losses due to glycogen depletion in the low-carbohydrate group, emerged as better than the rest, and if calorie restriction invokes SUMMARY Fine, E.J., and R.D. Feinman (2004). Thermodynamics of weight loss diets. this cannot explain all of the weight loss. Several possibilities metabolic and behavioral responses that “sabotage” efforts Nutr. Metab. (Lond.), 1(1):15. should be examined in light of bioenergetic principles. On the toward permanent weight loss, is there any hope for obese and Energy balance is best explained using a dynamic, as opposed to Flatt, J.P. (1995). Use and storage of carbohydrate and fat. Am. J. Clin. Nutr., energy intake side, there may be lower energy consumption overweight persons to achieve permanent weight loss? Data a static, equation in which changes on one side of the scale result 61(4 Suppl):952S-959S. Sports Science Exchange 99 on the low-carbohydrate diets. The investigations cited above from the National Weight Loss Registry suggests that all is in compensatory metabolic and/or behavioral changes on the were outpatient studies in which no attempt was made to match not lost (Wing & Hill, 2001). There are many individuals who other side. In the face of our current environment of low physical Foster, G.D., H.R. Wyatt, J.O. Hill, B.G. McGuckin, C. Brill, B.S. Mohammed, P.O. Szapary, D.J. Rader, J.S. Edman, and S. Klein (2003). A randomized trial VOLUME 18 (2005) n Number 4 energy intake between dietary conditions. Thus, energy intake are able to successfully maintain weight loss over many years. activity and an abundance of highly palatable, low-cost food, of a low-carbohydrate diet for obesity. N. Engl. J. Med., 348(21):2082-2090. on the low-carb diets might have been reduced because of Characteristics of “maintainers” include dietary restraint, most human regulatory systems are ill-equipped to suffi ciently Information herein is intended for professional audiences, including scientists, coaches, medical professionals, athletic trainers, dietary monotony, greater satiety because of higher protein following a fat-reduced diet, and engaging in a considerable protect against gains in body weight and fat. Body fat stores Guesbeck, N.R., M.S. Hickey, K.G. MacDonald, W.J. Pories, I. Harper, E. nutritionists and other sports health professionals who have a fundamental understanding of human physiology. can be reduced by creating an energy defi cit, but severe energy Ravussin, G.L. Dohm, and J.A. Houmard (2001). Substrate utilization during intakes (Schoeller & Buchholz, 2005) and higher levels of blood amount of regular exercise (Wing & Hill, 2001). There is exercise in formerly morbidly obese women. J. Appl. Physiol., 90(3):1007- ketones (products of fat catabolism). While excretion of urinary increasing evidence in animal studies that chronic exercise can restriction produced by many extreme diets may cause metabolic 1012. ketones on a low carbohydrate diet may contribute to the loss of attenuate increases in metabolic effi ciency and lessen the biologic adaptations that sabotage the dieter’s ability to avoid regaining ENERGY BALANCE AND BODY WEIGHT REGULATION metabolizable energy, this energy loss is thought to be negligible drive to re-establish body fat stores at an obese level. the lost weight. A long-term approach to body weight regulation Leibel, R.L., M. Rosenbaum, and J. Hirsch (1995). Changes in energy expenditure resulting from altered body weight. N. Engl. J. Med., 332(10):621- for most individuals on a low carbohydrate diet. and health is recommended, with an emphasis on a variety of 628. It seems likely that a “one-diet-fi ts-all” approach is ill-suited nutritious whole foods including fresh fruits, vegetables, whole Chris Melby, Dr.P.H. On the energy expenditure side of the energy balance equation, to the human population with its substantial heterogeneity grains, slowly-absorbed carbohydrates, lean proteins, and Levine, J.A., N.L. Eberhardt, and M.D. Jensen (1999). Role of nonexercise Professor of Nutritional Science and Head, it is possible that the low-carbohydrate diet induces greater (Cornier et al., 2005). As more research is conducted, the future activity thermogenesis in resistance to fat gain in humans. Science, Dept. of Food Science and Human Nutrition INTRODUCTION smaller serving sizes. Regular exercise is a critical aspect of 283(5399):212-214. metabolic ineffi ciency. There is no evidence that either exercise holds promise for tailoring dietary and exercise prescriptions maintaining a healthy body weight and remains the best predictor Nutrition and Metabolic Fitness Laboratory Colorado State University, Fort Collins, CO Despite a host of recommendations established by various health energy expenditure or non-exercise activity thermogenesis are to one’s genetic constitution. At present, however, the following of successful long-term weight loss. McAuley, K.A., C.M. Hopkins, K.J. Smith, R.T. McLay, S.M. Williams, R.W. higher on the reduced-carbohydrate diet. The high protein content suggestions are offered, recognizing that these fail to account for Taylor, and J.I. Mann (2005). Comparison of high-fat and high-protein diets organizations for improving diet and increasing physical activity, Matt Hickey, Ph. D. of the diet could result in a greater thermic effect of food, but variable responses in the human population: with a high-carbohydrate diet in insulin-resistant obese women. Diabetologia, the prevalence of obesity has increased dramatically in the REFERENCES 48(1):8-16. Associate Professor and Director, fat has the lowest thermic effect of the three macronutrients, and Human Performance/Clinical Research Lab U.S. during the past two decades. The fattening of America has its high dietary content may attenuate the effect of high protein n Focus on long-term rather than short-term success. Adherence Melby, C.L., R.C. Ho, K. Jeckel, L. Beal, M. Goran, and W.T. Donahoo (2000). Department of Health and Exercise Science spawned a billion-dollar weight-loss industry, with advertising of Bouchard, C., A. Tremblay, J.P. Despres, A. Nadeau, P.J. Lupien, G. Theriault, on the thermic effect of food. The greater dietary protein intake to extreme diets is poor, especially if they promote rapid Comparison of risk factors for obesity in young, nonobese African-American Colorado State University, Fort Collins, CO diet books, exercise programs, and supplements offering quick- J. Dussault, S. Moorjani, S. Pinault, and G. Fournier (1990). The response to and Caucasian women. Int. J. Obes. Relat. Metab. Disord., 24(11):1514-1522. could cause greater protein and amino acid turnover, which is weight loss with large energy defi cits. A long-term approach long-term overfeeding in identical twins. N. Engl. J. Med., 322(21):1477-1482. fi x remedies to boost metabolism and melt away fat. Given the energetically expensive. Additionally, it is likely that at least will likely help to minimize the increases in hunger and Samaha, F.F., N. Iqbal, P. Seshadri, K.L. Chicano, D.A. Daily, J. McGrory, T. confusion, misinformation, and pursuit of the ‘magic bullet’ that 100 g of glucose are required per day by the central nervous metabolic effi ciency that occur with rapid weight loss that Brehm, B.J., R.J. Seeley, S.R. Daniels, and D.A. D’Alessio (2003). A Williams, M. Williams, E.J. Gracely, and J. Stern (2003). A low-carbohydrate characterizes the weight loss industry in the U.S., it is especially randomized trial comparing a very low carbohydrate diet and a calorie- as compared with a low-fat diet in severe obesity. N Engl J Med, 348(21):2074- system, red blood cells, and other glucose-dependent tissues. eventually push the dieter toward weight regain. important for health professionals to re-examine the scientifi c restricted low fat diet on body weight and cardiovascular risk factors in healthy 2081. KEY POINTS With the extremely low availability of carbohydrate early in the women. J. Clin. Endocrinol. Metab., 88(4):1617-1623. principles of body weight regulation. n Choose a healthy diet for life and adjust energy intake to diet (i.e., the induction phase), the synthesis of the necessary Schoeller, D.A., and A.C. Buchholz (2005). Energetics of obesity and weight achieve realistic weight loss goals. A whole-food approach Brehm, B.J., S.E. Spang, B.L. Lattin, R.J. Seeley, S.R. Daniels, and D.A. n Thermodynamic laws dictate that an excess of food energy glucose from amino acids, and to a lesser extent from glycerol, is control: does diet composition matter? J. Am. Diet. Assoc., 105(5 Pt 2):24-28. emphasizing consumption of a variety of fresh fruits, D’Alessio (2005). The role of energy expenditure in the differential weight loss intake relative to energy expenditure will lead to energy energetically expensive. Fine and Fineman (2005) have suggested in obese women on low-fat and low-carbohydrate diets. J. Clin. Endocrinol. Schwartz, M.W., S.C. Woods, R.J. Seeley, G.S. Barsh, D.G. Baskin, and R.L. vegetables, whole grains, and lean, protein-rich foods is storage—an accumulation of fat. Conversely, a defi cit of that increased energy would be required to synthesize the needed Metab., 90(3):1475-1482. Leibel (2003). Is the energy homeostasis system inherently biased toward energy intake relative to expenditure will lead to a loss of RESEARCH REVIEW recommended. There is accumulating evidence that such a weight gain? Diabetes, 52(2):232-238. glucose, which would in effect, contribute to increased metabolic body energy stores and a reduced body weight. “real-world” diet which favors more lean proteins and slowly Buchholz, A.C., and D.A. Schoeller (2004). Is a calorie a calorie? Am. J. Clin. Basic Concepts in Bioenergetics ineffi ciency. However, Brehm et al. (2005) reported that estimates absorbed carbohydrates in place of high-fat, high-sugar Nutr., 79(5):899S-906S. Stern, L., N. Iqbal, P. Seshadri, K.L. Chicano, D.A. Daily, J. McGrory, M. of energy expenditure during resting and postprandial periods Williams, E.J. Gracely, and F.F. Samaha (2004). The effects of low-carbohydrate n But regulation of body weight is not quite so simple. When foods enhances satiety and may help attenuate metabolic and A brief review of bioenergetic principles will provide the basis were no higher on the low-carbohydrate diet compared to the Cornier, M.A., W.T. Donahoo, R. Pereira, I. Gurevich, R. Westergren, S. versus conventional weight loss diets in severely obese adults: one-year follow- individuals undergo a weight-loss diet, they often fail to Enerback, P.J. Eckel, M.L. Goalstone, J.O. Hill, R.H. Eckel, and B. Draznin for understanding many of the issues in body weight regulation. behavioral factors that “sabotage” weight loss and promote up of a randomized trial. Ann. Intern. Med., 140(10):778-785. lose the amount of weight predicted by considering only high-carbohydrate diet. Clearly more research is needed to (2005). Insulin sensitivity determines the effectiveness of dietary macronutrient In humans, energy is required to perform biologic work such weight regain. the reduced amount of calories consumed. In fact, energy examine these issues. composition on weight loss in obese women. Obes. Res., 13(4):703-709. Tremblay, A., J. Seale, N. Almeras, J. Conway, and P. Moe (1991). Energy as muscle contraction, biosynthesis of glycogen and protein, requirements of a postobese man reporting a low energy intake at weight balance is best explained using a dynamic equation in which n Increase energy expenditure by exercising regularly, transport of ions and molecules against a concentration gradient, In an experimental study examining the effi cacy of four different Dansinger, M.L., J.A. Gleason, J.L. Griffi th, H.P. Selker, and E.J. Schaefer maintenance. Am. J. Clin. Nutr., 54(3):506-508. changes on one side of the “energy in/energy out” scale increasing the activities of daily living, and limiting time spent (2005). Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets etc. The primary energy “currency” required for such work is popular diets (Atkins, Ornish, Weight Watchers, and the Zone), result in compensatory metabolic and/or behavioral changes in sedentary activities. Regular exercise may be the best tool for weight loss and heart disease risk reduction: a randomized trial. JAMA, Wing, R.R., and J.O. Hill (2001). Successful weight loss maintenance. Annu. found in the chemical bonds of the adenosine triphosphate (ATP) weight loss was not signifi cantly different among the diet groups 293(1):43-53. Rev. Nutr., 21:323-341. in the other side. For example, when one begins a calorie- available to offset the behavioral and metabolic adjustments molecule. This energy is released upon the breakdown of ATP to after 12 months (Dansinger et al., 2005). Importantly, the best restricted diet, metabolic rate often declines so that weight that accompany weight loss. Specifi cally: adenosine diphosphate (ADP) and inorganic phosphate (Pi). Most predictor of weight loss was not the type of diet, but rather loss is less than expected. dietary adherence, regardless of diet used. Some of the popular of our daily ATP requirement is met by synthesizing ATP from – Although exercise does not appear to protect against loss ADP and Pi in the mitochondria of the cells, with the necessary books on low-carbohydrate diets portray carbohydrates in a of lean body mass in severe energy restriction, it may n There is increasing evidence that human physiology is set energy for this process provided indirectly by the oxidation of bad light because they stimulate insulin release, which in turn help to preserve lean body mass in situations of modest The Gatorade Sports Science Institute® was created to provide current information on developments in up to minimize the potentially negative consequences of suppresses fat breakdown and oxidation. However, carbohydrates energy defi cit as well as promote losses of fat inside exercise science, sports nutrition, and sports medicine and to support the advancement of sports science research. low energy intake (e.g., starvation) better than the negative macronutrients (carbohydrates, fats, and proteins). Figure 1 cannot be the entire problem because in the experiment by the abdominal cavity. (Abdominal fat is considered a consequences of excess calories. This causes a marked shows that when a molecule of glucose undergoes oxidation to For additional information: CO and H O, energy is provided for ATP synthesis. The energy Dansinger et al. the high-carbohydrate Ornish Diet produced signifi cant risk to health. tendency towards weight gain when people eat too much 2 2 In the U.S.A. and Canada: 1-800-616-GSSI (4774) comparable or even greater long-term weight loss than did the food and participate in minimal physical activity. released by the breakdown of ATP is then used for biologic – Exercise appears to be important in enabling individuals www.gssiweb.org reduced-carbohydrate diets. Again, bioenergetic principles work. Note that only a portion of the energy released from the to regulate energy intake to more accurately match n The twin pillars of an effective long-term approach to body oxidation of glucose is conserved in the newly synthesized ATP dictate that even if the diet has a high percentage of calories as Gatorade Sports Science Institute® energy expenditure. In the current environment of fast weight regulation are a healthy diet and regular physical molecule. In actuality, more than half of the energy contained carbohydrate, fat oxidation will be greater than fat intake if the foods, and large serving sizes, it is extremely diffi cult Worldwide Distribution Services diet provides fewer calories than are expended. P.O. Box 1750, Barrington, IL 60010-1750 activity. Crash diets are rarely appropriate because they within the glucose molecule is lost as heat, a phenomenon for the sedentary person to suffi ciently limit energy invoke metabolic adaptations (decreased resting energy described by the second law of thermodynamics, which dictates intake to prevent positive energy balance and body fat expenditure, reduced levels of satiety hormones, and that chemical reactions are always less than perfectly effi cient. If Is the Quest for Weight Loss Hopeless? accumulation. ©2005GatoradeSportsScienceInstitute increases in hunger hormones) that antagonize efforts toward the proportion of energy from glucose conserved as ATP were to PRINTEDONRECYCLEDPAPER If human physiology is biased toward weight gain in our – Regular exercise is the single best predictor of weight-loss This article may be reproduced for non-profi t, educational purposes only. permanent weight loss. Regular exercise remains the major decrease and heat production increase, the process would be even current environment, if no single weight-loss diet plan has maintenance. predictor of long-term weight loss maintenance. less energetically effi cient than normal.

