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Milk Thistle (Silybum Marianum)

James Meschino DC, MS, ROHP

General Features

Milk Thistle has been used medicinally for several thousand years. 1 Medical use of Milk Thistle can be traced back to the well-known 17th century pharmacist Nicholas Culpeper, who cited the use of Milk Thistle as a medicinal agent for opening “obstruction” of the liver and spleen, and recommended it for the treatment of jaundice.  46   The Greeks and the Romans also noted its ability to protect against and repair certain liver conditions.  Scientific investigation into the use of liver-related conditions began in the 1960’s, with the isolation of silymarin (a combination of flavonolignans) from the ripe seeds.  It is essentially the silymarin content of Milk Thistle extract, which has been shown to provide its medicinal effects, especially in regards to the treatment and prevention of various liver conditions. 42, 46    In 1986, the German Commission E approved an oral extract of Milk Thistle standardized to 70% crude silymarin content as a treatment for liver disease.  47

Principle Active Constituents

Silymarin – Silymarin is a mixture of flavonolignans consisting chiefly of silibinin, silidianin, and silicristin.  Silibinin is the silymarin component that yields the greatest degree of biological activity and is largely responsible for the benefits attributed to silymarin
Milk Thistle extracts are usually standardized to contain 70 to 80 percent silymarin content 2,6, 46,47

Clinical Application and Mechanism of Action

  1. Mechanism of Action

Extensive investigation into the biological activities of silymarin have uncovered the following mechanisms of action:

  1. Antioxidant Function: Silymarin has been shown to be at least ten times more potent in its antioxidant activity than vitamin E, in the liver, stomach, and intestine. 2,3,4,5,6
    Experimental evidence reveals that silymarin protects animals from liver damage upon exposure to diverse toxic chemicals, such as carbon tetrachloride, ethanol, galactosamine and amanita phalloides or its toxins – a very lethal agent from the toadstool mushroom.  2,3,4,5,6,7,8,9
  2. Increases Liver Glutathione: Silymarin increases liver glutathione content by over 35 percent in healthy human subjects and by over 50 percent in rats. In the liver, glutathione participates in both phase I and phase II detoxification processes, facilitating the detoxification of a wide range of hormones, drugs and chemicals. Glutathione also acts as an intracellular antioxidant that protects cells against dangerous free radicals from various sources.  3,4,5,9,10,11,12   In many liver and immune-related diseases, glutathione liver concentrations are depleted permitting faster advancement of liver damage and disease progression.  The ability of Milk Thistle to help restore liver glutathione levels is considered to be a primary means by which silymarin has been shown to be an effective treatment for various liver diseases.  46,47,48
  3. Inhibits the formation of pro-inflammatory leukotrienes (eicosanoids): This effect may help to control swelling and inflammation from various types of mechanical and chemical insults. 13,14
  4. Stimulates Protein Synthesis: Silibinin stimulates RNA polymerase A (also known as polymerase I) and DNA synthesis, which in turn increase the synthesis of ribosome proteins and thus, stimulates cell development. This ultimately increases the regenerative capacity of liver cells and results in the production of new liver cells to replace the damaged old ones. As such, silymarin has been shown to aid in the repair of liver cells that have been damaged by various microorgamisms, alcohol, and other damaging chemicals. However, silymarin has not been shown to have a stimulatory effect on malignant liver tissue.  6,15,16,10,17
  5. Competitive Binding with Some Toxins: Silymarin appears to compete with amanita phalloides – based toxins (from toadstool (deathcap) mushrooms) for a receptor on the cell membrane. Under experimented conditions, silymarin prevents death in animals exposed to these very lethal liver toxins when given prior to the amanita phalloides toxins, or within 10 minutes after exposure to these toxins.  10,7,8,18
  6. Increased Superoxide Dismutase Concentrations: Silymarin has been shown to increase the concentrations of superoxide dismutase – a very powerful intracellular antioxidant, which quenches the superoxide anion (a very aggressive damaging and reactive, free radical oxygen species). 19
  7. Clinical Applications: (Primarily The Treatment of Various Liver Conditions)
  8. Cirrhosis: Patients with liver damage due to excess alcohol consumption have shown improvement in laboratory, and liver biopsy assessment after silymarin treatment. Another study revealed improved survival in patients with cirrhosis who were treated with silymarin versus placebo, in a 4-year study involving 87 patients.  20,21,22   A double-blind, placebo-controlled study involving 106 Finnish soldiers with alcoholic liver disease revealed that treatment with Milk Thistle produced improvement in regards to a reduction in liver enzyme blood levels and histological improvement of liver cells, as evidenced by liver biopsy samples in 29 subjects.  49 Two other studies have provided similar evidence   50, 51, although not all studies performed to date have demonstrated these types of positive results in alcoholic liver disease.  52,53
  9. Chronic Viral Hepatitis and Acute Hepatitis: Most, but not all, studies have shown the effectiveness of silymarin in treating both acute and chronic hepatitis.  10,23,24,47   In the majority of these studies improvement in bilirubin levels and liver serum enzymes have been documented, and a reduction in abdominal discomfort, fatigue, and improved appetite have been reported in patients treated with silymarin.  To date the majority of successful clinical trials have administered silymarin intravenously (I.V.) and therefore, the applicability of these findings to the oral ingestion of silymarin is not completely known.  10,23,24,25   However, one recently completed, well-designed clinical trial showed that the oral intake of Milk Thistle (yielding 240 mg per day) decreased blood levels of AST, ALT, and gamma-glutamyltransferase (GGT) in a study of 20 patients with chronic viral hepatitis.  These are all known to be important liver enzyme blood tests that are highly correlated with the degree of liver damage.  23
  10. Protection from Chemical Toxins: Animal studies reveal that Milk Thistle extract protects the liver from a variety of toxins including alpha-amanitin and phalloidin (both from the extremely poisonous Deathcap or Toadstool mushroom), carbon tetrachloride, thioacetamide, DL-ethionine, phenothiazines acetaminophen and ethanol (alcohol). 10,26,27,28,29,47
    Several human studies have shown that silymarin can reverse certain instances of liver damage induced by alcohol consumption (treated subjects demonstrated improved values for amino transferase (AST) and alanine aminotransferase (ALT) in blood testing).  There was also a trend in the concentrations of total and conjugated serum bilirubins in the silymarin group, compared to the controls.  10,30
    Another study with patients taking the psychotropic drugs phenothiazines or butyrophenones, demonstrated that silymarin decreased liver damage induced by these drugs and decreased serum levels of malondialdehyde (MDA), which is a biomarker for the production of free radicals.  31   However, a study examining the protective role of Milk Thistle in Alzheimer’s patients taking the drug tacrine, failed to show that Milk Thistle could prevent the liver inflammation that is known to be a side effect of this medication.  54
  11. Enhance Detoxification: For general support of liver detoxification in anti-aging medicine silymarin has been shown to significantly increase liver concentrations of glutathione, increase solubility of bile and provides additional antioxidant support to liver cells. As such, it is recommended by anti-aging and holistic practitioners as supplement that may help to slow the biological processes of aging and exert a number of health-promoting effects that are consistent with principles of disease prevention practices. 10,32,11,12
  12. Psoriasis: A number of reports suggest that silymarin may be of value in the treatment of psoriasis, likely due to its ability to inhibit the synthesis of pro-inflammatory leukotrienes and improve the liver’s capacity to detoxify foreign compounds and contaminants.  Some evidence suggests that certain bioactive agents absorbed in the intestinal tract, that escape detoxification by the liver and intestinal mucosal cells, may trigger inflammatory reactions involved in the exacerbation of skin conditions, such as psoriasis.  33,34   This application, however, requires further substantiation, according to certain authorities.  47
  13. Sluggish Liver or Minor Hepatic Insufficiency: This term is usually used by European physicians and American Naturopaths to describe a myriad of symptoms involving aching beneath the ribs, fatigue, unhealthy skin appearance, general malaise, constipation, allergies, premenstrual syndrome, and/or chemical sensitivities, for which Milk Thistle has been recommended. 55

