Skip to main content

Advertisement

Log in

Effects of branched-chain amino acid-rich supplementation on EWGSOP2 criteria for sarcopenia in older adults: a systematic review and meta-analysis

  • Review
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

According to criteria recommended by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), we analyzed the effects of branched-chain amino acid (BCAA)-rich supplements on muscle strength, muscle mass, and physical performance in older people.

Methods

We searched PubMed, Embase, Cochrane Library, and CINAHL from inception until March 2021. Randomized controlled trials that examined the effect of BCAA-rich supplements on older people were included. Random-effects meta-analyses and sensitivity analyses were performed. Subgroup analyses were stratified by participant and supplementation characteristics. Meta-regression analyses were performed to examine the effect of continuous variables.

Results

Thirty-five studies were included in this meta-analysis. Quality assessment revealed that 14 of 35 RCTs had some potential bias. The overall standardized mean difference (SMD) in muscle strength, muscle mass, and physical performance between the supplement and control groups was 0.35 (95% CI = [0.15, 0.55], P = 0.0007), 0.25 (95% CI = [0.10, 0.40], P = 0.0008), and 0.29 (95% CI = [0.00, 0.57], P = 0.05), respectively. Subgroup analysis revealed that essential amino acid supplementation improved handgrip strength more significantly than whey protein supplementation in older people. Meta-regression analysis revealed a significant linear relationship between improvements in handgrip strength and body mass index.

Conclusions

BCAA-rich supplementation by older people may have beneficial effects on muscle mass and strength. However, the included studies had high heterogeneity, and the results must be interpreted with caution.

Prospero registration number

CRD42020206674.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Availability of data, material, and code

Data described in the manuscript, the code book, and the analytic code will not be made available, because this study is a secondary data analysis of 35 previously published RCTs.

Abbreviations

BCAA:

Branched-chain amino acid

EAA:

Essential amino acid

EWGSOP2:

European Working Group on Sarcopenia in Older People 2

ASMM:

Appendicular skeletal muscle mass

CSA:

Cross-sectional area

CST:

Chair stand test

TUG:

Timed Up and Go

SPPB:

Short physical performance battery

SMD:

Standardized mean difference

References

  1. Larsson L, Degens H, Li M, Salviati L, Lee YI, Thompson W, Kirkland JL, Sandri M (2019) Sarcopenia: aging-related loss of muscle mass and function. Physiol Rev 99(1):427–511. https://doi.org/10.1152/physrev.00061.2017

    Article  PubMed  Google Scholar 

  2. Makanae Y, Fujita S (2015) Role of exercise and nutrition in the prevention of sarcopenia. J Nutr Sci Vitaminol (Tokyo) 61(Suppl):S125-127. https://doi.org/10.3177/jnsv.61.S125

    Article  CAS  Google Scholar 

  3. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M, Writing Group for the European Working Group on Sarcopenia in Older P, the Extended Group for E (2019) Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 48(4):601. https://doi.org/10.1093/ageing/afz046

    Article  Google Scholar 

  4. Marzetti E, Sanna T, Calvani R, Bernabei R, Landi F, Cesari M (2016) Brand new medicine for an older society. J Am Med Dir Assoc 17(6):558–559

    Article  PubMed  Google Scholar 

  5. Landi F, Calvani R, Cesari M, Tosato M, Martone AM, Ortolani E, Savera G, Salini S, Sisto A, Picca A, Marzetti E (2018) Sarcopenia: an overview on current definitions, diagnosis and treatment. Curr Protein Pept Sci 19(7):633–638. https://doi.org/10.2174/1389203718666170607113459

    Article  CAS  PubMed  Google Scholar 

  6. Jindal A, Jagdish RK (2019) Sarcopenia: ammonia metabolism and hepatic encephalopathy. Clin Mol Hepatol 25(3):270–279. https://doi.org/10.3350/cmh.2019.0015

    Article  PubMed  PubMed Central  Google Scholar 

  7. Cheng H, Kong J, Underwood C, Petocz P, Hirani V, Dawson B, O’Leary F (2018) Systematic review and meta-analysis of the effect of protein and amino acid supplements in older adults with acute or chronic conditions. Br J Nutr 119(5):527–542. https://doi.org/10.1017/S0007114517003816

    Article  CAS  PubMed  Google Scholar 

  8. Ten Haaf DSM, Nuijten MAH, Maessen MFH, Horstman AMH, Eijsvogels TMH, Hopman MTE (2018) Effects of protein supplementation on lean body mass, muscle strength, and physical performance in nonfrail community-dwelling older adults: a systematic review and meta-analysis. Am J Clin Nutr 108(5):1043–1059. https://doi.org/10.1093/ajcn/nqy192

