Intake of low-dose leucine-rich essential amino acids stimulates muscle anabolism equivalently to bolus whey protein in older women at rest and after exercise

American Journal of Physiology - Endocrinology and Metabolism

Volumn 308, Issue 12, 2015, Pages E1056-E1065

  Bukhari, Syed S I ^a   Phillips, Bethan E ^a   Wilkinson, Daniel J ^a   Limb, Marie C ^a   Rankin, Debbie ^a   Mitchell, William K ^a   Kobayashi, Hisamine ^b   Greenhaff, Paul L ^a   Smith, Kenneth ^a   Atherton, Philip J ^a  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^b AJINOMOTO CO INC   (Japan)

Author keywords

Aging; Amino acids; Blood flow; Exercise; Protein synthesis; Skeletal muscle

Indexed keywords

ALBUMIN; ESSENTIAL AMINO ACID; INSULIN; LEUCINE; MILK PROTEIN; AMINO ACIDS, ESSENTIAL; DIETARY PROTEINS; MILK PROTEINS; MUSCLE PROTEINS; WHEY PROTEIN;

AGED; AMINO ACID COMPOSITION; ARTICLE; BLOOD FLOW; DIETARY INTAKE; EXERCISE; FEMALE; HUMAN; INSULIN BLOOD LEVEL; INSULINEMIA; MUSCLE METABOLISM; NUTRITIONAL HEALTH; PHYSICAL ACTIVITY; PRIORITY JOURNAL; PROTEIN SYNTHESIS; REST; SARCOPENIA; SKELETAL MUSCLE; ADMINISTRATION AND DOSAGE; BIOSYNTHESIS; BLOOD; CONTROLLED STUDY; DIET; DIETARY PROTEINS; DIETARY SUPPLEMENTS; DRUG EFFECTS; HUMANS; METABOLISM; MIDDLE AGED; MUSCLE, SKELETAL; PHYSIOLOGY; RANDOMIZED CONTROLLED TRIAL;

AGED; AMINO ACIDS, ESSENTIAL; DIET; DIETARY PROTEINS; DIETARY SUPPLEMENTS; EXERCISE; FEMALE; HUMANS; INSULIN; LEUCINE; MIDDLE AGED; MILK PROTEINS; MUSCLE PROTEINS; MUSCLE, SKELETAL; REST;

EID: 84931051232     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00481.2014     Document Type: Article

References (63)

