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5 Energy SUMMARY Energy is required to sustain the body’s various functions, includ- ing respiration, circulation, physical work, and maintenance of core body temperature. The energy in foods is released in the body by oxidation, yielding the chemical energy needed to sustain metabolism, nerve transmission, respiration, circulation, and physical work. The heat produced during these processes is used to maintain body temperature. Energy balance in an individual depends on his or her dietary energy intake and energy expenditure. Imbalances between intake and expenditure result in gains or losses of body components, mainly in the form of fat, and these determine changes in body weight. The Estimated Energy Requirement (EER) is defined as the average dietary energy intake that is predicted to maintain energy balance in a healthy, adult of a defined age, gender, weight, height, and level of physical activity consistent with good health. To calculate the EER, prediction equations for normal weight individuals were developed from data on total daily energy expenditure measured by the doubly labeled water technique. In children and pregnant or lactating women, the EER includes the needs associated with the deposition of tissues or the secretion of milk at rates consistent with good health. While the expected between-individual variabil- ity is calculated for the EER, there is no Recommended Dietary Allowance (RDA) for energy because energy intakes above the EER would be expected to result in weight gain. Similarly, the Tolerable Upper Intake Level (UL) concept does not apply to 107
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108 DIETARY REFERENCE INTAKES energy, because any intake above an individual’s energy require- ment would lead to undesirable (and potentially hazardous) weight gain. BACKGROUND INFORMATION Humans and other mammals constantly need to expend energy to perform physical work; to maintain body temperature and concentration gradients; and to transport, synthesize, degrade, and replace small and large molecules that make up body tissue. This energy is generated by the oxidation of various organic substances, primarily carbohydrates, fats, and amino acids. In 1780, Lavoisier and LaPlace measured the heat produc- tion of mammals by calorimetry (Kleiber, 1975). They demonstrated that it was equal to the heat released when organic substances were burned, and that the same quantities of oxygen were consumed by animal metabo- lism as were used during the combustion of the same organic substrates (Holmes, 1985). Indeed, it has been verified by numerous experiments on animals and humans since then that the energy produced by oxidation of carbohydrates and fats in the body is the same as the heat of combustion of these substances (Kleiber, 1975). The crucial difference is that in organ- isms oxidation proceeds through many steps, allowing capture of some of the energy in an intermediate chemical form—the high energy pyrophos- phate bond of adenosine triphosphate (ATP). Hydrolysis of these high- energy bonds can then be coupled to various chemical reactions, thereby driving them to completion, even if by themselves they would not proceed (Lipmann, 1941). Typically, the rates of energy expenditure in adults at rest are slightly less than 1 kcal/min in women (i.e., 0.8 to 1.0 kcal/min or 1,150 to 1,440 kcal/d), and slightly more than 1 kcal/min in men (i.e., 1.1 to 1.3 kcal/min or 1,580 to 1,870 kcal/d) (Owen et al., 1986, 1987). One kcal/min corresponds approximately to the heat released by a burning candle or by a 75-watt light bulb (i.e., 1 kcal/min corresponds to 70 J/sec or 70 W). Energy Yields from Substrates Carbohydrate, fat, protein, and alcohol provide all of the energy sup- plied by foods and are generally referred to as macronutrients (in contrast to vitamins and elements, usually referred to as micronutrients). The amount of energy released by the oxidation of carbohydrate, fat, protein, and alcohol (also known as Heat of Combustion, or ∆H) is shown in Table 5-1. When alcohol (ethanol or ethyl alcohol) is consumed, it promptly appears in the circulation and is oxidized at a rate determined largely by its concentration and by the activity of liver alcohol dehydrogenase. Oxi-
