A Lot More On HMB Part 1


I previously wrote an article answering the very common question about HMB and is correlation to being as effective as anabolic steroids. But now that that simple question is answered, we can look further into HMB itself and the benefits it does offer and why I recommend it as a very potent ergogenic aid. HMB is a leucine metabolite. Roughly only 5% of leucine is actually oxidized into HMB. There are two supplement forms of HMB. Those being calcium HMB or as a free acid (which simply means its HMB without the calcium salt.) Between these two forms, we see that the free acid form of HMB is the superior option as it is more readily absorbed while simultaneously reaching a higher serum peak level (1.) Fuller et al looked at the free acid gel form of β-hydroxy-β-methylbutyrate and its clearance rates. Two studies were conducted and in each study four males and four females were given three treatments in a randomised, cross-over design. Treatments were CaHMB (gelatin capsule, 1 g), equivalent HMB free acid gel swallowed (FASW) and free acid gel held sublingual for 15 s then swallowed (FASL). Plasma HMB was measured for 3 h following treatment in study 1 and 24 h with urine collection in study 2. In both the studies, the times to peak plasma HMB were 128 (sem 11), 38 (sem 4) and 38 (sem 1) min (P < 0·0001) for CaHMB, FASW and FASL, respectively. The peak concentrations were 131 (sem 6), 249 (sem 14) and 239 (sem 14) μmol/l (P < 0·0001) for CaHMB, FASW and FASL, respectively. The areas under the curve were almost double for FASW and FASL (P < 0·0001). Daily urinary HMB excretion was not significantly increased resulting in more HMB retained (P < 0·003) with FASW and FASL. Half-lives were 3·17 (sem 0·22), 2·50 (sem 0·13) and 2·51 (sem 0·14) h for CaHMB, FASW and FASL, respectively (P < 0·004). Free acid gel resulted in quicker and greater plasma concentrations (+185%) and improved clearance (+25%) of HMB from plasma. In conclusion, HMB free acid gel could improve HMB availability and efficacy to tissues in health and disease.

HMB acts within the body very similarly to leucine meaning that they both inhibit muscle protein breakdown as well as increasing muscle protein synthesis. Maintenance of skeletal muscle mass is contingent upon the dynamic equilibrium (fasted losses-fed gains) in protein turnover. Of all nutrients, the single amino acid leucine (Leu) possesses the most marked anabolic characteristics in acting as a trigger element for the initiation of protein synthesis. While the mechanisms by which Leu is ‘sensed’ have been the subject of great scrutiny, as a branched-chain amino acid, Leu can be catabolized within muscle, thus posing the possibility that metabolites of Leu could be involved in mediating the anabolic effect(s) of Leu. Our objective was to measure muscle protein anabolism in response to Leu and its metabolite HMB. Using [1,2-(13)C2]Leu and [(2)H5]phenylalanine tracers, and GC-MS/GC-C-IRMS we studied the effect of HMB or Leu alone on MPS (by tracer incorporation into myofibrils), and for HMB we also measured muscle proteolysis (by arteriovenous (A-V) dilution). Orally consumed 3.42 g free-acid (FA-HMB) HMB (providing 2.42 g of pure HMB) exhibited rapid bioavailability in plasma and muscle and, similarly to 3.42 g Leu, stimulated muscle protein synthesis (MPS; HMB +70% vs. Leu +110%). While HMB and Leu both increased anabolic signalling (mechanistic target of rapamycin; mTOR), this was more pronounced with Leu (i.e. p70S6K1 signalling 90 min vs. 30 min for HMB). HMB consumption also attenuated muscle protein breakdown (MPB; -57%) in an insulin-independent manner. We conclude that exogenous HMB induces acute muscle anabolism (increased MPS and reduced MPB) albeit perhaps via distinct, and/or additional mechanism(s) to Leu (2.)


