Scientific Name: Milk Thistle
Other Names: Cardui mariae, Carduus marianum, Holy Thistle, Lady's Thistle, Legalon, Marian Thistle, Mariendistel, Mary Thistle, Our Lady's Thistle, Silimarina, Silybin, Silybum marianum, Silymarin, St. Mary Thistle

Who is this for?

Uses

Milk thistle contains several chemicals with possible medical effects. Most current research focuses on a mixture of them, collectively called silymarin, which may have specific protective effects on cells in the liver. In multiple human, animal, and laboratory studies, silymarin has shown differing degrees of effectiveness for protecting the liver from damage caused by alcohol, chemicals, drugs, diseases, and poisonous plants. It is used to treat both acute conditions (such as poisoning) and long-term diseases (such as hepatitis C). Silymarin and other chemicals in milk thistle are believed to protect liver cells in several different ways:

Silymarin has antioxidant properties. Oxidation is a natural process necessary to convert foods into components the body can use, but it also produces by-products known as oxygen free radicals, which may damage body cells. Antioxidants are thought to prevent or lessen damage.

Anti-inflammatory effects of silymarin help keep liver cells from swelling after being injured.

Silymarin seems to encourage the liver to grow new cells, while discouraging the formation of inactive fibrous tissue.

By changing the outside layer of liver cells, silymarin actually may keep certain harmful chemicals from getting into liver cells.

Milk thistle may also cause the immune system to be more active.

Silymarin has also been tested in multiple laboratory studies involving various types of human cancer cells. In general, chemicals in silymarin seem to interrupt cancer cell division, keep cancer cells from spreading, and shorten the time that cancer cells live. They may also stop or limit the formation of new blood vessels that supply tumors. Because silymarin attaches to places in cells where the sex hormones androgen and estrogen usually stick, most earlier research centered on hormone-dependent cancers, such as breast cancer and prostate cancer. Due to possible estrogen-like effects of milk thistle, however, certain types of breast cancer tumors actually increased in number and/or seriousness when milk thistle was given to female animals with existing breast tumors. Milk thistle has also been tested for treating other cancers such as leukemia. In addition, some chemicals from milk thistle may increase the effectiveness of current anticancer drugs or reduce the toxicity that some drugs cause to non-cancerous cells. Some of these anticancer effects are being studied in human trials, but none is confirmed, yet.

The application of one silymarin component, silibinin, to the skin of laboratory animals has protected the animals against the development of skin cancer--either before or immediately after exposure to damaging radiation. Silibinin may even help to restore damaged skin somewhat by mending DNA that has been harmed by ultraviolet (UV) rays. In a separate animal study, both topical and oral silymarin helped lessen the systemic effects of burns on the skin.

Milk thistle and chemicals derived from it are being studied for a number of additional possible effects. For example, in animal studies and one small study of humans, milk thistle produced modest reductions in cholesterol levels. A growing amount of information from laboratory, animal, and human studies suggests that milk thistle helps to lower blood sugar levels. Apparently, it works by making the body use insulin better and not by affecting the body's production of insulin. Results of separate laboratory studies show that milk thistle may help to protect the heart muscle from damage caused by certain drugs. However, these potential uses have not been well studied in humans nor have they been proved in animal or laboratories studies.

Although it is being investigated for treating certain cancers, not enough is known about milk thistle's possible estrogenic effects to recommend it for cancer patients. Women who have cancers of the breast, ovaries, or uterus or who have other hormone-dependent conditions such as endometriosis or uterine fibroids should not take or use milk thistle plant extract due to its possible estrogenic effects.

Pregnant women should not take milk thistle because of it could interfere with normal development of the baby.

Precautions

Men who have prostate cancer should not take milk thistle without the approval of a doctor.

Some cases of skin rash from touching milk thistle plants have been reported in the medical literature. Milk thistle belongs to the same family of plants as chrysanthemums, daisies, and ragweed. Individuals who are sensitive to those plants may also be sensitive to milk thistle.

What side effects should I watch for?

No severe side effects have been reported from taking milk thistle. Doses greater than 2500 mg (2.5 grams) per day have been reported to have a slight laxative effect, however.

Occasionally, individuals taking milk thistle have reported:

• Abdominal bloating
• Diarrhea
• Gas
• Loss of appetite
• Nausea
• Stomach upset

What interactions should I watch for?

