Human studies of silymarin have shown minimal adverse effects in multiple large, blinded, placebo-controlled, randomized studies. Silymarin is well tolerated, with only rare reports of a mild laxative effect. Mild allergic reactions have been seen at high doses (>1,500 mg /day), although the details of these allergic reactions were not reported.[1] A recent case report from Australia described a reaction to a milk thistle extract that included intermittent episodes of sweating, abdominal cramping, nausea, vomiting, diarrhea, and weakness.[2] All symptoms resolved when the silymarin was discontinued. The authors suggested that the capsules were contaminated; the type of contamination was unknown.

According to the German Commission E, there are no reported side effects with milk thistle within the recommended doses. Rare cases of milk thistle having a laxative effect have been reported. Human studies have reported stomach upset, heartburn, and transient headaches; however, none of these symptoms were attributed to supplementation with milk thistle, and supplementation was not discontinued.[3] One human dosing study reported nausea, heartburn, and dyspepsia in patients treated with 160 mg/day, dyspepsia in patients treated with 240 mg/day, and postprandial nausea and meteorism in patients treated with 360 mg/day. None of these side effects were dose related.

Silymarin has been well tolerated in high doses. Silymarin has been used in pregnant women with intrahepatic cholestasis at doses of 560 mg/day for 16 days, with no toxicity to the patient or the fetus.[4] The published data on silymarin use in children focuses on intravenous doses of 20 to 50 mg/kg body weight for mushroom poisoning.[5] Silymarin has also proved nontoxic in rats and mice when administered in doses as high as 5,000 mg/kg body weight. Rats and dogs have received silymarin at doses of 50 to 2,500 mg/kg body weight for a 12-month period. Investigations, including postmortem analyses, showed no evidence of toxicity.

It is not known whether milk thistle may reduce, enhance, or have no effect on the effectiveness of chemotherapy. Silymarin decreases the activity of the cytochrome P450 enzyme system, which is involved in the clearance of certain chemotherapy drugs.[6] However, the dose at which inhibition is observed is high and not achieved with oral intake of silymarin.[7] Milk thistle may also interact adversely with chemotherapy drugs that exert their cytotoxic effects through generation of free radicals. Silymarin and its metabolite inhibit P-glycoprotein-mediated cellular efflux, leading to potentiation of doxorubicin cytotoxicity.[8] No trials have been performed to support or negate these theoretical considerations. No effects on indinavir and alcohol pharmacokinetics has been observed. Enhancement of antiarrhythmic effects of amiodarone in rats has been observed.[8]

References

1. PDR® for Herbal Medicines™. 2nd ed. Montvale, NJ: Medical Economics, 2000. 
   
   
2. An adverse reaction to the herbal medication milk thistle (Silybum marianum). Adverse Drug Reactions Advisory Committee. Med J Aust 170 (5): 218-9, 1999.  [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. Hernández R, Nazar E: [Effect of silymarin in intrahepatic cholestasis of pregnancy (preliminary communication)] Rev Chil Obstet Ginecol 47 (1): 22-9, 1982.  [PUBMED Abstract]
   
   
5. 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]
   
   
6. Venkataramanan R, Ramachandran V, Komoroski BJ, et al.: Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 28 (11): 1270-3, 2000.  [PUBMED Abstract]
   
   
7. Zuber R, Modrianský M, Dvorák Z, et al.: Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities. Phytother Res 16 (7): 632-8, 2002.  [PUBMED Abstract]
   
   
8. Hu Z, Yang X, Ho PC, et al.: Herb-drug interactions: a literature review. Drugs 65 (9): 1239-82, 2005.  [PUBMED Abstract]
   
   

Glossary Terms

An unwanted side effect of treatment.

A type of study in which the patients (single-blinded) or the patients and their doctors (double-blinded) do not know which drug or treatment is being given. The opposite of a blinded study is an open label study.

Treatment with drugs that kill cancer cells.

Any condition in which the release of bile from the liver is blocked. The blockage can occur in the liver (intrahepatic cholestasis) or in the bile ducts (extrahepatic cholestasis).

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 trial.

Cell-killing.

Frequent and watery bowel movements.

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

Upset stomach.

A protein that speeds up chemical reactions in the body.

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.

The German Federal Institute for Drugs and Medical Devices Commission E. A committee made up of scientists, toxicologists, doctors, and pharmacists formed by the German government in 1978 to find out if herbs sold in Germany are safe and effective. The Commission has published information on the uses, side effects, and drug interactions of more than 300 herbs.

Within the liver.

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..

A substance that promotes bowel movements.

Swelling of the abdomen caused by gas in the intestines or peritoneal cavity. Also called tympanites.

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.

Not harmful or destructive.

By or having to do with the mouth.

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

After death. Often used to describe an autopsy.

After a meal.

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 problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

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

Adding nutrients to the diet.

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