Milk Thistle

Milk thistle has reportedly been used since the 4th century BCE ^{33Reference 33DerMarderosian A · 2010ReviewThe review of natural products: the most complete source of natural product information (6th ed.) — reference text}. Dioscorides recommended the seeds, taken in drink, for infants with cramped muscles and for snakebite ^{35Reference 35A Modern Herbal · 1931Thistle (Milk) — historical herbal (traditional-use source)View study →}.

The English herbalists treated milk thistle as a liver herb. Gerard called it the best remedy against all melancholy diseases, which Maud Grieve read as another way of saying that it acted on the liver ^{35Reference 35A Modern Herbal · 1931Thistle (Milk) — historical herbal (traditional-use source)View study →}.

Culpeper used it for fevers and the plague, for obstructions of the liver and spleen, for jaundice, for kidney stones and for dropsy. He also applied it externally over the liver ^{35Reference 35A Modern Herbal · 1931Thistle (Milk) — historical herbal (traditional-use source)View study →}.

John Evelyn described the boiled plant as “a great breeder of milk” and a proper diet for nursing women. With the prickles removed, the young plant was boiled and eaten in spring as a blood cleanser ^{35Reference 35A Modern Herbal · 1931Thistle (Milk) — historical herbal (traditional-use source)View study →}.

Milk thistle seed was in popular use in Germany for jaundice and other bile complaints, and as a soothing remedy for catarrh and pleurisy ^{35Reference 35A Modern Herbal · 1931Thistle (Milk) — historical herbal (traditional-use source)View study →}. In nineteenth-century Germany it was used for jaundice, hepatitis and haemorrhoids, which led to its modern use as a bile and liver remedy ^{34Reference 34Bone K · 2013ReviewPrinciples and Practice of Phytotherapy — textbook}.

A decoction applied externally was said to help in cases of cancer ^{35Reference 35A Modern Herbal · 1931Thistle (Milk) — historical herbal (traditional-use source)View study →}.

An old Saxon remedy held that the plant, hung around the neck, would drive snakes away ^{35Reference 35A Modern Herbal · 1931Thistle (Milk) — historical herbal (traditional-use source)View study →}. The seeds were also once thought to cure rabies ^{35Reference 35A Modern Herbal · 1931Thistle (Milk) — historical herbal (traditional-use source)View study →}.

A 2017 meta-analysis of eight randomized trials (587 patients) found that silymarin reduced AST and ALT more than control in NAFLD ^{1Reference 1Zhong S et al. · 2017Meta-analysisThe therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease: a meta-analysis (PRISMA) of randomized control trials — meta-analysisView study →}.

In a 12-month trial in 179 patients, silybin combined with phosphatidylcholine and vitamin E (Realsil) improved liver enzymes, insulin resistance and liver histology compared with placebo ^{4Reference 4Loguercio C et al. · 2012RCTSilybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial — randomised controlled trialView study →}. Smaller silymarin-plus-vitamin-E pilots showed improvements in enzymes and steatosis ^{5Reference 5Aller R et al. · 2015RCTEffect of silymarin plus vitamin E in patients with non-alcoholic fatty liver disease: a randomized clinical pilot study — randomised controlled trialView study →}.

Two trials used liver biopsy as the endpoint. In 99 patients with NASH, silymarin 700 mg three times daily for 48 weeks did not improve the overall activity score more than placebo, although more patients on silymarin had reduced fibrosis (22% vs 6%) ^{2Reference 2Wah Kheong C et al. · 2017RCTA randomized trial of silymarin for the treatment of nonalcoholic steatohepatitis — randomised placebo-controlled trial (biopsy endpoint)View study →}. A US phase II trial of 420 or 700 mg three times daily also did not meet its histology endpoint ^{3Reference 3Navarro VJ et al. · 2019RCTSilymarin in non-cirrhotics with non-alcoholic steatohepatitis: a randomized, double-blind, placebo controlled trial — randomised controlled trialView study →}.

Network and umbrella meta-analyses rank silymarin among the better-supported natural products for NAFLD enzyme markers, with high heterogeneity between trials ^{6,7Reference 6Yang K et al. · 2022Meta-analysisEfficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: a systematic review and meta-analysis — systematic review and meta-analysisView study →Reference 7Liu H et al. · 2024Meta-analysisEffects of different natural products in patients with non-alcoholic fatty liver disease — a network meta-analysis of randomized controlled trials — network meta-analysisView study →}.

