Milk Thistle (Silybum marianum), Silymarin

Milk Thistle (Silybum marianum), Silymarin
Natural Standard evidence-based abbreviated summary monograph, Copyright © 2004 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.

While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

Related Terms:

Bull thistle, cardo blanco, Cardui mariae fructus, Cardui mariae herba, Cardum marianum L., Carduus marianus L., Chardon-Marie, Emetic root, Frauendistel, Fructus Silybi mariae, fruit de chardon Marie, heal thistle, Holy thistle, Isosilibinin, Kanger, Kocakavkas, Kuub, Lady's thistle, Marian thistle, mariana mariana, Mariendistel, Marienkrörner, Mary thistle, mild thistle, milk ipecac, pig leaves, royal thistle, shui fei ji, silidianin, Silybi mariae fructus, silybin, silybinin, silychristin, silymarin, snake milk, sow thistle, St. Mary's thistle, Venue thistle, variegated thistle, wild artichoke.

	Milk thistle has been used medicinally for over 2000 years, most commonly for the treatment of liver and gallbladder disorders. A flavonoid complex called silymarin can be extracted from the seeds of milk thistle, and is believed to be the biologically active component. The terms "milk thistle" and "silymarin" are often used interchangeably.
	Milk thistle products are popular in Europe and the United States for various types of liver disease. Although numerous human trials have been published, most studies have not been well designed or reported.

Uses These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.	Grade^*
Cirrhosis Multiple studies from Europe suggest benefits of oral milk thistle for cirrhosis. In experiments up to 5 years long, milk thistle has improved liver function and decreased the number of deaths that occur in cirrhotic patients. Although these results are promising, most studies have been poorly designed. Better research is necessary before a strong recommendation can be made.	B
Chronic hepatitis (liver inflammation) Several studies of oral milk thistle for hepatitis caused by viruses or alcohol report improvements in liver tests. However, most studies have been small and poorly designed. More research is needed before a recommendation can be made.	C
Acute viral hepatitis Research on milk thistle for acute viral hepatitis has not provided clear results, and milk thistle cannot be recommended for this potentially life-threatening condition.	C
Amanita phalloides mushroom poisoning Milk thistle has been used traditionally to treat Amanita phalloides mushroom poisoning, and several animal studies and isolated human cases have suggested possible benefits. However, there are not enough reliable studies in humans to support this use of milk thistle.	C
Cancer prevention There are early reports from laboratory experiments that the chemicals silymarin and silibinin in milk thistle reduce the growth of human breast, cervical, and prostate cancer cells. There is also one report of a patient with liver cancer who improved following treatment with milk thistle. However, this research is too early to draw firm conclusions, and effects have not been shown in high-quality human trials.	C
Liver damage from drugs or toxins Several studies suggest possible benefits of milk thistle to treat or prevent liver damage caused by drugs or toxic chemicals. Results of this research are not clear, and most studies have been poorly designed. Therefore, there is not enough scientific evidence to recommend milk thistle for this use.	C
High cholesterol Although animal and laboratory research suggests cholesterol-lowering effects of milk thistle, human studies have provided unclear results. Further studies are necessary before a recommendation can be made.	C
Diabetes (in patients with cirrhosis) A small number of studies suggest possible improvements of blood sugar control in cirrhotic patients with diabetes. However, there is not enough scientific evidence to recommend milk thistle for this use.	C
*Key to grades: A: Strong scientific evidence for this use; B: Good scientific evidence for this use; C: Unclear scientific evidence for this use; D: Fair scientific evidence against this use (it may not work); F: Strong scientific evidence against this use (it likely does not work).

The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

Amiodarone toxicity reactions, asthma, bleeding, bronchitis, cough, diabetic nerve pain, dyspepsia, gallstones, hemorrhoids, liver "cleansing," liver cancer, malaria, menstrual problems, plague, prostate cancer, psoriasis, radiation sickness, skin cancer, snakebites, spleen disorders, sunscreen, varicose veins.

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Standardization

Standardization involves measuring the amount of certain chemicals in products to try to make different preparations similar to each other. It is not always known if the chemicals being measured are the "active" ingredients. Milk thistle is often standardized to contain 70-80% silymarin. Silymarin is a mixture of three flavonolignans: silybin, silidianin, and silychristin. Despite standardization, different preparations and brands may have different effects in the body. Silipide® (IdB 1016) is a special milk thistle product that is designed to be absorbed better into the body. Doses of Silipide® are measured by "silybin equivalents."

