Herb & supplement monograph

Milk Thistle Drug Interactions, Uses, Effectiveness, Safety & More

Medically reviewed by Dr. Brian Staiger, PharmD, BCPS ·Updated July 2026

What is this page for?

First and foremost: how Milk Thistle interacts with medications. The heart of this page is the interaction list — every drug Milk Thistle is known to interact with, and how serious each one is.

But these pages have grown well beyond that into a full monograph — what Milk Thistle is, what people use it for and how strong the evidence is, its safety and side effects, and answers to the questions we’re asked most — written and reviewed by the clinical staff at HelloPharmacist. It’s educational information from our licensed clinical databases, not medical advice, and we don’t sell or endorse products. Our editorial policy

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Milk Thistle Drug Interactions: The Bottom Line

From the HelloPharmacist Editorial Team · Updated July 2026

Based on the available evidence, the overall risk of a clinically significant Milk Thistle drug interaction appears low for most people. None of the listed interactions are rated major, and the great majority are minor, with a smaller group rated moderate.

Interactions deserving the most attention

The combinations with the best human data deserve the most care. Milk thistle can lower blood sugar, so people taking diabetes medications could see an added glucose-lowering effect. It may also slow the body's clearance of sirolimus, a transplant drug where levels are watched closely, though this was seen in patients with liver impairment. One case report links milk thistle to a raised INR with warfarin, so anyone on this blood thinner should be aware. Possible effects on tamoxifen, morphine, and some hepatitis C drugs come from animal or lab research only.

What the rest of the list means

A long list of interacting medications does not mean each combination is harmful. Most entries here are theoretical, based on lab findings that milk thistle might affect enzymes or transporters the body uses to clear certain drugs. In several cases, human studies found the predicted effect did not cause meaningful changes.

Check your medications against Milk Thistle

Based on HelloPharmacist’s Milk Thistle interaction data and reviewed under our editorial standards.

Interaction report

Drugs that interact with Milk Thistle

954 medications have a known interaction with Milk Thistle, graded by severity. Select any drug for the full evidence-based detail.

Don’t want to scroll the list? Just ask.

Tell us the medications you take and we’ll check each one against Milk Thistle using our pharmacist-reviewed interaction data.

AI summaries are generated from our Milk Thistle interaction data for education only — always confirm with your pharmacist. How we use AI

2,830 drugs

Read The List Like a Pharmacist

What Severity, Likelihood & Evidence Mean

Severity — How Serious It Can Be

Major. Clinically significant; generally best avoided, or used only under direct professional supervision.
Moderate. May need monitoring, a dose adjustment, or separating the times you take each one.
Minor. Generally not clinically significant, but still worth noting and mentioning to your pharmacist.
No known interaction. Checked against our sources with nothing documented — not the same as proven safety.

Likelihood — How Well It’s Documented

Likely. Well-controlled human studies have demonstrated the likely existence of this interaction
Probable. Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
Possible. Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists
Unlikely. Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.

Where This Data Comes From

Interaction records are evidence-graded and sourced from the Natural Medicines database (TRC Healthcare), the same reference used by pharmacists and hospitals.
Each drug listed above links to the full report for that exact Milk Thistle combination — clinical detail, likelihood, evidence level, and citations.
Content is reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

The big picture

The kinds of drugs Milk Thistle affects

Every type of medication (drug category) Milk Thistle is known to interact with. Open any category for the detail — or search your exact drug in the checker above.

All 17 drug categories Milk Thistle interacts with

Antidiabetes DrugsCytochrome P450 2b6 (cyp2b6) SubstratesGlucuronidated DrugsLedipasvirMorphineRaloxifene (evista)Sirolimus (rapamune)Sofosbuvir (solvaldi)Tamoxifen (nolvadex)Warfarin (coumadin)Cytochrome P450 2c9 (cyp2c9) SubstratesCytochrome P450 3a4 (cyp3a4) SubstratesEstrogensHmg-coa Reductase Inhibitors ("statins")Indinavir (crixivan)Organic Anion-transporting Polypeptide Substrates (oatp)P-glycoprotein Substrates

Antidiabetes Drugs

Taking milk thistle with antidiabetes drugs may increase the risk of hypoglycemia.
Clinical research shows that milk thistle extract, alone or along with tree turmeric extract, can lower blood glucose levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, including those already taking antidiabetes drugs. Additionally, animal research shows that milk thistle extract increases the metformin maximum plasma concentration and area under the curve and decreases the renal clearance of metformin, due to inhibition of the multi-drug and toxin extrusion protein 1 (MATE1) renal tubular transport protein.

Likelihood Possible Evidence B

Cytochrome P450 2B6 (Cyp2B6) Substrates

Theoretically, milk thistle might inhibit CYP2B6.
An in vitro study shows that silybin, a constituent of milk thistle, binds to and noncompetitively inhibits CYP2B6. Additionally, silybin might downregulate the expression of CYP2B6 by decreasing mRNA and protein levels.

Likelihood Possible Evidence D

Glucuronidated Drugs

Theoretically, milk thistle might affect the clearance of drugs that undergo glucuronidation.
Laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation. Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs. Other laboratory research suggests that a milk thistle extract of silymarin might inhibit beta-glucuronidase, although the significance of this effect is unclear.