Milk thistle may interfere with the effectiveness of estrogen by blocking an enzyme that helps the body use estrogen. As a result, estrogen products may not be as effective in reducing the symptoms of menopause or preventing osteoporosis. In addition, oral contraceptives may not be as effective and an unintended pregnancy could result.

Because it is broken down by certain enzymes in the liver, milk thistle may possibly interfere with the effectiveness of prescription drugs that are processed by the same enzymes. Some of these drugs are:

• Allergy drugs such as fexofenadine
• Antianxiety drugs such as alprazolam, diazepam, and lorazepam
• Antifungal drugs such as itraconazole and ketoconazole
• Antiviral drugs such as Crixivan, Fortovase, and Norvir
• Cancer drugs such as etoposide, paclitaxel, vinblastine, and vincristine
• Drugs for high cholesterol such as lovastatin

No interactions have been reported between milk thistle and non-prescription drugs, other herbal supplements, or foods. However, because few reliable studies of milk thistle have been conducted, its possible interactions with drugs, foods, and other dietary supplements are not completely understood. Individuals who decide to take milk thistle should be sure that a doctor or pharmacist is aware of all the prescription and non-prescription medicines they take before beginning to use milk thistle or any other herbal supplement.

Some interactions between herbal products and medications can be more severe than others. The best way for you to avoid harmful interactions is to tell your doctor and/or pharmacist what medications you are currently taking, including any over-the-counter products, vitamins, and herbals. For specific information on how milk thistle interacts with drugs, other herbals, and foods and the severity of those interactions, please use our Drug Interactions Checker to check for possible interactions.

Should I take it?

Milk thistle gets its name from the thick white fluid that seeps from the leaves when they are broken. Its long leaves have prominent white veins and sharp spines that can scratch unprotected skin. Purple or pink flowers that grow individually on tall stems bloom in mid-to-late summer. Each milk thistle plant has up to 50 flowers; each flower contains about a hundred seeds. The seeds resemble dandelion seeds, since they are attached to feathery structures that blow in the wind. Thought to have originated in areas around the Mediterranean Sea and possibly regions of India, milk thistle is now found growing wild in most parts of the world with moderate temperatures--including Canada, Europe, and the United States. In cooler climates, it grows as an annual. In warmer areas, it is a biennial bush that can be as tall as 10 feet. Because it spreads rapidly, grows in marginal areas such as vacant lots, and crowds out other plants; milk thistle is often considered to be a weed. Its very strong taproots make it hard to pull up. It may poison cattle and other livestock that eat large amounts of whole plants.

Currently, milk thistle seeds are the part most commonly used in medicine. All the parts that grow above the ground may be used, however, to make extracts. In the past, milk thistle products have been used to stimulate the flow of breast milk in women who were breast-feeding infants. That use is no longer encouraged due to uncertainty about possible effects for the infant. Milk thistle was also a folk remedy for depression. Its leaves, roots, and stems have been eaten as vegetables in some parts of the world, it may be sprouted like alfalfa or beans for salads, and its seeds may be toasted and then boiled into a coffee-type beverage.

Dosage and Administration

Most of the milk thistle products used in human studies were standardized to contain between 70% and 80% of silymarin. Standardization by the manufacturer should assure the same amount of active ingredient in every batch of the commercial preparation. Standardization of herbal products is not required by the U.S. Food and Drug Administration (FDA), so not every product sold in the United States will contain the same amounts of active ingredients.

Standardized commercial preparations of milk thistle are common in Europe. An injectable form of silymarin is also used by European physicians, but it is not available in the United States. In North America, milk thistle is sold most often as an extract, which is a concentrated liquid preparation made by soaking one or more of the chopped or mashed "aerial" parts of milk thistle plants (flowers, leaves, seeds, and stems) in a liquid such as alcohol. This semi-liquid preparation is then strained to filter out the solid parts. It can be packaged as a liquid or dried and made into capsules or tablets. Extracts made only from the seeds of milk thistle are thought not to have estrogen-like effects. The active chemicals in milk thistle do not dissolve very well in water, so making a tea from dried milk thistle is not very useful.

A typical daily dose of milk thistle extract is 200 mg to 420 mg in one, two, or three doses. In clinical studies, the most common length of dosing was 4 weeks to 8 weeks.

