title: A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis.
abstract: OBJECTIVE
  Milk thistle or its purified extract, silymarin (Silybum marianum), is widely used in treating acute or chronic hepatitis. Although silymarin is hepatoprotective in animal experiments and some human hepatotoxic exposures, its efficacy in ameliorating the symptoms of acute clinical hepatitis remains inconclusive. In this study, our purpose was to determine whether silymarin improves symptoms, signs and laboratory test results in patients with acute clinical hepatitis, regardless of etiology.
  
  
  METHODS
  This is a randomized, placebo-controlled trial in which participants, treating physicians and data management staff were blinded to treatment group. The study was conducted at two fever hospitals in Tanta and Banha, Egypt where patients with symptoms compatible with acute clinical hepatitis and serum alanine aminotransferase (ALT) levels >2.5 times the upper limit of normal were enrolled. The intervention consisted of three times daily ingestion of either a standard recommended dose of 140 mg of silymarin (Legalon, MADAUS GmbH, Cologne, Germany), or a vitamin placebo for four weeks with an additional four-week follow-up. The primary outcomes were symptoms and signs of acute hepatitis and results of liver function tests on days 2, 4 and 7 and weeks 2, 4, and 8. Side-effects and adverse events were ascertained by self-report.
  
  
  RESULTS
  From July 2003 through October 2005, 105 eligible patients were enrolled after providing informed consent. No adverse events were noted and both silymarin and placebo were well tolerated. Patients randomized to the silymarin group had quicker resolution of symptoms related to biliary retention: dark urine (p=0.013), jaundice (p=0.02) and scleral icterus (p=0.043). There was a reduction in indirect bilirubin among those assigned to silymarin (p=0.012), but other variables including direct bilirubin, ALT and aspartate aminotransferase (AST) were not significantly reduced.
  
  
  CONCLUSIONS
  Patients receiving silymarin had earlier improvement in subjective and clinical markers of biliary excretion. Despite a modest sample size and multiple etiologies for acute clinical hepatitis, our results suggest that standard recommended doses of silymarin are safe and may be potentially effective in improving symptoms of acute clinical hepatitis despite lack of a detectable effect on biomarkers of the underlying hepatocellular inflammatory process.
authors.affiliation: Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. selkamar@epi.umaryland.edu
authors.forename: Samer S
authors.initials: SS
authors.lastname: El-Kamary
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Shardell
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Hamid
authors.forename: Soheir
authors.initials: S
authors.lastname: Ismail
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Ateek
authors.forename: Mohamed
authors.initials: M
authors.lastname: Metwally
authors.forename: Nabiel
authors.initials: N
authors.lastname: Mikhail
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hashem
authors.forename: Amr
authors.initials: A
authors.lastname: Mousa
authors.forename: Amr
authors.initials: A
authors.lastname: Aboul-Fotouh
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Kassas
authors.forename: Gamal
authors.initials: G
authors.lastname: Esmat
authors.forename: G Thomas
authors.initials: GT
authors.lastname: Strickland
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000652:urine; D004311:Double-Blind Method; D004534:Egypt; D005260:Female; D006525:Hepatitis, Viral, Human / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D006801:Humans; D007565:Jaundice / Q000188:drug therapy; D008099:Liver / Q000187:drug effects*; D008297:Male; D020944:Silybum marianum; D008517:Phytotherapy; D010936:Plant Extracts / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012590:Sclera; D012639:Seeds; D012838:Silymarin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014556:Urine / Q000737:chemistry; D055815:Young Adult
chemical_list: D015415:Biomarkers; D010936:Plant Extracts; D012838:Silymarin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin