Milk Thistle

Milk Thistle

Milk Thistle

Common Names

  • Holy thistle
  • lady's thistle
  • Mary thistle
  • Marian thistle

For Patients & Caregivers

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 protective effects. For example, when rats fed milk thistle are given 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.
Studies also show 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.

  • 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.
  • As supportive therapy for chronic inflammatory liver disease
    Laboratory studies show that milk thistle protects and promotes regeneration of the liver.

Liver toxicity
Fifty children with acute lymphoblastic leukemia (ALL) and liver toxicity 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.

  • 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).
  • 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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For Healthcare Professionals

Silybum marianum, Carduus marianum

Derived from the seed, pod, or fruit of milk thistle, silymarin, a flavolignan, is used primarily to manage various liver diseases. 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).

Placebo-controlled clinical studies show efficacy of silymarin in reducing aminotransferases in alcoholic liver disease (9) and conclusions from a systematic review suggest its usefulness for liver cirrhosis (19). Milk thistle was also shown to reduce liver toxicity associated with chemotherapy in children with acute lymphoblastic leukemia (20)and cisplatin-induced nephrotoxicity (28). 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).
A case study indicates the utility of intravenous silibinin in patients coinfected with HIV and HCV (Hepatitis C virus) (21).

Silymarin demonstrated estrogenic activity with mild proliferative effects in rat uteri (27). Human studies are warranted.

  • Cancer prevention
  • Cirrhosis
  • Drug-induced hepatotoxicity
  • Food poisoning
  • Hepatitis
  • Indigestion
  • Liver disease
  • Flavolignans: Silymarin, a mixture of silybinin, silidyanin, silychristin
  • Tocopherol sterols: Cholesterol, capesterol, stigmasterol, and sitosterol
  • Other constituents: Taxifolin, quercetin, dihydrokaempferol, kaempferol, apigenin, naringin, eriodyctiol, chrysoeriol, linoleic acid, palmitic acid
    (37)

Silymarin, a mixture of flavonoids derived from the seeds of milk thistle, is believed to be the active component responsible for the herb’s hepatoprotective effects. Studies done in mice show that silymarin confers hepatoprotection, attributed to its down regulation of extracellular matrix proteins such as collagen, against thioacetamide-induced liver damage in mice (2). It may also be useful against liver carcinogenesis by negatively affecting the activity of mast cells, a source of matrix metalloproteins that are involved in invasion and angiogenesis (29). Silymarin reduced cisplatin-induced kidney damage in rats without diminishing its anti-tumor activity (7). It may play a role in preventing Alzheimer’s disease: studies show that it suppressed formation of amyloid beta-protein and neurotoxicity in mice (30).

Silibinin, one of the flavonoids, demonstrated antioxidant and anti-inflammatory effects by inhibiting release of hydrogen peroxide and production of tumor necrosis factor alpha (31). Another study showed improvement in endothelial dysfunction in mice by silibinin via reduction in circulating and vascular asymmetric dimethylarginine (ADMA) levels. ADMA is an endogenous inhibitor of nitric oxide synthase (NOS) and is believed to play a role in endothelial dysfunction, associated with cardiovascular disease (32). Silibinin also inhibits the early phase of HepatitisC viral infection by affecting endosomal trafficking of virions (34).
Silybin and isosilybin were also shown to act as strong inhibitors of PXR-mediated CYP3A4 induction (35).
Other studies indicate the flavonoids in milk thistle exert anticancer effects by arresting G1 and S phases of the cell cycle (8). Silibinin suppressed the epidermal growth factor receptor (EGFR)-induced expression of CD44 (the transmembrane receptor for hyaluronan, implicated in tumor cell invasion and metastasis) by inhibiting EGFR activity in breast cancer cells (33).
Silybin was also shown to inhibit growth of hepatocellular carcinoma cells via the Notch signaling pathway (36).

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 can be recovered from the bile as both glucuronide or sulfate conjugates and 2-5% is excreted in the urine (4).

