Energy Metabolism and Balance

*Luboš Sobotka*

## **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.

**Keywords:** energy, indirect calorimetry, energy expenditure, energy balance, energy metabolism

#### **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:


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**.

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:


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].



**Table 1.**

*Energy content in the basic components of nutrition.*

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:


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:

$$\begin{aligned} \text{1 mol glucose} + \text{6 mol O}\_2 &\rightarrow \text{6 mol H}\_2\text{O} + \text{6 mol CO}\_2, \\ \text{1 mol plantate} + \text{23 mol O}\_2 &\rightarrow \text{16 mol H}\_2\text{O} + \text{16 mol CO}\_2. \end{aligned} \tag{1}$$

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

Then:

Oxygen consumption:

$$\text{VO}\_2 = 0.829 \,\text{CHO} + 2.01 \,\text{Fats} + 6.04 \,\text{nitrogen in urine } [\text{g}]. \tag{2}$$

Carbon dioxide production:

$$\text{VCO}\_2 = 0.829 \,\text{CHO} + 1.43 \,\text{Fats} + 4.84 \,\text{nitrogen in wire} \,\text{[g]}.\tag{3}$$

Oxidation of energy substrates:

$$\begin{aligned} \text{CHO} &= 4.59 \text{ VCO}\_2 - 3.25 \text{ VO}\_2 - 3.68 \text{ nitrogen in urine } [\text{g}], \\ \text{Fat} &= 1.69 \text{ VO}\_2 - 1.69 \text{ VCO}\_2 - 1.72 \text{ nitrogen in urine } [\text{g}], \\ &\text{Protein} = 6.25 \text{ urine nitrogen.} \end{aligned} \tag{4}$$

Total energy expenditure (EV):

EE ¼ 3*:*87 VO2 þ 1*:*19 VCO2–5*:*99 *N* ð Þ total urine nitrogen in grams *:* (5)

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:


**Table 2.**

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

*Energy Metabolism and Balance DOI: http://dx.doi.org/10.5772/intechopen.105093*

$$\text{EE} = \text{3.84 VO}\_2 + \text{1.12 VCO}\_2 \text{ (Brouwer's formula)}.\tag{6}$$

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:

$$\text{EE} = \text{VO}\_2 \,(\text{3.84} + \text{1.12 RQ}). \tag{7}$$

Energy expenditure calculated from VCO2:

$$\text{EV} = \text{VCO}\_2 \,(\text{1.12} + \text{3.84}/\text{RQ}). \tag{8}$$

#### **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—<sup>2</sup> H). Twelve hours after drinking this double-labeled water, the concentrations of 18O and <sup>2</sup> H are measured in any body fluid (urine, saliva, or plasma). During the following observed period, both stable isotopes are eliminated from the organism differently:


For this reason, the elimination rate of 18O is greater than the elimination rate of 2 H. 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:

$$\begin{aligned} \text{REE} &= \text{655.0955} + (9.5634 \times \text{weight in kg}) + (1.8496 \times \text{height in cm}) \\ &- (4.6756 \times \text{age in years}). \end{aligned} \tag{9}$$

Men:

$$\begin{aligned} \text{REE} &= 66.473 + (13.7516 \times \text{weight in kg}) + (5.0033 \times \text{height in cm}) \\ &- (6.755 \times \text{age in years}). \end{aligned} \tag{10}$$

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:

$$\text{BEE} = 24 \,\text{x body weight in kg}.\tag{11}$$

#### **3.6 Components of total energy expenditure**

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


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

## **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.


#### **Table 3.**

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

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 [32–34]. 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**.

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 *Energy Metabolism and Balance DOI: http://dx.doi.org/10.5772/intechopen.105093*

**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].*

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 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:


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


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:


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**


## **Author details**

Luboš Sobotka 3rd Department of Medicine Metabolic Care and Gerontology, Faculty Hospital, Medical Faculty—Charles University, Hradec Kralove, Czech Republic

\*Address all correspondence to: pustik@lfhk.cuni.cz

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

## **References**

[1] Stirbet A, Lazar D, Guo Y, Govindjee G. Photosynthesis: Basics, history and modelling. Annals of Botany. 2020;**126**(4):511-537

[2] Wunder T, Mueller-Cajar O. Biomolecular condensates in photosynthesis and metabolism. Current Opinion in Plant Biology. 2020;**58**:1-7

[3] Sobotka L, Sobotka O. The predominant role of glucose as a building block and precursor of reducing equivalents. Current Opinion in Clinical Nutrition and Metabolic Care. 2021; **24**(6):555-562

[4] Henry RJ, Furtado A, Rangan P. Pathways of photosynthesis in non-leaf tissues. Biology (Basel). 2020;**9**(12):438

[5] Sjoholm J, Bergstrand J, Nilsson T, Sachl R, Ballmoos CV, Widengren J, et al. The lateral distance between a proton pump and ATP synthase determines the ATP-synthesis rate. Scientific Reports. 2017;**7**(1):2926

[6] Heskamp L, Lebbink F, van Uden MJ, Maas MC, Claassen J, Froeling M, et al. Post-exercise intramuscular O2 supply is tightly coupled with a higher proximal-to-distal ATP synthesis rate in human tibialis anterior. The Journal of Physiology. 2021;**599**(5):1533-1550

[7] Soeters PB, Shenkin A, Sobotka L, Soeters MR, de Leeuw PW, Wolfe RR. The anabolic role of the Warburg, Coricycle and Crabtree effects in health and disease. Clinical Nutrition. 2021;**40**(5): 2988-2998

[8] Watanuki S, Kobayashi H, Sorimachi Y, Yamamoto M, Okamoto S, Takubo K. ATP turnover and glucose dependency in hematopoietic stem/ progenitor cells are increased by

proliferation and differentiation. Biochemical and Biophysical Research Communications. 2019;**514**(1):287-294

