β-hydroxy-β-methylbutyrate (or HMB) is a popular muscle building supplement. HMB is a metabolite derived from the essential amino acid leucine. Some studies have suggested that HMB is an anabolic compound that increases muscle building after resistance exercise training and improves lean body mass. There are also claims that it decreases fat mass alongside the increase in muscle mass. A further claim is that HMB increases muscle strength after resistance exercise training. But how strong is this evidence? Does HMB really have all these effects or is it largely hype?
What is known about HMB?
HMB has been shown to stimulate protein synthesis in cells in vitro. This means that it seems to work in a petri dish. Similarly, some studies have provided evidence for an effect of HMB on protein degradation. The studies in humans on the functional effects (body composition, muscle mass, muscle strength), however, have provided mixed results. Over the last few years several meta-analyses have been performed trying to draw conclusions from all the human studies but even those analyses did not result in convincing conclusions. HMB is available in two different forms as a supplement: HMB that is calcium bound or HMB in a free form (HMB Free acid). There is, however, little evidence that these two forms have different effects.
A new meta-analysis on HMB
Most recently a comprehensive meta-analysis was performed by Jakubowski et al (1) and what I like about this paper is that apart from a thorough meta-analysis, this review also includes a more qualitative point of view and asks critical questions about the results of published studies.
When the authors of this new meta-analysis searched the literature, they initially found 1731 papers and this was narrowed down to 303 for more detailed screening. In the end, 11 double blinded clinical trials were included in the analysis. In these 11 studies, both forms of the available HMB were included. The average study duration was just under 8 weeks. Below are the results of the meta-analysis.
Effects of HMB on body weight
After careful analysis of the 11 studies, they reported the effects of HMB on body weight. There was an average weight gain after the training program of 0.78 kg. This was increased to 1.12 kg with HMB. The mean difference between placebo and HMB-groups was 0.34 kg. A modest increase. The initial study by Nissen et al (1) (the patent holder of HMB, which showed the largest increase ever reported was still included in this increase and removing this study from the analysis would mean there would be no difference at all).
Effects of HMB on lean body mass
Eleven studies also measured changes in lean body mass. Here, the mean difference between supplemented and placebo groups was a few hundred grams. The HMB-supplemented groups gained an average of 1.57 kg and the placebo groups gained 1.17 kg of lean body mass.
Effects of HMB on fat loss
The mean fat loss was equivalent in these same studies. There was no significant difference in the amount of fat that was lost.
Effects of HMB on muscle strength
The analysis of muscle strength with or without HMB revealed no differences. For example, subjects that undertook resistance exercise training with placebo increased their total 1RM (repetition max) strength by 30.6 kg. HMB-supplemented individuals increased their total 1RM strength by 32.0 kg. This difference was not significantly different.
Some studies showed abnormal improvements
The authors point out that some studies have reported extraordinarily greater lean mass
and strength gains by individuals ingesting HMB (2, 3), or HMB + ATP (4) when undertaking resistance exercise training.
The results of these studies were excluded from the analysis because the results were so far from what is considered a “normal” response. These studies met the inclusion criteria for the meta-analysis but were excluded due to the fact that there were so far removed from the average response. For comparison: the average gain in fat free mass of all other studies was 1.57kg versus 1.17kg with placebo (training without HMB). Increases of more than 7kg are therefore way out of the normal physiological range. In one study 9.3 kg (2) gain of fat free mass was reported after 12 weeks of training and supplementation and in the other (3) 7.4 kg of fat free mass was reported. Such changes are normally only seen in subjects using anabolic steroids.
HMB, as would be expected as a metabolite of leucine, can acutely activate skeletal muscle protein synthesis and the main signaling pathways leading to protein synthesis. But there is little or no reason to believe that HMB would have a superior effect to leucine or to meals containing leucine containing foods (5, 6). In fact, the large changes seen by Nissen et al (7) may have been because HMB was ingested with 37 g of milk protein.
Summary and bottom line
The authors of the review concluded: systematic review and meta-analysis showed that HMB supplementation during resistance exercise training may result in a small increase in body weight but does not result in a significant enhancement of gains in free fat mass or losses of fat mass. Thus, there is no rationale for prescription of HMB as a supplement to improve body composition caused by RET in young subjects. In addition, effects on strength were also not significant.
Jakubowski et al. Supplementation with the Leucine metabolite hydroxy-methylbutyrate (HMB) does not Improve Resistance Exercise-Induced Changes in Body Composition or Strength in Young Subjects: A Systematic Review and Meta-Analysis Nutrients 12, 1523, 2020.
Kraemer, W.J.; Hatfield, D.L.; Volek, J.S.; Fragala, M.S.; Vingren, J.L.; Anderson, J.M.; Spiering, B.A. Thomas, G.A.; Ho, J.Y.; Quann, E.E.; et al. Effects of amino acids supplement on physiological adaptations to resistance training. Med. Sci. Sports Exerc. 41, 1111–1121, 2009.
Wilson, J.M.; Lowery, R.P.; Joy, J.M.; Andersen, J.C.; Wilson, S.M.; Stout, J.R.; Duncan, N.; Fuller, J.C.; Baier, S.M.; Naimo, M.A.; et al. The e_ects 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, 1217–1227, 2014.
Lowery, R.P.; Joy, J.M.; Rathmacher, J.A.; Baier, S.M.; Fuller, J.C., Jr.; Shelley, M.C., 2nd; Jager, R.; Purpura, M.; Wilson, S.M.; Wilson, J.M. Interaction of Beta-Hydroxy-Beta-Methylbutyrate Free Acid and Adenosine Triphosphate on Muscle Mass, Strength, and Power in Resistance Trained Individuals. J. Strength Cond. Res. 30, 1843–1854, 2016.
Wilkinson, D.J.; Hossain, T.; Hill, D.S.; Phillips, B.E.; Crossland, H.; Williams, J.; Loughna, P. Churchward-Venne, T.A.; Breen, L.; Phillips, S.M.; et al. Effects of leucine and its metabolite beta-hydroxy-beta-methylbutyrate on human skeletal muscle protein metabolism. J. Physiol. 591, 2911–2923, 2013.
Jakubowski, J.S.;Wong, E.P.T.; Nunes, E.A.; Noguchi, K.S.; Vandeweerd, J.K.; Murphy, K.T.; Morton, R.W.; McGlory, C.; Phillips, S.M. Equivalent Hypertrophy and Strength Gains in beta-Hydroxy-beta-Methylbutyrate or leucine-supplemented Men. Med. Sci. Sports Exerc. 51, 65–74, 2019.
Nissen, S.; Sharp, R.; Ray, M.; Rathmacher, J.A.; Rice, D.; Fuller, J.C., Jr.; Connelly, A.S.; Abumrad, N. Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on muscle metabolism during resistance-exercise training. J. Appl. Physiol. 81, 2095–2104, 1996.