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109 E NERGY TABLE 5-1 Heat of Combustion of Various Macronutrients Heat of Combustiona Atwater Factord kcalb/L O 2 RQc (CO2/O2) Macronutrient (kcal/g) (kcal/g) Starch 4.18 5.05 1.0 4.0 Sucrose 3.94 5.01 1.0 4.0 Glucose 3.72 4.98 1.0 4.0 Fat 9.44 4.69 0.71 9.0 Protein by 5.6 combustiona Protein through 4.70 4.66 0.835 4.0 metabolisma Alcohole 7.09 4.86 0.67 — a The energy derived by protein oxidation in living organisms is less than the heat of combustion of protein, because the nitrogen-containing end product of metabolism in mammals is urea (or uric acid in birds and reptiles), whereas nitrogen is converted into nitrous oxide when protein is combusted. The heat liberated by biological oxidation of proteins was long thought to be 4.3 kcal/g (Merrill and Watt, 1973), but a more recent demonstration showed that the actual value is 4.7 kcal/g (Livesey and Elia, 1988). b One calorie is the amount of energy needed to increase the temperature of 1 g of water from 14.5˚ to 15.5˚C. In the context of foods and nutrition, “large calorie” (i.e., Calories, with a capital C), which is more properly referred to as “kilocalorie” (kcal), has been traditionally used. In the International System of Units, the basic energy unit is the Joule (J). One J = 0.239 calories, so that 1 kcal = to 4.186 kJ. A daily energy expenditure of 2,400 kcal corresponds to the expenditure of 10,000 kJ, or 10 MJ (Mega Joules)/d. c RQ = respiratory quotient, which is defined as the ratio of CO produced divided by O 2 2 consumed (in terms of mols, or in terms of volumes of CO2 and O2). d Atwater, a pioneer in the study and characterization of nutrients and metabolism, proposed to use the values of 4, 9, and 4 kcal/g of carbohydrate, fat, and protein, respectively (Merrill and Watt, 1973). This equivalent is now uniformly used in nutrient labeling and diet formulation. Nutrition Labeling of Food. 21 C.F.R. §101.9 (1991). e Alcohol (ethanol) content of beverages is usually described in terms of percent by volume. The heat of combustion of alcohol is 5.6 kcal/mL. (One mL of alcohol weighs 0.789 g.) dation of alcohol elicits a prompt reduction in the oxidation of other substrates used for ATP regeneration, demonstrating that ethanol oxida- tion proceeds in large part via conversion to acetate and oxidative phos- phorylation. The phenomenon has been precisely measured by indirect calorimetry in human subjects, in whom ethanol consumption was found to primarily reduce fat oxidation (Suter et al., 1992). About 80 percent of the energy liberated by ethanol oxidation is used to drive ATP regenera- tion, so that the thermic effect of ethanol comes to about 20 percent (Siler et al., 1999). The thermic effect of food is the increase in energy expendi-
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110 DIETARY REFERENCE INTAKES ture as measured by heat produced upon ingestion of that food. The thermic effect of alcohol is about twice the thermic effect of carbohydrate, but less than the thermic effect of protein (see later section, “Thermic Effect of Food”). Reported food intake in individuals consuming alcohol is often similar to that of individuals who do not consume alcohol (de Castro and Orozco, 1990). As a result, it has sometimes been questioned whether alcohol con- tributes substantially to energy production. However, the biochemical and physiological evidence about the contribution made by ethanol to oxidative phosphorylation is so unambiguous that the apparent discrepancies between energy intake data and body weights must be attributed to inaccuracies in reported food intakes. In fact, in individuals consuming a healthy diet, the additional energy provided by alcoholic beverages can be a risk factor for weight gain (Suter et al., 1997), as opposed to alcoholics in whom the pharmacological impact of excessive amounts of ethanol tends to inhibit normal eating and may cause emaciation. Energy Requirements Versus Nutrient Requirements Recommendations for nutrient intakes are generally set to provide an ample supply of the various nutrients needed (i.e., enough to meet or exceed the requirements of almost all healthy individuals in a given life stage and gender group). For most nutrients, recommended intakes are thus set to correspond to the median amounts sufficient to meet a specific criterion of adequacy plus two standard deviations to meet the needs of nearly all healthy individuals (see Chapter 1). However, this is not the case with energy because excess energy cannot be eliminated, and is eventually deposited in the form of body fat. This reserve provides a means to main- tain metabolism during periods of limited food intake, but it can also result in obesity. The first alternate criterion that may be considered as the basis for a recommendation for energy is that energy intake should be commensu- rate with energy expenditure, so as to achieve energy balance. Although frequently applied in the past, this is not appropriate as a sole criterion, as described by the FAO/WHO/UNU publication, Energy and Protein Require- ments (1985): The energy requirement of an individual is a level of energy intake from food that will balance energy expenditure when the indi- vidual has a body size and composition, and level of physical activity, consistent with long-term good health; and that would allow for the maintenance of economically necessary and socially desirable physical activity. In children and pregnant or lactating women the energy requirement includes the energy needs associated with
