Thistle

Other Names

Acanos spinaAcanthium onopordonAsses' thistleBitter thistleBlessed milk thistleBlessed milkthistleBlessed thistleBull thistleCabbage thistleCanada thistleCarbenia benedictaCardinCardo SantoCarduus acanthiumCarduus acanthoidesCarduus benedictusCarduus lanceolatusCarduus marianusCarduus nutansCentaurea benedictaChardon aux ânesChardon BenitCirsium arvenseCirsium eriophorumCirsium vulgareCnici benedicti herbaCnicusCnicus benedictusCotton thistleCreeping thistleEselsdistelField thistleGundagai thistleGundyHeraldic thistleHoly Ghost herbHoly thistleJackass thistleKardo-benedictenkrautKrebsdistelLady's milkLady's thistleMarian thistleMariana marianumMary thistleMediterranean milk thistleMilk thistleMusk thistleNodding thistleOnopordon acanthiumOnopordum acanthiumOur Lady's thistlePlumeless thistleQueen Mary's thistleSaint Mary's thistleScotch cottonthistleScotch thistleScottish thistleSilver thistleSilybum mariaeSilybum marianumSpear thistleSpotted milk thistleSpotted thistleSt. Benedict thistleSt. Benedict's thistleSt. Mary's milk thistleSt. Mary's thistleVariegated artichokeVariegated thistleVirgin Mary's thistleWhite thistleWinged thistleWoolly thistle

Synopsis

Milk Thistle (Silybum marianum): A Comprehensive Reference

1. Identity: Botanical Names, Source, and Common Forms

Botanical and Chemical Identity

The botanical name for milk thistle is Silybum marianum (L.) Gaertn. Scientifically known as Silybum marianum, milk thistle belongs to the Asteraceae family, a diverse group of flowering plants that includes sunflowers, daisies, and dandelions. Native to the Mediterranean region, this robust biennial herb is characterized by its large, glossy leaves with distinctive white marbling and striking purple-pink flower heads. The plant is indigenous to Europe but can also be found in the United States and South America.

Milk thistle is also referred to by a number of common names, including Holy thistle, Marian thistle, Mary thistle, Our Lady's thistle, St. Mary thistle, Wild artichoke, Mariendistel (German), and Chardon-Marie (French). It has earned its botanical epithet marianum from the white marbling on its leaves. Tradition holds that the milky-white veins of the leaves originated from the milk of the Virgin Mary, which once fell upon a plant of the thistle, giving rise to the names St. Mary's thistle and Our Lady's thistle, and the epithets marianus and marianum.

Medicinal Parts and Active Constituent

The seed-like fruits (achenes) of milk thistle are the medicinal parts of the plant. The active constituent of milk thistle is silymarin, which is a complex mixture of flavonoids and flavonoid derivatives, the flavonolignans. Silymarin represents 1.5–3% of the fruit's dry weight and is an isomeric mixture of unique flavonoid complexes — flavonolignans. Thanks to its hepatoprotective properties, silymarin — an extract of milk thistle fruits — was classified by the WHO in the 1970s as an official medicine with hepatoprotective properties.

Key Flavonolignan Constituents

The major constituents of silymarin are the three diastereomeric pairs: silybins A and B (also called silibinin), isosilybins A and B, silychristin, isosilychristin, and silydianin. The main component of S. marianum fruit extract (silymarin) is a flavonolignan called silybin, which is not only the major silymarin element but is also the most active ingredient of this extract, as confirmed in various studies. Silybin's structure consists of two main units: the first is based on taxifolin, the second a phenylpropanoid unit (coniferyl alcohol), linked together into one structure by an oxerane ring.

The composition of flavonolignans within the silymarin complex is genetically determined. According to the literature, two chemotypes of Silybum marianum are recognized: chemotype A, characterized by a predominance of silybin and silychristin, and chemotype B, where silydianin is the dominant component. Total silymarin content in seeds can range from 12.69 to 20.28 mg·g⁻¹ dry weight, with silychristin, silybin A, and silybin B as major constituents.

