History of protein requirements/measurements

  • Humayun MA, Elango R, Ball RO, Pencharz PB. Reevaluation of the protein requirement in young men with the indicator amino acid oxidation techniqueAm J Clin Nutr. 2007;86(4):995–1002
  • Hegsted DM. Assessment of nitrogen requirements. Am J Clin Nutr 31:1669–77 (1978)
  • Wolfe RR, Miller S. The recommended dietary allowance of protein: a misunderstood concept. JAMA 299:2891–3. (2008)

Reference intakes

  • 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(1):109–27.
  • World Health Organization, Food and Agriculture Organization of the United Nations, United Nations University Protein and amino acid requirements in human nutrition. Report of a joint FAO/WHO/UNU expert consultation. Singapore: WHO; 2007. 
  • Institute of Medicine. 10 Protein and Amino Acids. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. (2005)
  • Elango R, et al. Evidence that protein requirements have been significantly underestimated. Curr Opin Clin Nutr Metab Care. (2010)

Protein quality, Indicator amino acids, protein signalling pathways

Leucine Threshold

  • Devries MC, McGlory C, Bolster DR, Kamil A, Rahn M, Harkness L, Baker SK, Phillips SM. Leucine, not total protein, content of a supplement is the primary determinant of muscle protein anabolic responses in healthy older women. J Nutr. 148(7):1088–95. (2018)
  • Devries MC, McGlory C, Bolster DR, Kamil A, Rahn M, Harkness L, Baker SK, Phillips SM. Protein leucine content is a determinant of shorter- and longer-term muscle protein synthetic responses at rest and following resistance exercise in healthy older women: a randomized, controlled trial. Am J Clin Nutr. 107(2):217–26. (2018)
  • 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. 291(2):E381–E7. (2006)
  • Murphy CH, Saddler NI, Devries MC, McGlory C, Baker SK, Phillips SM. Leucine supplementation enhances integrative myofibrillar protein synthesis in free-living older men consuming lower- and higher-protein diets: a parallel-group crossover study. Am J Clin Nutr. 104(6):1594–606. (2016)

Intakes per meal

  • Layman DK, Anthony TG, Rasmussen, BB. Defining meal requirements for protein to optimize metabolic roles of amino acids. Am Jour Clinical Nutri. 101(6):June1.(2015).
  • 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. 35(6):1506–11. (2016)
  • Farsijani S, Payette H, Morais JA, Shatenstein B, Gaudreau P, Chevalier S. Even mealtime distribution of protein intake is associated with greater muscle strength, but not with 3-year physical function decline, in free-living older adults: The NuAge Study. Am J Clin Nutr. 106(1):113–24. (2017)
  • Farsijani S, Morais JA, Payette H, Gaudreau P, Shatenstein B, Gray-Donald K, Chevalier S. Relation between mealtime distribution of protein intake and lean mass loss in free-living older adults of the NuAge study. Am J Clin Nutr. 104(3):694–703. (2016)
  • Deutz NE, Wolfe RR. Is there a maximal anabolic response to protein intake with a meal?. Clin Nutr. 32(2):309–13. (2013)
  • Kim IY, Deutz NEP, Wolfe RR. Update on maximal anabolic response to dietary protein. Clin Nutr. 37(2):411–18. (2017)
  • Nair KS, Schwartz RG, Welle S. Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans. Am J Physiol. 263(5 Pt 1):E928–E34. (1992)
  • Murphy CH, Oikawa SY, Phillips SM. Dietary protein to maintain muscle mass in aging: a case for per-meal protein recommendations. J Frailty Aging. 5(1):49–58. (2016)

Metabolic responses 

Pregnancy and breastfeeding



  • Paddon-Jones D, Rasmussen B. Dietary protein recommendations and the prevention of sarcopenia. Curr Opin Clin Nutr Metab Care 12:86–90. (2009)
  • Atherton PJ, Greenhaff PL, Phillips SM, Bodine SC, Adams CM, Lang CH. Control of skeletal muscle atrophy in response to disuse: clinical/preclinical contentions and fallacies of evidenceAm J Physiol Endocrinol Metab. 311(3):E594–604. (2016)


