Current Concepts and Unresolved Questions in Dietary Protein Requirements and Supplements in Adults

Stuart M Phillips, Stuart M Phillips

Abstract

Protein needs for otherwise healthy individuals older than 19 years are defined by the recommended dietary allowance (RDA) at 0.80 g protein/kg/day. There is no recommendation in the current RDA for subpopulations of older adults or people in various pathological situations. Despite the lack of a separate recommendation, there exists a growing body of evidence that is strongly suggestive of an increased need and/or benefit for protein in older persons. That is, intakes beyond the RDA are, in older persons, associated with benefits. In addition, a number of catabolic states including critical illness also result in a sharp elevation in the needs for protein and amino acids. An underappreciated issue in protein nutrition is the impact of protein quality on clinically relevant outcomes. The introduction of a new protein scoring system-the digestible indispensable amino acid score (DIAAS)-for protein quality has raised a forgotten awareness of protein quality. The DIAAS, which replaces the protein digestibility-corrected amino acid score (PDCAAS), is based on ileal digestibility of protein and a different test protein than PDCAAS and has values greater than 1.0. The aim of this article is a brief review and summary recommendations for protein nutrition and protein requirements in populations who would benefit from more protein than the RDA. The emphasis of the review is on muscle protein turnover, and there is a discussion of the impact of protein quality, particularly as it applies to commercially available protein sources. The evidence for more optimal protein intakes is considered in light of the potential health risks of consumption of protein at levels greater than the RDA.

Keywords: chronic illness; creatine; critical illness; lean body mass; leucine; sarcopenia.

References

    1. Rennie MJ. Exercise- and nutrient-controlled mechanisms involved in maintenance of the musculoskeletal mass. Biochem Soc Trans (2007) 35:1302–5.10.1042/BST0351302
    1. Rennie MJ, Wackerhage H, Spangenburg EE, Booth FW. Control of the size of the human muscle mass. Annu Rev Physiol (2004) 66:799–828.10.1146/annurev.physiol.66.052102.134444
    1. Morton RW, McGlory C, Phillips SM. Nutritional interventions to augment resistance training-induced skeletal muscle hypertrophy. Front Physiol (2015) 6:245.10.3389/fphys.2015.00245
    1. Carraro F, Hartl WH, Stuart CA, Layman DK, Jahoor F, Wolfe RR. Whole body and plasma protein synthesis in exercise and recovery in human subjects. Am J Physiol (1990) 258:E821–31.
    1. Nakshabendi IM, McKee R, Downie S, Russell RI, Rennie MJ. Rates of small intestinal mucosal protein synthesis in human jejunum and ileum. Am J Physiol (1999) 277:E1028–31.
    1. Bohe J, Low JF, Wolfe RR, Rennie MJ. Latency and duration of stimulation of human muscle protein synthesis during continuous infusion of amino acids. J Physiol (2001) 532:575–9.10.1111/j.1469-7793.2001.0575f.x
    1. Nair KS, Schwartz RG, Welle S. Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans. Am J Physiol (1992) 263:E928–34.
    1. Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: National Academies Press; (2005).
    1. Leidy HJ, Clifton PM, Astrup A, Wycherley TP, Westerterp-Plantenga MS, Luscombe-Marsh ND, et al. The role of protein in weight loss and maintenance. Am J Clin Nutr (2015) 10:1320S–9S.10.3945/ajcn.114.084038
    1. Paddon-Jones D, Campbell WW, Jacques PF, Kritchevsky SB, Moore LL, Rodriguez NR, et al. Protein and healthy aging. Am J Clin Nutr (2015) 101:1339–45S.10.3945/ajcn.114.084061
    1. Layman DK, Anthony TG, Rasmussen BB, Adams SH, Lynch CJ, Brinkworth GD, et al. Defining meal requirements for protein to optimize metabolic roles of amino acids. Am J Clin Nutr (2015) 101:1330S–8S.10.3945/ajcn.114.084053
    1. Young VR. Nutritional balance studies: indicators of human requirements or of adaptive mechanisms? J Nutr (1986) 116:700–3.
