Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism.
Level 3 - non-randomized controlled study
Controlled human metabolic tracer study (randomization not stated in abstract)
PubMed 23551944 · doi:10.1113/jphysiol.2013.253203
What was done
Stable isotope tracers ([1,2-¹³C₂]leucine and [²H₅]phenylalanine) and mass spectrometry were used to determine the acute effects of oral free-acid HMB (3.42 g FA-HMB, providing 2.42 g pure HMB) versus 3.42 g leucine on human muscle protein metabolism. Muscle protein synthesis (MPS) was measured by myofibrillar tracer incorporation, mTOR/p70S6K1 signalling was assessed, and muscle protein breakdown (MPB) was measured for HMB via arteriovenous dilution.
What was found
Both compounds stimulated MPS, with leucine inducing a larger increase (HMB +70% vs. leucine +110%). Anabolic mTOR pathway activation occurred with both, but p70S6K1 signalling remained elevated longer with leucine (90 min vs. 30 min for HMB). HMB ingestion reduced MPB by 57% through an insulin-independent mechanism.
Why it matters
This trial provides direct human physiological evidence that HMB independently stimulates muscle protein synthesis and inhibits breakdown, demonstrating distinct kinetic and mechanistic actions relative to leucine.
Limits
The abstract omits sample size, participant demographics (age, sex, training status), and whether treatments were randomized or administered in a crossover format. Muscle protein breakdown was measured only for HMB, precluding direct comparison of anti-catabolic efficacy against leucine. Measurements reflect acute metabolic responses rather than chronic hypertrophy or functional strength changes.
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