Milk Thistle

Purported Benefits, Side Effects & More
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Milk Thistle

Purported Benefits, Side Effects & More
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Milk Thistle

Common Names

  • Holy thistle
  • Lady's thistle
  • Mary thistle
  • Marian thistle

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For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.

What is it?

Milk thistle is an herb related to the daisy and ragweed family. It is used in traditional medicine to treat liver issues. It comes in supplements as capsules, softgels, tablets, and liquid extracts.

What are the potential uses and benefits?

Milk thistle is used to:

  • Treat liver damage caused by drinking a lot of alcohol.
  • Treat hepatitis (swelling of the liver).
  • Treat liver damage caused by some medications.

Milk thistle has other uses, but doctors have not studied them to see if they work.

Talk with your healthcare providers before taking milk thistle supplements. Herbal supplements are stronger than the herbs you would use in cooking.

They can also interact with some medications and affect how they work. For more information, read the “What else do I need to know?” section below.

What are the side effects?

Side effects of using high doses of milk thistle may include:

  • Increase in levels of bilirubin (a substance released when your older red blood cells are replaced by newer ones. Normally your liver helps clear this substance). Most people will not have any symptoms.
  • Increase in levels of liver enzymes. Most people will not have any symptoms.
What else do I need to know?
  • Talk with your healthcare provider if you’re taking sirolimus (Rapamune®). Milk thistle may increase the side effects of this medication.
  • Talk with your doctor if you had or plan to have a kidney transplant. Taking milk thistle with sirolimus (Rapamune ®) and nivolumab (Opdivo®) may lead to your body rejecting the donor kidney.
  • Talk with your healthcare provider if you’re on Haloperidol (Haldol Decanoate®) or Risperidone (Risperdal M-TAB®, Risperdal Consta®, Risperdal®). Milk thistle may cause pancreatitis (swelling of pancreas) if you take it with these medications.    
  • Do not take milk thistle if you’re allergic to plants in the daisy or ragweed family.
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For Healthcare Professionals

Scientific Name
Silybum marianum, Carduus marianum
Clinical Summary

Derived from the seed, pod, or fruit of milk thistle, the flavolignan silymarin is used primarily to manage various liver diseases. Preclinical studies suggest flavonoids in milk thistle have antioxidant and anticancer effects (7) (8) (12) (16) (17), and may protect against Alzheimer’s disease (23) (24).

Supplementation with milk thistle or silymarin improved lipid profiles and glycemic indices in type 2 diabetic patients (18) (40) and biomarkers related to obesity and its comorbidities (53). It may also be useful against alcoholic liver disease (9), cirrhosis (11) (19), for improving fibrosis associated with nonalcoholic steatohepatitis (39), and for reducing risk of anti tuberculosis drug-induced liver injury (50). However, in both a large survey and a subsequent multi-center trial of patients with chronic hepatitis C, silymarin did not significantly reduce serum ALT levels (41) (42), and despite its association with reduced progression from fibrosis to cirrhosis, had no impact on clinical outcomes (43). Milk thistle was also reported ineffective against trichotillomania (46) but topical use may accelerate wound healing following episiotomy (54) and improve severity of acne (55).

Small studies suggest benefits of milk thistle in reducing chemo-induced hepatotoxicity in children with acute lymphoblastic leukemia (20) and in non-metastatic breast cancer patients (56); and radiation therapy-induced mucositis in those with head and neck cancer (3). Topical use of a silymarin gel decreased the severity of capecitabine-induced hand-foot syndrome in GI cancer patients (6) and radiodermatitis in patients with breast cancer (47).

Both silymarin (27) and silibinin (48) have estrogenic effects with greater affinity for estrogen receptor (ER-beta), and activation of ER-beta results in suppression of cell growth.
Silibinin can also exacerbate the negative effects of chronic alcohol consumption on liver cancer (10).

Purported Uses and Benefits
  • Cirrhosis
  • Hepatitis
  • Drug-induced liver damage
Mechanism of Action

Animal models suggest that silymarin confers hepatoprotection via downregulation of extracellular matrix proteins such as collagen (2). It may also be useful against liver carcinogenesis by inhibiting mast cells, a source of matrix metalloproteins that are involved in invasion and angiogenesis (29). In addition, silymarin reduced cisplatin-induced kidney damage in rats without diminishing the drug’s antitumor activity (7), and suppressed formation of amyloid beta-proteins 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 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 hepatitis C viral infection by affecting endosomal trafficking of virions (34).

