require for general use in the civilian population. Therefore, in considering any of the materials that have been discussed as agents capable of enhancing performance, it is important to recognize that none of these materials has been demonstrated to be “safe,” notwithstanding the fact that all of these agents exist in natural foods. Importantly, the proposed uses (to enhance performance) require exposure levels that are in excess of what would be consumed in foods.
It would seem that the intended uses as performance enhancers, with the exception of candy bars or CHO supplements, would classify the compounds in question in the drug category. The testing requirements are not necessarily more stringent for a drug, in fact, as noted by John E.Vanderveen, a drug classification permits a benefit-risk consideration that is not possible for a food category consideration. Thus, it would be necessary to generate data demonstrating minimal risk from the expected exposures and data clearly demonstrating a benefit from the proposed doses.
The increasing sophistication of weapon systems and the complexity of military operations place heavy demands on the soldier to effectively use these systems in military operations. Although thorough training can prepare the individual for effective use of these systems, these sophisticated weapons and the associated training do not eliminate and, in fact, may not reduce the physical demands on the individual soldier in combat. Also, although computers and other information processing aids may help the soldier to process information for effective decision making, the consequences of errors in cognition are multiplied. Therefore, maintaining or enhancing physical and mental performance of the individual engaged in combat is an important objective and deserves a major effort in the identification and evaluation of systems for delivery of those components that pass the rigorous tests for enhancing performance. Although the November 1992 workshop and this report form a good starting point in the selective evaluation of nutrients or food components, it is important that there be a continuing evaluation of the basic nutrition, biochemical, and neuroscience research literature to further identify possible candidates for evaluation. In the following chapter, the CMNR discusses the specific evaluation of the nutrients or components covered in this workshop and makes recommendations for their evaluation. Future research recommendations are also presented.
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