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The Role of Protein and Amino Acids in Sustaining and Enhancing Performance Protein and Amine Acids, 1999 Pp. 85-91. Washington, D.C. National Academy Press 3 Protein and Amino Acids: Physiological Optimization for Current and Future Military Operational Scenarios LTC Karl E. Friedl1 INTRODUCTION In conceptualizations of the battlefield of the future, the battle space involves three-dimensional swarms instead of conventional lines of attack; the tempo is faster; and war fighters are fewer in number, are more dispersed, and perform more functions. Increased technological complexity and lethality add to the already considerable stress on the individual. In this setting, individual lapses in judgment and less-than-perfect performance may be catastrophic. Furthermore, new tactics and equipment may be wasted if their requirements outstrip human capabilities. The protein content of operational rations as well as 1 Karl E. Friedl, Army Operational Medicine Research Program, U.S. Army Medical Research and Materiel Command, Fort Detrick, MD 21702-5012.
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The Role of Protein and Amino Acids in Sustaining and Enhancing Performance specific amine acid supplements may provide a decisive advantage in such high-stress scenarios, including improved resistance to disease, preservation of muscular strength through maintenance of muscle tissue, and optimal cognitive performance even in the face of intense stressors. One of the near-term requirements is to produce a limited-use operational ration that supports optimal cognitive and physical metabolic function while promoting utilization of the soldier's existing fat stores. This ration could be useful in short-duration, direct-action missions and in survival kits (Jones et al., 1993). Such a ration is not a new concept in military nutrition research; nearly 20 years ago, Consolazio and his colleagues (1979) asked: Would a planned ration of 600 kcal, if consumed, be more beneficial to the soldier than the remnants of a 3600 kcal ration, the majority of which was indiscriminately discarded because of its heavy weight? Consolazio's studies reiterated previous findings that 100 g of glucose and some electrolytes were important constituents of such a limited-use ration just to ensure minimal function (Taylor et al., 1957). Within the past 3 years, carbohydrate drink and food bar supplements have been developed because of the clearly demonstrated benefits to military performance (Murphy et al., 1994). Current scientific advances may now allow us to consider the specific protein and amine acid content that could be sustaining and even enhancing. The purpose of this review by the Committee on Military Nutrition Research is to evaluate the state of knowledge from basic research and suggest promising research directions in protein and amine acid modulation of military performance in stressful operational scenarios. The principal operational ration, the Meal, Ready-to-Eat (MRE), is highly fortified in protein (providing 2 g/kg body weight [BW]/d for the typical 75 kg male soldier). This ensures that the estimated daily requirement for protein is met even by Ranger students subsisting largely on MREs but offered less than a full daily ration. Thus, even with an average dally deficit of 1200 kcal/d for 8 weeks, Ranger students still average in excess of 100 g of protein/d (Moore et al., 1992). Although more sensitive markers of protein status such as circulating insulin-like growth factor-I and retinol-binding protein were markedly suppressed during periods of reduced food intake (Nindl et al., 1997), the soldiers developed no clinical, biochemical (e.g., serum protein and albumin), or gross physiological signs of protein deficiency (Martinez-Lopez et al., 1993). The Ranger students also lost a considerable amount of lean mass, although the proportion lost was inversely related to initial fat energy stores (Friedl et al., 1997). The question remains whether a higher protein diet or a carefully crafted supplement could provide any protection to lean mass in comparison with a group receiving the same total (and deficient) calories. A possible approach may come from consideration of factors altered in exercise, which have been