    1. Wolfe RR, Miller SL. The recommended dietary allowance of protein: a misunderstood concept. JAMA (2008) 299:2891–3.10.1001/jama.299.24.2891
    1. Rand WM, Pellett PL, Young VR. Meta-analysis of nitrogen balance studies for estimating protein requirements in healthy adults. Am J Clin Nutr (2003) 77:109–27.
    1. Humayun MA, Elango R, Ball RO, Pencharz PB. Reevaluation of the protein requirement in young men with the indicator amino acid oxidation technique. Am J Clin Nutr (2007) 86:995–1002.
    1. Elango R, Humayun MA, Ball RO, Pencharz PB. Evidence that protein requirements have been significantly underestimated. Curr Opin Clin Nutr Metab Care (2010) 13:52–7.10.1097/MCO.0b013e328332f9b7
    1. Elango R, Ball RO, Pencharz PB. Recent advances in determining protein and amino acid requirements in humans. Br J Nutr (2012) 108(Suppl 2):S22–30.10.1017/S0007114512002504
    1. Elango R, Ball RO, Pencharz PB. Indicator amino acid oxidation: concept and application. J Nutr (2008) 138:243–6.
    1. Elango R, Humayun MA, Ball RO, Pencharz PB. Protein requirement of healthy school-age children determined by the indicator amino acid oxidation method. Am J Clin Nutr (2011) 94:1545–52.10.3945/ajcn.111.012815
    1. Rafii M, Chapman K, Elango R, Campbell WW, Ball RO, Pencharz PB, et al. Dietary protein requirement of men >65 years old determined by the indicator amino acid oxidation technique is higher than the current estimated average requirement. J Nutr (2016) 146:681–7.10.3945/jn.115.225631
    1. Rafii M, Chapman K, Owens J, Elango R, Campbell WW, Ball RO, et al. Dietary protein requirement of female adults >65 years determined by the indicator amino acid oxidation technique is higher than current recommendations. J Nutr (2015) 145:18–24.10.3945/jn.114.197517
    1. Tang M, McCabe GP, Elango R, Pencharz PB, Ball RO, Campbell WW. Assessment of protein requirement in octogenarian women with use of the indicator amino acid oxidation technique. Am J Clin Nutr (2014) 99:891–8.10.3945/ajcn.112.042325
    1. Fulgoni VL, III. Current protein intake in America: analysis of the National Health and Nutrition Examination Survey, 2003-2004. Am J Clin Nutr (2008) 87:1554S–7S.
    1. FAO. Report of an FAO Expert Consultation. Dietary Protein Quality Evaluation in Human Nutrition. Rome: FAO; (2013).
    1. Rutherfurd SM, Moughan PJ. Available versus digestible dietary amino acids. Br J Nutr (2012) 108(Suppl 2):S298–305.10.1017/S0007114512002528
    1. Rutherfurd SM, Fanning AC, Miller BJ, Moughan PJ. Protein digestibility-corrected amino acid scores and digestible indispensable amino acid scores differentially describe protein quality in growing male rats. J Nutr (2015) 145:372–9.10.3945/jn.114.195438
    1. Stuart PS, Bell SJ, Molnar J. Use of tryptophan-fortified hydrolyzed collagen for nutritional support. J Diet Suppl (2008) 5:383–400.10.1080/19390210802519689
    1. Castellanos VH, Litchford MD, Campbell WW. Modular protein supplements and their application to long-term care. Nutr Clin Pract (2006) 21:485–504.10.1177/0115426506021005485
    1. Anthony JC, Lang CH, Crozier SJ, Anthony TG, MacLean DA, Kimball SR, et al. Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucine. Am J Physiol Endocrinol Metab (2002) 282:E1092–101.10.1152/ajpendo.00208.2001
    1. Anthony JC, Anthony TG, Kimball SR, Jefferson LS. Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine. J Nutr (2001) 131:856S–60S.
    1. Anthony JC, Yoshizawa F, Anthony TG, Vary TC, Jefferson LS, Kimball SR. Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway. J Nutr (2000) 130:2413–9.
    1. Crozier SJ, Kimball SR, Emmert SW, Anthony JC, Jefferson LS. Oral leucine administration stimulates protein synthesis in rat skeletal muscle. J Nutr (2005) 135:376–82.