One study analyzing stability of milk thistle tincture found a shelf life of approximately 3 months.

Adults (18 years and older)

	Cirrhosis: Silymarin (Legalon®) 280mg-420mg per day divided into 2-3 doses. Up to 450mg daily divided into three doses has been studied.
	Hepatitis (chronic): Silipide® (IdB 1016) 160-480mg per day in silybin equivalents, or silymarin (Legalon®) 420mg daily divided into three doses.
	Hepatitis (acute, viral): Silymarin 420mg daily divided into three doses.
	Drug/toxin-induced hepatotoxicity: Silymarin (Legalon®) 280-420mg daily divided into three doses. Up to 800mg daily has been studied.
	High cholesterol: Silymarin 420mg per day has been studied.
	Diabetes (insulin-dependent) associated with cirrhosis: Silymarin (Legalon®) 230-600mg per day has been studied. Effectiveness and safety have not been proven.

Children (younger than 18 years)

There is not enough scientific data to recommend milk thistle for use in children.

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

People with allergies to plants in the aster family (Compositea, Asteraceae) or to daisies, artichokes, common thistle, kiwi, or to any of milk thistle's constituents (silibinin, silychistin, silydianin, silymonin, siliandrin) may have allergic reactions to milk thistle. Anaphylactic shock (a severe allergic reaction) from milk thistle tea or tablets has been reported in several patients.

Side Effects and Warnings

Milk thistle appears to be well tolerated in recommended doses for up to 6 years. Some patients in studies have experienced stomach upset, headache, and itching. There are rare reports of appetite loss, gas, heartburn, diarrhea, joint pain, and impotence with milk thistle use. One person experienced sweating, nausea, stomach pain, diarrhea, vomiting, weakness and collapse after taking milk thistle. This reaction may have been due to an allergic reaction, and improved after 24 hours. High liver enzyme levels in one person taking milk thistle returned to normal after the person stopped taking the herb.

In theory, milk thistle may lower blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugars. Serum glucose levels may need to be monitored by a healthcare provider, and medication adjustments may be necessary.

Pregnancy and Breastfeeding

Milk thistle has been used historically to improve breast milk flow, and two brief studies of milk thistle in pregnant women reported no side effects. However, there is not enough scientific evidence to support the safe use of milk thistle during pregnancy or breastfeeding at this time.

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

	Animal studies suggest that milk thistle may interfere with the way the body processes certain drugs using the liver's "cytochrome P450" enzyme system. As a result, the levels of these drugs may be increased in the blood, and may cause increased effects or adverse reactions. Many types of drugs may be affected. You should speak with a qualified health care provider to obtain a list of these drugs and their possible interactions.In theory, milk thistle may lower blood sugar levels. Caution is advised when using medications that may also lower blood sugar. Patients taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare provider. Medication adjustments may be necessary.
	A possible interaction with phenytoin (Dilantin®) has been reported with milk thistle. However, the facts are unclear.
	Milk thistle ingredients have been reported to prevent amiodarone toxicity in animal studies.

Interactions with Herbs and Dietary Supplements

	Animal studies suggest that milk thistle may interfere with the way the body processes certain herbs or supplements using the liver's "cytochrome P450" enzyme system. As a result, the levels of other herbs or supplements to be too high in the blood. It may also alter the effects that other herbs or supplements have on the P450 system, such as bloodroot, cat's claw, chamomile, chaparral, chasteberry, damiana, Echinacea angustifolia, goldenseal, grapefruit, licorice, oregano, red clover, St. John's wort, wild cherry, and yucca.
	Milk thistle may lower blood sugar levels. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment. Some examples include: Aloe vera, American ginseng, bilberry, bitter melon, burdock, fenugreek, fish oil, gymnema, horse chestnut/horse chestnut seed extract (HCSE), marshmallow, milk thistle, Panax ginseng, rosemary, Siberian ginseng, stinging nettle, vitamin E.
	Silymarin and vitamin E have been reported to prevent amiodarone toxicity in animal studies.

	Last updated: November 2004.
	This information is based on a professional level monograph edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Natural Standard developed the above evidence-based information based on a systematic review of more than 250 scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references effectiveness are listed below.

