About Herbs, Botanicals & Other Products

Scientific Name
Silybum marianum, Carduus marianum
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Common Name

Holy thistle, lady's thistle, Mary thistle, Marian thistle

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Clinical Summary

Derived from the seed, pod, or fruit of the plant. Silymarin, a flavolignan from milk thistle, is used primarily to manage various liver diseases. Placebo-controlled clinical studies show its efficacy in reducing aminotransferases in alcoholic liver disease (9) and conclusions from a systematic review suggest usefulness of silymarin for liver cirrhosis (19). Milk thistle was also shown to reduce liver toxicity associated with chemotherapy in children with acute lymphoblastic leukemia (20). Studies for other types of hepatic disease are flawed (10) (11).
Data from a randomized controlled study indicate benefits of milk thistle supplementation in improving glycemic profile in type II diabetic patients (18).

In vitro and animal studies suggest that flavonoids in milk thistle have antioxidant, anticancer effects (7) (8) (12) (16) (17), and may protect against Alzheimer's disease (23) (24); Silymarin demonstrated estrogenic activity with mild proliferative effects in rat uteri (27).
Human studies are warranted.

A case study indicates the utility of intravenous silibinin in patients coinfected with HIV and HCV (Hepatitis C virus) (21).
Toxicity (sweating, nausea, vomiting, and weakness) has been reported from use of milk thistle (5). Milk thistle inhibits cytochrome p450 3A4 (4), which may result in increased levels of medications that are metabolized via this pathway.

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Purported Uses
  • Alcoholism
  • Cancer prevention
  • Cirrhosis
  • Drug-induced hepatotoxicity
  • Food poisoning
  • Hepatitis
  • Indigestion
  • Liver disease
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Constituents
  • Flavolignan: 1.5% silymarin; a mixture of three compounds silybinin, silidyanin, and silychristin. Also dehydrosilybin, siliandrin, silybinome, and silyhermin
  • Tocopherol sterols: Cholesterol, capesterol, stigmasterol, and sitosterol
  • Other constituents: Taxifolin, quercetin, dihydrokaempferol, kaempferol, apigenin, naringin, eriodyctiol, chrysoeriol, linoleic acid, palmitic acid
    (1)
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Mechanism of Action

Milk thistle provides hepatocellular protection by stabilizing hepatic cell membranes. It alters the structure of the outer cell membrane of the hepatocytes in such a way as to prevent the penetration of the liver toxins into the interior of the cell. The stimulation effect on nucleolar polymerase A results in an increase in ribosomal protein synthesis, and thus increases the regenerative ability of the liver and the formation of new hepatocytes. Other actions include interruption of enterohepatic recirculation of toxins and regeneration of damaged hepatocytes (2). An animal study performed in rats demonstrated a reduction in kidney damage following administration of cisplatin without diminished anti-tumor activity (7). Other studies indicate the flavonoids in milk thistle have anticancer effects by inducing G1 and S phase arrest in cells (8). Anecdotal data suggests that milk thistle may prevent liver damage from hepatotoxic medications including butyrophenones, phenothiazines, and phenytoin (6).

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Pharmacokinetics

Following oral administration, milk thistle is poorly absorbed from the gastrointestinal tract with a bioavailability of approximately 23-47%. Peak plasma concentrations occur within 2-4 hours (3). Milk thistle inhibits cytochrome p450 isoenzyme 3A4 and has an elimination half-life of approximately 4 hours. 30-40% of administered dose is recoverable from the bile as both glucuronide or sulfate conjugates and 2-5% is excreted in the urine (4).

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Adverse Reactions

Common: Diarrhea caused by mild laxative effect, uterine and menstrual stimulation.
Case report: One report of a patient who experienced intermittent episodes of sweating, nausea, vomiting, diarrhea, abdominal pain, weakness and collapse that resolved after discontinuation of supplement (5).
Case report: A 25-year-old man developed a severe case of epistaxis, which may have been due to his self medication with aspirin, garlic, and milk thistle. His symptoms improved following treatment (22).
Clinical study: At high dosage, silibinin can elevate bilirubin and liver enzymes (25).

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Herb-Drug Interactions
  • Cytochrome P-450 3A4 substrates: Milk thistle inhibits cytochrome P-450 3A4 (4) and can affect the intracellular concentration of drugs metabolized by this enzyme. However, conflicting data indicate no such effects (13) (14).
    According to another study, consumption of milk thistle did not reduce levels of indinavir, an AIDS drug (15).
  • UGT (Uridine 5'-diphospho-glucuronosyltransferase) substrates: Milk thistle modulates UGT enzymes in vitro and can increase the side effects of drugs metabolized by them (26).
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Herb Lab Interactions

Liver function tests may be altered. Reduced aminotransferases.