[9] Westerterp KR. Perception, passive overfeeding and energy metabolism. Physiology & Behavior. 2006;**89**(1): 62-65

[10] Villet S, Chiolero RL, Bollmann MD, Revelly JP, Cayeux RNM, Delarue J, et al. Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patients. Clinical Nutrition. 2005; **24**(4):502-509

[11] van Mil EG, Westerterp KR, Kester AD, Saris WH. Energy metabolism in relation to body composition and gender in adolescents. Archives of Disease in Childhood. 2001; **85**(1):73-78

[12] Camps SG, Verhoef SP, Roumans N, Bouwman FG, Mariman EC, Westerterp KR. Weight loss-induced changes in adipose tissue proteins associated with fatty acid and glucose metabolism correlate with adaptations in energy expenditure. Nutrition & Metabolism (London). 2015;**12**:37

[13] Elia M. Hunger disease. Clinical Nutrition. 2000;**19**(6):379-386

[14] Wierdsma NJ, Peters JH, van der Schueren MA, Mulder CJ, Metgod I, van Bodegraven AA. Bomb calorimetry, the gold standard for assessment of intestinal absorption capacity: Normative values in healthy ambulant adults. Journal of Human Nutrition and Dietetics. 2014;**27**(Suppl. 2):57-64

[15] Basolo A, Parrington S, Ando T, Hollstein T, Piaggi P, Krakoff J. Procedures for measuring excreted and ingested calories to assess nutrient absorption using bomb calorimetry. Obesity (Silver Spring). 2020;**28**(12): 2315-2322

[16] Getts KM, Quinn EL, Johnson DB, Otten JJ. Validity and interrater reliability of the visual quarter-waste method for assessing food waste in middle school and high school cafeteria settings. Journal of the Academy of Nutrition and Dietetics. 2017;**117**(11): 1816-1821

[17] Hegerova P, Dedkova Z, Sobotka L. Early nutritional support and physiotherapy improved long-term selfsufficiency in acutely ill older patients. Nutrition. 2015;**31**(1):166-170

[18] Jequier E, Felber JP. Indirect calorimetry. Baillière's Clinical Endocrinology and Metabolism. 1987; **1**(4):911-935

[19] Kinney JM, Gump FE, Long CL. Energy and tissue fuel in human injury and sepsis. Advances in Experimental Medicine and Biology. 1972;**33**:401-407

[20] Kipp S, Byrnes WC, Kram R. Calculating metabolic energy expenditure across a wide range of exercise intensities: The equation matters. Applied Physiology, Nutrition, and Metabolism. 2018;**43**(6):639-642

[21] Bossi AH, Timmerman WP, Hopker JG. Energy expenditure equation choice: Effects on cycling efficiency and its reliability. International Journal of Sports Physiology and Performance. 2020;**15**(2):288-291

[22] Speakman JR. Doubly-labelled Water: Theory and Practice. London: Chapman and Hall; 1997

[23] Bendavid I, Lobo DN, Barazzoni R, Cederholm T, Coeffier M, de van der

Schueren M, et al. The centenary of the Harris-Benedict equations: How to assess energy requirements best? Recommendations from the ESPEN expert group. Clinical Nutrition. 2021; **40**(3):690-701

[24] Westerterp KR. Diet induced thermogenesis. Nutrition & Metabolism (London). 2004;**1**(1):5

[25] Westerterp KR. Reliable assessment of physical activity in disease: An update on activity monitors. Current Opinion in Clinical Nutrition and Metabolic Care. 2014;**17**(5):401-406

[26] Westerterp KR, Singer P. Energy Metabolism. Galen: Basics in Clinical Nutrition; 2019

[27] Carpentier YA, Sobotka L. Substrates Used in Parenteral and Enteral Nutrition —Energy. Galen: Basics in Clinical Nutrition; 2019

[28] Speakman JR, Westerterp KR. Associations between energy demands, physical activity, and body composition in adult humans between 18 and 96 y of age. The American Journal of Clinical Nutrition. 2010;**92**(4):826-834

[29] Singer P, Berger MM, Van den Berghe G, Biolo G, Calder P, Forbes A, et al. ESPEN guidelines on parenteral nutrition: Intensive care. Clinical Nutrition. 2009;**28**(4):387-400

[30] Soeters MR, Soeters PB, Schooneman MG, Houten SM, Romijn JA. Adaptive reciprocity of lipid and glucose metabolism in human shortterm starvation. American Journal of Physiology. Endocrinology and Metabolism. 2012;**303**(12):E1397-E1407

[31] Muller MJ, Enderle J, Pourhassan M, Braun W, Eggeling B, Lagerpusch M, et al. Metabolic adaptation to caloric

*Energy Metabolism and Balance DOI: http://dx.doi.org/10.5772/intechopen.105093*

restriction and subsequent refeeding: The Minnesota Starvation Experiment revisited. The American Journal of Clinical Nutrition. 2015;**102**(4):807-819

[32] Beylot M, Guiraud M, Grau G, Bouletreau P. Regulation of ketone body flux in septic patients. The American Journal of Physiology. 1989;**257**(5 Pt 1): E665-E674

[33] Soeters MR, Soeters PB. The evolutionary benefit of insulin resistance. Clinical Nutrition. 2012; **31**(6):1002-1007

[34] Singer P, Blaser AR, Berger MM, Alhazzani W, Calder PC, Casaer MP, et al. ESPEN guideline on clinical nutrition in the intensive care unit. Clinical Nutrition. 2019;**38**(1):48-79

[35] Singer P, Anbar R, Cohen J, Shapiro H, Shalita-Chesner M, Lev S, et al. The tight calorie control study (TICACOS): A prospective, randomized, controlled pilot study of nutritional support in critically ill patients. Intensive Care Medicine. 2011;**37**(4):601-609

