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Project Overview and Committee Summary

PROJECT OVERVIEW

As the U.S. military faces the twenty-first century, it must contend with changes in the nature of warfare and deployment that have significant implications for individual performance. The more frequent redeployment of soldiers (necessitated by downsizing and by changing military strategies) mandates greater concern for their physical health and well-being and, therefore, the development of cutting-edge techniques for field assessment of health and nutritional status. Such assessment tools must demonstrate reproducibility and reliability in field tests, must be noninvasive, and must cause minimal interference with battlefield operations. Reliance upon techniques that are tied to laboratories must give way to ambulatory assessment. At the same time, the increasingly technological orientation of modern warfare raises the spectre of battles being waged by soldiers seated at computer terminals, with the capability for mass destruction at their fingertips, and necessitates great concern for the assessment and optimization of cognitive performance in those soldiers. Finally,



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Emerging Technologies for Nutrition Research: Potential for Assessing Military Performance Capability 1 Project Overview and Committee Summary PROJECT OVERVIEW As the U.S. military faces the twenty-first century, it must contend with changes in the nature of warfare and deployment that have significant implications for individual performance. The more frequent redeployment of soldiers (necessitated by downsizing and by changing military strategies) mandates greater concern for their physical health and well-being and, therefore, the development of cutting-edge techniques for field assessment of health and nutritional status. Such assessment tools must demonstrate reproducibility and reliability in field tests, must be noninvasive, and must cause minimal interference with battlefield operations. Reliance upon techniques that are tied to laboratories must give way to ambulatory assessment. At the same time, the increasingly technological orientation of modern warfare raises the spectre of battles being waged by soldiers seated at computer terminals, with the capability for mass destruction at their fingertips, and necessitates great concern for the assessment and optimization of cognitive performance in those soldiers. Finally,

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Emerging Technologies for Nutrition Research: Potential for Assessing Military Performance Capability budgetary constraints, coupled with the need to stay at the forefront of research, dictate that careful consideration be given to identifying the best available and emerging technologies and making priority decisions regarding which ones should be undertaken directly by the military, which deserve investment of funds to foster military applications, and which are best left to the private sector. THE COMMITTEE'S TASK As part of its responsibility to the Military Nutrition Division (MND) (currently the Military Nutrition and Biochemical Division) at the U.S. Army Research Institute of Environmental Medicine (USARIEM), the Committee on Military Nutrition Research (CMNR) on many occasions has provided evaluation of both research plans and ongoing research efforts funded by Department of Defense (DoD) appropriations. Examples include 1992 and 1996 reviews of research activities at the Louisiana State University's Pennington Biomedical Research Center, 1991 and 1993 reviews of a nutrition intervention project's results conducted during a U.S. Army Ranger training program, and a 1995 review of issues related to iron status of women enrolled in U.S. Army Basic Combat Training. In 1994, the CMNR was asked by the MND to identify and evaluate new technologies to determine whether the technologies will provide useful tools to help solve important issues in military nutrition research in the areas identified by MND, USARIEM. The committee was requested: (1) to provide a survey of newly available and emerging techniques for the assessment and optimization of nutritional and physiological status and performance, and (2) to evaluate the potential of these techniques to contribute to future research efforts involving military personnel. In addition, the committee was asked to make recommendations regarding the practicality and the application of such techniques in field settings. The MND asked the CMNR to include in its response the answers to the six questions listed in Table 1-1. To assist the CMNR in responding to these questions, a workshop was convened on May 22–23, 1995, in Washington, D.C., that included presentations from individuals with expertise in: techniques of body composition assessment, tracer techniques for the study of metabolism, ambulatory techniques for determination of energy expenditure, molecular and cellular approaches to nutrition, assessment of immune function, and functional and behavioral measures of nutritional status.