The chemical composition of milk thistle fruit, besides flavonolignans, also includes other flavonoids (such as taxifolin, quercetin, dihydrokaempferol, kaempferol, apigenin, naringin, eriodyctiol, and chrysoeriol), 5,7-dihydroxy chromone, dehydroconiferyl alcohol, fixed oil (60% linoleic acid; 30% oleic acid; 9% palmitic acid), tocopherol, sterols (cholesterol, campesterol, stigmasterol, and sitosterol), sugars (arabinose, rhamnose, xylose, and glucose), and proteins.

Common Preparations and Commercial Forms

Capsules range in strength from 100 to 250 mg and most are standardized to contain 80 percent silymarin. Because Silybum has been so widely studied, medicinal products and clinical studies are often standardized to approximately 80% silymarin content. Most supplements are standardized according to their silybin content. Traditionally, the leaves have also been used in salads, and the fruit of the flower has been roasted as a coffee substitute.

The clinical application of silymarin-based therapies remains limited by poor aqueous solubility, low oral bioavailability, rapid metabolism, and physicochemical instability. Key innovations to address this include nanotechnology-enabled delivery systems, lipid-based carriers, water-soluble derivatives, bioavailability enhancers, parenteral and transdermal formulations, as well as controlled and synchronous release technologies. In Europe, intravenous preparations of purified silibinin are approved as an antidote to Amanita phalloides, a mushroom toxin that causes severe liver damage.

2. Traditional and Historical Use

Ancient Greco-Roman Use

For more than 2,000 years, Silybum marianum (milk thistle) has been used for treating different complications such as jaundice, hepatitis, and cancers. The Greek physician and botanist Dioscorides (40–90 AD) was the first to document milk thistle's healing properties, and this early recognition of its potential medicinal value set the stage for centuries of use in traditional medicine. The Roman naturalist Pliny the Elder (AD 23–79) wrote about the plant's juice and its virtues of "carrying of bile," which in his time referred to a general description of any internal fluid. Ancient Romans and Greeks often turned to this herb as a remedy for liver-related concerns, believing it could cleanse the blood and restore the organ.

Medieval European Use

During the Middle Ages, herbalists and healers expanded its use, applying it to treat conditions such as jaundice, liver congestion, and insect stings. By the Middle Ages, milk thistle had spread throughout Europe where it became a staple in monastery gardens, and herbalists prescribed it for melancholy (depression) and liver congestion. Pliny the Elder recommended the juice of the plant mixed with honey for "carrying off bile." Milk thistle was first served as an antidote for liver toxins in the Middle Ages and later by the British herbalist Culpepper to relieve "obstructions of the liver."

18th–19th Century European Use

In the 18th century, milk thistle was used for liver conditions. In Middle Europe, and especially in Prussia, the plant was cultivated in the 17th and 18th centuries. In the mid-19th century, milk thistle was used for hepatic diseases, as well as for flatulence, constipation, and haemorrhoids. When silymarin was discovered in fruit extracts, and its protective effect on the liver was confirmed in scientific trials, the role of milk thistle in therapy was reinstated.

Other Ethnobotanical Traditions

American Eclectic physicians used a seed tincture for lack of menstruation, bleeding, dysuria (difficulties with urination), gallstones, hyperaemia, haematuria, liver diseases, chronic vomiting, and nephrotic syndrome. Silybum marianum is an ancient medicinal plant that has been used for centuries for treatment of different diseases such as liver and gallbladder disorders, protecting the liver against snake bites and insect stings, mushroom poisoning, and alcohol abuse. Historically, milk thistle was also used for liver disorders and to increase breast milk production.

3. Key Constituents and Mechanisms of Action

Antioxidant Mechanisms

Silymarin is a potent scavenger of reactive oxygen species (ROS), harmful byproducts of cellular metabolism that can lead to oxidative stress and cellular damage. The hepatoprotective and antioxidant activity of silymarin is caused by its ability to inhibit the free radicals that are produced from the metabolism of toxic substances such as ethanol, acetaminophen, and carbon tetrachloride. It enhances endogenous antioxidant defenses by increasing glutathione levels, a crucial intracellular antioxidant.

