Non-enzymatic cyclization of creatine ethyl ester to creatinine

Biochem Biophys Res Commun. 2009 Oct 16;388(2):252-5. doi: 10.1016/j.bbrc.2009.07.151. Epub 2009 Aug 4.


Creatine ethyl ester was incubated at 37 degrees C in both water and phosphate-buffered saline and the diagnostic methylene resonances in the (1)H NMR spectrum were used to identify the resultant products. It was found that mild aqueous conditions result in the cyclization of creatine ethyl ester to provide inactive creatinine as the exclusive product, and this transformation becomes nearly instantaneous as the pH approaches 7.4. This study demonstrates that mild non-enzymatic conditions are sufficient for the cyclization of creatine ethyl ester into creatinine, and together with previous results obtained under enzymatic conditions suggests that there are no physiological conditions that would result in the production of creatine. It is concluded that creatine ethyl ester is a pronutrient for creatinine rather than creatine under all physiological conditions encountered during transit through the various tissues, thus no ergogenic effect is to be expected from supplementation.

MeSH terms

  • Creatine / analogs & derivatives*
  • Creatine / chemistry
  • Creatinine / chemical synthesis*
  • Cyclization
  • Magnetic Resonance Spectroscopy


  • Creatinine
  • creatine ethyl ester
  • Creatine