Advertisement

Drugs & Aging

, Volume 34, Issue 11, pp 833–840 | Cite as

The Potential of β-Hydroxy-β-Methylbutyrate as a New Strategy for the Management of Sarcopenia and Sarcopenic Obesity

  • Andrea P. RossiEmail author
  • Alessia D’Introno
  • Sofia Rubele
  • Cesare Caliari
  • Stefano Gattazzo
  • Elena Zoico
  • Gloria Mazzali
  • Francesco Fantin
  • Mauro Zamboni
Review Article

Abstract

Sarcopenia is defined as an age-related loss of skeletal muscle mass and function and is recognized as a major clinical problem for older people. Essential amino acid supplementation, particularly β-hydroxy-β-methylbutyrate (HMB), a metabolite of leucine that is produced in skeletal muscle, has been evaluated in several studies as a nutritional approach to enhancing muscle protein synthesis in healthy or frail elderly subjects. Studies performed in in vitro conditions show that HMB may be effective in the treatment of muscle wasting, increasing myogenesis, reducing muscle apoptosis, and having a positive effect on muscle protein turnover; however, studies of the effects of HMB conducted in old animals have reported conflicting results. Clinical trials performed in older adults confirm that HMB can attenuate the progression of sarcopenia in elderly subjects. HMB supplementation results in an increase in skeletal muscle mass and strength in the elderly and its effect is even greater when combined with physical exercise. The role of HMB in sarcopenic obesity management is still under debate and a general lack of intervention studies in this population must be recognized. In conclusion, HMB appears to be effective for enhancing muscle mass and strength in the elderly. Less certain is the role of HMB supplementation in reducing fat mass and, thus, in the treatment of sarcopenic obesity.

Notes

Acknowledgements

The article was revised by a native English speaker, Professor Mark J. Newman.

Compliance with Ethical Standards

Funding

No sources of funding were used to assist in the preparation of this article.

Conflict of interest

Andrea Rossi, Alessia D’Introno, Sofia Rubele, Cesare Caliari, Stefano Gattazzo, Elena Zoico, Gloria Mazzali, Francesco Fantin and Mauro Zamboni declare they have no conflicts of interest relevant to the content of this review.

