Clinical Review | Published:

Milk Thistle for Alcoholic and/or Hepatitis B or C Liver Diseases—A Systematic Cochrane Hepato-Biliary Group Review with Meta-Analyses of Randomized Clinical Trials

The American Journal of Gastroenterology volume 100, pages 25832591 (2005) | Download Citation




Our objectives were to assess the beneficial and harmful effects of milk thistle (MT) or MT constituents versus placebo or no intervention in patients with alcoholic liver disease and/or hepatitis B and/or C liver diseases.


Randomized clinical trials studying patients with alcoholic and/or hepatitis B or C liver diseases were included (December 2003). The randomized clinical trials were evaluated by components of methodological quality.


Thirteen randomized clinical trials assessed MT in 915 patients with alcoholic and/or hepatitis B or C liver diseases. The methodological quality was low: only 23% of the trials reported adequate allocation concealment and only 46% were considered double blind. MT versus placebo or no intervention for a median duration of 6 months had no significant effects on all-cause mortality (relative risk (RR) 0.78, 95% confidence interval (CI) 0.53–1.15), complications of liver disease, or liver histology. Liver-related mortality was significantly reduced by MT in all trials (RR 0.50, 95% CI 0.29–0.88), but not in high-quality trials (RR 0.57, 95% CI 0.28–1.19). MT was not associated with a significantly increased risk of adverse events.


Based on high-quality trials, MT does not seem to significantly influence the course of patients with alcoholic and/or hepatitis B or C liver diseases. MT could potentially affect liver injury. Adequately conducted randomized clinical trials on MT versus placebo may be needed.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    , , , et al. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 1998;93(2):139–143.

  2. 2.

    . A review of plants used in the treatment of liver disease: Part 1. Altern Med Rev 1998;3(6):410–421.

  3. 3.

    , , . The use of silymarin in the treatment of liver diseases. Drugs 2001;61: 2035–2063.

  4. 4.

    , , , et al. Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetamiophen on rat liver. Planta Med 1989;55(5):417–419.

  5. 5.

    , , , et al. Silymarin protects against paracetamol-induced lipid peroxidation and liver damage. J Appl Toxicol 1992;12: 439–442.

  6. 6.

    , . The effect of silymarin and gamma radiation on nucleid acids in rat organs. J Pharm Pharmacol 1993;45: 910–912.

  7. 7.

    , , . Protective effect of Legalon® in workers exposed to organic solvent. Acta Med Hung 1988;45(2):249–256.

  8. 8.

    , , , et al. Effects of penicillin and silymarin on liver enzymes and blood clotting factors in dogs given a boiled preparation of Amanita phalloides. Toxicol Appl Pharmacol 1978;46(2):455–462.

  9. 9.

    , , . Prevention of silybin of phalloidin-induced acute hepatotoxicity. Toxicol Appl Pharmacol 1979;51: 265–275.

  10. 10.

    , . Die antihepatotoxische Wirkung von Silymarin bei experimentellen Leberschädigunug der Ratte durch Tetrachlorkohlenstoff, D-Galaktosamin und Allylalkohol [The antihepatotoxic effect of silymarin on liver damage induced by carbon tetrachloride, D-galactosamine, and allyl alcohol]. Arzneimittel Forschung 1971;21: 1194–1212.

  11. 11.

    , . Die antihepatotoxische Wirkung von parenteral verabreichten Silymarin bei der Leberbeschädigung der Ratte durch carbonium tetrachloride (CCL4) [The antihepatotoxic effect of parenteral silymarin liver injury caused by CCL4 in the rat]. Arzneimittel Forschung 1973;23: 148–149.

  12. 12.

    , , , et al. Biochemical effect of antioxidants on lipids and liver function in experimentally-induced liver damage. Ann Clin Biochem 1997;34(Pt 6):656–663.

  13. 13.

    , , , et al. The anti-hepatoxic effect of silymarin on thioacetamide-induced liver-damage. Arzneimittel Forschung 1973;23: 160.

  14. 14.

    , . Stabilization of isolated rat liver plasma membranes by treatment in vitro with silymarin. Arzneimittel Forschung 1974;24(5):806–808.

  15. 15.

    , , . Inhibitory action of silymarin of lipid peroxide formation in rat liver mithochondria and microsomes. Biochem Pharmacol 1977;26: 2405–2409.

  16. 16.

    , , , et al. Inhibitory effect of the flavonoid silymarin on the erythrocyte hemolysis induced by phenylhydrazine. Biochem Biophys Res Commun 1985;126: 712–715.

  17. 17.

    , , , et al. Monitoring oxidative damage in patients with liver cirrhosis and different daily alcohol intake. Gut 1994;35: 1637–1643.

  18. 18.

    , , , et al. Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats. Hepatology 1997;26: 643–649.

  19. 19.

    , , , et al. Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons. J Clin Gastroenterol 2003;37: 336–339.

  20. 20.

    , , , et al. Attributable risk for symptomatic liver cirrhosis in Italy. Collaborative Groups for the Study of Liver Diseases in Italy. J Hepatol 1998;28(4):608–614.

