Nutrition 31 (2015) 612–614
Contents lists available at ScienceDirect
Nutrition journal homepage: www.nutritionjrnl.com
Special article
Tailoring the nutritional regimen in the elderly cancer patient Federico Bozzetti M.D. * Faculty of Medicine, University of Milan, Italy
a b s t r a c t Keywords: Water requirement Energy requirement Protein requirement Macronutrient requirement
Our knowledge of the macronutrient requirement of elderly cancer patient is still incomplete and mainly relies on studies of elderly (healthy) people and populations of cancer patients including both adult and elderly subjects. Patients with minor nutritional deterioration do not require any specific nutritional regimen, but cachectic patients do. Total energy expenditure can be unchanged or lower in advanced weight-losing patients (when compared with matched healthy controls) because the higher resting metabolic expenditure can be offset by reduced physical activity, and it approximates to 25-28 Kcal/kg/d. Protein requirement is probably 1.5 g amino acid (AA)/kg/d or more, especially if the goal is increased lean body mass. However, the final balance depends not only on the quantity of AA but also their quality: diets including a high percentage of essential AA and especially of branched-chain ones and leucine in particular, are advocated. Total fluid load should be prudent, around 25-30 ml/kg/d. Ó 2015 Elsevier Inc. All rights reserved.
The regimen The nutritional regimen varies according to whether the nutritional support is a “supplementation” or whether it aims to cover the patient’s full nutritional requirements. Only in this latter event is it important to plan a specific nutritional approach. There is little specific clinical or metabolic experience for the nutritional support of the geriatric cancer patient and hence our knowledge relies on data available on the enteral and parenteral nutrition of the healthy geriatric population and in patients with cancer regardless of age. It is noteworthy, however, that the majority of patients with cancer are older than 65. Table 1 summarizes the requirements of the main nutrients, especially when nutrition is delivered intravenously. In fact, not only might the unbalance of nutrients be better compensated by homeostatic mechanisms of the patient when nutritional support is oral or enteral than when it is totally intravenous (IV), but patients fed by IV are usually more compromised. Water requirement A restriction in water administration usually is advised. Advanced cancer often is associated with the expansion of the extracellular fluid volume, which may be due to the tumor * Corresponding author. Tel.: þ39 329 765 5385; fax: þ39 0226410267. E-mail address: [email protected] http://dx.doi.org/10.1016/j.nut.2014.12.007 0899-9007/Ó 2015 Elsevier Inc. All rights reserved.
producing an excess of antidiuretic hormone [1]; to the presence of nausea, which frequently occurs in advanced stages of disease; or to the administration of morphine. Wasting is associated with loss of intracellular water and solutes that, through the activation of the hypothalamic osmoreceptor cells, stimulate the antidiuretic hormone release at levels that maintain serum osmolality and sodium concentration at subnormal values [2]. As a consequence, the clearance of free water is decreased, also because the urea load presented to the kidney is reduced due to the protein depletion secondary to the undernutrition. In contrast, the synthesis of endogenous water is maintained by the oxidation of energetic substrates (carbohydrates and fats) [3] and the insensible water loss drops because of reduced physical activity [4]. Hence, an overzealous administration of water, glucose, and sodium can sharply result in a fluid overload with edema in peripheral tissues as well as in the central organs. According to the European Society for Clinical Nutrition and Metabolism guidelines [5], the total volume of fluid and sodium should not exceed 25 to 30 mL and 1 mmol/kg daily, respectively, provided that the patient is not dehydrated. Energy requirement There is a paucity of data regarding the energy requirements of older cancer patients. The daily resting energy expenditure (REE) was quantified as 24.6 kcal/kg: In older weight-stable patients daily REE was