[36] Reid C. Frequency of under- and overfeeding in mechanically ventilated ICU patients: Causes and possible consequences. Journal of Human Nutrition and Dietetics. 2006;**19**(1): 13-22

## **Chapter 4** Malnutrition and Sarcopenia

*Muneshige Shimizu and Kunihiro Sakuma*

## **Abstract**

Malnutrition caused by aging or disease can be defined as a state resulting from the lack of intake or uptake of nutrition, which leads to a change in body composition and the consequent impairment of physical and mental functions. Sarcopenia is a geriatric syndrome characterized by a progressive loss of skeletal muscle mass, strength, and performance. In this chapter, we (a) summarize the relationship between malnutrition and sarcopenia in various subjects, (b) review nutritional epidemiological evidence related to the prevention of sarcopenia, and (c) show evidence for the efficacy of nutrient supplementation in attenuating muscle atrophy in several patients. Malnutrition is closely related to severe sarcopenia, especially in older hospitalized adults, patients with chronic kidney disease (CKD), those undergoing hemodialysis, and those with cancer. Healthy diets (i.e., those ensuring a sufficient intake of beneficial foods, such as vegetables, fish, nuts, fruits, low-fat foods, and whole-grain products) are useful in preventing sarcopenia. The Mediterranean diet is a particularly healthy diet, but other diets, such as the healthy Nordic diet and traditional Asian diet, also help attenuate sarcopenia in older adults. Proteins, vitamins, minerals, and n-3 polyunsaturated fatty acids are important nutrients for patients with CKD, those on hemodialysis, and those with cancer.

**Keywords:** malnutrition, sarcopenia, diet quality, nutrients, muscle atrophy

## **1. Introduction**

Adequate nutrition is important for all generations, especially the elderly, and is known to contribute significantly not only to maintaining good health and reducing the risk of chronic diseases but also to prevent future diseases [1–3]. The risk for malnutrition increases with age and is often attributed to inadequate recommended nutrient intake. Malnutrition in the elderly exacerbates their risk of developing several health problems and chronic diseases, such as sarcopenia and cardiovascular disease [4]. There is an ever-increasing need to implement nutritional screening as a method of routine health screening for older patients. Malnutrition in the elderly tends to be overlooked owing to physical and physiological changes associated with aging [5, 6]. There are three main approaches to nutritional assessment—the use of physiological and clinical indicators; a connection of physical measurements, motor skills, and cognitive status; and self-perception of health and nutrition [7].

The European Society for Clinical Nutrition and Metabolism (ESPEN) recommends that individuals at risk for malnutrition be identified using defined screening


#### **Table 1.**

*GLIM diagnostic scheme for screening, assessment, diagnosis and grading malnutrition.*

tools. Moreover, the diagnosis of malnutrition should be made by a composite finding of either a low body mass index (BMI) value (<18.5 kg/m<sup>2</sup> ) or a low fat-free mass index, with BMI cutoffs for age, weight loss, and sex [8]. The Global Leadership Initiative on Malnutrition (GLIM) was formed by the world's leading clinical nutrition societies. A two-step approach was opted to diagnose malnutrition: first, screening to identify "at risk" conditions; and second, assessment to diagnose and grade the severity of malnutrition. Diagnostic assessment includes three phenotypic criteria (low BMI, nonvolitional weight loss, and decreased muscle weight) and two classifications by etiology (inflammation or disease burden and reduced food intake or assimilation) (**Table 1**).

Recently, Maeda et al. have reported the optimal BMI threshold for identifying severe malnutrition using the GLIM criteria and the prevalence of malnutrition by GLIM definition in clinical practice [9]. Patients with GLIM-defined malnutrition were found to exhibit significantly higher inpatient mortality compared to patients with adequate nutritional intake. On the contrary, Clark et al. compared the prevalence of and risk for malnutrition in patients admitted to a subacute geriatric rehabilitation facility using both GLIM and ESPEN criteria [10]. According to the GLIM criteria, approximately half of the elderly rehabilitation patients were malnourished. However, when the ESPEN definition was applied, the prevalence of malnutrition was found to be much lower. The authors suggest that various studies are needed to clarify the diagnostic accuracy of the GLIM and ESPEN criteria. Furthermore, overlap with syndromes such as cachexia and sarcopenia should be identified, and information dissemination and validation studies should be accelerated with the cooperation and support of nutrition-related professional societies.

### **2. Sarcopenia**

Sarcopenia is defined as age-related loss of skeletal muscle mass, function, and strength [11]. Four years ago, the European Working Group on Sarcopenia in Older People (EWGSOP) revised the definition of sarcopenia [12]. The revised version proposed a simple decision tree for diagnosing sarcopenia (**Figure 1**). The most

*Malnutrition and Sarcopenia DOI: http://dx.doi.org/10.5772/intechopen.104967*

#### **Figure 1.**

*Decision tree for the diagnosis of sarcopenia.*

significant part of this revision is that muscle strength and function are the primary factors considered, which shows that they are more important than muscle mass [13].

Handgrip strength is used as an indicator of muscle strength. The simple and available methods of assessing physical ability contain the short physical performance battery and walking speed measurement that combines the get-up-and-go test, walking speed, and a balance measurement [14]. In addition, a sarcopenia-screening questionnaire is useful for patients over 65 years of age [15].

Approximate muscle weight can be estimated from simple measurements that calculate the corrected arm muscle area after measuring the skin thickness of the triceps skinfold thickness [16]. The bioimpedance method has the advantage of rapidly measuring lean body mass, but it cannot assess muscle volume directly. Data from dual-energy X-ray absorptiometry is typically utilized to calculate a skeletal muscle volume by correcting four limbs lean body mass by height or BMI [15, 17].