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Literature Summary and Critique

Ladas EJ, Kroll DJ, Oberlies NH, et al. A Randomized, Controlled, Double-Blind, Pilot Study of Milk Thistle for the Treatment of Hepatotoxicity in Childhood Acute Lymphoblastic Leukemia (ALL).Cancer 2010;116(2):506-13.
Fifty children with acute lymphoblastic leukemia (ALL) and hepatotoxicity were randomized to receive milk thistle (240 mg capsule containing 80 mg of silibinin) or placebo orally for 28 days. Supplementation began the day after the children received intravenous chemotherapy. Liver function tests were conducted through the study period. At day 56, researchers observed significant reductions in the levels of aspartate amino transferase (AST) and amino alanine transferase (ALT) in patients on milk thistle compared to those who took placebo. Further, milk thistle did not interfere with the chemotherapy.
Larger studies are needed to establish the efficacy of milk thistle as a supportive agent because the sample size in this study is small. Also, the enzymes AST and ALT are not specific markers of chemotherapy-induced hepatotoxicity.

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References
  1. Bissett N, et al. Herbal Drugs and Phytopharmaceuticals. New York: Medpharm, CRC Press; 1994.
  2. Blumenthal M. Herbal Medicine, Expanded Commission E Monographs, 1st ed. Austin: American Botanical Council; 2000.
  3. Schandalik R, Perucca E. Pharmacokinetics of silybin following oral administration of silipide in patients with extrahepatic biliary obstruction. Drugs Exp Clin Res 1994;20:37-42.
  4. Venkataramanan R, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucoronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 2000;28:1270-3.
  5. Adverse Drug Reactions Advisory Committee. An adverse reaction to the herbal medication milk thistle (Silybum marianum). Med J Aust 1999;170:218-9.
  6. Brinker F. Herb Contraindications and Drug Interactions, 2nd ed. Sandy (OR): Eclectic Med; 1998.
  7. Kohno H, et al. Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats. Int J Cancer 2002;101:461-8.
  8. Tyagi A, et al. Antiproliferative and apoptotic effects of silibinin in rat prostate cancer cells. Prostate 2002 ;53:211-217.
  9. Feher J, et al. Liver-protective action of silymarin therapy in chronic alcoholic liver diseases. Orv Hetil 1989;130:2723-7.
  10. Salmi HA, et al.Effect of Silymarin on chemical, functional, and morphological alterations of the liver: a double blind study. Scand J Gastroenterol 1982;17:517-21.
  11. Ferenci P, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 1989;1:105-13.
  12. Thelen P, Wuttke W, Jarry H, Grzmil M, Ringert RH. Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells. J Urol. 2004 May;171(5):1934-8.
  13. Gurley B, Hubbard MA, Williams KD, et al. Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: comparison of a milk thistle and black cohosh product to rifampin and clarithromycin. J Clin Pharmacol. 2006 ;46(2):201-13.
  14. Fuhr U, Beckmann-Knopp S, Jetter A, et al. The effect of silymarin on oral nifedipine pharmacokinetics. Planta Med 2007;73(14):1429-35.
  15. Mills E, Wilson K, Clarke M, et al. Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis. Eur J Clin Pharmacol. 2005;61(1):1-7.
  16. Ramasamy K and Agarwal R. Multitargeted therapy of cancer by silymarin. Cancer Lett 2008 May 8.
  17. Verschoyle RD, Greaves P, Patel K, et al. Evaluation of the cancer chemopreventive efficacy of silibinin in genetic mouse models of prostate and intestinal carcinogenesis: relationship with silibinin levels. Eur J Cancer 2008 ;44(6):898-906.
  18. Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother Res 2006;20(12):1036-9.
  19. Saller R, Brignoli R, Melzer J, Meier R. An updated systematic review with meta-analysis for the clinical evidence of silymarin.Forsch Komplementmed 2008;15(1):9-20.
  20. Ladas EJ, Kroll DJ, Oberlies NH, et al. A Randomized, Controlled, Double-Blind, Pilot Study of Milk Thistle for the Treatment of Hepatotoxicity in Childhood Acute Lymphoblastic Leukemia (ALL).Cancer 2010;116(2):506-13.
  21. Payer BA, Reiberger T, Rutter K, et al. Successful HCV eradication and inhibition of HIV replication by intravenous silibinin in an HIV-HCV coinfected patient. J Clin Virol. 2010 Aug 13. [Epub ahead of print]
  22. Shakeel M, Trinidade A, McCluney N, Clive B. Complementary and alternative medicine in epistaxis: a point worth considering during the patient's history. Eur J Emerg Med. 2010 Feb;17(1):17-9.
  23. Murata N, Murakami K, Ozawa Y, et al. Silymarin attenuated the amyloid â plaque burden and improved behavioral abnormalities in an Alzheimer's disease mouse model. Biosci Biotechnol Biochem. 2010 Nov 23;74(11):2299-306.
  24. Yin F, Liu J, Ji X, et al. Silibinin: A novel inhibitor of Aâ aggregation. Neurochem Int. 2011 Feb;58(3):399-403.
  25. Flaig TW, Gustafson DL, Su LJ, et al. A phase I and pharmacokinetic study of silybin-phytosome in prostate cancer patients. Invest New Drugs. 2007 Apr;25(2):139-46.
  26. Mohamed ME, Frye RF. Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. Planta Med. 2011 Mar;77(4):311-21.
  27. El-Shitany NA, Hegazy S, El-Desoky K. Evidences for antiosteoporotic and selective estrogen receptor modulator activity of silymarin compared with ethinylestradiol in ovariectomized rats. Phytomedicine. 2010 Feb;17(2):116-25.