F. Bozzetti / Nutrition 31 (2015) 612–614 Table 1 Adequate nutritional regimen for the advanced cancer patient Nutrient
Daily dose
Water Nonprotein energy Glucose Fat (L/ MCT þ u-3) Amino acid Sodium
30 mL/kg 30 kcal/kg w3.7 g/kg (50% nonprotein energy) w1.6 g/kg (50% nonprotein energy) 1.5 g/kg 1 mEq/kg
MCT, medium chain triacylglycerol
22.7 kcal/kg, a value significantly lower than in weight-losing cancer patients but higher than in weight-stable controls [6]. The total energy/basal energy expenditure of older outpatients with small cell lung cancer was only 1.36 according to a previous study, which supports the concept that the energy requirements of these patients are not increased because their mild basal hypermetabolism may be overbalanced by decreased physical activity [7]. A more recent study reported that in older, hospitalized patients with advanced cancer, daily total energy expenditure was 28 3 kcal/kg [8]. It is clinically relevant the finding that older cancer patients have significantly higher fat oxidation rates and significantly lower carbohydrate oxidation rates compared with controls. Additionally, weight-losing cancer patients have significantly higher fat oxidation rates compared with weight-stable cancer patients, weight-stable controls, and weight-losing controls [6]. The capacity to clear and oxidize a high triacylglycerol (TG) load of older healthy individuals or older patients, equally or better than younger individuals, has been reported [9,10]. These data argue for a high fat-to-carbohydrate ratio in the nutritional regimen. However, clinicians should be aware that daily parenteral administration (1 g/kg) of u-6 long chain TGs is associated with severe liver toxicity after 2 y in >50% of patients and mixed emulsions containing medium-chain TG and u-3 or u-9 fatty acids should be considered in these cases.
Protein requirements Most of the available evidence refers to healthy older individuals or sarcopenic patients [11]. Because of age-dependent metabolic alterations, in general older individuals may synthetize less muscle protein than younger persons from the same amount of dietary protein. However, even if aging is associated with an inability to respond to low load of protein (20 g) or essential amino acids (25 g; essential amino acids 10–15 g) is able to stimulate muscle protein synthesis in older adults to a similar extent as in the young [12–15]. One study reported that a moderate (113 g) serving of an intact protein (i.e., lean beef) contains sufficient essential amino acids (30 g total: w12 g essential amino acids) to increase mixed-muscle protein synthesis by 50% in young and older men and women [16]. A previous study was the first to demonstrate that the acute intravenous administration of amino acids stimulates net muscle protein synthesis in the healthy geriatric population [17]. Essential amino acids appear to be the primary stimulus of protein synthesis and act synergistically with exercise to increase fractional protein synthesis [18]. Leucine seems to be the most active of the amino acids [19] and the anabolic effect of leucineenriched essential amino acids act not only as building blocks for protein synthesis but also due to the stimulation, in muscle, of the mammalian target of rapamycin pathway, a serine/threonine
613
