This cancer information summary provides an overview of the use of milk thistle as a treatment and adjunct agent for people with cancer.
The summary includes a brief history of milk thistle, a review of the laboratory studies and clinical trials, and a description of adverse effects associated with milk thistle use.
This summary contains the following key information:
Many of the medical and scientific terms used in this summary are hypertext linked (at first use in each section) to the NCI Dictionary of Cancer Terms, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window.
Reference citations in some PDQ cancer information summaries may include links to external websites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the websites, or of any treatment or product, by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board or the National Cancer Institute.
The botanical name for milk thistle is Silybum marianum (L.) Gaertn. Milk thistle is also referred to as the following:[
The plant is indigenous to Europe but can also be found in the United States and South America. Traditionally, the leaves have been used in salads, and the fruit of the flower has been roasted as a coffee substitute. The seed-like fruits (achenes) of milk thistle are the medicinal parts of the plant.[
Several companies distribute milk thistle as a dietary supplement. In the United States, dietary supplements are regulated as foods, not drugs. Therefore, premarket evaluation and approval by the U.S. Food and Drug Administration (FDA) are not required unless specific disease prevention or treatment claims are made. Because dietary supplements are not formally reviewed for manufacturing consistency, ingredients may vary considerably from lot to lot and there is no guarantee that ingredients claimed on product labels are present (or are present in the specified amounts). The FDA has not approved the use of milk thistle as a treatment for cancer or any other medical condition.
Despite milk thistle's long history of being used to treat liver and biliary complaints, it was not until 1968 that silymarin was isolated from the seeds of the plant, and it was proposed that silymarin might be the active ingredient.[
Silymarin is most well known for its purported effects on the liver. In laboratory studies, silymarin has been found to stabilize cell membranes, thus preventing toxic chemicals from entering the cell.[
Laboratory experiments conducted using cancer cell lines have suggested that silibinin enhances the efficacy of cisplatin and doxorubicin against ovarian and breast cancer cells.[
Most clinical trials have investigated silymarin's effectiveness in the treatment of patients with hepatitis, cirrhosis, or biliary disorders.[
Milk thistle has been used for more than 2,000 years, primarily as a treatment for liver dysfunction. The oldest reported use of milk thistle was by Dioscorides (A.D. 40–90), who recommended the herb as a treatment for serpent bites.[
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.
Several research studies have investigated the effects of silymarin or silybin in a noncancer context. These studies have tested silymarin or silybin:
Silymarin or silybin has also been investigated in cancer models. The effects of silymarin and/or silybin have been investigated in the following cell lines:
In animal tumor models, tongue cancer,[
Laboratory data suggest that silymarin and silybin protect the liver from damage induced by toxic chemicals. Animal studies have found that liver cells treated with silybin and then exposed to toxins do not incur cell damage or death at the same rate as liver cells that are not treated with silybin. This finding suggests that silybin can prevent toxins from entering the cell or effectively exports toxins out of the cell before damage ensues.[
Silymarin and silybin have also been found to accelerate cell regeneration in the liver through stimulation of precursors to DNA synthesis and enhancement of production of the cellular enzymes required for DNA synthesis.[
While some reports exist about the estrogenic effects assigned to silybin and silybin-containing materials,[
Silibinin inhibits prostate cancer cell–induced osteoclastogenesis, suggesting that silibinin may be useful clinically for the treatment of bone metastases. Silibinin targets prostate cancer cell–induced osteoclast differentiation and activity of murine macrophage cells.[
Although many of these studies have produced encouraging results, none of the findings have been replicated in human clinical trials.