    1. Churchward-Venne TA, Burd NA, Phillips SM. Nutritional regulation of muscle protein synthesis with resistance exercise: strategies to enhance anabolism. Nutr Metab (Lond) (2012) 9:40.10.1186/1743-7075-9-40
    1. Churchward-Venne TA, Burd NA, Mitchell CJ, West DW, Philp A, Marcotte GR, et al. Supplementation of a suboptimal protein dose with leucine or essential amino acids: effects on myofibrillar protein synthesis at rest and following resistance exercise in men. J Physiol (2012) 590:2751–65.10.1113/jphysiol.2012.228833
    1. Churchward-Venne TA, Breen L, Di Donato DM, Hector AJ, Mitchell CJ, Moore DR, et al. Leucine supplementation of a low-protein mixed macronutrient beverage enhances myofibrillar protein synthesis in young men: a double-blind, randomized trial. Am J Clin Nutr (2014) 99:276–86.10.3945/ajcn.113.068775
    1. Chantranupong L, Wolfson RL, Orozco JM, Saxton RA, Scaria SM, Bar-Peled L, et al. The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. Cell Rep (2014) 9:1–8.10.1016/j.celrep.2014.09.014
    1. Wolfson RL, Chantranupong L, Saxton RA, Shen K, Scaria SM, Cantor JR, et al. Sestrin2 is a leucine sensor for the mTORC1 pathway. Science (2016) 351:43–8.10.1126/science.aab2674
    1. Kimball SR, Gordon BS, Moyer JE, Dennis MD, Jefferson LS. Leucine induced dephosphorylation of Sestrin2 promotes mTORC1 activation. Cell Signal (2016) 28:896–906.10.1016/j.cellsig.2016.03.008
    1. 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:E381–7.10.1152/ajpendo.00488.2005
    1. Wall BT, Hamer HM, de LA, Kiskini A, Groen BB, Senden JM, et al. Leucine co-ingestion improves post-prandial muscle protein accretion in elderly men. Clin Nutr (2012) 32:412–9.10.1016/j.clnu.2012.09.002
    1. Yang Y, Breen L, Burd NA, Hector AJ, Churchward-Venne TA, Josse AR, et al. Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. Br J Nutr (2012) 108:1–9.10.1017/S0007114511007422
    1. Yang Y, Churchward-Venne TA, Burd NA, Breen L, Tarnopolsky MA, Phillips SM. Myofibrillar protein synthesis following ingestion of soy protein isolate at rest and after resistance exercise in elderly men. Nutr Metab (Lond) (2012) 9:57.10.1186/1743-7075-9-57
    1. Bauer JM, Verlaan S, Bautmans I, Brandt K, Donini LM, Maggio M, et al. Effects of a vitamin D and leucine-enriched whey protein nutritional supplement on measures of sarcopenia in older adults, the PROVIDE study: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc (2015) 16:740–7.10.1016/j.jamda.2015.05.021
    1. Phillips SM, Chevalier S, Leidy HJ. Protein “requirements” beyond the RDA: implications for optimizing health. Appl Physiol Nutr Metab (2016) 41:565–72.10.1139/apnm-2015-0550
    1. Rosendahl-Riise H, Spielau U, Ranhoff AH, Gudbrandsen OA, Dierkes J. Vitamin D supplementation and its influence on muscle strength and mobility in community-dwelling older persons: a systematic review and meta-analysis. J Hum Nutr Diet (2017) 30(1):3–15.10.1111/jhn.12394
    1. Beaudart C, Buckinx F, Rabenda V, Gillain S, Cavalier E, Slomian J, et al. The effects of vitamin D on skeletal muscle strength, muscle mass, and muscle power: a systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab (2014) 99:4336–45.10.1210/jc.2014-1742
    1. Rondanelli M, Klersy C, Terracol G, Talluri J, Maugeri R, Guido D, et al. Whey protein, amino acids, and vitamin D supplementation with physical activity increases fat-free mass and strength, functionality, and quality of life and decreases inflammation in sarcopenic elderly. Am J Clin Nutr (2016) 103:830–40.10.3945/ajcn.115.113357
    1. Komar B, Schwingshackl L, Hoffmann G. Effects of leucine-rich protein supplements on anthropometric parameter and muscle strength in the elderly: a systematic review and meta-analysis. J Nutr Health Aging (2015) 19:437–46.10.1007/s12603-014-0559-4
    1. Churchward-Venne TA, Breen L, Phillips SM. Alterations in human muscle protein metabolism with aging: protein and exercise as countermeasures to offset sarcopenia. Biofactors (2014) 40:199–205.10.1002/biof.1138
    1. Cesari M, Landi F, Vellas B, Bernabei R, Marzetti E. Sarcopenia and physical frailty: two sides of the same coin. Front Aging Neurosci (2014) 6:192.10.3389/fnagi.2014.00192
    1. Bauer J, Biolo G, Cederholm T, Cesari M, Cruz-Jentoft AJ, Morley JE, et al. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. J Am Med Dir Assoc (2013) 14:542–59.10.1016/j.jamda.2013.05.021
    1. Deutz NE, Bauer JM, Barazzoni R, Biolo G, Boirie Y, Bosy-Westphal A, et al. Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group. Clin Nutr (2014) 33:929–36.10.1016/j.clnu.2014.04.007
    1. Houston DK, Nicklas BJ, Ding J, Harris TB, Tylavsky FA, Newman AB, et al. Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the Health, Aging, and Body Composition (Health ABC) Study. Am J Clin Nutr (2008) 87:150–5.
