Blood Flow Restriction Training, Molecular Modulators, and Musculoskeletal Health: A Scoping Review and Translational Perspective.

backgroundBlood flow restriction training (BFRT) is a low-load resistance training modality capable of inducing muscle hypertrophy and strength adaptations that are comparable to traditional high-load resistance training. Beyond athletic performance settings, BFRT has growing relevance for musculoskeletal health, rehabilitation and populations unable to tolerate high mechanical loads. However, substantial inter-individual variability in adaptive responses has been reported. Genetic and molecular factors may partly contribute to this variability and inform more individualised exercise strategies. Other intrinsic and extrinsic factors, including age, sex, training status, nutrition, and protocol-related differences, may also influence adaptive responses.

objectiveThis scoping review aimed to map available evidence on molecular modulators of adaptation to BFRT and to identify gaps in the literature regarding genetic influences on BFRT responses.

methodsA structured search of PubMed, Web of Science and Google Scholar was conducted till 1 February 2026. Experimental and quasi-experimental studies examining BFRT in relation to genetic polymorphisms, gene expression, and molecular signalling pathways associated with strength and hypertrophy outcomes were included. Primary outcomes were genetic and molecular factors relevant to BFRT adaptation, including genetic polymorphisms, gene expression, and molecular signalling markers. Secondary outcomes included muscle strength, hypertrophy, vascular responses, and related functional outcomes where reported. Study selection and data extraction were conducted according to PRISMA-ScR guidelines. The methodological quality of randomised controlled trials was assessed using the PEDro scale. This scoping review was registered retrospectively in the Open Science Framework on 17 March 2026, after completion of the literature search.

resultsFrom an initial 47 records, only three studies (

conclusionsThis scoping review therefore identifies a critical evidence gap, with genotype-informed BFRT prescription remaining unsupported by the current literature. Limited evidence supports the possible role of BFRT in molecular responses associated with muscle adaptation. Future research should prioritise well-designed studies integrating both genetic and molecular analyses to better understand inter-individual variability in BFRT adaptations.