Mario Mancini, MD, Emeritus Professor of Medicine, Department of Clinical and Experimental Medicine, Federico II University Medical School, Naples, Italy

José M. Ordovas, PhD, Senior Scientist and Director, Nutrition and Genomics Laboratory, Jean Mayer USDA HNRCA at Tufts University, Boston, MA, USA

Gabriele Riccardi, MD, Professor of Endocrine and Metabolic Disease, Department of Clinical and Experimental Medicine, Federico II University Medical School, Naples, Italy

Paolo Rubba, MD, Professor of Medicine, Department of Clinical and Experimental Medicine, Federico II University Medical School, Naples, Italy

Pasquale Strazzullo, MD, Professor of Medicine, Department of Clinical and Experimental Medicine, Federico II University Medical School, Naples, Italy

Nutritional and Metabolic Bases of Cardiovascular Disease

John Wiley & Sons

Copyright © 2011 Blackwell Publishing Ltd.
All right reserved.
ISBN: 978-1-4051-8276-8

Chapter One

Basics of Energy Balance

Luca Scalfi, Fabrizio Pasanisi, & Franco Contaldo Federico II University, Naples, Italy

Introduction

The aim of this chapter is to concisely discuss the basic concepts related to the utilization of energy in the human body. In addition, background information is provided about the practical use of these concepts. These issues are considered in more detail in chapters of books and other major publications on human nutrition to whom the reader may refer for further explanations. Other references are indicated in the text only for more specific points. The human being needs energy to sustain life and maintain the structural and functional integrity of the body. The energy is used by cells to perform chemical work (synthesis and degradation of molecules), mechanical work (muscular contraction), and electrical work (maintenance of ionic gradients across membranes), and eventually lost in the form of heat or external work or is stored (mostly in the adipose tissue as triacylglycerols) if energy balance is positive.

The first law of thermodynamics states that energy cannot be created or destroyed, but only transformed. Human body attains energy from foods where it is stored in the chemical bonds of macronutrients (carbohydrates, fats, and proteins) and alcohol. Through biochemical transformation the energy of nutrients is made available to the body mostly as adenosine triphosphate (ATP), but this conversion into high-energy biochemical compounds is an inefficient process, with 50% of the original energy lost as heat. Furthermore, since a certain percentage of ATP is needed for the transport, storage, and recycling of macronutrients, actual ATP yields correspond to 90%, 75%, and 55% of those expected on the basis of pure oxidation of fats, carbohydrates, and proteins, respectively. In other words, the synthesis of one mole of ATP that can be used by the body requires about 20 kcal for fats, 24 kcal for carbohydrates, and 33 kcal for proteins.

Since all the energy used by the body is ultimately lost as heat (including that related to external work), energy is usually expressed using the calorie, which is defined as the amount of heat energy needed to raise the temperature of 1 ml of water at 15 °C by 1 °C. Actually, according to the SI system, the unit for energy is the joule (J), which measures energy in terms of the mechanical work required to accelerate a mass of 1 kg with a force of 1 newton through 1 m along the direction of the force. Because calorie and joule are small units, considering energy balance, for practical reasons, kilocalorie (kcal = 1,000 cal), kilojoule (kJ = 1,000 J), and sometimes megajoule (MJ = 1,000,000 J) are commonly used in human nutrition. The equivalence is indicated as 1 kcal = 4.184 kJ (in some texts, 4.186) with the inverse ratio of 0.239.

Food Energy

The gross energy of food is the energy contained in the chemical bonds of macronutrients (carbohydrates, fats, and proteins) and alcohol and can be determined using a bomb calorimeter, which is an instrument that measures heat production due to complete oxidation of organic molecules. The gross energy of food (in kcal/g: 4.10 for carbohydrates, 9.45 for fats, 5.65 for proteins, and 7.10 for alcohol) is not entirely available to the body. First, some energy is lost in feces because of incomplete absorption of macronutrients from the digestive tract; the energy available after ingestion of food is termed digestible energy. The absorption rate of macronutrients is usually considered very high–97% for carbohydrates, 95% for fats, and 92% for proteins–but it could be much lower for high-fiber diets, especially with respect to protein digestibility. Once in the body, carbohydrates and fats are completely oxidized to water and carbon dioxide, but this is not the case for proteins. Nitrogen is not oxidized to nitrogen oxides, which are toxic, but to urea, which is much less toxic, and this molecule still contains a quarter of the chemical energy of original proteins. Small amounts of other, not completely oxidized nitrogenous molecules such as amino acids, 3-methyl-hystidine, and creatinine are also lost in the urine. The energy made available to the body after taking into account losses in feces and urine is termed metabolizable energy; the corresponding energy values (kcal/g) are the ones commonly used in human nutrition: 3.75 for monosaccharides, 3.94 for disaccharides, 4.13 for starch, 9.00 for fats (triglycerides composed of long-chain fatty acids), 4.00 for proteins, and 7.00 for alcohol. A figure of about 1.5 kcal/g has also been proposed for dietary fiber, as it can be metabolized (fermented) in the large bowel by bacteria to short-chain fatty acids, which can be subsequently absorbed and utilized in the body.