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Emerging Technologies for Nutrition Research: Potential for Assessing Military Performance Capability TABLE 1-1 Questions Posed by the Army State of the Art Will the technologies be a significant improvement over current technologies? Maturity and Availability How likely are the technologies to mature sufficiently for practical use? Practicality What is the cost/benefit ratio of the new technologies, and how expensive (in both monetary and personnel terms) will they be to employ compared with the importance of the information they will provide? Military Relevance Are the technologies of such critical value that their development should be supported by DoD funds—such as can be provided by the Small Business Innovative Research program? Complicating Factors and Methodological Questions How practical are the technologies? Will they require dedicated personnel and complex, exotic equipment? Will the data provided be difficult to analyze? Possible Use in the Field Can the technologies be used in the field (could they be used in the field or used to analyze samples collected in the field)? As a background to these presentations, a representative of the MND provided an overview of the military nutrition program and its research activities. For the preparation of their presentations, the invited speakers were asked to address the questions posed by the Army. The speakers discussed their presentations with committee members at the workshop and submitted written reports based on their verbal presentations. The committee met after the workshop to discuss the techniques presented and the information provided. Later, the CMNR reviewed the workshop presentations, summarized the information pertinent to each technique, and drew heavily on its collective expertise and the scientific literature to evaluate the potential contribution of each technique to military nutrition research and make recommendations regarding development of capabilities in these areas. In preparing this report, the committee limited its evaluation to technologies discussed at the workshop. The committee's conclusions and recommendations, as well as the responses to the six questions posed by the Army, appear in Chapter 2. THE CURRENT ARMY PROGRAM AND ITS FUTURE NEEDS The Army's nutrition research program is driven by the need of the Armed Forces to maintain and enhance performance in all operational environments.

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Emerging Technologies for Nutrition Research: Potential for Assessing Military Performance Capability Key to the performance requirements is understanding how nutritional status affects physical and cognitive performance and long-term health. The research program to provide the knowledge about these relationships is discussed by James A. Vogel in Chapter 3 in this volume. Vogel indicates that this program is composed of four main areas: development of nutritional strategies, evaluation of operational rations, establishment of nutritional requirements under diverse field situations, and assessment of nutritional status of military populations. In these areas of research, the technical requirements include methods for measurement of changes in body composition, plus the determination of lean mass and fat mass; measurement of protein metabolism; monitoring the metabolism of energy-yielding nutrients; measurement of energy expenditure under a wide variety of environmental conditions; measurement of molecular and cellular changes in nutrient utilization; measurement of immune function (status); measurement of physiological performance; and measurement of cognitive performance. The unique requirements of the Armed Forces' nutrition research program are the need to make measurements in extremes of environmental conditions (high and low temperatures, high altitude, high and low humidity, noise, vibration, concussion, or combinations thereof) and stress (sleep deprivation, battle fatigue, prolonged physical exertion, dehydration, and underconsumption of nutrients) and the desire to extend performance while holding logistical requirements to a minimum. This research agenda makes consideration of new research technologies very attractive, especially in terms of cost and timeliness. At the same time, consideration must be given to the relative chances of successful outcome and cost or cost/benefit considerations. Relative to this latter consideration, Vogel suggests that attention be given to the relative potential for performance enhancement or the health benefit that is inherent in ration modification, ration supplementation, or other nutrition interventions. Although the relative military benefit of performance outcomes may be beyond the capacity of the CMNR to evaluate, some assessment can be made on the basis of improvement in the variability and certainty of research data. COMMITTEE SUMMARY TECHNIQUES OF BODY COMPOSITION ASSESSMENT In Chapter 4 of this report, LTC Karl E. Friedl presents an overview of the use of body composition (BC) assessment by the military, the available technologies, and suggestions for future development. More detailed discussions