Likelihood Possible Evidence D

Ledipasvir

Theoretically, milk thistle might increase the levels and clinical effects of ledipasvir.
Animal research in rats shows that milk thistle increases the area under the curve (AUC) for ledipasvir and slows its elimination.

Likelihood Possible Evidence D

Morphine

Theoretically, concomitant use of milk thistle with morphine might affect serum levels of morphine and either increase or decrease its effects.
Animal research shows that milk thistle reduces serum levels of morphine by up to 66%. In contrast, laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation. Theoretically, this could decrease the clearance and increase morphine levels. The effect of taking milk thistle on morphine metabolism in humans is not known.

Likelihood Possible Evidence D

Raloxifene (Evista)

Theoretically, milk thistle might decrease the clearance and increase levels of raloxifene.
Laboratory research suggests that the milk thistle constituents silibinin and silymarin inhibit the glucuronidation of raloxifene in the intestines.

Likelihood Possible Evidence D

Sirolimus (Rapamune)

Milk thistle might decrease the clearance of sirolimus.
Pharmacokinetic research shows that a milk thistle extract of silymarin decreases the apparent clearance of sirolimus in hepatically impaired renal transplant patients. It is unclear if this interaction occurs in patients without hepatic impairment.

Likelihood Possible Evidence B

Sofosbuvir (Solvaldi)

Theoretically, milk thistle might decrease the levels and clinical effects of sofosbuvir.
Animal research in rats shows that milk thistle reduces the metabolism of sofosbuvir, as well as the hepatic uptake of its active metabolite.

Likelihood Possible Evidence D

Tamoxifen (Nolvadex)

Theoretically, the milk thistle constituent silibinin might increase tamoxifen levels and interfere with its conversion to an active metabolite.
Animal research suggests that the milk thistle constituent silibinin might increase plasma levels of tamoxifen and alter its conversion to an active metabolite. The mechanism appears to involve inhibition of pre-systemic metabolism of tamoxifen by cytochrome P450 (CYP) 2C9 and CYP3A4, and inhibition of P-glycoprotein-mediated efflux of tamoxifen into the intestine for excretion. Whether this interaction occurs in humans is not known.

Likelihood Possible Evidence D

Warfarin (Coumadin)

Theoretically, milk thistle might increase the effects of warfarin.
In one case report, a man stabilized on warfarin experienced an increase in INR from 2.64 to 4.12 after taking a combination product containing milk thistle 200 mg daily, as well as dandelion, wild yam, niacinamide, and vitamin B12. Levels returned to normal after stopping the supplement. Although a direct correlation between milk thistle and the change in INR cannot be confirmed, some in vitro research suggests that milk thistle might inhibit cytochrome P450 2C9 (CYP2C9), an enzyme involved in the metabolism of various drugs, including warfarin.

Likelihood Possible Evidence D

Cytochrome P450 2C9 (Cyp2C9) Substrates

It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
In vitro research suggests that milk thistle might inhibit CYP2C9. Additionally, 3 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP2C9 substrates, including imatinib and capecitabine. However, contradictory clinical research shows that milk thistle extract does not inhibit CYP2C9 or significantly affect levels of the CYP2C9 substrate tolbutamide. Differences in results could be due to differences in dosages or formulations utilized.

Likelihood Unlikely Evidence B

Cytochrome P450 3A4 (Cyp3A4) Substrates

It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
While laboratory research shows conflicting results, pharmacokinetic research shows that taking milk thistle extract 420-1350 mg daily does not significantly affect the metabolism of the CYP3A4 substrates irinotecan, midazolam, or indinavir. However, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP3A4 substrates, including gefitinib, sorafenib, doxorubicin, and vincristine.

Likelihood Unlikely Evidence D

Estrogens

Theoretically, milk thistle might interfere with estrogen therapy through competition for estrogen receptors.
Animal research suggests that a milk thistle extract of silymarin binds to estrogen receptor beta.

Likelihood Possible Evidence D

Hmg-Coa Reductase Inhibitors ("Statins")

Theoretically, milk thistle might interfere with statin therapy by decreasing the activity of organic anion transporting polypeptide 1B1 (OATB1B1) and inhibiting breast cancer resistance protein (BCRP).
Preliminary evidence suggests that a milk thistle extract of silymarin can decrease the activity of the OATP1B1, which transports HMG-CoA reductase inhibitors into the liver to their site of action, and animal research shows this increases the maximum plasma concentration of pitavastatin and pravastatin. The silibinin component also inhibits BCRP, which transports statins from the liver into the bile for excretion. However, in a preliminary study in healthy males, silymarin 140 mg three times daily had no effect on the pharmacokinetics of a single 10 mg dose of rosuvastatin.