    1. McDonald CK, Ankarfeldt MZ, Capra S, Bauer J, Raymond K, Heitmann BL. Lean body mass change over 6 years is associated with dietary leucine intake in an older Danish population. Br J Nutr (2016) 115:1556–62.10.1017/S0007114516000611
    1. Geirsdottir OG, Arnarson A, Ramel A, Jonsson PV, Thorsdottir I. Dietary protein intake is associated with lean body mass in community-dwelling older adults. Nutr Res (2013) 33:608–12.10.1016/j.nutres.2013.05.014
    1. Isanejad M, Mursu J, Sirola J, Kroger H, Rikkonen T, Tuppurainen M, et al. Association of protein intake with the change of lean mass among elderly women: The Osteoporosis Risk Factor and Prevention – Fracture Prevention Study (OSTPRE-FPS). J Nutr Sci (2015) 4:e41.10.1017/jns.2015.31
    1. Gregorio L, Brindisi J, Kleppinger A, Sullivan R, Mangano KM, Bihuniak JD, et al. Adequate dietary protein is associated with better physical performance among post-menopausal women 60-90 years. J Nutr Health Aging (2014) 18:155–60.10.1007/s12603-013-0391-2
    1. Loenneke JP, Loprinzi PD, Murphy CH, Phillips SM. Per meal dose and frequency of protein consumption is associated with lean mass and muscle performance. Clin Nutr (2016) 35:1506–11.10.1016/j.clnu.2016.04.002
    1. Murphy CH, Oikawa SY, Phillips SM. Dietary protein to maintain muscle mass in aging: a case for per-meal protein recommendations. J Frailty Aging (2016) 5:49–58.10.14283/jfa.2016.80
    1. Norton C, Toomey C, McCormack WG, Francis P, Saunders J, Kerin E, et al. Protein supplementation at breakfast and lunch for 24 weeks beyond habitual intakes increases whole-body lean tissue mass in healthy older adults. J Nutr (2016) 146:65–9.10.3945/jn.115.219022
    1. Gruther W, Benesch T, Zorn C, Paternostro-Sluga T, Quittan M, Fialka-Moser V, et al. Muscle wasting in intensive care patients: ultrasound observation of the M. quadriceps femoris muscle layer. J Rehabil Med (2008) 40:185–9.10.2340/16501977-0139
    1. Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, et al. Acute skeletal muscle wasting in critical illness. JAMA (2013) 310:1591–600.10.1001/jama.2013.278481
    1. Klaude M, Mori M, Tjader I, Gustafsson T, Wernerman J, Rooyackers O. Protein metabolism and gene expression in skeletal muscle of critically ill patients with sepsis. Clin Sci (Lond) (2012) 122:133–42.10.1042/CS20110233
    1. Willis PE, Chadan S, Baracos V, Parkhouse WS. Acute exercise attenuates age-associated resistance to insulin-like growth factor I. Am J Physiol (1997) 272:E397–404.