A remarkable decline in muscle strength (2.5%–3.0% per year) and mass (approximately 1% per year) has been reported in those over age 60 [18]. The prevalence of sarcopenia in people aged 65–70 years is 13–24%, and in those >80 years of age, it is >50% [19]. The prevalence of sarcopenia based on sex in individuals aged the 60s is 80% in women and 10% in men, whereas, in those >80 years of age, it is 18% in women and 40% in men [20].

Sarcopenia exerts major adverse effects on metabolism, function, mortality, and morbidity. The condition is associated with quality-of-life impairments, osteoporosis,

**Figure 2.** *Mechanisms underlying sarcopenia.*

functional disabilities, falls, metabolic syndrome, cardiovascular disease, and other problems. Loss of both muscle function and muscle mass increases mortality by 3.7-fold [21] and increases the risk of falls by 2-fold [22].

The muscle is a biocontractile organ that enables movement by applying force to the bone. Muscle is essential for metabolic homeostasis because of its critical role in energy production, lipid oxidation, amino acid release, glycogen storage, and glucose uptake. In addition, muscle is indirectly involved in mediating immune responses and is also a reservoir of amino acids that can be used by immune cells and other cells. Although the molecular and cellular mechanisms of sarcopenia require clarification, certain common biological mechanisms, such as oxidative stress, mitochondrial dysfunction, hormonal regulation impairment, nutritional deficiency, and inflammation, have been suggested to be involved. Therefore, sarcopenia needs a multimodal management approach that combines nutrition, exercise, and anabolic and anti-inflammatory drugs (**Figure 2**).

### **3. Malnutrition and sarcopenia**

The relationship between malnutrition and sarcopenia has been investigated in a range of subjects, particularly in studies published in the last 10 years, all of which concluded that malnutrition is strongly correlated with severe sarcopenia. We reviewed articles published after 2015, with a minimum of 67 subjects, that statistically revealed an association between malnutrition and sarcopenia (**Table 2**).

Dolores et al. investigated the association between malnutrition diagnosed according to the ESPEN and GLIM criteria and the development of severe sarcopenia/sarcopenia judged by the EWGSOP2 criteria [23]. In this study, 411 subjects were recruited, and their risk of developing severe sarcopenia/sarcopenia was assessed during the 4-year follow-up period. The results showed that those who were malnourished by the ESPEN definition had sarcopenia (adjusted hazard ratio of 4.28) and severe sarcopenia (adjusted hazard ratio of 3.86) and that those who were malnourished by the GLIM criteria had sarcopenia (adjusted hazard ratio of 3.23) and severe sarcopenia (adjusted hazard ratio of 2.87). The authors emphasized the importance of early action against malnutrition because it was shown to increase the risk of developing severe sarcopenia/sarcopenia two-fold during the 4-year follow-up.

Gerdien et al. summarized the association between sarcopenia and the prevalence of malnutrition in elderly hospitalized patients [24]. While reviewing seven studies



#### *Combating Malnutrition through Sustainable Approaches*


#### **Table 2.**

*Summary of malnutrition and sarcopenia in various subjects.*

(2506 patients), the researchers found a high association and overlap between sarcopenia and malnutrition. The results revealed that about half of the older hospitalized patients suffered from sarcopenia and malnutrition.

Sato et al. evaluated the prevalence and associated factors of sarcopenia in longlived elderly people [25]. In this study, 100 eligible older adults were examined, and the mean age was 77.2 years in the elderly and 86.3 years in the long-lived elderly. The authors summarized that the risk of sarcopenia was 6 times higher in the elderly individuals >80 years of age and 13 times higher in the malnourished elderly individuals and those at risk for malnutrition.

Verstraeten et al. evaluated the prevalence of malnutrition and sarcopenia and the association between them in geriatric rehabilitation inpatients [26]. Out of the 506 geriatric rehabilitation inpatients, 51% were malnourished, 19% were severely sarcopenic, 49% were probably sarcopenic, and 0.4% were sarcopenic (nonsevere). Malnutrition with confirmed/severe sarcopenia and malnutrition with probable sarcopenia coexisted in 13% and 23% of the subjects, respectively. Almost half of the rehabilitation patients exhibited both malnutrition and sarcopenia.

Dolores et al. investigated malnutrition (diagnosed as per ESPEN) in elderly inpatients debilitated by acute illness and its connection to sarcopenia [27]. The 88 inpatients (mean age: 84.1 years, 62% women) with a BMI of <30 kg/m<sup>2</sup> were assessed with biochemical markers, and mini nutritional assessment strips were used to investigate the risk of malnutrition and sarcopenia. The results showed that the prevalence of malnutrition was 19.3% as per the ESPEN definitions. The prevalence of sarcopenia was 37.5%, of which 90.9% were malnutrition due to ESPEN, further indicating a strong association between the two.

Beatriz et al. investigated the association between sarcopenia diagnosis and nutritional status in nursing home residents [28]. This cross-sectional study included 339 elderly patients (mean age: 84.9 years, population: 64.3% women) in nursing homes, and their nutritional status was assessed using the ®Mini Nutritional Assessment. More than one-third of the residents had sarcopenia, and its prevalence was particularly high in women. Of the participants, 32.4% were at risk of malnutrition and 42.5% were malnourished. Rates of malnutrition were statistically higher

#### *Malnutrition and Sarcopenia DOI: http://dx.doi.org/10.5772/intechopen.104967*

in sarcopenia than in non-sarcopenia. Furthermore, the prevalence of malnutrition was the highest among those with reduced grip strength (62.8%) and in patients with severe sarcopenia (60.8%).