1. Arango-Lopera VE, Arroyo P, Gutiérrez-Robledo LM, Pérez-Zepeda MU, Cesari M. Mortality as an adverse outcome of sarcopenia. J Nutr Health Aging 17: 259–262, 2013.
2. Atherton PJ, Etheridge T, Watt PW, Wilkinson D, Selby A, Rankin D, Smith K, Rennie MJ. Muscle full effect after oral protein: time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling. Am J Clin Nutr: 1080–1088, 2010.
3. Atherton PJ, Smith K, Etheridge T, Rankin D, Rennie MJ. Distinct anabolic signalling responses to amino acids in C2C12 skeletal muscle cells. Amino Acids 38: 1533–1539, 2010.
4. Baumgartner RN, Koehler KM, Romero L, Garry PJ. Serum albumin is associated with skeletal muscle in elderly men and women. Am J Clin Nutr 64: 552–558, 1996.
5. 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 532: 575–579, 2001.
6. Breen L, Stokes KA, Churchward-Venne TA, Moore DR, Baker SK, Smith K, Atherton PJ, Phillips SM. Two weeks of reduced activity decreases leg lean mass and induces “anabolic resistance” of myofibrillar protein synthesis in healthy elderly. J Clin Endocrinol Metab 98: 2604–2612, 2013.
7. Casperson SL, Sheffield-Moore M, Hewlings SJ, Paddon-Jones D. Leucine supplementation chronically improves muscle protein synthesis in older adults consuming the RDA for protein. Clin Nutr 31: 512–519, 2012.
8. Chalé A, Cloutier GJ, Hau C, Phillips EM, Dallal GE, Fielding RA. Efficacy of whey protein supplementation on resistance exercise-induced changes in lean mass, muscle strength, and physical function in mobility-limited older adults. J Gerontol A Biol Sci Med Sci 68: 682–690, 2013.
9. Churchward-Venne TA, Burd NA, Phillips SM. Nutritional regulation of muscle protein synthesis with resistance exercise: strategies to enhance anabolism. Nutr Metab (Lond) 9: 40, 2012.
10. Churchward-Venne TA, Breen L, Di Donato DM, Hector AJ, Mitchell CJ, Moore DR, Stellingwerff T, Breuille D, Offord EA, Baker SK, Phillips SM. Leucine supplementation of a low-protein mixed macronu-trient beverage enhances myofibrillar protein synthesis in young men: a double-blind, randomized trial. Am J Clin Nutr 99: 276–286, 2014.
11. Churchward-Venne TA, Burd NA, Mitchell CJ, West DW, Philp A, Marcotte GR, Baker SK, Baar K, Phillips SM. 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 590: 2751–2765, 2012.
12. Corti MC, Guralnik JM, Salive ME, Sorkin JD. Serum albumin level and physical disability as predictors of mortality in older persons. JAMA 272: 1036–1042, 1994.
13. Dickinson JM, Gundermann DM, Walker DK, Reidy PT, Borack MS, Drummond MJ, Arora M, Volpi E, Rasmussen BB. Leucine-enriched amino acid ingestion after resistance exercise prolongs myofibrillar protein synthesis and amino acid transporter expression in older men. J Nutr 144: 1694–702, 2014.
14. Dietrichson P, Coakley J, Smith PE, Griffiths RD, Helliwell TR, Edwards RH. Conchotome and needle percutaneous biopsy of skeletal muscle. J Neurol Neurosurg Psychiatry 50: 1461–7, 1987.
15. Dillon EL, Casperson SL, Durham WJ, Randolph KM, Urban RJ, Volpi E, Ahmad M, Kinsky MP, Sheffield-Moore M. Muscle protein metabolism responds similarly to exogenous amino acids in healthy younger and older adults during NO-induced hyperemia. Am J Physiol Regul Integr Comp Physiol 301: R1408–R1417, 2011.
16. Farnfield MM, Breen L, Carey KA, Garnham A, Cameron-Smith D. Activation of mTOR signalling in young and old human skeletal muscle in response to combined resistance exercise and whey protein ingestion. Appl Physiol Nutr Metab 37: 21–30, 2012.
17. Fielding RA, Vellas B, Evans WJ, Bhasin S, Morley JE, Newman AB, Abellan van Kan G, Andrieu S, Bauer J, Breuille D, Cederholm T, Chandler J, De Meynard C, Donini L, Harris T, Kannt A, Keime Guibert F, Onder G, Papanicolaou D, Rolland Y, Rooks D, Sieber C, Souhami E, Verlaan S, Zamboni M. Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. J Am Med Dir Assoc 12: 249–256, 2011.
18. 18. Fry CS, Drummond MJ, Glynn EL, Dickinson JM, Gundermann DM, Timmerman KL, Walker DK, Dhanani S, Volpi E, Rasmussen BB. Aging impairs contraction-induced human skeletal muscle mTORC1 signaling and protein synthesis. Skelet Muscle 1: 11, 2011.
19. Fukagawa NK. Protein and amino acid supplementation in older humans. Amino Acids 44: 1493–1509, 2013.
20. Glover EI, Phillips SM, Oates BR, Tang JE, Tarnopolsky MA, Selby A, Smith K, Rennie MJ. Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion. J Physiol 586: 6049–6061, 2008.
21. Gran P, Cameron-Smith D. The actions of exogenous leucine on mTOR signalling and amino acid transporters in human myotubes. BMC Physiol 11: 10, 2011.
