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Milk Thistle

Plant Part Used


Active Constituents

Silymarin (consisting of the flavonoids silibinin, isosilybin, silydianin and silychristin).(1)

[span class=alert]This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]


Native to Europe, milk thistle has a long history of use as both a food and a medicine. Historically, milk thistle was used as a digestive tonic, a general tonic for the spleen, stomach and liver, for the gallbladder, to promote bile flow, and as a stimulant for milk flow in nursing mothers.(2) Milk thistle is routinely used in Europe as a hepatoprotective agent and for the treatment of various liver disorders.(3),(4) One possible application of milk thistle is the reduction of raised liver enzymes such as SGPT and SGOT. Individuals with health conditions such as cirrhosis and on medications (prescription and over-the-counter) that may elevate liver enzymes may see protective effects from using milk thistle supplements.

Interactions and Depletions


Dosage Info

Dosage Range

80-200 mg (standardized extract), 1-3 times daily.

Most Common Dosage

80 mg (standardized extract), 3 times a day.


[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 80% silymarin.


Frequently Reported Uses

  • Antioxidant
  • Hepatoprotective
  • Alcoholic Liver Damage
  • Fatty Liver Degeneration
  • Jaundice
  • Liver Detoxification

Other Reported Uses

  • Chronic Alcohol And Recreational Drug Abuse
  • Detoxification
  • Hepatobiliary Disorders,
  • Cholagogue, Increases Bile Flow
  • Hypercholesterolemia
  • Cancer
  • Type 2 diabetes
  • Psoriasis

Toxicities & Precautions


None known in recommended dosages.

Side Effects

May loosen stools or possibly aggravate hemorrhoidal veins with extended use.

Pregnancy/ Breast Feeding

If pregnant or nursing, consult a physician before use.

Age Limitations

Do not use in children under 2 years of age unless recommended by a physician.



The constituents of milk thistle with hepatoprotective activity are a combination of flavonoids collectively termed silymarin. There have been a number of human clinical trials demonstrating the efficacy of milk thistle as a hepatoprotective agent.(6),(29) The mechanism of silymarin’s reported hepatoprotective activity includes inhibition of the transport of toxins into the liver cells, enhanced liver detoxification via inhibition of Phase 1 detoxification, enhanced glucuronidation, stabilization of the hepatic cell membranes, stimulation of new liver cell regeneration through increased protein synthesis, selective inhibition of leukotriene formation by Kupffer cells, and inhibition of membrane peroxidation.(7),(8),(9) Silymarin has been demonstrated to increase glutathione content in the liver by more than 35 percent, increasing its antioxidant capacity.(10)

Milk thistle is also reported to inhibit the inflammatory leukotrienes, which increased levels may normally lead to the destruction of liver tissue.(12) Inhibition of NF-kappa B and kinase activation may provide in part the molecular basis for the anticarcinogenic and anti-inflammatory effects of silymarin.(13) Also, 5-lipoxygenase inhibition contributes to milk thistle’s antiinflammatory and antiarthritic activities.(14)

Milk thistle’s most celebrated use is in the antidoting of death cup mushroom poisoning.(15),(16) If administered before the poisoning, it is claimed to be 100 percent effective. In animal studies, even if given as much as 24 hours after the poison was ingested, it exerted hepatoprotective properties and prevented death.(15) Because of its reported liver enzyme and cell protection capabilities, it is used in a wide variety of conditions, such as chemical-induced liver damage (including industrial chemicals, alcohol and pharmaceutical drugs), hepatitis, gallbladder dysfunctions, and psoriasis.(17),(18) Studies have reported protective benefits in liver function in alcoholics and viral hepatitis.(19),(30) Another study reported that silymarin reduced the side effects of various classes of psychotropic drugs through protection of the liver and reduction of liver enzyme induction.(20) A standardized milk thistle product was recently reported to protect liver damage induced by acetaminophen (Tylenol) poisoning.(21),(22) A small pilot study found that milk thistle extract did not affect serum hepatitis C virus RNA, alanin aminotransferase levels or well being in patients with Hepatitis C.(31)

A 2008 systmatic review with meta-analysis for the clinical evidence of milk thistle extract found that enough evidence exists to employ silymarin as a supportive element in the therapy of Amanita phalloides poisoning and also (alcoholic and grade Child 'A') liver cirrhosis.(32) A 2007 Cochrane Database System Review looked at 18 human trials in 1008 patients and found liver-related mortality was significantly reduced by milk thistle in all trials, but not in high-quality trials.(33)

