MILK THISTLE
| Also Known As: | |
| Blessed Milk Thistle, Cardui mariae fructus, Cardui Mariae Herba, Holy Thistle, Lady’s Thistle, Legalon, Marian Thistle, Mariendistel, Mary Thistle, Milk Thistle Above Ground Parts, Milk Thistle Fruit, Milk Thistle Seed, Our Lady’s Thistle, St. Mary Thistle, Silybin, Silybum, Silymarin. CAUTION: See separate listing for Blessed Thistle. |
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| Scientific Name: | |
| Silybum marianum, synonym Carduus marianus. Family: Asteraceae/Compositae. |
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| People Use This For: | |
| Orally, milk thistle is used as a liver protectant to lessen damage from potentially hepatotoxic drugs, and for treating liver disorders including toxic liver damage caused by chemicals, Amanita phalloides mushroom poisoning, jaundice, chronic inflammatory liver disease, hepatic cirrhosis, and chronic hepatitis. It is also used orally for loss of appetite, dyspeptic and gallbladder complaints, hangover, and diseases of the spleen. Milk thistle is used orally for prostate cancer, pleurisy, malaria, depression, uterine complaints, stimulating breast milk flow, and stimulating menstrual flow. Intravenously, milk thistle is used as a supportive treatment for Amanita phalloides mushroom poisoning. In foods, the milk thistle leaves and flowers are eaten as a vegetable and seeds are roasted for use as a coffee substitute. |
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| Safety: | |
| POSSIBLY SAFE …when used orally and appropriately. Milk thistle extracts standardized to contain 70-80% of the silymarin constituent seems to be safe when used for up to 41 months (2614, 2616). There is insufficient reliable information available about the safety of intravenous formulations of milk thistle and its constituents. PREGNANCY AND LACTATION: Insufficient reliable information available; avoid using. |
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| Effectiveness: | |
| INSUFFICIENT RELIABLE EVIDENCE to RATE Alcohol-related liver disease. Preliminary clinical research suggests that milk thistle taken orally might be helpful for treating alcoholic liver disease (2613, 2616, 2618, 7321, 7322, 7355). Amanita mushroom poisoning. Administering silibinin, a constituent of milk thistle, intravenously (IV) may lessen liver damage due to Amanita phalloides mushroom (death cap) poisoning (2615). Silibinin is not readily available in the US. Diabetes. Preliminary clinical evidence suggests that the milk thistle constituent silymarin can reduce insulin resistance in people with coexisting diabetes and alcoholic cirrhosis (2617). Hepatitis B or Hepatitis C. Preliminary clinical research suggests a specific oral preparation of silibinin, an active constituent extracted from milk thistle, complexed with phosphatidylcholine (Silipide), may improve liver function tests (LFTs) in patients with chronic active hepatitis. Silibinin is complexed with phosphatidylcholine to theoretically improve the bioavailability of silibinin (7356). Toxin-induced liver damage. Some research suggests milk thistle may limit liver damage after exposure to industrial toxicants such as toluene and xylene (2614). |
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| Mechanism of Action: | |
| The applicable parts of milk thistle are the seed and above ground parts. The seed is most commonly used medicinally. Silymarin, the active constituent of the milk thistle seed, consists of four flavonolignans called silibinin (silybin), isosilybinin, silichristin (silychristin), and silidianin. Silibinin makes up about 70% of silymarin (7318, 8956). When ingested, silymarin undergoes enterohepatic recirculation and has higher concentrations in liver cells. Silymarin is a potent inhibitor of tumor necrosis factor (TNF). The cytotoxicity, inflammation, and apoptosis induced by TNF are effectively blocked by silymarin. Although the mechanism of this effect is not clear, it probably involves intracellular signaling (7859). Silybin is an antioxidant, a free radical scavenger, and an inhibitor of lipid peroxidation (8957). In vitro silybin has shown an affinity for binding to p-glycoprotein, a transporter thought to be involved in the drug resistance of cancer cells (11481). Several activities seem to contribute to the therapeutic effect of silymarin in liver disease. Silymarin seems to cause an alteration of the outer hepatocyte cell membrane that prevents toxin penetration. It also stimulates nucleolar polymerase A, resulting in increased ribosomal protein synthesis, which can stimulate liver regeneration and the formation of new hepatocytes. There is also some evidence that suggests that silymarin might have antifibrotic, anti-inflammatory, and immunomodulating effects that could also be beneficial in liver disease (6879). Silymarin and silybin inhibit beta-glucuronidase, which might help protect against hepatic injury and possibly colon cancer. Inhibition of beta-glucuronidase is thought to reduce the hydrolysis of glucuronides into toxic metabolites in the liver and intestine (7354). Preliminary evidence indicates that milk thistle constituents might protect against kidney damage. In vitro, silibinin and silicristin can protect the kidney cells from nephrotoxic drugs such as acetaminophen, cisplatin, and vincristine. Silibinin and silicristin also appear to have a regenerative effect on kidney cells, similar to the effects on hepatic cells (7320). There is some interest in using milk thistle for prostate cancer. In vitro research shows that silymarin