Description
Milk thistle herbal products are made from seeds of Silybum marianum. Milk thistle has a long history of medicinal use, particularly in the treatment of digestive and liver disorders. Claims in relation to cancer are that milk thistle prevents cancer initiation and development, reduces adverse effects of chemotherapy and radiotherapy, and supports the action of some anticancer drugs.
Efficacy
Numerous animal and in vitro models support these claims; however, there is limited data from clinical studies.
Chemotherapy-induced hepatotoxicity:
- Among children, improved markers of liver function were reported in 4 RCTs, including AST, ALT, ALP (moderate-certainty evidence).
- Studies conducted among adults are inconclusive, while 2 RCTs showed no improvements in liver toxicity, two CCTs showed improvements in AST and ALT (low-certainty evidence).
Chemotherapy-induced nephrotoxicity:
- Results from two small RCTs are conflicting, while one reported reduced blood urea nitrogen and creatinine, another did not report any improvements (low-certainty evidence).
Chemotherapy-induced cardiotoxicity
- Silymarin may decreased early doxorubicin-induced cardiotoxicity among children based on one RCT (moderate-certainty evidence).
- Silymarin may be a useful agent as it resulted in more beneficial effects on the iron profile reported in one small RCT (low-certainty evidence).
Chemotherapy-induced mucositis:
- Evidence from three small RCTs is conflicting: two reported reduced severity of mucositis, one thereof also delayed onset while the third reported no differences between groups for these outcomes (low-certainty evidence).
Radiation dermatitis:
- Milk thistle may delay radiodermatitis occurrence and slow down its progression according to two CCTs (low-certainty evidence).
Hand-foot syndrome:
- One RCT found topical silymarin to be the most useful for preventing capecitabine-induced hand-food syndrome compared with six other regimens (moderate-certainty evidence).
Safety
Milk thistle is generally considered safe in most populations.
Description and background
Milk thistle (Silybum marianum L. Gaertn.), also known as St. Mary’s thistle, holy thistle, and lady’s thistle, is a herb from the Asteraceae family. The seeds are used medicinally and are the source of silymarin, a key active compound. (USDA 2012) Commercial products include standardized extracts like Legalon SIL®, Thisilyn™ (80% silymarin content), extracts complexed with lipids like Siliphos™, and topical formulations like Leviaderm™. (NatMed 2023)
Originally native to North Africa, Asia Minor, and southern Europe, milk thistle is now naturalized globally. Traditionally, the seeds have been used for over 2,000 years to treat liver and digestive issues, melancholy, headaches, detoxification, and to promote lactation. (USDA 2012; NatMed 2023)
Scientific interest in milk thistle began in the 1960s with the identification of silymarin. Since then, research has focused mainly on liver protection and treatment of liver disorders. (NatMed 2023; Loguercio 2011). In the 1990s, pre-clinical studies also suggested potential anti-cancer properties, prompting further investigation. (Kroll 2007; Greenlee 2007; Post-White 2007).
Ingredients and quality issues
Milk thistle’s main effects are attributed to silymarin, a flavonolignan complex making up 65–80% of the dried seed extract. (NatMed 2023; Cheung 2010; Kroll 2007) Silymarin includes at least seven flavonolignans—mainly silybin A and B, isosilybin A and B, silychristin, isosilychristin, and silydianin—along with the flavonoid taxifolin. Silybin, considered the most active component, is a processed form of silymarin containing equal parts of silybin A and B. (Loguercio 2011, Brantley 2010). The seeds also contain fatty acids like linoleic acid.
Alleged indications
Milk thistle is primarily claimed to protect the liver, with recognized therapeutic use for toxic liver damage and support in chronic liver conditions and cirrhosis, as per the ESCOP monograph. (NatMed 2023, Braun 2010; ESCOP 2009).