Agoston M, Orsi F, Feher E, Hagymasi K, Orosz Z, Blazovics A, Feher J, Vereckei A. Silymarin and vitamin E reduce amiodarone-induced lysosomal phospholipidosis in rats. Toxicology 2003;190(3):231-241. View Abstract
Allain H, Schuck S, Lebreton S, et al. Aminotransferase levels and silymarin in de novo tacrine-treated patients with Alzheimer's disease. Dement Geriatr Cogn Disord 1999;10(3):181-185. View Abstract
Bettini R, Gorini M. [Use of ursodeoxycholic acid combined with silymarin in the treatment of chronic ethyl-toxic hepatopathy] Clin Ter. 2002 Sep-Oct;153(5):305-307 View Abstract
Bilia AR, Bergonzi MC, Gallori S, Mazzi G, Vincieri FF. Stability of the constituents of Calendula, milk-thistle and passionflower tinctures by LC-DAD and LC-MS. J Pharm Biomed Anal 2002;30(3):613-24. View Abstract
Breschi MC, Martinotti E, Apostoliti F, Nieri P. Protective effect of silymarin in antigen challenge- and histamine-induced bronchoconstriction in in vivo guinea-pigs. View Abstract
Buzzelli G, Moscarella S, Giusti A, et al. A pilot study on the liver protective effect of silybinphosphatidylcholine complex (IdB1016) in chronic active hepatitis. Int J Clin Pharmacol Ther Toxicol 1993;31(9):456-460. View Abstract
De Martiis M, Fontana M, Assogna G, D'Ottavi R, D'Ottavi O. [Milk thistle (Silybum marianum) derivatives in the therapy of chronic hepatopathies] Clin Ter 1980;94(3):283-315. View Abstract
DiCenzo R, Shelton M, Jordan K, Koval C, Forrest A, Reichman R, Morse G. Coadministration of milk thistle and indinavir in healthy subjects. Pharmacotherapy. 2003 Jul;23(7):866-70. 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 1989;9(1):105-113. View Abstract
Flora K, Hahn M, Rosen H, et al. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol 1998; 93(2):139-143. View Abstract
Lawrence V, Jacobs B, Dennehy C, et al. Report on milk thistle: effects on liver disease and cirrhosis and clinical adverse effects. Evidence Report/Technology Assessment No. 21 (Contract 290-97-0012 to the San Antonio Evidence-based Practice Center, based at the University of Texas Health Science Center at San Antonio, and The Veterans Evidence-based Research, Dissemination, and Implementation Center, a Veterans Affairs Services Research and Development Center of Excellence). AHRQ Publication No. 01-E025. Rockville, MD: Agency for Healthcare Research and Quality. October 2000.
Lirussi F, Nassuato G, Orlando R, et al. Treatment of active cirrhosis with ursodeoxycholic acid and a free radical scavenger: A two year prospective study. Med Sci Ress 1995;23:31-33.
Lucena MI, Andrade RJ, de la Cruz JP, et al. Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo- controlled clinical study. Int J Clin Pharmacol Ther 2002;40(1):2-8. View Abstract
Madisch A, Melderis H, Mayr G, Sassin I, Hotz J. [A plant extract and its modified preparation in functional dyspepsia. Results of a double-blind placebo controlled comparative study] Z Gastroenterol 2001;39(7):511-517. View Abstract
Marcelli R, Bizzoni P, Conte D, et al. Randomized controlled study of the efficacy and tolerability of a short course of IdB 1016 in the treatment of chronic persistent hepatitis. Eur Bull Drug Res 1992;1(3):131-135.
Palasciano G, Portincasa P, Palmieri V, et al. The effect of silymarin on plasma levels of malon-dialdehyde in patients receiving long-term treatment with psychotropic drugs. Curr Ther Res 1994;55(5):537-545.
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. J Hepatol 1998;28(4):615-621. View Abstract
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):551-6. View Abstract
Salmi HA, Sarna S. Effect of silymarin on chemical, functional, and morphological alterations of the liver. A double-blind controlled study. Scand J Gastroenterol 1982;17(4):517-521. View Abstract
Szilard S, Szentgyorgyi D, Demeter I. Protective effect of Legalon in workers exposed to organic solvents. Acta Med Hung 1988;45(2):249-256. View Abstract
Velussi M, Cernigoi AM, De Monte A, et al. Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatol 1997;26(4):871-879. View Abstract
Velussi M, Cernigoi AM, Viezzoli L, et al. Silymarin reduces hyperinsulinemia, malondialdehyde levels, and daily insulin need in cirrhotic diabetic patients. Curr Ther Res 1993;53(5):533-545.

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.