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Emerging Technologies for Nutrition Research: Potential for Assessing Military Performance Capability of specific methods are provided by Steven Heymsfield and coworkers, Wendy M. Kohrt, and Wm. Cameron Chumlea and Shumei S. Guo (see Chapters 5, 6, and 7 in this volume). The composition of the body reflects a number of factors, including the status of energy stores, training level, and other aspects of nutritional and hydration status. Characteristics that may be inferred indirectly from BC assessments include muscular strength, physical performance, and potential risk for musculoskeletal injury (Reynolds et al., 1994). Body Composition Standards in the Military The military utilizes the results of BC research and analysis to develop appropriate standards for selection (accession and retention) and for fitness. While the primary goal of military BC standards is to ensure military readiness (physical fitness, performance, and risk of chronic disease) (Friedl, 1992), a secondary goal is to maintain military appearance (Hodgdon et al., 1990), which is considered a part of readiness. The BC standards utilized by the military are specific to age, gender, and branch of military service. In addition to utilization in standards development, BC is used by the military to assess training programs and the risks and benefits of a wide variety of optimization strategies, including physical, nutritional, and pharmacological interventions. The first tier of BC analysis by the U.S. Army consists of a semiannual weight-for-height screen, based on body mass index (BMI, weight/height2) (AR 600-9, 1986). Personnel who exceed the weight-for-height standards are permitted to undergo a second tier of analysis consisting of body fat assessment by anthropometric (circumference) measurement. As Friedl points out, the method of body fat assessment utilized by the Army must be part of a regulation and must be limited to one method that is accurate and does not inadvertently undermine the goals of classification by declaring those with the greatest muscle mass to be overweight or by requiring inappropriate energy restriction to ''make weight." BC standards utilized by the military are based primarily on the ability to predict body fat from BMI and secondarily on equations that estimate the percentage of body fat from anthropometric measurements (AR 600-9, 1986). Validation of the equations, which differ according to age, gender, and branch, traditionally has been accomplished by comparison with body fat estimations using hydrodensitometry, the "criterion" measure. Hydrodensitometric determination of body fat is based on a two-compartment model of BC (fat and fat-free mass) (Siri, 1961). This method may be unreliable for both technical and theoretical reasons. From a technical standpoint, residual air volume (air left in the body after voluntary expulsion) and body volume measurements are subject to significant error. From a theoretical standpoint, the method relies on assumptions regarding the two compartments' constancy of composition. These latter assumptions are based primarily on data collected either from men (Keys et al., 1950) or guinea pigs (Pace and Rathbun, 1945) and do not account for

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Emerging Technologies for Nutrition Research: Potential for Assessing Military Performance Capability changes in hydration level or differences because of race (ethnicity) or gender. The military's equations tend to overestimate body fat in lean individuals and underestimate body fat in overweight individuals (Friedl and Vogel, 1992). Recent attempts to validate the military's body fat equations have included the use of a four-compartment model combining hydrodensitometry with dualenergy x-ray absorptiometry (DEXA or DXA) to determine bone mineral density and soft tissue mass, according to Friedl (see Chapter 4 in this volume). Body Composition Assessment Techniques Proposed to Replace Hydrodensitometry as the Criterion Method Dual-Energy X-Ray Absorptiometry The use of DXA for BC assessment is reviewed in Chapter 6 by Wendy M. Kohrt. According to Kohrt, the primary clinical application of DXA (which has replaced dual-photon absorptiometry) is the measurement of bone mineral content and bone mineral density (BMD) to assess risk for osteoporosis. As a tool for BMD assessment, DXA is considered highly reliable and precise; however, its validity, particularly for measuring changes in BMD, remains questionable because of interinstrument measurement discrepancies (see Kohrt, Chapter 6 in this volume), as well as intrainstrument errors resulting from changes in other tissue compartments (Schneider and Reiners, 1997). The use of DXA to measure BC is based on the principle that the composition of an object can be determined by the attenuation of two distinct low-and high-energy x-ray beams. This technique can distinguish three compartments or materials: bone mineral, nonbone lean tissue, and fat (Nord and Payne, 1990). The x-ray attenuation of each pixel is compared to the known attenuation of reference materials (see Kohrt, Chapter 6 in this volume). As a means of measuring BC, DXA appears to be more precise, reproducible, and convenient than hydrodensitometry for both the patient and the investigator (Hansen et al., 1993). In addition, DXA yields information about regional BC (Jensen et al., 1995) and has the advantage of producing results that are independent of ethnic differences. Also, DXA allows measurement of bone, which is one of the compartments with the greatest interindividual variability. With DXA, less reliance needs to be placed upon assumptions regarding the consistency of the chemical composition of fat-free mass (FFM) than is the case with hydrodensitometry; thus, DXA could potentially replace hydrodensitometry as the criterion method for validation of anthropometric measurements of fat, according to Kohrt (see Chapter 6 in this volume). Other investigators point out that, although DXA shows much promise in its ability to assess fat accurately (Haarbo et al., 1991), the susceptibility of DXA estimations of FFM to changes in hydration status (Formica et al., 1993; Horber et al., 1992) and protein content, and its inability to analyze the composition of soft tissues that lie close to bone (Tothill and Nord, 1995)

