Is beta‑hydroxy‑beta‑methylbutyrate (HMB) supplementation safe and effective for increasing lean body mass and strength in healthy adults, and what dosage and duration are recommended?

HMB Supplementation: Safety and Efficacy for Lean Body Mass and Strength

HMB supplementation at 3 g/day is safe and can increase lean body mass in specific populations, but the evidence for healthy trained adults is mixed and insufficient to make a strong recommendation for routine use in this group.

Safety Profile

HMB supplementation demonstrates an excellent safety profile across multiple populations:

• No adverse events have been reported with short-term use, and chronic consumption appears safe for up to at least one year 1, 2
• No negative effects on glucose tolerance or insulin sensitivity have been observed, with potential improvements in glucose metabolism in younger adults 1
• The safety profile is unequivocal across all studied populations 2

Efficacy in Different Populations

Healthy Untrained Individuals

HMB shows the most consistent benefits in previously untrained individuals:

• Some support exists for HMB's anti-catabolic effects in young, previously untrained individuals at the standard 3 g/day dose 3
• Studies demonstrate minimal to moderate gains in strength and lean body mass specifically in untrained populations 4
• The most pronounced improvements occur when combined with robust resistance training programs and dietary control 1

Healthy Trained Athletes

The evidence becomes considerably weaker for trained individuals:

• Benefits in trained athletes are mixed and appear to increase only with study durations exceeding 6 weeks 1
• HMB use in athletes involved in regular high-intensity exercise has not been proven beneficial when multiple variables are evaluated 4
• HMB cannot be recommended as an ergogenic for trained athletes until further studies in larger groups reproduce early data 4

Older Adults

The evidence is more favorable in elderly populations:

• Meta-analysis shows HMB supplementation significantly increases fat-free mass in older adults (effect size: 0.37; 95% CI 0.16,0.58; P = 0.001) 5
• HMB supplementation alone (without exercise) shows even greater improvement in fat-free mass (effect size: 0.59; 95% CI 0.32,0.87; P < 0.001) 5
• However, HMB combined with exercise shows no additional benefit over exercise alone (effect size: 0.06; P = 0.705) 5
• A separate meta-analysis confirmed greater muscle mass gain compared to controls (standard mean difference = 0.352 kg; P = 0.004) 6

Clinical Populations

For patients with muscle wasting conditions:

• HMB may be effective in preventing muscle disuse atrophy during periods of inactivity due to illness or injury 1
• In hospitalized patients, high-protein HMB oral nutritional supplements showed decreased 90-day mortality (4.8% vs 9.7%; RR 0.49, P = 0.018) 3
• During 10 days of bedrest in healthy volunteers, HMB significantly reduced muscle loss and increased muscle mass gain during the 8-week rehabilitation phase 3

Cancer Patients - Important Caveat

ESPEN guidelines explicitly state there are insufficient consistent clinical data to recommend HMB supplementation to improve fat-free mass in cancer patients 3:

• A large RCT in 472 cachectic cancer patients failed due to compliance difficulties; only 37% completed the protocol with no statistically significant differences observed 3
• While some smaller studies showed promise, the data remain inconsistent 3

Mechanism of Action

HMB works through a dual mechanism:

• Enhances muscle protein synthesis via mTORC1 activation independent of the leucine-sensing pathway 1
• Suppresses muscle protein breakdown as an anti-catabolic agent 3, 1
• May reduce muscle damage and promote recovery through anti-inflammatory effects 1
• Modulates mitochondrial dynamics and lipid metabolism, potentially preventing disuse atrophy 1

Dosage and Duration Recommendations

Based on the available evidence:

• Standard dose: 3 g/day is the most commonly studied and recommended dose 3, 1, 2
• Alternative dosing: 38 mg/kg body weight daily when combined with exercise training 1
• Duration: Minimum 6 weeks appears necessary for performance benefits, with longer durations showing greater effects 1
• For body composition changes, studies showing benefit typically lasted 8-24 weeks 3

Timing Considerations

• HMB consumption in close proximity to exercise may be beneficial to increase muscle protein synthesis and attenuate inflammatory response 1
• Both acute and chronic consumption can provide beneficial physiological effects 1

Clinical Bottom Line

For healthy adults seeking to increase lean body mass and strength through HMB supplementation:

• Untrained individuals: May consider 3 g/day HMB with resistance training for at least 6-12 weeks, as this population shows the most consistent benefits 1, 2, 4
• Trained athletes: Evidence is insufficient to recommend routine use; benefits are mixed and inconsistent 1, 4
• Older adults: Consider 3 g/day HMB supplementation alone (without mandatory exercise) for muscle mass preservation, as the combination with exercise shows no additional benefit 5, 6
• Clinical populations: May be beneficial during periods of immobilization or muscle wasting, but should not be routinely recommended for cancer cachexia 3, 1

The safety profile supports that 3 g/day may be routinely used without concern for adverse effects, but the efficacy for increasing lean body mass and strength in healthy trained adults remains unproven 2, 4.