Summary

Milk thistle is effective at protecting the liver from toxic substances. In many parts of the world, it is used as an emergency measure to prevent death among individuals who have eaten poisonous mushrooms. It is also taken to prevent or lessen liver damage caused by some medications and industrial chemicals. Milk thistle may have some usefulness for treating liver diseases such as hepatitis and cirrhosis--including alcohol-induced liver damage. Formerly used to promote milk production for women who were breast-feeding, milk thistle has possible mild estrogenic effects that may make it useful for treating certain types of cancer. It is thought to reduce cholesterol to some degree, but more studies are needed to prove its usefulness in the treatment of high cholesterol.

Risks

Due to the estrogen-like effect that may be associated with taking milk thistle, pregnant women and women with hormone-dependent conditions should not take it. Men who have prostate cancer should not take it without the approval of a doctor. Touching milk thistle plants may cause a skin rash.

Side Effects

Side effects from using milk thistle are reported to be mild. They include general gastrointestinal (GI) upset.

Interactions

Milk thistle may interfere with the effects of estrogen replacement therapy and oral contraceptives due to its possible estrogenic effects. The effectiveness of drugs that are broken down by the same enzymes that break down milk thistle may also be affected. Individuals who take prescription medications should ask a doctor or pharmacist about possible interactions before taking milk thistle.

Last Revised October 16, 2007

References

Agarwal R, Agarwal C, Ichikawa H, Singh RP, Aggarwal BB. Anticancer potential of silymarin: from bench to bed side. Anticancer Research. 2006;26(6B):4457-4498.

Agency for Health Care Policy and Research. Milk thistle: effects on liver disease and cirrhosis and clinical adverse effects. Summary. Evidence Report/Technology Assessment Number 21. September 2000. Available at: http://ahcpr.gov/clinic/epscums/milktsum.htm Accessed February 12, 2003.

Anon: Milk thistle. In: DerMarderosian A, Beutler JA, eds. Facts and Comparisons: The Review of Natural Products. St. Louis, MO, Facts and Comparisons. January 1997.

Arizona Board of Regents. An Illustrated Guide to Arizona Weeds. Tucson, Arizona. The University of Arizona Press. 1972. Available at: http://wwwuapress.arizona.edu/online.bks/weds/milkthis.htm Accessed March 6, 2003.

Awang D. Milk thistle. Canadian Pharmaceutical Journal. 1993;126:402-404 and 422.

Bean C. The Nature Conservancy. Element Stewardship Abstract for Silybum marianum. Available at: http://tncweeds.ucdavis.edu/esadocs/documnts/silymar.html Accessed March 6, 2003.

Ball KR, Kowdley KV. A review of Silybum marianum (milk thistle) as a treatment for alcoholic liver disease. Journal of Clinical Gastroenterology. 2005;39(6):520-528.

Bean P. The use of alternative medicine in the treatment of hepatitis C. American Clinical Laboratory. 2002;21(4):19-21.

Buzzelli G, Moscarella S, Giusti A, Duchini A, Marena C, Lampertico M. A pilot study of the liver protective effect of silybin-phosphatidylcholine complex (idb1016) in chronic active hepatitis. International Journal of Clinical Pharmacology, Therapy, and Toxicology. 1993. 31(9):456-460.

Chlopcikova S, Psotova J, Miketova P, Simanek V. Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part I. Silymarin and its flavonolignans. Phytotherapy Research. 2004;18(2):107-110.

Chu SC, Chiou HL, Chen PN, Yang SF, Hsieh YS. Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2. Molecular Carcinogens. 2004;40(3):143-149.

Comelli MC, Mengs U, Schneider C, Prosdocimi M. Toward the definition of the mechanism of action of silymarin: activities related to cellular protection from toxic damage induced by chemotherapy. Integrative Cancer Therapies. 2007;6(2):120-129.

Crocenzi FA, Roma MG. Silymarin as a new hepatoprotective agent in experimental cholestasis: new possibilities for an ancient medication. Current Medicinal Chemistry. 2006;13(9):1055-1074.

Crocenzi FA, Sanchez Pozzi EJ, Pellegrino JM, et al. Beneficial effects of silymarin on estrogen-induced cholestasis in the rat: a study in vivo and in isolated hepatocyte couplets. Hepatology. 2001;34(2):329-339.