protein kinase that drives protein synthesis. It has been demonstrated that leucine coingestion (2.5 g) with a bolus of pure dietary protein (20 g) in healthy older individuals further stimulates the postprandial muscle protein synthesis rate [20]. Similarly it has been reported that supplementation with b-hydroxy-b-methylbutyrate (a leucine metabolite) was able to prevent the decline in lean body mass over bed rest [21]. Furthermore, the efficacy of a leucine-enriched oral supplement in stimulating muscle protein synthesis in cancer patients has been confirmed [22]. Consequently, many authors argue that the recommended daily allowance for protein (1 g/kg), although sufficient to maintain muscle mass [23] in healthy individuals, fails to prevent muscle loss with aging [12,14,24,25]. In contrast, levels of daily protein intake as high as 1.6 g of protein/kg have been demonstrated to increase exercise-induced muscle hypertrophy [26]. The recommendation by the International Cachexia Society for older persons is to ingest between 1 and 1.5 g of protein/kg daily. Additionally, because a threefold increase in protein and energy content (90 g total: w36 g essential amino acids) was not able to achieve a further increase in protein synthesis in the young and the elderly [16], it is recommended that the amount of protein ingested should be spread equally throughout the day (i.e., equivalent amounts at breakfast, lunch, and dinner) [27]. If additional protein supplementation is given, it should be administered between meals. However, it is worthy of note to consider that increase in muscle protein synthesis does not necessarily imply an anabolic response unless it is clear that this process of synthesis overrides the protein breakdown and theoretically it is possible that a higher intake of amino acid are able to further promote muscle anabolism because further increases in intracellular amino acid concentrations provide a signal to limit the rate of protein breakdown [28]. In a recent study, the administration 1.3 g/kg of protein to older patients had a better effect on lean mass, appendicular skeletal muscle mass, and body cell mass index when 72% of protein (48 g) was given by pulse feeding (noon meal) than when it was given throughout the day [29]. From the clinical point of view, it is important to consider that protein sources of high biological value, namely those from animal sources, provide the highest concentrations of branched chain amino acids such as leucine, which are capable of stimulating muscle protein synthesis [13,30,31] and preventing muscle protein loss that occur in humans during bed rest [13]. Milk proteins, whey, and casein are high-quality proteins but produce a different response in young people compared with older people. Whey protein ingestion improves skeletal muscle protein accrual in older individuals through mechanisms that are beyond those attributed to its essential amino acid content [32].Whey is digested faster than casein and produces a relatively better response on protein balance in older people [33,34]. It has been hypothesized that fast protein might be able to overflow the splanchnic tissue extraction, whereas slow proteins are unable to escape it. In a long-term study of older sarcopenic patients [35], the provision of 8 g/d of essential amino over 18 mo increased muscle mass, reduced tumor necrosis factor-a, and improved insulin sensitivity. The optimal nitrogen supply for older cancer patients cannot be determined at present. Recommendations (expert opinion) for malnourished cancer patients range between a minimum daily protein supply of 1 g/kg [36] and a target supply of 1.5 g/ kg daily [37]. Of course, the load of amino acid to be administered
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F. Bozzetti / Nutrition 31 (2015) 612–614