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Emerging Technologies for Nutrition Research: Potential for Assessing Military Performance Capability demonstrate that more development is necessary. In addition, DXA is expensive (analyzer costs range from $120,000 to $150,000) and cannot be used in the field. Bioelectrical Impedance Analysis and Other Techniques Other techniques that have been utilized, particularly in the field, include near-infrared (NIR) spectroscopy, ultrasound, and bioelectric impedance analysis (BIA). Using hydrodensitometric determinations and anthropometric measurements as the standard, NIR spectroscopy has proven no better than simple height and weight measures (Israel et al., 1989), while ultrasound has proven no better than anthropometric measurements (Hodgdon and Fitzgerald, 1987; see Friedl, Chapter 4 in this volume). BIA, reviewed in Chapter 7 by Wm. Cameron Chumlea and Shumei S. Guo, measures current flow through the body and was first used to assess hydration status (Nyboer, 1959). The measurements are based upon the assumption that the body is a water-and electrolyte-filled cylinder. When BIA is used to assess body composition, there is a requirement to generate mathematical equations that must be validated against some other criterion method of BC assessment. BIA has the dual advantages of being noninvasive and relying upon equipment that is relatively portable. The use of BIA to assess body composition has, until recently, relied on measurements at a single frequency (of 50 Hz). Such estimates of body composition are often unreliable (Chumlea et al., 1996). Further, single-frequency BIA is not recommended for use in longitudinal studies since it is not a valid indicator of changes in BC within the same individual over time, particularly if the change is slow or is accounted for primarily by a change in fat content (Forbes et al., 1992). An alternative method of BIA performs measurements at multiple frequencies. This method is an improvement over single-frequency methods in that data are fitted to a theoretical curve, and the frequencies that best fit the curve are used to estimate BC (Chumlea et al., 1996). A third alternative is the use of bioimpedance spectroscopy (BIS), which measures multiple components of impedance over a spectrum of frequencies and shows considerable promise for longitudinal assessment of body composition (Lukaski, 1996). The placement of electrodes also influences the utility of BIA measurements. While electrodes are routinely placed on the distal extremities, proximal (toward the trunk) placement of electrodes has been shown to improve the precision of body composition assessment, although fluid accumulation in the extremities must be monitored (Lukaski, 1996). Segmental impedance measures, particularly when performed with BIS, have shown promise in the assessment of changes in body fat (Chumlea et al., 1996). Because BIA is based on the assessment of total body water, its utility is affected by interindividual differences in hydrational status as well as any

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Emerging Technologies for Nutrition Research: Potential for Assessing Military Performance Capability factors that influence intraindividual hydrational status, such as fluid intake, physical activity, nutritional status, illness, and environmental factors (Kushner et al., 1996). Among the recommendations of the 1994 National Institutes of Health Technology Assessment Conference on Bioelectrical Impedance Analysis in Body Composition Measurement (NIH, 1996) are that such variables be standardized and controlled and that additional research, validation, and standardization of procedures be performed. Computerized Axial Tomography and Magnetic Resonance Imaging The use of computerized axial tomography (CAT) and magnetic resonance imaging (MRI) (also known as nuclear magnetic resonance) for BC assessment is reviewed by Steven Heymsfield, Robert Ross, ZiMian Wang, and David Frager in Chapter 5 in this volume. CAT is based on the ability of tissues of varying composition to attenuate an x-ray beam to differing extents, with image reconstruction based on mathematical techniques such as Fourier analysis. MRI is based on the action of hydrogen nuclei in the presence of a strong magnetic field, which causes the nuclei to align either with or against the field in a predictable manner. Each orientation has a slightly different energy state; oscillation of the magnetic field at a designated frequency causes the nuclei to flip or precess between orientations with a resulting release or absorption of energy (Gadian, 1982). When the magnet is "turned off," the nuclei return to their original energy state (relax), and the released energy generates an image. The nuclear density and relaxation times are tissue-type dependent. Both CAT and MRI produce high-resolution, cross-sectional images of the whole body or body regions. These images are then analyzed by computer to estimate tissue-and organ-level body composition, and algorithms are applied to reconstruct and estimate the total volume of the tissue or system in question (see Heymsfield et al., Chapter 5 in this volume). While both CAT and MRI permit clear visualization of the boundaries between adipose tissue, muscle, and bone and quantification of all major tissue components, CAT has the relative disadvantages of causing some radiation exposure and being extremely costly, according to Heymsfield and coworkers (see Chapter 5 in this volume). In contrast, MRI has no known health risks and has the added advantage of permitting the calculation of tissue volumes but is expensive. Both CAT and MRI have been validated using phantoms (composed of tissue or analogous materials), laboratory animals, and human cadavers and both appear to be accurate and reproducible, with MRI having the advantage of even greater precision. Because of its accuracy, its ability to provide cross-sectional imaging and make regional and whole-body measures, and its availability and apparent safety, MRI could provide criterion data for generation of equations to predict BC in diverse populations as well as permitting longitudinal and intervention studies that require multiple or serial measures.