Das SK, Vasudevan DM. Protective effects of silymarin, a milk thistle (Silybium [sic] marianum) derivative on ethanol-induced oxidative stress in liver. Indian Journal of Biochemistry and Biophysics. 2006;43(5):306-311.

Dattner AM. From medical herbalism to phytotherapy in dermatology: back to the future. Dermatological Therapy. 2003;16(2):106-113.

Davis-Searles PR, Nakanishi Y, Kim NC, et al. Milk thistle and prostate cancer: differential effects of pure flavonolignans from Silybum marianum on antiproliferative end points in human prostate carcinoma cells. Cancer Research. 2005;65(10):4448-4457.

Dhanalakshmi S, Agarwal P, Glode LM, Agarwal R. Silibinin sensitizes human prostate carcinoma DU145 cells to cisplatin- and carboplatin-induced growth inhibition and apoptotic death. International Journal of Cancer. 2003;106(5):699-705.

Dhanalakshmi S, Mallikarjuna GU, Singh RP, Agarwal R. Silibinin prevents ultraviolet radiation-caused skin damages in SKH-1 hairless mice via a decrease in thymine dimer positive cells and an up-regulation of p53-p21/Cip1 in epidermis. Carcinogenesis. 2004;25(8):1459-1465.

DiCenzo R, Shelton M, Jordan K, et al. Coadministration of milk thistle and indinavir in healthy subjects. Pharmacotherapy. 2003;23(7):866-870.

Dryden GW, Song M, McClain C. Polyphenols and gastrointestinal diseases. Current Opinion in Gastroenterology. 2006;22(2):165-170.

Ferenci P, Dragosics B, Dittrich H, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. Journal of Hepatology. 1989;9(1):105-113.

Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease. American Journal of Gastroenterology. 1998;93(2):139-143.

Fraschini F, Demartini G, Esposti D. Pharmacology of silymarin. Clinical Drug Investigation. 2002;22(1):51-65.

Gazak R, Walterova D, Kren V. Silybin and silymarin--new and emerging applications in medicine. Current Medicinal Chemistry. 2007;14(3):315-338.

Giese LA. Milk thistle and the treatment of hepatitis. Gastroenterology Nursing. 2001;24(2):95-97.

Gordon A, Hobbs DA, Bowden DS, et al. Effects of Silybum marianum on serum hepatitis C virus RNA, alanine aminotransferase levels and well-being in patients with chronic hepatitis C. Journal of Gastroenterology and Hepatology. 2006;21(1 Pt 2):275-280.

Greenlee H, Abascal K, Yarnell E, Ladas E. Clinical applications of Silybum marianum in oncology. Integrative Cancer Therapies. 2007;6(2):158-165.

Gurley BJ, Barone GW, Williams DK, et al. Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin pharmacokinetics in humans. Drug Metabolism and Disposition. 2006;34(1):69-74.

Hernandez R, Nazar E. Effect of silymarin in intrahepatic cholestasis of pregnancy (preliminary communication) [Article in Spanish] Rev Chil Obstet Ginecol. 1982;47(1):22-29.

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. Clinical Cancer Research. 2006;12(9):2944-2950.

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. Phytotherapy Research.2006;20(12):1036-1039.

Hussain SA. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. Journal of Medical Food. 2007;10(3):543-547.

Ioannides C. Pharmacokinetic interactions between herbal remedies and medicinal drugs. Xenobiotica. 2002;32(6):451-478.

Jacobs BP, Dennehy C, Ramirez G, Sapp J, Lawrence VA. Milk thistle for the treatment of liver disease: a systematic review and meta-analysis. American Journal of Medicine. 2002;113(6):506-515.

Jellin JM, Gregory P, Batz F, Hitchens K, et al, eds. Pharmacist's Letter/Prescriber's Letter. Natural Medicines Comprehensive Database, 3rd Edition. Stockton CA: Therapeutic Research Facility, 2000.

Johnson VJ, He Q, Osuchowski MF, Sharma RP. Physiological responses of a natural antioxidant flavonoid mixture, silymarin, in BALB/c mice: III. Silymarin inhibits T-lymphocyte function at low doses but stimulates inflammatory processes at high doses. Planta Medica. 2003;69(1):44-49.

Karimi G, Ramezani M, Tahoonian Z. Cisplatin nephrotoxicity and protection by milk thistle extract in rats. Evidence Based Complementary and Alternative Medicine. 2005;2(3):383-386.