Anti-Inflammatory Mechanisms

Another significant mechanism of action of silymarin is its anti-inflammatory effects. Silymarin modulates various inflammatory pathways by inhibiting nuclear factor kappa B (NF-κB) activation. By inhibiting this pathway, silymarin reduces the inflammatory response in the liver, which is crucial in conditions such as hepatitis and liver fibrosis. Furthermore, silymarin has been shown to decrease the levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6).

Hepatocyte Membrane Stabilization and Regeneration

The mechanism of action includes inhibition of hepatotoxin binding to receptor sites on the hepatocyte membrane; reduction of glutathione oxidation to enhance its level in the liver and intestine; antioxidant activity; and stimulation of ribosomal RNA polymerase and subsequent protein synthesis, leading to enhanced hepatocyte regeneration. Silymarin forms a complex that impedes the entrance of toxins into the interior of liver cells. Its ability to stabilize cell membranes and promote hepatic regeneration further underscores its therapeutic potential in chronic liver diseases.

Anti-Fibrotic and Broader Actions

Existing research reveals that silymarin has potent antioxidant and anti-inflammatory effects, coupled with anti-fibrotic, anti-carcinogenic, neuro-regenerative, and immunomodulatory actions, with broad therapeutic relevance in both neurological and hepatic disorders, albeit with the drawback of low solubility. The possible known mechanisms of action of silymarin protection include blockade and adjustment of cell transporters, p-glycoprotein, estrogenic, and nuclear receptors.

Bioavailability Constraints

Silymarin is orally absorbed but has very poor bioavailability due to its poor water solubility. Nonlinear pharmacokinetics of silybin A and silybin B suggests the low bioavailability associated with customary doses of silymarin may be overcome with doses above 700 mg. Pharmacokinetic studies in human HCV patients have shown a nonlinear dose–blood level curve where doses of 140, 280, and 560 mg result in similar blood levels that suddenly jump at a dose of 700 mg. Typically, following oral administration of a milk thistle extract, the concentrations of silybin A, silybin B, and isosilybin B are found in much higher concentrations in the systemic circulation relative to isosilybin A, silychristin A and B, and silydianin.

4. Scientific Evidence by Area of Use

4.1 Liver Disease: Chronic Hepatitis, Cirrhosis, and Alcoholic Liver Disease

Silymarin, a flavonoid complex derived from the milk thistle plant, has emerged as a promising antioxidant therapy for managing chronic liver diseases (CLDs) such as NAFLD, chronic hepatitis, alcoholic liver disease (ALD), and cirrhosis. Through its potent antioxidant, anti-inflammatory, and hepatoprotective properties, silymarin has shown efficacy in improving liver function, reducing oxidative stress, and mitigating liver inflammation.

A systematic review following PRISMA 2020 guidelines identified 29 randomized clinical trials (RCTs) from 1992 to 2023, encompassing 3,846 participants with diverse underlying conditions. A 2017 systematic review and meta-analysis of a total of 23 trials evaluated the effect of silymarin on the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transpeptidase (γGT) in patients with liver diseases. The authors concluded that silymarin minimally reduced the serum levels of ALT and AST; however, the results were without clinical relevance. They also noted the need to conduct studies with more appropriate methodological designs.

A Cochrane-affiliated systematic review assessed 13 randomized clinical trials involving 915 patients with alcoholic and/or hepatitis B or C liver diseases. The methodological quality was low: only 23% of the trials reported adequate allocation concealment and only 46% were considered double blind. Based on high-quality trials, milk thistle does not appear to significantly influence the course of patients with alcoholic and/or hepatitis B or C liver diseases. A systematic review concluded that milk thistle had no significant effects on mortality in patients with alcoholic liver disease or chronic hepatitis B or C, and was not associated with an increased risk of adverse events.

One large meta-analysis found a greater reduction in alanine aminotransferase levels among patients with chronic liver disease assigned to milk thistle (−9 IU/L, 95% CI: −18 to −1 IU/L; P = 0.05), but this reduction was of negligible clinical importance and was no longer statistically significant after limiting analyses to studies of longer duration or of higher quality. There is insufficient evidence to support or refute recommending this herbal compound to patients for the treatment of liver diseases.