has to take into account the polymorbidity of the older patients [38] and dose should be limited if the glomerular filtration rate is < 30 mL/min. References [1] Moses AM, Streeten DHP. Disorders of neurohypophysis. In: Fauci SA, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kaspers DL, Hauser SL, Longo DL, editors. Harrison’s Principles of Internal medicine. 14th ed. New York: Mc Graw-Hill; 1998. p. 2003–12. [2] Steiner N, Bruera E. Methods of hydration in palliative care patients. J Palliat Care 1998;14:6–13. [3] Kerndt P, Naughton J, Driscoll G, Loxterkamp A. Fasting: the history, pathophysiology and complications. West J Med 1982;137:379–99. [4] Bruera E, Belzile M, Watanabe S, Fainsinger RL. Volume of hydration in terminal cancer patients. Support Care Cancer 1996;4:147–50. [5] Bozzetti F, Arends J, Lundholm K, Micklewright A, Zurcher G, Muscaritoli M. ESPEN Guidelines on Parenteral Nutrition: Non-surgical oncology. Clin Nutr 2009;28:445–54. [6] Hansell DT, Davies JW, Shenkin A, Burns HJ. The oxidation of body fuel stores in cancer patients. Ann Surg 1986;204:637–42. [7] Gibney E, Elia M, Jebbs SA, Murgatroyd P, Jennings G. Total energy expenditure with small-cell lung cancer: results of a validated study using the bicarbonate-urea method. Metabolism 1997;46:1412–7. [8] Bencini L, Di Leo A, Pozzessere D, Bozzetti F. Total energy expenditure in patients with advanced solid tumours: a preliminary report. Nutr Ther Met 2008;26:45–7. [9] Aberg W, Thörne A, Olivecrona T, Nordenström J. Fat oxidation and plasma removal capacity of an intravenous fat emulsion in elderly and young men. Nutrition 2006;22:738–43. buterne X. Effect of age on sub[10] Al-Jaouni R, Schneider SM, Rampal P, He strate oxidation during total parenteral nutrition. Nutrition 2002;18:20–51. [11] Horstman AM, Sheffield Moore M. The nutritional/metabolic response. Nutrition 2015;31:605–7. [12] Ferrando AA, Paddon-Jones D, Hays NP, Kortebein P, Ronsen O, Williams RH, et al. EAA supplementation to increase nitrogen intake improves muscle function during bed rest in the elderly. Clin Nutr 2010;29:18–23. [13] Paddon-Jones D, Rasmussen BB. Dietary protein recommendations and the prevention of sarcopenia. Curr Opin Clin Nutr Metab Care 2009;12:86–90. [14] Paddon-Jones D, Sheffield-Moore M, Aarsland A, Wolfe RR, Ferrando AA. Exogenous amino acids stimulate human muscle anabolism without interfering with the response to mixed meal ingestion. Am J Physiol Endocrinol Metab 2005;288:E761–7. [15] Katsanos CS, Kobayashi H, Sheffield-Moore M, Aarsland A, Wolfe RR. Aging is associated with diminished accretion of muscle proteins after the ingestion of a small bolus of essential amino acids. Am J Clin Nutr 2005;82:1065–73. [16] Symons TB, Sheffield-Moore M, Wolfe RR, Paddon-Jones D. A moderate serving of high-quality protein maximally stimulates skeletal muscle protein synthesis in young and elderly subjects. J Am Diet Assoc 2009;109:1582–6. [17] Volpi E, Ferrando AA, Yeckel CW, Tipton KD, Wolfe RR. Exogenous amino acids stimulate net muscle protein synthesis in the elderly. J Clin Invest 1998;101:2000–7. [18] Layman DK. Protein quantity and quality at levels above the RDA improves adult weight loss. J Am Coll Nutr 2004;23(6 Suppl):631S–6S.
[19] Rieu I, Balage M, Sornet C, Giraudet C, Pujos E, Grizard J, et al. Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia. J Physiol 2006;575:305–15. [20] Wall BT, Hamer HM, de Lange A, Kiskini A, Groen BB, Senden JM, et al. Leucine co-ingestion improves postprandial muscle protein accretion in elderly men. Clin Nutr 2013;32:412–9. [21] Deutz NE, Pereira SL, Hays NP, Oliver JS, Edens NK, Evans CM, et al. Effect of b-hydroxy-b-methylbutyrate (HMB) on lean body mass during 10 d of bed rest in older adults. Clin Nutr 2013;32:704–12. [22] Deutz NE, Safar A, Schutzler S, Memelink R, Ferrando A, Spencer H, et al. Muscle protein synthesis in cancer patients can be stimulated with a specially formulated medical food. Clin Nutr 2011;30:759–68. [23] Arnal MA, Mosoni L, Boirie Y, Houlier ML, Morin L, Verdier E, et al. Protein pulse feeding improves protein retention in elderly women. Am J Clin Nutr 1999;69:1202–8. [24] Wolfe