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100589BRO_r2_MelbySSE_Brochure.i1 1 BLACK 349 2/3/06 12:59:31 PM be accommodated by expansion of the fat stores. Based on such Possible Explanations for Apparent Contradictions to the is that of metabolic effi ciency, i.e., the amount of weight gain or evidence, some Americans have mistakenly assumed that a high- Laws of Thermodynamics loss relative to energy ingested. The effi ciency of energy storage carbohydrate diet would not promote weight gain. However, if in response to overfeeding is determined by dividing the excess energy intake exceeds expenditure, it is possible for an individual Accurate measurement of both energy intake and expenditure is energy stored by the excess energy ingested. For example, Levine to become obese even on a low-fat, high-carbohydrate diet – not fraught with diffi culties, and sizeable errors are common. Self- et al. (1999) overfed 24 volunteers for 8 weeks and determined usually because carbohydrate is used to produce fat, but rather reported dietary intake, which is typically used by practitioners the fate of the excess energy. Out of the initial daily excess of because more dietary fat is stored than is oxidized, as the body to estimate energy intake, is notoriously inaccurate. In an 1000 kcal, 432 kcal were stored per day (389 kcal/d as fat, 43 rapidly adjusts to oxidizing carbohydrates to meet its energy FIGURE1.Biologicalenergyproduction.Thecompleteoxidationof interesting case study, Tremblay et al. (1991) described a 45 kcal/d as fat-free tissue). Metabolic effi ciency varied greatly, with needs. For example, suppose that a normal-weight individual aglucosemoleculeprovidesenergyrequiredforATPsynthesis,which year-old male weighing 216 pounds with 26% body fat, who a range of less than 100 kcal/d stored (low metabolic effi ciency) inturnprovidesenergyforcellularwork.Inthisprocess,moreenergyis requiring 2400 kcal to maintain energy balance consumes a was unable to lose weight despite a reported energy intake of to storage of more than 700 kcal/d (high metabolic effi ciency). In lostasheatthanisconservedasATPmolecules. diet with 50% of the energy from carbohydrate, 35% from fat, only 1900 kcal/day under free-living conditions. However, when this study, the resistance to fat gain (i.e., low metabolic effi ciency) FIGURE2.Thecomponentsoftotaldailyenergyexpenditure and 15% from protein. Believing that fat is a dietary villain and tested under controlled experimental conditions, the individual’s was primarily the result of increased non-exercise activity inapersonwhoexercises.Forsedentaryandmoderatelyactive carbohydrates are the key to health, the individual decreases Calorimetry. Determination of the energy available in food is 24-h energy expenditure was greater than 3000 kcal. When he thermogenesis, with smaller contributions from increased resting individuals,restingenergyexpenditureiseasilythelargestcomponent. dietary fat while greatly increasing carbohydrate intake, based on its combustion in a bomb calorimeter. None of the Itsmaindeterminantisbodysize,specificallyleanmass,including was provided a diet of 1900 kcal in the controlled environment energy expenditure and the thermic effect of food. energy is captured as ATP, but rather all is converted to heat; internalorgansandskeletalmuscle.Thecontributionofbodyfat for 5 days, he was in negative energy balance by greater than resulting in a surplus of energy consumed (2600 kcal) relative hence the use of the kilocalorie (a unit of heat energy) to quantify torestingenergyexpenditureismuchsmallerbutincreaseswith 1000 kcal per day, and weight loss resulted from this energy In our current environment characterized by an abundance to expenditure (2400 kcal). Fat balance is positive (fat intake the energy available in food. Correction of bomb calorimetry increasingfatmass.Thethermiceffectoffoodistheincreaseinenergy defi cit. This obviously points to inaccuracies in his self-reported of food, sedentary lifestyles, and high risk for obesity and exceeds oxidation), even with the reduced fat intake (because expenditurefordigestion,absorption,andassimilationofmacronutrients FIGURE3.EnergyBalanceandBiologicalThermodynamics. energy intake exceeds expenditure), and weight gain occurs over data for how well the body can actually utilize each of the energy intake. In agreement with this fi nding, we have used its harmful effects, it should be apparent that low metabolic Thefigurepresentsasimplifiedoverviewofenergybalance.Available (obligatorythermogenesis)aswellasadditionalenergyexpenditure time despite the reduced fat intake. This positive fat balance macronutrients provides the metabolizable energy values of resultingfromincreasedsympatheticnervoussystemactivity.The doubly-labeled water to measure total daily energy expenditure effi ciency (i.e., ineffi ciency) would be advantageous in terms energyforthebodyiscalledmetabolizableenergy,whichreflectsgross 4 kcal/g for carbohydrates and proteins, and 9 kcal/g for fats. physicalactivityenergyexpenditureaccountsfortheremainderofdaily in free-living adults and have found substantial underreporting to of limiting weight gain. In their study of twins, Bouchard et energyintakelessfecalandurinaryenergylosses.Bothgrossintakeand occurs primarily because a surplus of energy as carbohydrate Beverage alcohol (ethanol) provides 7 kcal/g. calorieexpenditureandincludesbothexercisethermogenesisand be common (Guesbeck et al., 2001; Melby et al., 2000). Because al. (1990) found a greater concordance in weight gain within thecorrespondingmetabolizableenergyintakeareaffectedbyahostof suppresses fat oxidation, so that with the positive energy balance, non-exerciseactivitythermogenesis.Thelatterincludesmaintenance self-reported physical activity energy expenditure can also be twin pairs than between twin pairs, suggesting that genetic factors,includingenvironmentalcues,macronutrient-specificeffectson much of the dietary fat is stored rather than oxidized. ofposture,theactivitiesofdailyliving,andevenfidgeting.Theamount satiety,energydensity,andthehedonic(sensory)qualitiesoffood.In Energy Balance Equation. The fi rst law of thermodynamics inaccurate, one must interpret the attendant estimates of energy factors likely play a major role in determining one’s response to states that energy is neither created nor destroyed; rather, it ofenergyexpendedinphysicalactivityisundersubstantialvoluntary addition,biologicalhunger/satietysignalsinteractwiththeenvironmental Popular Diets and Bioenergetic Principles controlandvariesconsiderablyamongindividualsandevenwithinthe balance with caution. overfeeding. The biological factors that contribute to differences andnutrient-specificfactorstocontributetogrossenergyintake.Oncethe undergoes transformation from one form to another. Because the sameindividualondifferentdays. in metabolic effi ciency are complex and incompletely understood. metabolizableenergyisavailableinthebody,therearemanymetabolic High-fat meals promote high energy intake because the energy energy ingested and energy expended must be accounted for, this However, even if accurate measures of energy intake and reactionsthatconsumeATP.Inaddition,thereareseveralprocesseswhich Candidates include differences in non-exercise activity content (at least in the stomach) is relatively “unnoticed.” This law serves as the basis for the energy balance equation. Simply expenditure could be obtained at the start of an energy-reduced contributeto“adaptive”or“flexible”thermogenesis(substrateorfutile thermogenesis (as discussed above), thermogenic hormones phenomenon has been called “passive overconsumption.” When put, an excess of energy intake relative to expenditure will lead diet, the typical calculation used to predict weight change has cycles,ionleaks,etc).Itisimportanttonotethathumanmetabolismand to consider the body as a dynamic system, capable of substantial (thyroid hormone T3), insulin, catecholamines, etc), and various theattendantregulationofenergybalanceconformstoboththe1stand coupled with the observations that dietary fat is the weakest of to body energy storage; conversely, a defi cit of energy intake two faulty underlying assumptions: 1) all the weight loss will metabolic and behavioral adjustments in energy expenditure in changes in energy metabolism that cause greater energy loss as 2ndlawsofthermodynamics;nometabolizableenergyis“lost.”Anyenergy the three macronutrients in promoting satiety, and is also the relative to expenditure will cause loss of body energy stores. be fat tissue; and 2) changes in energy intake have no impact on response to changes in energy intake. heat (Figure 3). thatisnotstoredordirectedtowardATPutilizationisaccountedforinheat weakest at inducing its own oxidation, it is not surprising that energy expenditure. Both assumptions are false. First, while the loss.Moreover,virtuallyALLenergy-transferreactionsthatoccurinhuman high-fat diets are usually high in energy and are more likely to The factors that regulate human energy intake and expenditure majority of diet-induced weight loss results from reductions in An increase in metabolic effi ciency induced by calorie restric- metabolismare“inefficient”(i.e.,notallofthepotentialenergyis“captured” Apparent Contradictions to the Laws of Thermodynamics lead to weight gain. At fi rst glance, it may appear diffi cult to are many and complex. In regard to intake, the hypothalamus body fat, lean tissue is lost as well. Also, with underfeeding there tion will serve to attenuate weight loss and may also contribute asATP),inaccordwiththe2ndlaw.Inter-individualdifferencesinthe “efficiency”ofenergytransferandstoragearenotviolationsofthelawsof reconcile this evidence with results of recent studies showing integrates gastrointestinal-related signals, signals arising from are adaptive decreases in energy expenditure that are invoked to to weight loss plateaus and/or weight regain. With a diet-induced There are many anecdotal reports and even scientifi c fi ndings thermodynamics;theyoccurduetodifferencesinadaptivethermogenesis, that low-carbohydrate diets cause greater weight loss than a macronutrient metabolism (principally in the liver), and chemical “defend” the original body mass. Acute reductions in both resting energy-defi cit, metabolic ineffi ciency would be advantageous for in humans that appear contrary to the commonly used energy theenergycostofmetabolicinterconversionsamongthemacronutrients,and conventional low-fat, calorie-reduced diet during the fi rst 6 signals from both central and peripheral nervous systems that energy expenditure and the thermic effect of food will occur, an obese individual attempting to lower body fat stores. Greater other“energywasting”processessuchasmotor/mechanicalinefficiencies, balance equation. In many studies, the mean weight loss in months on the diet (Brehm et al., 2003; Foster et al., 2003; are anabolic (hunger-stimulating, e.g., neuropeptide Y) or with the decline in resting energy expenditure being greater than weight loss will occur for any given level of energy restriction non-exerciseactivitythermogenesis,etc. volunteers is markedly less than predicted based on the purported McAuley et al., 2005; Samaha et al., 2003; Stern et al., 2004). catabolic (hunger-suppressing, e.g., leptin) to determine the can be explained by loss of body mass (i.e., there is an increase in one who is less metabolically effi cient compared to one who magnitude of the energy defi cits. Conversely, Bouchard and However, based on bioenergetic principles, it should not be biological drive to eat or not to eat. In addition, such “biological” in metabolic effi ciency), and there are attendant reductions in exhibits higher effi ciency. It has been repeatedly suggested that response to overeating, but a very rapid and substantial increase colleagues (1990) fed identical twins 1000 kcal above their initial surprising that such a diet could cause weight loss, even though signals are coordinated with psychosocial factors (e.g., culture), thermogenic hormones (i.e., thyroid hormone, insulin, leptin). the “typical” energetic challenge for much of human history has in metabolic effi ciency and appetite stimulation in response energy requirements every day for 84 days. The energy balance the diet is not promoted as a calorie-reduced approach. For behavioral factors (e.g., eating snacks during television Due to the lower energy intake in the diet, less energy will be been an