 

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How It Works


Bottom Line: Milk thistle protects against alcohol-induced liver damage, and even reverses its effects in some cases. Whether it can treat other liver diseases is not clear.Laboratory studies support milk thistle's liver protectant effects. For example, when rats fed milk thistle are fed toxins and drugs that are known to be toxic to the liver, they are protected from liver damage compared to rats not given milk thistle. Scientists think that silymarin, a compound in milk thistle, alters and stabilizes the structure of the liver cells so that toxins cannot enter them as easily. In addition, it stimulates the synthesis of proteins, which is an important part of cell growth and regeneration after damage.

Recent laboratory studies have found that milk thistle may protect against Alzheimer's disease and has anticancer activity against colon and prostate cancer cells. Silymarin was shown to have estrogenic effects in rats. It is not known if these effects occur in the human body.

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Purported Uses
  • To prevent and treat alcohol-induced liver damage
    Laboratory data and several clinical trials support this use.
  • As an antidote to poisonous mushrooms (such as Amanita phalloides)
    No scientific evidence supports this use.
  • To prevent and treat drug-induced liver damage
    Laboratory, animal, and clinical trials support this use, although the effect varies by drug.
  • To treat dyspepsia (gastrointestinal upset)
    Some clinical trials support this use.
  • To treat cirrhosis of the liver
    Clinical trials support this use, specifically for patients with alcohol-induced cirrhosis.
  • To treat hepatitis
    Laboratory studies show that milk thistle protects and promotes regeneration of the liver, but there is no proof from clinical trials that milk thistle can treat hepatitis.
  • As supportive therapy for chronic inflammatory liver disease
    Laboratory studies show that milk thistle protects and promotes regeneration of the liver, but there is no proof from clinical trials that milk thistle can treat inflammatory liver disease.
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Research Evidence

Liver diseaseFifty children with acute lymphoblastic leukemia (ALL) and hepatotoxicity were randomized to receive milk thistle (240 mg capsule containing 80 mg of silibinin) or placebo orally for 28 days. Supplementation began the day after the children received intravenous chemotherapy. Liver function tests were conducted through the study period. Researchers observed significant reductions in the levels of aspartate amino transferase (AST) and amino alanine transferase (ALT) in patients on milk thistle compared to those who took placebo. Further, milk thistle did not interfere with the chemotherapy. Larger studies are needed to establish the efficacy of milk thistle as a supportive agent.

A clinical trial studied 170 patients with cirrhosis of the liver to determine the effect of silymarin on their survival. For at least two years, 87 patients randomly received 140 mg of silymarin three times a day, while 83 patients received a similar regimen of placebo medication. Overall, patients taking silymarin had a higher four-year survival rate (58%) than those taking the placebo (39%). Further analysis showed that silymarin was most effective in patients with alcohol-induced cirrhosis.

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Do Not Take If
  • You are taking drugs that are substrates of Cytochrome P450 3A4 (milk thistle may increase the risk of side effects of these drugs).
  • You are taking drugs that are substrates of UGT (Uridine 5'-diphospho-glucuronosyltransferase) enzymes (Milk thistle may increase the risk of side effects of these drugs).
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Side Effects
  • Diarrhea
  • Uterine and menstrual stimulation
  • Case report: A patient experienced episodes of sweating, nausea, vomiting, diarrhea, abdominal pain, weakness, and collapse after taking milk thistle. These symptoms resolved after the patient discontinued use of milk thistle.
  • Case report: A 25-year-old man developed a severe case of epistaxis (nosebleed), which may have been due to his self medication with aspirin, garlic, and milk thistle. His symptoms improved following treatment.
  • Clinical study: At high dosage, silibinin can elevate bilirubin and liver enzymes.
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Dosage (Inside MSKCC Only)
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Aliases
Silybum Marianum
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E-mail your questions and comments to aboutherbs@mskcc.org.
Last updated: December 28, 2011