In cancer care, it is claimed to help inhibit tumour growth, alleviate adverse events from cancer treatment and enhance chemotherapy, based on pre-clinical studies and case reports. (Greenlee 2007; Post-White 2007; Deep 2010; Olaku 2011; McBride 2012; Deep 2007)
Application and dosage
Milk thistle is taken orally as tablets, tea or tincture (NatMed 2023, Wichtl 2004), can be applied topically as cream, and in some location is available as injectable preparations (Legalon SIL®).
Various oral dosages have been used often in the range of 12-15g milk thistle (NatMed 2023, Braun 2010) containing 200 - 600 mg silymarin/ day in divided doses.
The most common dosing regimen in clinical trials for cancer has been 420mg of silymarin daily in three divided doses (Shahbazi 2015, Hagag 2018, Elyasi 2016). Silymarin is poorly water-soluble; bioavailability is increased by lipid formulations (Barzaghi 2014). Maximum tolerated dose is not known. (NatMed 2023; Siegel 2014)
Mechanisms of action
The main bioactive ingredient of milk thistle (Silybum marianum) is silymarin, which is a complex of flavonolignans including silybinin, silydianin, and taxifolin (Albahri 2024). Preclinical studies suggest that milk thistle may exhibit anticancer properties through several mechanisms (Sharma 2025). These findings are primarily preclinical (in vitro/in vivo models), with limited human data. Clinical relevance remains investigational.
- Antioxidant and anti-inflammatory activity: Demonstrated in animal models, potentially contributing to cellular protection.(NatMed 2023, Loguercio 2011, Albahri 2024).
- Pro-apoptotic effects: Induces cancer cell apoptosis, including cancer stem cells. Especially in combination with agents like sorafenib. (Sharma 2025)
- Cell growth inhibition and anti-proliferative effects: Observed across various cancer cell lines. (Albahri 2024)
- Anti-angiogenic activity: May inhibit new blood vessel formation, potentially limiting tumor growth. (Sharma 2025)
- Autophagy modulation: Induces autophagy in cancer cells (e.g., via taxifolin), contributing to growth suppression. (Sharma 2025)
- Enhanced chemotherapy response: Shown to increase sensitivity to agents such as cisplatin, doxorubicin, paclitaxel, and vincristine; also reported to reduce cisplatin-induced nephrotoxicity in animal studies. (Sharma 2025; Cheung 2010; Colombo 2011; Scambia 1996; Ladas 2010).
- DNA repair and protection: In vitro data suggest improved DNA repair (Emadi 2022) and reduced UVB-induced DNA damage in skin models. (Wingren 2023).
- Animal studies suggest reduced tumour initiation, growth, and volume, particularly in skin and prostate models (Deep 2007, Deep 2010).
Legal issues
Milk thistle products are widely available over the counter. In the EU, milk thistle is considered a traditional herbal medicinal product for the symptomatic relief of digestive disorders, sensation of fullness and indigestion, and to support the liver function exclusively based upon long-standing use (“traditional use”). (EMA 2018)
In the US, milk thistle is included in the United States Pharmacopoeia-National Formulary. It is available as a “dietary supplement” under the Dietary Supplement Health and Education act 1994 (NatMed 2023, Braun 2010, Mills 2000). In the UK, it is available as a registered traditional medicine under the Traditional Herbal Medicines Directive (MHRA 2022).
A comprehensive review of silymarin as a preventive or therapeutic measure for chemotherapy and radiotherapy-induced adverse reactions was published in 2023. (Ghodousi 2023).
It includes 16 randomized clinical trials (RCTs), one non-randomized controlled clinical trials (CCT), three case reports, and 42 in vivo/in vitro studies. Most trials have small sample sizes and methodological shortcomings.
The RCTs and CCT are summarized below and full details can be found in Table 1.
Chemotherapy-induced (liver toxicity) hepatotoxicity
Seven RCTs and CCTs are available, mostly in children with leukemia (Ladas 2010, Hagag 2016, Ghazizadeh 2021) and adults with breast cancer (Moezian 2022, Mohaghegh 2015, Mshemish 2011) or colorectal cancer (Chang 2021).