    Article  PubMed  Google Scholar 

  9. Hanach NI, McCullough F, Avery A (2019) The impact of dairy protein intake on muscle mass, muscle strength, and physical performance in middle-aged to older adults with or without existing sarcopenia: a systematic review and meta-analysis. Adv Nutr 10(1):59–69. https://doi.org/10.1093/advances/nmy065

    Article  PubMed  PubMed Central  Google Scholar 

  10. Liao CD, Chen HC, Huang SW, Liou TH (2019) The role of muscle mass gain following protein supplementation plus exercise therapy in older adults with sarcopenia and frailty risks: a systematic review and meta-regression analysis of randomized trials. Nutrients. https://doi.org/10.3390/nu11081713

    Article  PubMed  PubMed Central  Google Scholar 

  11. Tu DY, Kao FM, Tsai ST, Tung TH (2021) Sarcopenia among the elderly population: a systematic review and meta-analysis of randomized controlled trials. Healthcare (Basel). https://doi.org/10.3390/healthcare9060650

    Article  PubMed Central  Google Scholar 

  12. Zanini B, Simonetto A, Zubani M, Castellano M, Gilioli G (2020) The effects of cow-milk protein supplementation in elderly population: systematic review and narrative synthesis. Nutrients. https://doi.org/10.3390/nu12092548

    Article  PubMed  PubMed Central  Google Scholar 

  13. Harper AE, Miller RH, Block KP (1984) Branched-chain amino acid metabolism. Annu Rev Nutr 4:409–454. https://doi.org/10.1146/annurev.nu.04.070184.002205

    Article  CAS  PubMed  Google Scholar 

  14. Chen L, Chen Y, Wang X, Li H, Zhang H, Gong J, Shen S, Yin W, Hu H (2015) Efficacy and safety of oral branched-chain amino acid supplementation in patients undergoing interventions for hepatocellular carcinoma: a meta-analysis. Nutr J 14:67. https://doi.org/10.1186/s12937-015-0056-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gluud LL, Dam G, Les I, Marchesini G, Borre M, Aagaard NK, Vilstrup H (2017) Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD001939.pub4

    Article  PubMed  PubMed Central  Google Scholar 

  16. Tajiri K, Shimizu Y (2018) Branched-chain amino acids in liver diseases. Transl Gastroenterol Hepatol 3:47. https://doi.org/10.21037/tgh.2018.07.06

    Article  PubMed  PubMed Central  Google Scholar 

  17. Foure A, Bendahan D (2017) Is branched-chain amino acids supplementation an efficient nutritional strategy to alleviate skeletal muscle damage? a systematic review. Nutrients. https://doi.org/10.3390/nu9101047

    Article  PubMed  PubMed Central  Google Scholar 

  18. Rahimi MH, Shab-Bidar S, Mollahosseini M, Djafarian K (2017) Branched-chain amino acid supplementation and exercise-induced muscle damage in exercise recovery: a meta-analysis of randomized clinical trials. Nutrition 42:30–36. https://doi.org/10.1016/j.nut.2017.05.005

    Article  CAS  PubMed  Google Scholar 

  19. Valenzuela PL, Morales JS, Emanuele E, Pareja-Galeano H, Lucia A (2019) Supplements with purported effects on muscle mass and strength. Eur J Nutr 58(8):2983–3008. https://doi.org/10.1007/s00394-018-1882-z

    Article  CAS  PubMed  Google Scholar 

  20. Komar B, Schwingshackl L, Hoffmann G (2015) 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 19(4):437–446. https://doi.org/10.1007/s12603-014-0559-4

    Article  CAS  PubMed  Google Scholar 

  21. Tang JE, Manolakos JJ, Kujbida GW, Lysecki PJ, Moore DR, Phillips SM (2007) Minimal whey protein with carbohydrate stimulates muscle protein synthesis following resistance exercise in trained young men. Appl Physiol Nutr Metab 32(6):1132–1138. https://doi.org/10.1139/H07-076

    Article  CAS  PubMed  Google Scholar 

  22. Tang JE, Moore DR, Kujbida GW, Tarnopolsky MA (1985) Phillips SM (2009) Ingestion of whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men. J Appl Physiol 107(3):987–992. https://doi.org/10.1152/japplphysiol.00076.2009

    Article  CAS  Google Scholar 

  23. Blomstrand E, Eliasson J, Karlsson HK, Kohnke R (2006) Branched-chain amino acids activate key enzymes in protein synthesis after physical exercise. J Nutr 136(1 Suppl):269S-273S. https://doi.org/10.1093/jn/136.1.269S

    Article  CAS  PubMed  Google Scholar 

  24. Norton LE, Layman DK (2006) Leucine regulates translation initiation of protein synthesis in skeletal muscle after exercise. J Nutr 136(2):533S-537S. https://doi.org/10.1093/jn/136.2.533S

