Energy Metabolism and Balance

Abstract

Malnutrition is a typical consequence of a disturbed energy balance. The intake of energy substrates should meet the requirements of organism and reflect the ability to metabolize the received substrates in various clinical situations. That means that required energy intake is dependent not only on energy expenditure (measured as substrate oxidation during indirect calorimetry) but also on requirements of organism for growth, defense against infection, healing process, regeneration, and so on. Many malnourished patients experience a combination of stress and underfeeding. Both nutritional status and disease activity must be considered when nutritional support is required; this information is important for selection of energy substrates and prediction of suitable energy balance. Therefore, proper knowledge of energy metabolism principles is important as well as information about methods of energy expenditure measurement. During an acute catabolic phase, the energy balance should be neutral, because efficient anabolic reaction is not possible. However, after the acute condition has subsided, the undernourished subject should be in positive energy balance with the goal to ensure the restoration of original “healthy” condition. The period of positive energy balance should be long enough and combined with rehabilitation therapy and increased protein intake.

1. Introduction

Most energy substrates found in nature come from water and carbon dioxide. These simple molecules are used by plants wherein the energy of sunlight is transferred to the molecules ATP and NADPH, with oxygen being formed as a by-product [1]. Subsequently, carbon dioxide is fixed in the Calvin cycle, and glucose is synthetized using NADPH and ATP [2]. Carbohydrate molecules form a large part of the plant structure (especially cellulose and starch); at the same time, these molecules themselves are the basis for the molecules and energy substrates (e.g., fats and amino acids and proteins or vitamins) [3, 4].

Unlike plants, animals require energy intake in the form of energy substrates (sugars, fats, and proteins), which are primarily produced by plants. These substrates are used by organisms as building blocks for their own growth and development and are oxidized in the body to form carbon dioxide and water (the primary compounds, from which plants synthetize energy substrates). This fantastic cycle of dependence on the plant and animal kingdoms ensures stability and, gradually, development and results in the existence of countless plant and animal species that are constantly evolving and disappearing, with their energy laws and intermediate metabolism following very similar rules [3].

2. Energy metabolism

2.1 Energy phosphates

The universal way for energy transfer in all cells is the phosphorylation and dephosphorylation of some molecules [5]. These are mainly the adenosine diphosphate (ADP) and creatine (C) molecules that are phosphorylated to the ATP (adenosine triphosphate) and CP (creatine phosphate). However, only ATP can be termed as universal energy currency of all energy demanding processes in the cell and body [6]. The turnover of the ATP molecule is extremely high; it is about 100–150 moles per day in resting conditions. This corresponds to 50–75 kg of newly formed ATP per day. As the whole amount of ATP in the human body is much lower, the turnover of this ATP is extremely high. The ATP present in the human body is thus consumed and newly synthetized within 1–2 min, and constant ATP synthesis is thus an obligatory condition for living organisms [7]. In animals, this rapid ATP turnover is provided by constant oxidation processes in mitochondria and, to a lesser extent, pathways related to phosphate transfer from other metabolites (e.g., dephosphorylation of 1, 3-bisphosphoglycerate and phosphoenolpyruvate). Nevertheless, the oxidation of energy substrates in mitochondria is the main mechanism for ATP synthesis. The energy substrates are consumed in food as carbohydrates, lipids, and proteins.

2.2 Energy expenditure and energy intake

Knowledge of energy balance is very important for the management of malnutrition. Energy balance is composed of two parts:

1. Energy expenditure

2. Energy intake

Energy expenditure is a continual process that fluctuates only in intensity due to the constant presence of essential metabolic processes that require energy (such as cell division, protein synthesis and breakdown, neuronal function, membrane potential); thus, continual production of energy phosphates is essential for life [8]. Moreover, processes requiring more energy take place during physical activity and other conditions (such as increased body temperature and disease process). On the other hand, the intake of energy (food intake) is habitually an intermittent process. Thus, the energy substrates present in the food must be either directly oxidized, directly stored, or converted into substrates that are stored. When energy intake is low or absent, these stored substrates (especially lipids) are oxidized to create the energy necessary for survival [9]. In this way, the energy from the food must be either converted into ATP that is essential for ongoing metabolic and physiological processes or stored for period when energy intake is not ensured [10]. Moreover, certain part of the energy substrates that are absorbed in the gastrointestinal tract is utilized for systemic and local anabolic processes such as growth, regeneration, production of immune cells, and renewal of epithelial cells. In this way, energy metabolism and energy balance are not constant, but they change over days, months, and years depending on food intake, physical activity, growth, and health status [11].