energy defi cit. Accordingly, the biological response to to a calorie-reduced diet. Stated simply, human physiology is equation would predict a 24-pound weight gain in all subjects. example, assume an overweight sedentary individual is in commercials), and environmental factors (e.g., serving sizes, required to digest and assimilate nutrients, and the thermic effect an energy defi cit is quite robust; it includes a rapid “contraction” biased more to protect against weight loss than unwanted weight However, the average weight gain was only 17.8 pounds. energy and macronutrient balance on a diet of 2400 kcal, with sensory qualities of food). The resulting behavior is not merely of food will fall. Over a longer time period, as weight loss occurs, in resting energy expenditure, reductions in the thermic effect gain. In response to reduced-calorie diets, changes in metabolic Interestingly, among the 12 pairs of twins, there was a three-fold 50% of the energy from carbohydrate, 35% from fat, and 15% the result of an elevated or reduced biological drive to eat, but there will be additional declines in resting energy expenditure, of food, and, if the energy defi cit is severe, a reduction in physi- signals reduce energy expenditure (e.g., decreases in T3, leptin, higher weight gain in some subjects compared to others, despite from protein. Upon initiating a low-carbohydrate diet, despite rather stems from the complex integration of many internal and and the energy required for movement will decrease as a result cal activity energy expenditure, including non-exercise activity and insulin) and stimulate the drive to eat (e.g., increases in the same targeted energy surplus in all individuals. Similarly, the unlimited access to protein and fat, the individual loses external factors. of the lower body mass. Non-exercise activity thermogenesis thermogenesis (Keys et al., 1950). Because the energetic “stress” neuropeptide Y and decreases in leptin). These metabolic changes Levine and coworkers (1999) overfed individuals 1000 kcal per weight in this example for three reasons. First, fat is not added may also decline in response to a hypocaloric diet and declining of abundant, energy-dense foods and a sedentary lifestyle is are then associated with weight regain. Total daily energy expenditure is also determined by numerous day for eight weeks and found more than a 10-fold difference in to a constant amount of carbohydrate; rather, the decrease in the amount of fat gain among study volunteers. Taken together, body mass (Leibel et al., 1995). Given the foregoing evidence, relatively recent on the evolutionary time scale, the regulatory factors as shown in Figure 2. Metabolic Effects of Modifying Macronutrient Intake carbohydrate energy is greater than the increase in fat calories, it is clear that any attempt to predict weight loss based only system is less well-equipped to make adjustments, and weight these fi ndings highlight the substantial inter-individual variability and thus the diet is now hypocaloric. Second, the signifi cant on reduced caloric intake is likely to be in error. Even with an gain ensues (or is at least more likely). The energy balance equation is often used in weight loss in response to changes in energy intake. Other evidence which Alterations in carbohydrate and protein intake produce rapid decrease in carbohydrate intake occurs because fruits, most understanding of the dynamics of biological systems, the sizeable counseling to predict the magnitude of body fat losses in seems contrary to bioenergetic principles includes data from changes in carbohydrate and amino acid oxidation that serve vegetables, cereal, bread, pasta, legumes, desserts, candy, juices, individual differences in metabolic responses to calorie reduction Metabolic Bias towards Weight Gain response to reduced energy intake and/or increased physical recent clinical trials reporting a two-fold greater 6-month weight to maintain carbohydrate and protein balance, respectively. and sugar-sweetened beverages are ‘off-limits,’ so energy intake activity energy expenditure. For example, an overweight loss with the low-carbohydrate Atkins diet compared to a more preclude predicting with any accuracy how much body mass a However, alterations in fat intake produce little, if any, immediate Much attention has been directed toward the hypothesis that drops—often below 1600 kcal/day—while energy expenditure individual may be advised to create a daily 500 kcal defi cit by conventional low-fat diet. These results have sparked much person will lose in the long term. This brings us to the concept of changes in fat oxidation. Accordingly, in the short term there the energy balance regulatory system in humans might favor remains relatively high. Finally, despite the high fat intake, fat reducing intake of specifi c foods in the diet. With a pound of discussion among scientists and health practitioners regarding metabolic effi ciency. is little regulatory effort to maintain fat balance (Flatt, 1995). weight gain (Schwartz et al., 2003). Specifi cally, while the balance is negative (fat oxidation exceeds fat intake) due to the fat equivalent to approximately 3500 kcal, it might be predicted bioenergetics and weight loss (Buchholz & Schoeller, 2004; Fine Thus, weight changes following challenges to energy balance Changes in Metabolic Effi ciency. Whatever the biologic basis system responds rapidly and robustly to energy defi cits, it is hypocaloric state. that the person would have a weekly defi cit of 3500 kcal (500 & Feinman, 2004). Based on these apparent contradictions to are due primarily to disruptions in fat balance, which account for individual differences in weight gain or loss in response to less responsive to energy excess (i.e., it is both slower and less kcal/day X 7 days/wk), which would lead to a total body fat loss bioenergetic principles, should the energy balance equation be for most of the imbalance produced in total energy. Because Why there is a two-fold greater 6-month weight loss on the low- energetic challenges, the laws of thermodynamics still hold. An robust). In practical terms, this results in a slow and modest of over 50 pounds for the year. However, as will be discussed, discarded? Do the laws of thermodynamics hold little utility for carbohydrate and protein balance are maintained more tightly, carbohydrate compared to the conventional diet is a more diffi cult often overlooked issue in explaining some of these diffi cult cases decrease in metabolic effi ciency and appetite suppression in such predictions are tenuous at best, overly simplistic, and fail human body weight regulation? any surplus of dietary energy beyond a few days must necessarily question to answer. While there would initially be greater water

2 3 4

1100589BRO_r2_MelbySSE_Brochure.i200589BRO_r2_MelbySSE_Brochure.i2 2 BLACK 349 22/3/06/3/06 112:59:432:59:43 PMPM be accommodated by expansion of the fat stores. Based on such Possible Explanations for Apparent Contradictions to the is that of metabolic effi ciency, i.e., the amount of weight gain or evidence, some Americans have mistakenly assumed that a high- Laws of Thermodynamics loss relative to energy ingested. The effi ciency of energy storage carbohydrate diet would not promote weight gain. However, if in response to overfeeding is determined by dividing the excess energy intake exceeds expenditure, it is possible for an individual Accurate measurement of both energy intake and expenditure is energy stored by the excess energy ingested. For example, Levine to become obese even on a low-fat, high-carbohydrate diet – not fraught with diffi culties, and sizeable errors are common. Self- et al. (1999) overfed 24 volunteers for 8 weeks and determined usually because carbohydrate is used to produce fat, but rather reported dietary intake, which is typically used by practitioners the fate of the excess energy. Out of the initial daily excess of because more dietary fat is stored than is oxidized, as the body to estimate energy intake, is notoriously inaccurate. In an 1000 kcal, 432 kcal were stored per day (389 kcal/d as fat, 43 rapidly adjusts to oxidizing carbohydrates to meet its energy FIGURE1.Biologicalenergyproduction.Thecompleteoxidationof interesting case study, Tremblay et al. (1991) described a 45 kcal/d as fat-free tissue). Metabolic effi ciency varied greatly, with needs. For example, suppose that a normal-weight individual aglucosemoleculeprovidesenergyrequiredforATPsynthesis,which year-old male weighing 216 pounds with 26% body fat, who a range of less than 100 kcal/d stored (low metabolic effi ciency) inturnprovidesenergyforcellularwork.Inthisprocess,moreenergyis requiring 2400 kcal to maintain energy balance consumes a was unable to lose weight despite a reported energy intake of to storage of more than 700 kcal/d (high metabolic effi ciency). In lostasheatthanisconservedasATPmolecules. diet with 50% of the energy from carbohydrate, 35% from fat, only 1900 kcal/day under free-living conditions. However, when this study, the resistance to fat gain (i.e., low metabolic effi ciency) FIGURE2.Thecomponentsoftotaldailyenergyexpenditure and 15% from protein. Believing that fat is a dietary villain and tested under controlled experimental conditions, the individual’s was primarily the result of increased non-exercise activity inapersonwhoexercises.Forsedentaryandmoderatelyactive carbohydrates are the key to health, the individual decreases Calorimetry. Determination of the energy available in food is 24-h energy expenditure was greater than 3000 kcal. When he thermogenesis, with smaller contributions from increased resting individuals,restingenergyexpenditureiseasilythelargestcomponent. dietary fat while greatly increasing carbohydrate intake, based on its combustion in a bomb calorimeter. None of the Itsmaindeterminantisbodysize,specificallyleanmass,including was provided a diet of 1900 kcal in the controlled environment energy expenditure and the thermic effect of food. energy is captured as ATP, but rather all is converted to heat; internalorgansandskeletalmuscle.Thecontributionofbodyfat for 5 days, he was in negative energy balance by greater than resulting in a surplus of energy consumed (2600 kcal) relative hence the use of the kilocalorie (a unit of heat energy) to quantify torestingenergyexpenditureismuchsmallerbutincreaseswith 1000 kcal per day, and weight loss resulted from this energy In our current environment characterized by an abundance to expenditure (2400 kcal). Fat balance is positive (fat intake the energy available in food. Correction of bomb calorimetry increasingfatmass.Thethermiceffectoffoodistheincreaseinenergy defi cit. This obviously points to inaccuracies in his self-reported of food, sedentary lifestyles, and high risk for obesity and exceeds oxidation), even with the reduced fat intake (because expenditurefordigestion,absorption,andassimilationofmacronutrients FIGURE3.EnergyBalanceandBiologicalThermodynamics. energy intake exceeds expenditure), and weight gain occurs over data for how well the body can actually utilize each of the energy intake. In agreement with this fi nding, we have used its harmful effects, it should be apparent that low metabolic Thefigurepresentsasimplifiedoverviewofenergybalance.Available (obligatorythermogenesis)aswellasadditionalenergyexpenditure time despite the reduced fat intake. This positive fat balance macronutrients provides the metabolizable energy values of resultingfromincreasedsympatheticnervoussystemactivity.The doubly-labeled water to measure total daily energy expenditure effi ciency (i.e., ineffi ciency) would be advantageous in terms energyforthebodyiscalledmetabolizableenergy,whichreflectsgross 4 kcal/g for carbohydrates and proteins, and 9 kcal/g for fats. physicalactivityenergyexpenditureaccountsfortheremainderofdaily in free-living adults and have found substantial underreporting to of limiting weight gain. In their study of twins, Bouchard et energyintakelessfecalandurinaryenergylosses.Bothgrossintakeand occurs primarily because a surplus of energy as carbohydrate Beverage alcohol (ethanol) provides 7 kcal/g. calorieexpenditureandincludesbothexercisethermogenesisand be common (Guesbeck et al., 2001; Melby et al., 2000). Because al. (1990) found a greater concordance in weight gain within thecorrespondingmetabolizableenergyintakeareaffectedbyahostof suppresses fat oxidation, so that with the positive energy