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111 E NERGY the deposition of tissues or the secretion of milk at rates consis- tent with good health (p. 12). This definition indicates that desirable energy intakes for obese indi- viduals are less than their current energy expenditure, as weight loss and establishment of a steady state at a lower body weight is desirable for them. In underweight individuals, on the other hand, desirable energy intakes are greater than their current energy expenditure to permit weight gain and maintenance of a higher body weight. Thus, it seems logical to base estimated values for energy intake on the amounts of energy that need to be consumed to maintain energy balance in adult men and women who are maintaining desirable body weights, taking into account the incre- ments in energy expenditure elicited by their habitual level of activity. There is another fundamental difference between the requirements for energy and those for other nutrients. Body weight provides each indi- vidual with a readily monitored indicator of the adequacy or inadequacy of habitual energy intake, whereas a comparably obvious and individualized indicator of inadequate or excessive intake of other nutrients is not usually evident. Energy Balance Because of the effectiveness in regulating the distribution and use of metabolic fuels, man and animals can survive on foods providing widely varying proportions of carbohydrates, fats, and proteins. The ability to shift from carbohydrate to fat as the main source of energy, coupled with the presence of substantial reserves of body fat, makes it possible to accom- modate large variations in macronutrient intake, energy intake, and energy expenditure. The amount of fat stored in an adult of normal weight com- monly ranges from 6 to 20 kg. Since one gram of fat provides 9.4 kcal, body fat energy reserves thus range typically from approximately 50,000 to 200,000 kcal, providing a large buffer capacity as well as the ability to provide energy to survive for extended periods (i.e., several months) of severe food deprivation. Large daily deviations from energy balance are thus readily tolerated, and accommodated primarily by gains or losses of body fat (Abbott et al., 1988; Stubbs et al., 1995). Coefficients of variation for intra-individual variability in daily energy intake average ± 23 percent (Bingham et al., 1994); variations in physical activity are not closely syn- chronized with adjustments in food intake (Edholm et al., 1970). Thus, substantial positive as well as negative energy balances of several hundred kcal/d occur as a matter of course under free-living conditions among normal and overweight subjects. Yet over the long term, energy balance is maintained with remarkable accuracy. Indeed, during long periods in the
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112 DIETARY REFERENCE INTAKES life of most individuals, gains or losses of adipose tissue are less than 1 to 2 kg over a year (McCargar et al., 1993), implying that the cumulative error in adjusting energy intake to expenditure amounts to less than 2 percent of energy expenditure. Components of Energy Expenditure Basal and Resting Metabolism The basal metabolic rate (BMR) describes the rate of energy expendi- ture that occurs in the postabsorptive state, defined as the particular con- dition that prevails after an overnight fast, the subject having not consumed food for 12 to 14 hours and resting comfortably, supine, awake, and motion- less in a thermoneutral environment. This standardized metabolic state corresponds to the situation in which food and physical activity have minimal influence on metabolism. The BMR thus reflects the energy needed to sustain the metabolic activities of cells and tissues, plus the energy needed to maintain blood circulation, respiration, and gastrointestinal and renal processing (i.e., the basal cost of living). BMR thus includes the energy expenditure associated with remaining awake (the cost of arousal), reflect- ing the fact that the sleeping metabolic rate (SMR) during the morning is some 5 to 10 percent lower than BMR during the morning hours (Garby et al., 1987). BMR is commonly extrapolated to 24 hours to be more meaningful, and it is then referred to as basal energy expenditure (BEE), expressed as