|Study Type/Reference||Cancer Type||Outcome|
||Prostate, breast, cervical||Cancer chemopreventive andanticarcinogeniceffects of silymarin were reported|
||Leukemia||Silybinin stimulated HL-60cell differentiationalong the monocytic pathway|
||Epidermal||Silymarin inhibited cell growth by inducing G1 and G2-M arrest in cell cycle progression|
||Epidermal||Silymarin inhibitedcell proliferationand induced cell growth arrest|
||Colon||Silibinin suppressedcolorectal cancercell growth and progression, possibly through itsanti-inflammatoryactivity, by interfering withnuclear factor-kappa B(NF-kappa B) activation; In human colorectal cancer SW480, LoVo, and HT29 cells, silibinin treatment strongly inhibitedtumor necrosis factoralpha–induced NF-kappa B activation and decreased nuclear levels of both p65 and p50 subunits|
||Various||Inhibitedtumor volume; reduced tumorincidence; exerted protective and preventive effects against tumor promotion|
Several in vitro studies have explored anticancer effects of milk thistle extracts. Silybinin has been shown to inhibit cell proliferation by inducing cell cycle arrest at the G1 and G2-M transition in epidermal,[
||Glioma||Silibinin potentiated the effect ofetoposidebut notirinotecanin LN229 cells|
||Ovarian, breast||Silybin potentiated the cytotoxic effect ofcisplatinand doxorubicin in MCF-7 and A2780 cells|
||Ovarian||Silybin potentiated the cytotoxic effect of cisplatin in A2780 cells|
||Prostate||Silybin potentiated the cytotoxic effect of DU145 cells|
Other in vitro studies have demonstrated that components of milk thistle extract can enhance the effects of certain cytotoxic agents against various cancer types (i.e., etoposide against LN229 glioma cells,[
Several small studies have investigated silymarin for its direct treatment of cancer or for its effects on treatment-related toxicity.
A phase I study was designed to determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction.[
In a double-blind, placebo-controlled trial, 50 children who were undergoing treatment for acute lymphoblastic leukemia, and who had chemotherapy -related hepatotoxicity, were randomly assigned to receive silymarin or placebo for a 4-week period.[
A randomized placebo-controlled study of 37 men, who had a status of post–radical prostatectomy, investigated whether a 6-month daily administration of a silymarin and selenium combination would alter basic clinical chemistry, oxidative stress markers, and improve the quality-of-life (QOL) score in men after radical prostatectomy.[
Another randomized placebo-controlled study of 30 patients with head and neck cancer investigated a 6-week course of silymarin for the prevention of radiation therapy –associated mucositis. Mucositis scores (World Health Organization, National Cancer Institute Common Toxicity Criteria) were significantly lower in the silymarin group.[
In a nonrandomized observational trial of 101 women with breast cancer who had undergone breast-conserving surgery followed by radiation therapy with 50.4 Gy plus a boost of 9 Gy to 16 Gy, a silymarin-based cream (Leviaderm) was tested in 51 women compared with panthenol-containing cream, the standard of care (SOC), which was given interventionally if local skin lesions occurred and administered to 50 women.[
Most clinical trials of milk thistle have been conducted in patients with either hepatitis or cirrhosis. Other studies have investigated the use of milk thistle in patients with hyperlipidemia, diabetes, and Amanita phalloides (Fr.) mushroom poisoning. Ten randomized trials [
A randomized, controlled trial supported by the National Institute of Diabetes and Digestive and Kidney Diseases examined patients with chronic hepatitis C who had failed previous antiviral therapy. All patients had advanced chronic liver disease consisting of histologic evidence of either marked fibrosis or cirrhosis. The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis trial used a half dose of pegylated interferon versus no treatment; the treatment was to be administered for 3.5 years.[
Although there are many reports on the use of herbals for the treatment of chronic liver diseases, most treatment trials have suffered because of the following:
A review of complementary and alternative medications (CAM) to treat liver diseases focused on classification, epidemiology, and the philosophy of CAM and reviewed the criteria needed to conduct a scientifically valid research study focusing on herbal products.[