balance, non-exerciseactivitythermogenesis.Thelatterincludesmaintenance self-reported physical activity energy expenditure can also be twin pairs than between twin pairs, suggesting that genetic factors,includingenvironmentalcues,macronutrient-specificeffectson much of the dietary fat is stored rather than oxidized. ofposture,theactivitiesofdailyliving,andevenfidgeting.Theamount satiety,energydensity,andthehedonic(sensory)qualitiesoffood.In Energy Balance Equation. The fi rst law of thermodynamics inaccurate, one must interpret the attendant estimates of energy factors likely play a major role in determining one’s response to states that energy is neither created nor destroyed; rather, it ofenergyexpendedinphysicalactivityisundersubstantialvoluntary addition,biologicalhunger/satietysignalsinteractwiththeenvironmental Popular Diets and Bioenergetic Principles controlandvariesconsiderablyamongindividualsandevenwithinthe balance with caution. overfeeding. The biological factors that contribute to differences andnutrient-specificfactorstocontributetogrossenergyintake.Oncethe undergoes transformation from one form to another. Because the sameindividualondifferentdays. in metabolic effi ciency are complex and incompletely understood. metabolizableenergyisavailableinthebody,therearemanymetabolic High-fat meals promote high energy intake because the energy energy ingested and energy expended must be accounted for, this However, even if accurate measures of energy intake and reactionsthatconsumeATP.Inaddition,thereareseveralprocesseswhich Candidates include differences in non-exercise activity content (at least in the stomach) is relatively “unnoticed.” This law serves as the basis for the energy balance equation. Simply expenditure could be obtained at the start of an energy-reduced contributeto“adaptive”or“flexible”thermogenesis(substrateorfutile thermogenesis (as discussed above), thermogenic hormones phenomenon has been called “passive overconsumption.” When put, an excess of energy intake relative to expenditure will lead diet, the typical calculation used to predict weight change has cycles,ionleaks,etc).Itisimportanttonotethathumanmetabolismand to consider the body as a dynamic system, capable of substantial (thyroid hormone T3), insulin, catecholamines, etc), and various theattendantregulationofenergybalanceconformstoboththe1stand coupled with the observations that dietary fat is the weakest of to body energy storage; conversely, a defi cit of energy intake two faulty underlying assumptions: 1) all the weight loss will metabolic and behavioral adjustments in energy expenditure in changes in energy metabolism that cause greater energy loss as 2ndlawsofthermodynamics;nometabolizableenergyis“lost.”Anyenergy the three macronutrients in promoting satiety, and is also the relative to expenditure will cause loss of body energy stores. be fat tissue; and 2) changes in energy intake have no impact on response to changes in energy intake. heat (Figure 3). thatisnotstoredordirectedtowardATPutilizationisaccountedforinheat weakest at inducing its own oxidation, it is not surprising that energy expenditure. Both assumptions are false. First, while the loss.Moreover,virtuallyALLenergy-transferreactionsthatoccurinhuman high-fat diets are usually high in energy and are more likely to The factors that regulate human energy intake and expenditure majority of diet-induced weight loss results from reductions in An increase in metabolic effi ciency induced by calorie restric- metabolismare“inefficient”(i.e.,notallofthepotentialenergyis“captured” Apparent Contradictions to the Laws of Thermodynamics lead to weight gain. At fi rst glance, it may appear diffi cult to are many and complex. In regard to intake, the hypothalamus body fat, lean tissue is lost as well. Also, with underfeeding there tion will serve to attenuate weight loss and may also contribute asATP),inaccordwiththe2ndlaw.Inter-individualdifferencesinthe “efficiency”ofenergytransferandstoragearenotviolationsofthelawsof reconcile this evidence with results of recent studies showing integrates gastrointestinal-related signals, signals arising from are adaptive decreases in energy expenditure that are invoked to to weight loss plateaus and/or weight regain. With a diet-induced There are many anecdotal reports and even scientifi c fi ndings thermodynamics;theyoccurduetodifferencesinadaptivethermogenesis, that low-carbohydrate diets cause greater weight loss than a macronutrient metabolism (principally in the liver), and chemical “defend” the original body mass. Acute reductions in both resting energy-defi cit, metabolic ineffi ciency would be advantageous for in humans that appear contrary to the commonly used energy theenergycostofmetabolicinterconversionsamongthemacronutrients,and conventional low-fat, calorie-reduced diet during the fi rst 6 signals from both central and peripheral nervous systems that energy expenditure and the thermic effect of food will occur, an obese individual attempting to lower body fat stores. Greater other“energywasting”processessuchasmotor/mechanicalinefficiencies, balance equation. In many studies, the mean weight loss in months on the diet (Brehm et al., 2003; Foster et al., 2003; are anabolic (hunger-stimulating, e.g., neuropeptide Y) or with the decline in resting energy expenditure being greater than weight loss will occur for any given level of energy restriction non-exerciseactivitythermogenesis,etc. volunteers is markedly less than predicted based on the purported McAuley et al., 2005; Samaha et al., 2003; Stern et al., 2004). catabolic (hunger-suppressing, e.g., leptin) to determine the can be explained by loss of body mass (i.e., there is an increase in one who is less metabolically effi cient compared to one who magnitude of the energy defi cits. Conversely, Bouchard and However, based on bioenergetic principles, it should not be biological drive to eat or not to eat. In addition, such “biological” in metabolic effi ciency), and there are attendant reductions in exhibits higher effi ciency. It has been repeatedly suggested that response to overeating, but a very rapid and substantial increase colleagues (1990) fed identical twins 1000 kcal above their initial surprising that such a diet could cause weight loss, even though signals are coordinated with psychosocial factors (e.g., culture), thermogenic hormones (i.e., thyroid hormone, insulin, leptin). the “typical” energetic challenge for much of human history has in metabolic effi ciency and appetite stimulation in response energy requirements every day for 84 days. The energy balance the diet is not promoted as a calorie-reduced approach. For behavioral factors (e.g., eating snacks during television Due to the lower energy intake in the diet, less energy will be been an energy defi cit. Accordingly, the biological response to to a calorie-reduced diet. Stated simply, human physiology is equation would predict a 24-pound weight gain in all subjects. example, assume an overweight sedentary individual is in commercials), and environmental factors (e.g., serving sizes, required to digest and assimilate nutrients, and the thermic effect an energy defi cit is quite robust; it includes a rapid “contraction” biased more to protect against weight loss than unwanted weight However, the average weight gain was only 17.8 pounds. energy and macronutrient balance on a diet of 2400 kcal, with sensory qualities of food). The resulting behavior is not merely of food will fall. Over a longer time period, as weight loss occurs, in resting energy expenditure, reductions in the thermic effect gain. In response to reduced-calorie diets, changes in metabolic Interestingly, among the 12 pairs of twins, there was a three-fold 50% of the energy from carbohydrate, 35% from fat, and 15% the result of an elevated or reduced biological drive to eat, but there will be additional declines in resting energy expenditure, of food, and, if the energy defi cit is severe, a reduction in physi- signals reduce energy expenditure (e.g., decreases in T3, leptin, higher weight gain in some subjects compared to others, despite from protein. Upon initiating a low-carbohydrate diet, despite rather stems from the complex integration of many internal and and the energy required for movement will decrease as a result cal activity energy expenditure, including non-exercise activity and insulin) and stimulate the drive to eat (e.g., increases in the same targeted energy surplus in all individuals. Similarly, the unlimited access to protein and fat, the individual loses external factors. of the lower body mass. Non-exercise activity thermogenesis thermogenesis (Keys et al., 1950). Because the energetic “stress” neuropeptide Y and decreases in leptin). These metabolic changes Levine and coworkers (1999) overfed individuals 1000 kcal per weight in this example for three reasons. First, fat is not added may also decline in response to a hypocaloric diet and declining of abundant, energy-dense foods and a sedentary lifestyle is are then associated with weight regain. Total daily energy expenditure is also determined by numerous day for eight weeks and found more than a 10-fold difference in to a constant amount of carbohydrate; rather, the decrease in the amount of fat gain among study volunteers. Taken together, body mass (Leibel et al., 1995). Given the foregoing evidence, relatively recent on the evolutionary time scale, the regulatory factors as shown in Figure 2. Metabolic Effects of Modifying Macronutrient Intake carbohydrate energy is greater than the increase in fat calories, it is clear that any attempt to predict weight loss based only system is less well-equipped to make adjustments, and weight these fi ndings highlight the substantial inter-individual variability and thus the diet is now hypocaloric. Second, the signifi cant on reduced caloric intake is likely to be in error. Even with an gain ensues (or is at least more likely). The energy balance equation is often used in weight loss in response to changes in energy intake. Other evidence which Alterations in carbohydrate and protein intake produce rapid decrease in carbohydrate intake occurs because fruits, most understanding of the dynamics of biological systems, the sizeable counseling to predict the magnitude of body fat losses in seems contrary to bioenergetic principles includes data from changes in carbohydrate and amino acid oxidation that serve vegetables, cereal, bread, pasta, legumes, desserts, candy, juices, individual differences in metabolic responses to calorie reduction Metabolic Bias towards Weight Gain response to reduced energy intake and/or increased physical recent clinical trials reporting a two-fold greater 6-month weight to maintain carbohydrate and protein balance, respectively. and sugar-sweetened beverages are ‘off-limits,’ so energy intake activity energy expenditure. For example, an overweight loss with the low-carbohydrate Atkins diet compared to a more preclude predicting with any accuracy how much body mass a However, alterations in fat intake produce little, if any, immediate Much attention has been directed toward the hypothesis that drops—often below 1600 kcal/day—while energy expenditure individual may be advised to create a daily 500 kcal defi cit by conventional low-fat diet. These results have sparked much person will lose in the long term. This brings us to the concept of changes in fat oxidation. Accordingly, in the short term there the energy balance regulatory system in humans might favor remains relatively high. Finally, despite the high fat intake, fat reducing intake of specifi c foods in the diet. With a pound of discussion among scientists and health practitioners regarding metabolic effi ciency. is little regulatory effort to maintain fat balance (Flatt, 1995). weight gain (Schwartz et al., 2003). Specifi cally, while the balance is negative (fat oxidation exceeds fat intake) due to the fat equivalent to approximately 3500 kcal, it might be predicted bioenergetics and weight loss (Buchholz & Schoeller, 2004; Fine Thus, weight changes following challenges to energy balance Changes in Metabolic Effi ciency. Whatever the biologic basis system responds rapidly and robustly to energy defi cits, it is hypocaloric state. that the person would have a weekly defi cit of 3500 kcal (500 & Feinman, 2004). Based on these apparent contradictions to are due primarily to disruptions in fat balance, which account for individual differences in weight gain or loss in response to less responsive to energy excess (i.e., it is both slower and less kcal/day X 7 days/wk), which would lead to a total body fat loss bioenergetic principles, should the energy balance equation be for most of the imbalance produced in total energy. Because Why there is a two-fold greater 6-month weight loss on the low- energetic challenges, the laws of thermodynamics still hold. An robust). In practical terms, this results in a slow and modest of over 50 pounds for the year. However, as will be discussed, discarded? Do the laws of thermodynamics hold little utility for carbohydrate and protein balance are maintained more tightly, carbohydrate compared to the conventional diet is a more diffi cult often overlooked issue in explaining some of these diffi cult cases decrease in metabolic effi ciency and appetite suppression in such predictions are tenuous at best, overly simplistic, and fail human body weight regulation? any surplus of dietary energy beyond a few days must necessarily question to answer. While there would initially be greater water