Gap: Enzyme (ALT/AST) improvements are consistent but modest; the two biopsy-endpoint trials did not meet their primary endpoints, so an effect on steatohepatitis or fibrosis is not established.

A 2016 meta-analysis of five randomized trials (270 patients) found silymarin lowered fasting blood glucose by about 27 mg/dL and HbA1c by about 1 percentage point in type 2 diabetes, with no effect on blood lipids ^{8Reference 8Voroneanu L et al. · 2016Meta-analysisSilymarin in type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials — systematic review and meta-analysisView study →}.

In a four-month double-blind trial in 51 patients, silymarin 200 mg three times daily added to standard therapy reduced HbA1c, fasting glucose, total and LDL cholesterol and triglycerides compared with placebo ^{9Reference 9Huseini HF et al. · 2006RCTThe efficacy of Silybum marianum (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled clinical trial — randomised placebo-controlled trialView study →}.

Later meta-analyses report improvements in fasting glucose, HbA1c, insulin resistance and some lipid and oxidative-stress measures ^{10,11Reference 10Hadi A et al. · 2018Meta-analysisThe effects of silymarin supplementation on metabolic status and oxidative stress in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of clinical trials — systematic review and meta-analysisView study →Reference 11Soleymani S et al. · 2022Meta-analysisThe effects of silymarin on the features of cardiometabolic syndrome in adults: a systematic review and meta-analysis — systematic review and meta-analysisView study →}. A 2024 trial reported improvements in both glycemic control and lipid profile ^{12Reference 12Ferdowsi S et al. · 2024RCTEffect of silymarin on lipid profile and glycemic control in patients with type 2 diabetes mellitus — randomised controlled trialView study →}.

The trials are small, short and mostly from a few research groups, with no large multicentre trial and no hard outcomes beyond glucose markers.

Silymarin and silybin scavenge free radicals, raise glutathione inside cells, reduce lipid peroxidation and increase catalase activity, protecting liver cells from oxidative injury in laboratory studies ^{13,14Reference 13Aghemo A et al. · 2022ReviewRole of silymarin as antioxidant in clinical management of chronic liver diseases: a narrative review — reviewView study →Reference 14Miguez MP et al. · 1994In vitroHepatoprotective mechanism of silymarin: no evidence for involvement of cytochrome P450 2E1 — in vitro / animal mechanistic studyView study →}.

This protection does not depend on inhibiting the liver enzyme CYP2E1, which points to direct radical scavenging and membrane stabilisation ^{14Reference 14Miguez MP et al. · 1994In vitroHepatoprotective mechanism of silymarin: no evidence for involvement of cytochrome P450 2E1 — in vitro / animal mechanistic studyView study →}.

In humans the antioxidant effect has been seen only indirectly, through the liver-enzyme and oxidative-stress markers in the NAFLD and diabetes trials ^{10,13Reference 10Hadi A et al. · 2018Meta-analysisThe effects of silymarin supplementation on metabolic status and oxidative stress in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of clinical trials — systematic review and meta-analysisView study →Reference 13Aghemo A et al. · 2022ReviewRole of silymarin as antioxidant in clinical management of chronic liver diseases: a narrative review — reviewView study →}.

Silymarin has been tested as a preventive during treatment with drugs that can damage the liver. In a double-blind trial in 55 people starting tuberculosis treatment, drug-induced liver injury developed in 1 of 27 on silymarin and 9 of 28 on placebo ^{15Reference 15Luangchosiri C et al. · 2015RCTA double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury — randomised placebo-controlled trialView study →}. A separate trial of a liver protectant during tuberculosis treatment reported similar protection ^{16Reference 16Zhang S et al. · 2016RCTPreventive use of a hepatoprotectant against anti-tuberculosis drug-induced liver injury: a randomized controlled trial — randomised controlled trialView study →}.

A 2019 meta-analysis of five trials (1,198 patients) found silymarin cut the risk of tuberculosis-drug liver injury at four weeks by about two-thirds ^{17Reference 17Tao L et al. · 2019Meta-analysisProphylactic therapy of silymarin (milk thistle) on antituberculosis drug-induced liver injury: a meta-analysis of randomized controlled trials — meta-analysisView study →}.