    Article  CAS  PubMed  Google Scholar 

  25. Busquets S, Alvarez B, Llovera M, Agell N, Lopez-Soriano FJ, Argiles JM (2000) Branched-chain amino acids inhibit proteolysis in rat skeletal muscle: mechanisms involved. J Cell Physiol 184(3):380–384. https://doi.org/10.1002/1097-4652(200009)184:3%3c380::AID-JCP13%3e3.0.CO;2-F

    Article  CAS  PubMed  Google Scholar 

  26. Eley HL, Russell ST, Tisdale MJ (2007) Effect of branched-chain amino acids on muscle atrophy in cancer cachexia. Biochem J 407(1):113–120. https://doi.org/10.1042/BJ20070651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. https://doi.org/10.1371/journal.pmed.1000097

    Article  Google Scholar 

  28. Campbell M, McKenzie JE, Sowden A, Katikireddi SV, Brennan SE, Ellis S, Hartmann-Boyce J, Ryan R, Shepperd S, Thomas J, Welch V, Thomson H (2020) Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. BMJ 368:l6890. https://doi.org/10.1136/bmj.l6890

    Article  PubMed  PubMed Central  Google Scholar 

  29. Shimomura Y, Murakami T, Nakai N, Nagasaki M, Harris RA (2004) Exercise promotes BCAA catabolism: effects of BCAA supplementation on skeletal muscle during exercise. J Nutr 134(6 Suppl):1583S-1587S. https://doi.org/10.1093/jn/134.6.1583S

    Article  CAS  PubMed  Google Scholar 

  30. Higgins JP, Green SE (2011) The Cochrane Collaboration. In: Cochrane handbook for systematic reviews of interventions, vol 4, issue 6. Wiley, New York

  31. Peel NM, Kuys SS, Klein K (2013) Gait speed as a measure in geriatric assessment in clinical settings: a systematic review. J Gerontol A Biol Sci Med Sci 68(1):39–46. https://doi.org/10.1093/gerona/gls174

    Article  PubMed  Google Scholar 

  32. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188. https://doi.org/10.1016/0197-2456(86)90046-2

    Article  CAS  PubMed  Google Scholar 

  33. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634. https://doi.org/10.1136/bmj.315.7109.629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Khoury B, Lecomte T, Fortin G, Masse M, Therien P, Bouchard V, Chapleau M-A, Paquin K, Hofmann SG (2013) Mindfulness-based therapy: a comprehensive meta-analysis. Clin Psychol Rev 33(6):763–771

    Article  PubMed  Google Scholar 

  35. Kirk B, Mooney K, Cousins R, Angell P, Jackson M, Pugh JN, Coyles G, Amirabdollahian F, Khaiyat O (2020) Effects of exercise and whey protein on muscle mass, fat mass, myoelectrical muscle fatigue and health-related quality of life in older adults: a secondary analysis of the Liverpool Hope University-Sarcopenia Ageing Trial (LHU-SAT). Eur J Appl Physiol 120(2):493–503. https://doi.org/10.1007/s00421-019-04293-5

    Article  CAS  PubMed  Google Scholar 

  36. Gade J, Beck AM, Andersen HE, Christensen B, Ronholt F, Klausen TW, Vinther A, Astrup A (2019) Protein supplementation combined with low-intensity resistance training in geriatric medical patients during and after hospitalisation: a randomised, double-blind, multicentre trial. Br J Nutr 122(9):1006–1020. https://doi.org/10.1017/S0007114519001831

    Article  CAS  PubMed  Google Scholar 

  37. Ikeda T, Matsunaga Y, Kanbara M, Kamono A, Masuda T, Watanabe M, Nakanishi R, Jinno T (2019) Effect of exercise therapy combined with branched-chain amino acid supplementation on muscle strength in elderly women after total hip arthroplasty: a randomized controlled trial. Asia Pac J Clin Nutr 28(4):720–726. https://doi.org/10.6133/apjcn.201912_28(4).0007

    Article  CAS  PubMed  Google Scholar 

  38. Kirk B, Mooney K, Amirabdollahian F, Khaiyat O (2019) Exercise and dietary-protein as a countermeasure to skeletal muscle weakness: Liverpool Hope University—sarcopenia aging trial (LHU-SAT). Front Physiol 10:445. https://doi.org/10.3389/fphys.2019.00445

    Article  PubMed  PubMed Central  Google Scholar 

  39. Markofski MM, Jennings K, Timmerman KL, Dickinson JM, Fry CS, Borack MS, Reidy PT, Deer RR, Randolph A, Rasmussen BB, Volpi E (2019) Effect of aerobic exercise training and essential amino acid supplementation for 24 weeks on physical function, body composition, and muscle metabolism in healthy, independent older adults: a randomized clinical trial. J Gerontol A Biol Sci Med Sci 74(10):1598–1604. https://doi.org/10.1093/gerona/gly109

    Article  CAS  PubMed  Google Scholar 

  40. Negro M, Perna S, Spadaccini D, Castelli L, Calanni L, Barbero M, Cescon C, Rondanelli M, D’Antona G (2019) Effects of 12 weeks of essential amino acids (EAA)-based multi-ingredient nutritional supplementation on muscle mass, muscle strength, muscle power and fatigue in healthy elderly subjects: a randomized controlled double-blind study. J Nutr Health Aging 23(5):414–424. https://doi.org/10.1007/s12603-019-1163-4

    Article  CAS  PubMed  Google Scholar 

  41. Kemmler W, Grimm A, Bebenek M, Kohl M, von Stengel S (2018) Effects of combined whole-body electromyostimulation and protein supplementation on local and overall muscle/fat distribution in older men with sarcopenic obesity: the randomized controlled Franconia Sarcopenic Obesity (FranSO) Study. Calcif Tissue Int 103(3):266–277. https://doi.org/10.1007/s00223-018-0424-2

    Article  CAS  PubMed  Google Scholar 

  42. Mori H, Tokuda Y (2018) Effect of whey protein supplementation after resistance exercise on the muscle mass and physical function of healthy older women: a randomized controlled trial. Geriatr Gerontol Int 18(9):1398–1404. https://doi.org/10.1111/ggi.13499

    Article  PubMed  Google Scholar 

  43. Bell KE, Snijders T, Zulyniak M, Kumbhare D, Parise G, Chabowski A, Phillips SM (2017) A whey protein-based multi-ingredient nutritional supplement stimulates gains in lean body mass and strength in healthy older men: a randomized controlled trial. PLoS ONE 12(7):e0181387. https://doi.org/10.1371/journal.pone.0181387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Chanet A, Verlaan S, Salles J, Giraudet C, Patrac V, Pidou V, Pouyet C, Hafnaoui N, Blot A, Cano N, Farigon N, Bongers A, Jourdan M, Luiking Y, Walrand S, Boirie Y (2017) Supplementing breakfast with a vitamin D and leucine-enriched whey protein medical nutrition drink enhances postprandial muscle protein synthesis and muscle mass in healthy older men. J Nutr 147(12):2262–2271. https://doi.org/10.3945/jn.117.252510

    Article  CAS  PubMed  Google Scholar 

  45. Ispoglou T, White H, Preston T, McElhone S, McKenna J, Hind K (2016) Double-blind, placebo-controlled pilot trial of l-Leucine-enriched amino-acid mixtures on body composition and physical performance in men and women aged 65–75 years. Eur J Clin Nutr 70(2):182–188. https://doi.org/10.1038/ejcn.2015.91

    Article  CAS  PubMed  Google Scholar 

  46. Verreijen AM, Verlaan S, Engberink MF, Swinkels S, de Vogel-van den Bosch J, Weijs PJ (2015) A high whey protein-, leucine-, and vitamin D-enriched supplement preserves muscle mass during intentional weight loss in obese older adults: a double-blind randomized controlled trial. Am J Clin Nutr 101(2):279–286. https://doi.org/10.3945/ajcn.114.090290

    Article  CAS  PubMed  Google Scholar 

  47. Arnarson A, Gudny Geirsdottir O, Ramel A, Briem K, Jonsson PV, Thorsdottir I (2013) Effects of whey proteins and carbohydrates on the efficacy of resistance training in elderly people: double blind, randomised controlled trial. Eur J Clin Nutr 67(8):821–826. https://doi.org/10.1038/ejcn.2013.40

    Article  CAS  PubMed  Google Scholar 

  48. Björkman M, Finne-Soveri H, Tilvis R (2012) Whey protein supplementation in nursing home residents. A randomized controlled trial. Eur Geriatr Med 3(3):161–166

    Article  Google Scholar 

  49. Dal Negro RW, Testa A, Aquilani R, Tognella S, Pasini E, Barbieri A, Boschi F (2012) Essential amino acid supplementation in patients with severe COPD: a step towards home rehabilitation. Monaldi Arch Chest Dis 77(2):67–75. https://doi.org/10.4081/monaldi.2012.154

    Article  Google Scholar 

  50. Rondanelli M, Opizzi A, Antoniello N, Boschi F, Iadarola P, Pasini E, Aquilani R, Dioguardi FS (2011) Effect of essential amino acid supplementation on quality of life, amino acid profile and strength in institutionalized elderly patients. Clin Nutr 30(5):571–577. https://doi.org/10.1016/j.clnu.2011.04.005

    Article  CAS  PubMed  Google Scholar 

  51. Godard MP, Williamson DL, Trappe SW (2002) Oral amino-acid provision does not affect muscle strength or size gains in older men. Med Sci Sports Exerc 34(7):1126–1131. https://doi.org/10.1097/00005768-200207000-00012

    Article  CAS  PubMed  Google Scholar 

  52. Boutry-Regard C, Gerard VP, Denis B, Toshio M (2020) Supplementation with whey protein, omega-3 fatty acids and polyphenols combined with electrical muscle stimulation increases muscle strength in elderly adults with limited mobility: a randomized controlled trial. Nutrients. https://doi.org/10.3390/nu12061866

