Valproic acid metabolism and its effects on mitochondrial fatty acid oxidation: a review

J Inherit Metab Dis. 2008 Apr;31(2):205-16. doi: 10.1007/s10545-008-0841-x. Epub 2008 Apr 4.


Valproic acid (VPA; 2-n-propylpentanoic acid) is widely used as a major drug in the treatment of epilepsy and in the control of several types of seizures. Being a simple fatty acid, VPA is a substrate for the fatty acid beta-oxidation (FAO) pathway, which takes place primarily in mitochondria. The toxicity of valproate has long been considered to be due primarily to its interference with mitochondrial beta-oxidation. The metabolism of the drug, its effects on enzymes of FAO and their cofactors such as CoA and/or carnitine will be reviewed. The cumulative consequences of VPA therapy in inborn errors of metabolism (IEMs) and the importance of recognizing an underlying IEM in cases of VPA-induced steatosis and acute liver toxicity are two different concepts that will be emphasized.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / toxicity*
  • Biotransformation
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Fatty Acids / metabolism*
  • Fatty Liver / chemically induced
  • Fatty Liver / metabolism
  • Humans
  • Metabolism, Inborn Errors / complications
  • Metabolism, Inborn Errors / metabolism
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Oxidation-Reduction
  • Risk Assessment
  • Risk Factors
  • Valproic Acid / pharmacokinetics
  • Valproic Acid / toxicity*


  • Anticonvulsants
  • Fatty Acids
  • Valproic Acid