Exercise-Induced Cell-Free DNA Correlates with Energy Expenditure in Multiple Exercise Protocols

Purpose Exercise-induced cell-free DNA (ei-cfDNA) has been studied in response to various types of exercise. Its correlation with exercise intensity and duration has been observed consistently. However, comprehensive measurements and exploration of the tissue of origin are lacking. The aim of this study is to establish precise connections between exercise variables and the distribution of tissue of origin, aiming to provide further evidence supporting its use as a biomarker for exercise. Methods Twelve self-identified active adults (six men and six women) performed a crossover study starting with either endurance testing or resistance testing under different intensities and protocols. We obtained blood before and after each exercise session and measured the levels of cfDNA and determined its tissue of origin utilizing cell type-specific DNA methylation patterns in plasma. Results We found that when duration and intensity are fixed, ei-cfDNA fold change correlates with energy expenditure (P = 0.001) in endurance testing and years trained (P = 0.001) in resistance testing. Most of the ei-cfDNA comes from increases in white blood cells (∼95%) where neutrophils make up the majority (∼74%) and the distribution is different between exercise modalities and protocols. Conclusions This study highlights the potential of exercise-induced cfDNA as a biomarker for exercise, showing correlations with energy expenditure and a consistent pattern of tissue origin. Additional research is needed to investigate potential sex differences in the response of cfDNA to exercise, further exploring its clinical implications.