    Article  PubMed  PubMed Central  Google Scholar 

  53. Englund DA, Kirn DR, Koochek A, Zhu H, Travison TG, Reid KF, von Berens A, Melin M, Cederholm T, Gustafsson T, Fielding RA (2017) Nutritional supplementation with physical activity improves muscle composition in mobility-limited older adults, the VIVE2 Study: a randomized, double-blind, placebo-controlled trial. J Gerontol A Biol Sci Med Sci 73(1):95–101. https://doi.org/10.1093/gerona/glx141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Fielding RA, Travison TG, Kirn DR, Koochek A, Reid KF, von Berens A, Zhu H, Folta SC, Sacheck JM, Nelson ME, Liu CK, Aberg AC, Nydahl M, Lilja M, Gustafsson T, Cederholm T (2017) Effect of structured physical activity and nutritional supplementation on physical function in mobility-limited older adults: results from the VIVE2 randomized trial. J Nutr Health Aging 21(9):936–942. https://doi.org/10.1007/s12603-017-0936-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chale A, Cloutier GJ, Hau C, Phillips EM, Dallal GE, Fielding RA (2013) 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(6):682–690. https://doi.org/10.1093/gerona/gls221

    Article  CAS  PubMed  Google Scholar 

  56. Buondonno I, Sassi F, Carignano G, Dutto F, Ferreri C, Pili FG, Massaia M, Nisoli E, Ruocco C, Porrino P, Ravetta C, Riganti C, Isaia GC, D’Amelio P (2020) From mitochondria to healthy aging: the role of branched-chain amino acids treatment: MATeR a randomized study. Clin Nutr 39(7):2080–2091. https://doi.org/10.1016/j.clnu.2019.10.013

    Article  CAS  PubMed  Google Scholar 

  57. Kim CO, Lee KR (2013) Preventive effect of protein-energy supplementation on the functional decline of frail older adults with low socioeconomic status: a community-based randomized controlled study. J Gerontol A Biol Sci Med Sci 68(3):309–316. https://doi.org/10.1093/gerona/gls167

    Article  CAS  PubMed  Google Scholar 

  58. Lin CC, Shih MH, Chen CD, Yeh SL (2021) Effects of adequate dietary protein with whey protein, leucine, and vitamin D supplementation on sarcopenia in older adults: an open-label, parallel-group study. Clin Nutr 40(3):1323–1329. https://doi.org/10.1016/j.clnu.2020.08.017

    Article  CAS  PubMed  Google Scholar 

  59. Bjorkman MP, Suominen MH, Kautiainen H, Jyvakorpi SK, Finne-Soveri HU, Strandberg TE, Pitkala KH, Tilvis RS (2020) Effect of protein supplementation on physical performance in older people with sarcopenia-a randomized controlled trial. J Am Med Dir Assoc 21(2):226–232. https://doi.org/10.1016/j.jamda.2019.09.006

    Article  PubMed  Google Scholar 

  60. Rondanelli M, Cereda E, Klersy C, Faliva MA, Peroni G, Nichetti M, Gasparri C, Iannello G, Spadaccini D, Infantino V, Caccialanza R, Perna S (2020) Improving rehabilitation in sarcopenia: a randomized-controlled trial utilizing a muscle-targeted food for special medical purposes. J Cachexia Sarcopenia Muscle 11(6):1535–1547. https://doi.org/10.1002/jcsm.12532

    Article  PubMed  PubMed Central  Google Scholar 

  61. Amasene M, Besga A, Echeverria I, Urquiza M, Ruiz JR, Rodriguez-Larrad A, Aldamiz M, Anaut P, Irazusta J, Labayen I (2019) Effects of leucine-enriched whey protein supplementation on physical function in post-hospitalized older adults participating in 12-weeks of resistance training program: a randomized controlled trial. Nutrients. https://doi.org/10.3390/nu11102337

    Article  PubMed  PubMed Central  Google Scholar 

  62. Bo Y, Liu C, Ji Z, Yang R, An Q, Zhang X, You J, Duan D, Sun Y, Zhu Y, Cui H, Lu Q (2019) A high whey protein, vitamin D and E supplement preserves muscle mass, strength, and quality of life in sarcopenic older adults: a double-blind randomized controlled trial. Clin Nutr 38(1):159–164. https://doi.org/10.1016/j.clnu.2017.12.020

    Article  CAS  PubMed  Google Scholar 

  63. Yoshimura Y, Bise T, Shimazu S, Tanoue M, Tomioka Y, Araki M, Nishino T, Kuzuhara A, Takatsuki F (2019) Effects of a leucine-enriched amino acid supplement on muscle mass, muscle strength, and physical function in post-stroke patients with sarcopenia: a randomized controlled trial. Nutrition 58:1–6. https://doi.org/10.1016/j.nut.2018.05.028