References

  1. 1.
    Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010;39(4):412–23.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Volpi E, Rasmussen BB. Nutrition and muscle protein metabolism in the elderly. Diabetes Nutr Metab. 2000;13:99–107.PubMedGoogle Scholar
  3. 3.
    Morley JE, Argiles JM, Evans WJ, Society for Sarcopenia, Cachexia, and Wasting Disease, et al. Nutritional recommendations for the management of sarcopenia. J Am Med Dir Assoc. 2010;11:391–6.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Kerstetter JE, O’Brien KO, Insogna KL. Low protein intake: the impact on calcium and bone homeostasis in humans. J Nutr. 2003;133:855S–61S.PubMedGoogle Scholar
  5. 5.
    Fulgoni VL 3rd. Current protein intake in America: analysis of the National Health and Nutrition Examination Survey, 2003–2004. Am J Clin Nutr. 2008;87:1554S–7S.PubMedGoogle Scholar
  6. 6.
    Eley HL, Russell ST, Baxter JH, et al. Signaling pathways initiated by beta-hydroxy-beta-methylbutyrate to attenuate the depression of protein synthesis in skeletal muscle in response to cachectic stimuli. Am J Physiol Endocrinol Metab. 2007;293:E923–31.CrossRefPubMedGoogle Scholar
  7. 7.
    Girón MD, Vílchez JD, Salto R, et al. Conversion of leucine to β-hydroxy-β-methylbutyrate by α-keto isocaproate dioxygenase is required for a potent stimulation of protein synthesis in L6 rat myotubes. Cachexia Sarcopenia Muscle. 2016;7:68–78.CrossRefGoogle Scholar
  8. 8.
    Schiaffino S, Dyar KA, Ciciliot S, et al. Mechanisms regulating skeletal muscle growth and atrophy. FEBS J. 2013;280:4294–314.CrossRefPubMedGoogle Scholar
  9. 9.
    Eley HL, Russell ST, Tisdale MJ. Attenuation of depression of muscle protein synthesis induced by lipopolysaccharide, tumor necrosis factor, and angiotensin II by beta-hydroxy-beta-methylbutyrate. Am J Physiol Endocrinol Metab. 2008;295:E1409–16.CrossRefPubMedGoogle Scholar
  10. 10.
    Aversa Z, Alamdari N, Castillero E, et al. β-hydroxy-β-methylbutyrate (HMB) prevents dexamethasone-induced myotube atrophy. Biochem Biophys Res Commun. 2012;423:739–43.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Kornasio R, Riederer I, Butler-Browne G, et al. Beta-hydroxy-beta-methylbutyrate (HMB) stimulates myogenic cell proliferation, differentiation and survival via the MAPK/ERK and PI3K/Akt pathways. Biochim Biophys Acta. 2009;1793:755–63.CrossRefPubMedGoogle Scholar
  12. 12.
    Eley HL, Russell ST, Tisdale MJ. Mechanism of attenuation of muscle protein degradation induced by tumor necrosis factor-alpha and angiotensin II by beta-hydroxy-beta-methylbutyrate. Am J Physiol Endocrinol Metab. 2008;295:E1417–26.CrossRefPubMedGoogle Scholar
  13. 13.
    Hao Y, Jackson JR, Wang Y, et al. β-Hydroxy-β-methylbutyrate reduces myonuclear apoptosis during recovery from hind limb suspension-induced muscle fiber atrophy in aged rats. Am J Physiol Regul Integr Comp Physiol. 2011;301:R701–15.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Smith HJ, Mukerji P, Tisdale MJ. Attenuation of proteasome-induced proteolysis in skeletal muscle by (beta)-hydroxy-(beta)-methylbutyrate in cancer-induced muscle loss. Cancer Res. 2005;65:277–83.CrossRefPubMedGoogle Scholar
  15. 15.
    Girón MD, Vílchez JD, Shreeram S, et al. β-Hydroxy-β-methylbutyrate (HMB) normalizes dexamethasone-induced autophagy-lysosomal pathway in skeletal muscle. PLoS One. 2015;10:e0117520.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Nissen S, Sharp R, Ray M, et al. The effect of the leucine metabolite β-hydroxy β-methylbutyrate on muscle metabolism during resistance-exercise training. J Appl Physiol (1985). 1996;81:2095–104.Google Scholar
  17. 17.
    Wilson JM, Grant SC, Lee SR, et al. Beta-hydroxy-beta-methyl-butyrate blunts negative age-related changes in body composition, functionality and myofiber dimensions in rats. J Int Soc Sports Nutr. 2012;9:18.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Alway SE, Pereira SL, Edens NK, et al. β-Hydroxy-β-methylbutyrate (HMB) enhances the proliferation of satellite cells in fast muscles of aged rats during recovery from disuse atrophy. Exp Gerontol. 2013;48:973–84.CrossRefPubMedGoogle Scholar
