Oral Bioavailability of Beta-Hydroxy Beta-Methylbutyrate (HMB)
The oral bioavailability of HMB varies significantly depending on its form, with the calcium salt form (HMB-Ca) having approximately 49-80% greater bioavailability than the free acid form (HMB-FA), despite previous claims to the contrary. 1, 2
Forms of HMB and Their Bioavailability
Calcium Salt Form (HMB-Ca)
- Demonstrates superior bioavailability compared to the free acid form 2
- Systemic bioavailability measured at approximately:
- Lower systemic clearance compared to HMB-FA, contributing to higher bioavailability 1
Free Acid Form (HMB-FA)
- Despite some marketing claims, recent research shows lower bioavailability compared to the calcium salt form 2
- Relative bioavailability approximately 61.5% compared to HMB-Ca in water (set as reference at 100%) 2
Pharmacokinetic Differences Between Forms
Absorption Characteristics
- HMB-Ca in water shows the fastest absorption with time to peak plasma concentration (Tmax) of approximately 43 minutes 2
- HMB-Ca in capsules reaches peak concentration in about 79 minutes 2
- HMB-FA reaches peak concentration in approximately 78 minutes 2
- Both forms lead to rapid increases in plasma HMB, but with different magnitudes 2, 4
Peak Plasma Concentrations (Cmax)
- HMB-Ca demonstrates significantly higher peak plasma concentrations:
- HMB-Ca in capsules: ~229 μmol/L
- HMB-Ca in water: ~250 μmol/L
- HMB-FA: ~139 μmol/L 2
Area Under the Curve (AUC)
- HMB-Ca shows substantially higher AUC values compared to HMB-FA:
- HMB-Ca in capsules: ~50,078 μmol/L × 720 min
- HMB-Ca in water: ~47,871 μmol/L × 720 min
- HMB-FA: ~29,130 μmol/L × 720 min 2
Clinical Implications
Despite differences in bioavailability, both forms appear to effectively stimulate muscle protein synthesis and suppress muscle protein breakdown 5. The International Society of Sports Nutrition notes that while HMB-FA was previously thought to lead to increased appearance of HMB in the bloodstream compared to HMB-Ca, recent results are mixed 6.
Common Pitfalls and Considerations
- Earlier studies and marketing materials may have claimed superior bioavailability for the free acid form, but more recent research contradicts this 1, 2
- The pharmaceutical form affects absorption rates but not distribution or elimination kinetics 2
- Food intake may affect absorption of HMB, similar to other orally administered compounds 7
- The calcium salt form may be preferable for supplementation due to its higher bioavailability 1, 2
When considering HMB supplementation, the calcium salt form appears to offer better bioavailability and may provide better value for achieving desired physiological effects.