RR, Miller SL, Miller KB. Optimal protein intake in the elderly. Clin Nutr 2008;27:675–84. [25] Evans WJ. Protein nutrition, exercise and aging. J Am Coll Nutr 2004;23(Suppl):601S–9S. [26] Campbell WW, Leidy HJ. Dietary protein and resistance training effects on muscle and body composition in older persons. J Am Coll Nutr 2007;26:696S–703S. [27] Sloane PD, Ivey J, Helton M, Barrick AL, Cerna A. Nutritional issues in longterm care. J Am Med Dir Assoc 2008;9:476–85. [28] Wolfe RR, Miller SL. Amino acid availability controls muscle protein metabolism. Diabetes Nutr Metab 1999;12:322–8. tien P, Schauer N, et al. [29] Bouillanne O, Curis E, Hamon-Vilcot B, Nicolis I, Chre Impact of protein pulse feeding on lean mass in malnourished and at-risk hospitalized elderly patients: a randomized controlled trial. Clin Nutr 2013;32:186–92. [30] Symons TB, Schutzler SE, Cocke TL, Chinkes DL, Wolfe RR, Paddon-Jones D. Aging does not impair the anabolic response to a protein-rich meal. Am J Clin Nutr 2007;86:451–6. [31] Katsanos CS, Kobayashi H, Sheffield-Moore M, Aarsland A, Wolfe RR. A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab 2006;291:E381–7. [32] Katsanos CS, Chinkes DL, Paddon-Jones D, Zhang XJ, Aarsland A, Wolfe RR. Whey protein ingestion in elderly persons results in greater muscle protein accrual than ingestion of its constituent essential amino acid content. Nutr Res 2008;28:651–8. [33] Dangin M, Guillet C, Garcia-Rodenas C, Gachon P, Bouteloup-Demange C, Reiffers-Magnani K, et al. The rate of protein digestion affects protein gain differently during aging in humans. J Physiol 2003;549:635–44. C, Bonhomme C, et al. [34] Gryson C, Walrand S, Giraudet C, Rousset P, Migne “Fast proteins” with a unique essential amino acid content as an optimal nutrition in the elderly: growing evidence. Clin Nutr 2014;33:642–8. [35] Solerte SB, Gazzaruso C, Bonacasa R, Rondanelli M, Zamboni M, Basso C, et al. Nutritional supplements with oral amino acid mixtures increases whole-body lean mass and insulin sensitivity in elderly subjects with sarcopenia. Am J Cardiol 2008;101:69E–77E. [36] Nitenberg G, Raynard B. Nutritional Support of the cancer patient: issues and dilemmas. Crit Rev Oncol Hematol 2000;34:137–68. [37] Bozzetti F, Bozzetti V. Is the intravenous supplementation of amino acid to cancer patients adequate? A critical appraisal of literature. Clin Nutr 2012;32:142–6. [38] Sieber C. Practical aspects of nutritional support of the elderly patient. Nutrition; 2015.
Contents lists available at ScienceDirect
Nutrition journal homepage: www.nutritionjrnl.com
Special article
Tailoring the nutritional regimen in the elderly cancer patient Federico Bozzetti M.D. * Faculty of Medicine, University of Milan, Italy
a b s t r a c t Keywords: Water requirement Energy requirement Protein requirement Macronutrient requirement
Our knowledge of the macronutrient requirement of elderly cancer patient is still incomplete and mainly relies on studies of elderly (healthy) people and populations of cancer patients including both adult and elderly subjects. Patients with minor nutritional deterioration do not require any specific nutritional regimen, but cachectic patients do. Total energy expenditure can be unchanged or lower in advanced weight-losing patients (when compared with matched healthy controls) because the higher resting metabolic expenditure can be offset by reduced physical activity, and it approximates to 25-28 Kcal/kg/d. Protein requirement is probably 1.5 g amino acid (AA)/kg/d or more, especially if the goal is increased lean body mass. However, the final balance depends not only on the quantity of AA but also their quality: diets including a high percentage of essential AA and especially of branched-chain ones and leucine in particular, are advocated. Total fluid load should be prudent, around 25-30 ml/kg/d. Ó 2015 Elsevier Inc. All rights reserved.