Of interest are a few laboratory animal studies which suggest that fetal damage resulting from maternal alcohol and drug consumption may be limited when the mother is administered standardized milk thistle products.(26)

Other Uses

Studies also suggest that silymarin may protect against genomic injury, decrease the activity of tumor promoters, stabilize mast cells, chelate iron, and slow calcium metabolism.(3) Silibinin has been reported in laboratory studies to have anti-cancer activity on various human cancer cell lines.(34),(35),(36) Silibinin was found to inhibit hypoxia-inducible factor-1alpha (HIF-1alpha) expression in prostate cancer cells in vitro.(37) An in vitro study using human colon cancer cells found that silibinin significantly inhibits proliferation through cell-cycle arrest via inhibition of cyclin-CDK promoter activity.(38) Laboratory trials also suggest milk thistle modulates imbalance between cell survival and apoptosis through interference with the expressions of cell cycle regulators and proteins involved in apoptosis, as well as anti-inflammatory, anti-metastatic, and chemo/radioprotective effects.(39),(40) Silibinin has been reported to modulate insulin-like growth factor (IGF) system by increasing circulating levels of IGF-binding protein 3 (IGFBP-3) and decreasing levels of IGF-I.(41)

In vitro experiments with kidney cells damaged by paracetamol, cisplatin, and vincristin and then treated with isolated silibinin before or after the chemical-induced injury, reported a decrease in the nephrotoxic effects of these toxic agents.(11)

Silbinin’s antioxidant activity has been reported to modulate many molecular changes caused by xenobiotics and ultraviolet radiation to protect the skin, leading the industry to use silibinin in cosmetics as a novel antioxidant.(42) UV protection involves activation of the SIRT1 pathway, inactivation of caspase-8 pathway and modulation of the cell cycle distribution.(43),(44)


Milk thistle has been reported to have galactagogue activity in animals and humans. A small human study found that women orally treated for 63 days with milk thistle showed a clear galactagogue role for the product with daily milk production increasing 86% vs. placebo at 32%.(45)

The liver plays an important role in regulation of metabolism of plasma lipoproteins, and liver injury is often reflected as a secondary dyslipoproteinaemia, which may lead to the development of atherosclerosis, particularly when associated with hypercholesterolaemia. Due to the inhibition of lipid peroxidation by silymarin as reported in the literature, milk thistle has also been reported to be a possible new agent in hypercholesterolemia. A laboratory animal study found that the cholesterol lowering effect of silymarin was parallel to that of probucol (dose-dependent).(23) Unlike probucol, however, silymarin caused an increase in high density lipoprotein (HDL)-cholesterol, a decrease in liver cholesterol content, and partially prevented the HCD-induced decrease in liver reduced glutathione, which are all of benefit in patients with hypercholesterolemia. Results suggest that silymarin’s hypocholesterolemic activity could be due to an inhibition of cholesterol biosynthesis and/or by inhibiting of resorption of dietary cholesterol.(24),(25) Milk thistle’s antioxidant activity has also been reported to decrease LDL oxidation in laboratory studies.(46)

In a 4 month, randomized, double-blind placebo controlled human trial in 51 patients with Type 2 diabetes, milk thistle was reported to produce a significant decrease in HbA(1)c, FBS, total cholesterol, LDL, triglyceride, SGOT and SGPT levels compared with placebo.(47)


