Skip to main content
Log in

Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Older Adults with Sarcopenia: A Randomized, Double-Blind, Placebo-Controlled Study

  • Original Research
  • Published:
The journal of nutrition, health & aging



Sarcopenia is recognized as a major public health concern because of its association with several adverse health events. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation reportedly delays the loss of muscle mass and function; however, the effect of HMB on sarcopenia remains inconclusive. We aimed to evaluate the impact of HMB intervention on muscle strength, physical performance, body compositions, and inflammatory factors in older adults with sarcopenia.


Randomized, double-blind, placebo-controlled trial.

Setting and Participants

This study included subjects aged ≥60 years with sarcopenia which were assigned to the HMB group (HMBG, n=18) and the placebo group (PG, n=16).


The HMBG and PG were supplied with HMB and placebo products twice daily for 12 weeks, and both received resistance exercise training twice a week in 12 weeks.


Hand grip strength was selected as the primary outcome; gait speed, five-time chair stand test, body composition and inflammatory indicators were selected as the secondary outcomes. The differences in changes from baseline between the two groups were analyzed using the analysis of covariance(ANCOVA).


After the 12-week intervention, the HMBG demonstrated significantly greater improvements in handgrip strength (4.61(95%CI:2.93,6.28) kg, P<0.001), gait speed (0.11(95%CI:0.02,0.20)m/s, P=0.014), five-time chair stand test (−3.65 (95%CI:−5.72, −1.58)s, P=0.001), muscle quality (2.47(95%CI:1.15,3.80),kg·kg−1 P=0.001) and tumor necrosis factorlike weak inducer of apoptosis (−15.23(95%CI:−29.80,−0.66)pmol/mL, P=0.041) compared with the PG; no significant differences in skeletal muscle mass, skeletal muscle index, and other body composition parameters were found between the two groups.


In older adults with sarcopenia, HMB significantly enhance the effect of resistance exercise training on muscle strength, physical performance, muscle quality, and reduced inflammatory factors. Therefore, HMB supplementation could be an effective treatment for sarcorpenia. The trial protocol was registered at as ChiCTR2000028778.

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.

Figure 1
Figure 2

Similar content being viewed by others

Data Availability Statement

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy and ethical.


  1. Phillips SM. (2015). Nutritional supplements in support of resistance exercise to counter age-related sarcopenia. Adv Nutr. 6(4):452–460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chen LK, Woo J, Assantachai P, Auyeung TW, Chou MY, Iijima K, Jang HC, Kang L, Kim M, Kim S, et al. (2020). Asian Working Group for Sarcopenia: 2019 Consensus Update on Sarcopenia Diagnosis and Treatment. J Am Med Dir Assoc. 21(3):300–307.e2.

    Article  PubMed  Google Scholar 

  3. Holecek M. (2017). Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions. J Cachexia Sarcopenia Muscle. 8(4):529–541.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wilson JM, Lowery RP, Joy JM, Andersen JC, Wilson SM, Stout JR, Duncan N, Fuller JC, Baier SM, Naimo MA, et al. (2014). The effects of 12 weeks of beta-hydroxy-beta-methylbutyrate free acid supplementation on muscle mass, strength, and power in resistance-trained individuals: a randomized, double-blind, placebo-controlled study. Eur J Appl Physiol. 114(6):1217–1227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rossi AP, D’Introno A, Rubele S, Caliari C, Gattazzo S, Zoico E, Mazzali G, Fantin F, Zamboni M. (2017). The Potential of β-Hydroxy-β-Methylbutyrate as a New Strategy for the Management of Sarcopenia and Sarcopenic Obesity. Drugs Aging. 34(11):833–840.

    Article  CAS  PubMed  Google Scholar 

  6. Asadi A, Arazi H, Suzuki K. (2017). Effects of β-Hydroxy-β-methylbutyrate-free Acid Supplementation on Strength, Power and Hormonal Adaptations Following Resistance Training. Nutrients. 9(12):1316.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Nissen S, Sharp R, Ray M, Rathmacher JA, Rice D, Fuller JCJr, Connelly AS, Abumrad N. (1996). Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on muscle metabolism during resistance-exercise training. J Appl Physiol (1985). 81(5):2095–2104.

