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

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.