Simone et al. investigated the relationship of nutrition with sarcopenia, behavior, and inflammatory patterns in 113 older adults with advanced CKD [29]. Psychological and physical performance were assessed. The nutritional condition was evaluated by an inflammatory score for malnutrition, which also confirmed the presence of protein–energy wasting syndrome (PEW). The results demonstrated that 24% of the patients had sarcopenia. Patients with sarcopenia had relatively low creatinine clearance levels and low BMI values. Furthermore, patients with sarcopenia showed not only a higher prevalence of PEW (52% vs. 20%, *p* < 0.0001), but also a trend toward higher inflammation scores indicating malnutrition (6.6 vs. 4.5, *p* = 0.09).

Catarina et al. assessed the relationship of sarcopenia with malnutrition and nutrition-related markers, quality of life, and mortality in a cohort study of elderly patients undergoing chronic hemodialysis [30]. The subjects were 170 patients receiving hemodialysis for at least 3 months who were aged ≥60 years. Malnutrition, sarcopenia, and pre sarcopenia were found in 58.8%, 14.1%, and 35.3% of the patients, respectively. Patients with malnutrition and sarcopenia were older and showed significantly lower BMI, body fat, mid-arm muscle and calf circumferences, phage angle, and somatic cell mass. In addition, subjects with sarcopenia and malnutrition had a significantly higher hazard ratio for mortality (2.99) than those without these conditions.

Kiss et al. reported that all cancer patients are recommended to be screened for malnutrition and sarcopenia at the time of diagnosis or when clinical conditions change during treatment and recovery [31]. Malnutrition occurs with all cancer diagnoses, but certain cancers, such as neck and head, lung, and gastrointestinal cancers, exhibit up to a four-fold higher risk of malnutrition than breast cancer. In addition, Blauwhoff-Buskermolen et al. examined skeletal muscle changes during palliative chemotherapy in patients with metastatic colorectal cancer [32]. The muscle area of these patients decreased significantly by 6.1% during 3 months of chemotherapy. Additionally, patients who experienced a muscle loss of >9% during treatment had a significantly lower survival rate than those who faced a muscle loss of <9%.

## **4. Nutritional approach for the prevention of sarcopenia**

The effects of diet quality on sarcopenia prevention in elderly individuals have been summarized as per the results of nutritional epidemiological studies. We reviewed epidemiological studies published since 2011 with at least 192 subjects that confirmed the impact of dietary quality on muscle function (**Table 3**).

Six studies have conducted human trials on the relationship between sarcopenia and diet quality (i.e., the intake of specific nutrients via food and/or the amount of nutrients consumed) [33–38].

Martin et al. explored the connection between physical ability (a short physical performance battery) and diet in the residents of West Hertfordshire [33]. Nutrient intakes were determined for the foods consumed using the manufacturer's composition data or the nutrients indicated in the UK National Food Composition Database. The preferred dietary patterns involved a high consumption of fish, shellfish, vegetables, and fruits but low consumption of sugar, fat, chips, and white bread. In women, the higher the dietary score, the greater the reduction in 3-min walking time and chair rise time. In addition, an inverse correlation was observed between


#### **Table 3.**

*Summary of nutritional epidemiological studies on the diet of quality in preventing sarcopenia.*

the intake of vegetables, white fish, and shellfish and physical function. These findings indicated the presence of a relationship between diet quality and physical function in elderly women.

#### *Malnutrition and Sarcopenia DOI: http://dx.doi.org/10.5772/intechopen.104967*

Bollwein et al. investigated whether the risk for frailty was lowered in subjects with higher Mediterranean diet (MED) consumption scores [34]. This score replaces the MED score proposed by Fung et al. [39]. The basic MED score introduced by Trichopoulou et al. was utilized [40]. The authors found that the MED score and walking speed were inversely correlated. Additionally, they observed a strong correlation between slow walking speed and good diet quality (high in vegetables, legumes, fruit, unrefined cereals, nuts, and fish) in aging people.

Granic et al. summarized the correlation between diet and decline in muscle power and physical performance in elderly people [35]. The study followed 791 elderly people for 5 years and detected changes in the Timed Up and Go test (TUG) scores and grip strength. Dietary intake was entered in a Microsoft Access dietary data system based on unique food codes (2000 above) and 118 additional categories by food groups based on the McCance and Widdowson food composition [40, 41]. The participants were divided into dietary pattern 1 (DP1—high in red meat), dietary pattern 2 (DP2—low in meat), and dietary pattern 3 (DP3—high in butter) based on the results of the dietary survey. The results showed that men with DP1 had decreased grip strength, and men with DP3 had a steeper decrease in grip strength than men with DP2. Furthermore, the TUG scores were significantly higher in DP1 men and DP3 women than in DP2 men and women. The results, therefore, suggested that a diet high in potatoes, red meat, butter, and gravy may exert a negative effect on physical performance and muscle strength in older adults.

Perälä et al. focused on the healthy Nordic diet and studied whether it was associated with improved physical performance indicators [36]. The 1072 subjects (mean age of 67 years) were investigated using the 128-item food frequency questionnaire (FFQ ), after which an *a priori* Nordic diet score was derived. Physical ability was assessed using the Senior Fitness Test (SFT). The results of the SFT score showed that in women with the highest dietary score, the walking ability was improved by 17%, arm curl by 16%, and chair stand by 20% compared with women with the lowest dietary score. These results were considered meaningful evidence that women consume the healthy Nordic diet, which is based on fruits and berries (berries, pears, and apples), vegetables (lettuce, tomatoes, cabbages, lettuce, roots, roots, and legumes), cereals (oats, rye, and barley), low-fat milk (fat-free milk and milk with fat content <2%), and fish (Baltic herring, salmon), exhibit improved physical performance (upper and lower body muscular strength and aerobic endurance) after 10 years.