kcal/24 h. Resting metabolic rate (RMR), energy expenditure under rest- ing conditions, tends to be somewhat higher (10 to 20 percent) than under basal conditions due to increases in energy expenditure caused by recent food intake (i.e., by the “thermic effect of food”) or by the delayed effect of recently completed physical activity (see Chapter 12). Thus, it is impor- tant to distinguish between BMR and RMR and between BEE and resting energy expenditure (REE) (RMR extrapolated to 24 hours). Basal, resting, and sleeping energy expenditures are related to body size, being most closely correlated with the size of the fat-free mass (FFM), which is the weight of the body less the weight of its fat mass. The size of the FFM generally explains about 70 to 80 percent of the variance in RMR (Nelson et al., 1992; Ravussin et al., 1986). However, RMR is also affected by age, gender, nutritional state, inherited variations, and by differences in the endocrine state, notably (but rarely) by hypo- or hyperthyroidism. The relationships among RMR, body weight, and FFM are illustrated in Figures 5-1 and 5-2 (Owen, 1988), which show that differences in RMR relative to body weight among diverse individuals such as men, women, and athletes mostly disappear when RMR is considered relative to FFM.
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113 E NERGY 3,000 RMR (k cal/24 h) 2,000 1,000 0 Weight (kg) FIGURE 5-1 Resting metabolic rates (RMR) are contrasted against the weights of 44 lean ( ) and obese (●) healthy women, 8 of whom were athletes (⊕), and 60 lean (∆) and obese ( ) healthy men. Reprinted, with permission, from Owen (1988). Copyright 1988 by W.B. Saunders. 3,000 2,000 RMR (k cal/24 h) 1,000 0 FFM (kg) FIGURE 5-2 Resting metabolic rates (RMR) are contrasted against the fat-free masses (FFM) of 44 lean ( ) and obese (●) healthy women, 8 of whom were athletes (⊕), and 60 lean (∆) and obese ( ) healthy men. Reprinted, with permis- sion, from Owen (1988). Copyright 1988 by W.B. Saunders.
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114 DIETARY REFERENCE INTAKES BEE has been predicted from age, gender, and body size. Prediction equations were developed for each gender (WN Schofield, 1985) by pool- ing and analyzing reported measurements made in 7,393 individuals. A recent re-evaluation of all available data performed by Henry (2000) has led to a new set of predicting equations. Thermic Effect of Food It has long been known that food consumption elicits an increase in energy expenditure (Kleiber, 1975). Originally referred to as the Specific Dynamic Action (SDA) of food, this phenomenon is now more commonly referred to as the thermic effect of food (TEF). The intensity and duration of meal-induced TEF is determined primarily by the amount and composi- tion of the foods consumed, mainly due to the metabolic costs incurred in handling and storing ingested nutrients (Flatt, 1978). Activation of the sympathetic nervous system elicited by dietary carbohydrate and by sensory stimulation causes an additional, but modest, increase in energy expendi- ture (Acheson et al., 1983). The increments in energy expenditure during digestion above baseline rates, divided by the energy content of the food consumed, vary from 5 to 10 percent for carbohydrate, 0 to 5 percent for fat, and 20 to 30 percent for protein. The high TEF for protein reflects the relatively high metabolic cost involved in processing the amino acids yielded by absorption of dietary protein, for protein synthesis, or for the synthesis of urea and glucose (Flatt, 1978; Nair et al., 1983). Consumption of the usual mixture of nutrients is generally considered to elicit increases in energy expenditure equivalent to 10 percent of the food’s energy con- tent (Kleiber, 1975). Since TEF occurs during a limited part of the day only, it can result in noticeable increases in REE if energy expenditure is measured during the hours following meals. Thermoregulation Birds and mammals, including humans, regulate their body tempera- ture within narrow limits. This process, termed thermoregulation, can elicit increases in energy expenditure that are greater when ambient tempera- tures are below the zone of thermoneutrality. The environmental tem- perature at which oxygen consumption and metabolic rate are lowest is described as the critical temperature or thermoneutral zone (Hill, 1964). Because most people adjust their clothing and environment to maintain comfort, and thus thermoneutrality, the additional energy cost of thermo- regulation rarely affects total energy expenditure to an appreciable extent. However, there does appear to be a small influence of ambient tempera- ture on energy expenditure as described in more detail below.
