Pharmacokinetic Profile of the Calcium-salt and Free Acid Forms of β-hydroxy-β-methylbutyrate in Humans
Condition: Healthy
Study type: Interventional

Summary: 
      HMB supplementation has been shown to have potential to optimize resistance training
      responses, which may have important implications for sport, exercise, and health. However,
      HMB literature shows uncertainties as to which is the superior pharmaceutical form of
      supplemental HMB (i.e., the calcium salt or the free acid form) in terms of pharmacokinetic
      profile and bioavailability when consumed by humans. This research project investigated the
      bioavailability and pharmacokinetics of two different forms of supplemental HMB, namely HMB
      calcium-salt (HMB-Ca) and HMB Free Acid (HMB-FA). Further, HMB-Ca was provided both diluted
      in water and encapsulated in gelatine capsules. This pharmacokinetics study adopted a
      crossover design, open-label design in which male and female participants visited the
      laboratory on 3 different occasions to receive one the 3 treatments: 1g of HMB; the
      equivalent of 1g of HMB-Ca in water; the equivalent of 1g of HMB-Ca in gelatine capsules.
      Venous blood samples were collected before and multiple time points after treatment
      ingestion, for a period of 12 hours in total. A pre-ingestion midstream urine sample was
      collected as well as a 24-h post-ingestion total urine sample. All plasma and urine samples
      were analysed for their HMB concentrations via LC/MS. Time to peak, maximum concentration,
      area under the curve, half-life time and slope of the incremental phase were calculated to
      examine the pharmacokinetic profile of HMB and compare the 3 different pharmaceutical forms.
    

Detailed description: 
      This study aimed to investigate whether the different pharmaceutical forms of HMB show
      distinct bioavailability and pharmacokinetic profile in humans. A counterbalanced crossover
      open-label study was conducted. 20 male and female participants were recruited, of which 18
      met the inclusion criteria and 16 enrolled in the study. All participants visited the
      laboratory on 3 different occasions, 5-7 days apart to receive one of the following
      treatments: 1) 1 g of HMB-FA, or 2) HMB-Ca (equivalent of 1 g of HMB) in capsules, or 3)
      HMB-Ca (equivalent of 1 g of HMB) dissolved in water. The order of treatments was
      counterbalanced to control for carryover and order effects using a 3-by-6
      (treatment-by-participant) Latin square table (www.statpages.info/latinsq.html). To randomly
      allocate participants to treatment sequences, participants were recruited in blocks of 6,
      each containing 3 males and 3 females so that sexes were counterbalanced too. The allocation
      sequence within each block was defined using a random sequence generator (www.random.org).
      Blood samples were collected before HBM ingestion and 15, 30, 45, 60, 90, 120, 180, 240, 360
      and 720 minutes after HMB ingestion. Urine samples were collected before HMB ingestion
      (midstream sample) and 24 hours post ingestion (24h total urine). A standardised breakfast
      was provided to all participants 1h before treatment ingestion. A standardised snack was
      given to all participants 4 hours after treatment ingestion, and a standardised meal was
      given 6 hours after treatment ingestion. Water ingestion was standardised in the first 360
      minutes after ingestion. In the last 6 hours of the protocol, the participants were dismissed
      from the lab and returned for the 720 post-ingestion blood collection. They consumed food and
      water ad-libitum. HMB concentrations were determined in urine and plasma samples by LC/MS
      using tandem electrospray ionization (ESI). The following pharmacokinetic parameters were
      calculated: Time to peak, maximum concentration, area under the curve, half-life time and
      slope of the incremental phase. Plasma and urine HMB concentrations were compared between
      treatments across time with a 2-factor mixed models analysis. Fixed factors were treatment
      and time, and participants were the random factor. All pairwise comparisons were adjusted
      with the Tukey-Kraemer correction. AUC, relative bioavailability, Cmax and Tmax were compared
      between treatments with repeated measures one-way ANOVA with post-hoc tests adjusted for
      multiple comparisons using the Bonferroni correction.
    

Intervention name(s): Supplement administation
Intervention type(s): Other
Intervention description(s): HMB was administred in 3 different forms: 1) HMB-FA in clear capsules; 2) HMB-Ca in gelatine capsules; 3) HMB-Ca dissolved in water. All treatments provided 1g of HMB. Blood samples were taken before and on multiple time points following ingestion.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Crossover Assignment The order of treatments was be randomized.
Masking: None (Open Label)
Primary purpose: Other