Short-term protein intake increases fractional synthesis rate of muscle protein in the elderly: meta-analysis

  • Gweon, Hyun-Soo (Department of Social Welfare, Kyungnam University) ;
  • Sung, Hee-Ja (Department of Social Welfare, Kyungbook National University) ;
  • Lee, Dae-Hee (R&D Center, Sempio Foods Company)
  • Received : 2010.04.25
  • Accepted : 2010.09.10
  • Published : 2010.10.31


The precise effects of protein intake on fractional synthesis rate (FSR) of muscle protein are still under debate. The sample size of these studies was small and the conclusions in young and elderly subjects were inconsistent. To assess the effect of dietary protein intake on the FSR level, we conducted a meta-analysis of controlled protein intake trials. Random-effects models were used to calculate the weighted mean differences (WMDs). Ten studies were included and effects of short-term protein intake were evaluated. In an overall pooled estimate, protein intake significantly increased the FSR (20 trials, 368 participants; WMD: 0.025%/h; 95%CI: 0.019-0.031; P < 0.0001). Meta-regression analysis suggested that the protein dose was positively related to the effect size (regression coefficient = 0.108%/h; 95%CI: 0.035, 0.182; P = 0.009). A subgroup analysis indicated that protein intake significantly increased FSR when the protein dose was ${\leq}$ 0.80 g/kg BW (16 trials, 308 participants; WMD: 0.027%/h; 95%CI: 0.019-0.031; P < 0.0001), but did not affect FSR when the protein dose was > 0.80 g/kg BW (4 trials, 60 participants; WMD: 0.016%/h; 95%CI: 0.004-0.029; P = 0.98). In conclusion, this study is the first integrated results showing that a short-term protein intake is effective at improving the FSR of muscle protein in the healthy elderly as well as young subjects. This beneficial effect seems to be dose-dependent when the dose levels of protein range from 0.08 to 0.80 g/kg BW.