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115 E NERGY Physical Activity The energy expended for physical activity varies greatly among indi- viduals as well as from day to day. In sedentary individuals, about two- thirds of total energy expenditure goes to sustain basal metabolism over 24 hours (the BEE), while one-third is used for physical activity. In very active individuals, 24-hour total energy expenditure can rise to twice as much as basal energy expenditure (Grund et al., 2001), while even higher total expenditures occur among heavy laborers and some athletes. The efficiency with which energy from food is converted into physical work is remarkably constant when measured under conditions where body weight and athletic skill are not a factor, such as on bicycle ergometers (Kleiber, 1975; Nickleberry and Brooks, 1996; Pahud et al., 1980). For weight-bearing physical activities, the cost is roughly proportional to body weight. In the life of most persons, walking represents the most significant form of physical activity, and many studies have been performed to deter- mine the energy expenditures induced by walking or running at various speeds (Margaria et al., 1963; Pandolf et al., 1977; Passmore and Durnin, 1955). Walking at a speed of 2 mph is considered to correspond to a mild degree of exertion, walking speeds of 3 to 4 mph correspond to moderate degrees of exertion, and a walking speed of 5 mph to vigorous exertion (Table 12-1, Fletcher et al., 2001). Over this range of speeds, the increment in energy expenditure amounts to some 60 kcal/mi walked for a 70-kg individual, or 50 kcal/mi walked for a 57-kg individual (see Chapter 12, Figure 12-4). The exertion caused by walking/jogging increases progres- sively at speeds of 4.5 mph and beyond, reaching 130 kcal/mi at 5 mph for a 70-kg individual. The increase in daily energy expenditure is somewhat greater, how- ever, because exercise induces an additional small increase in expenditure for some time after the exertion itself has been completed. This excess post-exercise oxygen consumption (EPOC) depends on exercise intensity and duration and has been estimated at some 15 percent of the increment in expenditure that occurs during exertions of the type described above (Bahr et al., 1987). This raises the cost of walking at 3 mph to 69 kcal/mi (60 kcal/mi × 1.15) for a 70-kg individual and to 58 kcal/mi (50 kcal/mi × 1.15) for a 57-kg individual. Taking into account the dissipation of 10 percent of the energy consumed on account of the thermic effect of food to cover the expenditure associated with walking, then walking 1 mile raises daily energy expenditure to 76 kcal/mi (69 kcal/mi × 1.1) in individuals weighing 70 kg, or 64 kcal/mi (58 kcal/mi × 1.1) for individuals weighing 57 kg. Since the cost of walking is proportional to body weight, it is convenient to consider that the overall cost of walking at moderate speeds is approximately 1.1 kcal/mi/kg body weight (75 kcal/mi/70 kg or 64 kcal/mi/57 kg). The effects of varia-
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116 DIETARY REFERENCE INTAKES tions in body weights and the impact of various physical activities on energy expenditure are considered in more detail in Chapter 12. Physical Activity Level The level of physical activity is commonly described as the ratio of total to basal daily energy expenditure (TEE/BEE). This ratio is known as the Physical Activity Level (PAL), or the Physical Activity Index. Describ- ing physical activity habits in terms of PAL is not entirely satisfactory because the increments above basal needs in energy expenditure, brought about by most physical activities where body weight is supported against gravity (e.g., walking, but not cycling on a stationary cycle ergometer), are directly proportional to body