Evidence strength: Preliminary to weak. Large systematic reviews find minimal or no clinically significant effects on mortality or histological outcomes in chronic hepatitis B/C and alcoholic liver disease, though biochemical markers show modest improvement in some studies. Methodological quality of primary trials remains low.

4.2 Drug-Induced and Toxin-Induced Liver Injury

Preliminary evidence suggests that milk thistle extract standardized to 70–80% silymarin may protect the liver against damage from certain toxins, including acetaminophen (Tylenol) and phenytoin (Dilantin). An analysis of 1,198 patients across 5 studies found that silymarin, used at 140 mg to 420 mg daily, reduced the rate of drug-induced liver injury (measured by liver enzymes) associated with anti-tuberculosis therapy.

In a study of children with acute lymphoblastic leukemia (ALL) receiving maintenance chemotherapy, milk thistle extract standardized to 33% silibinin was given at a daily dose of 80 mg to 320 mg of silibinin (approximately 5.1 mg/kg/day).

Evidence strength: Moderate for prevention of drug-induced liver injury in anti-tuberculosis therapy (based on pooled data from multiple studies), but individual trial quality varies. Evidence for chemotherapy-related liver protection is preliminary.

4.3 Amanita phalloides (Death Cap Mushroom) Poisoning

In Europe, silybin is administered intravenously as the only effective antidote for Amanita phalloides poisoning. Humans exposed to this mushroom toxin develop serious liver failure. Silibinin, a proven antioxidative and anti-inflammatory flavonolignan isolated from milk thistle extracts, has been shown to interact with specific hepatic transport proteins, blocking cellular amatoxin re-uptake and thus interrupting enterohepatic circulation of the toxin. There are no controlled clinical studies available due to ethical reasons, but uncontrolled trials and case reports describe successful treatment with intravenous silibinin (Legalon® SIL). In nearly 1,500 documented cases, the overall mortality in patients treated with Legalon® SIL is less than 10%, in comparison to more than 20% when using penicillin or a combination of silibinin and penicillin. Patients were administered doses of 35 to 55 mg/kg of body weight, with no reports of adverse events.

Evidence strength: Clinically significant in this emergency setting, based on substantial case series data, though controlled trials are ethically not feasible. The intravenous formulation (Legalon® SIL) is specifically approved in Europe for this indication.

4.4 Non-Alcoholic Fatty Liver Disease (NAFLD)

Silymarin offers protective effects on the liver and shows promise in improving liver function and histological outcomes in various chronic liver conditions. One study aimed to evaluate the efficacy of combined treatment, which included vitamin E, silybin, and phospholipids, and demonstrated that this complex improves liver damage, especially plasma markers of liver fibrosis and insulin resistance. Despite the promising results, further research is needed to fully elucidate the optimal dosing regimens, long-term safety, and potential drug interactions of silymarin.

Evidence strength: Preliminary to moderate. Several clinical studies report benefit in hepatic biomarkers and histology, but larger, better-controlled trials are needed to confirm clinical significance.

4.5 Type 2 Diabetes Mellitus and Glycemic Control

In a systematic review and meta-analysis including five randomized controlled trials and 270 patients, routine silymarin administration determined a significant reduction in fasting blood glucose levels (−26.86 mg/dL; 95% CI −35.42–18.30) and HbA1c levels (−1.07; 95% CI −1.73–0.40) and had no effect on lipid profile. A meta-analysis conducted on 7 studies and 350 patients showed that silymarin supplementation can decrease fasting blood sugar (FBS), hemoglobin A1C (HbA1C), and low-density lipoprotein cholesterol (LDL-C), but has no effect on total cholesterol (TC) or total triglycerides.

However, being aware of the low quality of the available evidence and elevated heterogeneity of these studies, no recommendation can be made and further studies are needed.

Evidence strength: Moderate but with significant limitations. Meta-analyses suggest statistically significant improvements in glycemic markers in type 2 diabetic patients, but heterogeneity across trials and methodological limitations prevent definitive clinical recommendations.

4.6 Cardiovascular and Lipid Profiles

In clinical trials, the most important findings are improved glycemic and lipid profiles in patients with type 2 diabetes mellitus and/or hyperlipidemia, while anti-hypertensive effects are less well established. A direct amelioration of atherosclerosis and endothelial dysfunction after silymarin administration appears weak based on scarce data. Some patient groups also demonstrated significantly reduced total cholesterol, triglycerides, and LDL levels.