  1. Wichtl M in Bissett NA, ed. Herbal Drugs and Phytopharmaceuticals. Stuttgart: Scientific Press; 1994:121-23.
  2. Cardui mariae fructus (Milk Thistle fruit). Commission E Monograph. Mar1986;Bundesanzeiger:no. 50.
  3. View Abstract: Flora K, et al. Milk Thistle (Silybum marianum) for the Therapy of Liver Disease. Am J Gastroenterol. 1998;93(2):139-43.
  4. View Abstract: Salmi H, et al. Effect of Silymarin on Chemical, Functional, and Morphological Alterations of the Liver. A Double-blind Controlled Study. Scand J Gastroent. 1982;17:517-21.
  5. PDR for Herbal Medicines, 2nd edition. Montvale, NJ: Medical Economics Company; 2000:518.
  6. View Abstract: Ferenci P, Dragosics B, Dittrich H, et al. Randomized Controlled Trial of Silymarin Treatment in Patients with Cirrhosis of the Liver. J Hepatol. Jul1989;9(1):105-13.
  7. View Abstract: Rue YC. Advances in Pharmacological Studies of Silymarin. Mem Inst Oswaldo Cruz. 1991;86(Suppl 2):79-85.
  8. View Abstract: Dehmlow C, Erhard J, de Groot H. Inhibition of Kupffer Cell Functions as an Explanation for the Hepatoprotective Properties of Silibinin. Hepatology. Apr1996;23(4):749-54.
  9. View Abstract: Campos R, et al. Silybin Dihemisuccinate Protects Against Glutathione Depletion and Lipid Peroxidation Induced by Acetaminophen on Rat Liver. Planta Medica. 1989;55:417-19.
  10. View Abstract: Valenzuela A, et al. Selectivity of Silymarin on the Increase of the Glutathione Content in Different Tissues of the Rat. Planta Medica. 1989;55:1550-52.
  11. View Abstract: Sonnenbichler J, Scalera F, Sonnenbichler I, et al. Stimulatory Effects of Silibinin and Silicristin from the Milk Thistle Silybum marianum on Kidney Cells. J Pharmacol Exp Ther. Sep1999;290(3):1375-83.
  12. View Abstract: Fiebrich F, et al. Silymarin, an Inhibitor of Prostaglandin Synthetase. Experimenta. 1979;35:150-52.
  13. View Abstract: Manna SK, Mukhopadhyay A, Van NT, et al. Silymarin Suppresses TNF-induced Activation of NF-kappa B, c-Jun N-terminal Kinase, and Apoptosis. J Immunol. Dec1999;163(12):6800-9.
  14. View Abstract: Gupta OP, Sing S, Bani S, et al. Anti-inflammatory and Anti-arthritic Activities of Silymarin Acting Through Inhibition of 5-lipoxygenase. Phytomedicine. Mar2000;7(1):21-4.
  15. View Abstract: Vogel G, et al. Protection by Silibinin Against Amanita Phalloides Intoxication in Beagles. Toxicol Appl Pharm. 1984;73:355-62.
  16. View Abstract: Desplaces A, et al. The Effects of Silymarin on Experimental Phalloidine Poisoning. Arzneim-Forsch/Drug Res. 1975;25:89-96.
  17. Schopen RD, et al. Therapy of Hepatoses. Therapeutic Use of Silymarin. Med Welt. 1969;21:691-98.
  18. Valenzuela A, et al. Silymarin Protection Against Hepatic Lipid Peroxidation Induced by Acute Ethanol Intoxication in the Rat. Biochem Pharm. 1985;34:2209-12.
  19. View Abstract: Varga M, et al. Ethanol Elimination in Man Under Influence of Hepatoprotective Silibinin. Blutalkohol. Nov1991;28(6):405-08.
  20. Carrescia O, et al. Silymarin in the Prevention of Hepatic Damage by Psychopharmacologic Drugs. Experimental Premises and Clinical Evaluations. Clin Ter. 1980;95(2):157-64.
  21. Dehpour AR, et al. Liquorice Components Protect Liver Damage Induced by Actaminophen. Poster Presentation, 48th Annual Meeting of the International Congress of the Society of Medicinal Plant Research, P2A/23. Sep2000.
  22. View Abstract: Shear NH, Malkiewicz IM, Klein D, et al. Acetaminophen-induced Toxicity to Human Epidermoid Cell Line A431 and Hepatoblastoma Cell Line Hep G2, In Vitro, is Diminished by Silymarin. Skin Pharmacol. 1995;8(6):279-91.
  23. View Abstract: Krecman V, Skottova N, Walterova D, et al. Silymarin Inhibits the Development of Diet-induced Hypercholesterolemia in Rats. Planta Med. Mar1998;64(2):138-42.
  24. View Abstract: Skottova N, Krecman V, Walterova D, et al. Effect of Silymarin on Serum Cholesterol Levels in Rats. Acta Univ Palacki Olomuc Fac Med. 1998;141:87-9.
  25. View Abstract: Skottova N, Krecman V. Silymarin as a Potential Hypocholesterolaemic Drug. Physiol Res. 1998;47(1):1-7.
  26. View Abstract: Edwards J, Grange LL, Wang M, et al. Fetoprotectivity of the Flavanolignan Compound Siliphos Against Ethanol-induced Toxicity. Phytother Res. Nov2000;14(7):517-21.