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Emerging Technologies for Nutrition Research: Potential for Assessing Military Performance Capability According to Heymsfield and coworkers (see Chapter 5 in this volume), the primary disadvantage of MRI is the preclusion from study until recently of individuals with claustrophobia and the very obese. The availability of open MRI facilities will eliminate this problem. Other disadvantages include cost; sensitivity to motion artifacts, especially in the abdominal region; time required to analyze images; and a technical question regarding the (mathematical) conversion of adipose tissue volume to fat mass. Included among the future trends for these technologies are CAT spiral imaging, which should permit better reconstruction of BC components and decrease required radiation dose (Fishman, 1994); linkage of MRI to magnetic resonance spectroscopy to permit the study of metabolic processes in vivo; and decrease in the time required to take and analyze MRI images because of technical advances (Jolesz, 1992). Correlation between Body Composition, Health Status, and Physical Performance The correlation of total body fat content or fat distribution with actual health, nutritional status, physical activity (fitness), and appearance measures is a major concern for the military (see Friedl, Chapter 4 in this volume). The correlation between intra-abdominal fat stores, abdominal girth, and cardiovascular (CV) disease risk is well known (Larsson et al., 1984; Metropolitan Life Insurance Company, 1937); thus, there may be reason to assess fat content in that region rather than to assess total fat. In men, intra-abdominal fat deposition is highly correlated with abdominal girth (Despres et al., 1991), which is one of the anthropometric measures included in the Army's BC equation. No such relationship exists for women, however, except for the very heaviest women (Kvist et al., 1986; Vogel and Friedl, 1992; Weits et al., 1988). In women with the highest lean body mass (i.e., those with greatest physical strength), percentage of body fat tends to be overestimated by equations that include a measure of abdominal girth (Hodgdon and Beckett, 1984). Because such women also tend to exhibit male-type fat distribution with the same CV risk factors, the abdominal girth that correlates with greatest physical strength also may predispose these women to increased CV risk (Evans et al., 1983). Thus, women whose physical performance is greatest (as measured by lifting and carrying) are those most likely to exceed body fat standards and to carry the greatest health risk. It is fairly well established that physical strength is independent of body fat (Sharp et al., 1994). The current military (Army) weight control programs do not select for physical performance nor do they predict strength. While the association between total or regional muscle mass and specific measures of physical performance remains unclear, FFM is the BC component most likely to correlate with physical performance as measured by lifting and carrying