  • Drummond MJ, Dickenson J, Fry C, Walker D, Gundermann D, Reidy P, Timmerman K, Markofski M, Paddon-Jones D, Rasmussen B, et al. Bed rest impairs skeletal muscle amino acid transporter expression, mTORC 1 signaling, and protein synthesis in response to essential amino acids in older adults. Am J Physiol Endocrinol Metab 2012;302:E1113–22.
  • Burd NA, Gorissen SH, van Loon LJ. Anabolic resistance of muscle protein synthesis with agingExerc Sport Sci Rev. (2013)
  • Ten Haaf DSM, et al. Protein supplementation improves lean body mass in physically active older adults: a randomized placebo-controlled trialJ Cachexia Sarcopenia Muscle. (2019)
  • Cuthbertson D, Smith K, Babraj J, Leese G, Waddell T, Atherton P, Wackerhage H, Taylor PM, Rennie MJ. Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J. 19(3):422–4.(2005)
  • Institute of Medicine Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. Washington, DC: National Academies Press; 2005. 
  • Traylor DA, Gorissen SH, Philips SM. Protein requirements and optimal intakes in aging: are we ready to recommend more than the RDA?. Adv Nutr. ;9(3):171–82. (2018)
  • Kumar V, Selby A, Rankin D, Patel R, Atherton P, Hildebrandt W, Williams J, Smith K, Seynnes O, Hiscock N et al. . Age-related differences in the dose-response relationship of muscle protein synthesis to resistance exercise in young and old men. J Physiol. 587(Pt 1):211–17. (2009)
  • Moore DR, Churchward-Venne TA, Witard O, Breen L, Burd NA, Tipton KD, Phillips SM. 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(1):57–62. 
  • Wall BT, Gorissen SH, Pennings B, Koopman R, Groen BB, Verdijk LB, van Loon LJ. Aging is accompanied by a blunted muscle protein synthetic response to protein ingestion. PLoS One. 10(11):e0140903. (2015)
  • Campbell WW, Johnson CA, McCabe GP, Carnell NS. Dietary protein requirements of younger and older adults. Am J Clin Nutr. 88(5):1322–9. (2008)
  • Kim IY, Schutzler S, Schrader A, Spencer H, Kortebein P, Deutz NE, Wolfe RR, Ferrando AA. Quantity of dietary protein intake, but not pattern of intake, affects net protein balance primarily through differences in protein synthesis in older adults. Am J Physiol Endocrinol Metab. 2015;308(1):E21–8. 
  • Santesso N, et al. Effects of higher- versus lower-protein diets on health outcomes: a systematic review and meta-analysis. Eur J Clin Nutr. (2012)
  • English KL, Paddon-Jones D. Protecting muscle mass and function in older adults during bed rest. Curr Opin Clin Nutr Metab Care 13:34–9. (2010)
  • Katsanos CS, Kobayashi H, Sheffield-Moore M, Aarsland A, Wolfe R. Aging is associated with diminished accretion of muscle proteins after the ingestion of a small bolus of essential amino acids. Am J Clin Nutr 82:1065–73. (2005)
  • Fry CS, Drummond M, Glynn E, Dickinson J, Gundermann D, Timmerman K, Walker D, Dhanani S, Volpi E, Rasmussen B. Aging impairs contraction-induced human skeletal muscle mTORC1 signaling and protein synthesis. Skeletal Muscle 1:11–21. (2011)
  • Bauer J, Biolo G, Cederholm T, Cesari M, Cruz-Jentoft A, Morley J, Phillips S, Sieber C, Stehle P, Teta D, 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. (2013)