Case report: A patient experienced intermittent episodes of sweating, nausea, vomiting, diarrhea, abdominal pain, weakness and collapse that resolved after discontinuation of milk thistle supplementation (5).
Case report: A 25-year-old man developed a severe case of epistaxis, which may have been due to his self medicating with aspirin, garlic, and milk thistle. His symptoms improved following treatment  (22).
Clinical study: At high doses, silibinin can elevate bilirubin and liver enzymes (25).

  • 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)(38).
    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).

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.

  1. Bissett N, et al. Herbal Drugs and Phytopharmaceuticals. New York: Medpharm, CRC Press; 1994.

  2. Chen IS, Chen YC, Chou CH, et al. Hepatoprotection of silymarin against thioacetamide-induced chronic liver fibrosis. J Sci Food Agric. 2012 May;92(7):1441-7.

  3. Adverse Drug Reactions Advisory Committee. An adverse reaction to the herbal medication milk thistle (Silybum marianum). Med J Aust. 1999;170:218-9.

  4. Brinker F. Herb Contraindications and Drug Interactions, 2nd ed. Sandy (OR): Eclectic Med; 1998.

  5. 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.

  6. Fuhr U, Beckmann-Knopp S, Jetter A, et al. The effect of silymarin on oral nifedipine pharmacokinetics. Planta Med. 2007;73(14):1429-35.

  7. 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.

  8. Ramasamy K and Agarwal R. Multitargeted therapy of cancer by silymarin. Cancer Lett. 2008 May 8.

  9. 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.

  10. 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.

  11. 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.

  12. Yin F, Liu J, Ji X, et al. Silibinin: A novel inhibitor of Aâ aggregation. Neurochem Int. 2011 Feb;58(3):399-403.

  13. 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.

  14. Ninsontia C, Pongjit K, Chaotham C, Chanvorachote P. Silymarin selectively protects human renal cells from cisplatin-induced cell death. Pharm Biol. 2011 Oct;49(10):1082-90.

  15. Ramakrishnan G, Jagan S, Kamaraj S, Anandakumar P, Devaki T.  Silymarin attenuated mast cell recruitment thereby decreased the expressions of matrix metalloproteinases-2 and 9 in rat liver carcinogenesis. Invest New Drugs. 2009 Jun;27(3):233-40.

  16. Murata N, Murakami K, Ozawa Y, et al. Silymarin attenuated the amyloid β plaque burden and improved behavioral abnormalities in an Alzheimer’s disease mouse model. Biosci Biotechnol Biochem. 2010;74(11):2299-306.

  17. Bannwart CF, Peraçoli JC, Nakaira-Takahagi E, Peraçoli MT. Inhibitory effect of silibinin on tumour necrosis factor-alpha and hydrogen peroxide production by human monocytes. Nat Prod Res. 2010 Nov;24(18):1747-57.

  18. Li Volti G, Salomone S, Sorrenti V, et al. Effect of silibinin on endothelial dysfunction and ADMA levels in obese diabetic mice. Cardiovasc Diabetol. 2011 Jul 14;10:62.

  19. Blaising J, Lévy PL, Gondeau C, et al. Silibinin inhibits hepatitis C virus entry into hepatocytes by hindering clathrin-dependent trafficking. Cell Microbiol. Cell Microbiol. 2013 Nov;15(11):1866-82.

  20. Mooiman KD, Maas-Bakker RF, Moret EE, et al. Milk Thistle’s Active Components Silybin and Isosilybin: Novel Inhibitors of PXR-mediated CYP3A4 Induction. Drug Metab Dispos. 2013 Aug;41(8):1494-504.

  21. Abenavoli L, Capasso R, Milic N, Capasso F. Milk thistle in liver diseases: past, present, future. Phytother Res. 2010 Oct;24(10):1423-32.

  22. Kawaguchi-Suzuki M, Frye RF, Zhu HJ, et al. The Effects of Milk Thistle (Silybum marianum) on Human Cytochrome P450 Activity. Drug Metab Dispos. 2014 Oct;42(10):1611-6.

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