There has been skepticism regarding the evidence that silymarin has a direct impact on the hepatitis C virus (HCV)—some studies suggest that it does, but most studies cannot confirm these reports. However, at least two articles in major journals have suggested that silymarin or its congeners may inhibit HCV. In one report, investigators found that a standardized silymarin extract inhibited tumor necrosis factor -alpha in anti-CD3–stimulated human peripheral blood mononuclear cells and nuclear factor-kappa B –dependent transcription in human hepatoma Huh-7 cells.[
In a case series /phase I study, patients with HCV were treated with intravenous (IV) silibinin with and without PEG-interferon and ribavirin.[
Patients in a phase I pharmacokinetics study for the evaluation of absorption characteristics and determination of effective doses received increasing oral doses of silymarin.[
Another published report describes the use of silibinin as the only effective antidote in patients with liver damage from Amanita phalloides (Fr.) poisoning.[
Silymarin was found to be beneficial as an adjunct to the iron chelator desferrioxamine in patients with transfusion -dependent beta-thalassemia major.[
|ALL = acute lymphoblastic leukemia; ALT = alanine aminotransferase; AST = aspartate aminotransferase; HCV = hepatitis C virus; IV = intravenous; LFT = liver function test; No. = number; QOL = quality of life; SGOT = serum glutamic-oxaloacetic transaminase; SGPT = serum glutamate pyruvate transaminase.|
|a Number of patients treated plus number of patients controlled may not equal number of patients enrolled; number of patients enrolled = number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated = number of enrolled patients who were administered the treatment being studiedAND for whom results were reported;historical control subjectsare not included in number of patients enrolled.|
|b Nine patients were excluded from the final analysis (seven patients missed appointments, and two patients were missing data requirements).|
|c Study investigated dose-response relationships. Patients were randomly assigned to receive 80 mg 2 times a day (n = 20), 120 mg 2 times a day (n = 20), or 120 mg 3 times a day (n = 20). The effective dose was 120 mg 2 times a day and 120 mg 3 times a day.|
|d Patients were randomly assigned to the misoprostol and silymarin groups. Twelve nonrandomized patients served as controls.|
|e Fifteen patients were lost to follow-up, 18 patients weredeceased, and 42 patients withdrew from the study (adverse events, noncompliance, and voluntary withdrawal).|
|f Eleven patients did not complete the trial (voluntary withdrawal,disease progression, and one adverse event).|
|g For information about levels of evidence analysis and an explanation of the level of evidence scores, refer to Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.|
|Prevention or Treatment of Liver Disease/Dysfunction|
|Reference||Condition or Cancer Type||Trial Design||Route of Administration and Dose||Treatment Groups (Enrolled; Treated; Placebo or No Treatment Control)a||Results||Level of Evidence Score g|
||Acute and subacute liver disease||Double-blind, placebo-controlled, randomized clinical trial||Silymarin; 420 mg/d; oral (tablets)||106b; 47; 50||Decreased LFTs; improved histology||1iD|
||Advanced hepatocellular carcinoma and hepatic dysfunction||Phase I, open-label, dose-escalation trial||Silybin phosphatidylcholine; 3 g/d in 3 divided doses; oral (powder mixed in applesauce)||3; 3; none||Nodose-limitingtoxicity was identified||2D|
||Viral hepatitis B||Controlled, randomized trial||Silymarin; 210 mg/d; oral||52d; 20-silymarin, 20-misoprostol; 12||Silymarin did not have an effect on the course of disease, but misoprostol reduced the degree ofhepatocytedamage during the course of the disease||1iiD|
||Viral oralcoholichepatitis||Phase II, randomized, open trial||Silybin and phosphatidylcholine; 80 mg twice/d, 120 mg twice/d, or 120 mg 3 times/d; oral||60c; 60; 0||Reduction in ALT and gamma-glutamyl transpeptidase||1iiD|
||Chronic hepatitis C||Randomized, controlled trial||Silymarin; no dose listed; oral||1145; 195; 772||Decreasedfatigue,nausea, liver pain,anorexia, and muscle andjointpain||1iiC|
||HCV nonresponder patients||Nonrandomized, controlled trial||Silibinin; 10 mg/kg/d; IV||16; 16; 0 (protocol1) and 20; 20; 0 (protocol 2)||Increased antiviral effect with silibinin when antiviral therapy began after silibinin was started||2D|
||Cirrhosis||Double-blind, placebo-controlled, randomized clinical trial||Silymarin; 140 mg/d; oral||170; 87; 83||Decrease in SGOT and SGPT in silymarin-treated group||1iB|
||Diabetic patients with cirrhosis||Controlled, randomized trial||Silymarin; 600 mg (200 mg 3 times/d); oral||60; 30; 30||Decrease in SGOT and SGPT in silymarin-treated group||1iiD|
