Epigenetic Markers of Enhanced Athletic Performance Associated with Creatine Monohydrate Supplementation

Abstract

Purpose – This study investigates whether long-term creatine monohydrate supplementation is associated with distinct epigenetic modifications linked to enhanced athletic performance. While creatine’s physiological effects are well documented, its potential to influence gene regulation through DNA methylation remains largely unexplored.
Design /methodology/ approach – We compared genome-wide DNA methylation profiles (Illumina EPIC850k array) in saliva from resistance-trained adults who had used creatine monohydrate for an average of 6.2 years (n = 107) and non-creatine users with similar training backgrounds (n = 243). Differentially methylated CpG sites were identified using linear modelling with a significance threshold of p ≤ 0.001 and mapped to genes relevant to muscle physiology, energy metabolism, neuromuscular function, and recovery.
Findings – Sixty-four CpG sites (mapping to 34 genes) showed significant methylation differences between groups. Creatine users exhibited hypomethylation in promoters of genes that support muscle differentiation, angiogenesis, fatty acid oxidation, and cellular recovery (e.g., DYRK2, TLE1, CDH5, PEX10, CYP1A1). Conversely, hypermethylation occurred at loci associated with inhibitory or fatigue-related pathways, such as SST (somatostatin. These methylation patterns collectively suggest an epigenetic profile that may enhance training adaptations, including improved vascularisation, metabolic efficiency, neuromuscular resilience, and anabolic potential.
Originality/ value – This study is the first to demonstrate that chronic creatine supplementation is associated with specific epigenetic signatures related to athletic performance. The findings highlight a potential mechanism by which long-term supplementation could contribute to physiological adaptation through modulation of gene regulation.
Research limitations – As a cross-sectional analysis, causality cannot be inferred, and saliva-based methylation profiles may not fully reflect muscle-tissue epigenetics. Future longitudinal and tissue-specific studies are needed to confirm mechanistic pathways.
Practical implications – These results suggest that creatine supplementation may exert long-term biological effects beyond its immediate ergogenic role, offering potential for personalised training, recovery strategies, and epigenetic monitoring in athletic populations.