    Article  CAS  PubMed  Google Scholar 

  64. Rondanelli M, Peroni G, Gasparri C, Infantino V, Nichetti M, Cuzzoni G, Spadaccini D, Perna S (2018) Is a combination of melatonin and amino acids useful to sarcopenic elderly patients? A randomized trial. Geriatrics (Basel). https://doi.org/10.3390/geriatrics4010004

    Article  Google Scholar 

  65. Takeuchi I, Yoshimura Y, Shimazu S, Jeong S, Yamaga M, Koga H (2019) Effects of branched-chain amino acids and vitamin D supplementation on physical function, muscle mass and strength, and nutritional status in sarcopenic older adults undergoing hospital-based rehabilitation: a multicenter randomized controlled trial. Geriatr Gerontol Int 19(1):12–17. https://doi.org/10.1111/ggi.13547

    Article  PubMed  Google Scholar 

  66. Kim H, Kim M, Kojima N, Fujino K, Hosoi E, Kobayashi H, Somekawa S, Niki Y, Yamashiro Y, Yoshida H (2016) Exercise and nutritional supplementation on community-dwelling elderly japanese women with sarcopenic obesity: a randomized controlled trial. J Am Med Dir Assoc 17(11):1011–1019. https://doi.org/10.1016/j.jamda.2016.06.016

    Article  PubMed  Google Scholar 

  67. Rondanelli M, Klersy C, Terracol G, Talluri J, Maugeri R, Guido D, Faliva MA, Solerte BS, Fioravanti M, Lukaski H, Perna S (2016) 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 103(3):830–840. https://doi.org/10.3945/ajcn.115.113357

    Article  CAS  PubMed  Google Scholar 

  68. Bauer JM, Verlaan S, Bautmans I, Brandt K, Donini LM, Maggio M, McMurdo ME, Mets T, Seal C, Wijers SL, Ceda GP, De Vito G, Donders G, Drey M, Greig C, Holmback U, Narici M, McPhee J, Poggiogalle E, Power D, Scafoglieri A, Schultz R, Sieber CC, Cederholm T (2015) 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 16(9):740–747. https://doi.org/10.1016/j.jamda.2015.05.021

    Article  PubMed  Google Scholar 

  69. Kim HK, Suzuki T, Saito K, Yoshida H, Kobayashi H, Kato H, Katayama M (2012) 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(1):16–23. https://doi.org/10.1111/j.1532-5415.2011.03776.x

    Article  PubMed  Google Scholar 

  70. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinkova E, Vandewoude M, Zamboni M, European Working Group on Sarcopenia in Older P (2010) Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing 39(4):412–423. https://doi.org/10.1093/ageing/afq034

    Article  Google Scholar 

  71. Chen LK, Liu LK, Woo J, Assantachai P, Auyeung TW, Bahyah KS, Chou MY, Chen LY, Hsu PS, Krairit O, Lee JS, Lee WJ, Lee Y, Liang CK, Limpawattana P, Lin CS, Peng LN, Satake S, Suzuki T, Won CW, Wu CH, Wu SN, Zhang T, Zeng P, Akishita M, Arai H (2014) Sarcopenia in Asia: consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc 15(2):95–101. https://doi.org/10.1016/j.jamda.2013.11.025

    Article  PubMed  Google Scholar 

  72. Chen LK, Woo J, Assantachai P, Auyeung TW, Chou MY, Iijima K, Jang HC, Kang L, Kim M, Kim S, Kojima T, Kuzuya M, Lee JSW, Lee SY, Lee WJ, Lee Y, Liang CK, Lim JY, Lim WS, Peng LN, Sugimoto K, Tanaka T, Won CW, Yamada M, Zhang T, Akishita M, Arai H (2020) Asian Working Group for Sarcopenia: 2019 consensus update on sarcopenia diagnosis and treatment. J Am Med Dir Assoc 21(3):300–307. https://doi.org/10.1016/j.jamda.2019.12.012

    Article  PubMed  Google Scholar 

  73. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M, Writing Group for the European Working Group on Sarcopenia in Older P, the Extended Group for E (2019) Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 48(1):16–31. https://doi.org/10.1093/ageing/afy169

    Article  Google Scholar 

  74. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101

    Article  CAS  PubMed  Google Scholar 

  75. Duval S, Tweedie R (2000) Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56(2):455–463. https://doi.org/10.1111/j.0006-341x.2000.00455.x

    Article  CAS  PubMed  Google Scholar 

  76. Devries MC, Phillips SM (2015) Supplemental protein in support of muscle mass and health: advantage whey. J Food Sci 80(Suppl 1):A8–A15. https://doi.org/10.1111/1750-3841.12802