Suthutvoravut et al. studied the dietary contents and the development of sarcopenia in community-dwelling elderly Japanese people [37]. The subjects included 1241 individuals aged over 65 years who were not undergoing long-term medical treatment. The participants' diets were assessed using a simple descriptive dietary questionnaire. The dietary contents were surveyed by both Principal Component Analysis and Japanese dietary scores (fish, vegetables, fruits, soy products, mushrooms, pickles, and seaweed). The participants were categorized into dietary pattern 1 (DP1—typical Japanese diet, with high factor loadings for fish, fruits, vegetables, and tofu), dietary pattern 2 (DP2—high-factor loadings for rice, miso soup, and fish), and dietary pattern 3 (DP3: high factor loadings for noodles). The results suggest that men with the lowest DP1 are more likely to develop sarcopenia, and women with the lowest DP2 are moderately likely to develop sarcopenia. Furthermore, the findings alluded that low adherence to the Japanese dietary pattern, which comprises rice, fish, miso soup, tofu, vegetables, and fruits, was associated with a high prevalence of sarcopenia, regardless of sex.

Davis et al. investigated the alterations in the skeletal muscle mass and muscle function due to diet quality and dietary patterns over a 15-year period in 522 men [38]. The dietary survey was extracted from an FFQ and calculated the Australian Recommended Food Score and the Inflammation Index. Three dietary patterns were characterized—plant-based, Western, and traditional (Anglo–Australian). Higher scores in an anti-inflammatory diet rich in protein and vegetables predicted greater skeletal muscle mass, whereas the inflammatory diet was associated with lower TUG scores during the 15-year period. These associations were also significant when adjusted for the confounding variables.

Nutrition is an important factor that regulates muscle mass and muscle function and developing effective nutritional strategies to reduce muscle loss in several diseases warrants further studies. A few studies that have assessed the efficacy of nutritional interventions have been discussed below.

Kishimoto et al. demonstrated the changes in nutritional status and outcomes in adult stroke patients admitted for rehabilitation [41]. The 134 enrolled patients were divided into two categories—those with improved or normal nutritional conditions and those with poor or reduced nutritional status. Functional recovery was better in the category with improved nutritional status than that in the other categories. The authors concluded that improved or maintained nutritional condition was correlated with improved functional recovery in the rehabilitation of adult patients with stroke.

Patients with CKD are known to have a high prevalence of protein–energy malnutrition; hence, it is necessary to meet the patient's energy requirements and maintain the nitrogen balance to avoid the extra breakdown of muscle protein. Hoshino reported that a dietary protein intake of 1.0–1.2 g/kg/day, which is 1.2 times higher than that recommended for healthy individuals, is advised for patients with CKD [42]. In addition to the protein intake, an energy intake of 30–35 kcal/kg/day is necessary because the estimated energy leak during dialysis is approximately 300 kcal. Furthermore, an adequate intake of vitamins and minerals, such as vitamin D and iron, is essential to prevent protein catabolism.

Kiebalo et al. summarized the recommendations of the Society of Nephrology regarding the nutritional intake for dialysis patients [43]. The Polycystic Kidney Disease (PKD) Foundation has set the daily protein recommendation at 1.2–1.4 g/kg/ day, slightly higher than the European guideline of 1.0–1.2 g/kg/day. The Foundation further suggests a daily calcium intake of 1000 mg and up to 3000 mg of sodium per day. For dietary phosphorus, the Kidney Disease Improving Global Outcome states that the daily intake should not exceed 4000 mg, which includes mineral as well as protein.

Ford et al. investigated the appropriate amount of dietary protein for preventing or treating skeletal muscle mass loss in cancer patients [44]. 40 patients with diagnosed stage II–IV colorectal cancer who were to receive chemotherapy were randomly assigned to a 12-week high-protein (HP) or normal-protein (NP) diet, with the HP group receiving 2.0 g/kg/day and the NP group receiving 1.0 g/kg/day of protein. The energy recommendations were based on the measured energy expenditure. The results showed that changes in skeletal muscle mass and physical functional muscle strength were higher in the HP group than that in the NP group, suggesting the importance of protein intake in cancer patients.

Schueren et al. published a systematic review of randomized trials using high-energy oral nutraceuticals (ONS) or ONS fortified with protein and n-3

#### *Malnutrition and Sarcopenia DOI: http://dx.doi.org/10.5772/intechopen.104967*

polyunsaturated fatty acids to modulate cancer-related metabolic changes [45]. Interventions fortified with protein diets (i.e., an extra 32–33 g/day) and n-3 polyunsaturated fatty acids (i.e., an extra 2.0–2.2 g/day) of eicosapentaenoic acid) were observed to significantly improve cancer-related markers compared with the isocaloric controls.

Malnutrition during cancer chemotherapy is a factor associated with delayed disease improvement. Many investigations have been conducted on nutritional interventions during cancer treatment, but the evidence is highly limited. Hence, there is a need for further research to establish the desired timing and duration of nutritional intake and the know-how necessary for continuous nutritional intake.

## **5. Conclusions**

In this chapter, we have summarized the relationship between malnutrition and sarcopenia in various subjects, reviewed the nutritional epidemiological evidence related to preventing sarcopenia, and showed data on the efficacy of nutrient intake in attenuating muscle atrophy in several patients. Malnutrition is closely related to severe sarcopenia, especially in older hospitalized adults, geriatric rehabilitation inpatients, patients with CKD, those undergoing hemodialysis, and those with cancer. An appropriate quality diet pattern (i.e., one that provides an adequate intake of beneficial foods, such as low-fat foods, fish, vegetables, fruits, nuts, and whole-grain products) is effective in preventing sarcopenia. The MED is a particularly popular healthy diet, but other diets of appropriate quality, such as a healthy Nordic diet or a traditional Asian diet, are useful in preventing sarcopenia in older adults worldwide. Proteins, vitamins, minerals, and n-3 polyunsaturated fatty acids are key nutrients for patients with CKD, those undergoing hemodialysis, and those with cancer. Further high-quality studies with large sample sizes, isocaloric placebo supplementation, and controlled diet quality are needed to clearly understand the effect of nutrient dose and duration on the prevention of malnutrition and sarcopenia.