The regimen The nutritional regimen varies according to whether the nutritional support is a “supplementation” or whether it aims to cover the patient’s full nutritional requirements. Only in this latter event is it important to plan a specific nutritional approach. There is little specific clinical or metabolic experience for the nutritional support of the geriatric cancer patient and hence our knowledge relies on data available on the enteral and parenteral nutrition of the healthy geriatric population and in patients with cancer regardless of age. It is noteworthy, however, that the majority of patients with cancer are older than 65. Table 1 summarizes the requirements of the main nutrients, especially when nutrition is delivered intravenously. In fact, not only might the unbalance of nutrients be better compensated by homeostatic mechanisms of the patient when nutritional support is oral or enteral than when it is totally intravenous (IV), but patients fed by IV are usually more compromised. Water requirement A restriction in water administration usually is advised. Advanced cancer often is associated with the expansion of the extracellular fluid volume, which may be due to the tumor * Corresponding author. Tel.: þ39 329 765 5385; fax: þ39 0226410267. E-mail address: [email protected] http://dx.doi.org/10.1016/j.nut.2014.12.007 0899-9007/Ó 2015 Elsevier Inc. All rights reserved.
producing an excess of antidiuretic hormone [1]; to the presence of nausea, which frequently occurs in advanced stages of disease; or to the administration of morphine. Wasting is associated with loss of intracellular water and solutes that, through the activation of the hypothalamic osmoreceptor cells, stimulate the antidiuretic hormone release at levels that maintain serum osmolality and sodium concentration at subnormal values [2]. As a consequence, the clearance of free water is decreased, also because the urea load presented to the kidney is reduced due to the protein depletion secondary to the undernutrition. In contrast, the synthesis of endogenous water is maintained by the oxidation of energetic substrates (carbohydrates and fats) [3] and the insensible water loss drops because of reduced physical activity [4]. Hence, an overzealous administration of water, glucose, and sodium can sharply result in a fluid overload with edema in peripheral tissues as well as in the central organs. According to the European Society for Clinical Nutrition and Metabolism guidelines [5], the total volume of fluid and sodium should not exceed 25 to 30 mL and 1 mmol/kg daily, respectively, provided that the patient is not dehydrated. Energy requirement There is a paucity of data regarding the energy requirements of older cancer patients. The daily resting energy expenditure (REE) was quantified as 24.6 kcal/kg: In older weight-stable patients daily REE was
F. Bozzetti / Nutrition 31 (2015) 612–614 Table 1 Adequate nutritional regimen for the advanced cancer patient Nutrient
Daily dose
Water Nonprotein energy Glucose Fat (L/ MCT þ u-3) Amino acid Sodium
30 mL/kg 30 kcal/kg w3.7 g/kg (50% nonprotein energy) w1.6 g/kg (50% nonprotein energy) 1.5 g/kg 1 mEq/kg
MCT, medium chain triacylglycerol
22.7 kcal/kg, a value significantly lower than in weight-losing cancer patients but higher than in weight-stable controls [6]. The total energy/basal energy expenditure of older outpatients with small cell lung cancer was only 1.36 according to a previous study, which supports the concept that the energy requirements of these patients are not increased because their mild basal hypermetabolism may be overbalanced by decreased physical activity [7]. A more recent study reported that in older, hospitalized patients with advanced cancer, daily total energy expenditure was 28 3 kcal/kg [8]. It is clinically relevant the finding that older cancer patients have significantly higher fat oxidation rates and significantly lower carbohydrate oxidation rates compared with controls. Additionally, weight-losing cancer patients have significantly higher fat oxidation rates compared with weight-stable cancer patients, weight-stable controls, and weight-losing controls [6]. The capacity to clear and oxidize a high triacylglycerol (TG) load of older healthy individuals or older patients, equally or better than younger individuals, has been reported [9,10]. These data argue for a high fat-to-carbohydrate ratio in the nutritional regimen. However, clinicians should be aware that daily parenteral administration (1 g/kg) of u-6 long chain TGs is associated with severe liver toxicity after 2 y in >50% of patients and mixed emulsions containing medium-chain TG and u-3 or u-9 fatty acids should be considered in these cases.