In a 2025 triple-blind trial in children receiving chemotherapy for leukaemia, both silymarin and a traditional Persian fruit infusion lowered liver enzymes, and the fruit infusion lowered ALT more ^{18Reference 18Ettehadi F et al. · 2025RCTEfficacy of a traditional Persian fruit infusion versus silymarin in reducing chemotherapy-induced hepatotoxicity in pediatric ALL: a triple-blind randomized clinical trial — randomised controlled trialView study →}.

The tuberculosis findings rest on a handful of modest-sized trials, and other drug-injury settings lack consistent data.

Intravenous silibinin (Legalon SIL), made from purified silybin, is used as a rescue treatment in death cap (Amanita phalloides) poisoning. Silibinin blocks the liver transport proteins that carry amatoxins into liver cells and interrupts the toxin’s recirculation through the bile ^{19Reference 19Mengs U et al. · 2012Clinical trialLegalon SIL: the antidote of choice in patients with acute hepatotoxicity from amatoxin poisoning — clinical review (case series)View study →}.

The evidence is observational, because a randomized trial in a lethal poisoning would be unethical. In nearly 1,500 documented cases, mortality with intravenous silibinin was under 10%, against over 20% with penicillin-based treatment ^{19Reference 19Mengs U et al. · 2012Clinical trialLegalon SIL: the antidote of choice in patients with acute hepatotoxicity from amatoxin poisoning — clinical review (case series)View study →}. In an early series of 18 patients, all but one survived ^{21Reference 21Hruby K et al. · 1983Case reportChemotherapy of Amanita phalloides poisoning with intravenous silibinin — clinical case seriesView study →}.

A 2022 review of 877 reported cases found survival of 90% with silibinin against 59% with supportive care alone, while noting that uncontrolled data cannot prove cause and effect ^{20Reference 20Tan JL et al. · 2022Systematic reviewAmanitin intoxication: effects of therapies on clinical outcomes — a review of 40 years of reported cases — systematic review of reported casesView study →}.

Gap: No randomized evidence exists or is feasible; the benefit is inferred from uncontrolled case series, and it applies to pharmaceutical intravenous silibinin, not to oral milk thistle.

In cultured human hepatic stellate cells, the cells that drive liver scarring, silybin has anti-inflammatory and anti-fibrotic effects ^{13Reference 13Aghemo A et al. · 2022ReviewRole of silymarin as antioxidant in clinical management of chronic liver diseases: a narrative review — reviewView study →}.

In cell and animal models, silymarin inhibits NF-κB signalling and reduces TNF-α and nitric-oxide production ^{13,14Reference 13Aghemo A et al. · 2022ReviewRole of silymarin as antioxidant in clinical management of chronic liver diseases: a narrative review — reviewView study →Reference 14Miguez MP et al. · 1994In vitroHepatoprotective mechanism of silymarin: no evidence for involvement of cytochrome P450 2E1 — in vitro / animal mechanistic studyView study →}. In animals it slows collagen build-up in experimental biliary fibrosis ^{23Reference 23Singh RP · 2006In vitroProstate cancer chemoprevention by silibinin: bench to bedside — review; animal model / in vitroView study →}.

In humans these effects have been seen only indirectly, through the enzyme and histology changes in the NAFLD trials ^{2,4Reference 2Wah Kheong C et al. · 2017RCTA randomized trial of silymarin for the treatment of nonalcoholic steatohepatitis — randomised placebo-controlled trial (biopsy endpoint)View study →Reference 4Loguercio C et al. · 2012RCTSilybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial — randomised controlled trialView study →}. They have not been confirmed as a biopsy-proven anti-fibrotic benefit in controlled trials.

In a double-blind trial in 50 mothers of preterm infants, 420 mg a day of a micronized milk thistle extract (252 mg silymarin) for 28 days did not increase milk production compared with placebo. It caused no adverse events in mothers or babies, and silymarin was not detected in breast milk. The mothers were not selected for low milk supply, and the authors called for trials in mothers who have it ^{28Reference 28Peila C et al. · 2015RCTEvaluation of the galactogogue effect of silymarin on mothers of preterm newborns (<32 weeks) — randomised controlled trialView study →}.

