What is HMB Supplement?
HMB (beta-hydroxy-beta-methylbutyrate) is a metabolite of the essential amino acid leucine that functions as an anti-catabolic agent, typically dosed at 3 grams per day, and is promoted to reduce muscle protein breakdown and enhance muscle mass and strength, particularly during periods of physical stress or muscle wasting. 1
Biochemical Properties and Mechanism
HMB is derived from leucine metabolism, specifically from its keto acid alpha-ketoisocaproate, and represents a downstream product of branched-chain amino acid metabolism 2, 3
The compound works through multiple mechanisms: it stimulates muscle protein synthesis via the mTOR pathway, inhibits protein degradation through the ubiquitin-proteasome pathway, enhances sarcolemma integrity, decreases cell apoptosis, and stimulates the growth hormone/IGF-1 axis 3, 1
HMB also promotes muscle stem cell proliferation and differentiation, contributing to muscle regeneration and repair 3
Clinical Applications and Effectiveness
In Athletic Performance
HMB shows effectiveness in untrained individuals and those exposed to strenuous exercise, where it attenuates exercise-induced muscle damage and enhances muscle hypertrophy, strength, and aerobic performance 4
The effectiveness is less pronounced in strength-trained athletes, likely because training adaptation already suppresses proteolysis, potentially blunting HMB's anti-catabolic effects 4
In Older Adults
HMB supplementation significantly increases fat-free mass in older adults (effect size: 0.37; 95% CI 0.16-0.58), particularly when used alone rather than combined with exercise 5
In bedrest studies, HMB preserved muscle mass during 10 days of immobilization and enhanced muscle mass gain during the 8-week rehabilitation phase in healthy volunteers 1
In Cancer and Critical Illness
ESPEN guidelines state there are insufficient consistent clinical data to recommend HMB supplementation for improving fat-free mass in cancer patients 1
A large RCT of 472 cachectic cancer patients failed due to poor compliance (only 37% completed the 8-week protocol), with no significant differences observed between HMB/glutamine/arginine mixture versus control 1
In ICU settings, two recent studies showed no difference in muscle loss with HMB supplementation, though the intervention duration may have been too short for benefit 1
Standard Dosing
- The typical dose is 3 grams per day, which has been established as the standard in most clinical trials and is considered safe for routine use 1, 6
Important Clinical Caveats
HMB appears most effective during periods of high physical stress or in untrained individuals, not in healthy, non-exercising subjects or well-trained athletes 4
Compliance is a major practical limitation, particularly when HMB is combined with other amino acids (glutamine, arginine) in complex supplementation regimens 1
The safety profile is well-established with no significant adverse effects reported across multiple studies in various populations 6
HMB supplementation alone (without exercise) may be more effective than combined with exercise in older adults, contrary to common assumptions 5