Clinical trial NCT05444959: The Impact of Exercise / Stress Stimuli on HMB Supplementation Efficacy
Official title: Evaluation of the Impact of Exercise / Stress Stimuli on the Mechanisms and Efficacy of Beta-hydroxy-beta-methylbutyric Acid (HMB) in Trained and Malnourished Subjects
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Supplementation
Sport
Sports Nutrition
Sports Dietetics
Protein Kinases
Aerobic Capacity
Fat Free Mass
Lead sponsor: Poznan University of Physical Education
Sponsor class: OTHER
Collaborators: name: National Science Centre, Poland
name: Faculty of Physical Education and Sport at Charles University, Czech Republic
name: Poznan University of Life Sciences, Poland
First posted: 2022-07-06
Enrollment: 120
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study aims at assessing the influence of β-hydroxy-β-methylbutyrate (HMB) free acid supplementation (90 mg/kg of fat free body mass/day) supplemented for 21 days on protein kinases activity and selected hormones levels, and subsequent improvements in muscle protein synthesis, lean body mass content and aerobic capacity.

Detailed description: The main aim of the project is to assess the effects of 21 days of HMB (90 mg/kg of fat free body mass per day) or Placebo (PLA) supplementation under two distinct exercise/stress stimulus conditions in the groups of exercise trained participants (S group) and individuals showing features of malnutrition (W group) on the activity of Akt/PBK/mTOR/p70S6K and MAPK/ERK protein kinase pathway in peripheral blood mononuclear cells and muscle; blood concentrations of free and total testosterone, cortisol, IGF-1 and growth hormone; level of resting and exercise energy metabolism rate and alternations in energy sources utilization during exercise, as well as aerobic capacity and body composition.

The study is a double-blind, randomized, placebo-controlled, parallel-group trial. The study protocol consists of two 21-days supplementation periods. Within the first period of the trial the participants will follow their customary physical exercise (S group) / lifestyle (W group). In turn, in the second period of the trial the routine training (S group) or customary lifestyle (W group) will be supplemented twice a week with a functional training program, as a source of an additional exercise/stress stimulus.

Investigators aim to recruit 60 exercise trained individuals (S group) and 60 will be inactive individuals showing features of malnutrition (W group). Random allocation of participants to the HMB and PLA treatments will be done using a random sequence generator, with groups being equalised by fat-free mass level (within S group and W group separately).

At the first preliminary visit anthropometric measurements, and familiarization with exercise test procedures \[i.e., incremental cycling test with ergorespirometry, maximal voluntary isometric contraction test (MVIC; performed in a Biodex isokinetic dynamometer)\] will be performed. After the completion of the preliminary tests, the participants within S group and W group will be divided randomly into two treatments: 90mg/kgFFM per day of HMB or the same amount of PLA. There will be two 21-days supplementation periods differing in the type of exercise/stress stimulus of the organism.

Before the start of supplementation period (T1) and after their completion (T2 and T3) the series of testing procedures will be performed, each of the series will consist of one day. Each testing series (T1, T2, and T3) will include anthropometric measurements followed by pre-exercise (pre-Ex) blood collection (for the determination of the activity of signaling protein kinases in peripheral blood mononuclear cells; hormone concentrations: free and total testosterone, cortisol, IGF-1 and growth hormone; concentrations of alternative energy sources: ketone bodies \<acetoacetate and beta-hydroxybutyrate\> and free fatty acids; activity of selected enzymes: lactate dehydrogenase \<LDH\>, and creatine kinase \<CK\>; gasometric indices: pH, pCO2, pO2 and electrolytes: Ca2+, Na+, K+, Cl-; concentrations of other biochemical indices: myoglobin, urea, creatinine, glucose, lactate, bilirubins ), the m. vastus lateralis ultrasound and collection of the m. vastus lateralis samples using the percutaneous muscle microbiopsy technique (for the determination of the activity of signaling protein kinases). After the resting pre-Ex procedures, the ICT will be performed. Then the post-exercise (post-Ex) blood sampling and second muscle microbiopsy will be carried out. Finally, at the end of the procedures the MVIC will be assessed.