    Article  CAS  PubMed  Google Scholar 

  8. Nissen S. (1997). Measurement of muscle proteolysis and the impact on muscle wasting. Proc Nutr Soc. 56(2):793–799.

    Article  CAS  PubMed  Google Scholar 

  9. Deutz NE, Pereira SL, Hays NP, Oliver JS, Edens NK, Evans CM, Wolfe RR.(2013). Effect of β-hydroxy-β-methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults. Clin Nutr. 32(5):704–712.

    Article  CAS  PubMed  Google Scholar 

  10. Matheson EM, Nelson JL, Baggs GE, Luo M, Deutz NE. (2021). Specialized oral nutritional supplement (ONS) improves handgrip strength in hospitalized, malnourished older patients with cardiovascular and pulmonary disease: A randomized clinical trial. Clin Nutr. 40(3):844–849.

    Article  CAS  PubMed  Google Scholar 

  11. Engelen MPKJ, Deutz NEP. (2018). Is β-hydroxy β-methylbutyrate an effective anabolic agent to improve outcome in older diseased populations?. Curr Opin Clin Nutr Metab Care. 21(3):207–213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Shreeram S, Ramesh S, Puthan JK, Balakrishnan G, Subramanian R, Reddy MT, Pereira SL. (2016). Age associated decline in the conversion of leucine to β-Hydroxy-β-Methylbutyrate in rats. Exp Gerontol. 80:6–11.

    Article  CAS  PubMed  Google Scholar 

  13. Cui D, Drake JC, Wilson RJ, Shute RJ, Lewellen B, Zhang M, Zhao H, Sabik OL, Onengut S, Berr SS, et al. (2020). A novel voluntary weightlifting model in mice promotes muscle adaptation and insulin sensitivity with simultaneous enhancement of autophagy and mTOR pathway. FASEB J. 34(6):7330–7344.

    Article  CAS  PubMed  Google Scholar 

  14. Silva VR, Belozo FL, Micheletti TO, Conrado M, Stout JR, Pimentel GD, Gonzalez AM. (2017). β-hydroxy-β-methylbutyrate free acid supplementation may improve recovery and muscle adaptations after resistance training: a systematic review. Nutr Res. 45:1–9.

    Article  CAS  PubMed  Google Scholar 

  15. Wu, H., Xia, Y., Jiang, J., Du, H., Guo, X., Liu, X., Li, C., Huang, G., & Niu, K. (2015). Effect of beta-hydroxy-beta-methylbutyrate supplementation on muscle loss in older adults: a systematic review and meta-analysis. Archives of gerontology and geriatrics, 61(2), 168–175.

    Article  CAS  PubMed  Google Scholar 

  16. Berton, L., Bano, G., Carraro, S., Veronese, N., Pizzato, S., Bolzetta, F., De Rui, M., Valmorbida, E., De Ronch, I., Perissinotto, E., Coin, A., Manzato, E., & Sergi, G. (2015). 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, 10(11), e0141757.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Chew, S., Tan, N. C., Cheong, M., Oliver, J., Baggs, G., Choe, Y., How, C. H., Chow, W. L., Tan, C., Kwan, S. C., Husain, F. S., Low, Y. L., Huynh, D., & Tey, S. L. (2021). Impact of specialized oral nutritional supplement on clinical, nutritional, and functional outcomes: A randomized, placebo-controlled trial in community-dwelling older adults at risk of malnutrition. Clinical nutrition (Edinburgh, Scotland), 40(4), 1879–1892.

