Free acid gel form of β-hydroxy-β-methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt

Journal Title (Medline/Pubmed accepted abbreviation): Br. J. Nutr.
Year: 2011
Volume: 105
Page numbers: 367-372
doi (if applicable): 10.1017/S0007114510003582

Summary of Background and Research Design

Background:β-Hydroxy-β-methylbutyrate (HMB) is a natural metabolite of the amino acid leucine. It is thought to be involved in regulating protein metabolism and is used as a supplement to increase the synthesis of muscle protein. HMB can be found as a free acid or as a salt. Most HMB supplements that are sold currently are calcium HMB (CaHMB). Plasma HMB levels peak roughly 60-120 min after oral ingestion of CaHMB.

Study 1) Free acid HMB in a gel matrix will be absorbed more completely and at a faster rate than CaHMB.
Study 2) HMB will be utilized and excreted faster as a free acid gel than a calcium salt.

Subjects:Both studies recruited 4 males and 4 females, age 19-29.

Experimental design:randomized, cross-over (both studies)

Treatments:CaHMB was consumed in capsule form. Free acid HMB was made into a gel and either swallowed or held sublingually (under the tongue) for 15 sec. All treatments contained 0.8 g HMB and were washed down with 355 mL (1.5 cups) of water. Each subject consumed each treatment one time.

Protocol:Two experiments were discussed assessing the uptake and utilization of HMB. First, blood levels of HMB for 3 hrs following oral ingestion were investigated. Second, the half-life of HMB in the body was assessed by acquiring blood and urine samples for 24 hrs post-HMB ingestion.
     In both studies, after an overnight fast, a baseline blood sample was drawn and 11 samples were drawn between 2 and 180 min post HMB ingestion. In the second study, additional blood samples were drawn at 6 hrs, 12 hrs, and 24 hrs post-HMB ingestion. Plasma was analyzed for numerous medical safety variables (e.g., blood urea nitrogen, creatinine, liver enzymes, blood lipids, serum proteins, etc).

Summary of research findings:
  • Plasma HMB levels reached a peak of about 245 µM about 30 min post-free acid HMB gel ingestion (swallowed immediately or after being held sublingually for 15 sec). Peak HMB plasma levels were only 131 ± 10 µM after ingestion of CaHMB and were not obtained until about 120 min. These differences are statistically significant (p < 0.001).Plasma levels of HMB were not significantly different between any treatment at 180 min.
  • Between 3 and 24 hrs, blood levels of HMB from the calcium salt were slightly higher than that from the free acid at 6 and 12 hrs (p < 0.05). HMB from all treatments was metabolized and/or excreted by 24 hrs.
  • The area under the curve (AUC) for plasma HMB concentration vs. time after ingestion of the free acid gel was nearly double that from the calcium salt in 3 hrs and about 15% greater when calculated for 24 hrs.
  • Urinary losses of HMB were similar with all treatments. For the immediately swallowed gel, 18 ± 3% was accounted for, 17 ± 3% of the sublingually held gel was accounted for, and 15 ± 2% of the calcium HMB was accounted for.
  • There were no abnormalities in any of the measured blood parameters following ingestion of either form of HMB. There were also no differences between the treatments. This suggests that all forms of HMB are safe in this 0.8 g acute dose.

Interpretation of findings/Key practice applications:

HMB in the free acid- gel appears to be a superior delivery system for HMB than the calcium salt due to the higher peak plasma levels of HMB and the more efficient utilization. Higher levels of HMB in the blood may have greater effects on protein synthesis, especially when ingested close to a workout.


The authors did not measure the effects of free acid HMB on muscle protein synthesis or exercise performance. There is no guarentee that the higher levels of HMB in the plasma is the same as higher levels of HMB in muscle cells.
     It is unknown what concentration of CaHMB is required to reach the plasma HMB concentrations achieved with the free acid form. It would be interesting to see if high HMB levels could be sustained throughout the day and if that would be easier with CaHMB.
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