Other studies indicate milk thistle flavonoids exert anticancer effects by arresting G1 and S phases of the cell cycle (8). Silybin inhibited hepatocellular carcinoma cell growth via the Notch signaling pathway (36). 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). Suggested mechanisms for reduced efficacy of silibinin in liver tumor-bearing animals that were co-administered ethanol include impaired hepatic processing of silibinin (10).

Silybin and isosilybin were shown to strongly inhibit PXR-mediated CYP3A4 induction (35).

Adverse Reactions

High doses of silibinin can elevate bilirubin and liver enzymes (25).

Case reports
Intermittent GI symptoms: A patient experienced intermittent episodes of sweating, nausea, vomiting, diarrhea, abdominal pain, weakness, and collapse that resolved after discontinuation of milk thistle supplementation (5).
Severe epistaxis: In a 25-year-old man, possibly due to self-medication with aspirin, garlic, and milk thistle. His symptoms improved following treatment  (22).
Allergy involving episodes of itching and burning in the mouth, tongue swelling, difficulty swallowing, feeling of anxiety, and rapid pulse: In a 29-year old, likely due to occupational exposure. His symptoms resolved following appropriate treatment (51).
Bullous pemphigoid characterized by generalized itchy tense blisters and erosions: In a 49-year-old woman with an anxiety disorder with milk thistle use for GI discomfort. Clinical remission was achieved with prednisone and methotrexate (58).