    Article  CAS  PubMed  Google Scholar 

  18. Courel-Ibáñez J, Pallares JG; HEAL study group. (2019). Effects of β-hydroxy-β-methylbutyrate(HMB) supplementation in addition to multicomponent exercise in adults older than 70 years living in nursing homes, a cluster randomized placebo-controlled trial: the HEAL study protocol. BMC Geriatr. 19(1):188.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Stout, J. R., Smith-Ryan, A. E., Fukuda, D. H., Kendall, K. L., Moon, J. R., Hoffman, J. R., Wilson, J. M., Oliver, J. S., & Mustad, V. A. (2013). 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. Experimental gerontology, 48(11), 1303–1310.

    Article  CAS  PubMed  Google Scholar 

  20. Zhu LY, Chan R, Kwok T, Cheng KC, Ha A, Woo J. (2019). Effects of exercise and nutrition supplementation in community-dwelling older Chinese people with sarcopenia: a randomized controlled trial. Age Ageing. 48(2):220–228.

    Article  PubMed  Google Scholar 

  21. Courel-Ibáñez, J., Vetrovsky, T., Dadova, K., Pallares, J. G., & Steffi, M. (2019). Health Benefits of β-Hydroxy-β-Methylbutyrate (HMB) Supplementation in Addition to Physical Exercise in Older Adults: A Systematic Review with Meta-Analysis. Nutrients, 11(9), 2082.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Faul, F., Erdfelder, E., Lang, A. G., & Buchner, A. (2007). G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behavior research methods, 39(2), 175–191.

    Article  PubMed  Google Scholar 

  23. Swain David P, Brawner Clinton A, American College of Sports Medicine. (2014). ACSM’s Resource Manual for Guidelines for Exercise Testing and Prescription, Wolters Kluwer Health/Lippincott Williams & Wilkins: Philadelphia, Pennsylvania. ISBN: 9781609139568

    Google Scholar 

  24. Kim J. (2021). Handgrip Strength to Predict the Risk of All-Cause and Premature Mortality in Korean Adults: A 10-Year Cohort Study. Int J Environ Res Public Health. 19(1):39.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Kaegi-Braun N, Tribolet P, Baumgartner A, Fehr R, Baechli V, Geiser M, Deiss M, Gomes F, Kutz A, Hoess C, et al. (2021). Value of handgrip strength to predict clinical outcomes and therapeutic response in malnourished medical inpatients: Secondary analysis of a randomized controlled trial. Am J Clin Nutr. 114(2):731–740.

    Article  PubMed  Google Scholar 

  26. Mendes J, Amaral TF, Borges N, Santos A, Padrào P, Moreira P, Afonso C, Negräo R. (2017). Handgrip strength values of Portuguese older adults: a population based study. BMC Geriatr. 17(1):191.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bohannon RW, Bubela DJ, Magasi SR, Wang YC, Gershon RC. (2010). Sit-to-stand test: Performance and determinants across the age-span. Isokinet Exerc Sci. 18(4):235–240.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lynch NA, Metter EJ, Lindle RS, Fozard JL, Tobin JD, Roy TA, Fleg JL, Hurley BF. (1999). Muscle quality. I. Age-associated differences between arm and leg muscle groups. J Appl Physiol (1985). 86(1):188–194.

    Article  CAS  PubMed  Google Scholar 

  29. Landrum, M. B., & Becker, M. P. (2001). A multiple imputation strategy for incomplete longitudinal data. Statistics in medicine, 20(17–18), 2741–2760.

    Article  CAS  PubMed  Google Scholar 

  30. Nasimi, N., Sohrabi, Z., Dabbaghmanesh, M. H., Eskandari, M. H., Bedeltavana, A., Famouri, M., & Talezadeh, P. (2021). A Novel Fortified Dairy Product and Sarcopenia Measures in Sarcopenic Older Adults: A Double-Blind Randomized Controlled Trial. Journal of the American Medical Directors Association, 22(4), 809–815.

    Article  PubMed  Google Scholar 

  31. Osuka Y, Kojima N, Sasai H, Wakaba K, Miyauchi D, Tanaka K, Kim H. (2021). Effects of exercise and/or β-hydroxy-β-methylbutyrate supplementation on muscle mass, muscle strength, and physical performance in older women with low muscle mass: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 114(4):1371–1385.