    Article  CAS  PubMed  Google Scholar 

  77. Gkekas NK, Anagnostis P, Paraschou V, Stamiris D, Dellis S, Kenanidis E, Potoupnis M, Tsiridis E, Goulis DG (2021) The effect of vitamin D plus protein supplementation on sarcopenia: a systematic review and meta-analysis of randomized controlled trials. Maturitas 145:56–63. https://doi.org/10.1016/j.maturitas.2021.01.002

    Article  CAS  PubMed  Google Scholar 

  78. Volpi E, Kobayashi H, Sheffield-Moore M, Mittendorfer B, Wolfe RR (2003) Essential amino acids are primarily responsible for the amino acid stimulation of muscle protein anabolism in healthy elderly adults. Am J Clin Nutr 78(2):250–258. https://doi.org/10.1093/ajcn/78.2.250

    Article  CAS  PubMed  Google Scholar 

  79. Rennie MJ, Bohe J, Wolfe RR (2002) Latency, duration and dose response relationships of amino acid effects on human muscle protein synthesis. J Nutr 132(10):3225S-3227S. https://doi.org/10.1093/jn/131.10.3225S

    Article  CAS  PubMed  Google Scholar 

  80. Wolfe RR (2002) Regulation of muscle protein by amino acids. J Nutr 132(10):3219S-3224S. https://doi.org/10.1093/jn/131.10.3219S

    Article  CAS  PubMed  Google Scholar 

  81. Wolfe RR (2017) Branched-chain amino acids and muscle protein synthesis in humans: myth or reality? J Int Soc Sports Nutr 14:30. https://doi.org/10.1186/s12970-017-0184-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Tessari P, Lante A, Mosca G (2016) Essential amino acids: master regulators of nutrition and environmental footprint? Sci Rep 6:26074. https://doi.org/10.1038/srep26074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kimball SR, Jefferson LS (2006) Signaling pathways and molecular mechanisms through which branched-chain amino acids mediate translational control of protein synthesis. J Nutr 136(1 Suppl):227S-231S. https://doi.org/10.1093/jn/136.1.227S

    Article  CAS  PubMed  Google Scholar 

  84. Jackman SR, Witard OC, Philp A, Wallis GA, Baar K, Tipton KD (2017) Branched-chain amino acid ingestion stimulates muscle myofibrillar protein synthesis following resistance exercise in humans. Front Physiol 8:390. https://doi.org/10.3389/fphys.2017.00390

    Article  PubMed  PubMed Central  Google Scholar 

  85. Dreyer HC, Drummond MJ, Pennings B, Fujita S, Glynn EL, Chinkes DL, Dhanani S, Volpi E, Rasmussen BB (2008) Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. Am J Physiol Endocrinol Metab 294(2):E392-400. https://doi.org/10.1152/ajpendo.00582.2007

    Article  CAS  PubMed  Google Scholar 

  86. Moberg M, Apro W, Ekblom B, van Hall G, Holmberg HC, Blomstrand E (2016) Activation of mTORC1 by leucine is potentiated by branched-chain amino acids and even more so by essential amino acids following resistance exercise. Am J Physiol Cell Physiol 310(11):C874-884. https://doi.org/10.1152/ajpcell.00374.2015

    Article  PubMed  Google Scholar 

  87. Tipton KD, Elliott TA, Cree MG, Aarsland AA, Sanford AP, Wolfe RR (2007) Stimulation of net muscle protein synthesis by whey protein ingestion before and after exercise. Am J Physiol Endocrinol Metab 292(1):E71-76. https://doi.org/10.1152/ajpendo.00166.2006

    Article  CAS  PubMed  Google Scholar 

  88. Hulmi JJ, Lockwood CM, Stout JR (2010) Effect of protein/essential amino acids and resistance training on skeletal muscle hypertrophy: a case for whey protein. Nutr Metab (Lond) 7:51. https://doi.org/10.1186/1743-7075-7-51

    Article  CAS  Google Scholar 

  89. Witard OC, Jackman SR, Breen L, Smith K, Selby A, Tipton KD (2014) 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(1):86–95. https://doi.org/10.3945/ajcn.112.055517

    Article  CAS  PubMed  Google Scholar 

  90. Chae M, Park HS, Park K (2021) Association between dietary branched-chain amino acid intake and skeletal muscle mass index among Korean adults: Interaction with obesity. Nutr Res Pract 15(2):203–212. https://doi.org/10.4162/nrp.2021.15.2.203

    Article  CAS  PubMed  Google Scholar 

  91. Gannon NP, Schnuck JK, Vaughan RA (2018) BCAA metabolism and insulin sensitivity—dysregulated by metabolic status? Mol Nutr Food Res 62(6):e1700756. https://doi.org/10.1002/mnfr.201700756