Most clinical trials are often characterized by inconclusive findings or have inadequate power, and the results cannot be generalized to the entire population.

Evidence strength: Preliminary. While individual trials report improvement in lipid and glycemic parameters in diabetic populations, evidence for broader cardiovascular benefit remains inconclusive.

4.7 Cancer: Chemopreventive and Adjuvant Evidence

Early laboratory studies suggest that silymarin and other active molecules in milk thistle may exhibit anti-cancer effects, including interfering with cancer cell division and reproduction, shortening cancer cell lifespan, and reducing the blood supply to tumors. Other research suggests milk thistle acts synergistically with chemotherapy. Milk thistle and silymarin have been used as complementary treatments for cancers such as skin, prostate, and colorectal cancers. Silymarin exerts a chemopreventive effect on reactivating cell death pathways by modulation of the antiapoptotic proteins and synergizing with agonists of death domain receptors.

Research studies conducted in the laboratory have investigated the properties of silymarin or its isomer silybin using cell lines and animal models. Other substances in milk thistle have not been extensively studied.

Evidence strength: Preclinical only for most cancer applications. The bulk of anticancer evidence comes from in vitro cell-line and animal studies. Human clinical trials in oncology are limited, and no conclusions about cancer treatment or prevention in humans can be drawn from current evidence.

4.8 Iron Overload and Thalassemia

Silymarin was found to be beneficial as an adjunct to the iron chelator desferrioxamine in patients with transfusion-dependent beta-thalassemia major. In a study of 97 patients, significant decreases in markers of iron overload (serum ferritin, serum iron, hepcidin, and soluble transferring receptor) were observed in the patients who received silymarin. In patients with thalassemia treated with chronic blood transfusions, silymarin is shown to improve the efficacy of the iron chelator desferrioxamine compared with desferrioxamine plus placebo, with silymarin showing significant improvements.

Evidence strength: Preliminary but positive in limited trials. This is a niche but clinically interesting application that warrants further investigation.

5. Body Systems and Health Areas Associated with Milk Thistle

Hepatobiliary system: Silymarin is the most used natural compound for the treatment of hepatic diseases worldwide due to its antioxidant, anti-inflammatory, and anti-fibrotic activities.
Metabolic/Endocrine: Silymarin, an herbal drug with antioxidant and anti-inflammatory properties, may improve glycemic control and prevent the progression of diabetic complications.
Cardiovascular: Beyond reported hepatoprotectant effects, milk thistle extracts have also been shown to produce generalized antioxidant effects and potential antitumor, anti-inflammatory, antifibrotic, and antihyperglycemic actions.
Neurological: Silymarin, extracted from the seeds of Silybum marianum (milk thistle), has been utilized in traditional medicine for many years and is recognised for its neuroprotective and hepatoprotective properties.
Dermatological: Topical applications of silybin display a large array of beneficial actions on skin: anti-inflammatory effects, protection against UV-B radiations and sunburns, antiglycation action, and prevention of skin cancers.
Hematological (Iron Metabolism): Silymarin demonstrated benefit as an adjunct to iron chelation in transfusion-dependent thalassemia, as described in Section 4.8 above.
Oncology (preclinical): As detailed in Section 4.7, effects on multiple cancer types have been observed in laboratory models.

6. Dosage Forms and Dosages Reported in Studies

Oral Dosage Forms

Capsules range in strength from 100 to 250 mg and most are standardized to contain 80 percent silymarin. Dosages in clinical use and research may range from 50 to 200 mg or more of Silybum taken two or three times daily to support liver function, reduce cholesterol, and improve glycemic control.