    Article  PubMed  Google Scholar 

  32. Nissen, S., Sharp, R., Ray, M., Rathmacher, J. A., Rice, D., Fuller, J. C.,Jr, Connelly, A. S., & Abumrad, N. (1996). Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on muscle metabolism during resistance-exercise training. Journal of applied physiology (Bethesda, Md.: 1985), 81(5), 2095–2104.

    Article  CAS  PubMed  Google Scholar 

  33. Malhotra R, Tareque MI, Tan NC, Ma S. (2020). Association of baseline hand grip strength and annual change in hand grip strength with mortality among older people. Arch Gerontol Geriatr. 86:103961.

    Article  PubMed  Google Scholar 

  34. Dardevet D, Rémond D, Peyron MA, Papet I, Savary-Auzeloux I, Mosoni L. (2012). Muscle wasting and resistance of muscle anabolism: the ”anabolic threshold concept” for adapted nutritional strategies during sarcopenia. ScientificWorldJournal.2012:269531.

  35. Cruz-Jentoft, A. J., Bahat, G., Bauer, J., Boirie, Y., Bruyère, O., Cederholm, T., Cooper, C., Landi, F., Rolland, Y., Sayer, A. A., Schneider, S. M., Sieber, C. C., Topinkova, E., Vandewoude, M., Visser, M., Zamboni, M., & Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2 (2019). Sarcopenia: revised European consensus on definition and diagnosis. Age and ageing, 48(4), 601.

    Article  PubMed  PubMed Central  Google Scholar 

  36. McGregor, R. A., Cameron-Smith, D., & Poppitt, S. D. (2014). It is not just muscle mass: a review of muscle quality, composition and metabolism during ageing as determinants of muscle function and mobility in later life. Longevity & healthspan, 3(1), 9.

    Article  Google Scholar 

  37. Barbat-Artigas, S., Rolland, Y., Zamboni, M., & Aubertin-Leheudre, M. (2012). How to assess functional status: a new muscle quality index. The journal of nutrition, health & aging, 16(1), 67–77.

    Article  CAS  Google Scholar 

  38. Goldberg, E. L., & Dixit, V. D. (2015). Drivers of age-related inflammation and strategies for healthspan extension. Immunological reviews, 265(1), 63–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Li, C. W., Yu, K., Shyh-Chang, N., Li, G. X., Jiang, L. J., Yu, S. L., Xu, L. Y., Liu, R. J., Guo, Z. J., Xie, H. Y., Li, R. R., Ying, J., Li, K., & Li, D. J. (2019). Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention. Journal of cachexia, sarcopenia and muscle, 10(3), 586–600.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Yonamine, C. Y., Teixeira, S. S., Campello, R. S., Gerlinger-Romero, F., Rodrigues, C. F., Jr, Guimaräes-Ferreira, L., Machado, U. F., & Nunes, M. T. (2014). Beta hydroxy beta methylbutyrate supplementation impairs peripheral insulin sensitivity in healthy sedentary Wistar rats. Acta physiologica (Oxford, England), 212(1), 62–74.

    Article  CAS  PubMed  Google Scholar 

Download references


We would like to thank all the community workers who participated in this study, and Editage ( for English language editing.


This work was supported by the Danone Dietary Nutrition Research and Education Fund [grant number DIC2019-10]. The supporting source had no involvement or restrictions regarding publication.

Author information

Authors and Affiliations



Chan Yang and Yu Song performed the statistical analysis, drafted the manuscript. Tingting Li conceived the idea, designed and conducted the trial, managed the project and subjects. Hong Jia supervised the study and review the manuscript. Xinyu Chen and Junliang Zhou performed the investigation, intervention and data collection. Qing Pan: performed the statistical analysis; Wei Jiang and Min Wang: instructed the intervention. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Hong Jia.

Additional information

Conflict of Interest

The research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, C., Song, Y., Li, T. et al. Effects of Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Older Adults with Sarcopenia: A Randomized, Double-Blind, Placebo-Controlled Study. J Nutr Health Aging 27, 329–339 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Key words