Protein intakes;fractional synthesis rate;muscle protein;meta-analysis


Supported by : Kyungnam University


  1. Dutta C, Hadley EC. The significance of sarcopenia in old age. J Gerontol A Biol Sci Med Sci 1995;50:1-4.
  2. Evans W. Functional and metabolic consequences of sarcopenia. J Nutr 1997;127:998S-1003S.
  3. Roberts SB. Effects of aging on energy requirements and the control of food intake in men. J Gerontol A Biol Sci Med Sci 1995;50:101-6.
  4. Wolfe RR. The underappreciated role of muscle in health and disease. Am J Clin Nutr 2006;84:475-82.
  5. Balagopal P, Rooyackers OE, Adey DB, Ades PA, Nair KS. Effects of aging on in vivo synthesis of skeletal muscle myosin heavychain and sarcoplasmic protein in humans. Am J Physiol 1997;273:E790-800.
  6. Welle S, Thornton C, Jozefowicz R, Statt M. Myofibrillar protein synthesis in young and old men. Am J Physiol 1993;264:E693-8.
  7. Yarasheski KE, Pak-Loduca J, Hasten DL, Obert KA, Brown MB, Sinacore DR. Resistance exercise training increases mixed muscle protein synthesis rate in frail women and men $\geq$76 yr old. Am J Physiol 1999;277:E118-25.
  8. Marzetti E, Lees HA, Wohlgemuth SE, Leeuwenburgh C. Sacopenia of aging: Underlying cellular mechanisms and protection by calorie restriction. Biofactors 2009;35:28-35.
  9. Paddon-Jones D, Short KR, Campbell WW, Volpi E, Wolfe RR. Role of dietary protein in the sacopenia of aging. Am J Clin Nutr 2008;87:1562S-1566S.
  10. Baumgartner RN, Koehler KM, Gallagher D. Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 1998;147:755-63.
  11. Aniansson A, Sperling L, Rundgren A, Lehnberg E. Muscle function in 75-year-old men and women. A longitudinal study. Scand J Rehabil Med Suppl 1983;9:92-102.
  12. Janssen I, Shepard DS, Katzmarzyk PT, Roubenoff R. The healthcare costs of sarcopenia in the United States. J Am Geriatr Soc 2004;52:80-5.
  13. Rennie MJ, Edwards RH, Halliday D, Matthews DE, Wolman SL, Millward DJ. Muscle protein synthesis measured by stable isotope techniques in man: the effects of feeding and fasting. Clin Sci (Lond) 1982;63:519-23.
  14. Katsanos CR, 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.
  15. Borsheim E, Bui QUT, Tissier S, Kobayashi H, Ferrando AA, Wolfe RR. Effect of amino acid supplementation on muscle mass, strength and physical function in elderly. Clin Nutr 2008;27:189-95.
  16. Short KR, Vittone JL, Bigelow ML, Proctor DN, Nair KS. Age and aerobic exercise training effects on whole body and muscle protein metabolism. Am J Physiol Endocrinol Metab 2004;286: E92-101.
  17. Paddon-Jones D, Sheffield-Moore M, Zhang XJ, Volpi E, Wolf SE, Aarsland A, Ferrando AA, Wolfe RR. Amino acid ingestion improves muscle protein synthesis in the young and elderly. Am J Physiol Endocrinol Metab 2004;286:E321-8.
  18. Rieu I, Balage M, Sornet C, Giraudet C, Pujos E, Grizard J, Mosoni L, Dardevet D. Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia. J Physiol 2006;575:305-15.
  19. Volpi E, Mittendorfer B, Wolf SE, Wolfe RR. Oral amino acids stimulate muscle protein anabolism in the elderly despite higher first-pass splanchnic extraction. Am J Physiol 1999;277:E513-20.
  20. 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 2005;19:422-4.
  21. Paddon-Jones D, Sheffield-Moore M, Katsanos CS, Zhang XJ, Wolfe RR. Differential stimulation of muscle protein synthesis in elderly humans following isocaloric ingestion of amino acids or whey protein. Exp Gerontol 2006;41:215-9.
  22. Koopman R, Verdijk L, Manders RJF, Gijsen AP, Gorselink M, Pijpers E, Wagenmakers AJM, van Loon LJC. Co-ingestion of protein and leucine stimulates muscle protein synthesis rates to the same extent in young and elderly lean men. Am J Clin Nutr 2006;84:623-32.
  23. 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.
  24. Welle S, Thornton CA. High-protein meals do not enhance myofibrillar synthesis after resistance exercise in 62- to 75-yr-old men and women. Am J Physiol 1998;274:E677-83.
  25. Moore DR, Robinson MJ, Fry JL, Tang JE, Glover EI, Wilkinson SB, Prior T, Tarnopolsky MA, Phillips SM. Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. Am J Clin Nutr 2009;89:161-8.
  26. Caso G, Feiner J, Mileva I, Bryan LJ, Kelly P, Autio K, Gelato MC, McNurlan MA. Response of albumin synthesis to oral nutrients in young and elderly subject. Am J Clin Nutr 2007; 85:446-51.
  27. Bos C, Benamouzig R, Bruhat A, Roux C, Mahé S, Valensi P, Gaudichon C, Ferrière F, Rautureau J, Tomé D. Short-term protein and energy supplementation activates nitrogen kinetics and accretion in poorly nourished elderly subjects. Am J Clin Nutr 2000;71:1129-37.