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The Role of Protein and Amino Acids in Sustaining and Enhancing Performance suggested to reduce whole-body protein catabolism even in hypocaloric settings (Carraro et al., 1990). Excessive levels of protein in operational rations may have undesirable effects. In a study of combat engineers engaged in a 30-d field-bridging exercise, men subsisting on the MRE consumed only 2,500 kcal/d during the study. However, even with wastage of at least one-third of the rations provided, they consumed components that provided 103 g protein per day, achieving 100 percent of the military Recommended Daily Allowance (Thomas et al., 1995). As further evidence of the high protein intake, 24-h urinary nitrogen excretion doubled by 30 days on the MRE diet. This level of intake was equivalent to that of energy-restricted Ranger students, except that for the engineers this was a voluntary restriction. High protein intake and positive balance may even produce premature satiety in field feeding. Tyrosine augments the anorectic action of sympathomimetic drugs in rats (Hull and Maher, 1990); the right mix in a high-protein food might similarly augment the sympathetic activation of soldiers working hard in the field and produce an anorectic effect. Although highly speculative, it is conceivable that this explains the inadequate energy intake observed in field studies with the MRE, where the average intake is 3000 kcal/d, and the average estimated energy requirement is 4000 kcal/d. High protein content of the rations also potentially increases calcium excretion, although studies feeding protein up to 2 g/kg BW indicate no calciuretic effects (Spencer and Kramer, 1986). Protein intake in excess of requirements increases water loss with increasing urea excretion, a factor that could be decisive in isolated desert environments. Conceivably, a low protein ration could be developed for limited use in dry environments to reduce the logistical burden of water transport requirements. The potential brain effects of some of the amino acids that serve as neurotransmitter precursors, such as tyrosine and tryptophan, are intriguing for actions beyond appetite control. Manipulation of serotonin levels with tryptophan (Spring, 1984) might prove useful in the prevention of stress casualties, estimated to be as high as one in every four medical casualties in future conflicts. Tyrosine, acting as a precursor of catecholamines, may be useful in sustaining soldiers' performance in high-stress environments. Several human and animal studies suggest that 85-179 mg/kg of tyrosine can improve mental performance and reduce anxiety in stressful conditions and with inadequate rest (Lieberman, 1994; Neri et al., 1995). John Thomas and his colleagues at the Naval Medical Research Institute have reported preliminary data from studies with Marine sharpshooters on maneuvers in Alaska that indicated a trend toward restoring marksmanship performance degraded by cold and fatigue (Shurtleff et al., 1994). Improved field tests for assessment of military performance still need to be developed to better evaluate such ration benefits, as recommended following the first major workshop of the Committee on Military Nutrition Research (CMNR) (National Research Council, 1986).
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The Role of Protein and Amino Acids in Sustaining and Enhancing Performance In the study of Ranger students in stressful training, infection rates were notably elevated in association with derangements in indices of immune function (Kramer et al., 1997; Martinez-Lopez et al., 1993). Medical researchers were asked to determine if a simple fix such as a vitamin pill or other supplement could sustain the health of soldiers in stressful training without having to ease the rigors of the Ranger course; however, plasma biochemical measures indicated no vitamin or nutrient deficiencies (Moore et al., 1992). A similar model of stress-induced alteration in immune function indices was established by Colonel Fairbrother in soldiers during the 21-d Special Forces Assessment and Selection (SFAS) course (Fairbrother et al., 1995), although there was no significant incidence of infectious disease. This model has since been used for empirical test and evaluation of various "magic bullet" nutritional interventions. On the basis of the important role of glutamine in lymphocyte function, several researchers have suggested that this might sustain immune function in catabolic subjects (Ziegler et al., 1998). In fact, in the review of data from the 1991 Ranger study, the CMNR recommended that the effects of training and associated stressors on protein and amine acid (including glutamine) metabolism should be studied, particularly for the purpose of potential special supplements (CMNR, 1992). A second study of soldiers in the SFAS course tested such an intervention, comparing glutamine supplementation with an isonitrogenous control. The results demonstrated no effect on a wide variety of immune parameters (Shippee et al., 1995). This result does not exclude a benefit from glutamine supplementation but suggests that the solution may be more complex than simply adding back the