  27. LaValle JB, Krinsky D, Hawkins EB, et al. Natural Therapeutics Pocket Guide. Hudson, OH: LexiComp, Inc; 2000:479-480.
  28. Wu JW, Lin LC, Tsai TH. Drug-drug interactions of silymarin on the perspective of pharmacokinetics. J Ethnopharmacol. 2009;121(2):185-193.
  29. Fuhr U, Beckmann-Knopp S, Jetter A, Lück H, Mengs U. The effect of silymarin on oral nifedipine pharmacokinetics. Planta Med. Nov 2007;73(14):1429-1435. Epub 2007 Oct 30.
  30. El-Kamary SS, Shardell MD, Abdel-Hamid M, et al. A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis. Phytomedicine. May 2009;16(5):391-400. Epub 2009 Mar 19.
  31. Ferenci P, Scherzer TM, Kerschner H, et al. Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. Gastroenterology. Nov 2008;135(5):1561-1567. Epub 2008 Aug 3.
  32. 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. Jan 2006;21(1 Pt 2):275-280.
  33. Saller R, Brignoli R, Melzer J, Meier R. An updated systematic review with meta-analysis for the clinical evidence of silymarin. Forsch Komplementmed. Feb 2008;15(1):9-20. Review.
  34. Rambaldi A, Jacobs BP, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database Syst Rev. 17 Oct 2007;(4):CD003620. Review.
  35. Kim S, Choi JH, Lim HI, et al. Silibinin prevents TPA-induced MMP-9 expression and VEGF secretion by inactivation of the Raf/MEK/ERK pathway in MCF-7 human breast cancer cells. Phytomedicine. Jun 2009;16(6-7):573-580.
  36. García-Maceira P, Mateo J. Silibinin inhibits hypoxia-inducible factor-1alpha and mTOR/p70S6K/4E-BP1 signaling pathway in human cervical and hepatoma cancer cells: implications for anticancer therapy. Oncogene. 22 Jan 2009;28(3):313-324.
  37. Bang CI, Paik SY, Sun DI, Joo YH, Kim MS. Cell growth inhibition and down-regulation of survivin by silibinin in a laryngeal squamous cell carcinoma cell line. Ann Otol Rhinol Laryngol. Oct 2008;117(10):781-785.
  38. Jung HJ, Park JW, Lee JS, Lee SR, Jang BC, Suh SI, Suh MH, Baek WK. Silibinin inhibits expression of HIF-1alpha through suppression of protein translation in prostate cancer cells. Biochem Biophys Res Commun. 4 Dec 2009;390(1):71-76. Epub  2009 Sep 22.
  39. Hogan FS, Krishnegowda NK, Mikhailova M, Kahlenberg MS. Flavonoid, silibinin, inhibits proliferation and promotes cell-cycle arrest of human colon cancer. J Surg Res. Nov 2007;143(1):58-65.
  40. Ramasamy K, Agarwal R. Multitargeted therapy of cancer by silymarin. Cancer Lett. 8 Oct 2008;269(2):352-362. Review.
  41. Greenlee H, Abascal K, Yarnell E, Ladas E. Clinical applications of Silybum marianum in oncology. Integr Cancer Ther. Jun 2007;6(2):158-165. Review.
  42. Hoh C, Boocock D, Marczylo T, et al. Pilot study of oral silibinin, a putative chemopreventive agent, in colorectal cancer patients: silibinin levels in plasma, colorectum, and liver and their pharmacodynamic consequences. Clin Cancer Res. 1 May 2006;12(9):2944-2950.
  43. Singh RP, Agarwal R. Cosmeceuticals and silibinin. Clin Dermatol. Sep-Oct 2009;27(5):479-484. Review.
  44. Li LH, Wu LJ, Tashiro SI, Onodera S, Uchiumi F, Ikejima T. Activation of the SIRT1 pathway and modulation of the cell cycle were involved in silymarin's protection against UV-induced A375-S2 cell apoptosis. J Asian Nat Prod Res. Apr-Aug 2007;9(3-5):245-252.
  45. Li LH, Wu LJ, Tashiro S, Onodera S, Uchiumi F, Ikejima T. Silibinin prevents UV-induced HaCaT cell apoptosis partly through inhibition of caspase-8 pathway. Biol Pharm Bull. Jun 2006;29(6):1096-1101.
  46. Di Pierro F, Callegari A, Carotenuto D, Tapia MM. Clinical efficacy, safety and tolerability of BIO-C (micronized Silymarin) as a galactagogue. Acta Biomed. Dec 2008;79(3):205-210.
  47. Wallace S, Vaughn K, Stewart BW, Viswanathan T, Clausen E, Nagarajan S, Carrier DJ. Milk thistle extracts inhibit the oxidation of low-density lipoprotein (LDL) and subsequent scavenger receptor-dependent monocyte adhesion. J Agric Food Chem. 11 Jun 2008;56(11):3966-3972.
  48. Huseini HF, Larijani B, Heshmat R, Fakhrzadeh H, Radjabipour B, Toliat T, Raza M. 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. Dec 2006;20(12):1036-1039.

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