Potential toxicity of chronic creatine supplementation in mice

Creatine is alleged to be a popular nutrition to enhance sports performance. It can be metabolized to methylamine, which is further converted to formaldehyde, hydrogen peroxide and ammonium by semicarbazied-sensitive amine oxidases (SSAO). Until now, there is no scientific available data for demonstration the long-term health risks of chronic creatine ingestion. In this study, we demonstrated that after chronic oral administration of creatine to mice, the level of methylamine and formaldehyde in urine were increased, SSAO activity of serum and tissue were increased simultaneously. SSAO inhibitor (2-bromoethylamine hydrobromide) could substantially increase the methylamine level and decrease the formaldehyde content respectively. A novel high-performance liquid chromatography (HPLC) and electrospray ionization (ESI) mass spectrometry method for the determination of SSAO activity was developed for the first time. Potential toxicity after chronic creatine administration was discussed according to the increase of toxic products content and SSAO activity. To our knowledge, this is the first report on the research of relationship between SSAO and creatine.