amine acid (Ziegler et al., 1996). Glutamine may be beneficial in the same setting for other reasons. Presumably as a consequence of the semistarvation in the Ranger studies, a subclinical edema was noted that was reflected in an increased proportion of total body water in the lean mass. In studies with hospitalized catabolic patients, extracellular fluid excess was successfully attenuated with glutamine feeding (Scheltinga et al., 1991). Since we don't understand the mechanism or potential adaptive value of this disproportionate fluid retention in otherwise healthy subjects, interventions to prevent it may be premature. The specific protein requirements of servicewomen may not differ from those of servicemen, but these requirements have been inadequately studied. At least two Defense Womens' Health Research Program grants center on this issue. In one, Vernon Young (Massachusetts Institute of Technology) is testing substrate utilization in subjects working intensively while on energy-deficient diets in a partial simulation of Army Ranger training. The key experiment in this study is a 21-d hypocaloric challenge to men and women, where the protein content of the diet is kept high (1.2 g/kg/d). This experiment will address gender differences in metabolic, physical, and mental performance in chronic hypocaloria. In another study, Anne Loucks (Ohio University) is attempting to define a threshold of energy deficiency that produces amenorrhea, having previously demonstrated an effect of inadequate protein intake on thyroid
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The Role of Protein and Amino Acids in Sustaining and Enhancing Performance hormone and menstrual status in exercising women. The central thesis is that men are less susceptible to dietary disruption of luteinizing hormone pulsatility than are women. Conceivably, in future ration supplements, servicewomen could benefit from a high-protein or high-amino acid supplement that modifies endocrine responses to stress and hypocaloria. In the distant future, regulation of urea formation and recycling of protein, using something like a biochemical hibernation trigger observed in bears (Nelson et al., 1975), may be important in manipulations of soldiers in stasis during long-term travel, during special surveillance missions, or after injury. Instead of increasing protein intake in an attempt to preserve lean mass, the strategy would be to prevent the loss of urea nitrogen. Some of these adaptations appear to be present already in endurance-trained athletes where intensive prolonged exercise does not shift the balance to one of net protein catabolism (Stein et al., 1989). Future research on nutritional interventions to counter the effects of operational stressors may rely heavily on protein and amino acid components because of the important potential for these nutrients to modulate cognitive function and sustain performance. REFERENCES Carraro, F., W.H. Hartl, C.A. Stuart, D.K. Layman, F. Jahoor, and R.R. Wolfe. 1990. Whole body and plasma protein synthesis in exercise and recovery in human subjects. J. Appl. Physiol. 258:E821-E831. Consolazio, C.F., H.L. Johnson, R.A. Nelson, R. Dowdy, and H.J. Krzywicki. 1979. The relationship of diet to the performance of the combat soldier: Minimal calorie intake during combat patrols in n hot humid environment (Panama). Technical Report 76. San Francisco, Calif.: Letterman Army Institute of Research. Fairbrother, B., R.E. Shippee, T.R. Kramer, E.W. Askew, and M.Z. Mays. 1995. Nutritional and immunological assessment of soldiers during the Special Forces Assessment and Selection Course. Report USARIEM-T95-22, AD-A299 556. Natick, Mass.: Army Research Institute of Environmental Medicine. Friedl, K.E. 1997. Variability of fat and lean tissue loss during physical exertion with energy deficit. Pp. 431-450 in Physiology, Stress, and Malnutrition: Functional Correlates, Nutritional Intervention. J.M. Kinney and H.N. Tucker eds. New York: Lippincott-Raven Publishers. Hoffer, L.J., and R.A. Forse. 1990. Protein metabolic effects of a prolonged fast and hypocaloric refeeding. Am. J. Physiol. 258:E832-E840. Hull, K.M., and T.L. Maher. 1990. L-tyrosine potentiates the anorexia induced by mixed-acting sympathomimetic drugs in hyperphagic rats. J. Pharmacol. Exp. Ther. 255:403-409. IOM (Institute of Medicine). 1992. A Nutritional Assessment of U.S. Army Ranger Training Class 11/91. March 23. Washington, D.C. Jones, T.E., S.H. Mutter, J.M. Aylward, J.P. DeLany, and R.L. Stephens. 1993. Nutrition end hydration status of aircrew members consuming the Food Packet, Survival, General Purpose, Improved during a simulated survival scenario. Report USARIEM-T1-93. Natick, Mass.: U.S. Army Research Institute of Environmental Medicine.