    1. Wolfe RR. Protein supplements and exercise. Am J Clin Nutr (2000) 72:551S–7S.
    1. Hoffer LJ, Bistrian BR. Appropriate protein provision in critical illness: a systematic and narrative review. Am J Clin Nutr (2012) 96:591–600.10.3945/ajcn.111.032078
    1. Hoffer LJ, Bistrian BR. Why critically ill patients are protein deprived. JPEN J Parenter Enteral Nutr (2013) 37:441.10.1177/0148607113478192
    1. Forslund AH, Hambraeus L, Olsson RM, El Khoury AE, Yu YM, Young VR. The 24-h whole body leucine and urea kinetics at normal and high protein intakes with exercise in healthy adults. Am J Physiol (1998) 275:E310–20.
    1. Dickerson RN, Maish GO, III, Croce MA, Minard G, Brown RO. Influence of aging on nitrogen accretion during critical illness. JPEN J Parenter Enteral Nutr (2015) 39:282–90.10.1177/0148607113506939
    1. Dickerson RN. Nitrogen balance and protein requirements for critically ill older patients. Nutrients (2016) 8:226.10.3390/nu8040226
    1. Moore DR, Churchward-Venne TA, Witard O, Breen L, Burd NA, Tipton KD, et al. Protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in healthy older versus younger men. J Gerontol A Biol Sci Med Sci (2015) 70:57–62.10.1093/gerona/glu103
    1. Allingstrup MJ, Esmailzadeh N, Wilkens KA, Espersen K, Hartvig JT, Wiis J, et al. Provision of protein and energy in relation to measured requirements in intensive care patients. Clin Nutr (2012) 31:462–8.10.1016/j.clnu.2011.12.006
    1. Nicolo M, Heyland DK, Chittams J, Sammarco T, Compher C. Clinical outcomes related to protein delivery in a critically ill population: a multicenter, multinational observation study. JPEN J Parenter Enteral Nutr (2016) 40:45–51.10.1177/0148607115583675
    1. Weijs PJ, Stapel SN, de Groot SD, Driessen RH, de JE, Girbes AR, et al. Optimal protein and energy nutrition decreases mortality in mechanically ventilated, critically ill patients: a prospective observational cohort study. JPEN J Parenter Enteral Nutr (2012) 36:60–8.10.1177/0148607111415109
    1. Lozano-Montoya I, Velez-Diaz-Pallares M, Abraha I, Cherubini A, Soiza RL, O’Mahony D, et al. Nonpharmacologic interventions to prevent pressure ulcers in older patients: an overview of systematic reviews (The Software ENgine for the Assessment and optimization of drug and non-drug Therapy in Older peRsons [SENATOR] definition of Optimal Evidence-Based Non-drug Therapies in Older People [ONTOP] Series). J Am Med Dir Assoc (2016) 17:370–310.10.1016/j.jamda.2015.12.091
    1. Posthauer ME, Banks M, Dorner B, Schols JM. The role of nutrition for pressure ulcer management: national pressure ulcer advisory panel, European pressure ulcer advisory panel, and pan pacific pressure injury alliance white paper. Adv Skin Wound Care (2015) 28:175–88.10.1097/01.ASW.0000461911.31139.62
    1. Cereda E, Klersy C, Serioli M, Crespi A, D’Andrea F, OligoElement Sore Trial Study Group . A nutritional formula enriched with arginine, zinc, and antioxidants for the healing of pressure ulcers: a randomized trial. Ann Intern Med (2015) 162:167–74.10.7326/M14-0696
    1. Cereda E, Gini A, Pedrolli C, Vanotti A. Disease-specific, versus standard, nutritional support for the treatment of pressure ulcers in institutionalized older adults: a randomized controlled trial. J Am Geriatr Soc (2009) 57:1395–402.10.1111/j.1532-5415.2009.02351.x