  • Mathus-Vliegen EM, Obesity Management Task Force of the European Association for the Study of Obesity. Prevalence, pathophysiology, health consequences and treatment options of obesity in the elderly: a guidelineObes Facts. (2012)
  • Jensen MD, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity SocietyJ Am Coll Cardiol. (2014)
  • Blüher M. Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance?Clin Sci (Lond). (2016)
  • Layman DK, Evans E, Erickson D, Seyler J, Weber J, Bagshaw D, Griel A, Psota T, Kris-Etherton P. A moderate-protein diet produces sustained weight loss and long-term changes in body composition and blood lipids in obese adults. J Nutr ;139:514–21. (2009)
  • Leidy HJ, Ortinau L, Douglas S, Hoertel H. Beneficial effect of a higher-protein breakfast on the appetitive, hormonal, and neural signals controlling energy intake regulation in overweight/obese, “breakfast-skipping,” late-adolescent girls. Am J Clin Nutr 97:677–88. (2013).
  • Simpson SJ, Raubenheimer D. Obesity: the protein leverage hypothesis. Obes Rev 6:133–42. (2005) 
  • Fujita S, Rasmussen B, Cadenas J, Drummond M, Glynn E, Sattler F, Volpi E. Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling. Diabetes 56:1615–22. (2007)
  • Newgard CB, An J, Bain J, Muehlbauer M, Stevens R, Lien L, Hagg, Shah S, Arlotto M, Slentz C, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab 9:311–26. (2009)
  • Adams SH. Emerging perspectives on essential amino acid metabolism in obesity and the insulin-resistant state. Adv Nutr 2:445–56. (2011)
  • DK Layman, E Evans, JI Baum, J Seyler, DJ Erickson, RA Boileau. Dietary protein and exercise have additive effects on body composition during weight loss in adult women. The Journal of nutrition 135 (8), 1903-1910. (2005).

Athletes and exercise

Issues with nutritional epidemiology

  • Cainzos-Achirica, M; Biall, U; et al. Methodological Isssues in Nutritional Epidemiology Research – Sorting Through the Confusion. Current Cardiovascular Risk Reports. Volume 12, article number 4. (2018).
  • Prentice, RL.Dietary assessment and the reliability of Nutritional Epidemiology research reports. jnci.oxfordjournals.org. (2010).
  • Kamangar, F; Karimi, P. The State of Nutritional Epidemiology: Why We Are Still Unsure of What We Should Eat? Achiives of Iranian Medicine: 16(8):483-6. (2013)
  • Prentice, RL; Huang, Y. Nutritional epidemiology methods and related statistical challenges and opportunities. Statistical Theory and Related Fields. Vol-2; Issue 1. (2018)
  • Peace, KE; Yin, J; et al. A serious flaw in nutritional epidemiology: A meta-analysis study. The International Journal of Biostatistics. Vol 14:Issue 2. (2018)

Plant Proteins

  • Gorissen SHM, Crombag JJR, Senden JMG, Waterval WAH, Bierau J, Verdijk LB, van Loon LJC. Protein content and amino acid composition of commercially available plant-based protein isolates. Amino Acids. 50(12):1685–95. (2018)
  • Food and Agriculture Organization of the United Nations Dietary protein quality evaluation in human nutrition. Report of an FAO expert consultation. FAO Food and Nutrition Paper 92. Rome: FAO; 2013.

Protein intakes and health risks

  • Wolfe RR. The underappreciated role of muscle in health and disease. Am J Clin Nutr 2006;84:475–82.
  • Devries MC, Sithamparapillai A, Brimble KS, Banfield L, Morton RW, Phillips SM. Changes in kidney function do not differ between healthy adults consuming higher- compared with lower- or normal-protein diets: a systematic review and meta-analysis. J Nutr. 148(11):1760–75. (2018)
  • Van Elswyk ME, Weatherford CA, McNeill SH. A systematic review of renal health in healthy individuals associated with protein intake above the US recommended daily allowance in randomized controlled trials and observational studies. Adv Nutr. 9(4):404–18. (2018)
  • 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. 9(5):e97656. (2014)
  • Surdykowski AK, Kenny AM, Insogna KL, Kerstetter JE. Optimizing bone health in older adults: the importance of dietary protein. Aging Health. 6(3):345–57. (2010) 
  • Groenendijk I, den Boeft L, van Loon LJC, de Groot L. High versus low dietary protein intake and bone health in older adults: a systematic review and meta-analysis. Comput Struct Biotechnol J. 17:1101–12. (2019).
  • Bilancio G, Cavallo P, Ciacci C, Cirillo M. Dietary protein, kidney function and mortality: review of the evidence from epidemiological studies. Nutrients. 11(1):196–205. (2019)
  • Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F, Fontana L, Mirisola MG, Guevara-Aguirre J, Wan J et al. . Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. (3):407–17. (2019)
  • Ikizler T, Cano N, Franch H, Fouque D, Himmelfarb J, Kalantar-Zadeh K, Kuhlmann M, Stenvinkel P, Terwee P, Teta D, et al. Prevention and treatment of protein energy wasting in chronic kidney disease patients: a consensus statement by the International Society of Renal Nutrition and Metabolism. Kidney Int ;84:1096–107.(2013)