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The Role of Protein and Amino Acids in Sustaining and Enhancing Performance Kramer, T.R., R.J. Moore, R.L Shippee, K.E. Friedl, L.E. Martinez-Lopez, M.M. Chan, and E.W. Askew. 1997. Effects of food restriction in military training on T-lymphocyte responses. Int. J. Sports Med. 18(1):S84-S90. Lieberman, H.R. 1994. Tyrosine and stress: Human and animal studies. Pp. 277-299 in Food Components to Enhance Performance. An Evaluation of Potential Performance—Enhancing Food Components for Operational Rations. Marriott B.M. ed. Institute of Medicine. Washington D.C.: National Academy Press. Loucks A.B., and E.M. Heath. 1994. Induction of low-T3 syndrome in exercising women occurs at a threshold of energy availability. Am. J. Physiol. 266:R817-R823. Martinez-Lopez, L.E., K.E. Friedl, R.J. Moore, and T.R. Kramer. 1993. A prospective epidemiological study of infection rates and injuries of Ranger students. Mil. Med. 158:433-437. Moore, R.J., K.E. Friedl, T.R. Kramer, L.E. Martinez-Lopez, R.W. Hoyt, R.E. Tulley, J.P. DeLany, E.W. Askew, and J.A. Vogel. 1992. Changes in soldier nutritional status and immune function during the Ranger training course. Report USARIEM-T13-92, AD-A257 437. Natick, Mass.: Army Research Institute of Environmental Medicine. Murphy, T.C., R.W. Hoyt, T.E. Jones, C.L. Gabaree, and E.W. Askew. 1994. Performance enhancing ration components program: Supplemental carbohydrate test. Report USARIEM-T95-2, AD-A288 560. Natick Mass.: Army Research Institute of Environmental Medicine. Nelson. R.A., J.D. Jones, H.W. Wahner, D.B. McGill, and C.F. Code. 1975. Nitrogen metabolism in bears: Urea metabolism in summer starvation and in winter sleep and role of urinary bladder in water and nitrogen conservation . Mayo Clin. Proc. 50:141-146. Neri, D.F., D. Wiegmann, R.R. Stanny, S.A. Shappell, A. McCardie, and D.L. McKay. 1995. The effects of tyrosine on cognitive performance during extended wakefulness. Aviat. Space Environ. Med. 66:313-319. Nindl, B.C., K.E. Friedl, P.N. Frykman, L.J. Marchitelli, R.L. Shippee, and J.F. Patton. 1997. Physical performance and metabolic recovery among lean, healthy men following a prolonged energy deficit. Int. J. Sports Med. 18:1-8. NRC (National Research Council). 1986. Cognitive Testing Methodology. Washington, DC: National Academy Press. Scheltinga, M.R., L.S. Young, K. Benfell, R.L. Bye, T.R. Ziegler, A.A. Santos, J.H. Antin, P.R. Schloerb, and D.W. Wilmore. 1991. Glutamine-enriched intravenous feedings attenuate extracellular fluid expansion after a standard stress. Ann. Surg. 214:385-393. Shippee, R.L., S. Wood, P. Anderson, T.R. Kramer, M. Neita, and K. Wolcott. 1995. Effects of glutamine supplementation on immunological responses of soldiers during the Special Forces Assessment and Selection Course [abstract]. FASEB J. 9:731. Shurtleff, D., J.R. Thomas, J. Schrot, K. Kowalski, and R. Harford. 1994. Tyrosine reverses a cold-induced working memory deficit in humans. Pharmacol. Biochem. Behav. 47:935-941. Spencer, H., and L. Kramer. 1986. The calcium requirements and factors causing calcium loss. Fed. Proc.. 45(12):2758-2762. Spring, B. 1984. Recent research on the behavioral effects of tryptophan and carbohydrate. Nutr. Health 3:55-67. Stein, T.P., R.W. Hoyt, M.O. Toole, M.J. Leskiw, and M.D. Schluter. 1989. Protein and energy metabolism during prolonged exercise in trained athletes. Int. J. Sports Med. 10:311-316. Taylor, H.L., E.R. Buskirk, J. Brozek, J.T. Anderson, and F. Grande. 1957. Performance capacity and effects of caloric restriction with hard physical work on young men. J. Appl. Physiol. 10:421-429. Thomas, C.D., K.E. Friedl, M.Z. Mays, S.H. Mutter, and R.J. Moore. 1995. Nutrient intakes and nutritional status of soldiers consuming the Meal, Ready-to-Eat (MRE XII) during a
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The Role of Protein and Amino Acids in Sustaining and Enhancing Performance 30-day field training exercise. USARIEM Technical Report T95-6. Natick, Mass.: U.S. Army Research Institute of Environmental Medicine. Ziegler, T.R., R.L. Bye, R.L. Persinger, L.S. Young, J.H. Antin, and D.W. Wilmore. 1998. Effects of glutamine supplementation on circulating lymphocytes after bone marrow transplantation: A pilot study. Am. S. Med. Sci. 315:4-10. Ziegler, T.R., M.P. Mantell, J.C. Chow, J.H. Rombeau, and R.J. Smith. 1996. Gut adaptation and the insulin-like growth factor system: Regulation by glutamine and IGF-I administration. Am. J. Physiol. 271:G866-G875.
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