2 3 4

1100589BRO_r2_MelbySSE_Brochure.i200589BRO_r2_MelbySSE_Brochure.i2 2 BLACK 349 22/3/06/3/06 112:59:432:59:43 PMPM be accommodated by expansion of the fat stores. Based on such Possible Explanations for Apparent Contradictions to the is that of metabolic effi ciency, i.e., the amount of weight gain or evidence, some Americans have mistakenly assumed that a high- Laws of Thermodynamics loss relative to energy ingested. The effi ciency of energy storage carbohydrate diet would not promote weight gain. However, if in response to overfeeding is determined by dividing the excess energy intake exceeds expenditure, it is possible for an individual Accurate measurement of both energy intake and expenditure is energy stored by the excess energy ingested. For example, Levine to become obese even on a low-fat, high-carbohydrate diet – not fraught with diffi culties, and sizeable errors are common. Self- et al. (1999) overfed 24 volunteers for 8 weeks and determined usually because carbohydrate is used to produce fat, but rather reported dietary intake, which is typically used by practitioners the fate of the excess energy. Out of the initial daily excess of because more dietary fat is stored than is oxidized, as the body to estimate energy intake, is notoriously inaccurate. In an 1000 kcal, 432 kcal were stored per day (389 kcal/d as fat, 43 rapidly adjusts to oxidizing carbohydrates to meet its energy FIGURE1.Biologicalenergyproduction.Thecompleteoxidationof interesting case study, Tremblay et al. (1991) described a 45 kcal/d as fat-free tissue). Metabolic effi ciency varied greatly, with needs. For example, suppose that a normal-weight individual aglucosemoleculeprovidesenergyrequiredforATPsynthesis,which year-old male weighing 216 pounds with 26% body fat, who a range of less than 100 kcal/d stored (low metabolic effi ciency) inturnprovidesenergyforcellularwork.Inthisprocess,moreenergyis requiring 2400 kcal to maintain energy balance consumes a was unable to lose weight despite a reported energy intake of to storage of more than 700 kcal/d (high metabolic effi ciency). In lostasheatthanisconservedasATPmolecules. diet with 50% of the energy from carbohydrate, 35% from fat, only 1900 kcal/day under free-living conditions. However, when this study, the resistance to fat gain (i.e., low metabolic effi ciency) FIGURE2.Thecomponentsoftotaldailyenergyexpenditure and 15% from protein. Believing that fat is a dietary villain and tested under controlled experimental conditions, the individual’s was primarily the result of increased non-exercise activity inapersonwhoexercises.Forsedentaryandmoderatelyactive carbohydrates are the key to health, the individual decreases Calorimetry. Determination of the energy available in food is 24-h energy expenditure was greater than 3000 kcal. When he thermogenesis, with smaller contributions from increased resting individuals,restingenergyexpenditureiseasilythelargestcomponent. dietary fat while greatly increasing carbohydrate intake, based on its combustion in a bomb calorimeter. None of the Itsmaindeterminantisbodysize,specificallyleanmass,including was provided a diet of 1900 kcal in the controlled environment energy expenditure and the thermic effect of food. energy is captured as ATP, but rather all is converted to heat; internalorgansandskeletalmuscle.Thecontributionofbodyfat for 5 days, he was in negative energy balance by greater than resulting in a surplus of energy consumed (2600 kcal) relative hence the use of the kilocalorie (a unit of heat energy) to quantify torestingenergyexpenditureismuchsmallerbutincreaseswith 1000 kcal per day, and weight loss resulted from this energy In our current environment characterized by an abundance to expenditure (2400 kcal). Fat balance is positive (fat intake the energy available in food. Correction of bomb calorimetry increasingfatmass.Thethermiceffectoffoodistheincreaseinenergy defi cit. This obviously points to inaccuracies in his self-reported of food, sedentary lifestyles, and high risk for obesity and exceeds oxidation), even with the reduced fat intake (because expenditurefordigestion,absorption,andassimilationofmacronutrients FIGURE3.EnergyBalanceandBiologicalThermodynamics. energy intake exceeds expenditure), and weight gain occurs over data for how well the body can actually utilize each of the energy intake. In agreement with this fi nding, we have used its harmful effects, it should be apparent that low metabolic Thefigurepresentsasimplifiedoverviewofenergybalance.Available (obligatorythermogenesis)aswellasadditionalenergyexpenditure time despite the reduced fat intake. This positive fat balance macronutrients provides the metabolizable energy values of resultingfromincreasedsympatheticnervoussystemactivity.The doubly-labeled water to measure total daily energy expenditure effi ciency (i.e., ineffi ciency) would be advantageous in terms energyforthebodyiscalledmetabolizableenergy,whichreflectsgross 4 kcal/g for carbohydrates and proteins, and 9 kcal/g for fats. physicalactivityenergyexpenditureaccountsfortheremainderofdaily in free-living adults and have found substantial underreporting to of limiting weight gain. In their study of twins, Bouchard et energyintakelessfecalandurinaryenergylosses.Bothgrossintakeand occurs primarily because a surplus of energy as carbohydrate Beverage alcohol (ethanol) provides 7 kcal/g. calorieexpenditureandincludesbothexercisethermogenesisand be common (Guesbeck et al., 2001; Melby et al., 2000). Because al. (1990) found a greater concordance in weight gain within thecorrespondingmetabolizableenergyintakeareaffectedbyahostof suppresses fat oxidation, so that with the positive energy balance, non-exerciseactivitythermogenesis.Thelatterincludesmaintenance self-reported physical activity energy expenditure can also be twin pairs than between twin pairs, suggesting that genetic factors,includingenvironmentalcues,macronutrient-specificeffectson much of the dietary fat is stored rather than oxidized. ofposture,theactivitiesofdailyliving,andevenfidgeting.Theamount satiety,energydensity,andthehedonic(sensory)qualitiesoffood.In Energy Balance Equation. The fi rst law of thermodynamics inaccurate, one must interpret the attendant estimates of energy factors likely play a major role in determining one’s response to states that energy is neither created nor destroyed; rather, it ofenergyexpendedinphysicalactivityisundersubstantialvoluntary addition,biologicalhunger/satietysignalsinteractwiththeenvironmental Popular Diets and Bioenergetic Principles controlandvariesconsiderablyamongindividualsandevenwithinthe balance with caution. overfeeding. The biological factors that contribute to differences andnutrient-specificfactorstocontributetogrossenergyintake.Oncethe undergoes transformation from one form to another. Because the sameindividualondifferentdays. in metabolic effi ciency are complex and incompletely understood. metabolizableenergyisavailableinthebody,therearemanymetabolic High-fat meals promote high energy intake because the energy energy ingested and energy expended must be accounted for, this However, even if accurate measures of energy intake and reactionsthatconsumeATP.Inaddition,thereareseveralprocesseswhich Candidates include differences in non-exercise activity content (at least in the stomach) is relatively “unnoticed.” This law serves as the basis for the energy balance equation. Simply expenditure could be obtained at the start of an energy-reduced contributeto“adaptive”or“flexible”thermogenesis(substrateorfutile thermogenesis (as discussed above), thermogenic hormones phenomenon has been called “passive overconsumption.” When put, an excess of energy intake relative to expenditure will lead diet, the typical calculation used to predict weight change has cycles,ionleaks,etc).Itisimportanttonotethathumanmetabolismand to consider the body as a dynamic system, capable of substantial (thyroid hormone T3), insulin, catecholamines, etc), and various theattendantregulationofenergybalanceconformstoboththe1stand coupled with the observations that dietary fat is the weakest of to body energy storage; conversely, a defi cit of energy intake two faulty underlying assumptions: 1) all the weight loss will metabolic and behavioral adjustments in energy expenditure in changes in energy metabolism that cause greater energy loss as 2ndlawsofthermodynamics;nometabolizableenergyis“lost.”Anyenergy the three macronutrients in promoting satiety, and is also the relative to expenditure will cause loss of body energy stores. be fat tissue; and 2) changes in energy intake have no impact on response to changes in energy intake. heat (Figure 3). thatisnotstoredordirectedtowardATPutilizationisaccountedforinheat weakest at inducing its own oxidation, it is not surprising that energy expenditure. Both assumptions are false. First, while the loss.Moreover,virtuallyALLenergy-transferreactionsthatoccurinhuman high-fat diets are usually high in energy and are more likely to The factors that regulate human energy intake and expenditure majority of diet-induced weight loss results from reductions in An increase in metabolic effi ciency induced by calorie restric- metabolismare“inefficient”(i.e.,notallofthepotentialenergyis“captured” Apparent Contradictions to the Laws of Thermodynamics lead to weight gain. At fi rst glance, it may appear diffi cult to are many and complex. In regard to intake, the hypothalamus body fat, lean tissue is lost as well. Also, with underfeeding there tion will serve to attenuate weight loss and may also contribute asATP),inaccordwiththe2ndlaw.Inter-individualdifferencesinthe “efficiency”ofenergytransferandstoragearenotviolationsofthelawsof reconcile this evidence with results of recent studies showing integrates gastrointestinal-related signals, signals arising from are adaptive decreases in energy expenditure that are invoked to to weight loss plateaus and/or weight regain. With a diet-induced There are many anecdotal reports and even scientifi c fi ndings thermodynamics;theyoccurduetodifferencesinadaptivethermogenesis, that low-carbohydrate diets cause greater weight loss than a macronutrient metabolism (principally in the liver), and chemical “defend” the original body mass. Acute reductions in both resting energy-defi cit, metabolic ineffi ciency would be advantageous for in humans that appear contrary to the commonly used energy theenergycostofmetabolicinterconversionsamongthemacronutrients,and conventional low-fat, calorie-reduced diet during the fi rst 6 signals from both central and peripheral nervous systems that energy expenditure and the thermic effect of food will occur, an obese individual attempting to lower body fat stores. Greater other“energywasting”processessuchasmotor/mechanicalinefficiencies, balance equation. In many studies, the mean weight loss in months on the diet (Brehm et al., 2003; Foster et al., 2003; are anabolic (hunger-stimulating, e.g., neuropeptide Y) or with the decline in resting energy expenditure being greater than weight loss will occur for any given level of energy restriction non-exerciseactivitythermogenesis,etc. volunteers is markedly less than predicted based on the purported McAuley et al., 2005; Samaha et al., 2003; Stern et al., 2004). catabolic (hunger-suppressing, e.g., leptin) to determine the can be explained by loss of body mass (i.e., there is an increase in one who is less metabolically effi cient compared to one who magnitude of the energy defi cits. Conversely, Bouchard and However, based on bioenergetic principles, it should not be biological drive to eat or not to eat. In addition, such “biological” in metabolic effi ciency), and there are attendant reductions in exhibits higher effi ciency. It has been repeatedly suggested that response to overeating, but a very rapid and substantial increase colleagues (1990) fed identical twins 1000 kcal above their initial surprising that such a diet could cause weight loss, even though signals are coordinated with psychosocial factors (e.g., culture), thermogenic hormones (i.e., thyroid hormone, insulin, leptin). the “typical” energetic challenge for much of human history has in metabolic effi ciency and appetite stimulation in response energy requirements every day for 84 days. The energy balance the diet is not promoted as a calorie-reduced approach. For behavioral factors (e.g., eating snacks during television Due to the lower energy intake in the diet, less energy will be been an energy defi cit. Accordingly, the biological response to to a calorie-reduced diet. Stated simply, human physiology is equation would predict a 24-pound weight gain in all subjects. example, assume an overweight sedentary individual is in commercials), and environmental factors (e.g., serving sizes, required to digest and assimilate nutrients, and the thermic effect an energy defi cit is quite robust; it includes a rapid “contraction” biased more to protect against weight loss than unwanted weight However, the average weight gain was only 17.8 pounds. energy and macronutrient balance on a diet of 2400 kcal, with sensory qualities of food). The resulting behavior is not merely of food will fall. Over a longer time period, as weight loss occurs, in resting energy expenditure, reductions in the thermic effect gain. In response to reduced-calorie diets, changes in metabolic Interestingly, among the 12 pairs of twins, there was a three-fold 50% of the energy from carbohydrate, 35% from fat, and 15% the result of an elevated or reduced biological drive to eat, but there will be additional declines in resting energy expenditure, of food, and, if the energy defi cit is severe, a reduction in physi- signals reduce energy expenditure (e.g., decreases in T3, leptin, higher weight gain in some subjects compared to others, despite from protein. Upon initiating a low-carbohydrate diet, despite rather stems from the complex integration of many internal and and the energy required for movement will decrease as a result cal activity energy expenditure, including non-exercise activity and insulin) and stimulate the drive to eat (e.g., increases in the same targeted energy surplus in all individuals. Similarly, the unlimited access to protein and fat, the individual loses external factors. of the lower body mass. Non-exercise activity thermogenesis thermogenesis (Keys et al., 1950). Because the energetic “stress” neuropeptide Y and decreases in leptin). These metabolic changes Levine and coworkers (1999) overfed individuals 1000 kcal per weight in this example for three reasons. First, fat is not added may also decline in response to a hypocaloric diet and declining of abundant, energy-dense foods and a sedentary lifestyle is are then associated with weight regain. Total daily energy expenditure is also determined by numerous day for eight weeks and found more than a 10-fold difference in to a constant amount of carbohydrate; rather, the decrease in the amount of fat gain among study volunteers. Taken together, body mass (Leibel et al., 1995). Given the foregoing evidence, relatively recent on the evolutionary time scale, the regulatory factors as shown in Figure 2. Metabolic Effects of Modifying Macronutrient Intake carbohydrate energy is greater than the increase in fat calories, it is clear that any attempt to predict weight loss based only system is less well-equipped to make adjustments, and weight these fi ndings highlight the substantial inter-individual variability and thus the diet is now hypocaloric. Second, the signifi cant on reduced caloric intake is likely to be in error. Even with an gain ensues (or is at least more likely). The energy balance equation is often used in weight loss in response to changes in energy intake. Other evidence which Alterations in carbohydrate and protein intake produce rapid decrease in carbohydrate intake occurs because fruits, most understanding of the dynamics of biological systems, the sizeable counseling to predict the magnitude of body fat losses in seems contrary to bioenergetic principles includes data from changes in carbohydrate and amino acid oxidation that serve vegetables, cereal, bread, pasta, legumes, desserts, candy, juices, individual differences in metabolic responses to calorie reduction Metabolic Bias towards Weight Gain response to reduced energy intake and/or increased physical recent clinical trials reporting a two-fold greater 6-month weight to maintain carbohydrate and protein balance, respectively. and sugar-sweetened beverages are ‘off-limits,’ so energy intake activity energy expenditure. For example, an overweight loss with the low-carbohydrate Atkins diet compared to a more preclude predicting with any accuracy how much body mass a However, alterations in fat intake produce little, if any, immediate Much attention has been directed toward the hypothesis that drops—often below 1600 kcal/day—while energy expenditure individual may be advised to create a daily 500 kcal defi cit by conventional low-fat diet. These results have sparked much person will lose in the long term. This brings us to the concept of changes in fat oxidation. Accordingly, in the short term there the energy balance regulatory system in humans might favor remains relatively high. Finally, despite the high fat intake, fat reducing intake of specifi c foods in the diet. With a pound of discussion among scientists and health practitioners regarding metabolic effi ciency. is little regulatory effort to maintain fat balance (Flatt, 1995). weight gain (Schwartz et al., 2003). Specifi cally, while the balance is negative (fat oxidation exceeds fat intake) due to the fat equivalent to approximately 3500 kcal, it might be predicted bioenergetics and weight loss (Buchholz & Schoeller, 2004; Fine Thus, weight changes following challenges to energy balance Changes in Metabolic Effi ciency. Whatever the biologic basis system responds rapidly and robustly to energy defi cits, it is hypocaloric state. that the person would have a weekly defi cit of 3500 kcal (500 & Feinman, 2004). Based on these apparent contradictions to are due primarily to disruptions in fat balance, which account for individual differences in weight gain or loss in response to less responsive to energy excess (i.e., it is both slower and less kcal/day X 7 days/wk), which would lead to a total body fat loss bioenergetic principles, should the energy balance equation be for most of the imbalance produced in total energy. Because Why there is a two-fold greater 6-month weight loss on the low- energetic challenges, the laws of thermodynamics still hold. An robust). In practical terms, this results in a slow and modest of over 50 pounds for the year. However, as will be discussed, discarded? Do the laws of thermodynamics hold little utility for carbohydrate and protein balance are maintained more tightly, carbohydrate compared to the conventional diet is a more diffi cult often overlooked issue in explaining some of these diffi cult cases decrease in metabolic effi ciency and appetite suppression in such predictions are tenuous at best, overly simplistic, and fail human body weight regulation? any surplus of dietary energy beyond a few days must necessarily question to answer. While there would initially be greater water

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1100589BRO_r2_MelbySSE_Brochure.i200589BRO_r2_MelbySSE_Brochure.i2 2 BLACK 349 22/3/06/3/06 112:59:432:59:43 PMPM losses due to glycogen depletion in the low-carbohydrate group, emerged as better than the rest, and if calorie restriction invokes SUMMARY Fine, E.J., and R.D. Feinman (2004). Thermodynamics of weight loss diets. this cannot explain all of the weight loss. Several possibilities metabolic and behavioral responses that “sabotage” efforts Nutr. Metab. (Lond.), 1(1):15. should be examined in light of bioenergetic principles. On the toward permanent weight loss, is there any hope for obese and Energy balance is best explained using a dynamic, as opposed to Flatt, J.P. (1995). Use and storage of carbohydrate and fat. Am. J. Clin. Nutr., energy intake side, there may be lower energy consumption overweight persons to achieve permanent weight loss? Data a static, equation in which changes on one side of the scale result 61(4 Suppl):952S-959S. Sports Science Exchange 99 on the low-carbohydrate diets. The investigations cited above from the National Weight Loss Registry suggests that all is in compensatory metabolic and/or behavioral changes on the were outpatient studies in which no attempt was made to match not lost (Wing & Hill, 2001). There are many individuals who other side. In the face of our current environment of low physical Foster, G.D., H.R. Wyatt, J.O. Hill, B.G. McGuckin, C. Brill, B.S. Mohammed, P.O. Szapary, D.J. Rader, J.S. Edman, and S. Klein (2003). A randomized trial VOLUME 18 (2005) n Number 4 energy intake between dietary conditions. Thus, energy intake are able to successfully maintain weight loss over many years. activity and an abundance of highly palatable, low-cost food, of a low-carbohydrate diet for obesity. N. Engl. J. Med., 348(21):2082-2090. on the low-carb diets might have been reduced because of Characteristics of “maintainers” include dietary restraint, most human regulatory systems are ill-equipped to suffi ciently Information herein is intended for professional audiences, including scientists, coaches, medical professionals, athletic trainers, dietary monotony, greater satiety because of higher protein following a fat-reduced diet, and engaging in a considerable protect against gains in body weight and fat. Body fat stores Guesbeck, N.R., M.S. Hickey, K.G. MacDonald, W.J. Pories, I. Harper, E. nutritionists and other sports health professionals who have a fundamental understanding of human physiology. can be reduced by creating an energy defi cit, but severe energy Ravussin, G.L. Dohm, and J.A. Houmard (2001). Substrate utilization during intakes (Schoeller & Buchholz, 2005) and higher levels of blood amount of regular exercise (Wing & Hill, 2001). There is exercise in formerly morbidly obese women. J. Appl. Physiol., 90(3):1007- ketones (products of fat catabolism). While excretion of urinary increasing evidence in animal studies that chronic exercise can restriction produced by many extreme diets may cause metabolic 1012. ketones on a low carbohydrate diet may contribute to the loss of attenuate increases in metabolic effi ciency and lessen the biologic adaptations that sabotage the dieter’s ability to avoid regaining ENERGY BALANCE AND BODY WEIGHT REGULATION metabolizable energy, this energy loss is thought to be negligible drive to re-establish body fat stores at an obese level. the lost weight. A long-term approach to body weight regulation Leibel, R.L., M. Rosenbaum, and J. Hirsch (1995). Changes in energy expenditure resulting from altered body weight. N. Engl. J. Med., 332(10):621- for most individuals on a low carbohydrate diet. and health is recommended, with an emphasis on a variety of 628. It seems likely that a “one-diet-fi ts-all” approach is ill-suited nutritious whole foods including fresh fruits, vegetables, whole Chris Melby, Dr.P.H. On the energy expenditure side of the energy balance equation, to the human population with its substantial heterogeneity grains, slowly-absorbed carbohydrates, lean proteins, and Levine, J.A., N.L. Eberhardt, and M.D. Jensen (1999). Role of nonexercise Professor of Nutritional Science and Head, it is possible that the low-carbohydrate diet induces greater (Cornier et al., 2005). As more research is conducted, the future activity thermogenesis in resistance to fat gain in humans. Science, Dept. of Food Science and Human Nutrition INTRODUCTION smaller serving sizes. Regular exercise is a critical aspect of 283(5399):212-214. metabolic ineffi ciency. There is no evidence