There are no published clinical trials of milk thistle or silymarin in patients with cancer. Two published case reports describe the use of milk thistle as either a treatment or an adjunctive therapy in individuals with cancer. One case report describes the use of milk thistle in a 34-year-old woman with promyelocytic leukemia.[1] The investigators administered 800 mg of silymarin during the patient’s maintenance therapy, which consisted of treatment with methotrexate and 6-mercaptopurine. During the 4 months of treatment with silymarin, the patient who previously required intermittent breaks in therapy due to abnormal liver enzyme levels had normal liver enzyme levels with no further interruption of therapy. A second case report describes a 52-year-old man with hepatocellular carcinoma.[2] The patient began taking 450 mg of silymarin per day, and spontaneous regression of the tumor was reported in the absence of initiation of anticancer therapy. These findings have not been reproduced in a clinical trial.

Most clinical trials of milk thistle have been conducted in patients with either hepatitis or cirrhosis. Other studies have investigated milk thistle in patients with hyperlipidemia, diabetes, and Amanita phalloides mushroom poisoning. Eight randomized trials [3-10] have been reported in patients with hepatitis or cirrhosis, and one randomized trial has reported the use of silymarin as a prophylaxis to iatrogenic hepatic toxicity.[11] Endpoints for these trials have included serum levels of bilirubin and/or the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as higher levels are an indicator of liver inflammation, damage, or disease. The lowering of these serum levels is a sign of an improving condition. In patients with hepatitis A and B, one clinical trial found silymarin (140 mg daily for 3–4 weeks) resulting in lower levels of AST, ALT, and bilirubin by day 5, compared with a placebo group.[12] In another randomized, placebo-controlled study of patients with viral hepatitis B, silymarin (210 mg daily) had no effect on course of disease or enzyme levels.[6]

In patients with chronic liver disease, a randomized, placebo-controlled study found normalization of serum AST, ALT, and bilirubin levels after 1 month of treatment with silymarin (140 mg 3 times a day) in comparison to treatment with a placebo.[13] In one of the largest observational studies involving 2,637 patients with chronic liver disease, 8-week treatment with 560 mg/day of silymarin resulted in reductions of serum AST, ALT, and gamma-glutamyltranspeptidase ([GGT], a marker of bile duct disease) and a decrease in the frequency of palpable hepatomegaly.[14]

Another published report describes the use of silybin as the only effective antidote in patients with liver damage from Amanita phalloides (Fr.) Link poisoning.[15] Patients were administered doses of 35 to 55 mg/kg body weight, with no reports of adverse events. A recent retrospective review of the treatment for Amanita phalloides poisoning suggests that silymarin continues to be a promising drug in the treatment of this rare mushroom poisoning.[16] The beneficial effect of silymarin on liver histology suggests it has a role in the prevention of hepatitis and/or hepatocellular carcinoma; however, no clinical trials in humans have investigated the use of silymarin for prevention.

References

1. Invernizzi R, Bernuzzi S, Ciani D, et al.: Silymarine during maintenance therapy of acute promyelocytic leukemia. Haematologica 78 (5): 340-1, 1993 Sep-Oct.  [PUBMED Abstract]
   
   
2. Grossmann M, Hoermann R, Weiss M, et al.: Spontaneous regression of hepatocellular carcinoma. Am J Gastroenterol 90 (9): 1500-3, 1995.  [PUBMED Abstract]
   
   
3. 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. 
   
   
4. 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]
   
   
5. 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]
   
   
6. Flisiak R, Prokopowicz D: Effect of misoprostol on the course of viral hepatitis B. Hepatogastroenterology 44 (17): 1419-25, 1997 Sep-Oct.  [PUBMED Abstract]
   
   
7. Angulo P, Patel T, Jorgensen RA, et al.: Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid. Hepatology 32 (5): 897-900, 2000.  [PUBMED Abstract]
   
   
8. Ferenci P, Dragosics B, Dittrich H, et al.: Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 9 (1): 105-13, 1989.  [PUBMED Abstract]
   
   
9. 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 40 (1): 2-8, 2002.  [PUBMED Abstract]
   
   
10. 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 26 (4): 871-9, 1997.  [PUBMED Abstract]
    
    
11. 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. Current Therapeutic Research 55 (5): 537-45. 
    