  19. 19.
    Vallejo J, Spence M, Cheng AL, et al. Cellular and physiological effects of dietary supplementation with β-hydroxy-β-methylbutyrate (HMB) and β-alanine in late middle-aged mice. PLoS One. 2016;11:e0150066.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Park BS, Henning PC, Grant SC, et al. HMB attenuates muscle loss during sustained energy deficit induced by calorie restriction and endurance exercise. Metabolism. 2013;62:1718–29.CrossRefPubMedGoogle Scholar
  21. 21.
    Baptista IL, Silva WJ, Artioli GG, et al. Leucine and HMB differentially modulate proteasome system in skeletal muscle under different sarcopenic conditions. PLoS One. 2013;8:e76752.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Russ DW, Acksel C, Boyd IM, et al. Dietary HMB and β-alanine co-supplementation does not improve in situ muscle function in sedentary, aged male rats. Appl Physiol Nutr Metab. 2015;40:1294–301.CrossRefPubMedGoogle Scholar
  23. 23.
    Van Someren KA, Edwards AJ, Howatson G. Supplementation with β-hydroxy-β-methylbutyrate (HMB) and α-ketoisocaproic acid (KIC) reduces signs and symptoms of exercise-induced muscle damage in man. Int J Sport Nutr Exerc Metab. 2005;15:413–24.CrossRefPubMedGoogle Scholar
  24. 24.
    Wilkinson DJ, Hossain T, Hill DS, et al. Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism. J Physiol. 2013;591:2911–23.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Vukovich MD, Stubbs NB, Bohlken RM, et al. The effect of dietary β-hydroxy-β-methylbutyrate (HMB) on strength gains and body composition changes in older adults. FASEB J. 1997;11:A376.Google Scholar
  26. 26.
    Vukovich MD, Stubbs NB, Bohlken RM. Body composition in 70-year-old adults responds to dietary beta-hydroxy-beta-methylbutyrate similarly to that of young adults. J Nutr. 2001;131:2049–52.PubMedGoogle Scholar
  27. 27.
    Panton L, Rathmacher J, Fuller J, et al. Effect of β-hydroxy-β-ethylbutyrate and resistance training on strength and functional ability in the elderly. Med Sci Sports Exerc. 1998;30:194.CrossRefGoogle Scholar
  28. 28.
    Berton L, Bano G, Carraro S, et al. Effect of oral beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical performance in healthy old women over 65 years: an open label randomized controlled trial. PLoS One. 2015;10:e0141757.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Flakoll P, Sharp R, Baier S, et al. Effect of beta-hydroxy-beta-methylbutyrate, arginine, and lysine supplementation on strength, functionality, body composition, and protein metabolism in elderly women. Nutrition. 2004;20:445–51.CrossRefPubMedGoogle Scholar
  30. 30.
    Baier S, Johannsen D, Abumrad N, et al. Year-long changes in protein metabolism in elderly men and women supplemented with a nutrition cocktail of beta-hydroxy-beta-methylbutyrate (HMB), l-arginine, and l-lysine. J Parenter Enteral Nutr. 2009;33:71–82.CrossRefGoogle Scholar
  31. 31.
    Fuller JC Jr, Baier S, Flakoll PJ, et al. Vitamin D status affects strength gains in older adults supplemented with a combination of β-hydroxy-β-methylbutyrate, arginine and lysine: a cohort study. J Parenter Enteral Nutr. 2011;35:757–62.CrossRefGoogle Scholar
  32. 32.
    de Luis DA, Izaola O, Bachiller P, et al. Effect on quality of life and handgrip strength by dynamometry of an enteral specific supplements with beta-hydroxy-beta-methylbutyrate and vitamin D in elderly patients. Nutr Hosp. 2015;32:202–7.PubMedGoogle Scholar
  33. 33.
    Stout JR, Smith-Ryan AE, Fukuda DH, et al. Effect of calcium β-hydroxy-β-methylbutyrate (CaHMB) with and without resistance training in men and women 65 + yrs: a randomized, double-blind pilot trial. Exp Gerontol. 2013;48:1303–10.CrossRefPubMedGoogle Scholar
  34. 34.
    Cramer JT, Cruz-Jentoft AJ, Landi F, et al. Impacts of high-protein oral nutritional supplements among malnourished men and women with sarcopenia: a multicenter, randomized, double-blinded, controlled trial. J Am Med Dir Assoc. 2016;17:1044–55.CrossRefPubMedGoogle Scholar
  35. 35.
    Wu H, Xia Y, Jiang J, 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.CrossRefPubMedGoogle Scholar
  36. 36.
    Hasselgren PO. Beta-hydroxy-beta-methylbutyrate (HMB) and prevention of muscle wasting. Metabolism. 2014;63:5–8.CrossRefPubMedGoogle Scholar
  37. 37.
    Deutz NE, Matheson EM, Matarese LE, et al. NOURISH Study Group. 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.CrossRefPubMedGoogle Scholar
  38. 38.
    Deutz NE, Pereira SL, Hays NP, et al. Effect of β-hydroxy-β-methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults. Clin Nutr. 2013;32:704–12.CrossRefPubMedGoogle Scholar
  39. 39.
    Hsieh LC, Chow CJ, Chang WC, et al. Effect of beta-hydroxy-beta-methylbutyrate on protein metabolism in bed-ridden elderly receiving tube feeding. Asia Pac J Clin Nutr. 2010;19:200–8.PubMedGoogle Scholar
  40. 40.
    Hsieh LC, Chien SL, Huang MS, et al. Anti-inflammatory and anticatabolic effects of short-term beta-hydroxy-beta-methylbutyrate supplementation on chronic obstructive pulmonary disease patients in intensive care unit. Asia Pac J Clin Nutr. 2006;15:544–50.PubMedGoogle Scholar
  41. 41.
    Panton LB, Rathmacher JA, Baier S, et al. Nutritional supplementation of the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) during resistance training. Nutrition. 2000;16:734–9.CrossRefPubMedGoogle Scholar
  42. 42.
    Stout JR, Fukuda DH, Kendall KL, et al. β-Hydroxy-β-methylbutyrate (HMB) supplementation and resistance exercise significantly reduce abdominal adiposity in healthy elderly men. Exp Gerontol. 2015;64:33–4.CrossRefPubMedGoogle Scholar
  43. 43.
    Gerlinger-Romero F, Guimaraes-Ferreira L, Giannocco G, et al. Chronic supplementation of beta-hydroxy-beta methylbutyrate (HMbeta) increases the activity of the GH/IGF-I axis and induces hyperinsulinemia in rats. Growth Horm IGF Res. 2011;21:57–62.CrossRefPubMedGoogle Scholar
  44. 44.
    Pinheiro CH, Gerlinger-Romero F, Guimaraes-Ferreira L, et al. Metabolic and functional effects of beta-hydroxy-beta-methylbutyrate (HMB) supplementation in skeletal muscle. Eur J Appl Physiol. 2012;112:2531–7.CrossRefPubMedGoogle Scholar
  45. 45.
    Ransone J, Neighbors K, Lefavi R, et al. The effect of β-hydroxy β-methylbutyrate on muscular strength and body composition in collegiate football players. J Strength Cond Res. 2003;17:34–9.PubMedGoogle Scholar
  46. 46.
    Toledo FG, Watkins S, Kelley DE. Changes induced by physical activity and weight loss in the morphology of inter-myofibrillar mitochondria in obese men and women. J Clin Endocrinol Metab. 2006;92:1827–33.Google Scholar
  47. 47.
    Sun X, Zemel MB. Leucine and calcium regulate fat metabolism and energy partitioning in murine adipocytes and muscle cells. Lipids. 2007;42:297–305.CrossRefPubMedGoogle Scholar
  48. 48.
    Sun X, Zemel MB. Leucine modulation of mitochondrial mass and oxygen consumption in skeletal muscle cells and adipocytes. Nutr Metab. 2009;6:26.CrossRefGoogle Scholar
  49. 49.
    Bruckbauer A, Zemel MB, Thorpe T, et al. Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice. Nutr Metab. 2012;9:77.CrossRefGoogle Scholar
  50. 50.
    Liang C, Curry BJ, Brown PL, et al. Leucine modulates mitochondrial biogenesis and SIRT1-AMPK signaling in C2C12 myotubes. J Nutr Metab. 2014;2014:239750.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Sharawy MH, El-Awady MS, Megahed N, et al. The ergogenic supplement β-hydroxy-β-methylbutyrate (HMB) attenuates insulin resistance through suppressing GLUT-2 in rat liver. Can J Physiol Pharmacol. 2016;94:488–97.CrossRefPubMedGoogle Scholar
  52. 52.
    Yonamine CY, Teixeira SS, Campello RS, et al. Beta hydroxy beta methylbutyrate supplementation impairs peripheral insulin sensitivity in healthy sedentary Wistar rats. Acta Physiol. 2014;212:62–74.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Andrea P. Rossi
    • 1
    Email author
  • Alessia D’Introno
    • 2
  • Sofia Rubele
    • 1
  • Cesare Caliari
    • 1
  • Stefano Gattazzo
    • 1
  • Elena Zoico
    • 1
  • Gloria Mazzali
    • 1
  • Francesco Fantin
    • 1
  • Mauro Zamboni
    • 1
  1. 1.Section of Geriatrics, Department of MedicineUniversity of Verona, Ospedale MaggioreVeronaItaly
  2. 2.Division of Geriatrics, Department of MedicineUniversity of BariBariItaly

Personalised recommendations