    Article  CAS  PubMed  Google Scholar 

  92. Lynch CJ, Adams SH (2014) Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol 10(12):723–736. https://doi.org/10.1038/nrendo.2014.171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, Haqq AM, Shah SH, Arlotto M, Slentz CA, Rochon J, Gallup D, Ilkayeva O, Wenner BR, Yancy WS Jr, Eisenson H, Musante G, Surwit RS, Millington DS, Butler MD, Svetkey LP (2009) A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab 9(4):311–326. https://doi.org/10.1016/j.cmet.2009.02.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Schrager MA, Metter EJ, Simonsick E, Ble A, Bandinelli S, Lauretani F, Ferrucci L (2007) Sarcopenic obesity and inflammation in the InCHIANTI study. J Appl Physiol 102(3):919–925. https://doi.org/10.1152/japplphysiol.00627.2006

    Article  PubMed  Google Scholar 

  95. Forsythe LK, Wallace JM, Livingstone MB (2008) Obesity and inflammation: the effects of weight loss. Nutr Res Rev 21(2):117–133. https://doi.org/10.1017/S0954422408138732

    Article  CAS  PubMed  Google Scholar 

  96. Park HS, Park JY, Yu R (2005) Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6. Diabetes Res Clin Pract 69(1):29–35. https://doi.org/10.1016/j.diabres.2004.11.007

    Article  CAS  PubMed  Google Scholar 

  97. Ribeiro RV, Solon-Biet SM, Pulpitel T, Senior AM, Cogger VC, Clark X, O’Sullivan J, Koay YC, Hirani V, Blyth FM, Seibel MJ, Waite LM, Naganathan V, Cumming RG, Handelsman DJ, Simpson SJ, Le Couteur DG (2019) Of older mice and men: branched-chain amino acids and body composition. Nutrients. https://doi.org/10.3390/nu11081882

    Article  PubMed  PubMed Central  Google Scholar 

  98. Batsis JA, Villareal DT (2018) Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies. Nat Rev Endocrinol 14(9):513–537. https://doi.org/10.1038/s41574-018-0062-9

    Article  PubMed  PubMed Central  Google Scholar 

  99. Prokopidis K, Cervo MM, Gandham A, Scott D (2020) Impact of protein intake in older adults with sarcopenia and obesity: a gut microbiota perspective. Nutrients. https://doi.org/10.3390/nu12082285

    Article  PubMed  PubMed Central  Google Scholar 

  100. Muscogiuri G, Cantone E, Cassarano S, Tuccinardi D, Barrea L, Savastano S, Colao A, on behalf of the Obesity Programs of nutrition ER, Assessment g (2019) Gut microbiota: a new path to treat obesity. Int J Obes Suppl 9(1):10–19. https://doi.org/10.1038/s41367-019-0011-7

    Article  Google Scholar 

  101. Hamilton B (2011) Vitamin d and athletic performance: the potential role of muscle. Asian J Sports Med 2(4):211–219. https://doi.org/10.5812/asjsm.34736

    Article  PubMed  PubMed Central  Google Scholar 

  102. Pojednic RM, Ceglia L (2014) The emerging biomolecular role of vitamin D in skeletal muscle. Exerc Sport Sci Rev 42(2):76–81. https://doi.org/10.1249/JES.0000000000000013

    Article  PubMed  PubMed Central  Google Scholar 

  103. Paulsen G, Hamarsland H, Cumming KT, Johansen RE, Hulmi JJ, Borsheim E, Wiig H, Garthe I, Raastad T (2014) Vitamin C and E supplementation alters protein signalling after a strength training session, but not muscle growth during 10 weeks of training. J Physiol 592(24):5391–5408. https://doi.org/10.1113/jphysiol.2014.279950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Mero A (1999) Leucine supplementation and intensive training. Sports Med 27(6):347–358. https://doi.org/10.2165/00007256-199927060-00001

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Authors’ responsibilities: GHB, MCT, and WHH designed the research; GHB and MCT conducted the research; GHB and MCT analyzed the data; GHB, MCT, and WHH wrote the manuscript; GHB, MCT, and WHH had primary responsibility for final content. Wallace Academic Editing edited this manuscript

Funding

No funding, grants, or equipment were provided for the project from any source. The authors have received no financial benefits associated with this work. This work has not been presented previously.

Author information

Authors and Affiliations

Authors

Contributions

GHB, MCT, and WHH designed the research; GHB and MCT conducted the research; GHB and MCT analyzed the data; GHB, MCT, and WHH wrote the manuscript; GHB, MCT, and WHH had primary responsibility for final content.

Corresponding author

Correspondence to Wen-Hsuan Hou.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest in relation to this work.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 590 KB)

Supplementary file2 (DOCX 125 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bai, GH., Tsai, MC., Tsai, HW. et al. Effects of branched-chain amino acid-rich supplementation on EWGSOP2 criteria for sarcopenia in older adults: a systematic review and meta-analysis. Eur J Nutr 61, 637–651 (2022). https://doi.org/10.1007/s00394-021-02710-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-021-02710-0

Keywords

Navigation