Correlation between biomarkers of creatine metabolism and serum indicators of peripheral muscle fatigue during exhaustive exercise in active men

Exhaustive exercise induces various disturbances of homeostasis, with impaired bioenergetics often associated with strenuous muscular work. However, no study so far validated serum biomarkers of creatine metabolism vs. traditional markers of exhaustive exercise and fatigue. Here, we investigated how well changes in serum guanidinoacetic acid (GAA), creatine and creatinine correlate with responses in blood lactate, creatine kinase, interleukin-6 and cortisol in 11 young active men (age 23.2 +/- 3.7 years; VO2max 49.5 +/- 5.4 ml/kg/min) exposed to exhaustive exercise. All participants were subjected to running at individual running speed at anaerobic threshold until exhaustion, with venous blood drawn at baseline and during an exercise session at 5-min intervals. Running-to-exhaustion markedly affected serum GAA and creatine levels, with circulating GAA increased for 5.3 +/- 8.5%(95% CI, -0.4 to 11.0), and serum creatine elevated by 33.9 +/- 21.8% (95% CI, 19.3 to 48.6) compared to baseline levels (P <= 0.05). In addition, moderate-to-strong positive linear correlations were found between exhaustive exercise-induced changes in serum cortisol and GAA levels (r = 0.79; P = 0.03), and cortisol and creatine concentrations (r = 0.81; P = 0.03). This suggests a link between cortisol and heavy exercise-induced impaired bioenergetics, with future studies needed to evaluate a cause-and-effect interconnection between cortisol and GAA-creatine axis.