Abstract
Introduction: In the context of muscle regeneration, precise nutrition makes it possible to recover from muscle injuries in athletes. Muscle wasting results in reductions in basal muscle protein synthesis and muscle resistance to anabolic stimulation. Therefore, higher protein intakes are necessary. Regular physical training associated with nutritional health has broad benefits to the health of the gut microbiota. MicroRNAs (miRs) and exosomes have emerged as critical regulators of numerous biological processes, modulating gene expression at the post-transcriptional level. Objective: A systematic review of the literature was developed to highlight the process of muscle regeneration and increased muscle mass in athletes under the modulation of microRNAs and exosomes. Methods: The systematic review rules of the PRISMA Platform and the methodological quality of AMSTAR-2 were followed. The research was carried out from May to June 2025 in the Web of Science, Scopus, Embase, PubMed, Lilacs, Ebsco, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 134 articles were found, and 62 articles were evaluated in full and 52 were included and developed in this systematic review study. Clinical studies showed homogeneity in their results, with Chi-Square (X2) =75.5%>50%. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 12 studies with a high risk of bias and 20 studies that did not meet GRADE and AMSTAR-2. miRs play an important role as regulatory molecules during the muscle healing process. Myoblasts are known to secrete exosomes enriched with miRs into the inflammatory environment, whereby miR-224 is transferred to macrophages to inhibit M2 polarization. Additional data demonstrate that WNT-9a may be a direct target of miR-224 for macrophage polarization. The results showed that miR-122 and myogenic markers were downregulated in C2C12 cells after TGF-β stimulation, and overexpression of miR-122 can restore myogenesis inhibited by TGF-β. Evidence suggests that the exosome derived from mesenchymal stem cells exhibits functions similar to mesenchymal stem cells with low immunogenicity and without tumorization. High rates of intestinal self-renewal are enabled by intestinal stem cells (LGR5+) at the base of intestinal crypts. LGR5+ activity, including proliferation and differentiation rates, is affected by large shifts in nutrient availability, as occurs on a high-fat diet or fasting. The practice of physical activity, endogenous metabolites, and dietary nutrients can directly influence epigenetic enzymes. Dietary manipulations and metabolites can affect tissue stem cell fate decisions. Selfrenewal and differentiation of mesenchymal stem cells can be regulated by manipulating vitamin C, A, or D levels and valine restriction.