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A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis.

  • 2009-05
  • Phytomedicine : international journal of phytotherapy and phytopharmacology 16(5)
    • Samer S El-Kamary
    • Michelle D Shardell
    • Mohamed Abdel-Hamid
    • Soheir Ismail
    • Mohamed El-Ateek
    • Mohamed Metwally
    • Nabiel Mikhail
    • Mohamed Hashem
    • Amr Mousa
    • Amr Aboul-Fotouh
    • Mohamed El-Kassas
    • Gamal Esmat
    • G Thomas Strickland

Study Design

Type
Randomized Controlled Trial (RCT)
Population
patients with symptoms compatible with acute clinical hepatitis and serum alanine aminotransferase (ALT) levels >2.5 times the upper limit of normal
Methods
randomized, placebo-controlled trial; three times daily ingestion of either a standard recommended dose of 140 mg of silymarin or a vitamin placebo for four weeks with an additional four-week follow-up
Blinding
Double-blind
Duration
four weeks with an additional four-week follow-up
Funding
Unclear

Purpose

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.

Research Insights

  • Thistle→Reduced Alanine Aminotransferase Level

    other variables including direct bilirubin, ALT and aspartate aminotransferase (AST) were not significantly reduced

    Effect
    Neutral
    Effect size
    Small
    Dose
    140 mg three times daily
  • Thistle→Reduced Aspartate Aminotransferase Level

    other variables including direct bilirubin, ALT and aspartate aminotransferase (AST) were not significantly reduced

    Effect
    Neutral
    Effect size
    Small
    Dose
    140 mg three times daily
  • Thistle→Reduced Dark Urine Duration

    Patients randomized to the silymarin group had quicker resolution of symptoms related to biliary retention: dark urine (p=0.013)

    Effect
    Beneficial
    Effect size
    Small
    Dose
    140 mg three times daily
  • Thistle→Reduced Direct Bilirubin Level

    other variables including direct bilirubin, ALT and aspartate aminotransferase (AST) were not significantly reduced

    Effect
    Neutral
    Effect size
    Small
    Dose
    140 mg three times daily
  • Thistle→Reduced Indirect Bilirubin Level

    There was a reduction in indirect bilirubin among those assigned to silymarin (p=0.012)

    Effect
    Beneficial
    Effect size
    Small
    Dose
    140 mg three times daily
  • Thistle→Reduced Jaundice Duration

    Patients randomized to the silymarin group had quicker resolution of symptoms related to biliary retention: ... jaundice (p=0.02)

    Effect
    Beneficial
    Effect size
    Small
    Dose
    140 mg three times daily
  • Thistle→Reduced Scleral Icterus Duration

    Patients randomized to the silymarin group had quicker resolution of symptoms related to biliary retention: ... scleral icterus (p=0.043)

    Effect
    Beneficial
    Effect size
    Small
    Dose
    140 mg three times daily

Adverse Events Reported

  • Thistle→Overall tolerability

    No adverse events were noted and both silymarin and placebo were well tolerated.

    Finding
    Reported
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