Creatine and the Liver: Metabolism and Possible Interactions

Mini Rev Med Chem. 2016;16(1):12-8. doi: 10.2174/1389557515666150722102613.


The process of creatine synthesis occurs in two steps, catalyzed by L-arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT), which take place mainly in kidney and liver, respectively. This molecule plays an important energy/pH buffer function in tissues, and to guarantee the maintenance of its total body pool, the lost creatine must be replaced from diet or de novo synthesis. Creatine administration is known to decrease the consumption of Sadenosyl methionine and also reduce the homocysteine production in liver, diminishing fat accumulation and resulting in beneficial effects in fatty liver and non-alcoholic liver disease. Different studies have shown that creatine supplementation could supply brain energy, presenting neuroprotective effects against the encephalopathy induced by hyperammonemia in acute liver failure. Creatine is also taken by many athletes for its ergogenic properties. However, little is known about the adverse effects of creatine supplementation, which are barely described in the literature, with reports of mainly hypothetical effects arising from a small number of scientific publications. Antioxidant effects have been found in several studies, although one of the theories regarding the potential for toxicity from creatine supplementation is that it can increase oxidative stress and potentially form carcinogenic compounds.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Creatine / metabolism*
  • Humans
  • Kidney / metabolism
  • Liver / injuries
  • Liver / metabolism*
  • Performance-Enhancing Substances


  • Performance-Enhancing Substances
  • Creatine