    1. van Anholt RD, Sobotka L, Meijer EP, Heyman H, Groen HW, Topinkova E, et al. Specific nutritional support accelerates pressure ulcer healing and reduces wound care intensity in non-malnourished patients. Nutrition (2010) 26:867–72.10.1016/j.nut.2010.05.009
    1. Ohura T, Nakajo T, Okada S, Omura K, Adachi K. Evaluation of effects of nutrition intervention on healing of pressure ulcers and nutritional states (randomized controlled trial). Wound Repair Regen (2011) 19:330–6.10.1111/j.1524-475X.2011.00691.x
    1. Langer G, Fink A. Nutritional interventions for preventing and treating pressure ulcers. Cochrane Database Syst Rev (2014) 6:CD003216.10.1002/14651858.CD003216.pub2
    1. Hegerova P, Dedkova Z, Sobotka L. Early nutritional support and physiotherapy improved long-term self-sufficiency in acutely ill older patients. Nutrition (2015) 31:166–70.10.1016/j.nut.2014.07.010
    1. Gariballa S, Forster S, Walters S, Powers H. A randomized, double-blind, placebo-controlled trial of nutritional supplementation during acute illness. Am J Med (2006) 119:693–9.10.1016/j.amjmed.2005.12.006
    1. Morilla-Herrera JC, Martin-Santos FJ, Caro-Bautista J, Saucedo-Figueredo C, Garcia-Mayor S, Morales-Asencio JM. Effectiveness of food-based fortification in older people. A systematic review and meta-analysis. J Nutr Health Aging (2016) 20:178–84.10.1007/s12603-015-0591-z
    1. Milne AC, Potter J, Vivanti A, Avenell A. Protein and energy supplementation in elderly people at risk from malnutrition. Cochrane Database Syst Rev (2009) 2:CD003288.10.1002/14651858.CD003288.pub3
    1. Ferreira IM, Brooks D, White J, Goldstein R. Nutritional supplementation for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev (2012) 12:CD000998.10.1002/14651858.CD000998.pub3
    1. McCarthy B, Casey D, Devane D, Murphy K, Murphy E, Lacasse Y. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev (2015) 2:CD003793.10.1002/14651858.CD003793.pub3
    1. Finger D, Goltz FR, Umpierre D, Meyer E, Rosa LH, Schneider CD. Effects of protein supplementation in older adults undergoing resistance training: a systematic review and meta-analysis. Sports Med (2015) 45:245–55.10.1007/s40279-014-0269-4
    1. Wu H, Xia Y, Jiang J, Du H, Guo X, Liu X, et al. Effect of beta-hydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: a systematic review and meta-analysis. Arch Gerontol Geriatr (2015) 61:168–75.10.1016/j.archger.2015.06.020
    1. Molfino A, Gioia G, Rossi FF, Muscaritoli M. Beta-hydroxy-beta-methylbutyrate supplementation in health and disease: a systematic review of randomized trials. Amino Acids (2013) 45:1273–92.10.1007/s00726-013-1592-z
    1. Fitschen PJ, Wilson GJ, Wilson JM, Wilund KR. Efficacy of beta-hydroxy-beta-methylbutyrate supplementation in elderly and clinical populations. Nutrition (2013) 29:29–36.10.1016/j.nut.2012.05.005
    1. Wilkinson DJ, Hossain T, Hill DS, Phillips BE, Crossland H, Williams J, et al. Effects of leucine and its metabolite beta-hydroxy-beta-methylbutyrate on human skeletal muscle protein metabolism. J Physiol (2013) 591:2911–23.10.1113/jphysiol.2013.253203
    1. Bruce M, Constantin-Teodosiu D, Greenhaff PL, Boobis LH, Williams C, Bowtell JL. Glutamine supplementation promotes anaplerosis but not oxidative energy delivery in human skeletal muscle. Am J Physiol Endocrinol Metab (2001) 280:E669–75.