Findings from these trials suggest the silymarin can improve liver function markers (AST, ALT) and may thus contribute to reducing liver damage from chemotherapy.
However, one trial in colorectal cancer patients found no benefit (Chang 2021).
Chemotherapy-induced kidney toxicity (nephrotoxicity)
In two RCTs, additional administration of silymarin during cisplatin treatment was compared to no additional treatment.
One RCT (n=60) showed reduced kidney damage markers, blood urea nitrogen and creatinine, with silymarin before cisplatin treatment compared to no additional treatment. (Momeni 2015)
A pilot RCT (n=24) while another found no benefit to acute kidney injury or urinary electrolyte wasting prior to cisplatin infusion. (Shahbazi 2015)
These contradictory findings are possibly due to differences in outcome measures and treatment periods.
Chemotherapy-induced heart toxicity (cardiotoxicity)
Two RCTs, including one in children, assessed additional administration of silymarin as a cardioprotective agent during anthracycline chemotherapy.
The first RCT (n=80 children) trial found that silymarin significantly decreased early Doxorubicin-induced left ventricular systolic function disturbances. (Hagag 2019, also in Singh 2023)
The second RCT (n=83) found silymarin to be more beneficial effects on iron profile compared with l-carnitine or no additional treatment. (Zalat 2020)
Treatment-induced mucositis
Three RCTs evaluated the effect of silymarin on the severity and onset of mucositis induced by chemotherapy or radiotherapy.
One RCT found that silymarin reduced the incidence and severity of chemotherapy-induced mucositis compared to groups receiving indomethacin or placebo (Altaei 2012, n =65).
One pilot RCT found reduced incidence and severity of radiation therapy induced mucositis in head and neck cancer patients compared with no other additional treatment (Elyasi 2016, n=27).
One RCT in patients with head and neck cancer showed no significant differences between the treatment and placebo groups in the prevention of radiotherapy induced mucositis. (Hosseini 2021, n=31)
Radiation dermatitis
Two trials suggested topical silymarin gel or cream may delay and reduce skin damage during radiotherapy, though evidence is limited due to methodological issues.
One RCT among breast cancer patients found that the application of silymarin 1% gel compared with placebo may delay radiodermatitis occurrence and slow down its progression. (Karbasforooshan 2019, n=40)
In a CCT, a combination cream including milk thistle as an adjunct to radiotherapy was associated with a significantly longer median time to toxicity compared to controls receiving standard care. This study was not randomized and as a combination product was used, the specific effect of silymarin cannot be established. (Becker-Schiebe 2011, n=101)
These two trials were also included in a SR measuring the efficacy of medicinal plant preparations in the alleviation of radiodermatitis in patients with breast cancer. (Baharara 2023)
Chemotherapy-induced hand-foot syndrome
A placebo-controlled RCT showed that 1% silymarin gel significantly reduced symptoms median WHO score during capecitabine chemotherapy. (Elyasi 2017, n=40)
A systematic review found it was the most effective regimen compared with pyridoxine, TJ-28, Mapisal, urea cream, celecoxib, Evoskin PSMC. (Kao 2022)
Milk thistle and its key constituents, particularly silymarin and silybinin, are generally well-tolerated and considered safe in clinical and preclinical settings.(Jaffar 2024).
