Pharmacokinetic Profile of the Calcium-salt and Free Acid Forms of β-hydroxy-β-methylbutyrate in Humans

March 1, 2023 updated by: Bruno Gualano, University of Sao Paulo
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • Sao Paulo, Brazil, 05508030
        • School of Physical Education and Sport - USP

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 35 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. age between 18-35 years;
  2. ≥150 min of moderate to intense physical activity per week

Exclusion Criteria.

  1. smoking,
  2. use of statins, anti-inflammatory, or any other medications that could affect lipid metabolism or blood parameters;
  3. current or past use of androgenic anabolic steroids;
  4. diagnosis of gastric or intestinal disorders that could affect nutrient absorption;
  5. diagnosis of kidney or liver disorders that could affect nutrient metabolisation and elimination;
  6. any other condition that could be perceived as a potential confounding factor or that could prevent participation in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: HMB-Ca in water
Investigate whether the pharmacological form of HMB has any impact on its bioavailability and pharmacokinetic profile.
Other: Supplement administation
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.
Experimental: HMB-Ca in capsules
Avaliate AUC of HMB-Calcium form supplementation.
Other: Supplement administation
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.
Experimental: HMB-FA
Avaliate AUC of HMB-free acid form supplementation.
Other: Supplement administation
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Plasma HMB concentration
Time Frame: Up to 720 minutes
Blood samples collected before and multiple times after treatment ingestion for later determination of plasma HMB concentrations
Up to 720 minutes

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Urine HMB
Time Frame: Up to 24 hours
Pre ingestion mid-stream urine sample and 24 hours post ingestion urine
Up to 24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Sao Paulo

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Heitor R Ribeiro, Bsc, University of Sao Paulo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 20, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 20, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 16, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 14, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 14, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HMB pharmacokinetics

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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