    1. Deutz NE, Matheson EM, Matarese LE, Luo M, Baggs GE, Nelson JL, et al. Readmission and mortality in malnourished, older, hospitalized adults treated with a specialized oral nutritional supplement: a randomized clinical trial. Clin Nutr (2016) 35:18–26.10.1016/j.clnu.2015.12.010
    1. Nunes EA, Phillips SM. Supplemental protein and energy likely account for multi-ingredient supplementation in mitigating morbidity and mortality in compromised elderly malnourished patients. Clin Nutr (2016) 35:976.10.1016/j.clnu.2016.03.026
    1. Devries MC, Phillips SM. Creatine supplementation during resistance training in older adults – a meta-analysis. Med Sci Sports Exerc (2014) 46:1194–203.10.1249/MSS.0000000000000220
    1. Moon A, Heywood L, Rutherford S, Cobbold C. Creatine supplementation: can it improve quality of life in the elderly without associated resistance training? Curr Aging Sci (2013) 6:251–7.10.2174/1874609806666131204153102
    1. Rawson ES, Venezia AC. Use of creatine in the elderly and evidence for effects on cognitive function in young and old. Amino Acids (2011) 40:1349–62.10.1007/s00726-011-0855-9
    1. Lopez RM, Casa DJ, McDermott BP, Ganio MS, Armstrong LE, Maresh CM. Does creatine supplementation hinder exercise heat tolerance or hydration status? A systematic review with meta-analyses. J Athl Train (2009) 44:215–23.10.4085/1062-6050-44.2.215
    1. Pline KA, Smith CL. The effect of creatine intake on renal function. Ann Pharmacother (2005) 39:1093–6.10.1345/aph.1E628
    1. Kley RA, Tarnopolsky MA, Vorgerd M. Creatine for treating muscle disorders. Cochrane Database Syst Rev (2013) 6:CD004760.10.1002/14651858.CD004760.pub4
    1. Schwingshackl L, Hoffmann G. Comparison of high vs. normal/low protein diets on renal function in subjects without chronic kidney disease: a systematic review and meta-analysis. PLoS One (2014) 9:e97656.10.1371/journal.pone.0097656
    1. WHO. WHO Technical Report Series 935. Protein and Amino Acid Requirements in Human Nutrition: Report of a Joint FAO/WHO/UNU Expert Consultation. Geneva: WHO; (2011). p. 93–103.
    1. Riccio E, Di NA, Pisani A. Nutritional treatment in chronic kidney disease: the concept of nephroprotection. Clin Exp Nephrol (2015) 19:161–7.10.1007/s10157-014-1041-7
    1. Goraya N, Wesson DE. Dietary management of chronic kidney disease: protein restriction and beyond. Curr Opin Nephrol Hypertens (2012) 21:635–40.10.1097/MNH.0b013e328357a69b
    1. Academy of Nutrition and Dietetics. CKD: Protein Intake 2010 (2010). Available from:
    1. KDOQI. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. (2007). Available from:
    1. Goraya N, Simoni J, Jo CH, Wesson DE. A comparison of treating metabolic acidosis in CKD stage 4 hypertensive kidney disease with fruits and vegetables or sodium bicarbonate. Clin J Am Soc Nephrol (2013) 8:371–81.10.2215/CJN.02430312
    1. Goraya N, Simoni J, Jo CH, Wesson DE. Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate. Kidney Int (2014) 86:1031–8.10.1038/ki.2014.83
    1. Feskanich D, Willett WC, Stampfer MJ, Colditz GA. Protein consumption and bone fractures in women. Am J Epidemiol (1996) 143:472–9.10.1093/oxfordjournals.aje.a008767
    1. Kerstetter JE, Kenny AM, Insogna KL. Dietary protein and skeletal health: a review of recent human research. Curr Opin Lipidol (2011) 22:16–20.10.1097/MOL.0b013e3283419441
    1. Mangano KM, Sahni S, Kerstetter JE. Dietary protein is beneficial to bone health under conditions of adequate calcium intake: an update on clinical research. Curr Opin Clin Nutr Metab Care (2014) 17:69–74.10.1097/MCO.0000000000000013
    1. Surdykowski AK, Kenny AM, Insogna KL, Kerstetter JE. Optimizing bone health in older adults: the importance of dietary protein. Aging health (2010) 6:345–57.10.2217/ahe.10.16
    1. Fenton TR, Lyon AW, Eliasziw M, Tough SC, Hanley DA. Meta-analysis of the effect of the acid-ash hypothesis of osteoporosis on calcium balance. J Bone Miner Res (2009) 24:1835–40.10.1359/jbmr.090515
    1. Wu AM, Sun XL, Lv QB, Zhou Y, Xia DD, Xu HZ, et al. The relationship between dietary protein consumption and risk of fracture: a subgroup and dose-response meta-analysis of prospective cohort studies. Sci Rep (2015) 5:9151.10.1038/srep09151
    1. Fenton TR, Tough SC, Lyon AW, Eliasziw M, Hanley DA. Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill’s epidemiologic criteria for causality. Nutr J (2011) 10:41.10.1186/1475-2891-10-41

Source: PubMed

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