22. Greenhaff PL, Karagounis LG, Peirce N, Simpson EJ, Hazell M, Layfield R, Wackerhage H, Smith K, Atherton P, Selby A, Rennie MJ. Disassociation between the effects of amino acids and insulin on signaling, ubiquitin ligases, and protein turnover in human muscle. Am J Physiol Endocrinol Metab 295: E595–E604, 2008.
23. Greig CA, Gray C, Rankin D, Young A, Mann V, Noble B, Atherton PJ. Blunting of adaptive responses to resistance exercise training in women over 75y. Exp Gerontol 46: 884–890, 2011.
24. Guillet C, Prod’homme M, Balage M, Gachon P, Giraudet C, Morin L, Grizard J, Boirie Y. Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans. FASEB J 18: 1586–1587, 2004.
25. Haegens A, Schols AM, van Essen AL, van Loon LJ, Langen RC. Leucine induces myofibrillar protein accretion in cultured skeletal muscle through mTOR dependent and -independent control of myosin heavy chain mRNA levels. Mol Nutr Food Res 56: 741–752, 2012.
26. Häkkinen K, Kraemer WJ, Newton RU, Alen M. Changes in electro-myographic activity, muscle fibre and force production characteristics during heavy resistance/power strength training in middle-aged and older men and women. Acta Physiol Scand 171: 51–62, 2001.
27. Han JM, Jeong SJ, Park MC, Kim G, Kwon NH, Kim HK, Ha SH, Ryu SH, Kim S. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell 149: 410–424, 2012.
28. Hulmi JJ, Lockwood CM, Stout JR. Effect of protein/essential amino acids and resistance training on skeletal muscle hypertrophy: A case for whey protein. Nutr Metab (Lond) 7: 51, 2010.
29. Ivey FM, Roth SM, Ferrell RE, Tracy BL, Lemmer JT, Hurlbut DE, Martel GF, Siegel EL, Fozard JL, Jeffrey Metter E, Fleg JL, Hurley BF. Effects of age, gender, and myostatin genotype on the hypertrophic response to heavy resistance strength training. J Gerontol A Biol Sci Med Sci 55: M641–M648, 2000.
30. Kim HK, Suzuki T, Saito K, Yoshida H, Kobayashi H, Kato H, Katayama M. Effects of exercise and amino acid supplementation on body composition and physical function in community-dwelling elderly Japanese sarcopenic women: a randomized controlled trial. J Am Geriatr Soc 60: 16–23, 2012.
31. Klonoff-Cohen H, Barrett-Connor EL, Edelstein SL. Albumin levels as a predictor of mortality in the healthy elderly. J Clin Epidemiol 45: 207–212, 1992.
32. Kosek DJ, Kim JS, Petrella JK, Cross JM, Bamman MM. Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic mechanisms in young vs. older adults. J Appl Physiol 101: 531–544, 2006.
33. Kumar V, Atherton P, Smith K, Rennie MJ. Human muscle protein synthesis and breakdown during and after exercise. J Appl Physiol 106: 2026–2039, 2009.
34. Kumar V, Atherton PJ, Selby A, Rankin D, Williams J, Smith K, Hiscock N, Rennie MJ. Muscle protein synthetic responses to exercise: effects of age, volume, and intensity. J Gerontol A Biol Sci Med Sci 67: 1170–1177, 2012.
35. Kumar V, Selby A, Rankin D, Patel R, Atherton P, Hildebrandt W, Williams J, Smith K, Seynnes O, Hiscock N, Rennie MJ. Age-related differences in the dose-response relationship of muscle protein synthesis to resistance exercise in young and old men. J Physiol 587: 211–217, 2009.
36. MacLennan WJ, Martin P, Mason BJ. Protein intake and serum albumin levels in the elderly. Gerontology 23: 360–367, 1977.
37. Martel GF, Roth SM, Ivey FM, Lemmer JT, Tracy BL, Hurlbut DE, Metter EJ, Hurley BF, Rogers MA. Age and sex affect human muscle fibre adaptations to heavy-resistance strength training. Exp Physiol 91: 457–464, 2006.
38. Merriwether EN, Host HH, Sinacore DR. Sarcopenic indices in community-dwelling older adults. J Geriatr Phys Ther 35: 118–125, 2012.
39. Mitchell WK, Phillips BE, Williams JP, Rankin D, Smith K, Lund JN, Atherton PJ. Development of a new SonovueTM contrast-enhanced ultrasound approach reveals temporal and age-related features of muscle microvascular responses to feeding. Physiol Rep 1: e00119, 2013.
40. Moreau K, Walrand S, Boirie Y. Protein redistribution from skeletal muscle to splanchnic tissue on fasting and refeeding in young and older healthy individuals. J Am Med Dir Assoc 14: 696–704, 2013.
41. 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 Endocri-nol Metab 286: E321–E328, 2004.
42. Parise G, Yarasheski KE. The utility of resistance exercise training and amino acid supplementation for reversing age-associated decrements in muscle protein mass and function. Curr Opin Clin Nutr Metab Care 3: 489–495, 2000.