that either exercise holds promise for tailoring dietary and exercise prescriptions maintaining a healthy body weight and remains the best predictor Nutrition and Metabolic Fitness Laboratory Colorado State University, Fort Collins, CO Despite a host of recommendations established by various health energy expenditure or non-exercise activity thermogenesis are to one’s genetic constitution. At present, however, the following of successful long-term weight loss. McAuley, K.A., C.M. Hopkins, K.J. Smith, R.T. McLay, S.M. Williams, R.W. higher on the reduced-carbohydrate diet. The high protein content suggestions are offered, recognizing that these fail to account for Taylor, and J.I. Mann (2005). Comparison of high-fat and high-protein diets organizations for improving diet and increasing physical activity, Matt Hickey, Ph. D. of the diet could result in a greater thermic effect of food, but variable responses in the human population: with a high-carbohydrate diet in insulin-resistant obese women. Diabetologia, the prevalence of obesity has increased dramatically in the REFERENCES 48(1):8-16. Associate Professor and Director, fat has the lowest thermic effect of the three macronutrients, and Human Performance/Clinical Research Lab U.S. during the past two decades. The fattening of America has its high dietary content may attenuate the effect of high protein n Focus on long-term rather than short-term success. Adherence Melby, C.L., R.C. Ho, K. Jeckel, L. Beal, M. Goran, and W.T. Donahoo (2000). Department of Health and Exercise Science spawned a billion-dollar weight-loss industry, with advertising of Bouchard, C., A. Tremblay, J.P. Despres, A. Nadeau, P.J. Lupien, G. Theriault, on the thermic effect of food. The greater dietary protein intake to extreme diets is poor, especially if they promote rapid Comparison of risk factors for obesity in young, nonobese African-American Colorado State University, Fort Collins, CO diet books, exercise programs, and supplements offering quick- J. Dussault, S. Moorjani, S. Pinault, and G. Fournier (1990). The response to and Caucasian women. Int. J. Obes. Relat. Metab. Disord., 24(11):1514-1522. could cause greater protein and amino acid turnover, which is weight loss with large energy defi cits. A long-term approach long-term overfeeding in identical twins. N. Engl. J. Med., 322(21):1477-1482. fi x remedies to boost metabolism and melt away fat. Given the energetically expensive. Additionally, it is likely that at least will likely help to minimize the increases in hunger and Samaha, F.F., N. Iqbal, P. Seshadri, K.L. Chicano, D.A. Daily, J. McGrory, T. confusion, misinformation, and pursuit of the ‘magic bullet’ that 100 g of glucose are required per day by the central nervous metabolic effi ciency that occur with rapid weight loss that Brehm, B.J., R.J. Seeley, S.R. Daniels, and D.A. D’Alessio (2003). A Williams, M. Williams, E.J. Gracely, and J. Stern (2003). A low-carbohydrate characterizes the weight loss industry in the U.S., it is especially randomized trial comparing a very low carbohydrate diet and a calorie- as compared with a low-fat diet in severe obesity. N Engl J Med, 348(21):2074- system, red blood cells, and other glucose-dependent tissues. eventually push the dieter toward weight regain. important for health professionals to re-examine the scientifi c restricted low fat diet on body weight and cardiovascular risk factors in healthy 2081. KEY POINTS With the extremely low availability of carbohydrate early in the women. J. Clin. Endocrinol. Metab., 88(4):1617-1623. principles of body weight regulation. n Choose a healthy diet for life and adjust energy intake to diet (i.e., the induction phase), the synthesis of the necessary Schoeller, D.A., and A.C. Buchholz (2005). Energetics of obesity and weight achieve realistic weight loss goals. A whole-food approach Brehm, B.J., S.E. Spang, B.L. Lattin, R.J. Seeley, S.R. Daniels, and D.A. n Thermodynamic laws dictate that an excess of food energy glucose from amino acids, and to a lesser extent from glycerol, is control: does diet composition matter? J. Am. Diet. Assoc., 105(5 Pt 2):24-28. emphasizing consumption of a variety of fresh fruits, D’Alessio (2005). The role of energy expenditure in the differential weight loss intake relative to energy expenditure will lead to energy energetically expensive. Fine and Fineman (2005) have suggested in obese women on low-fat and low-carbohydrate diets. J. Clin. Endocrinol. Schwartz, M.W., S.C. Woods, R.J. Seeley, G.S. Barsh, D.G. Baskin, and R.L. vegetables, whole grains, and lean, protein-rich foods is storage—an accumulation of fat. Conversely, a defi cit of that increased energy would be required to synthesize the needed Metab., 90(3):1475-1482. Leibel (2003). Is the energy homeostasis system inherently biased toward energy intake relative to expenditure will lead to a loss of RESEARCH REVIEW recommended. There is accumulating evidence that such a weight gain? Diabetes, 52(2):232-238. glucose, which would in effect, contribute to increased metabolic body energy stores and a reduced body weight. “real-world” diet which favors more lean proteins and slowly Buchholz, A.C., and D.A. Schoeller (2004). Is a calorie a calorie? Am. J. Clin. Basic Concepts in Bioenergetics ineffi ciency. However, Brehm et al. (2005) reported that estimates absorbed carbohydrates in place of high-fat, high-sugar Nutr., 79(5):899S-906S. Stern, L., N. Iqbal, P. Seshadri, K.L. Chicano, D.A. Daily, J. McGrory, M. of energy expenditure during resting and postprandial periods Williams, E.J. Gracely, and F.F. Samaha (2004). The effects of low-carbohydrate n But regulation of body weight is not quite so simple. When foods enhances satiety and may help attenuate metabolic and A brief review of bioenergetic principles will provide the basis were no higher on the low-carbohydrate diet compared to the Cornier, M.A., W.T. Donahoo, R. Pereira, I. Gurevich, R. Westergren, S. versus conventional weight loss diets in severely obese adults: one-year follow- individuals undergo a weight-loss diet, they often fail to Enerback, P.J. Eckel, M.L. Goalstone, J.O. Hill, R.H. Eckel, and B. Draznin for understanding many of the issues in body weight regulation. behavioral factors that “sabotage” weight loss and promote up of a randomized trial. Ann. Intern. Med., 140(10):778-785. lose the amount of weight predicted by considering only high-carbohydrate diet. Clearly more research is needed to (2005). Insulin sensitivity determines the effectiveness of dietary macronutrient In humans, energy is required to perform biologic work such weight regain. the reduced amount of calories consumed. In fact, energy examine these issues. composition on weight loss in obese women. Obes. Res., 13(4):703-709. Tremblay, A., J. Seale, N. Almeras, J. Conway, and P. Moe (1991). Energy as muscle contraction, biosynthesis of glycogen and protein, requirements of a postobese man reporting a low energy intake at weight balance is best explained using a dynamic equation in which n Increase energy expenditure by exercising regularly, transport of ions and molecules against a concentration gradient, In an experimental study examining the effi cacy of four different Dansinger, M.L., J.A. Gleason, J.L. Griffi th, H.P. Selker, and E.J. Schaefer maintenance. Am. J. Clin. Nutr., 54(3):506-508. changes on one side of the “energy in/energy out” scale increasing the activities of daily living, and limiting time spent (2005). Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets etc. The primary energy “currency” required for such work is popular diets (Atkins, Ornish, Weight Watchers, and the Zone), result in compensatory metabolic and/or behavioral changes in sedentary activities. Regular exercise may be the best tool for weight loss and heart disease risk reduction: a randomized trial. JAMA, Wing, R.R., and J.O. Hill (2001). Successful weight loss maintenance. Annu. found in the chemical bonds of the adenosine triphosphate (ATP) weight loss was not signifi cantly different among the diet groups 293(1):43-53. Rev. Nutr., 21:323-341. in the other side. For example, when one begins a calorie- available to offset the behavioral and metabolic adjustments molecule. This energy is released upon the breakdown of ATP to after 12 months (Dansinger et al., 2005). Importantly, the best restricted diet, metabolic rate often declines so that weight that accompany weight loss. Specifi cally: adenosine diphosphate (ADP) and inorganic phosphate (Pi). Most predictor of weight loss was not the type of diet, but rather loss is less than expected. dietary adherence, regardless of diet used. Some of the popular of our daily ATP requirement is met by synthesizing ATP from – Although exercise does not appear to protect against loss ADP and Pi in the mitochondria of the cells, with the necessary books on low-carbohydrate diets portray carbohydrates in a of lean body mass in severe energy restriction, it may n There is increasing evidence that human physiology is set energy for this process provided indirectly by the oxidation of bad light because they stimulate insulin release, which in turn help to preserve lean body mass in situations of modest The Gatorade Sports Science Institute® was created to provide current information on developments in up to minimize the potentially negative consequences of suppresses fat breakdown and oxidation. However, carbohydrates energy defi cit as well as promote losses of fat inside exercise science, sports nutrition, and sports medicine and to support the advancement of sports science research. low energy intake (e.g., starvation) better than the negative macronutrients (carbohydrates, fats, and proteins). Figure 1 cannot be the entire problem because in the experiment by the abdominal cavity. (Abdominal fat is considered a consequences of excess calories. This causes a marked shows that when a molecule of glucose undergoes oxidation to For additional information: CO and H O, energy is provided for ATP synthesis. The energy Dansinger et al. the high-carbohydrate Ornish Diet produced signifi cant risk to health. tendency towards weight gain when people eat too much 2 2 In the U.S.A. and Canada: 1-800-616-GSSI (4774) comparable or even greater long-term weight loss than did the food and participate in minimal physical activity. released by the breakdown of ATP is then used for biologic – Exercise appears to be important in enabling individuals www.gssiweb.org reduced-carbohydrate diets. Again, bioenergetic principles work. Note that only a portion of the energy released from the to regulate energy intake to more accurately match n The twin pillars of an effective long-term approach to body oxidation of glucose is conserved in the newly synthesized ATP dictate that even if the diet has a high percentage of calories as Gatorade Sports Science Institute® energy expenditure. In the current environment of fast weight regulation are a healthy diet and regular physical molecule. In actuality, more than half of the energy contained carbohydrate, fat oxidation will be greater than fat intake if the foods, and large serving sizes, it is extremely diffi cult Worldwide Distribution Services diet provides fewer calories than are expended. P.O. Box 1750, Barrington, IL 60010-1750 activity. Crash diets are rarely appropriate because they within the glucose molecule is lost as heat, a phenomenon for the sedentary person to suffi ciently limit energy invoke metabolic adaptations (decreased resting energy described by the second law of thermodynamics, which dictates intake to prevent positive energy balance and body fat expenditure, reduced levels of satiety hormones, and that chemical reactions are always less than perfectly effi cient. If Is the Quest for Weight Loss Hopeless? accumulation. ©2005GatoradeSportsScienceInstitute increases in hunger hormones) that antagonize efforts toward the proportion of energy from glucose conserved as ATP were to PRINTEDONRECYCLEDPAPER If human physiology is biased toward weight gain in our – Regular exercise is the single best predictor of weight-loss This article may be reproduced for non-profi t, educational purposes only. permanent weight loss. Regular exercise remains the major decrease and heat production increase, the process would be even current environment, if no single weight-loss diet plan has maintenance. predictor of long-term weight loss maintenance. less energetically effi cient than normal.

