The Effect of Creatine Monohydrate Supplementation on Tissue Creatine Concentrations in Male and Female Rats

Background Creatine is an essential compound that can store chemical energy and act as an energy buffer during times of metabolic stress in mammals. Creatine can be synthesized endogenously, however dietary supplementation with creatine monohydrate (CM) is a common medical intervention and is used as a common ergogenic aid in athletes. The aim of this study was to investigate the effect of increasing doses of dietary creatine on creatine uptake in brain, heart, skeletal muscle, and liver tissues in male and female rats in preparation for future dietary interventions. Methods 16 male (536g—670g) and 16 female (339g—487g) 12 week old Sprague‐Dawley rats were given access to drinking water with 0 g/L, 2.5 g/L, 5 g/L, or 10 g/L CM and 1% sucrose for 8 weeks. Free creatine and phosphocreatine tissue concentrations were measured using fluorometric assays and combined to report total creatine compound (TCr) concentrations in brain (BR), heart (HRT), liver (LIV), and skeletal muscle [soleus (SOL), extensor digitorum longus (EDL), and gastrocnemius (GAS)] tissues after the 8‐week dietary intervention. Results Males were significantly heavier than females (p<0.001) but there were no differences in body weight between groups of either sex. TCr concentrations in BR were higher with 2.5 g/L (p<0.01), 5 g/L (p<0.05), and 10 g/L (p<0.001) CM compared to control, with only the 2.5 g/L CM dose resulting in a higher TCr concentration in females (p<0.05) compared to males. TCr concentrations in SOL were higher with 5 g/L (p< 0.01) and 10 g/L (p<0.001) CM compared to controls. In EDL and GAS TCr concentrations were higher compared to controls with 2.5 g/L (p<0.01, p<0.05), 5 g/L (p<0.001, p<0.05), and 10 g/L (p<0.001, p<0.01) CM. TCr in GAS showed a trend with females (p<0.10) being higher than males. TCr concentrations in HRT of females were higher with 10 g/L (p<0.01) CM compared to controls and trending towards significance with 5 g/L (p<0.10) CM as compared to controls. TCr concentrations in HRT with 10 g/L CM were significantly higher in females (p<0.001) compared to males. No differences in TCr were observed between groups in LIV. Conclusions CM supplementation provided in water with 1% sucrose for 8 weeks leads to an increase in TCr in brain, heart, and skeletal muscle, but not in liver. Females appeared to be more responsive to CM supplementation in HRT, especially at the highest dose suggesting that dietary interventions involving CM may affect males and females differently. Support or Funding Information Supported by NSERC, Canada.