## **Conflict of interest**

The authors declare no conflict of interest.

## **Author details**

Muneshige Shimizu1 \* and Kunihiro Sakuma2

1 Department of Fisheries, School of Marine Science and Technology, Tokai University, Shizuoka, Japan

2 Institute for Liberal Arts, Environment and Society, Tokyo Institute of Technology, Tokyo, Japan

\*Address all correspondence to: shimizu.muneshige@tsc.u-tokai.ac.jp

© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

## **References**

[1] Cederholm T, Barazzoni R, Autin P, Ballmer P, Biolo G, Bischoff SC, et al. ESPEN guidelines on definition and terminology of clinical nutrition. Clinical Nutrition. 2017;**36**:49-64

[2] Volkert D, Beck AM, Cederholm T, Cruz-Jentoft A, Goisser S, Hooper L, et al. ESPEN guideline on clinical nutrition and hydration in geriatrics. Clinical Nutrition. 2018;**38**:10-47

[3] Zhao W, Ukawa S, Okada E, Wakai K, Kawamura T, Ando M, et al. The associations of dietary patterns with all-cause mortality and other lifestyle factors in the elderly: An age-specific prospective cohort study. Clinical Nutrition. 2018;**38**:288-296

[4] Agarwal E, Miller M, Yaxley A, Isenring E. Malnutrition in the elderly: A narrative review. Maturitas. 2013;**76**: 296-302

[5] Brownie S. Why are elderly individuals at risk of nutritional deficiency? International Journal of Nursing Practice. 2006;**12**:110-118

[6] Corcoran C, Murphy C, Culligan EP, Walton J, Sleator RD. Malnutrition in the elderly. Science Progress. 2019;**102**:171-180

[7] Ahmed T, Haboubi N. Assessment and management of nutrition in older people and its importance to health. Clinical Interventions in Aging. 2010;**5**:207-216

[8] Cederholm T, Bosaeus I, Barazzoni R, Bauer J, Gossum AV, Klek S, et al. Diagnostic criteria for malnutrition- an ESPEN consensus statement. Clinical Nutrition. 2015;**34**:335-340

[9] Maeda K, Ishida Y, Nonogaki T, Mori N. Reference body mass index values and the prevalence of malnutrition according to the global leadership initiative on malnutrition criteria. Clinical Nutrition. 2020;**39**:180-184

[10] Clark AB, Reijnierse EM, Lim WK, Maier AB. Prevalence of malnutrition comparing the GLIM criteria, ESPEN definition and MST malnutrition risk in geriatric rehabilitation patients. Clinical Nutrition. 2020;**39**:3504-3511

[11] Rosenberg IH. Sarcopenia: Origins and clinical relevance. The Journal of Nutrition. 1997;**127**:990S-991S

[12] Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, et al. Sarcopenia: Revised European consensus on definition and diagrosis. Age and Ageing. 2019;**48**:16-31

[13] Studenkski S, Perera S, Patel K, Rosano C, Faulkner K, Inzitari M, et al. Gait speed and survival in older adults. JAMA. 2011;**305**:50-58

[14] Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, et al. Sarcopenia: Revised European consensus on definition and diagnosis: Report of the European working group on sarcopenia in older people. Age and Ageing. 2010;**39**:412-423

[15] Biolo G, Cederholm T, Muscartoli M. Muscle contractile and metabolic dysfunction is a common feature of sarcopenia of aging and chronic disease: From sarcopenic obesity to cachexia. Clinical Nutrition. 2014;**33**:737-748

[16] Cao L, Morley JE. Sarcopenia is recognized as an independent condition by an international classification of disease. Journal of the American Medical Directors Association. 2016;**17**:676-677

[17] Studenski SA, Peters KW, Alley DE, Cawthon PM, McLean RR, Harris TB, et al. The FNIH sarcopenia project: Rationale, study description, conference recommendations, and final estimates. The Journals of Gerontology Series A, Biological Sciences and Medical Sciences. 2014;**69**:547-558

[18] Daly RM, Rosengren BE, Alwis G, Ahlborg HG, Sernbo I, Karlsson MK. Gender specific age-related changes in bone density, muscle strength and functional performance in the elderly: A-10 year prospective population-based study. BMC Geriatrics. 2013;**13**:71

[19] Kim T, Choi KM. Sarcopenia: Definition, epidemiology, and pathophysiology. Journal of Bone Metabolism. 2013;**20**:1-10

[20] Melton LJ, Khosla S, Crowson BS, O'Connor MK, O'Fallon WM, Riggs BL. Epidemiology of sarcopenia. Journal of the American Geriatrics Society. 2000;**48**:625-630

[21] Cheung CL, Lam SKL, Cheung BMY. Evaluation of cut points for low lean mass and slow gait speed in predicting death in the natural health and nutrition examination survey 1999-2001. The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences. 2016;**71**:90-95

[22] Bischoff-Ferrari HA, Orav JE, Kanis JA, Rizzoli R, Schlogl M, Staehelin HB, et al. Comparative performance of current definitions of sarcopenia against the prospective incidence of falls among community-dwelling seniors age 65 and older. Osteoporosis International. 2015;**26**:2973-2802

[23] Dolores SR, Medea L, Jeans YR, Etienne C, Olivier B, Charlotte B. Mortality in malnourished older adults diagnosed by ESPEN and GLIM criteria in the SarcoPhAge study. Journal of Cachexia, Sarcopenia and Muscle. 2020;**11**:1200-1211