In a follow-up of a trial in mothers of preterm infants, those who took a silymarin-phosphatidylserine and galega product in the first month were more often feeding only breast milk at three months (22 vs 12 mothers) ^{29Reference 29Serrao F et al. · 2018RCTThe long-term efficacy of a galactagogue containing silymarin-phosphatidylserine and galega on milk production of mothers of preterm infants — randomised controlled trialView study →}.

Because the second product also contains galega, the contribution of milk thistle itself, and its best dose, are hard to separate.

A Cochrane review of 18 randomized trials (1,088 patients) in alcoholic and hepatitis B or C liver disease found no significant effect of milk thistle on death, complications of liver disease or liver histology, and rated most trials as low quality ^{24Reference 24Rambaldi A et al. · 2007Meta-analysisMilk thistle for alcoholic and/or hepatitis B or C virus liver diseases — Cochrane systematic review and meta-analysisView study →}.

A 2012 NIH-funded multicentre trial in 154 people with hepatitis C who had not responded to interferon gave 420 or 700 mg of silymarin three times daily for 24 weeks. Neither dose lowered ALT more than placebo ^{25Reference 25Fried MW et al. · 2012RCTEffect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial — multicentre randomised controlled trialView study →}.

Silibinin has antiviral activity against hepatitis C in cell culture, but this has not translated into benefit from oral use ^{25Reference 25Fried MW et al. · 2012RCTEffect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial — multicentre randomised controlled trialView study →}.

Gap: Well-conducted human trials, including a rigorous NIH trial, are largely null for chronic viral and alcoholic hepatitis; the antiviral data from cell culture do not carry over to the oral herb.

Silibinin has an extensive preclinical anticancer literature, best developed in prostate cancer, where it affects growth-factor signalling, cell-cycle arrest and blood-vessel formation in cultured cells and animal models ^{22,23Reference 22Ting H et al. · 2013ReviewMolecular mechanisms of silibinin-mediated cancer chemoprevention with major emphasis on prostate cancer — review (mechanistic)View study →Reference 23Singh RP · 2006In vitroProstate cancer chemoprevention by silibinin: bench to bedside — review; animal model / in vitroView study →}.

Early-phase pharmacokinetic work has explored high-dose silibinin in men with prostate cancer ^{23Reference 23Singh RP · 2006In vitroProstate cancer chemoprevention by silibinin: bench to bedside — review; animal model / in vitroView study →}. No controlled trial has shown that milk thistle or silibinin prevents or treats any human cancer.

Gap: Human efficacy evidence is essentially absent; anticancer use remains investigational.

Side effects. The most common side effects in trials are mild digestive complaints such as loose stools, nausea and bloating, at rates close to placebo ^{24Reference 24Rambaldi A et al. · 2007Meta-analysisMilk thistle for alcoholic and/or hepatitis B or C virus liver diseases — Cochrane systematic review and meta-analysisView study →}.

Allergy. Milk thistle is in the daisy family, and people allergic to ragweed, chrysanthemums, marigolds or daisies can react to it. Rare anaphylaxis has been reported. No other contraindications are established.

Drug interactions. In laboratory studies silymarin reduces the activity of CYP enzymes, UGT enzymes and the P-glycoprotein transporter, but in people it has had limited effect on the levels of the drugs tested ^{26Reference 26Wu JW et al. · 2009ReviewDrug-drug interactions of silymarin on the perspective of pharmacokinetics — review (pharmacokinetics)View study →}. In a controlled study in 16 healthy men, silymarin did not meaningfully change the amount of nifedipine absorbed, and the authors concluded it is not a strong CYP3A4 inhibitor in the body ^{27Reference 27Fuhr U et al. · 2007RCTThe effect of silymarin on oral nifedipine pharmacokinetics — randomised crossover pharmacokinetic trialView study →}. Care is still sensible with drugs that have a narrow safety margin, such as warfarin, ciclosporin, tacrolimus and chemotherapy drugs ^{26Reference 26Wu JW et al. · 2009ReviewDrug-drug interactions of silymarin on the perspective of pharmacokinetics — review (pharmacokinetics)View study →}.