Potential Synergistic Effect of Combined Blood Flow Restriction Training and Betaine Supplementation on Skeletal Muscle

The Potential Synergistic Effect of Combined Blood Flow Restriction Training and Betaine Supplementation on Skeletal Muscle Mechanotransduction-Associated Cell Signaling

The purpose of the study is to determine whether there is a synergistic effect via combining both low-load blood flow restriction (BFR) training and betaine supplementation loading (6g/day for 14 days) on skeletal muscle anabolic signaling pathways that is mediated by enhancements in intracellular water. These effects are proposed to be greater than either BFR training or betaine supplementation alone or compared to control conditions (high-load non-occluded and/or placebo supplementation).

Study Overview

• Status: Completed
• Conditions: Blood Flow Restriction Training; Betaine Supplementation
• Intervention / Treatment: Other: Placebo; Dietary supplement: Betaine

Detailed Description

The purpose of the investigation is to determine whether the combination of blood flow restriction (BFR) training and betaine supplementation can synergistically augment phosphorylated targets associated with mechanotransduction and/or muscle protein synthesis relative to either modality alone and compared against control conditions (standard "high-intensity" resistance training and placebo supplementation) in healthy young males. Secondly, the investigators aim to determine if any potential synergistic effects are mediated by enhanced intracellular fluid volumes, as determined by the changes in water content between hydrated and dehydrated muscle samples, as well as through changes in both muscle and serum betaine concentrations. Finally, the investigators aim to assess differences in the aforementioned interventions on specific gene targets, the betaine/γ-aminobutyric acid transporter, myosin heavy chain I, IIa, and IIx lactate dehydrogenase A. Therefore, the specific aims of this study are to determine in healthy, young males: 1) whether combined BFR training and betaine supplementation significantly augment mechanotransductive growth-associated post-translational protein modifications via extra-to-intracellular fluid flux, alongside 2) potentially altered gene expression that otherwise characterizes phenotypical/biochemical changes in skeletal muscle.

The specific aims of the study are to determine whether:

1. The combination of BFR training and betaine supplementation demonstrates significantly greater phosphorylated FAK, ERK1/2, IRS1, and p70S6K, commensurate with greater wet-to-dry hydration changes, relative to any other combinations between BFR training, standard "high-load" training, betaine supplementation, and/or placebo ingestion.
2. The combination of BFR training and betaine supplementation will result in increased MYH2 gene expression, alongside decreases in MYH7 and MYH1 expression. Furthermore, this combination will also result in the highest degree of HIF-1 and Ldha, as well as the lowest BGT-1 gene expression relative to baseline levels.
3. The combination of BFR training and betaine supplementation will result in a higher load-volume accumulated relative to BFR-alone, and will not be statistically different than high-load-placebo training. Therein, the high-load-betaine group will have the greatest load-volume amidst any other combination of conditions.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Waco, Texas, United States, 76798
      • Baylor University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Only participants considered low risk for cardiovascular disease with no contraindications to exercise as outlined by the ACSM
• Have not consumed any nutritional supplements (aside from a multi-vitamin) one month prior to investigation
• Blood pressure <140/90mmHg
• Resting heart rate <90bpm-

Exclusion Criteria:

• sedentary individual as defined by the ACSM guidelines.
• inadequate resistance training experience (<12 months, <3x/week)
• vegetarian, vegan, or have dietary restrictions or supplements that potentially affect betaine metabolism.
• allergy to topical anesthetics.
• known metabolic or cardiovascular disorder including heart disease, arrhythmias, diabetes, thyroid disease, or hypogonadism.
• genetic disorders/polymorphisms that would act as direct contraindications to betaine supplementation (i.e. methyltetrahydrofolate reductase, hyperhomocysteinemia, etc.)
• bleeding disorder, history of pulmonary disease, hypertension, hepatorenal disease, musculoskeletal disorders, neuromuscular/ neurological diseases, autoimmune disease, cancer, peptic ulcers, anemia, or chronic infection (e.g., HIV).
• resting systolic/diastolic blood pressure and heart rate of more than 140/90 mmHg and 90, respectively.
• taking any blood thinning (e.g., warfarin, Jantoven, etc.), heart, pulmonary, thyroid, anti-hyperlipidemic, hypoglycemic, anti-hypertensive, endocrinologic (e.g, thyroid, insulin, etc), emotional/psychotropic (e.g., Prednisone, Ritalin, Adderall), or neuromuscular/neurological medications.
• taking anabolic androgenic steroids within the past year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 3g/ twice daily (separated by ~12 hours) cellulose placebo for 14 days	Other: Placebo; 3g/ twice daily (separated by ~12 hours) cellulose placebo
Experimental: Betaine Supplementation; 3g/twice daily (separated by ~12 hours) betaine anhydrous for 14 days	Dietary supplement: Betaine; 3g/ twice daily (separated by ~12 hours) betaine anhydrous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum/muscle phosphorylated FAK	Focal adhesion kinase	3 hours following exercise cessation
insulin receptor substrate 1	signalling adapter protein	3 hours following exercise cessation
gene expression of HIF-1	genes related to skeletal muscle adaptation	3 hours following exercise cessation
serum and muscle betaine concentrations	measure related to the supplementation protocol	3 hours following exercise cessation
gene expression BGT-1	genes related to skeletal muscle adaptation	3 hours following exercise cessation
gene expression MHC	genes related to skeletal muscle adaptation	3 hours following exercise cessation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pre-to-post exercise set tissue hydration	hydration status of the participant via multi-frequency bioelectrical impedance	both pre and immediately post exercise session
capillary blood lactate concentrations	blood lactate levels of the participant	both pre and immediately post exercise session
set-to-failure repetition number	as related to the exercise protocol	immediately post exercise session
exercise condition total load-volume.	as related to the exercise protocol and calculated at termination of the exercise session	immediately post exercise session

Collaborators and Investigators

• Sponsor: Baylor University
• Investigators: Principal Investigator: LesLee Funderburk, PhD, Baylor University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): July 30, 2021

Study Registration Dates

• First Submitted: October 20, 2022
• First Submitted That Met QC Criteria: March 28, 2023
• First Posted (Actual): March 29, 2023

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 28, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gastrointestinal Agents; Hypolipidemic Agents; Lipid Regulating Agents; Lipotropic Agents; Betaine
• Other Study ID Numbers: 1676709-6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No