Katiyar SK. UV-induced immune suppression and photocarcinogenesis: Chemoprevention by dietary botanical agents. Cancer Letter. 2007;255(1):1-11.

Kiruthiga PV, Shafreen RB, Pandian SK, Arun S, Govindu S, Devi KP. Protective effect of silymarin on erythrocyte haemolysate [sic] against benzo(a)pyrene and exogenous reactive oxygen species (H2O2) induced oxidative stress. Chemosphere. 2007;68(8):1511-1518.

Kohno H, Tanaka T, Kawabata K, et al. Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats. International Journal of Cancer. 2002;101(5):461-468.

Krecman V, Skottova N, Walterova D, Ulrichova J, Simanek V. Silymarin inhibits the development of diet-induced hypercholesterolemia in rats. Planta Medica. 1998;64(2):138-142.

Ladas EJ, Kelly KM. Milk thistle: is there a role for its use as an adjunct therapy in patients with cancer? Journal of Alternative and Complementary Medicine. 2003;9(3):411-416.

Lee DG, Kim HK, Park Y, et al. Gram-positive bacteria specific properties of silybin derived from Silybum marianum. Archives of Pharmaceutical Research. 2003;26(8):597-600.

Lee LS, Andrade AS, Flexner C. Interactions between natural health products and antiretroviral drugs: pharmacokinetic and pharmacodynamic effects. Clinical Infectious Diseases. 2006;43(8):1052-1059.

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. Biology and Pharmacy Bulletin. 2006;29(6):1096-1101.

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. Biology and Pharmacy Bulletin. 2006;29(6):1096-1101.

Li LH, Wu LJ, Zhou B, et al. Silymarin prevents UV irradiation-induced A375-S2 cell apoptosis. Biology and Pharmacology Bulletin. 2004;27(7):1031-1036.

Lieber CS, Leo MA, Cao Q, Ren C, DeCarli LM. Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons. Journal of Clinical Gastroenterology. 2003;37(4):336-339.

Maghrani M, Zeggwagh NA, Lemhadri A, El Amraoui M, Michel JB, Eddouks M. Study of the hypoglycaemic [sic] activity of Fraxinus excelsior and Silybum marianum in an animal model of type 1 diabetes mellitus. Journal of Ethnopharmacology. 2004;91(2-3):309-316.

Malewicz B, Wang Z, Jiang C, et al. Enhancement of mammary carcinogenesis in two rodent models by silymarin dietary supplements. Carcinogenesis. 2006;27(9):1739-1747.

Mayer KE, Myers RP, Lee SS. Silymarin treatment of viral hepatitis: a systematic review. Journal of Viral Hepatitis. 2005;12(6):559-567.

McCarty MF. Potential utility of natural polyphenols for reversing fat-induced insulin resistance. Medical Hypotheses. 2005;64(3):628-635.

Mills E, Wilson K, Clarke M, et al. Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis. European Journal of Clinical Pharmacology. 2005;61(1):1-7.

Muriel P, Mourelle M. The role of membrane composition in ATPase activities of cirrhotic rat liver: effect of silymarin. Journal of Applied Toxicology. 1990;10(4):281-284.

National Cancer Institute. Milk thistle (PDQ). Health professional version. Last modified June 23, 2004. Available at: www.nci.nih.gov/cancertopics/ pdq/cam/milkthistle/healthprofessional/allpages. Accessed October 14, 2004.

Natural Medicines Comprehensive Database, Online Edition. Pharmacist's Letter/Prescriber's Letter. Stockton CA: Therapeutic Research Facility, 2006. Available at: http://www.pharmacistsletter.com/(S(ulqz3s45omt3ag55um4kj345))/home.aspx?li=1&st=1&cs=&s=ND.

Pares A, Planas R, Torres M, et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. Journal of Hepatology. 1998. 28(4):615-621.

Peirce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York: Stonesong Press; 1999.

Piscitelli SC, Formentini E, Burstein AH, Alfaro R, Jagannatha S, Falloon J. Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy. 2002;22(5):551-556.

Post-White J, Ladas EJ, Kelly KM. Advances in the use of milk thistle (Silybum marianum). Integrative Cancer Therapies. 2007;6(2):104-109.