43. Pennings B, Groen B, de Lange A, Gijsen AP, Zorenc AH, Senden JM, van Loon LJ. Amino acid absorption and subsequent muscle protein accretion following graded intakes of whey protein in elderly men. Am J Physiol Endocrinol Metab 302: E992–E999, 2012.
44. Phillips B, Williams J, Atherton P, Smith K, Hildebrandt W, Rankin D, Greenhaff P, Macdonald I, Rennie MJ. Resistance exercise training improves age-related declines in leg vascular conductance and rejuvenates acute leg blood flow responses to feeding and exercise. J Appl Physiol 112: 347–353, 2012.
45. Phillips BE, Atherton PJ, Varadhan K, Wilkinson DJ, Limb M, Selby AL, Rennie MJ, Smith K, Williams JP. Pharmacological enhancement of leg and muscle microvascular blood flow does not augment anabolic responses in skeletal muscle of young men under fed conditions. Am J Physiol Endocrinol Metab 306: E168–E176, 2014.
46. Rondanelli M, Opizzi A, Antoniello N, Boschi F, Iadarola P, Pasini E, Aquilani R, Dioguardi FS. Effect of essential amino acid supplementation on quality of life, amino acid profile and strength in institutionalized elderly patients. Clin Nutr 30: 571–577, 2011.
47. Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L, Sabatini DM. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320: 1496–1501, 2008.
48. Schalk BW, Deeg DJ, Penninx BW, Bouter LM, Visser M. Serum albumin and muscle strength: a longitudinal study in older men and women. J Am Geriatr Soc 53: 1331–1338, 2005.
49. Schalk BW, Visser M, Penninx BW, Baadenhuijsen H, Bouter LM, Deeg DJ. Change in serum albumin and subsequent decline in functional status in older persons. Aging Clin Exp Res 17: 297–305, 2005.
50. Smith GI, Atherton P, Villareal DT, Frimel TN, Rankin D, Rennie MJ, Mittendorfer B. Differences in muscle protein synthesis and anabolic signaling in the postabsorptive state and in response to food in 65–80 year old men and women. PLoS One 3: e1875, 2008.
51. 51. Smith GI, Reeds DN, Hall AM, Chambers KT, Finck BN, Mittendor- fer B. Sexually dimorphic effect of aging on skeletal muscle protein synthesis. Biol Sex Differ 3: 11, 2012.
52. Smith K, Reynolds N, Downie S, Patel A, Rennie MJ. Effects of flooding amino acids on incorporation of labeled amino acids into human muscle protein. Am J Physiol Endocrinol Metab 275: E73-E78, 1998.
53. Srikanthan P, Hevener AL, Karlamangla AS. Sarcopenia exacerbates obesity-associated insulin resistance and dysglycemia: findings from the National Health and Nutrition Examination Survey III. PLoS One 5: e10805, 2010.
54. Symons TB, Schutzler SE, Cocke TL, Chinkes DL, Wolfe RR, Pad-don-Jones D. Aging does not impair the anabolic response to a protein-rich meal. Am J Clin Nutr 86: 451–456, 2007.
55. Symons TB, Sheffield-Moore M, Mamerow MM, Wolfe RR, Paddon-Jones D. The anabolic response to resistance exercise and a protein-rich meal is not diminished by age. J Nutr Health Aging 15: 376-381, 2011.
56. Thalacker-Mercer AE, Johnson CA, Yarasheski KE, Carnell NS, Campbell WW. Nutrient ingestion, protein intake, and sex, but not age, affect the albumin synthesis rate in humans. J Nutr 137:1734-1740, 2007.
57. Timmerman KL, Dhanani S, Glynn EL, Fry CS, Drummond MJ, Jennings K, Rasmussen BB, Volpi E. A moderate acute increase in physical activity enhances nutritive flow and the muscle protein anabolic response to mixed nutrient intake in older adults. Am J Clin Nutr 95: 1403-1412, 2012.
58. Verhoeven S, Vanschoonbeek K, Verdijk LB, Koopman R, Wodzig WK, Dendale P, van Loon LJ. Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men. Am J Clin Nutr 89: 1468-1475, 2009.
59. Welinder C, Ekblad L. Coomassie staining as loading control in Western blot analysis. J Proteome Res 10: 1416-1419, 2011.
60. Welle S, Totterman S, Thornton C. Effect of Age on Muscle Hypertrophy Induced by Resistance Training. J Gerontol Ser A Biol Sci Med Sci 51A: M270-M275, 1996.
61. Wilkinson DJ, Hossain T, Hill DS, Phillips BE, Crossland H, Williams J, Loughna P, Churchward-Venne TA, Breen L, Phillips SM, Ether-idge T, Rathmacher JA, Smith K, Szewczyk NJ, Atherton PJ. Effects of leucine and its metabolite fj-hydroxy-fj-methylbutyrate on human skeletal muscle protein metabolism. J Physiol 591: 2911-2923, 2013.
62. Witard OC, Jackman SR, Breen L, Smith K, Selby A, Tipton KD. Myofibrillar muscle protein synthesis rates subsequent to a meal in response to increasing doses of whey protein at rest and after resistance exercise. Am J Clin Nutr 99: 86-95, 2014.
63. Yang Y, Breen L, Burd NA, Hector AJ, Churchward-Venne TA, Josse AR, Tarnopolsky MA, Phillips SM. Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. Br J Nutr 108: 1780-1788, 2012.