The botanical name for milk thistle is Silybum marianum (L.) Gaertn. Milk thistle is also referred to as holy thistle, Marian thistle, Mary thistle, Our Lady’s thistle, St. Mary thistle, wild artichoke, Mariendistel (German), and Chardon-Marie (French). The plant is indigenous to Europe but can also be found in the United States and South America. Traditionally, the leaves have been used in salads, and the fruit of the flower has been roasted as a coffee substitute. The seeds of milk thistle are the medicinal parts of the plant.[1] The primary active constituent of milk thistle is silymarin, which is composed of four isomers: silybin, isosilybin, silychristin, and silydianin. Most supplements are standardized according to their silybin content. In turn, silybin and isosilybin are both mixtures of two diastereomers, silybins A and B and isosilybins A and B, respectively.[2] Special formulations of silybin have been developed to enhance the bioavailability of the herbal product; these forms are sold under the names Legalon, silipide, and Siliphos. Because of milk thistle’s lipophilic nature, it is usually administered in capsule or tablet form rather than as an herbal tea. In Europe, silybin is administered intravenously as the only effective antidote for Amanita phalloides (Fr.) Link toxin.[3] Humans exposed to this mushroom toxin develop serious liver failure that ultimately progresses to death.

Several companies distribute milk thistle as a dietary supplement. In the United States, dietary supplements are regulated as foods, not drugs. Therefore, premarket evaluation and approval by the Food and Drug Administration (FDA) are not required unless specific disease prevention or treatment claims are made. Because dietary supplements are not formally reviewed for manufacturing consistency, ingredients may vary considerably from lot to lot; in addition, there is no guarantee that ingredients identified on product labels are present at all or are present in the specified amounts. It is important to note that the FDA has not approved the use of milk thistle as a treatment for cancer patients or patients with any other medical condition.

To conduct clinical drug research in the United States, researchers must file an Investigational New Drug (IND) application with the FDA. The IND application process is confidential, and IND information can be disclosed only by the applicants. To date, only one investigator has announced holding an IND to study milk thistle as an adjunct cancer treatment.

Despite milk thistle’s long history of being used to treat liver and biliary complaints, it was not until 1968 that silymarin was isolated from the seeds of the plant, and it was proposed that silymarin might be the active ingredient.[4] Silymarin was later determined to be a flavonolignan that is composed of four structurally similar compounds: silybin, isosilybin, silydianin, and silychristin.[2] Researchers have investigated the role that silibinin may play in the treatment of hepatitis and cirrhosis. Most studies have investigated the isolated compound silymarin or its most active isomer silybin, rather than the herbal plant in its whole form.

Silymarin is most well known for its purported effects on the liver. In laboratory studies, silymarin has been found to stabilize cell membranes, thus preventing toxic chemicals from entering the cell.[3,5-7] Laboratory studies have also demonstrated that silymarin stimulates synthesis and activity of enzymes responsible for detoxification pathways and exhibits potent antioxidant properties.[6-17] Specifically, silymarin has been shown to stimulate the glutathione S-transferase pathway and alter the intracellular concentration of glutathione (a potent antioxidant). Silymarin has also been shown to neutralize a wide range of free radicals.

Laboratory experiments conducted using cancer cell lines have suggested that silibinin enhances the efficacy of cisplatin and doxorubicin against ovarian and breast cancer cells.[18] Silybin appears to have direct anticancer effects against prostate, breast, and ectocervical tumor cells.[19] Silybin may also affect the cell cycle in cancer cells by slowing down cell growth, as demonstrated with prostate cancer cell lines.[20] Laboratory studies using leukemia cell lines found that silybin did not stimulate growth of leukemia cells.[21]

No human clinical trials on milk thistle or silymarin as a cancer treatment or as an adjunctive therapy in individuals with cancer have been published. Most clinical trials have investigated silymarin’s effectiveness in the treatment of patients with hepatitis, cirrhosis, or biliary disorders.[22-31] These studies have employed a wide range of doses (120–560 mg /day) and have yielded conflicting results. Many of the well-designed, large-scale trials have reported a beneficial effect rather than no effect. The most commonly reported adverse effects are a mild laxative effect and gastrointestinal upset.