Qi L, Singh RP, Lu Y, Agarwal R, et al. Epidermal growth factor receptor mediates silibinin-induced cytotoxicity in a rat glioma cell line. Cancer Biology and Therapeutics. 2003;2(5):526-531.

Rainone F. Milk thistle. American Family Physician. 2005;72(7):1285-1258.

Rambaldi A, Jacobs BP, Iaquinto G, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database Systematic Review. 2005;(2):CD003620.

Rambaldi A, Jacobs BP, Iaquinto G, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C liver diseases--a systematic Cochrane hepato-biliary group review with meta-analyses of randomized clinical trials. American Journal of Gastroenterology. 2005;100(11):2583-2591.

Sagar SM. Future directions for research on Silybum marianum for cancer patients. Integrative Cancer Therapies. 2007;6(2):166-173.

Saller R, Meier R, Brignoli R. The use of silymarin in the treatment of liver diseases. Drugs. 2001;61(14):2035-2063.

Saller R, Melzer J, Reichling J, Brignoli R, Meier R. An updated systematic review of the pharmacology of silymarin. Forsch Komplementarmed. 2007;14(2):70-80.

Scambia G, De Vincenzo R, Ranelletti FO, et al. Antiproliferative effect of silybin on gynaecological [sic] malignancies: synergism with cisplatin and doxorubicin. European Journal of Cancer. 1996;32A(5):877-882.

Seidlova-Wuttke D, Becker T, Christoffel V, Jarry H, Wuttke W. Silymarin is a selective estrogen receptor beta (ERbeta) agonist and has estrogenic effects in the metaphysis of the femur but no or antiestrogenic effects in the uterus of ovariectomized (ovx) rats. Journal of Steroid Biochemistry and Molecular Biology. 2003;86(2):179-188.

Singh RP, Agarwal R. Mechanisms and preclinical efficacy of silibinin in preventing skin cancer. European Journal of Cancer. 2005;41(13):1969-1979.

Singh RP, Agarwal R. Prostate cancer prevention by silibinin. Current Cancer Drug Targets. 2004;4(1):1-11.

Singh RP, Deep G, Chittezhath M, et al. Effect of silibinin on the growth and progression of primary lung tumors in mice. Journal of the National Cancer Institute. 2006;98(12):846-855.

Skottova N, Krecman V. Silymarin as a potential hypocholesterolaemic [sic] drug. Physiology Research. 1998;47(1):1-7.

Skottova N, Vecera R, Urbanek K, Vana P, Walterova D, Cvak L. Effects of polyphenolic fraction of silymarin on lipoprotein profile in rats fed cholesterol-rich diets. Pharmacology Research. 2003;47(1):17-26.

Somogyi A, Ecsedi GG, Blazovics A, Miskolczi K, Gergely P, Feher J. Short term treatment of type II hyperlipoproteinaemia [sic] with silymarin. Acta Medica Hungaria. 1989;46(4):289-295.

Sridar C, Goosen TC, Kent UM, Williams JA, Hollenberg PF. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metabolism and Disposition. 2004;32(6):587-594.

Stickel F, Schuppan D. Herbal medicine in the treatment of liver diseases. Digestive and Liver Diseases. 2007;39(4):293-304.

Svagera Z, Skottova N, Vana P, et al. Plasma lipoproteins in transport of silibinin, an antioxidant flavonolignan from Silybum marianum. Phytotherapy Research. 2003;17(5):524-530.

Tamayo C, Diamond S. Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum marianum [L.] Gaertn.). Integrative Cancer Therapies. 2007;6(2):146-157.

Thelen P, Jarry H, Ringert RH, Wuttke W. Silibinin down-regulates prostate epithelium-derived Ets transcription factor in LNCaP prostate cancer cells. Planta Medica. 2004;70(5):397-400.

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. Journal of Urology. 2004;171(5):1934-1938.

Toklu HZ, Tunali-Akbay T, Erkanli G, Yuksel M, Ercan F, Sener G. Silymarin, the antioxidant component of Silybum marianum, protects against burn-induced oxidative skin injury. Burns. 2007;33(7):908-916.

Tyagi AK, Agarwal C, Chan DC, Agarwal R. Synergistic anti-cancer effects of silibinin with conventional cytotoxic agents doxorubicin, cisplatin and carboplatin against human breast carcinoma MCF-7 and MDA-MB468 cells. Oncology Reports. 2004;11(2):493-499.

Tyagi A, Agarwal C, Harrison G, Glode LM, Agarwal R. Silibinin causes cell cycle arrest and apoptosis in human bladder transitional cell carcinoma cells by regulating CDKI-CDK-cyclin cascade, and caspase 3 and PARP cleavages. Carcinogenesis. 2004;25(9):1711-1720.

Tyagi AK, Agarwal C, Singh RP, Shroyer KR, Glode LM, Agarwal R. Silibinin down-regulates survivin protein and mRNA expression and causes caspases activation and apoptosis in human bladder transitional-cell papilloma RT4 cells. Biochemistry and Biophysics Research Communications. 2003;312(4):1178-1184.

Tyagi A, Bhatia N, Condon MS, Bosland MC, Agarwal C, Agarwal R. Antiproliferative and apoptotic effects of silibinin in rat prostate cancer cells. Prostate. 2002;53(3):211-217.

van den Bout-van den Beukel CJ, Koopmans PP, van der Ven AJ, De Smet PA, Burger DM. Possible drug-metabolism interactions of medicinal herbs with antiretroviral agents. Drug Metabolism Review. 2006;38(3):477-514.

van Erp NP, Baker SD, Zhao M, et al. Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clinical Cancer Research. 2005;11(21):7800-7806.

Vaknin Y, Hadas R, Schafferman D, Murkhovsky L, Bashan N. The potential of milk thistle (Silybum marianum L.), an Israeli native, as a source of edible sprouts rich in antioxidants. International Journal of Food Science and Nutrition. Epublished ahead of print. August 20, 2007.

Varga Z, Ujhelyi L, Kiss A, Balla J, Czompa A, Antus S. Effect of silybin on phorbol myristate actetate-induced protein kinase C translocation, NADPH oxidase activity and apoptosis in human neutrophils. Phytomedicine. 2004;11(2-3):206-212.

Varghese L, Agarwal C, Tyagi A, Singh RP, Agarwal R. Silibinin efficacy against human hepatocellular carcinoma. Clinical Cancer Research. 2005;11(23):8441-8448.

Wilasrusmee C, Kittur S, Shah G, et al. Immunostimulatory effect of Silybum Marianum (milk thistle) extract. Medical and Science Monitor. 2002;8(11):BR439-BR443.

Wu DF, Peng RX, Ye LP, Yu P. The effects of silymarin on hepatic microsomal and mitochondrial membrane fluidity in mice. [Article in Chinese] Zhongguo Zhong Yao Za Zhi. 2003 Sep;28(9):870-872.

Yoo HG, Jung SN, Hwang YS, et al. Involvement of NF-kappaB and caspases in silibinin-induced apoptosis of endothelial cells. International Journal of Molecular Medicine. 2004;13(1):81-86.

Zhao J, Agarwal R. Tissue distribution of silibinin, the major active constituent of silymarin, in mice and its association with enhancement of phase II enzymes: implications in cancer chemoprevention. Carcinogenesis. 1999;20(11):2101-2108.

Zhou S, Lim LY, Chowbay B. Herbal modulation of P-glycoprotein. Drug Metabolism Review. 2004;36(1):57-104.

Zhou B, Wu LJ, Tashiro S, Onodera S, Uchiumi F, Ikejima T. Silibinin protects rat cardiac myocyte from isoproterenol-induced DNA damage independent on regulation of cell cycle. Biology and Pharmacy Bulletin. 2006;29(9):1900-1905.

Zielinska-Przyjemska M, Wiktorowicz K. An in vitro study of the protective effect of the flavonoid silydianin against reactive oxygen species. Phytotherapy Research. 2006;20(2):115-119.

Last Revised October 16, 2007

Note: The above information is not intended to replace the advice of your physician, pharmacist, or other healthcare professional. It is not meant to indicate that the use of the product is safe, appropriate, or effective for you.

In general, herbal products are not subject to review or approval by the U.S. Food and Drug Administration (FDA). They are not required to be standardized, meaning that the amounts of active ingredients or contaminants they contain may vary between brands or between different batches of the same brand. Not all of the risks, side effects, or interactions associated with the use of herbal products are known because few reliable studies of their use in humans have been done.

This information is provided for your education only. Please share this information with your healthcare provider and be sure that you talk to your doctor and pharmacist about all the prescription and non-prescription medicines you take before you begin to use any herbal product.

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