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Emerging Technologies for Nutrition Research: Potential for Assessing Military Performance Capability capacity (Fitzgerald et al., 1986; Johnson et al., 1994). However, an assessment of FFM is not currently a part of the military BC standards (AR 600-9, 1986). Because the assessment of changes in nutritional and/or hydration status during military operational activities is one of the primary interests of the MND, considerable effort has been expended to explore the use of BC assessment techniques both in the field and in the laboratory using pre-and posttreatment (exercise) sampling designs to monitor such changes. Unfortunately, as Friedl points out, the standard anthropometric measures of body composition fail to reflect accurately the true changes in weight and composition over time (Ballor and Katch, 1989). In terms of performance, the real factor of interest, and the more practical measure in field settings, is rate of weight loss. While skinfold thickness appears to detect changes in fat mass with greater reliability than does BIA or hydrodensitometry, it is still relatively insensitive for detecting small changes in fat mass (Jebb et al., 1993). Because changes in body weight or exposure to environmental extremes tends to lead to measurable changes in body water content, the use of DXA or hydrodensitometry to assess changes in body composition under such conditions may result in serious measurement artifacts. BIA may provide relatively precise assessments of changes in body water, but interpretation of changes in body composition are problematic (Friedl et al., 1994a, b; Fulco et al., 1992; Westphal et al., 1995). Thus, there is a need for more than one type of measure to assess changes in BC over time. Summary Body composition assessment is performed by the military for several purposes. The primary purpose is to establish adherence to weight-for-height standards. All branches of the military maintain such standards for active-duty personnel. The reasons for these standards, while somewhat branch specific, include concerns about readiness, appearance, and health. Personnel who fall outside of the weight range for their height must undergo an assessment of body fat by circumferential measurement. The gender-and branch-specific equations that use these circumferential measures to calculate body fat have been validated with the criterion measurement of hydrodensitometry. Because hydrodensitometry is based on assumptions that are not valid in the field (constancy of body compartment composition) and is problematic to perform, other criterion methods are sought by which to validate and, if necessary, refine the military equations. A four-compartment model that relies on DXA to assess bone, soft lean tissue, and fat and requires measurement of body water as well appears to offer such a criterion method for validation of existing equations for routine body composition assessment. Validated BC equations requiring only circumferential measures continue to be used by the military because of practicality and cost. Body composition measurement also is used by the military to assess the effects of field training exercises and fitness regimens on gain or loss of lean

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Emerging Technologies for Nutrition Research: Potential for Assessing Military Performance Capability tissue and fat mass, in a pre-and posttreatment type of design. Although useful in the laboratory, the techniques of DXA, MRI, and CAT were acknowledged to be generally impractical for field use because of their cost and relative immobility. They are also almost as limited in their ability to detect and accurately measure small changes (< 5 kg or 11 lb) in body composition as is hydrodensitometry. The utility of BIA for assessing body composition is still limited by the need for technical improvements aimed at increasing its validity. Muscle mass is the body compartment most closely predictive of physical performance. Many of the methods described could estimate muscle mass accurately enough to predict performance; however, at present the focus of military BC assessment remains on fat. Technology that would enable measurement of small changes in muscle mass has not yet been developed. Finally, the military utilizes the measurement of abdominal girth to predict long-term risk for cardiovascular disease in active-duty men but not women. TRACER TECHNIQUES FOR THE STUDY OF METABOLISM In this section, the use of stable isotopes for evaluation of metabolic processes is discussed by Dennis M. Bier, Robert R. Wolfe, and V. R. Young and coworkers (see Chapters 8, 9, and 10 in this volume). Gerald I. Shulman's description of nuclear magnetic resonance as a tool to study metabolism follows (see Chapter 11 in this volume). While James P. DeLany uses the doubly labeled water technique to measure energy expenditure (see Chapter 12 in this volume), a more detailed summary of his presentation is included in the following section due to its extensive use in the field. Use of Isotopic Tracers to Study Metabolism Stable isotopes are naturally occurring forms of atoms that, by nature of the increased number of neutrons in their nuclei, can be "traced" with mass spectrometry. Because these atoms are found naturally and can be concentrated in major biological pools and fuels, this technology can be used to monitor quantitatively the rate and outcome of metabolic processes in the body precisely and accurately (see Wolfe, Chapter 9 in this volume). Specifically, by monitoring the steady-state tracer dilution curve of a given isotopically labeled molecule (precursor evaluation) within a metabolic pool or the accumulation of a labeled product such as urea, ammonia, or lactate, the processes contributing to the utilization or production of that molecule and the relative rate of those processes can be monitored. This technique currently is used routinely to monitor rate of protein turnover using 15N-glycine or 13C-leucine (both synthesis and breakdown, see Wolfe, Chapter 9 in this volume), absolute energy expenditure using doubly labeled water (water labeled with both 2H and 18O; see committee summary below and DeLany, Chapter 12 in this volume), and the

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