||Alcohol-induced cirrhosis||Double-blind, placebo-controlled, randomized clinical trial||Silymarin; 450 mg (150 mg 3 times/d); oral||60f; 24; 25||No significant differences in liver function tests||1iD|
||Alcohol-induced cirrhosis||Double-blind, placebo-controlled, randomized clinical trial||Silymarin; 450 mg (150 mg 3 times/d); oral||200e; 58; 67||No significant differences in liver function tests||1iB|
||Primarybiliary cirrhosis||Nonrandomized, pilot clinical trial||Silymarin; 420 mg (140 mg 3 times/d); oral||27; 27; 0||No significant differences in liver function tests||2C|
||Prevention of drug-induced hepatic damage||Double-blind, placebo-controlled, randomized clinical trial||Silymarin; 800 mg (divided in 2 doses); oral||60; 15 psychotropic drug + silymarin; 15 silymarin alone; 15 psychotropic drug + placebo; 15 placebo alone||Silymarin effective at reducing ALT and AST levels when psychotropic drug use was suspended||1iC|
||Children with ALL experiencing elevated LFTs||Double-blind, placebo-controlled, randomized clinical trial||Silibinin and soy phosphatidylcholine; dose ranges: 15–20 kg = 80 mg/d; 21–40 kg = 160 mg/d; 41–60 kg = 240 mg/d; 61–70 kg = 320 mg/d; oral||50; 24; 26||Significant decrease in AST; trend towards reduction in ALT||1iD|
|Prevention or Treatment of Non-Liver Disease|
|Reference||Condition or Cancer Type||Trial Design||Route of Administration and Dose||Treatment Groups (Enrolled; Treated; Placebo or No Treatment Control)a||Results||Level of Evidence Score g|
||Radiation therapy–associated mucositis||Double-blind, placebo-controlled, randomized clinical trial||Silymarin; 420 mg (140 mg 3 times/d); oral||30; 13; 14||Lower mucositis scores||1iC|
||Prostate cancer||Double-blind, placebo-controlled, randomized clinical trial||Silymarin; 570 mg (190 mg 3 times/d); oral||37; 19; 18||Increased QOL, decreased low-density lipoproteins, decreased total cholesterol, and increased selenium levels||1iC|
||Breast cancer||Nonrandomized, observational clinical trial||Silymarin (Silybum marianum, content 0.25%); topical||101; 51; 50||Decreased dermatitis||2C|
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
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.[
According to the German Commission E, there are no reported side effects with milk thistle when the recommended doses are used. Rare cases of milk thistle producing 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.[
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.[
It is not known whether milk thistle may reduce, enhance, or have no impact on the effectiveness of chemotherapy. In vitro studies show that silymarin decreases the components of the cytochrome P450 enzyme system, which is involved in the clearance of certain chemotherapy drugs.[
Theoretically, milk thistle may also interact adversely with chemotherapy drugs that exert their cytotoxic effects through the generation of free radicals. Silymarin and its metabolite inhibit p-glycoprotein–mediated cellular efflux, leading to the potentiation of doxorubicin cytotoxicity.[
To assist readers in evaluating the results of human studies of integrative, alternative, and complementary therapies for cancer, the strength of the evidence (i.e., the levels of evidence) associated with each type of treatment is provided whenever possible. To qualify for a level of evidence analysis, a study must:
Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. For an explanation of the scores and additional information about levels of evidence analysis of CAM treatments for cancer, refer to the PDQ summary on Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.
Given the limited amount of human data, the use of milk thistle/silymarin as a treatment for cancer patients cannot be recommended outside the context of well-designed clinical trials.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
This summary is written and maintained by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of milk thistle in the treatment of people with cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
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Levels of Evidence
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PDQ® Integrative, Alternative, and Complementary Therapies Editorial Board. PDQ Milk Thistle. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/cam/hp/milk-thistle-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389223]
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Last Revised: 2022-02-17
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