    
12. Magliulo E, Gagliardi B, Fiori GP: [Results of a double blind study on the effect of silymarin in the treatment of acute viral hepatitis, carried out at two medical centres (author's transl)] Med Klin 73 (28-29): 1060-5, 1978.  [PUBMED Abstract]
    
    
13. Trinchet JC, Beaugrand M, Callard P, et al.: Treatment of alcoholic hepatitis with colchicine. Results of a randomized double blind trial. Gastroenterol Clin Biol 13 (6-7): 551-5, 1989.  [PUBMED Abstract]
    
    
14. Albrecht M, Frerick H, Kuhn U, et al.: Therapy of toxic liver pathologies with Legalon®. Z Klin Med 47: 87-92, 1992. 
    
    
15. 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]
    
    
16. Enjalbert F, Rapior S, Nouguier-Soulé J, et al.: Treatment of amatoxin poisoning: 20-year retrospective analysis. J Toxicol Clin Toxicol 40 (6): 715-57, 2002.  [PUBMED Abstract]
    
    

Glossary Terms

Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. Also called adjunct therapy.

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 tube through which bile passes in and out of the liver.

Substance formed when red blood cells are broken down. Bilirubin is part of the bile, which is made in the liver and is stored in the gallbladder. The abnormal buildup of bilirubin causes jaundice.

A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin).

A disease or condition that persists or progresses over a long period of time.

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

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 clinical study.

A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all.

Any of several diseases in which the kidneys make a large amount of urine. Diabetes usually refers to diabetes mellitus in which there is also a high level of glucose (a type of sugar) in the blood because the body does not make enough insulin or use it the way it should.

A clinical trial in which the medical staff, the patient, and the people who analyze the results do not know the specific type of treatment the patient receives until after the clinical trial is over.

In clinical trials, an event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial. The endpoints of a clinical trial are usually included in the study objectives. Some examples of endpoints are survival, improvements in quality of life, relief of symptoms, and disappearance of the tumor.

A protein that speeds up chemical reactions in the body.

A cell that carries oxygen to all parts of the body. Also called RBC and red blood cell.

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.

Refers to the liver.

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

A type of adenocarcinoma, the most common type of liver tumor.

Enlarged liver.

The study of tissues and cells under a microscope.

Redness, swelling, pain, and/or a feeling of heat in an area of the body. This is a protective reaction to injury, disease, or irritation of the tissues.

A hormone made by the islet cells of the pancreas. Insulin controls the amount of sugar in the blood by moving it into the cells, where it can be used by the body for energy.

A researcher in a clinical trial or clinical study.

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

Treatment that is given to help keep cancer from coming back after it has disappeared following the initial therapy. It may include treatment with drugs, vaccines, or antibodies that kill cancer cells, and it may be given for a long time.

A drug used to treat acute lymphatic leukemia. It belongs to the family of drugs called antimetabolites. Also called Purinethol.

A drug used to treat some types of cancer, rheumatoid arthritis, and severe skin conditions, such as psoriasis. Methotrexate stops cells from making DNA and may kill cancer cells. It is a type of antimetabolite. Also called amethopterin, MTX, and Rheumatrex.

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.

A clinical trial in which the participants are not assigned by chance to different treatment groups. Participants may choose which group they want to be in, or they may be assigned to the groups by the researchers.

A type of study in which individuals are observed or certain outcomes are measured. No attempt is made to affect the outcome (for example, no treatment is given).

A type of study in which both the health providers and the patients are aware of the drug or treatment being given.

A term used to describe cancer that can be felt by touch, usually present in lymph nodes, skin, or other organs of the body such as the liver or colon.

A study to test whether a new treatment has an anticancer effect (for example, whether it shrinks a tumor or improves blood test results) and whether it works against a certain type of cancer.

The initial study examining a new method or treatment.

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

Refers to a clinical study in which the control patients receive a placebo.

An aggressive (fast-growing) type of acute myeloid leukemia in which there are too many immature blood-forming cells in the blood and bone marrow. It is usually marked by an exchange of parts of chromosomes 15 and 17. Also called acute promyelocytic leukemia and APL.

An attempt to prevent disease.

When referring to an experiment or clinical trial, the process by which animal or human subjects are assigned by chance to separate groups that compare different treatments or other interventions. Randomization gives each participant an equal chance of being assigned to any of the groups.

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.