Components of Total Energy Expenditure

Total energy expenditure (TEE), usually expressed as 24-hour energy expenditure, comprises three main components (basal metabolic rate, thermic effect of food, and energy expenditure due to physical activity), plus a number of additional components that may be relevant in specific circumstances (Table 1.1).

Basal Metabolic Rate

Basal metabolic rate (BMR) is by far the most important component of TEE in a very large percentage (60%–75%) of individuals, and more markedly in sedentary people. BMR corresponds to the energy needed in basal conditions to sustain the metabolic activities of cells and tissues and to maintain vital functions (e.g., circulatory, respiratory, gastrointestinal and renal processes, and body temperature) when the subject is awake and alert; sleeping metabolic rate is 5%–10% lower than BMR.

BMR is determined in standard conditions avoiding any effect of food or physical activity, with the subject lying at physical and mental rest in a comfortably warm environment (thermoneutral environment) and in the post-absorptive state. In practice, according to a realistic protocol, BMR is measured in the first part of the morning after the subject has been in the supine position for 30 minutes, at least 12 hours after eating food or taking any stimulants such as coffee or smoking. Heavy physical activity should also be avoided during the day prior to the test. Resting metabolic rate (RMR) is the term used when the conditions for the measurement of BMR are substantially but not completely met (e.g., because of a shorter fasting period and heavy physical exercise the day before). RMR is, therefore, expected to be slightly higher than BMR. BMR and RMR are usually expressed in kcal/minor, if extrapolated to 24 hours to be more meaningful, in kcal/day. In the latter case, the terms basal energy expenditure (BEE) and resting energy expenditure (REE) are usually (and more appropriately) used.

A number of factors cause the BMR to vary among individuals. By far, body size (i.e., body weight) is the most important one. Heavier people have higher metabolic rates than lighter ones. As metabolic processes that require energy occur almost exclusively within the cytosol and mitochondria, BMR is strictly related to fat-free mass (i.e., body weight minus body lipids) and body cell mass. Brain, liver, kidney, and heart, which together represent 5%–6% of body weight, are the most metabolically active organs, accounting for more than 50% of BMR. For the same amount of tissue, their metabolic rate is much higher than that of skeletal muscles. Indeed, skeletal muscles contribute 20%–30% of BMR in adults because of its large mass, while adipose tissue (at least in people of average weigh) contributes to a small extent, as its metabolic rate per unit of weight is low. As far as metabolic processes are concerned, protein synthesis, Na-K ATPase pump, and gluconeogenesis account for a substantial proportion of energy utilization in basal conditions. Furthermore, BMR is subject to the control of the central nervous system and the sympathetic nervous system and is related to hormonal status (i.e., thyroid hormones and insulin).

In addition, for the same weight and height, BMR is higher in males than in females even after adjusting for body composition and, in women, is higher in the luteal compared to the follicular phase. Furthermore, BMR significantly declines with age in both genders. This trend is not entirely explained by the changes in body composition observed in older people; it may also be ascribed to a number of hormonal and metabolic changes related to senescence.

Thermic Effect of Food

The thermic effect of food (TEF) is the increase in energy expenditure occurring after the ingestion of energetic molecules (carbohydrates, fats, proteins, and alcohol) and is mostly associated with their digestion, absorption, and storage. An increase in energy expenditure can usually be observed from 4 to 6 hours after a mixed meal. Postprandial thermogenesis, specific dynamic action, thermic effect of feeding, and heat increment of feeding are other terms used to describe the same phenomenon.

TEF is influenced by the quantity and the type of macronutrients ingested. The thermogenic response is 5%–10% of ingested energy for carbohydrates, less than 5% for lipids, and 20%–30% for proteins, accounting on average for approximately 10%15% of total energy intake (and TEE, if energy balance is neutral). The high TEF for proteins is due not only to the more complex processes of digestion and absorption but also to substantial postprandial changes in amino acid metabolism, leading to an overall increase of protein turnover.

A number of other factors have been indicated to affect TEF, for instance, overfeeding and underfeeding or physical exercise on the days prior to the test. Several studies have also shown variations due to age, genetic factors, weight changes, and physical fitness. Although these studies are relevant to metabolic and physiological knowledge, from a practical perspective, it is unlikely that in healthy individuals, and in the long term, differences in TEF may significantly influence TEE and energy balance.

Physical Activity

The third main component of TEE is the energy expenditure due to physical activity (EEPA), which is the energy expenditure for physical activities of all kinds. It is important to stress that physical activity does not always match the strict definition of muscular work, which implies external work performed on the environment. In fact, an increase in energy expenditure can also occur without any work in the case of just tensed and stretched muscles (e.g., isometric thermogenesis for standing up and dynamic thermogenesis for climbing down a ladder, respectively).