and silibinin have antiproliferative effects on androgen-responsive prostate cancer cells (7319). The above ground parts seem to have some estrogenic activity. A milk thistle plant extract appears to enhance estradiol binding to estrogen receptors, induce transcription activity in estrogen-responsive cells, and enhance estradiol-induced transcription activity in estrogen-responsive cells (6180). There is also preliminary evidence that suggests that milk thistle might affect drug metabolism. In vitro, silymarin and its flavonolignan, silibinin, inhibit cytochrome P450 2C9 (CYP2C9) and cytochrome P450 3A4 (CYP3A4), the major phase 1 hepatic enzyme. However, silymarin does not seem to affect the metabolism of indinavir (Crixivan), a CYP3A4 substrate, in healthy volunteers (10427). In vitro, silymarin and silibinin also inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation (6450, 7089, 7318). |
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| Adverse Reactions: | |
| Orally, milk thistle is usually well-tolerated (6879, 8956). It can cause an occasional laxative effect (8956). Other less common gastrointestinal (GI) effects include nausea, diarrhea, dyspepsia, flatulence, abdominal bloating, fullness or pain, and anorexia (6879). There is one case of a woman who experienced intermittent episodes of sweating, nausea, abdominal pain, vomiting, diarrhea, weakness, and collapse, requiring hospitalization (3525). Some patients may have allergic reactions to milk thistle including pruritus, rash, urticaria, eczema, and anaphylaxis (6879, 8956). Allergic reactions may be more likely to occur in patients sensitive to the Asteraceae/Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs. |
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| Interactions with Herbs & Supplements: | |
| None known. | |
| Interactions with Drugs: | |
| CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES: There’s preliminary evidence that milk thistle might inhibit cytochrome P450 2C9 (CYP2C9) (7089, 8234). So far, this interaction has not been reported in humans. However, watch for an increase in the levels of drugs metabolized by CYP2C9 in patients taking milk thistle. Some drugs metabolized by CYP2C9 include amitriptyline (Elavil), diazepam (Valium), verapamil (Calan), warfarin (Coumadin), zileuton (Zyflo), and others. Use milk thistle cautiously or avoid in patients taking these drugs. CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES: There’s preliminary evidence that milk thistle might inhibit cytochrome P450 3A4 (CYP3A4) enzyme (6450, 7089, 7318, 8234). So far, this interaction has not been reported in humans. Milk thistle does not affect plasma concentrations of the CYP3A4 substrate indinavir in healthy volunteers, so interactions with drugs metabolized by CYP3A4 are not likely clinically significant (10427). ESTROGENS: Theoretically, silymarin, an active constituent of milk thistle, might increase the clearance of estrogen by inhibiting beta-glucuronidase (6879). GLUCURONIDATED DRUGS: Theoretically, silymarin, an active constituent of milk thistle, might increase the clearance of drugs that undergo glucuronidation. Some of these drugs include acetaminophen, atorvastatin (Lipitor), diazepam (Valium), digoxin, entacapone (Comtan), irinotecan (Camptosar), lamotrigine (Lamictal), lorazepam (Ativan), lovastatin (Mevacor), meprobamate, morphine, oxazepam (Serax), and others (7318, 7354). INDINAVIR (Crixivan): Milk thistle does not appear to affect the metabolism of indinavir in healthy volunteers (10427). Although preclinical research suggested milk thistle might inhibit CYP3A4 and potentially increase indinavir levels (7318), milk thistle does not appear to affect the pharmacokinetics of indinavir in humans. |
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| Interactions with Foods: | |
| None known. | |
| Interactions with Lab Tests: | |
| None known. | |
| Interactions with Diseases or Conditions: | |
| CROSS-ALLERGENICITY: Milk thistle may cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs. HORMONE SENSITIVE CANCERS/CONDITIONS: Because milk thistle plant extract might have estrogenic effects (6180), women with hormone sensitive conditions should avoid milk thistle above ground parts. Some of these conditions include breast cancer, uterine cancer, ovarian cancer, endometriosis, and uterine fibroids. The more commonly used milk thistle seed extracts are not known to have estrogenic effects. |
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| Dosage/Administration: | |
| ORAL: For hepatic cirrhosis, a milk thistle extract containing 70-80% silymarin (Legalon), 420 mg per day has been used (2616). For chronic active hepatitis, a milk thistle constituent, silibinin (Silibide), 240 mg twice daily as been used (7356). Some people make a milk thistle tea, but the active ingredients are not very soluble in water (515). INTRAVENOUS: For Amanita phalloides mushroom poisoning, the common dose is 20-50 mg/kg over 24 hours, divided into four infusions, each administered over a two hour period. This is usually started within 48 hours after mushroom ingestion (2615). Intravenous silibinin is not available in the US. |
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| Comments: | |
| The broken leaves of the milk thistle plant exude a milky sap. The leaves have distinctive white markings which, according to legend, were the Virgin Mary’s milk (7161). Milk thistle is grown as a vegetable for salads and as a substitute for spinach. Avoid confusion with blessed thistle (Cnicus benedictus). | |