References

1. PDR® for Herbal Medicines™. 2nd ed. Montvale, NJ: Medical Economics, 2000. 
   
   
2. Lee DY, Liu Y: Molecular structure and stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, Isolated from Silybum marianum (milk thistle). J Nat Prod 66 (9): 1171-4, 2003.  [PUBMED Abstract]
   
   
3. Hruby K, Csomos G, Fuhrmann M, et al.: Chemotherapy of Amanita phalloides poisoning with intravenous silibinin. Hum Toxicol 2 (2): 183-95, 1983.  [PUBMED Abstract]
   
   
4. Wagner H, Hörhammer L, Münster R: [On the chemistry of silymarin (silybin), the active principle of the fruits from Silybum marianum (L.) Gaertn. (Carduus marianus L.)] Arzneimittelforschung 18 (6): 688-96, 1968.  [PUBMED Abstract]
   
   
5. Campos R, Garrido A, Guerra R, et al.: Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Med 55 (5): 417-9, 1989.  [PUBMED Abstract]
   
   
6. Farghali H, Kameniková L, Hynie S, et al.: Silymarin effects on intracellular calcuim and cytotoxicity: a study in perfused rat hepatocytes after oxidative stress injury. Pharmacol Res 41 (2): 231-7, 2000.  [PUBMED Abstract]
   
   
7. Lettéron P, Labbe G, Degott C, et al.: Mechanism for the protective effects of silymarin against carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice. Evidence that silymarin acts both as an inhibitor of metabolic activation and as a chain-breaking antioxidant. Biochem Pharmacol 39 (12): 2027-34, 1990.  [PUBMED Abstract]
   
   
8. 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 20 (11): 2101-8, 1999.  [PUBMED Abstract]
   
   
9. Valenzuela A, Guerra R, Videla LA: Antioxidant properties of the flavonoids silybin and (+)-cyanidanol-3: comparison with butylated hydroxyanisole and butylated hydroxytoluene. Planta Med (6): 438-40, 1986.  [PUBMED Abstract]
   
   
10. Valenzuela A, Guerra R, Garrido A: Silybin dihemisuccinate protects rat erythrocytes against phenylhydrazine-induced lipid peroxidation and hemolysis. Planta Med 53 (5): 402-5, 1987.  [PUBMED Abstract]
    
    
11. Valenzuela A, Aspillaga M, Vial S, et al.: Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. Planta Med 55 (5): 420-2, 1989.  [PUBMED Abstract]
    
    
12. Mira ML, Azevedo MS, Manso C: The neutralization of hydroxyl radical by silibin, sorbinil and bendazac. Free Radic Res Commun 4 (2): 125-9, 1987.  [PUBMED Abstract]
    
    
13. Mira L, Silva M, Manso CF: Scavenging of reactive oxygen species by silibinin dihemisuccinate. Biochem Pharmacol 48 (4): 753-9, 1994.  [PUBMED Abstract]
    
    
14. Koch HP, Löffler E: Influence of silymarin and some flavonoids on lipid peroxidation in human platelets. Methods Find Exp Clin Pharmacol 7 (1): 13-8, 1985.  [PUBMED Abstract]
    
    
15. Garrido A, Arancibia C, Campos R, et al.: Acetaminophen does not induce oxidative stress in isolated rat hepatocytes: its probable antioxidant effect is potentiated by the flavonoid silybin. Pharmacol Toxicol 69 (1): 9-12, 1991.  [PUBMED Abstract]
    
    
16. Bosisio E, Benelli C, Pirola O: Effect of the flavanolignans of Silybum marianum L. on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. Pharmacol Res 25 (2): 147-54, 1992 Feb-Mar.  [PUBMED Abstract]
    
