Exercise and nutrition as epigenetic regulators of gene expression: an exploratory scoping review with bibliometric analysis.

Abstract

Epigenetic processes are increasingly discussed as a potential interface between environmental exposures and genomic function. However, systematic integration and forward-looking synthesis of how exercise and nutrition, considered modifiable lifestyle interventions, are studied in relation to epigenetic contexts and associated health outcomes remains limited. This study maps and summarizes the scope of existing evidence on combined interventions of exercise and nutrition in relation to epigenetic contexts and associated health outcomes using a scoping review and bibliometric analysis. It identifies research hotspots and knowledge gaps and characterizes the developmental trajectory of the field, with particular emphasis on its current exploratory stage and future research directions. This scoping review followed the five-step framework proposed by Arksey and O'Malley. A systematic search was conducted in PubMed, Web of Science, Scopus, EMBASE, and MEDLINE from database inception to 5 October 2025. Visualization analyses and strategic coordinate modeling were performed using CiteSpace, VOSviewer, and the R bibliometrix package to examine collaboration networks, thematic clusters, and research frontiers across countries, institutions, authors, and keywords. Seventeen studies involving 1,568 participants were included, with randomized controlled trials as the predominant design (13 studies, 76.5%). The findings indicate that combined interventions of exercise and nutrition are associated with multi-layered epigenetic changes within specific tissues and study contexts, with patterns suggestive of potential synergistic or additive interactions involving DNA methylation, histone modifications, and non-coding RNAs. These epigenetic observations have been reported alongside improvements in metabolic health, enhanced muscular adaptability, modulation of inflammatory processes, and markers related to aging-associated pathways. Bibliometric analysis indicated that publication output remains geographically concentrated, while keyword clustering revealed three core thematic dimensions: intervention strategies, mechanistic exploration, and health outcomes. Keywords with high betweenness centrality included "exercise," "inflammation," and "DNA methylation," whereas "tissue-specific responses" and "epigenetic clocks" appeared as emerging areas of research interest. Combined interventions of exercise and nutrition demonstrate promising but predominantly exploratory associations within epigenetic contexts and related health outcomes. Current evidence remains limited in scale and heterogeneous in design. Future research may benefit from standardizing epigenetic assessments, strengthening longitudinal and multi-tissue investigations, integrating multi-omics approaches, and enhancing international collaboration. Collectively, the available literature lays conceptual and methodological groundwork for future hypothesis-driven and validation-focused research, rather than supporting validated predictive or precision-oriented applications at present.