HMB’s effects on skeletal muscle appear to be due to its actions on both muscle protein synthesis and muscle protein breakdown. HMB promotes muscle protein synthesis by stimulating mammalian target of rapamycin (mTOR), which regulates cell growth and differentiation.[1] HMB may also increase the activity of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis.[2]
HMB reduces protein degradation (protein breakdown) by inhibiting the activity of the body’s ubiquitin-proteasome system and caspases. These two pathways are responsible for breaking down proteins (proteolysis) under catabolic states such as fasting, immobilization, disuse, aging, and disease.[3][4][5] Inhibiting protein breakdown explains why HMB can minimize the loss of lean body mass in certain conditions.