What is HMB (beta-hydroxy-beta-methylbutyrate) and its potential benefits for an older adult patient with a greater tuberosity fracture and underlying conditions such as osteoporosis?

What is HMB (Beta-Hydroxy-Beta-Methylbutyrate)?

HMB is a metabolite of the essential amino acid leucine that acts as an anticatabolic agent to preserve muscle mass and strength, particularly during periods of muscle disuse, bedrest, or catabolic stress. 1, 2

Mechanism of Action

• HMB works primarily by minimizing protein breakdown and reducing skeletal muscle damage rather than increasing protein synthesis like anabolic hormones 2, 3
• It reduces muscle apoptosis, increases myogenesis, and has positive effects on muscle protein turnover 4
• HMB functions as an mTOR activator, though clinical data for this mechanism remains inconsistent 5

Clinical Applications in Older Adults

Muscle Preservation During Bedrest and Immobilization

• In a randomized placebo-controlled trial, HMB supplementation during 10 days of bedrest significantly reduced muscle loss and increased muscle mass gain during the 8-week rehabilitation phase in both total lean mass and leg lean mass 1
• Muscle strength was also preserved during the bedrest period with HMB supplementation 1
• This is particularly relevant since just 7 days of bedrest results in 1 kg loss of lean leg muscle mass in older adults 1

Evidence for Muscle Mass Preservation

• A meta-analysis of seven randomized controlled trials (147 older adults receiving HMB vs 140 controls) showed greater muscle mass gain in HMB groups (standard mean difference = 0.352 kg, 95% CI: 0.11-0.594, p=0.004) 6
• HMB supplementation contributed to preservation of muscle mass in older adults and may be useful in preventing muscle atrophy induced by bedrest or other factors 6

Frailty Management

• High-protein oral nutrition shakes supplemented with HMB (HP-HMB) improved physical function and muscle mass in those with pre-frailty 1
• When combined with resistance-based training, protein supplements with HMB appeared to aid resistance training benefits 1

Dosing and Administration

• The usual dose is 3 grams per day, which may be routinely recommended to maintain or improve muscle mass and function 2
• HMB supplementation should be continued for at least one month to achieve beneficial effects, as nutritional interventions need time to be effective on nutritional status and clinical outcomes 1
• The safety profile of HMB is unequivocal with no significant adverse effects reported 2

Application to Your Patient Context

For an older adult with a greater tuberosity fracture and osteoporosis:

• HMB supplementation at 3 g/day should be strongly considered during the immobilization and recovery period to prevent the rapid muscle loss that occurs with bedrest 1, 2
• The fracture will likely require a period of reduced mobility, during which older adults lose approximately 1 kg of lean leg muscle mass per week 1
• HMB can be combined with adequate protein intake (>1 g/kg body weight/day) and resistance exercise when appropriate 1

Important Caveats

Conflicting Evidence on Effectiveness

• An umbrella review of 15 systematic reviews found heterogeneous results: only 5/15 studies found evidence that HMB augmented lean soft-tissue mass, while 10/15 found no difference or insufficient evidence 7
• Most reviews concluded HMB did not affect strength outcomes or studies were inconclusive, with no evidence of improved physical function 7
• The European Society for Clinical Nutrition and Metabolism notes insufficient consistent clinical data to recommend HMB for improving fat-free mass in cancer cachexia 5
• Two recent ICU studies reported no difference in muscle loss with HMB supplementation 5

Clinical Context Matters

• Despite mixed systematic review evidence, the highest quality single RCT in the specific context of bedrest-induced muscle loss in older adults showed clear benefit 1
• Most positive evidence comes from studies in previously untrained individuals or those undergoing bedrest/immobilization 2, 3
• Evidence is less clear in resistance-trained individuals 3

Post-Discharge Considerations

• A large multicenter RCT of 652 malnourished older hospitalized patients found that high-protein ONS containing HMB showed significantly lower 90-day mortality compared to placebo, though no difference in readmission rates 1
• This suggests potential mortality benefit beyond just muscle preservation in malnourished older adults 1