Exercise-induced redox remodeling: A scoping review of hormetic adaptation and translational clinical implications from animal and human studies
Ahmed Ashour Abbas Al-Omairi, Farnaz Seifi-Asgshahr, Reza FarzizadehBackground
Exercise-induced reactive oxygen and nitrogen species can be both damaging and adaptive; however, evidence from animal and human studies supporting a unified redox remodeling framework and its clinical impact has not been fully synthesized. This scoping review, to our knowledge, is the first to systematically map preclinical and clinical studies on exercise-induced redox modulation, delineate patterns across exercise modalities, intensities, and populations, and highlight key gaps for future research.
Methodology
This registered scoping review (PROSPERO: CRD420251144680) followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidance. Three major databases (PubMed, Scopus, and Web of Science; 2000–2025) were systematically searched using a prespecified exercise-redox strategy. Original quantitative human and animal studies involving structured exercise with quantifiable intensity and at least one redox biomarker were included. Two independent reviewers screened the records and charted study design, populations, exercise dose, redox outcomes, and functional or clinical endpoints using a piloted standardized form for thematic synthesis.
Results
A total of 141 studies met the inclusion criteria (37 animal and 104 human studies). In animal models, chronic aerobic, resistance, and combined training reduced oxidative damage (MDA, TBARS, carbonyls, and nitrotyrosine), downregulated pro-oxidant enzymes (Nox2), and upregulated antioxidant and cytoprotective systems (superoxide dismutase, CAT, GPx, Nrf2, PGC-1α, and Prdx2), with improvements in cardiovascular, renal, metabolic, and neurocentric endpoints. In humans, acute high-intensity exercise typically induced transient oxidative “eustress,” followed by mobilization of antioxidant defenses, whereas chronic exercise programs (≥6 weeks) shifted basal redox status toward a more reduced, vasculoprotective milieu across healthy, athletic, and clinical populations.
Conclusions
Evidence from diverse preclinical models and clinical populations converges on a conserved hormetic redox remodeling paradigm in response to exercise. However, these findings should be interpreted with caution given the absence of formal quality appraisal, substantial heterogeneity across studies, and the scoping review design. Future trials should use harmonized, multicompartment redox panels, consider individual redox phenotypes, and carefully control nutritional context to optimize mechanistic insight and clinical translation.