Response of circulating miRNAs to acute exercise: A systematic Review and Meta-Analysis

AimCell-free microRNAs (cf-miRNAs) are secreted from cells and transported via the blood to exert effects on target tissues. Numerous pathophysiological adaptations, including exercise, alter cf-miRNA levels. In this systematic review we examined miRNA expression at multiple timepoints following acute exercise to capture the temporal dynamics of the response. MethodThe systematic review was registered in PROSPERO (CRD42021256303). A multi-level meta-analysis was used to compare the changes in cf-miRNA levels and the influence of exercise modality. An exploratory machine-learning-based approach was used to capture influential moderators. Primary studies were retrieved from PubMed, Medline Complete, CINAHL and SPORTDiscuss from inception to 12 August 2025. Relative changes in cf-miRNA expression in response to exercise were computed. The ROBINS-I, GRADE, and AMSTAR2 tools were used to assess risk of bias, strength of evidence and methodological quality of the systematic review respectively. ResultsThirty-five studies that included an acute exercise intervention in healthy (N=736) males and females aged 18-45 years met the eligibility criteria. Muscle enriched cf-miR-1 (n=373), cf-miR-133a (n=373) and cf-miR-133b (n=295) levels increased (logFC [95%CI]) 1-2 hours (cf-miR1: 0.92 [0.14, 1.69]; cf-miR133a: 0.86 [0.45, 1.26]; cf-miR-133b: 0.94 [0.16, 1.72]) and 24 hours post-exercise (cf-miR1: 0.64 [0.03, 1.24]; cf-miR133a: 0.5 [0.16, 0.84]; cf-miR-133b: 0.44 [0.02, 0.86]). Interestingly, there were no differences in the overall expression levels of the included miRNAs between exercise modality groups. ConclusionMuscle enriched cf-miRNAs are dynamically regulated post-exercise, displaying distinct temporal expression patterns and provide critical insights to guide future research on cf-miRNA dynamics in exercise contexts. Key PointsO_LIOne of the first studies to apply a multi-level meta-analysis in cf-miRNA research, capturing the temporal dynamics of cf-miRNA responses to acute exercise. C_LIO_LIAcute exercise triggers distinct, time-dependent changes in cf-miRNA levels, with muscle-enriched miR-1, -133a, and -133b upregulated, and cf-miR-20a and -486 downregulated post-exercise. C_LIO_LIFindings are limited by small sample sizes and methodological variability across studies, underscoring the need for more rigorous and consistent research designs C_LI