HMB supplementation: clinical and athletic performance-related effects and mechanisms of action (A Review)

Journal Title (Medline/Pubmed accepted abbreviation): Amino Acids
Year: 2011
Volume: 40
Page numbers: 1015-1025
doi (if applicable): 10.1007-s00726-010-0678-0

Summary of the review
β-Hydroxy-β-methylbutyrate (HMB) has become popular due to its ability to reduce the rate of muscle damage and breakdown as well as increase the rate of protein synthesis. HMB is a metabolite of the amino acid leucine and is thought to contribute to the performance-related benefits of leucine. Supplementation with HMB is superior to leucine, however, because one would need to consume about 20 times the amount of leucine to achieve efficacious circulating levels of HMB. (Most of the leucine is metabolized into HMG-CoA, a precursor for cholesterol.) Current research supports an effective dose of 3 g/day, with 6 g/day showing the same benefits and 1.5 g/day showing less benefit.

     There have been individual differences in response to HMB with training, with untrained athletes showing the most benefits. This is likely due to the fact that their muscles are experiencing more damage than trained athletes would from a similar workout.

     HMB appears to be a safe supplement, as there have not been reported negative effects in regard to kidney or liver function in doses as high as 6 g/day.

     In addition to sports performance, HMB has potential to aid in the treatment of muscle wasting conditions such as immobilization, HIV, and cancer. Cachetic factors present in these condition trigger cell signaling pathways that promote muscle protein breakdown and studies of HMB, mainly in murine muscle tissue, indicate that HMB can block these effects to some degree. Several human studies indicate the potential for lessened muscle catabolism in these conditions as well.

     The biochemical mechanism of HMB is still not very well understood. It has been shown that HMB upregulates insulin-like growth factor 1 (IGF-1). IGF-1 and/or HMB then activate the mTOR cellular signaling pathway that promotes protein synthesis. It is well-established that IGF-1 promotes muscle synthesis, and it is difficult for scientists to distinguish direct or indirect activation of mTOR by HMB.

     The ubiquitin-proteosome system is responsible for protein breakdown and there is evidence that HMB inhibits this system. It is also unknown whether or not these effects are mediated by IGF-1. Some evidence indicates that HMB may inhibit certain caspases, which, if left unihibited, lead to greater stimulatory effects of NF-kβ on protein breakdown via the ubiquitin proteosome system.

Interpretation of findings/Key practice applications

HMB supplementation has been demonstrated to increase muscle mass and strength in certain populations, particular those who are more untrained or those who have cachetic conditions. Multiple human studies of HMB supplementation have been conducted without reports of adverse side effects.


The authors did not mention effects on timing of supplementation. Does it work best post-workout? Pre-workout? In smaller doses throughout the day?
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