Dosages Reported in Specific Clinical Contexts

Anti-tuberculosis drug-induced liver injury: Silymarin used at 140 mg to 420 mg daily across a pooled analysis of 1,198 patients in 5 studies.
Type 2 diabetes / metabolic: Dosages of 50 to 200 mg or more taken two or three times daily.
Amanita phalloides poisoning (intravenous): Patients were administered doses of 35 to 55 mg/kg of body weight, with no reports of adverse events.
Pediatric oncology (chemotherapy liver protection): Milk thistle extract standardized to 33% silibinin was given at a daily dose of 80 mg to 320 mg of silibinin (approximately 5.1 mg/kg/day) in children with acute lymphoblastic leukemia receiving maintenance chemotherapy.
Regulatory reference dose (Health Canada): The maximum daily therapeutic dose cited in the Health Canada NHP monograph is 600 mg per day silymarin, with a maximum single-dose limit of 200 mg of silymarin.

Standardization and Measurement Considerations

The official USP compendial method uses HPLC (high-performance liquid chromatography), which is more specific and accurate, reporting approximately 58% silymarin in standard extracts. Some manufacturers label products as "80% silymarin" based on UV-VIS spectrophotometry without disclosing the method, which can lead consumers to believe they are getting more silymarin than is actually present. Pharmacokinetic studies in human HCV patients have shown a nonlinear dose–blood level curve where doses of 140, 280, and 560 mg result in similar blood levels that suddenly jump at a dose of 700 mg.

7. Safety Considerations and Drug Interactions

General Safety Profile

Aside from mild gastrointestinal distress and allergic reactions, side effects are rare, and serious toxicity has rarely been reported. In an oral form standardized to contain 70 to 80 percent silymarin, milk thistle appears to be safe for up to 41 months of use. Oral silymarin has few if any adverse side effects and is well tolerated even in high daily doses. Despite its widespread use in patients with and without liver disease, milk thistle has not been implicated in causing serum enzyme elevations or clinically apparent acute liver injury. The frequency of adverse effects was low and, in clinical trials, indistinguishable from placebo.

Cytochrome P450 Interactions

In vitro studies have suggested that some milk thistle components may significantly inhibit specific cytochrome P450 (P450) enzymes. However, determining the potential for clinically significant drug interactions with milk thistle products has been complicated by inconsistencies between in vitro and in vivo study results. Results of chronic administration of a milk thistle supplement show that it does not have a clinically relevant effect on the major P450 enzymes in a standardized human study. In a pharmacokinetic study, 9 healthy subjects received four probe drugs — caffeine, tolbutamide, dextromethorphan, and midazolam — to test for the effect of milk thistle on CYP1A2, CYP2C9, CYP2D6, and CYP3A4, before and after receiving a standardized milk thistle extract three times daily for 14 days. Milk thistle had no effect on any of the drugs. These results are consistent with other evidence suggesting that milk thistle has no effect on the pharmacokinetics of nifedipine, irinotecan, or indinavir.

Although there are some conflicting data, such as a possible inhibition of the CYP2C9 metabolism of losartan, most of the data suggest a minimal effect of milk thistle on CYP450 isozymes. An interaction between silybin B and CYP2C9 might become clinically significant when patients are treated with sufficiently high doses and/or formulations with enhanced bioavailability of silybin B (e.g., phosphatidylcholine complexes, phytosomes).

Allergic Reactions

Aside from mild gastrointestinal distress and allergic reactions, side effects are rare, and serious toxicity has rarely been reported. Individuals with known hypersensitivity to members of the Asteraceae family (daisies, ragweed, chrysanthemums, marigolds) may be at elevated risk for allergic cross-reactivity, as milk thistle belongs to this botanical family.

Interactions with Specific Drug Classes

As many patients taking prescription medications are concomitantly using herbal supplements, there is considerable risk for adverse herbal drug interactions, especially for drugs with a narrow therapeutic index such as warfarin, cyclosporine A, and digoxin. In the United States and Europe, up to 65% of patients with liver disease may use botanical preparations. Given that this population is often on complex drug regimens, monitoring for potential pharmacokinetic interactions remains prudent, particularly with novel high-bioavailability formulations.

Quality and Labeling Concerns

Poor chemical and microbiological quality of commercial milk thistle-based dietary supplements may account for their reported unsatisfactory and non-reproducible clinical outcomes. Variability in product quality, combined with differing standardization methodologies, means that results across clinical studies and commercial products may not be directly comparable.

References

Health Conditions

Health conditions that Thistle may help support.

No conditions available.

Body Systems

Body systems that Thistle may help support.

No body systems available.