  1. Free acid gel form of β-hydroxy-β-methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt. John C. Fuller, Jr, Rick L. Sharp, Hector F. Angus, Shawn M. Baier, John A. Rathmacher. Br J Nutr. 2011 Feb; 105(3): 367–372. Published online 2010 Dec (https://www.ncbi.nlm.nih.gov/pubmed/21134325)
  2. Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism. D J Wilkinson, T Hossain, D S Hill, B E Phillips, H Crossland, J Williams, P Loughna, T A Churchward-Venne, L Breen, S M Phillips, T Etheridge, J A Rathmacher, K Smith, N J Szewczyk, P J Atherton. J Physiol. 2013 Jun 1; 591(Pt 11): 2911–2923. Published online 2013 Apr (https://www.ncbi.nlm.nih.gov/pubmed/23551944)
  3. Does leucine, leucyl-tRNA, or some metabolite of leucine regulate protein synthesis and degradation in skeletal and cardiac muscle? M. E. Tischler, M. Desautels, A. L. Goldberg. J Biol Chem. 1982 Feb (https://www.ncbi.nlm.nih.gov/pubmed/6915936)
  4. Mechanism of attenuation by beta-hydroxy-beta-methylbutyrate of muscle protein degradation induced by lipopolysaccharide. Steven T. Russell, Michael J. Tisdale. Mol Cell Biochem. 2009 Oct; 330(1-2): 171–179. Published online 2009 Apr (https://www.ncbi.nlm.nih.gov/pubmed/19404720)
  5. Beta-hydroxy-beta-methylbutyrate (HMB) stimulates myogenic cell proliferation, differentiation and survival via the MAPK/ERK and PI3K/Akt pathways. Reut Kornasio, Ingo Riederer, Gillian Butler-Browne, Vincent Mouly, Zehava Uni, Orna Halevy. Biochim Biophys Acta. 2009 May; 1793(5): 755–763. Published online 2009 Jan (https://www.ncbi.nlm.nih.gov/pubmed/19211028)
  6. Effects of nine weeks of beta-hydroxy-beta- methylbutyrate supplementation on strength and body composition in resistance trained men. Jasmine S. Thomson, Patricia E. Watson, David S. Rowlands. J Strength Cond Res. 2009 May (https://www.ncbi.nlm.nih.gov/pubmed/19387396)
  7. 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. Jacob M. Wilson, Ryan P. Lowery, Jordan M. Joy, J. C. Andersen, Stephanie M. C. Wilson, Jeffrey R. Stout, Nevine Duncan, John C. Fuller, Shawn M. Baier, Marshall A. Naimo, John Rathmacher. Eur J Appl Physiol. 2014 (https://www.ncbi.nlm.nih.gov/pubmed/24599749)
  8. The effect of HMB ingestion on the IGF-I and IGF binding protein response to high intensity military training. Redd et al. 2017. (http://www.growthhormoneigfresearch.com/article/S1096-6374(16)30061-2/fulltext)
  9. Serum insulin-like growth factor-1 and its binding protein-7: potential novel biomarkers for heart failure with preserved ejection fraction. Barroso, M. C., Kramer, F., Greene, S. J., Scheyer, D., Köhler, T., Karoff, M., … Dinh, W. (2016). BMC Cardiovascular Disorders, 16, 199. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073807/)
  10. IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways. Tania Benatar, Wenyi Yang, Yutaka Amemiya, Valentina Evdokimova, Harriette Kahn, Claire Holloway, Arun Seth. Breast Cancer Res Treat. 2012 (https://www.ncbi.nlm.nih.gov/pubmed/21997538)
  11. Insulin growth factor binding protein 7 is a novel target to treat dementia. Hope Y. Agbemenyah, Roberto C. Agis-Balboa, Susanne Burkhardt, Ivana Delalle, Andre Fischer. Neurobiol Dis. 2014 (https://www.ncbi.nlm.nih.gov/pubmed/24075854)
  12. Effect of β-hydroxy-β-methylbutyrate Supplementation During Energy Restriction in Female Judo Athletes. Wei Hung et al. Journal of Exercise Science & Fitness 2010. (http://www.sciencedirect.com/science/article/pii/S1728869X1060007X)
  13. Effects of Calcium β-HMB Supplementation During Training on Markers of Catabolism, Body Composition, Strength and Sprint Performance. Kreider et al. WAYNE STATE NUTRITION AND FOOD SCIENCE FACULTY RESEARCH PUBLICATIONS. 2013 (http://digitalcommons.wayne.edu/nfsfrp/7/)