[24] Gerdien CLM, Yvette CL, Alexia K, Tommy C, Andrea BM, Marian AE. Frailty, sarcopenia, and malnutrition frequently (co-)occur in hospitalized older adults: A systematic review and meta-analysis. Journal of the American Medical Directors Association. 2020;**21**:1216-1228

[25] Sato PHR, Ferreira AA, Rosado EL. The prevalence and risk factors for sarcopenia in older adults and long-living older adults. Archives of Gerontology and Geriatrics. 2020;**89**:104089

[26] Verstraeten LMG, van Wijngaarden JP, Pacifico J, Reijnierse EM, Meskers CGM, Maier AB. Association between malnutrition and stages of sarcopenia in geriatric rehabilitation inpatients. Clinical Nutrition. 2021;**6**:4090-4096

[27] Dolores SR, Ester M, Natalia RM, Ramon M, Olga VI, Ferran E, et al. Prevalence of malnutrition and sarcopenia in a post-acute care geriatric unit: Applying the new ESPEN definition and EWGSOP criteria. Clinical Nutrition. 2017;**36**:1339-1344

[28] Beatriz LS, Alejandro SP, Javier PN, Antonio SO, Maria ET, Alfonso JC. Influence of nutritional status in the diagnosis of sarcopenia in nursing home residents. Nutrition. 2017;**41**:51-57

[29] Simone V, Lara C, Silvia A, Camilla F, Matteo C, Piergiorgio M. Sarcopenia is associated with malnutrition but not with systematic inflammation in older persons with advanced CKD. Nutrients. 2019;**11**:1378

[30] Catarina M, Teresa FA, Juliana R, Fernanda S, Carla MA. Malnutrition and sarcopenia combined increases the risk for mortality in older adults on hemodialysis. Frontiers in Nutrition. 2021;**8**:721941

[31] Nicole K, Jenelle L, Merran F, Elizabeth I, Brenton JB, Anna B, et al. Clinical oncology society of Australia: Position statement on cancer-related malnutrition and sarcopenia. Nutrition and Dietetics. 2020;**77**:416-425

[32] Blauwhoff-Buskermolen S, Versteeg KS, MAE d v d S, den Braver NR, Berkhof J, JAE L, et al. Loss of muscle mass during chemotherapy is predictive for poor survival of patients with metastatic colorectal cancer. Journal of Clinical Oncology. 2016;**34**:1339-1344

[33] Martin H, Aihie-Sayer A, Jameson K, Syddall H, Dennison EM, Cooper C, et al. Does diet influence physical performance in community-dwelling older people? Findings from the Hertfordshire cohort study. Age and Ageing. 2011;**40**:181-186

[34] Bollwein J, Diekmann R, Kaiser MJ, Bauer JM, Uter W, Sieber CC, et al. Dietary quality is related to frailty in community-dwelling older adults. Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2013;**68**:483-489

[35] Granic A, Jagger C, Davies K, Adamson A, Kirkwood T, Hill TR, et al. Effect of dietary patterns on muscle strength and physical performance in the very old: Findings from the Newcastle 85+ study. PLoS One. 2016;**11**:e0149699

[36] Perälä MM, Von-Bonsdorff M, Mannisto S, Salonen MK, Simonen M, Kanerva N, et al. A healthy Nordic diet and physical performance in old age: Findings from the longitudinal Helsinki birth cohort study. The British Journal of Nutrition. 2016;**115**:878-886

[37] Suthuvoravut U, Takahashi K, Murayama H, Tanaka T, Akishita M, Iijima K. Association between traditional Japanese diet washoku and sarcopenia in community-dwelling older adults: Findings from the Kashiwa study. The Journal of Nutrition, Health & Aging. 2020;**24**:282-289

[38] Davis JA, Mohebbi M, Collier F, Loughman A, Staudacher H, Shivappa N, et al. The role of diet quality and dietary patterns in predicting muscle mass and function in men over a 15-year period. Osteoporosis International. 2021;**32**: 2193-2203

[39] Fung TT, McCullough ML, Newby PK, Manson JE, Meigs JB, Rifai N, et al. Diet-quality scores and plasma concentrations of markers of inflammation and endothelial dysfunction. The American Journal of Clinical Nutrition. 2005;**82**:163-173

[40] Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. The New England Journal of Medicine. 2003;**348**:2599-2608

[41] Kishimoto H, Yozu A, Kohno Y, Oose H. Nutritional improvement is associated with better functional outcome in stroke rehabilitation: A cross-sectional study using controlling nutritional status. Journal of Rehabilitation Medicine. 2020;**52**:jrm00029

[42] Hoshino J. Renal rehabilitation: Exercise intervention and nutritional support in dialysis patients. Nutrients. 2021;**13**:1444

[43] Kiebalo T, Holotka J, Habula I, Paulaczyk K. Nutritional status in peritoneal dialysis: Nutritional guidelines, adequacy and the management of malnutrition. Nutrients. 2020;**12**:1715

[44] Ford KL, Sawyer MB, Trottier CF, Ghosh S, Deutz NEP, Siervo M, et al.

Protein recommendation to increase muscle (PRIMe): Study protocol for a randomized controlled pilot trial investigating the feasibility of a high protein diet to halt loss of muscle mass in patients with colorectal cancer. Clinical Nutrition ESPEN. 2021;**41**:175-185

[45] Schueren MAE, Laviano A, Blanchard H, Jourdan M, Arends J, Baracos VE. Systematic review and metaanalysis of the evidence for oral nutritional intervention on nutritional and clinical outcomes during chemo(radio)therapy: Current evidence and guidance for design of future trials. Annals of Oncology. 2018;**29**:1141-1153

## **Chapter 5**