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100589BRO_r2_MelbySSE_Brochure.i1 1 BLACK 349 2/3/06 12:59:31 PM losses due to glycogen depletion in the low-carbohydrate group, emerged as better than the rest, and if calorie restriction invokes SUMMARY Fine, E.J., and R.D. Feinman (2004). Thermodynamics of weight loss diets. this cannot explain all of the weight loss. Several possibilities metabolic and behavioral responses that “sabotage” efforts Nutr. Metab. (Lond.), 1(1):15. should be examined in light of bioenergetic principles. On the toward permanent weight loss, is there any hope for obese and Energy balance is best explained using a dynamic, as opposed to Flatt, J.P. (1995). Use and storage of carbohydrate and fat. Am. J. Clin. Nutr., energy intake side, there may be lower energy consumption overweight persons to achieve permanent weight loss? Data a static, equation in which changes on one side of the scale result 61(4 Suppl):952S-959S. Sports Science Exchange 99 on the low-carbohydrate diets. The investigations cited above from the National Weight Loss Registry suggests that all is in compensatory metabolic and/or behavioral changes on the were outpatient studies in which no attempt was made to match not lost (Wing & Hill, 2001). There are many individuals who other side. In the face of our current environment of low physical Foster, G.D., H.R. Wyatt, J.O. Hill, B.G. McGuckin, C. Brill, B.S. Mohammed, P.O. Szapary, D.J. Rader, J.S. Edman, and S. Klein (2003). A randomized trial VOLUME 18 (2005) n Number 4 energy intake between dietary conditions. Thus, energy intake are able to successfully maintain weight loss over many years. activity and an abundance of highly palatable, low-cost food, of a low-carbohydrate diet for obesity. N. Engl. J. Med., 348(21):2082-2090. on the low-carb diets might have been reduced because of Characteristics of “maintainers” include dietary restraint, most human regulatory systems are ill-equipped to suffi ciently Information herein is intended for professional audiences, including scientists, coaches, medical professionals, athletic trainers, dietary monotony, greater satiety because of higher protein following a fat-reduced diet, and engaging in a considerable protect against gains in body weight and fat. Body fat stores Guesbeck, N.R., M.S. Hickey, K.G. MacDonald, W.J. Pories, I. Harper, E. nutritionists and other sports health professionals who have a fundamental understanding of human physiology. can be reduced by creating an energy defi cit, but severe energy Ravussin, G.L. Dohm, and J.A. Houmard (2001). Substrate utilization during intakes (Schoeller & Buchholz, 2005) and higher levels of blood amount of regular exercise (Wing & Hill, 2001). There is exercise in formerly morbidly obese women. J. Appl. Physiol., 90(3):1007- ketones (products of fat catabolism). While excretion of urinary increasing evidence in animal studies that chronic exercise can restriction produced by many extreme diets may cause metabolic 1012. ketones on a low carbohydrate diet may contribute to the loss of attenuate increases in metabolic effi ciency and lessen the biologic adaptations that sabotage the dieter’s ability to avoid regaining ENERGY BALANCE AND BODY WEIGHT REGULATION metabolizable energy, this energy loss is thought to be negligible drive to re-establish body fat stores at an obese level. the lost weight. A long-term approach to body weight regulation Leibel, R.L., M. Rosenbaum, and J. Hirsch (1995). Changes in energy expenditure resulting from altered body weight. N. Engl. J. Med., 332(10):621- for most individuals on a low carbohydrate diet. and health is recommended, with an emphasis on a variety of 628. It seems likely that a “one-diet-fi ts-all” approach is ill-suited nutritious whole foods including fresh fruits, vegetables, whole Chris Melby, Dr.P.H. On the energy expenditure side of the energy balance equation, to the human population with its substantial heterogeneity grains, slowly-absorbed carbohydrates, lean proteins, and Levine, J.A., N.L. Eberhardt, and M.D. Jensen (1999). Role of nonexercise Professor of Nutritional Science and Head, it is possible that the low-carbohydrate diet induces greater (Cornier et al., 2005). As more research is conducted, the future activity thermogenesis in resistance to fat gain in humans. Science, Dept. of Food Science and Human Nutrition INTRODUCTION smaller serving sizes. Regular exercise is a critical aspect of 283(5399):212-214. metabolic ineffi ciency. There is no evidence that either exercise holds promise for tailoring dietary and exercise prescriptions maintaining a healthy body weight and remains the best predictor Nutrition and Metabolic Fitness Laboratory Colorado State University, Fort Collins, CO Despite a host of recommendations established by various health energy expenditure or non-exercise activity thermogenesis are to one’s genetic constitution. At present, however, the following of successful long-term weight loss. McAuley, K.A., C.M. Hopkins, K.J. Smith, R.T. McLay, S.M. Williams, R.W. higher on the reduced-carbohydrate diet. The high protein content suggestions are offered, recognizing that these fail to account for Taylor, and J.I. Mann (2005). Comparison of high-fat and high-protein diets organizations for improving diet and increasing physical activity, Matt Hickey, Ph. D. of the diet could result in a greater thermic effect of food, but variable responses in the human population: with a high-carbohydrate diet in insulin-resistant obese women. Diabetologia, the prevalence of obesity has increased dramatically in the REFERENCES 48(1):8-16. Associate Professor and Director, fat has the lowest thermic effect of the three macronutrients, and Human Performance/Clinical Research Lab U.S. during the past two decades. The fattening of America has its high dietary content may attenuate the effect of high protein n Focus on long-term rather than short-term success. Adherence Melby, C.L., R.C. Ho, K. Jeckel, L. Beal, M. Goran, and W.T. Donahoo (2000). Department of Health and Exercise Science spawned a billion-dollar weight-loss industry, with advertising of Bouchard, C., A. Tremblay, J.P. Despres, A. Nadeau, P.J. Lupien, G. Theriault, on the thermic effect of food. The greater dietary protein intake to extreme diets is poor, especially if they promote rapid Comparison of risk factors for obesity in young, nonobese African-American Colorado State University, Fort Collins, CO diet books, exercise programs, and supplements offering quick- J. Dussault, S. Moorjani, S. Pinault, and G. Fournier (1990). The response to and Caucasian women. Int. J. Obes. Relat. Metab. Disord., 24(11):1514-1522. could cause greater protein and amino acid turnover, which is weight loss with large energy defi cits. A long-term approach long-term overfeeding in identical twins. N. Engl. J. Med., 322(21):1477-1482. fi x remedies to boost metabolism and melt away fat. Given the energetically expensive. Additionally, it is likely that at least will likely help to minimize the increases in hunger and Samaha, F.F., N. Iqbal, P. Seshadri, K.L. Chicano, D.A. Daily, J. McGrory, T. confusion, misinformation, and pursuit of the ‘magic bullet’ that 100 g of glucose are required per day by the central nervous metabolic effi ciency that occur with rapid weight loss that Brehm, B.J., R.J. Seeley, S.R. Daniels, and D.A. D’Alessio (2003). A Williams, M. Williams, E.J. Gracely, and J. Stern (2003). A low-carbohydrate characterizes the weight loss industry in the U.S., it is especially randomized trial comparing a very low carbohydrate diet and a calorie- as compared with a low-fat diet in severe obesity. N Engl J Med, 348(21):2074- system, red blood cells, and other glucose-dependent tissues. eventually push the dieter toward weight regain. important for health professionals to re-examine the scientifi c restricted low fat diet on body weight and cardiovascular risk factors in healthy 2081. KEY POINTS With the extremely low availability of carbohydrate early in the women. J. Clin. Endocrinol. Metab., 88(4):1617-1623. principles of body weight regulation. n Choose a healthy diet for life and adjust energy intake to diet (i.e., the induction phase), the synthesis of the necessary Schoeller, D.A., and A.C. Buchholz (2005). Energetics of obesity and weight achieve realistic weight loss goals. A whole-food approach Brehm, B.J., S.E. Spang, B.L. Lattin, R.J. Seeley, S.R. Daniels, and D.A. n Thermodynamic laws dictate that an excess of food energy glucose from amino acids, and to a lesser extent from glycerol, is control: does diet composition matter? J. Am. Diet. Assoc., 105(5 Pt 2):24-28. emphasizing consumption of a variety of fresh fruits, D’Alessio (2005). The role of energy expenditure in the differential weight loss intake relative to energy expenditure will lead to energy energetically expensive. Fine and Fineman (2005) have suggested in obese women on low-fat and low-carbohydrate diets. J. Clin. Endocrinol. Schwartz, M.W., S.C. Woods, R.J. Seeley, G.S. Barsh, D.G. Baskin, and R.L. vegetables, whole grains, and lean, protein-rich foods is storage—an accumulation of fat. Conversely, a defi cit of that increased energy would be required to synthesize the needed Metab., 90(3):1475-1482. Leibel (2003). Is the energy homeostasis system inherently biased toward energy intake relative to expenditure will lead to a loss of RESEARCH REVIEW recommended. There is accumulating evidence that such a weight gain? Diabetes, 52(2):232-238. glucose, which would in effect, contribute to increased metabolic body energy stores and a reduced body weight. “real-world” diet which favors more lean proteins and slowly Buchholz, A.C., and D.A. Schoeller (2004). Is a calorie a calorie? Am. J. Clin. Basic Concepts in Bioenergetics ineffi ciency. However, Brehm et al. (2005) reported that estimates absorbed carbohydrates in place of high-fat, high-sugar Nutr., 79(5):899S-906S. Stern, L., N. Iqbal, P. Seshadri, K.L. Chicano, D.A. Daily, J. McGrory, M. of energy expenditure during resting and postprandial periods Williams, E.J. Gracely, and F.F. Samaha (2004). The effects of low-carbohydrate n But regulation of body weight is not quite so simple. When foods enhances satiety and may help attenuate metabolic and A brief review of bioenergetic principles will provide the basis were no higher on the low-carbohydrate diet compared to the Cornier, M.A., W.T. Donahoo, R. Pereira, I. Gurevich, R. Westergren, S. versus conventional weight loss diets in severely obese adults: one-year follow- individuals undergo a weight-loss diet, they often fail to Enerback, P.J. Eckel, M.L. Goalstone, J.O. Hill, R.H. Eckel, and B. Draznin for understanding many of the issues in body weight regulation. behavioral factors that “sabotage” weight loss and promote up of a randomized trial. Ann. Intern. Med., 140(10):778-785. lose the amount of weight predicted by considering only high-carbohydrate diet. Clearly more research is needed to (2005). Insulin sensitivity determines the effectiveness of dietary macronutrient In humans, energy is required to perform biologic work such weight regain. the reduced amount of calories consumed. In fact, energy examine these issues. composition on weight loss in obese women. Obes. Res., 13(4):703-709. Tremblay, A., J. Seale, N. Almeras, J. Conway, and P. Moe (1991). Energy as muscle contraction, biosynthesis of glycogen and protein, requirements of a postobese man reporting a low energy intake at weight balance is best explained using a dynamic equation in which n Increase energy expenditure by exercising regularly, transport of ions and molecules against a concentration gradient, In an experimental study examining the effi cacy of four different Dansinger, M.L., J.A. Gleason, J.L. Griffi th, H.P. Selker, and E.J. Schaefer maintenance. Am. J. Clin. Nutr., 54(3):506-508. changes on one side of the “energy in/energy out” scale increasing the activities of daily living, and limiting time spent (2005). Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets etc. The primary energy “currency” required for such work is popular diets (Atkins, Ornish, Weight Watchers, and the Zone), result in compensatory metabolic and/or behavioral changes in sedentary activities. Regular exercise may be the best tool for weight loss and heart disease risk reduction: a randomized trial. JAMA, Wing, R.R., and J.O. Hill (2001). Successful weight loss maintenance. Annu. found in the chemical bonds of the adenosine triphosphate (ATP) weight loss was not signifi cantly different among the diet groups 293(1):43-53. Rev. Nutr., 21:323-341. in the other side. For example, when one begins a calorie- available to offset the behavioral and metabolic adjustments molecule. This energy is released upon the breakdown of ATP to after 12 months (Dansinger et al., 2005). Importantly, the best restricted diet, metabolic rate often declines so that weight that accompany weight loss. Specifi cally: adenosine diphosphate (ADP) and inorganic phosphate (Pi). Most predictor of weight loss was not the type of diet, but rather loss is less than expected. dietary adherence, regardless of diet used. Some of the popular of our daily ATP requirement is met by synthesizing ATP from – Although exercise does not appear to protect against loss ADP and Pi in the mitochondria of the cells, with the necessary books on low-carbohydrate diets portray carbohydrates in a of lean body mass in severe energy restriction, it may n There is increasing evidence that human physiology is set energy for this process provided indirectly by the oxidation of bad light because they stimulate insulin release, which in turn help to preserve lean body mass in situations of modest The Gatorade Sports Science Institute® was created to provide current information on developments in up to minimize the potentially negative consequences of suppresses fat breakdown and oxidation. However, carbohydrates energy defi cit as well as promote losses of fat inside exercise science, sports nutrition, and sports medicine and to support the advancement of sports science research. low energy intake (e.g., starvation) better than the negative macronutrients (carbohydrates, fats, and proteins). Figure 1 cannot be the entire problem because in the experiment by the abdominal cavity. (Abdominal fat is considered a consequences of excess calories. This causes a marked shows that when a molecule of glucose undergoes oxidation to For additional information: CO and H O, energy is provided for ATP synthesis. The energy Dansinger et al. the high-carbohydrate Ornish Diet produced signifi cant risk to health. tendency towards weight gain when people eat too much 2 2 In the U.S.A. and Canada: 1-800-616-GSSI (4774) comparable or even greater long-term weight loss than did the food and participate in minimal physical activity. released by the breakdown of ATP is then used for biologic – Exercise appears to be important in enabling individuals www.gssiweb.org reduced-carbohydrate diets. Again, bioenergetic principles work. Note that only a portion of the energy released from the to regulate energy intake to more accurately match n The twin pillars of an effective long-term approach to body oxidation of glucose is conserved in the newly synthesized ATP dictate that even if the diet has a high percentage of calories as Gatorade Sports Science Institute® energy expenditure. In the current environment of fast weight regulation are a healthy diet and regular physical molecule. In actuality, more than half of the energy contained carbohydrate, fat oxidation will be greater than fat intake if the foods, and large serving sizes, it is extremely diffi cult Worldwide Distribution Services diet provides fewer calories than are expended. P.O. Box 1750, Barrington, IL 60010-1750 activity. Crash diets are rarely appropriate because they within the glucose molecule is lost as heat, a phenomenon for the sedentary person to suffi ciently limit energy invoke metabolic adaptations (decreased resting energy described by the second law of thermodynamics, which dictates intake to prevent positive energy balance and body fat expenditure, reduced levels of satiety hormones, and that chemical reactions are always less than perfectly effi cient. If Is the Quest for Weight Loss Hopeless? accumulation. ©2005GatoradeSportsScienceInstitute increases in hunger hormones) that antagonize efforts toward the proportion of energy from glucose conserved as ATP were to PRINTEDONRECYCLEDPAPER If human physiology is biased toward weight gain in our – Regular exercise is the single best predictor of weight-loss This article may be reproduced for non-profi t, educational purposes only. permanent weight loss. Regular exercise remains the major decrease and heat production increase, the process would be even current environment, if no single weight-loss diet plan has maintenance. predictor of long-term weight loss maintenance. less energetically effi cient than normal.

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