Likelihood Unlikely Evidence D

Indinavir (Crixivan)

Theoretically, milk thistle may induce cytochrome P450 3A4 (CYP3A4) enzymes and increase the metabolism of indinavir; however, results are conflicting.
One pharmacokinetic study shows that taking milk thistle (Standardized Milk Thistle, General Nutrition Corp.) 175 mg three times daily in combination with multiple doses of indinavir 800 mg every 8 hours decreases the mean trough levels of indinavir by 25%. However, results from the same pharmacokinetic study show that milk thistle does not affect the overall exposure to indinavir. Furthermore, two other pharmacokinetic studies show that taking specific milk thistle extract (Legalon, Rottapharm Madaus; Thisilyn, Nature's Way) 160-450 mg every 8 hours in combination with multiple doses of indinavir 800 mg every 8 hours does not reduce levels of indinavir.

Likelihood Unlikely Evidence B

Organic Anion-Transporting Polypeptide Substrates (Oatp)

Milk thistle may inhibit one form of OATP, OATP-B1, which could reduce the bioavailability and clinical effects of OATP-B1 substrates.
In vitro research shows that milk thistle inhibits OATP-B1. Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are OATP substrates, including sorafenib and methotrexate. OATPs are expressed in the small intestine and liver and are responsible for the uptake of drugs and other compounds into the body. Inhibition of OATP may reduce the bioavailability of oral drugs that are substrates of OATP.

Likelihood Possible Evidence D

P-Glycoprotein Substrates

Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates. However, this effect does not seem to be clinically significant.
In vitro research shows that milk thistle can inhibit P-glycoprotein activity and 1 case report from the World Health Organization (WHO) adverse drug reaction database describes increased abdominal pain in a patient taking milk thistle and the cancer medication vincristine, a P-glycoprotein substrate, though this patient was also taking methotrexate. However, a small pharmacokinetic study in healthy volunteers shows that taking milk thistle (Enzymatic Therapy Inc.) 900 mg, standardized to 80% silymarin, in 3 divided doses daily for 14 days does not affect absorption of digoxin, a P-glycoprotein substrate.

Likelihood Unlikely Evidence B

Monograph

Milk Thistle: Uses, Safety & Side Effects

Medically reviewed by Dr. Brian Staiger, PharmD, BCPS · Reviewed July 2026 ·

The bottom line

Milk thistle is a popular herbal supplement most often used for liver health, and its main active component is a group of compounds called silymarin. While it is generally well tolerated, the scientific evidence that it meaningfully improves liver disease or other conditions is mixed and far from conclusive. Talk with your pharmacist or doctor before using it, especially if you have a liver condition or take other medicines.

Scientific name: Silybum marianum
Family: Asteraceae
Part used: Seeds (fruit)
Common forms: Capsules, tablets, softgels, liquid extracts, tinctures, tea

People commonly use it for

Liver health and protection
Hepatitis
Cirrhosis
Gallbladder problems
High cholesterol
Type 2 diabetes support

Popular and traditional uses — not proof it works. See “Uses & effectiveness” below for the evidence.

Safety at a glance

OverallUse caution

Generally well tolerated in most adults, but quality and effectiveness vary and a doctor should be involved for liver conditions.

PregnancyInsufficient reliable information

While research in an animal model shows that taking milk thistle during pregnancy and lactation does not adversely impact infant development, there is...

Read the full pregnancy detail

BreastfeedingInsufficient reliable information

While research in an animal model shows that taking milk thistle during pregnancy and lactation does not adversely impact infant development, there is...

Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center). Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

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Overview

Milk thistle (Silybum marianum) is a flowering plant in the aster family (Asteraceae). It is native to the Mediterranean region but now grows in many parts of the world. The plant gets its name from the milky-white veins on its leaves and the milky sap it produces.

Milk thistle has been used in traditional medicine for hundreds of years, mainly for problems affecting the liver and gallbladder. Today it is one of the most popular herbal supplements in the world. The seeds (fruit) are the part used to make supplements.

The active compounds are a group of plant chemicals called silymarin. Many supplements are standardized to contain a set percentage of silymarin, often around 70% to 80% in extracts.

How it works

The main active part of milk thistle is silymarin, a mix of plant compounds called flavonolignans. The most studied of these is silibinin (also called silybin).

In laboratory and animal studies, silymarin appears to act as an antioxidant, meaning it may help protect cells from a type of damage caused by unstable molecules. Researchers have also suggested it may reduce inflammation, help stabilize liver cell membranes, and support the liver's ability to repair itself.

It is important to know that much of this information comes from test-tube and animal research. How well these effects carry over to people, and at what doses, is still not fully understood.

Effectiveness

Does Milk Thistle work?

Here’s what the research actually shows for each use — graded by Natural Medicines and reviewed by Dr. Brian Staiger, PharmD.

Evidence overview · 47 uses evaluated

1 Possibly effective 46 Insufficient evidence

How to read these evidence grades

Natural Medicines’ 7-point scale. We show each rating’s label word-for-word.

1EffectiveStrong, consistent evidence it works.

2Likely EffectiveGood evidence, though not yet conclusive.

3Possibly EffectiveSome evidence suggests a benefit.

4Possibly IneffectiveSome evidence it may not help.

5Likely IneffectiveFairly strong evidence it doesn’t help.

6IneffectiveStrong evidence it doesn’t work.

7Insufficient Reliable Evidence to RateToo little research to say either way.

Possibly Effective Diabetes