Dosage and Standardized Grade

Most Milk Thistle products are standardized to 70 to 80 percent silymarin content.  Thus, a 200 mg (70% silymarin extract) tablet contains 140 mg of silymarin.  35,36, 46, 47,48

  1. Liver Conditions: for the liver conditions mentioned above a dosage of 140 mg of silymarin, three times daily is often used. 30, 46,47,48   After 8-12 weeks improvement should occur, allowing a reduction to 140 mg twice per day.  38
  2. Psoriasis: 140 mg of silymarin, three times daily. 34
  3. Therapeutic Detoxification Support: 140 mg of silymarin, twice daily. 38

Adverse Side Effects, Toxicity and Contraindications

Milk Thistle is extremely non-toxic and side effects are rare.  It increases bile flow and thus, may cause mild diarrhea in some individuals.  39,40,41   A study of 2,637 subjects reported in 1992 showed a low incidence of side effects, limited mainly to mild gastrointestinal disturbance.  On rare occasions more severe abdominal discomfort has occurred.  56,57

Drug-Nutrient Interactions

There are no known adverse drug interactions reported for milk thistle.  However, as it stimulates liver detoxification pathways it may potentially speed up the metabolism of some drugs.  Thus, practitioners should closely monitor patients on concurrent medications.  42,43,44,45

Milk Thistle may reduce the liver damage or side effects of certain medications, and thus its concurrent administration with the following medications may be advisable:

  • Acetaminophen
  • Anesthetics
  • Chemotherapy
  • Clofibrate
  • Halopersidol
  • Metronidazole
  • Pravastatin
  • Tacrine43
Pregnancy and Lactation

During pregnancy and lactation, the only supplements that are considered safe include standard prenatal vitamin and mineral supplements.  All other supplements or dose alterations may pose a threat to the developing fetus and there is generally insufficient evidence at this time to determine an absolute level of safety for most dietary supplements other than a prenatal supplement.  Any supplementation practices beyond a prenatal supplement should involve the cooperation of the attending physician (e.g., magnesium and the treatment of preeclampsia.)

References:  Pregnancy and Lactation

1.     Encyclopedia of Nutritional Supplements. Murray M. Prima Publishing 1998.

2.     Reavley NM. The New Encyclopedia of Vitamins, Minerals, Supplements, and Herbs. Evans and Company Inc. 1998.

3.     The Healing Power of Herbs (2nd edition). Murray M. Prima Publishing 1995.

4.     Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine. Institute of Applied Complementary Medicine Inc. 1997.


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