The character of stored energy substrates is dependent on ingested food. After consumption of mixed diet, lipids (especially long-chain fatty acids) reach bloodstream as chylomicrons via lymphatic system and are directly stored in adipose tissue. On the other hand, carbohydrates are either used for non-oxidative purposes (reducing processes, synthesis of amino acids and nucleotides, etc.) or they are oxidized for energy production; a small part of absorbed carbohydrates is converted into fat [7]. Proteins and amino acids are usually utilized for synthesis of cellular components and body proteins; the excess of protein is oxidized as an energy source.

The tendency to accumulate energy is habitual and is mainly associated with increased fat intake and storage that leads to the development of obesity when energy balance is positive for a long time. Since a satisfactory food intake has not been constantly guaranteed in the wild, the amount of food eaten was greater than the immediate expenditure and fat calories were preferentially consumed to increase the energy reserves for period of fasting or famine [12]. Moreover, most animals (including humans) tend to increase their energy intake whenever there is possibility to eat. Due to energy reserves in fat tissue, a regular adult subject can survive 2 months of absolute fasting. In case of increased fat reserves, a person can survive a significantly longer period of starvation. For example, the ability to starve for more than 200 days has been described in very obese individuals in whom starvation has been used to control weight loss [13].

2.3 Methods of energy balance assessment

For effective monitoring of energy metabolism and consequently the energy balance of each individual, it is always necessary to know both their energy intake and energy expenditure [9].

2.4 Energy intake

The knowledge of intake of energy substrates (macronutrients), as well as the intake of other nutrients, is essential for the nutritional therapy of malnourished patients, as well as for their additional rehabilitation of patients. Thus, methods of energy intake monitoring are shortly described in the next part.

2.4.1 Monitoring of energy intake

Bomb calorimetry is a method used to accurately determine the amount of energy in individual foodstuffs. The food as well as not consumed part of servings is completely burned in a special device called a bomb calorimeter [14]. During the complete burning (oxidation) of food, the energy is released as heat that can be measured [15]. Moreover, both the amount of oxygen required for complete oxidation (burning) and the quantity of carbon dioxide produced are measured at the same time. However, it should be stressed that the amount of energy released from food oxidation in our body is lower than the amount of energy calculated from bomb calorimetry. This is because of several reasons:

• Some substrates are not oxidized in the body to the same extent as in a bomb calorimeter (e.g., nitrogen from proteins is excreted by kidney as urea that still contains a certain amount of energy, and some part of the energy is spent on urea synthesis).

• Other nutrients are not fully oxidized in the body (e.g., dietary fiber is not absorbed and oxidized and part of it is fermented by intestinal bacteria).

Bomb calorimetry is an effective research method; it is also useful for measurement of energy loss in the stool and thus to monitor the overall energy utilization of various food items. However, it is not practical for routine clinical practice.

Calculation of energy intake in foods based on their composition is a method to calculate the energy content in food. Calculation of energy in food items is based on their composition and amounts of basic macronutrients (carbohydrates, lipids, and proteins) that have a constant quantity of energy—see Table 1.

Substrate	kcal/g	kJ/g
Carbohydrates	4.0	17
Lipids	9.0	37
Proteins	4.0	17
Alcohol	7.0	29

Table 1.

Energy content in the basic components of nutrition.

Using food tables and recognizing the composition of the individual food components and subsequently the whole meals from cooking recipes, it is possible to calculate the energy content of individual meals.

In addition to information about the composition of individual meals, the knowledge of the amount of the individual food items consumed during a particular time interval is essential. This can be achieved as follows:

• Weighing individual portions of food before consumption and then weighing any uneaten leftovers.

• Calculating the content of macronutrients and energy with the help of food tables.

This method is relatively accurate, but it is time and staff demanding (accurate weighing and calculation).

Quarter plate method is a method that can be used in institutionalized subjects (hospital and social care settings), where a standard diet is used [16].

• The content of energy and nutrients in the individual meals is defined in the hospital diet system.

• The nursing staff estimates the part of the portion that was consumed to the nearest one quarter of portion.