  28. Engelen MPKJ, Rutten EPA, De Castro CLN, Wouters EFM, Schols AMWJ, Deutz NEP. Supplementation of soy protein with branched-chain amino acids alters protein metabolism in healthy elderly and even more in patients with chronic obstructive pulmonary disease. Am J Clin Nutr 2007;85:431-9.
  29. Katsanos CS, Chinkes DL, Paddon-Jones D, Xiao-jun Zhang X, Aarsland A, Robert R, 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.
  30. Wilkinson SB, Tarnopolsky MA, MacDonald MJ, MacDonald JR, Armstrong D, Phillips SM. Consumption of fluid skim milk promotes greater muscle protein accretion after resistance exercise than does consumption of an isonitrogenous and isoenergetic soy-protein beverage. Am J Clin Nutr 2007;85:1031-40.
  31. 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.
  32. Volpi E, Sheffield-Moore M, Rasmussen BB, Wolfe RR. Basal muscle amino acid kinetics and protein synthesis in healthy young and older men. JAMA 2001;286:1206-12.
  33. Wolfe RR, Chinkes DL. Isotope Tracers in Metabolic Research: Principles and Practice of Kinetic Analysis. New Jersey: John Wiley & Sons Inc.; 2005. p.9-76.
  34. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88.
  35. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60.
  36. Egger M, Davey Smith G, Schneider M, Minder C. Bias in metaanalysis detected by a simple, graphical test. BMJ 1997;315: 629-34.
  37. Rosenthal R. The "file drawer problem" and tolerance for null results. Psychol Bull 1979;86:638-41.
  38. Donatelli F, Schricker T, Parrella P, Asenjo F, Wykes L, Carli F. Intraoperative infusion of amino acids induces anabolism independent of the type of anesthesia. Anesth Analg 2006;103: 1549-56.
  39. Tipton KD, Ferrando AA, Phillips SM, Doyle D Jr, Wolfe RR. Postexercise net protein synthesis in human muscle from orally administered amino acids. Am J Physiol 1999;276:E628-34.
  40. Verhoeven S, Vanschoonbeek K, Verdijk LB, Koopman R, Wodzig WKWH, Dendale P, van Loon LJC. Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men. Am J Clin Nutr 2009;89:1468-75.
  41. Drummond MJ, Dreyer HC, Pennings B, Fry CS, Dhanani S, Dillon EL, Sheffield-Moore M, Volpi E, Rasmussen BB. Skeletal muscle protein anabolic response to resistance exercise and essential amino acids is delayed with aging. J Appl Physiol 2008;104:1452-61.
  42. Wolfe RR. Protein supplements and exercise. Am J Clin Nutr 2000;72:551S-557S.
  43. Houston DK, Nicklas BJ, Ding J, Harris TB, Tylavsky FA, Newman AB, Lee JS, Sahyoun NR, Visser M, Kritchevsky SB; Health ABC Study. 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.
  44. Roth E. Skeletal muscle gain: how much can be achieved by protein and amino acid administration? Curr Opin Clin Nutr Metab Care 2008;11:32-3.
  45. Lord C, Chaput JP, Aubertin-Leheudre M, Labonte M, Dionne IJ. Dietary animal protein intake: association with muscle mass index in older women. J Nutr Health Aging 2007;11:383-7.
  46. Koopman R, Verdijk LB, Beelen M, Gorselink M, Kruseman AN, Wagenmakers AJM, Kuipers H, van Loon LJC. Co-ingestion of leucine with protein does not further augment post-exercise muscle protein synthesis rates in elderly men. Br J Nutr 2008;99: 571-80.
  47. 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.
  48. Kumar V, Selby A, Rankin D, Patel R, Atherton P, Hildebrandt W, Williams J, Smith K, Seynnes O, Hiscock N, Rennie M. Age-related differences in the dose-response relationship of muscle protein synthesis to resistance exercise in young and old men. J Physiol 2009;587:211-7.
  49. Wang X, Proud CG. The mTOR pathway in the control of protein synthesis. Physiology (Bethesda) 2006;21:362-9.
  50. Rasmussen BB, Wolfe RR, Volpi E. Oral and intravenously administered amino acids produce similar effects on muscle protein synthesis in the elderly. J Nutr Health Aging 2002;6: 358-62.
  51. Campbell WW, Johnson CA, McCabe GP, Carnell NS. Dietary protein requirements of younger and older adults. Am J Clin Nutr 2008;88:1322-9.
  52. Walrand S, Short KR, Bigelow ML, Sweatt AJ, Hutson SM, Nair KS. Functional impact of high protein intake on healthy elderly people. Am J Physiol Endocrinol Metab 2008;295:E921-8.
  53. O'Mahony D, O'Leary P, Quigley EM. Aging and intestinal motility: a review of factors that affect intestinal motility in the aged. Drugs Aging 2002;19:515-27.

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