Blood Flow Restriction Training, Genetic Variability and Musculoskeletal Health: A Scoping Review and Translational Perspective

This project is a scoping review designed to systematically map and synthesise the existing literature examining genetic and molecular influences on adaptive responses to blood flow restriction training (BFRT). BFRT is a low-load resistance training modality capable of inducing strength and hypertrophic adaptations comparable to traditional high-load resistance training. Beyond athletic performance contexts, BFRT has increasing relevance for rehabilitation, ageing populations, and individuals unable to tolerate high mechanical loads. However, marked inter-individual variability in training responsiveness has been observed, and the biological determinants of this variability remain poorly understood. The primary purpose of this review is to identify and characterise published human studies investigating BFRT in relation to genetic polymorphisms, gene expression, and molecular signalling pathways associated with muscle hypertrophy and strength development. Specifically, the review aims to: (1) describe molecular pathways reported to be modulated by BFRT, including anabolic, proteolytic, and angiogenic signalling markers; (2) determine whether direct genotype–BFRT interaction studies assessing morphological or functional outcomes have been conducted; and (3) identify gaps in the current evidence base that limit understanding of genetically mediated variability in BFRT adaptation. A structured search of electronic databases was conducted using predefined inclusion and exclusion criteria. Eligible studies were required to involve human participants undergoing BFRT interventions and to report genetic, genomic, or molecular outcomes relevant to strength or hypertrophy. Study selection followed a staged screening process, and data were extracted using a structured framework capturing study characteristics, participant demographics, BFRT protocol parameters, and reported molecular, morphological, and functional outcomes. Findings are synthesised descriptively, consistent with scoping review methodology, without quantitative meta-analysis or inferential statistical modelling. The expected outcomes of this review are to clarify the extent to which genetic and molecular mechanisms have been investigated in the context of BFRT, to highlight the absence or presence of genotype-stratified intervention trials, and to outline priorities for future research. It is anticipated that the review will demonstrate mechanistic plausibility for genetically influenced variability in BFRT responsiveness while revealing a substantial gap in direct genotype–training interaction evidence. By mapping this emerging area of research, the project aims to support the development of future well-powered, genotype-stratified trials and contribute to the advancement of personalised resistance training strategies to optimise musculoskeletal health across diverse populations.