• The nutrient and energy eaten is obtained by multiplying the daily nutrient content by the average value of the proportion consumed.

Although the method is not as precise as weighing portions before and after meal, it is fast and useful for obtaining information on whether energy intake is sufficient. It immediately identifies a patient whose actual intake is low and in whom nutritional support is indicated [17].

2.4.2 Energy intake in free living subjects

We do not have any suitable, simple, and sufficiently accurate method for monitoring food intake for outpatients. At present time, two basic methods are used:

• Recording method—the monitored person records the amount of all food consumed during some days (usually two working days and one weekend day). The amount of energy and other nutrients received is then calculated. Then, it is suggested that similar food intake is similar for the rest of time.

• Anamnestic methods—the assessed individual should answer questions related to eating habits (e.g., How many times a week do you drink a glass of milk, eat a bowl of nuts, or eat a slice of bread?).

Both methods are used in epidemiological studies, but they are hampered by a relatively large error. Besides others, this is because some subjects tend to “adjust” the data according to optimal recommendations.

3. Energy expenditure

3.1 Indirect calorimetry

The oxidation of energy substrates is the largest part of energy production in animals. Complete oxidation of carbohydrates and lipids leads oxygen consumption (VO₂) and production of carbon dioxide (VCO₂) and water (H₂O). Complete oxidation of proteins is also associated with VO₂ and VCO₂; moreover, nitrogen is excreted in the urine in the form of urea. Therefore, VO₂ and VCO₂ and nitrogen excretion are equivalent to the energy expenditure and oxidation of individual energy substrates. The measurement of energy expenditure based on VO₂ and VCO₂ is called indirect calorimetry [18].

3.2 History

As early as the eighteenth century, Antoine Lavoisier discovered that animals produce heat. At the same time, Joseph Priestley described that the lives of experimental animals depend on the presence of oxygen, which is gradually consumed. These findings led to the conclusion that the energy metabolism of animals is identical to the burning process. In the nineteenth century, Carl von Voit and Max Joseph von Pettenkofer built a calorimeter to measure the differences in CO₂ production and O₂ consumption when consuming different foods. At the beginning of the twentieth century, Claude Gordon Douglas invented a bag into which exhaled air could be collected and subsequently analyzed. The great development of indirect calorimetry for the purpose of nutritional support of patients escalated after development of a ventilated plexiglass box to that the patient head could be placed by John Kinney [19]. This allowed long-term monitoring of energy metabolism by indirect calorimetry [20].

3.3 Calculations

Substrate oxidation calculations obtained by indirect calorimetry are based on the stoichiometric equations of oxidation of basic energy substrates:

$$\begin{array}{c}1\mathrm{mol}\text{glucose}+6\mathrm{mol}{\mathrm{O}}_2➔6\mathrm{mol}{\mathrm{H}}_{\mathrm{2}}\mathrm{O}+6\mathrm{mol}{\mathrm{CO}}_2,\\ 1\mathrm{mol}\text{palmitate}+23\mathrm{mol}{\mathrm{O}}_2➔16\mathrm{mol}{\mathrm{H}}_2\mathrm{O}+16\mathrm{mol}{\mathrm{CO}}_2.\end{array}$$E1

The values of oxygen consumption and carbon dioxide production per 1 g of energy substrate are presented in Table 2.

Substrate	O2 consumption	CO2 production	RQ
	[l/g]	[l/g]
Carbohydrates (glucose)	0.829	0.829	1.0
Fats (palmitate)	2.01	1.43	0.7
Protein (mixed protein)	0.966	0.774	0.8

Table 2.

Oxygen consumption and carbon dioxide production during complete oxidation of basic energy substrates.

RQ (respiratory quotient) = VCO₂/VO₂ 1 g of nitrogen in urine = 6.25 oxidized proteins.

