Comparison of efficacy of folic acid and silymarin in the management of antiepileptic drug induced liver injury: a randomized clinical trial

Hepatobiliary Pancreat Dis Int. 2017 Jun;16(3):296-302. doi: 10.1016/s1499-3872(16)60142-x.


Background: Liver injury associated with antiepileptic drugs accounts for a large proportion of drug-induced liver injuries (DILI) in children. Although withdrawal of the causative agent is the only proved treatment for DILI, in some clinical situations it is not possible. Recent studies have reported promising results of using hepatoprotective drugs with antioxidant actions for the management of DILI. This study aimed to evaluate the efficacy of folic acid versus silymarin treatment in relation to decreasing liver enzymes in patients with DILI due to antiepileptic therapy.

Methods: This randomized, open-label, clinical trial evaluated 55 children with epilepsy who were on antiepileptic treatment and experienced DILI. The children were randomized to receive either silymarin (5 mg/kg per day) or folic acid (1 mg per day) for one month and were followed up for three months.

Results: Liver enzymes significantly decreased in both groups. The decrease trend in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were stronger in the folic acid group compared to silymarin group (P=0.04 and P=0.007, respectively). At the end of the study patients in the folic acid group had significantly lower ALT (P=0.04), AST (P=0.02), and gamma-glutamyl transferase (GGT) (P<0.001) levels and also higher percentage of normal ALT (30.7% vs 3.4%, P=0.009) and AST (42.3% vs 0%, P<0.001), and GGT (23.1% vs 0%, P=0.008) values compared to the patients in the silymarin group. No rebound elevations in ALT, AST and GGT levels or adverse reactions were noted in neither of the study groups.

Conclusion: Although both treatments were safe and effective in decreasing liver enzymes, folic acid seems to be superior to silymarin in the management of DILI.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Anticonvulsants / adverse effects*
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood
  • Chemical and Drug Induced Liver Injury / blood
  • Chemical and Drug Induced Liver Injury / diagnosis
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Child
  • Child, Preschool
  • Clinical Enzyme Tests
  • Cytoprotection
  • Drug Administration Schedule
  • Female
  • Folic Acid / administration & dosage*
  • Folic Acid / adverse effects
  • Humans
  • Infant
  • Iran
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / pathology
  • Liver Function Tests
  • Male
  • Prospective Studies
  • Protective Agents / administration & dosage*
  • Protective Agents / adverse effects
  • Silymarin / administration & dosage*
  • Silymarin / adverse effects
  • Time Factors
  • Treatment Outcome
  • gamma-Glutamyltransferase / blood


  • Anticonvulsants
  • Biomarkers
  • Protective Agents
  • Silymarin
  • Folic Acid
  • gamma-Glutamyltransferase
  • gamma-glutamyltransferase, human
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Alkaline Phosphatase