Adverse Events
Most clinical trials report no significant adverse events (AEs) or AEs unrelated to the intervention. (e.g. Ladas 2010; Vidlar 2010; Becker-Schiebe 2011; Shahbazi 2015; Lazzeroni 2016; Elyasi 2016; Elyasi 2017
- Mild-to-moderate AEs include: gastrointestinal symptoms (nausea, abdominal pain, diarrhoea), weight loss, myalgia, irritability, arthralgia, hyperglycaemia/cholesterolaemia, mild sweating, and transient bilirubin elevation. (Soleimani 2019; Jaffar 2024)
- Ungraded AEs: headache, rash, urticaria, and pruritus—typically self-limiting or resolved upon discontinuation. (Soleimani 2019)
- Rare/single case reports include:
- Non-significant hyperbilirubinemia, moderate (Soleimani 2019)
- Severe ALT elevation and asymptomatic liver toxicity (Flaig 2007)
- Postoperative thromboembolic event, unclear causality (Flaig 2010);
- Collapse with autonomic/GI symptoms (Jaffar 2024)
Contraindications
- Pregnancy and lactation: Limited human data suggest possible safety (e.g., 420 mg/day silymarin in lactating women), but evidence remains insufficient for clinical recommendation. (Soleimani 2019).
- Children: No toxicity reported in some studies (e.g., hepatic toxicity, beta-thalassemia, ALL), but overall paediatric data remain sparse. (Soleimani 2019; Hagag 2015).
- Preclinical risks: Limited evidence of teratogenicity (female mice) and sperm quality reduction (male animals). Mutagenicity observed in silymarin (but not silybin) in S. typhimurium assays. (Soleimani 2019)
Interactions
Available data are limited to isolated case reports, conflicting preclinical studies, and mechanistic hypotheses. No clinically significant interactions are currently established, and the clinical relevance is frequently unknown.
- CYP enzymes: Contradictory evidence exists. In humans, milk thistle extract showed no significant effects on CYP activity (Kawaguchi-Suzuki 2014; Gurley 2004, 2008) or irinotecan metabolism (van Erp 2005). However, in vitro studies report inhibition of specific CYPs and UGTs (Sridar 2004; NatMed 2024). The clinical risk of drug interactions remains unknown.
- P-glycoprotein (P-gp): Human data are limited to a WHO case report linking milk thistle to vincristine toxicity (mechanism unclear; NatMed 2024). While in vitro studies suggest P-gp inhibition (NatMed 2024), in vivo data found no modulation (Gurley 2006). Drug-drug interaction risk is uncertain.
- Pro-oxidant chemotherapy: Animal studies suggest silymarin may reduce cisplatin-induced oxidative stress (Mansour 2006), but whether this compromises chemotherapy efficacy in humans is unknown.
- Immune Checkpoint Inhibitors: In vitro, silymarin suppressed T-cell function (NATMED 2024) and silybin reduced PD-L1 expression (Lee 2021). Human implications, enhanced response or increased toxicity, are unconfirmed.
- Specific drug classes: Although compelling evidence is missing, in humans was reported synergism with hypoglycaemic agents, and one case of elevated INR with anticoagulants. (NatMed 2024). ER agonism was reported in humans (Dupis 2018), but toxicity risk is unconfirmed.
In WHO case reports, toxicity with imatinib, capecitabine, and vincristine (NatMed 2024) highlights potential risks, though causality is unproven.
Warnings
Caution has been recommended in patients with a known hypersensitivity to plants in the Asteraceae family (Braun 2010, Mills 2000, NatMed 2024).
Given its reported oestrogen receptor agonist activity caution may be warranted in oestrogen-sensitive tumours until further clinical data are available. (NatMed 2024)
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Citation
Dana Mora, Lisa Dal Pozzo, CAM Cancer Collaboration. Milk thistle (Silybum marianum) [online document], May 2025.
Document history
Update of “Mechanisms of action” and “Is it safe” sections in April 2025 by Lisa Dal Pozzo; “What is it” and “Does it work” sections by Dana Mora and the CAM Cancer Collaboration in October 2023 and May 2025. Updated literature search in April 2025.
Updated in January 2019 by Ellen Conte. Assessed as up to date in January 2015 by Barbara Wider.
Summary first published in May 2013, authored by Julia Green and Alexander Kalisch.
Next update due: June 2028
Photo: Mostphotos.com