  21. 21.

    Alderson P, Green S, Higgins JPT, eds. Cochrane reviewers' handbook 4.2.1 [updated December 2003]. In: The Cochrane Library, Issue 1. John Wiley & Sons, Ltd: Chichester, UK, 2004.

  22. 22.

    , , , et al. Milk thistle for alcoholic and/or hepatitis B or C liver diseases (Protocol for a Cochrane Review). In: The Cochrane library, Issue 2. Oxford: Update Software, 2002.

  23. 23.

    , , , et al. The hepato-biliary group. In: The Cochrane library, Issue 4. Oxford: Update Software, 2003.

  24. 24.

    , , , et al. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273(5):408–412.

  25. 25.

    , , , et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses. Lancet 1998;352: 609–613.

  26. 26.

    , , . Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 2001;135: 982–989.

  27. 27.

    , . Meta-analysis in clinical trials. Control Clin Trials 1986;7(3):177–188.

  28. 28.

    . Practical aspects in monitoring: A brief review. Stat Med 1987;6(7):753–760.

  29. 29.

    , , , et al. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557–560.

  30. 30.

    , , , et al. Estudio controlado sobre el efecto de la silimarina en la enfermedad hepatica alcoholica [Effects of silymarin on alcoholic liver disease. A controlled trial]. Rev Med Chile 1992;120(12):1370–1375.

  31. 31.

    , , , et al. A pilot study on the liver protective effect of silybinphosphatidylcholine complex (IdB1016) in chronic active hepatitis. Int J Clin Pharmacol Ther Toxicol 1993;31(9):456–460.

  32. 32.

    , , , et al. Therapeutic and antilipoperoxidant effects of silybin-phosphatidylcholine complex in chronic liver disease: Preliminary results. Curr Ther Res Clin Exp 1993;53(1):98–102.

  33. 33.

    , , , et al. Silymarin kezelés immunmoduláns hatása kronikus alkoholos májbetegségben [Immunomodulatory effects of silymarin treatment in chronic alcoholic liver disease]. Orv Hetil 1990;131(24):1291–1296.

  34. 34.

    , , , et al. Silymarin kezelés májvédö hatása idült alkoholos májbetegségben [Hepatoprotective activity of silymarin (Legalon®) therapy in patients with chronic alcoholic liver disease]. Orv Hetil 1989;130: 2723–2727.

  35. 35.

    , , . Oxidative stress in the liver and biliary tract diseases. Scand J Gastroenterol 1998;33(suppl 228):38–46.

  36. 36.

    , , , et al. Silymarin (Legalon®) kezelés hatása idült alkoholos májbetegek antioxidáns védörendszerére és a lipid peroxidációra (kettös vak protocoll) [Effects of silymarin (Legalon®) treatment on the antioxidant defense system and lipid peroxidation in patients with chronic alcoholic liver disease. A double blind study]. Orv Hetil 1990;131(16):863–866.

  37. 37.

    , , , et al. Zur Wirksamkeit von Silymarin auf die Uberlebenstrate von Patienten mit Leberzirrhose [The influence of therapy with silymarin on the survival rate of patients with liver cirrhosis]. Wien Klin Wochenschr 1980;92(19):678–683.

  38. 38.

    , , , et al. Treatment with silymarin in patients with cirrhosis of the liver—results of a controlled prospective study and of the post study surveillance. Hepatology 1986;6(4):790.

  39. 39.

    , , , et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 1989;9: 105–113.

  40. 40.

    , , , et al. Controlled prospective study on the effects of silymarin-treatment on patients with cirrhosis of the liver. J Hepatol 1985;1(suppl 2):S229.

  41. 41.

    , , , et al. Silybin-beta-cyclodextrin in the treatment of patients with diabetes mellitus and alcoholic liver disease. Efficacy study of a new preparation of an anti-oxidant agent. Diab Nutr Metab 2002;15(4):222–231.

  42. 42.

    , , , et al. Effects of silymarin on the oxidative stress in patients with alcoholic liver cirrhosis. Results from a controlled, double blind, randomized pilot clinical trial. Hepatology 1998;28(4):629A.

  43. 43.

    , , , et al. Antioxidants effects of silymarin MZ80 in patients with alcoholic liver cirrhosis: Results from a randomized, placebo-controlled, double-blind, clinical trial. J Hepatol 1999;30(suppl 1):150.

  44. 44.

    , , , et al. Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo-controlled clinical study. Int J Clin Pharmacol Ther 2002;40(1):2–8.

  45. 45.

    , , , et al. In vivo effect of free radical scavenger hepatoprotective agents on superoxide dismutase (SOD) activity in patients. Tokai J Exp Clin Med 1990;15(2,3):129–134.

  46. 46.

    , , , et al. Hepatoprotective and immunomodulatory effects of antioxidant therapy. Acta Med Hung 1988;45(3–4):287–295.

  47. 47.

    , , , et al. Hepatoprotective and immunological effects of antioxidant drugs. Tokai J Exp Clin Med 1990;15(2,3):123–127.

  48. 48.

    , , , et al. Immunomodulatory and hepatoprotective effects of in vivo treatment with free radical scavengers. Ital J Gastroenterol 1990;22: 283–287.

  49. 49.

    , , . Zur Wirkung von Silymarin bei der Behandlung der akuten Virushepatitis, Ergebnis einer an zwei medizinischen Zentren durchgeführten Doppelblinstudie [Results of a double blind study on the effect of silymarin in the treatment of acute viral hepatitis, carried out at two medical centers]. Medizinsche Klinik 1978;73(28/29):1060–1065.

  50. 50.

    , , , et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: Results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 1998;28(4):615–621.

  51. 51.

    , , , et al. Traitement de l´hépatite alcoolique par la silymarine. Une étude comparative en double insu chez 116 malades [A randomized double blind trial of silymarin in 116 patients with alcoholic hepatitis]. Gastroenterol Clin Biol 1989;13(2):120–124.

  52. 52.

    , , , et al. Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatol 1997;26(4):871–879.

  53. 53.

    , , , et al. Silymarin reduces hyperinsulinemia, malondialdehyde levels, and daily insulin need in cirrhotic diabetic patients. Curr Ther Res Clin Exp 1993;53(5):533–545.

  54. 54.

    , , , et al. Therapeutic effect of Silipide® in patients with chronic hepatitis C non-responders (NRs) to interferon (IFN) treatment. J Hepatol 1994;21(suppl 1):S100.

  55. 55.

    , , , et al. Silymarin treatment in alcoholic liver disease: A double blind randomized clinical trial (RCT). J Hepatol 1985;(suppl 1):S124.

  56. 56.

    . “Negative trials” are positive! J Hepatol 1998;28(4):731–733.

  57. 57.

    , , , et al. Empirical evidence for selective reporting of outcomes in randomized trials: Comparison of protocols to published articles. JAMA 2004;291(20):2457–2465.

  58. 58.

    , , , et al. Milk thistle: Effects on liver disease and cirrhosis and clinical adverse effects. Evidence Report/Technology Assessment No. 21 (Contract 290–97–0012 to the San Antonio Evidence-based Practice Centre, based at the University of Texas Health Science Center at San Antonio, and the Veterans Evidence-based Research, Dissemination, and Implementation Centre, a Veterans Affairs Services Research and Development Centre of Excellence), AHRQ Publication No. 01-E025. 2000.

  59. 59.

    , , , et al. Milk thistle for the treatment of liver disease: A systematic review and meta-analysis. Am J Med 2002;113(6):506–515.

  60. 60.

    , , . Randomisation to protect against selection bias in healthcare trials (Cochrane Methodology Review). In: The Cochrane library, Issue 4. John Wiley & Sons, Ltd: Chichester, UK, 2003.

  61. 61.

    , , , et al. Comparison of evidence of treatment effects in randomized and nonrandomized studies. JAMA 2001;286: 821–830.

  62. 62.

    . Acute, serious drug-induced liver injury. J Hepatol 2002;37: 675–677.

  63. 63.

    , , , et al. Use of the Romanian product Silimarina® in the treatment of chronic liver diseases. Med Interne 1988;26(4):311–322.

  64. 64.

    , , . Anaphylaktischer shock durch einen Mariendistel-Extrakt bei Soforttyp-Allergie auf Kiwi [Anaphylactic shock due to an extract of Silybum marianum in a patient with immediate-type allergy to kiwi fruit]. Allergologie 1990;10: S387–S388.

Download references


We are indebted to N. Salas for the expert technical computer assistance and to D. Nikolova and S.L. Klingenberg for expert assistance with the retrieval of publications. Special thanks to F. Lirussi, M.I. Lucena, and A. Parés for providing us with more information on the trials they were involved in. We thank the Cochrane Collaboration and the Cochrane Hepato-Biliary Group for assistance.This review will be published as a Cochrane Review in The Cochrane Library. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms. The Cochrane Library should therefore be consulted for the most recent version.

B.P.J. is author of a report and of a meta-analysis on milk thistle for liver diseases. The other authors have no known conflicts of interest.

This study was supported by The 1991 Pharmacy Foundation, Denmark; Copenhagen Hospital Corporation's Research Grant on Getting Research into Practice (GRIP), Denmark; The Danish Medical Research Council's Grant on Getting Research into Practice (GRIP), Denmark.

Author information


  1. Copenhagen Trial Unit, Center for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    • Andrea Rambaldi
    •  & Christian Gluud
  2. Osher Center for Integrative Medicine and Department of Medicine, University of California, San Francisco, California

    • Bradly P Jacobs
  3. Gastroenterology and Digestive Endoscopy Service, San G. Moscati Hospital, Avellino, Italy

    • Gaetano Iaquinto


  1. Search for Andrea Rambaldi in:

  2. Search for Bradly P Jacobs in:

  3. Search for Gaetano Iaquinto in:

  4. Search for Christian Gluud in:

Corresponding author

Correspondence to Christian Gluud.

About this article

Publication history





Further reading