HMB

HMB is short for hydroxymethylbutyrate or ꞵ-hydroxy ꞵ-methylbutyrate. It is an active metabolite of the essential amino acid leucine. All of the HMB present in the human body is derived from dietary sources of leucine, with about 5% of all dietary leucine being converted to HMB.^[1] HMB is thought to help reduce muscle protein breakdown and may mediate some of the effects of leucine on muscle protein synthesis.

HMB plays an anticatabolic role in muscle tissue. In other words, HMB prevents muscle protein breakdown and reduces the loss of fat-free mass. These effects seem to be most pronounced during catabolic states, including cancer cachexia,^[2] acquired immunodeficiency syndrome (AIDS),^[3] and aging.^[4][5] HMB seems to be particularly effective for preventing the age-related loss of muscle mass and for preserving strength and body composition in bedridden or sedentary older adults.^[4][5]

HMB stimulates muscle protein synthesis, but supplementation fails to increase fat-free mass, improve body composition, or increase measures of strength performance in athletes and trained individuals, and its use in these populations cannot be recommended.^[6][7][8] HMB may be effective for reducing exercise-associated muscle damage after high-intensity exercise.^[9]

Supplementing with HMB at a dose of 3 grams per day appears to be well tolerated and is not associated with any adverse side effects.^[10] This is the dose commonly used in research studies. Higher doses may be equally safe, but very few studies have investigated doses of HMB above 3 grams per day. One study found that 6 grams of HMB per day didn’t cause any concerning changes to cholesterol, blood glucose, red or white blood cells, and liver or kidney function.^[11] HMB also appears to be safe when taken with other amino acids (i.e., arginine, lysine, and glutamine) or supplemented alongside creatine.^[12][10][9]

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.^[13] HMB may also increase the activity of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis.^[14]

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.^[15][16][17] Inhibiting protein breakdown explains why HMB can minimize the loss of lean body mass in certain conditions.