weight, whereas BEE is more nearly propor- tional to body weight0.75. However, PAL is a convenient comparison and is used in this report to describe and account for physical activity habits. The effect of variations in activities on PAL is described in Chapter 12. Total Energy Expenditure Total Energy Expenditure (TEE) is the sum of BEE (which includes a small component associated with arousal, as compared to sleeping), TEF, physical activity, thermoregulation, and the energy expended in deposit- ing new tissues and in producing milk. With the emergence of informa- tion on TEE by the doubly labeled water (DLW) method (Schoeller, 1995), it has become possible to determine energy expenditure of infants, chil- dren, and adults under free-living conditions. TEE from doubly labeled water does not include the energy content of the tissue constituents laid down during normal growth and pregnancy or the milk produced during lactation, as it refers to energy expended during oxidation of energy- yielding nutrients to water and carbon dioxide. It should be noted that direct measurements of TEE represent a dis- tinct advantage over previous TEE evaluations, which had to rely on the factorial approach and on food intake data, which have limited accuracy due to the inability to reliably determine average physical activity cost and nutrient intakes. Estimated Energy Requirement Information on energy expenditure obtained by DLW studies con- ducted by a number of research units (see Appendix I) are used in this report to estimate energy requirements, taking into account estimates of the energy content of new body constituents during growth and preg-
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117 E NERGY nancy and of the milk produced during lactation. Energy expenditure depends on age and varies primarily as a function of body size and physical activity, both of which vary greatly among individuals. Recommendations about energy intake vary accordingly, and are also subject to the criterion that an individual adult’s body weight should remain stable and within the healthy range. SELECTION OF INDICATORS FOR ESTIMATING THE REQUIREMENT FOR ENERGY Reported Energy Intake The reported energy intakes of weight-stable subjects (i.e., those in energy balance) could, in principle, be used to predict energy require- ments for weight maintenance. However, it is now widely recognized that reported energy intakes in dietary surveys underestimate usual energy intake (Black et al., 1993). The most compelling evidence about underreporting has come from measurements of total energy expenditure (TEE) by the doubly labeled water (DLW) method (Schoeller, 1995). The use of a measure or estimate of TEE to validate instruments that measure food intake is dependent on the principle of energy balance. That is, in weight-stable adults, energy intake must equal TEE. By comparing reported energy intake to TEE, the accuracy of food intake reporting can be assessed (Goldberg et al., 1991a). A large body of literature documents the underreporting of food intake, which can range from 10 to 45 percent depending on the age, gender, and body composition of individuals in the sample population (Johnson, 2000). Underreporting tends to increase as children grow older (Livingstone et al., 1992b), is worse among women than in men (Johnson et al., 1994), and is more pronounced among overweight and obese than among lean individuals (Bandini et al., 1990a; Lichtman et al., 1992; Prentice et al., 1986). Low socioeconomic status, characterized by low income, low educational attainment, and low literacy levels increase the tendency to underreport energy intakes (Briefel et al., 1997; Johnson et al., 1998; Price et al., 1997; Pryer et al., 1997). Ethnic differences affecting sensitivities and psychological perceptions relating to eating and body weight can also affect the accuracy of reported food intakes (Tomoyasu et al., 2000). Finally, individuals with infrequent symptoms of hunger under- report to a greater degree than those who experience frequent hunger (Bathalon et al., 2000). There is some evidence suggesting that underreporters often fail to report foods perceived to be bad or sinful, such as cakes/pies, savory