After collection all the data, comparisons between supplementation treatment conditions (HMB vs PLA) within groups and supplementation periods, as well as comparisons between studied groups (S group vs W group) within supplementation treatment and supplementation period will be performed using T-test for independent variables. Comparisons between supplementation periods within studied groups and supplementation treatment will be performed via T-test for dependent variables. Statistical analysis will be performed using Statistica v. 13.3, StatSoft Polska Sp. z o.o., 2022.

Eligibility criteria: Inclusion Criteria:

* written informed consent from all participants before the study
* a current medical clearance to practice sports,
* Group S: regular physical activity (\> 250 minutes per week), training practice (\> 10 years),
* Group W: a subjects characterized by certain features of the body malnutrition (BMI \< 18.5), low lean body mass (FFMI \< 17.4) and lack of regular physical activity that never were trained in competitive sports,

Exclusion Criteria:

* current injury,
* any health-related contraindication,
* declared general feeling of being unwell,
* unwilling to follow the study protocol,
* serious disease or metabolic problems,
* intake of ergogenic supplements 3 months before the beginning of the study,
* history of anabolic androgenic steroids or drugs use that may interfere with muscle mass control (eg, corticosteroids), or affect physical performance,
* smoking and tobacco use,
* presence of infectious disease in the previous 4 weeks of the study

Primary outcomes:
measure: Change in the molecular potential after supplementation and exercises-induced stress stimuli on the organism
timeFrame: Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
Secondary outcomes:
measure: Changes in the muscle cholesterol and mevalonate content (in the vastus lateralis muscle samples) after supplementation and exercises-induced stress stimuli on the organism
timeFrame: Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
measure: Changes in blood concentrations of hormones: free and total testosterone, cortisol, IGF-1, growth hormone after supplementation and exercises-induced stress stimuli on the organism.
timeFrame: Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
measure: Changes in creatine kinase (CK) and lactate dehydrogenase (LDH) activity (IU) in blood after supplementation and exercises-induced stress stimuli on the organism
timeFrame: Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
measure: Changes in body mass and body mass composition after supplementation and exercises-induced stress stimuli on the organism
timeFrame: Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
measure: Changes in maximal oxygen uptake during the incremental cycling test after supplementation and exercises-induced stress stimuli on the organism
timeFrame: Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
measure: Changes in total body water content after supplementation and exercises-induced stress stimuli on the organism
timeFrame: Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
measure: Changes in other biochemical indices: myoglobin, urea, creatinine, glucose, lactate, bilirubins and electrolytes (Ca2+, Na+, K+, Cl-) after supplementation and exercises-induced stress stimuli on the organism
timeFrame: Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
measure: Changes in utilization of energy substrates during rest and physical exercise after supplementation and exercises-induced stress stimuli on the organism
timeFrame: Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
measure: Changes in resting and exercise energy expenditures after supplementation and exercises-induced stress stimuli on the organism
timeFrame: Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
measure: Changes in total daily energy expenditures after supplementation and exercises-induced stress stimuli on the organism
timeFrame: Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
measure: Changes in specific exercise performance test Fight Gone Bad after supplementation and exercises-induced stress stimuli on the organism
timeFrame: Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
measure: Changes in the maximum voluntary isometric contraction (MVIC) after supplementation and exercises-induced muscle damage
timeFrame: Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: Department of Physiology and Biochemisty at the Faculty of Physical Education and Sport (Charles University, Prague, Czech Republic)
state: Prague 6
city: Poznań
country: Poland
facility: Department of Sports Dietetics, Poznan University of Physical Education
state: Wielkopolska
Study officials:
affiliation: Department of Sports Dietetics, Poznan University of Physical Education
name: Krzysztof Durkalec-Michalski, Prof., PhD
role: PRINCIPAL_INVESTIGATOR
References: