Comparison of availability and plasma clearance rates of β-hydroxy-β-methylbutyrate delivery in the free acid and calcium salt forms

Br J Nutr. 2015 Nov 14;114(9):1403-9. doi: 10.1017/S0007114515003050. Epub 2015 Sep 16.


β-Hydroxy-β-methylbutyrate (HMB), a leucine metabolite, has long been supplemented as a Ca salt (Ca-HMB) to increase strength and performance gains with exercise and to reduce recovery time. Recently, the free acid form of HMB (HMB-FA) has become commercially available in capsule form (gelcap). The current study was conducted to compare the bioavailability of HMB using the two commercially available capsule forms of HMB-FA and Ca-HMB. We also compared the pharmacokinetics of each form when administered mixed in water. Ten human subjects (five male and five female) were studied in a randomised crossover design. There was no significant sex by treatment interaction for any of the pharmacokinetic parameters measured. HMB-FA administered in capsules was more efficient than Ca-HMB capsule at HMB delivery with a 37 % increase in plasma clearance rate (74·8 (sem 4·0) v. 54·5 (sem 3·2) ml/min, P<0·0001) and a 76 % increase in peak plasma HMB concentration (270·2 (sem 17·8) v. 153·9 (sem 17·9) μmol/l, P<0·006), which was reached in one-third the time (P<0·009). When HMB-FA and Ca-HMB were administered in water, the differences still favoured HMB-FA, albeit to a lesser degree. Plasma HMB with HMB-FA administered in water was greater during the early phase of absorption (up to 45 min postadministration, P<0·05); this resulted in increased AUC during the first 60 min after administration, when compared with Ca-HMB mixed in water (P<0·03). In conclusion, HMB-FA in capsule form improves clearance rate and availability of HMB compared with Ca-HMB in capsule form.

Keywords: Ca-HMB calcium salt of HMB; Calcium salt of hydroxy-β-methylbutyrate; Capsules; Clearance; Free acid form of hydroxy-β-methylbutyrate; Gelcaps; HMB β-hydroxy-β-methylbutyrate; HMB-FA free acid form of HMB; β-Hydroxy-β-methylbutyrate.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biological Availability
  • Calcium / administration & dosage
  • Calcium / blood*
  • Calcium / pharmacokinetics*
  • Cross-Over Studies
  • Dietary Supplements
  • Exercise
  • Female
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Valerates / administration & dosage
  • Valerates / blood*
  • Valerates / pharmacokinetics*
  • Young Adult


  • Valerates
  • beta-hydroxyisovaleric acid
  • Calcium