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254 DIETARY REFERENCE INTAKES Melanson KJ, Saltzman E, Vinken AG, Russell R, Roberts SB. 1998. The effects of age on postprandial thermogenesis at four graded energetic challenges: Find- ings in young and older women. J Gerontol A Biol Sci Med Sci 53:B409–B414. Merrill AL, Watt BK. 1973. Energy Value of Foods, Basis and Derivation. Agricultural Handbook No.74. Human Nutrition Research Branch, Agricultural Research Service, United States Department of Agriculture. U.S. Government Printing Office, Washington, D.C. Miller WC, Koceja DM, Hamilton EJ. 1997. A meta-analysis of the past 25 years of weight loss research using diet, exercise or diet plus exercise intervention. Int J Obes Relat Metab Disord 21:941–947. Minghelli G, Schutz Y, Charbonnier A, Whitehead R, Jequier E. 1990. Twenty-four- hour energy expenditure and basal metabolic rate measured in a whole-body indirect calorimeter in Gambian men. Am J Clin Nutr 51:563–570. Moore FS. 1963. The Body Cell Mass and Its Supporting Environment: Body Composition in Health and Disease. Philadelphia, PA: Saunders. Moore LL, Nguyen USDT, Rothman KJ, Cupples LA, Ellison RC. 1995. Preschool physical activity level and change in body fatness in young children. Am J Epidemiol 142:982–988. Morgan JB, York DA. 1983. Thermic effect of feeding in relation to energy balance in elderly men. Ann Nutr Metab 27:71–77. Morio B, Ritz P, Verdier E, Montaurier C, Beaufrere B, Vermorel M. 1997. Critical evaluation of the factorial and heart-rate recording methods for the determi- nation of energy expenditure of free-living elderly people. Br J Nutr 78:709–722. Morrison JA, Alfaro MP, Khoury P, Thornton BB, Daniels SR. 1996. Determinants of resting energy expenditure in young black girls and young white girls. J Pediatr 129:637–642. Motil KJ, Montandon CM, Garza C. 1990. Basal and postprandial metabolic rates in lactating and nonlactating women. Am J Clin Nutr 52:610–615. Murgatroyd PR, Goldberg GR, Diaz E, Prentice AM. 1990. The influence of mild cold on human energy expenditure: Is there a sex difference in the response? Br J Nutr 64:777. Must A, Strauss RS. 1999. Risks and consequences of childhood and adolescent obesity. Int J Obes Relat Metab Disord 23:S2–S11. Nagy LE, King JC. 1984. Postprandial energy expenditure and respiratory quotient during early and late pregnancy. Am J Clin Nutr 40:1258–1263. Nair KS, Halliday D, Garrow JS. 1983. Thermic response to isoenergetic protein, carbohydrate or fat meals in lean and obese subjects. Clin Sci 65:307–312. Nelson KM, Weinsier RL, Long CL, Schutz Y. 1992. Prediction of resting energy expenditure from fat-free mass and fat mass. Am J Clin Nutr 56:848–856. Neville MC. 1995. Determinants of milk volume and composition. In: Jensen RG, ed. Handbook of Milk Composition. San Diego, CA: Academic Press. Pp. 87–113. Neville MC, Keller R, Seacat J, Lutes V, Neifert M, Casey C, Allen J, Archer P. 1988. Studies in human lactation: Milk volumes in lactating women during the onset of lactation and full lactation. Am J Clin Nutr 48:1375–1386. Newman WP 3rd, Freedman DS, Voors AW, Gard PD, Srinivasan SR, Cresanta JL, Williamson GD, Webber LS, Berenson GS. 1986. Relation of serum lipoprotein levels and systolic blood pressure to early artherosclerosis. The Bolgalusa heart study. N Engl J Med 314:138–144.
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