    
17. Altorjay I, Dalmi L, Sári B, et al.: The effect of silibinin (Legalon) on the the free radical scavenger mechanisms of human erythrocytes in vitro. Acta Physiol Hung 80 (1-4): 375-80, 1992.  [PUBMED Abstract]
    
    
18. Scambia G, De Vincenzo R, Ranelletti FO, et al.: Antiproliferative effect of silybin on gynaecological malignancies: synergism with cisplatin and doxorubicin. Eur J Cancer 32A (5): 877-82, 1996.  [PUBMED Abstract]
    
    
19. Bhatia N, Zhao J, Wolf DM, et al.: Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: comparison with silymarin. Cancer Lett 147 (1-2): 77-84, 1999.  [PUBMED Abstract]
    
    
20. Zi X, Agarwal R: Silibinin decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: implications for prostate cancer intervention. Proc Natl Acad Sci U S A 96 (13): 7490-5, 1999.  [PUBMED Abstract]
    
    
21. Duthie SJ, Johnson W, Dobson VL: The effect of dietary flavonoids on DNA damage (strand breaks and oxidised pyrimdines) and growth in human cells. Mutat Res 390 (1-2): 141-51, 1997.  [PUBMED Abstract]
    
    
22. Vailati A, Aristia L, Sozzé E, et al.: Randomized open study of the dose-effect relationship of a short course of IdB 1016 in patients with viral or alcoholic hepatitis. Fitoterapia 64 (3), 219-28, 1993. 
    
    
23. Salmi HA, Sarna S: Effect of silymarin on chemical, functional, and morphological alterations of the liver. A double-blind controlled study. Scand J Gastroenterol 17 (4): 517-21, 1982.  [PUBMED Abstract]
    
    
24. Parés 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 28 (4): 615-21, 1998.  [PUBMED Abstract]
    
    
25. Moscarella S, Giusti A, Marra F, et al.: Therapeutic and antilipoperoxidant effects of silybin-phosphatidylcholine complex in chronic liver disease: preliminary results. Current Therapeutic Research 53 (1): 98-102. 
    
    
26. Marena C, Lampertico M: Preliminary clinical development of silipide: a new complex of silybin in toxic liver disorders. Planta Med 57 (Suppl 2): A124-5, 1991. 
    
    
27. 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. European Bulletin of Drug Research 1 (3): 131-5, 1992. 
    
    
28. Flisiak R, Prokopowicz D: Effect of misoprostol on the course of viral hepatitis B. Hepatogastroenterology 44 (17): 1419-25, 1997 Sep-Oct.  [PUBMED Abstract]
    
    
29. Ferenci P: [Therapy of chronic hepatitis C] Wien Med Wochenschr 150 (23-24): 481-5, 2000.  [PUBMED Abstract]
    
    
30. Buzzelli G, Moscarella S, Giusti A, et al.: Therapeutic effects of a new silybin complex in chronic active hepatitis (CAH). [Abstract] Hellenic Journal of Gastroenterology 5 (Suppl): A-151, 38, 1992. 
    
    
31. Albrecht M, Frerick H, Kuhn U, et al.: Therapy of toxic liver pathologies with Legalon®. Z Klin Med 47: 87-92, 1992. 
    
    

Glossary Terms

In cancer therapy, a drug or substance used in addition to the primary therapy.

An unwanted side effect of treatment.

A type of poisonous mushroom that has harmful effects on the kidneys and liver. It is responsible for most fatal cases of mushroom poisoning. Also called death cap.

A substance that protects cells from the damage caused by free radicals (unstable molecules made by the process of oxidation during normal metabolism). Free radicals may play a part in cancer, heart disease, stroke, and other diseases of aging. Antioxidants include beta-carotene, lycopene, vitamins A, C, and E, and other natural and manufactured substances.

Having to do with the liver, bile ducts, and/or gallbladder.

The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body.

Having to do with, or derived from, plants.

Glandular organ located on the chest. The breast is made up of connective tissue, fat, and breast tissue that contains the glands that can make milk. Also called mammary gland.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

A type of chronic, progressive liver disease in which liver cells are replaced by scar tissue.