Herb-Drug Interactions
  • Cytochrome P450 3A4 substrates: Milk thistle inhibits cytochrome P450 3A4 (4) and can affect the intracellular concentration of drugs metabolized by this enzyme. However, conflicting data indicate no such effects (13) (14) (38). In 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) (57).
  • Sirolimus: Milk thistle may decrease clearance. Monitor therapy especially when combined with nivolumab, which may interfere with the potential to help prevent rejection of donor kidney in transplant patients (44) (45).
  • Haloperidol or Risperidone: 7 cases of pancreatitis were reported following concomitant use of milk thistle (49)
  • Aripiprazole: A case of hepatotoxicity was reported with combined use of milk thistle (49).
  • Warfarin: Concurrent use of a liver cleanse supplement which contained milk thistle led to an increase in INR from 2.64 to 4.12 in a man on warfarin therapy for mitral valve replacement. His INR normalized after stopping the supplement (52).
Dosage (OneMSK Only)
References
  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. Elyasi S, Hosseini S, Niazi Moghadam MR et al. Aledavood SA, Karimi G. Effect of Oral Silymarin Administration on Prevention of Radiotherapy Induced Mucositis: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial. Phytother Res. 2016 Nov;30(11):1879-1885. doi: 10.1002/ptr.5704.
  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. Elyasi S, Shojaee FSR, Allahyari A, et al. Topical Silymarin Administration for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial. Phytother Res. 2017 Sep;31(9):1323-1329. doi: 10.1002/ptr.5857.
  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. Brandon-Warner E, Eheim AL, Foureau DM, et al. Silibinin (Milk Thistle) potentiates ethanol-dependent hepatocellular carcinoma progression in male mice. Cancer Lett. Dec 29 2012;326(1):88-95.
  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 Oct 8;269(2):352-62.
  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 Oct;49(2):131-3.
  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 β 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 Aβ 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.
  28. 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.
  29. 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.
  30. 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.
  31. 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.
  32. 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.
  33. Kim S, Han J, Kim JS, et al. Silibinin suppresses EGFR ligand-induced CD44 expression through inhibition of EGFR activity in breast cancer cells. Anticancer Res. 2011 Nov;31(11):3767-73.
  34. 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.
  35. 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.
  36. Zhang S, Yang Y, Liang Z, et al. Silybin-mediated inhibition of notch signaling exerts antitumor activity in human hepatocellular carcinoma cells. PLoS One. 2013 Dec 27;8(12):e83699.
  37. Abenavoli L, Capasso R, Milic N, Capasso F. Milk thistle in liver diseases: past, present, future. Phytother Res. 2010 Oct;24(10):1423-32.
  38. 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.
  39. Wah Kheong C, Nik Mustapha NR, Mahadeva S. A Randomized Trial of Silymarin for the Treatment of Nonalcoholic Steatohepatitis. Clin Gastroenterol Hepatol. Dec 2017;15(12):1940-1949.e1948.
  40. Ebrahimpour-Koujan S, Gargari BP, Mobasseri M, et al. Lower glycemic indices and lipid profile among type 2 diabetes mellitus patients who received novel dose of Silybum marianum (L.) Gaertn. (silymarin) extract supplement: A Triple-blinded randomized controlled clinical trial. Phytomedicine. May 15 2018;44:39-44.
  41. Seeff LB, Curto TM, Szabo G, et al. Herbal product use by persons enrolled in the hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial. Hepatology. Feb 2008;47(2):605-612.
  42. Fried MW, Navarro VJ, Afdhal N, et al. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial. JAMA. Jul 18 2012;308(3):274-282.
  43. Freedman ND, Curto TM, Morishima C, et al. Silymarin use and liver disease progression in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial. Aliment Pharmacol Ther. Jan 2011;33(1):127-137.
  44. Jiao Z, Shi XJ, Li ZD, et al. Population pharmacokinetics of sirolimus in de novo Chinese adult renal transplant patients. Br J Clin Pharmacol. Jul 2009;68(1):47-60.
  45. Barnett R, Barta VS, Jhaveri KD. Preserved Renal-Allograft Function and the PD-1 Pathway Inhibitor Nivolumab. N Engl J Med. Jan 12 2017;376(2):191-192.
  46. Grant JE, Redden SA, Chamberlain SR. Milk Thistle Treatment for Children and Adults with Trichotillomania: A Double-Blind, Placebo-Controlled, Crossover Negative Study. J Clin Psychopharmacol. 2019 Mar/Apr;39(2):129-134.
  47. Karbasforooshan H, Hosseini S, Elyasi S, Fani Pakdel A, Karimi G. Topical silymarin administration for prevention of acute radiodermatitis in breast cancer patients: A randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2019 Feb;33(2):379-386.
  48. Dupuis ML, Conti F, Maselli A, et al. The Natural Agonist of Estrogen Receptor β Silibinin Plays an Immunosuppressive Role Representing a Potential Therapeutic Tool in Rheumatoid Arthritis. Front Immunol. 2018 Aug 17;9:1903.
  49. Woroń J, Siwek M. Unwanted effects of psychotropic drug interactions with medicinal products and diet supplements containing plant extracts. Psychiatr Pol. 2018 Dec 29;52(6):983-996.
  50. Tao L, Qu X, Zhang Y, Song Y, Zhang SX. Prophylactic Therapy of Silymarin (Milk Thistle) on Antituberculosis Drug-Induced Liver Injury: A Meta-Analysis of Randomized Controlled Trials. Can J Gastroenterol Hepatol. 2019 Jan 10;2019:3192351.
  51. Wojas O, Krzych-Fałta E, Samel-Kowalik P, et al. A case of allergy to Silybum marianum (milk thistle) and Eragrostis tef (teff). Allergy Asthma Clin Immunol. 2020 Apr 15;16:23.
  52. Lash DB, Ward S. CYP2C9-mediated warfarin and milk thistle interaction. J Clin Pharm Ther. 2020 Apr;45(2):368-369.
  53. Nehmi-Filho V, Santamarina AB, de Freitas JA, et al. Novel nutraceutical supplements with yeast β-glucan, prebiotics, minerals, and Silybum marianum (silymarin) ameliorate obesity-related metabolic and clinical parameters: A double-blind randomized trial. Front Endocrinol (Lausanne). 2023 Jan 27;13:1089938.
  54. Toomari E, Hajian S, Mojab F, Omidkhah T, Nasiri M. Evaluation the effect of Silybum marianum ointment on episiotomy wound healing and pain intensity in primiparous women: a randomized triple blind clinical trial. BMC Complement Med Ther. 2021 Oct 7;21(1):253.
  55. Kim J, Lee YN, Lee J, et al. Efficacy and safety of silymarin containing antioxidant serum as an adjuvant treatment of mild-to-moderate acne vulgaris: A prospective, open-label pilot study. J Cosmet Dermatol. 2023 Feb;22(2):561-568.
  56. Moezian GSA, Javadinia SA, Sales SS, et al. Oral silymarin formulation efficacy in management of AC-T protocol induced hepatotoxicity in breast cancer patients: A randomized, triple blind, placebo-controlled clinical trial. J Oncol Pharm Pract. 2022 Jun;28(4):827-835.
  57. Li W, Chen YN, Chen YY, et al. Inhibition of UGT1A1*1 and UGT1A1*6 catalyzed glucuronidation of SN-38 by silybins. Chem Biol Interact. 2022 Dec 1;368:110248.
  58. Gamissans M, Expósito-Serrano V, López-Llunell C, et al. Bullous pemphigoid triggered by Silybum marianum: an unexpected side effect of an herbal remedy.
    Int J Dermatol. 2022 Mar;61(3):361-363.
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