Then:

Oxygen consumption:

$${\mathrm{VO}}_2=0.829\mathrm{CHO}+2.01\text{Fats}+6.04\text{nitrogen in urine}\left[g\right].$$E2

Carbon dioxide production:

$${\mathrm{VCO}}_2=0.829\mathrm{CHO}+1.43\text{Fats}+4.84\text{nitrogen in urine}\left[g\right].$$E3

Oxidation of energy substrates:

$$\begin{array}{c}\mathrm{CHO}=4.59{\mathrm{VCO}}_2–3.25{\mathrm{VO}}_2–3.68\text{nitrogen in urine}\left[g\right],\\ \mathrm{Fat}=1.69{\mathrm{VO}}_2–1.69{\mathrm{VCO}}_2–1.72\text{nitrogen in urine}\left[g\right],\\ \text{Protein}=6.25\text{urine nitrogen}.\end{array}$$E4

Total energy expenditure (EV):

$$\mathrm{EE}=3.87{\mathrm{VO}}_2+1.19{\mathrm{VCO}}_2–5.99N\left(\text{total urine nitrogen in grams}\right).$$E5

From the equations above, we can calculate both the total energy expenditure and the amount of oxidized carbohydrates, fats, and proteins from oxygen consumption, carbon dioxide production, and urinary nitrogen losses. Nitrogen loss has little effect on the results of energy expenditure calculated from VO₂ and VCO₂. Moreover, accurate measurement of nitrogen loss is difficult for clinical practice. Therefore, energy expenditure is routinely calculated from VO₂ and VCO₂:

$$\mathrm{EE}=3.84{\mathrm{VO}}_2+1.12{\mathrm{VCO}}_2\left({\text{Brouwer}}^{’}s\text{formula}\right).$$E6

Other formulas for the calculation of energy expenditure can be found in the literature (Weir, Lusk, Elia), the constants of which differ according to the representation of individual substrates in the studies of individual authors [20, 21]. However, the overall impact of the different formulas is not significant for usual clinical practice.

Energy expenditure can also be measured by monitoring oxygen consumption alone or by monitoring carbon dioxide production alone.

Energy expenditure calculated from VO₂:

$$\mathrm{EE}={\mathrm{VO}}_2\left(3.84+1.12\mathrm{RQ}\right).$$E7

Energy expenditure calculated from VCO₂:

$$\mathrm{EV}={\mathrm{VCO}}_2\left(1.12+3.84/\mathrm{RQ}\right).$$E8

3.4 Double-labeled water method for energy expenditure measurement

The subject drinks water that contains a stable isotope of oxygen (¹⁸O) and hydrogen (deuterium—²H). Twelve hours after drinking this double-labeled water, the concentrations of ¹⁸O and ²H are measured in any body fluid (urine, saliva, or plasma). During the following observed period, both stable isotopes are eliminated from the organism differently:

• ²H is excreted from the body only in the form of water.

• ¹⁸O is excreted from the body both in the form of water and in the form of CO₂, as part of ¹⁸O balances with the pool of plasma bicarbonate and is subsequently excreted by the lungs.

For this reason, the elimination rate of ¹⁸O is greater than the elimination rate of ²H. The difference between these values is equivalent to CO₂ production over the observed period. This method can be used in free living subjects for extended period. The optimal time interval is dependent on the metabolic rate. In very active individuals or newborns, it is 3–5 days, while in adults with minimal movement or the elderly, the measurement period is extended to 3–4 weeks [22]. The double-labeled water method has been used in numerous clinical studies or in extreme conditions (e.g., during the climbing to Mount Everest); however, due to high cost, it is not suitable for routine clinical practice.

3.5 Formulas used for calculation of energy expenditure

Resting energy expenditure (REE) is an individual’s energy expenditure under resting conditions after 12 h of fasting. The value of this energy expenditure can be estimated from basic anthropometrical values (body height and weight), age, and sex. Several formulas have been proposed for REE calculation; the most used of these is still the Harris-Benedict formula which has been used for a hundred years [23]. A different calculation is used for women and men:

Women:

$$\begin{array}{c}\mathrm{REE}=655.0955+\left(9.5634\times \text{weight in}\mathrm{kg}\right)+\left(1.8496\times \text{height in}\mathrm{cm}\right)\\ –\left(4.6756\times \mathrm{age}\text{in years}\right).\end{array}$$E9

Men:

$$\begin{array}{c}\mathrm{REE}=66.473+\left(13.7516\times \text{weight in}\mathrm{kg}\right)+\left(5.0033\times \text{height in}\mathrm{cm}\right)\\ –\left(6.755\times \mathrm{age}\text{in years}\right).\end{array}$$E10

For quick orientation, it is possible to use a simple assumption that the basic energy expenditure corresponds to 1 kcal per 1 kg of body weight per hour; the daily basic energy expenditure can be calculated as:

$$\mathrm{BEE}=24x\text{body weight in}\mathrm{kg}.$$E11

3.6 Components of total energy expenditure

Total energy expenditure (TEE) consists of three basic parts:

• Resting energy expenditure (REE)—this depends on body cell mass and represents energy expenses of the basic metabolic pathways, the activity of the heart and respiratory muscles, etc.

• Diet-induced thermogenesis (DIT)—10% increase in energy expenditure after food intake also called thermic effect of nutrition (TEN). This increase is due to energy spent for interconversion of metabolic substrates [24].

• Activity-induced energy expenditure (AEE)—the most variable component of the TEE that is dependent on physical activity. The activity associated with regular light work will increase energy expenditure by 50–70%. This increase can be doubled during physically demanding work or during sports activities [25].

During the stay in the hospital, especially in the intensive care unit, the values of energy expenditure can be modified according to Table 3.

EV is increased

Fever 13% at 1°C,

Tremor 100%,

Visiting relatives 40%,

Stressful breathing 25%,

Nutrition 9%,

Catecholamines 30%.

EV is reduced

Hypothermia 13% at 1°C,

Muscle relaxation 40%,

Analgesia 50%,

Adapted ventilation 20%,

Starvation 10–20%,

Beta blockers 25%.

Table 3.

Changes in energy expenditure during the stay in the intensive care unit [26].

3.7 Energy expenditure and nutritional support planning in malnourished patient

Knowledge of energy substrate oxidation and energy expenditure is still very important for research devoted to metabolism and nutrition. However, for routine planning nutritional support especially in malnourished subject the information about energy expenditure is not the most critical one. Knowledge of the goals of nutritional support is more important. If the goal of nutritional support is, for example, growth, regeneration, healing, or increase in muscle mass associated with rehabilitation, nutritional intake recommendations may differ by up to several tens of percent from the values measured by direct calorimetry. An example is a growing child for whom the recommended energy intake is up to twice the REE value or severely malnourished patient who needs extra 1000 kcal per day to gain 100 g of tissue.

Careful knowledge of nutritional goals and their monitoring during nutritional support is therefore far more important than accurate knowledge of energy expenditure. This issue will be further elaborated in the chapter devoted to the energy balance.

3.8 Energy balance and nutrition

In the early years of nutritional support (mostly parenteral), the prevailing theory was that catabolism associated with critical illness and subsequent malnutrition could be reversed by increased energy intake. Therefore, the goal of nutritional support was to increase energy intake to achieve positive energy balance. The so-called hypercaloric nutrition (or hyperalimentation) was used at that time [27].

However, with time this concept was proven to be wrong. Measurements of energy expenditure showed that elective operations do not considerably raise energy expenditure and that only patients with major trauma or very severe sepsis may show increased values by 20%–40% for a limited period [19]. In addition, the positive energy balance cannot reverse further catabolism caused by inflammation or injury in critically ill patients. An increase in skeletal muscle mass occurs only if the positive energy balance is combined with the corresponding physical activity [28].

Unfortunately, subsequently, we emptied the baby out with bath. As is the case, after finding out the above, the concept of hyperalimentation was criticized and abandoned altogether [29] and the concept of planned malnutrition was subsequently promoted in order to avoid the limited complications associated with a very positive energy balance. The problem is that the concept of a planned administration of a reduced energy dose can lead to a gradual loss of body cell mass (presented as muscle mass) of patients. This aggravates the malnutrition, and the patients are unable to leave the intensive care unit or hospital, or they die in subsequent healthcare facilities or even at home without achieving a tolerable quality of life.

As explained earlier, the human organism is very rarely found in a period of balanced energy balance. During the period of food intake, physical activity is usually limited and, conversely, during periods of maximum physical activity, food intake is limited [30]. Undoubtedly, the human body is able to very efficiently accumulate energy in the body’s stores (especially fat) and use this energy during fasting or starvation. The fact that a healthy young person can fast for about 60 days demonstrates the human body’s great ability to use accumulated energy [13, 31].

On the other side, the long period of negative energy balance always leads to the subsequent malnutrition and final exhaustion of the body. Protein stores are especially very important. When only 30–40% of the standard (original) protein content remains in the organism, there will be a resulting serious threat to life. Such losses occur in healthy individuals just after 50–70 days of uncomplicated starvation, when both adipose tissue and body proteins are lost from the body.

However, the ratio between the loss of adipose tissue and protein (especially muscle protein) depends on the inflammatory state of the body that significantly diminishes the ability to adapt to a negative energy balance. The loss of body protein is much faster during inflammatory disease than during uncomplicated starvation [32, 33, 34]. This is because systemic inflammation leads to an increase in the demand for amino acids for the purposes of the inflammatory response, which leads to a gradual loss of skeletal muscle proteins. For this reason, the length of survival of starvation during inflammatory conditions is significantly reduced. In addition, protein loss is associated with a consequent loss of bodily function and rehabilitation ability.

A common mistake is the fact that the supplied energy substrates (especially carbohydrates) are considered only as a source of energy, i.e., as those substrates that serve only to form ATP in the oxidation process [7]. However, these substrates have other and possibly more important functions for the organism; these substrates are needed as building blocks for growth and regeneration, for the reducing processes of the organism, for maintaining the internal environment, for defense against the invasion of microorganisms, for the transmission of nerve impulses, for communication between cells and organs, and the like [3]. Moreover, many energy substrates are lost from the body without being oxidized; these are, for example, energy losses in the stool but also losses in the form of other secretions or pus (originally formed by leukocytes) or peeled epithelium. For these reasons, the view of the needs of energy substrates for the organism must be more comprehensive. To satisfy all requirements, we cannot just follow the measurement of energy expenditure using indirect calorimetry, which reflects only one part of the energy substrates, namely the one that has been oxidized to water and carbon dioxide: see Figure 1.

Figure 1.

Energy intake and oxidation—variable parts of the provided energy substrates are not oxidized.

Reproduced with agreement of GALEN, authors, and editor in chief [27].

The planned energy intake and subsequent energy balance of malnourished or sick individuals in need of nutritional treatment must always be in accordance with the goals of a comprehensive treatment strategy. For this reason, the selection of individual energy substrates is extremely important in patient with malnutrition. The goals of nutritional support must be well defined, and the total amount of energy along with the representation of individual energy substrates must be planned according to these goals.

3.9 Goals of nutritional support in terms of energy supply in malnourished subject

The optional intake of energy substrates or macronutrients is not constant and does not depend exclusively only on energy expenditure, measured by indirect calorimetry [35]. This is because indirect calorimetry summarizes only the actual quantity of energy substrates that are completely oxidized. The proposed intake of energy substrates and the resulting energy balance may vary according to the clinical conditions and the objectives of nutritional support:

• In stable individuals, the nutritional goal is to maintain or gradually improve bodily function and to prevent excessive weight loss (especially body cell mass).

• In undernourished individuals who have lost body and especially cell mass, the intake of macronutrients should guarantee the restoration of the normal composition of the body and its sufficient function.

• For growing children, energy intake must ensure normal growth and development.

• In severe and critical illness, when muscle anabolism is not possible, the intake of macronutrients should minimize the negative energy balance and associated muscle loss.

• After improvement in a critical condition or during postsurgical regeneration, the intake of energy substrates should guarantee the regeneration of tissue and function that were lost during the catabolic circumstances.

• For malnourished patients requiring early surgery, energy intake should ensure a safe surgical procedure and subsequent healing.

• In morbidly obese patients who are not in a critical or severe inflammatory state, the intake of energy should lead to a harmless decrease in fat mass without losing the functional potential of the body.

It is obvious that energy intake should not only cover energy expenditure, but also reflect the nutritional status of the patient, the clinical situation, and the goals of nutritional support. In malnourished subject, an intake of energy substrates must reflect not only resting energy expenditure but must also provide substrates for growth, regeneration, replenishment of cell mass and energy stores, and improvement in physical activity. On the other hand, a disproportionately high energy intake that does not correspond to the patient’s clinical condition and nutritional goals is associated with accumulation of fat stores with all secondary metabolic changes [36].

Setting and satisfying nutritional goals is more important than the method of nutritional support (parenteral or enteral). If it is not possible to achieve these goals by oral or enteral nutrition, it is necessary to initiate supplementary or even complete parenteral nutrition.

3.10 Energy substrates during nutritional support

Regarding energy intake, it is necessary to address two aspects: the total amount of energy intake (how many calories or joules should be given) and the proportion of different substrates (carbohydrates, fats, and proteins) that provide this energy.

Energy intake depends on the goals of nutritional support:

• During acute or critical illness, provided energy should prevent or reduce the loss of body cell mass.

• During severe inflammation, nutritional support should also provide substrates necessary for inflammatory and immune processes.

• In severely malnourished patient, the nutritional support must guarantee the improvement in nutritional status, physical rehabilitation, and increase in skeletal muscle mass.

• Nutritional support should ensure or improve the growth of children.

Energy substrate intake should be also adapted to the following clinical condition:

• Critical illness

• Severe malnutrition

• Body composition (e.g., obesity)

Despite countless studies, it is still not easy to determine the exact energy intake required for an individual patient in a special condition. Moreover, metabolic conditions and energy needs change during the development of any disease. The goals of intake of energy substrates must also reflect the potential growth needs of the children and the recovery of body mass (i.e., muscle gains) in the depleted adult subjects during convalescence period. The adapting energy intake to individual circumstances requires careful patient monitoring and assessment of the effects of nutritional support.

3.11 Energy intake and phases of acute illness

Acute illness usually leads to negative energy balance that can result in deterioration of nutritional status and development of severe malnutrition. Therefore, nutritional treatment must be integral part of treatment. The intake of total energy and particular macronutrients is dependent on the stage of the disease and the nutritional status:

• Critically ill, hemodynamically unstable patients—usually, stabilization of blood pressure and tissue perfusion is the priority of treatment at this stage. The spontaneous food intake is absent that leads to loss of body mass. However, nutritional support usually cannot reverse catabolism. Therefore, it is recommended not to exceed 25 kcal kg⁻¹ h⁻¹ until stable hemodynamic parameters have been established.

• Stable critically ill patients and patients during acute illness—energy intake should be the same as energy expenditure. In these patients, energy expenditure is increased by disease-related factors, but decreased by immobility. However, achieving or exceeding these energy goals may not lead to a positive nitrogen balance or prevent further skeletal muscle loss. A negative nitrogen balance and subsequent loss of skeletal muscle are the results of malnutrition, inflammation, and immobilization. On the other hand, it should be emphasized that malnutrition in ICU patients for more than a few days can cause excessive protein loss and subsequent complications. Thus, after the improvement in the condition and the subsidence of inflammatory condition, the energy intake must be gradually increased to cover the needs for energy as well as synthetic processes in the organism.

• Convalescence phase—at this stage, the body is already sensitive to increased energy intake and can use energy substrates not only for ATP production but also for anabolic processes, such as growth of children and restoration of lean body mass. Nutritional support should be introduced slowly to avoid refeeding syndrome, starting with 20–30% of the requirements and increasing to meet the full requirements within a few days. In order to restore lost tissue, the energy intake must be higher than energy expenditure and must be combined with higher intake of protein. At the same time, rehabilitation and mobilization must be initiated to ensure muscle anabolism. It takes time to regain muscle tissue (remember how difficult it is to gain muscle mass even in a healthy person). In addition to restoring lost tissue mass, there are also requirements for wound healing, synthesis, and proliferation of immune cells.

• Growing children and very malnourished patients—in children and severely malnourished people after (e.g., after an acute illness), the energy intake must be higher than energy expenditure. However, as noted above, careful initiation of energy intake and careful monitoring of the clinical and biochemical status are essential in severely malnourished individuals to prevent the development of refeeding syndrome. During periods of positive energy balance and mixed food intake, carbohydrates are preferentially oxidized, while administered fat is stored in fat stores. The increased energy and protein intake must be combined with physical activity to optimize the rate of regeneration and gain of skeletal muscles.

4. Summary

• Energy requirements should be set in relation to the output but also to the patient’s ability to metabolize the administered substrates.

• Most acutely ill patients experience a combination of stress and negative energy balance, which leads to the development of malnutrition.

• Majority of acutely ill patients, including ICU patients, have energy requirements that do not exceed 2400 kcal/day. During the acute catabolic phase, sepsis, or trauma, the goal of nutritional support should not be to induce a positive or zero nitrogen balance through increased energy intake.

• The main goal of nutrition in the acute phase of the disease should be to maintain function and reduce catabolism and progression of malnutrition.

• After the acute condition has subsided and during convalescence, nutritional support should treat disease-related malnutrition and restore the original condition.

• In severely malnourished patients, the period of positive energy balance must be extended and combined with rehabilitation therapy. At this stage, it is necessary to induce anabolism by increasing protein intake.