A drug used to treat many types of cancer. Cisplatin contains the metal platinum. It kills cancer cells by damaging their DNA and stopping them from dividing. Cisplatin is a type of alkylating agent.

Having to do with the examination and treatment of patients.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical study.

Cells of a single type (human, animal, or plant) that have been adapted to grow continuously in the laboratory and are used in research.

A product that is added to the diet. A dietary supplement is taken by mouth, and usually contains one or more dietary ingredient (such as vitamin, mineral, herb, amino acid, and enzyme). Also called nutritional supplement.

The amount of medicine taken, or radiation given, at one time.

A drug that is used to treat many types of cancer and is being studied in the treatment of other types of cancer. Doxorubicin comes from the bacterium Streptomyces peucetius. It damages DNA (the molecules inside cells that carry genetic information) and stops cells from growing. Rapidly growing tumor cells that take up doxorubicin may die. It is a type of anthracycline antitumor antibiotic. Also called doxorubicin hydrochloride, Adriamycin PFS, Adriamycin RDF, and Rubex.

Having to do with the part of the cervix that protrudes into the vagina and is lined with epithelial cells.

A protein that speeds up chemical reactions in the body.

A member of a group of substances found in many plants and plant-based foods. Flavonoids have shown antioxidant effects.

A highly reactive chemical that often contains oxygen and is produced when molecules are split to give products that have unpaired electrons (a process called oxidation). Free radicals can damage important cellular molecules such as DNA or lipids or other parts of the cell.

GI. Refers to the stomach and intestines. Also called GI.

A substance found in plant and animal tissues that has many functions in a cell. These include activating certain enzymes and destroying toxic compounds and chemicals that contain oxygen.

A family of enzymes involved in metabolism and in making toxic compounds less harmful to the body.

Disease of the liver causing inflammation. Symptoms include an enlarged liver, fever, nausea, vomiting, abdominal pain, and dark urine.

Inside a cell.

Into or within a vein. Intravenous usually refers to a way of giving a drug or other substance through a needle or tube inserted into a vein. Also called I.V.

In clinical trials, refers to a drug (including a new drug, dose, combination, or route of administration) or procedure that has undergone basic laboratory testing and received approval from the U.S. Food and Drug Administration (FDA) to be tested in human subjects. A drug or procedure may be approved by the FDA for use in one disease or condition, but be considered investigational in other diseases or conditions. Also called experimental.

One of two or more compounds that have the same chemical formula but different arrangements of the atoms within the molecules and that may have different physical/chemical properties.

Research done in a laboratory. These studies may use test tubes or animals to find out if a drug, procedure, or treatment is likely to be useful. Laboratory studies take place before any testing is done in humans.

A substance that promotes bowel movements.

Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.

Able to dissolve, be dissolved in, or absorb lipids (fats).

A large organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile.

A very thin layer of tissue that covers a surface.

A plant that has been used in some cultures to treat certain medical problems, including stomach, liver, and gallbladder disorders. The active extract of milk thistle seeds is called silymarin. It is being studied in the prevention of liver damage caused by some cancer treatments. Also called Silybum marianum.

A measure of weight. A milligram is approximately 450,000 times smaller than a pound and 28,000 times smaller than an ounce.

Having to do with the ovaries, the female reproductive glands in which the ova (eggs) are formed. The ovaries are located in the pelvis, one on each side of the uterus.

A gland in the male reproductive system. The prostate surrounds the part of the urethra (the tube that empties the bladder) just below the bladder, and produces a fluid that forms part of the semen.

A plant that has been used in some cultures to treat certain medical problems, including stomach, liver, and gallbladder disorders. The active extract of Silybum marianum seeds is called silymarin. It is being studied in the prevention of liver damage caused by some cancer treatments. Also called milk thistle.

A substance obtained from milk thistle seeds that is being studied in the prevention of liver damage caused by certain cancer treatments.

Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects.