Milk thistle is an annual or biennial herb native to the Mediterranean region, which has been used for centuries as a food and as an herbal for treatment of liver conditions. Milk thistle has not been implicated in causing liver injury and is still used widely as a liver tonic in patients with acute and chronic liver diseases.
Milk thistle (Silybum marianum) is an herb native to Europe, Asia Minor and Northern Africa that has been used widely to treat liver disease. Extracts of milk thistle seeds contain multiple flavanolignans, known collectively as silymarin, consisting largely of silybinin, silychristin and silydianin. In cell culture and animal models, silymarin has been shown to prevent or ameliorate acute liver injury due to many toxins including acetaminophen and Amanita phalloides. Human studies of silymarin in patients with chronic liver disease have been promising but inconclusive. Milk thistle is marketed as capsules or tablets containing ethanol extracted silymarin in amounts of 250 to 750 mg and purported to be beneficial for liver disease, including alcoholic and viral liver disease. The daily dosage varies but it is typically taken 2 to 3 times daily. Intravenous preparations of purified silybinin are approved in Europe for therapy of Amanita phalloides mushroom poisoning. Recent human studies have shown that intravenous silybinin lowers hepatitis C virus RNA levels in serum and may be beneficial in combination with peginterferon alfa and ribavirin in treating chronic hepatitis C. Prospective controlled trials of intravenous silybinin are ongoing.
Despite its wide spread use in patients with and without liver disease, milk thistle has not been implicated in causing serum enzyme elevations or clinically apparent acute liver injury. While silymarin has effects on cytochrome P450 enzymes and hepatic transporters in vitro, there is little evidence that it causes clinically significant herb-drug interactions.
Other Names: Silybin, Silybum, Silymarin, Marian thistle
REPRESENTATIVE TRADE NAMES
Milk Thistle – Generic
Herbal and Dietary Supplements
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References updated: 05 January 2014
Zimmerman HJ. Unconventional drugs. Miscellaneous drugs and diagnostic chemicals. In, Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott,1999: pp. 731-4. (Expert review of hepatotoxicity published in 1999; milk thistle is not discussed).
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ed. Amsterdam: Elsevier, 2013, pp. 631-58. (Review of hepatotoxicity of
herbal and dietary supplements [HDS] mentions that silymarin is used to treat liver disease but evidence for its benefit is contradictory).
Milk thistle. In, PDR for Herbal Medicines. 4th ed. Montvale, New Jersey: Thomson Healthcare Inc. 2007: pp. 578-83. (Compilation of short monographs on herbal medications and dietary supplements).
Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 1998; 93: 139-43. PubMed Citation (Review of the evidence of hepatoprotective activities of milk thistle based upon its antioxidants and ability to scavenge free radicals and inhibit lipid peroxidation, but evidence in human trials has been inconclusive; intravenous silymarin protects laboratory animals exposed to Amanita phalloides and open label studies in humans have reported higher than expected survival rates).
Stedman C. Herbal hepatotoxicity. Semin Liver Dis 2002; 22: 195-206. PubMed Citation (Review and description of patterns of liver injury due to herbals, including discussion of potential risk factors, and herb-drug interactions; milk thistle is not discussed).
Schiano TD. Hepatotoxicity and complementary and alternative medicines. Clin Liver Dis 2003; 7: 453-73. PubMed Citation (Comprehensive review of herbal associated hepatotoxicity; milk thistle is not listed as causing hepatotoxicity).
Gordon A, Hobbs DA, Bowden DS, Bailey MJ, Mitchell J, Francis AJ, Roberts SK. Effects of Silybum marianum on serum hepatitis C virus RNA, alanine aminotransferase levels and well-being in patients with chronic hepatitis C. J Gastroenterol Hepatol 2006; 21: 275-80. PubMed Citation (17 patients with chronic hepatitis were treated for 12 weeks with silymarin or placebo in a cross over study; there were no significant changes in HCV RNA or ALT levels and adverse events were similar in the two groups).
Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P. Liver transplantation for acute liver failure from drug-induced liver injury in the United States. Liver Transpl 2004; 10: 1018-23. PubMed Citation (Among ~50,000 liver transplants reported to UNOS between 1990 and 2002, 270 [0.5%] were done for drug induced acute liver failure, including 7 [5%] for herbal medications, none attributed to milk thistle).
García-Cortés M, Borraz Y, Lucena MI, Peláez G, Salmerón J, Diago M, Martínez-Sierra MC, et al. [Liver injury induced by “natural remedies”: an analysis of cases submitted to the Spanish Liver Toxicity Registry]. Rev Esp Enferm Dig 2008; 100: 688-95. Spanish. PubMed Citation (Among 521 cases of drug induced liver injury submitted to Spanish registry, 13 [2%] were due to herbals, but none attributed to milk thistle).
Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135: 1924-34. PubMed Citation (Among 300 cases of drug induced liver disease in the US collected between 2004 and 2008, 9% of cases were attributed to herbal medications, milk thistle is not listed).
Ferenci P, Scherzer TM, Kerschner H, Rutter K, Beinhardt S, Hofer H, Schöniger-Hekele M, et al. Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. Gastroenterology 2008; 135: 1561-7. PubMed Citation (Intravenous infusion of silibinin daily for 7 days led to rapid and marked fall in serum HCV RNA levels in 30 patients with chronic hepatitis C, the decrease starting within one day, ranging from 1 to 5 log IU/mL, being dose dependent and usually followed by a rise once infusions were stopped).
Rambaldi A, Jacobs BP, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database Syst Rev 2007; (4): CD003620. PubMed Citation (Systematic review concluded that milk thistle had no significant effects on mortality in patients with alcoholic liver disease or chronic hepatitis B or C and was not associated with an increased risk of adverse events).
El-Kamary SS, Shardell MD, Abdel-Hamid M, Ismail S, El-Ateek M, Metwally M, Mikhail N, et al. A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis. Phytomedicine 2009; 16: 391-400. PubMed Citation (Controlled trial of 4 week course of silymarin vs placebo in 105 patients with acute viral hepatitis found no differences in outcome, but minimally faster resolution of dark urine and jaundice; there were no serious adverse events and side effects were uncommon and similar in frequency between the two groups).
Navarro VJ. Herbal and dietary supplement hepatotoxicity. Semin Liver Dis 2009; 29: 373-82. PubMed Citation (Overview of the regulatory environment, clinical patterns, and future directions in research with HDS; milk thistle is not listed as a potentially hepatotoxic botanical).
Abenavoli L, Capasso R, Milic N, Capasso F. Milk thistle in liver diseases: past, present, future. Phytother Res 2010; 24: 1423-32. PubMed Citation (Review of the history, active components, mechanism of action, in vitro and in vivo studies of activity and clinical efficacy and safety of milk thistle; the active component is found in lipophilic extracts of the plant seeds and is composed of flavonolignands, silybin, silydianin and silychristin, collectively known as silymarin, which acts as an antioxidant, antifibrotic and toxin blockading agent).
Wagoner J, Negash A, Kane OJ, Martinez LE, Nahmias Y, Bourne N, Owen DM, et al. Multiple effects of silymarin on the hepatitis C virus lifecycle. Hepatology 2010; 51: 1912-21. PubMed Citation (Silymarin inhibited hepatitis C virus replication in cell culture systems, inhibiting virus entry, viral RNA and protein production and production of infectious virus).
Payer BA, Reiberger T, Rutter K, Beinhardt S, Staettermayer AF,
Peck-Radosavljevic M, Ferenci P. Successful HCV eradication and inhibition of HIV replication by intravenous silibinin in an HIV-HCV coinfected patient. J Clin
Virol 2010; 49: 131-3. PubMed Citation (27 year old woman with chronic hepatitis C and HIV infection was treated with two weeks of daily intravenous silibinin overlapping by one week with 16 weeks of peginterferon and ribavirin, and had a sustained HCV and transient HIV virological response).
Schrieber SJ, Hawke RL, Wen Z, Smith PC, Reddy KR, Wahed AS, Belle SH, et al. Differences in the disposition of
silymarin between patients with nonalcoholic fatty liver disease and chronic
hepatitis C. Drug Metab Dispos 2011; 39: 2182-90. PubMed Citation Pharmacokinetic and safety study of escalating doses of silymarin in 18 patients with hepatitis C and 12 with nonalcoholic fatty liver found no evidence of toxicity when given in high doses of up to 8 days).
Loguercio C, Festi D. Silybin and the liver: from basic research to clinical
practice. World J Gastroenterol 2011; 17: 2288-301. PubMed Citation (Review of the chemical structure, mechanisms of action, and clinical efficacy of silybin, a component of milk thistle; no discussion of safety and no mention of hepatotoxicity).
Choi YH, Chin YW, Kim YG. Herb-drug interactions: focus on metabolic enzymes
and transporters. Arch Pharm Res 2011; 34: 1843-63. PubMed Citation (Summary and review of in vitro and clinical evidence of herb-drug interactions).
Fried MW, Navarro VJ, Afdhal N, Belle SH, Wahed AS, Hawke RL, Doo E, et al.; Silymarin in NASH and C Hepatitis (SyNCH) Study Group. Effect of
silymarin (milk thistle) on liver disease in patients with chronic hepatitis C
unsuccessfully treated with interferon therapy: a randomized controlled trial.
JAMA 2012; 308: 274-82. PubMed Citation (Controlled trial of 6 month course of two doses of silymarin vs placebo in 154 patients with chronic hepatitis C found no effect on ALT or HCV RNA levels, and side effects were similar in the silymarin and placebo treated groups).
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