Protein requirements Most of the available evidence refers to healthy older individuals or sarcopenic patients [11]. Because of age-dependent metabolic alterations, in general older individuals may synthetize less muscle protein than younger persons from the same amount of dietary protein. However, even if aging is associated with an inability to respond to low load of protein (20 g) or essential amino acids (25 g; essential amino acids 10–15 g) is able to stimulate muscle protein synthesis in older adults to a similar extent as in the young [12–15]. One study reported that a moderate (113 g) serving of an intact protein (i.e., lean beef) contains sufficient essential amino acids (30 g total: w12 g essential amino acids) to increase mixed-muscle protein synthesis by 50% in young and older men and women [16]. A previous study was the first to demonstrate that the acute intravenous administration of amino acids stimulates net muscle protein synthesis in the healthy geriatric population [17]. Essential amino acids appear to be the primary stimulus of protein synthesis and act synergistically with exercise to increase fractional protein synthesis [18]. Leucine seems to be the most active of the amino acids [19] and the anabolic effect of leucineenriched essential amino acids act not only as building blocks for protein synthesis but also due to the stimulation, in muscle, of the mammalian target of rapamycin pathway, a serine/threonine
613
protein kinase that drives protein synthesis. It has been demonstrated that leucine coingestion (2.5 g) with a bolus of pure dietary protein (20 g) in healthy older individuals further stimulates the postprandial muscle protein synthesis rate [20]. Similarly it has been reported that supplementation with b-hydroxy-b-methylbutyrate (a leucine metabolite) was able to prevent the decline in lean body mass over bed rest [21]. Furthermore, the efficacy of a leucine-enriched oral supplement in stimulating muscle protein synthesis in cancer patients has been confirmed [22]. Consequently, many authors argue that the recommended daily allowance for protein (1 g/kg), although sufficient to maintain muscle mass [23] in healthy individuals, fails to prevent muscle loss with aging [12,14,24,25]. In contrast, levels of daily protein intake as high as 1.6 g of protein/kg have been demonstrated to increase exercise-induced muscle hypertrophy [26]. The recommendation by the International Cachexia Society for older persons is to ingest between 1 and 1.5 g of protein/kg daily. Additionally, because a threefold increase in protein and energy content (90 g total: w36 g essential amino acids) was not able to achieve a further increase in protein synthesis in the young and the elderly [16], it is recommended that the amount of protein ingested should be spread equally throughout the day (i.e., equivalent amounts at breakfast, lunch, and dinner) [27]. If additional protein supplementation is given, it should be administered between meals. However, it is worthy of note to consider that increase in muscle protein synthesis does not necessarily imply an anabolic response unless it is clear that this process of synthesis overrides the protein breakdown and theoretically it is possible that a higher intake of amino acid are able to further promote muscle anabolism because further increases in intracellular amino acid concentrations provide a signal to limit the rate of protein breakdown [28]. In a recent study, the administration 1.3 g/kg of protein to older patients had a better effect on lean mass, appendicular skeletal muscle mass, and body cell mass index when 72% of protein (48 g) was given by pulse feeding (noon meal) than when it was given throughout the day [29]. From the clinical point of view, it is important to consider that protein sources of high biological value, namely those from animal sources, provide the highest concentrations of branched chain amino acids such as leucine, which are capable of stimulating muscle protein synthesis [13,30,31] and preventing muscle protein loss that occur in humans during bed rest [13]. Milk proteins, whey, and casein are high-quality proteins but produce a different response in young people compared with older people. Whey protein ingestion improves skeletal muscle protein accrual in older individuals through mechanisms that are beyond those attributed to its essential amino acid content [32].Whey is digested faster than casein and produces a relatively better response on protein balance in older people [33,34]. It has been hypothesized that fast protein might be able to overflow the splanchnic tissue extraction, whereas slow proteins are unable to escape it. In a long-term study of older sarcopenic patients [35], the provision of 8 g/d of essential amino over 18 mo increased muscle mass, reduced tumor necrosis factor-a, and improved insulin sensitivity. The optimal nitrogen supply for older cancer patients cannot be determined at present. Recommendations (expert opinion) for malnourished cancer patients range between a minimum daily protein supply of 1 g/kg [36] and a target supply of 1.5 g/ kg daily [37]. Of course, the load of amino acid to be administered
614
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has to take into account the polymorbidity of the older patients [38] and dose should be limited if the glomerular filtration rate is < 30 mL/min. References [1] Moses AM, Streeten DHP. Disorders of neurohypophysis. In: Fauci SA, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kaspers DL, Hauser SL, Longo DL, editors. Harrison’s Principles of Internal medicine. 14th ed. New York: Mc Graw-Hill; 1998. p. 2003–12. [2] Steiner N, Bruera E. Methods of hydration in palliative care patients. J Palliat Care 1998;14:6–13. [3] Kerndt P, Naughton J, Driscoll G, Loxterkamp A. Fasting: the history, pathophysiology and complications. West J Med 1982;137:379–99. [4] Bruera E, Belzile M, Watanabe S, Fainsinger RL. Volume of hydration in terminal cancer patients. Support Care Cancer 1996;4:147–50. [5] Bozzetti F, Arends J, Lundholm K, Micklewright A, Zurcher G, Muscaritoli M. ESPEN Guidelines on Parenteral Nutrition: Non-surgical oncology. Clin Nutr 2009;28:445–54. [6] Hansell DT, Davies JW, Shenkin A, Burns HJ. The oxidation of body fuel stores in cancer patients. Ann Surg 1986;204:637–42. [7] Gibney E, Elia M, Jebbs SA, Murgatroyd P, Jennings G. Total energy expenditure with small-cell lung cancer: results of a validated study using the bicarbonate-urea method. Metabolism 1997;46:1412–7. [8] Bencini L, Di Leo A, Pozzessere D, Bozzetti F. Total energy expenditure in patients with advanced solid tumours: a preliminary report. Nutr Ther Met 2008;26:45–7. [9] Aberg W, Thörne A, Olivecrona T, Nordenström J. Fat oxidation and plasma removal capacity of an intravenous fat emulsion in elderly and young men. Nutrition 2006;22:738–43. buterne X. Effect of age on sub[10] Al-Jaouni R, Schneider SM, Rampal P, He strate oxidation during total parenteral nutrition. Nutrition 2002;18:20–51. [11] Horstman AM, Sheffield Moore M. The nutritional/metabolic response. Nutrition 2015;31:605–7. [12] Ferrando AA, Paddon-Jones D, Hays NP, Kortebein P, Ronsen O, Williams RH, et al. EAA supplementation to increase nitrogen intake improves muscle function during bed rest in the elderly. Clin Nutr 2010;29:18–23. [13] Paddon-Jones D, Rasmussen BB. Dietary protein recommendations and the prevention of sarcopenia. Curr Opin Clin Nutr Metab Care 2009;12:86–90. [14] Paddon-Jones D, Sheffield-Moore M, Aarsland A, Wolfe RR, Ferrando AA. Exogenous amino acids stimulate human muscle anabolism without interfering with the response to mixed meal ingestion. Am J Physiol Endocrinol Metab 2005;288:E761–7. [15] Katsanos CS, Kobayashi H, Sheffield-Moore M, Aarsland A, Wolfe RR. Aging is associated with diminished accretion of muscle proteins after the ingestion of a small bolus of essential amino acids. Am J Clin Nutr 2005;82:1065–73. [16] Symons TB, Sheffield-Moore M, Wolfe RR, Paddon-Jones D. A moderate serving of high-quality protein maximally stimulates skeletal muscle protein synthesis in young and elderly subjects. J Am Diet Assoc 2009;109:1582–6. [17] Volpi E, Ferrando AA, Yeckel CW, Tipton KD, Wolfe RR. Exogenous amino acids stimulate net muscle protein synthesis in the elderly. J Clin Invest 1998;101:2000–7. [18] Layman DK. Protein quantity and quality at levels above the RDA improves adult weight loss. J Am Coll Nutr 2004;23(6 Suppl):631S–6S.
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