Energy expenditure due to physical activity can be further split into two components: Exercise activity thermogenesis (EAT) is the energy used during sport or fitness exercises, while non-exercise activity thermogenesis (NEAT) is due to occupational activities, leisure activities, and any other activity related to everyday life. In particular, NEAT also comprises fidgeting (spontaneous physical activity), which is a condition of restlessness, as manifested by continuous movements particularly of body segments. Finally, excess post-exercise oxygen consumption (EPOC) is an additional small increase in energy expenditure even after exercise has ceased, which is related to exercise intensity and duration.

EEPA, which widely varies among individuals as well as from day to day, depends on the type and intensity of a certain physical activity and on the combination of different physical activities over the day. It may also be influenced by the individual habits of motion, as well as the speed and dexterity with which an activity is performed. The energy cost of each physical activity is commonly expressed as a multiple of BMR, and the term correspondingly used by the World Health Organization (WHO) is physical activity ratio (PAR). The term metabolic equivalents (METs) is often used in the same way but is somewhat different. As a matter of fact, METs are multiples of resting oxygen consumption and the latter is not measured but calculated using a fixed rate of oxygen consumption (in adults, 3.5 mL/kg of body weight per minute). This means roughly 1.0 kcal/kg of body weight per hour, or 1.2 kcal/min in a man weighing 70 kg and 1.0 kcal/min in a woman weighing 60 kg. Comprehensive tables on the energy cost of different activities are easily available. In general, PAR (or METs) ranges from 1 to 5 (e.g., 1.4 for standing, 3.3–4.5 for walking) but can reach much higher values (>8) for jogging, running, and selected occupational activities.

The overall level of physical activity can be defined by computing the ratio of TEE to BEE, termed physical activity level (PAL), or sometimes physical activity index (PAI). PAL can be used to describe physical activity habits, or to express how sedentary is the lifestyle of individuals. The Institute of Medicine identified four categories in adults: sedentary, low active, active, and very active with respective PAL ranges of 1.0–1.3, 1.3–1.6, 1.6–1.9, and >1.9. The WHO proposed alternative classification criteria: sedentary or light activity lifestyle for PAL = 1.401.69, active or moderately active lifestyle for PAL = 1.70–1.99, and vigorous or vigorously active lifestyle for PAL >2.00. For instance, performing one hour of moderate to vigorous activity every day (brisk walking to jogging/running, aerobic dancing, cycling, etc.) is sufficient to maintain an active lifestyle. Indeed, PALs of >2.00 are uncommon in industrialized countries.

Other Components of TEE

In addition to the three components already referred to, other minor thermogenic stimuli may be mentioned: psychological thermogenesis, as anxiety and stress increase BMR; cold-induced thermogenesis, due to exposure to low temperature; and drug-induced thermogenesis, for instance, related to the consumption of caffeine, nicotine, or alcohol. The actual impact of these factors on TEE is questionable and cannot easily be evaluated in the single individual.

In terms of energy balance, additional energy needs should be considered in specific circumstances, such as growth, pregnancy, and lactation. Briefly, the energy cost of growth is very high in the first three months of life but declines rapidly to 5% of energy intake in the second year of life, and then to 1%–2% until puberty, including both the cost to synthesize new tissues and the energy deposited in those tissues. The overall energy cost of pregnancy is on average approximately 75,000 kcal, being higher in the second and third trimesters, while during the first six months postpartum, on average an additional 675 kcal/day are needed for milk production if infants are exclusively breastfed.

Variability of TEE

To a very large extent, TEE varies even in people living in developed countries, where technology, which promotes a sedentary lifestyle, is commonly and widely used. All the factors that affect BEE (e.g., body weight and composition, age, and gender)also influence TEE, whereas TEF represents a quite constant and limited component. Large differences in TEE between subjects of the same gender, age, and weight (even >2,000 kcal/day) are accounted for mostly by variance in EEPA. In particular, differences in NEAT may be of great importance since most adults are not regularly involved in sporting-like activities (EAT). The between-subject differences in NEAT may be related to environmental and biological factors affecting both occupational and leisure-time activities, with fidgeting still very difficult to assess. It should be noted that extremely high values of TEE can be observed both in individuals with high levels of physical activity and in severely obese individuals (see below).

Energy Requirements

Energy requirement is defined by the Food and Agriculture Organization of the United Nations (FAO)/WHO/United Nations University (UNU) Consultation as the amount of food energy needed to balance energy expenditure in order to maintain body size, body composition, and a level of necessary and desirable physical activity consistent with long-term well-being and good health. This also includes the energy needed for growth (children and adolescents), deposition of tissues during pregnancy, and production of milk during lactation. According to this definition, energy requirement does not automatically correspond to TEE in a given individual, for instance, in underweight or obese or very sedentary people.

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