Milk Thistle Ingredients & Drug Interactions
What is this page for?
First and foremost: checking Milk Thistle against your medications. The heart of this page is the interaction checker and the full interaction report — how this product’s ingredients may interact with prescription and over-the-counter medicines you may be taking.
Around that, we add a pharmacist’s high-level view of the product as a whole — what’s inside, the evidence for its stated use, how transparent the label is, and what safety data exists — so you can see the full picture in one place. It’s educational information from our licensed clinical databases and the clinical staff at HelloPharmacist — not medical advice — and we don’t sell or endorse products. Our editorial policy
Milk Thistle is a dietary supplement by Higher Nature with 1 active ingredient. Its ingredients are commonly taken for liver health and protection, hepatitis, cirrhosis.Based on those ingredients, 954 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are Milk Thistle fruits (Silybum marianum (L.) Gaetn.) standardised extract. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.
Check Your Meds Against Milk Thistle by Higher Nature
Ask about any prescription or over-the-counter medication and we check it for interactions with Milk Thistle by Higher Nature — and tell you which ingredient is responsible.
AI summaries are generated from our interaction database for education only — always confirm with your pharmacist. How we use AI
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HelloPharmacist Scorecard of Milk Thistle by Higher Nature
Our pharmacy team’s full take, with four database checks built into the cards below — a summary of what is known, not a grade of the product itself.
What’s inside
Low disclosure
This product contains one active ingredient: milk thistle fruits standardised extract (from Silybum marianum). Standardised extract means it's been processed to contain a consistent level of milk thistle's key compounds.
The capsule itself contains acetone as an inactive ingredient — a solvent used in the extraction process.
Does it work?
Not established
The evidence for milk thistle is mixed. For type 2 diabetes, it's rated possibly effective — clinical trials show it can lower blood sugar and HbA1c (a measure of long-term blood sugar control), even in people already taking diabetes drugs.
For acne, hay fever, gambling disorder, alcohol-related liver disease, and amanita mushroom poisoning, the evidence isn't established in the data we hold — we can't say whether it works or doesn't.
How safe is it?
Well-documented data
Milk thistle is generally well tolerated in most adults. The most common side effects — abdominal bloating, diarrhea, upset stomach, gas, and nausea — don't typically happen more often than with placebo.
Headache, dizziness, and sleep trouble have been reported. Allergic reactions, including severe ones (anaphylaxis), are rare but possible.
During pregnancy, there isn't enough reliable safety information, so it's best avoided. During breastfeeding, safety isn't well studied, so caution is advised.
Because quality and strength can vary between products, involve your doctor if you're taking it for a liver condition.
Meds to double-check
Moderate interaction found
Before taking this milk thistle product, double-check these medication types with your pharmacist: blood thinners like warfarin, antidiabetes drugs, antivirals (especially sofosbuvir and ledipasvir), morphine, sirolimus (a transplant drug), and any medication metabolized by the CYP2B6 enzyme or glucuronidation pathways. No interactions are documented for any ingredients we could not check — but that doesn't mean none exist.
The bottom line
Scorecard at a glanceFormula with limited ingredient disclosure with no established evidence rating for its marketed use. Moderate medication interactions have been identified, and safety information is well characterized.
Milk thistle may help with type 2 diabetes blood sugar control, but it interacts with many medications — especially blood thinners, diabetes drugs, antivirals, and transplant drugs. If you take any prescription medication, check it against this product before starting.
Talk to your pharmacist or doctor about whether it's right for you.
Educational only — not medical advice; always confirm with your pharmacist. Our editorial policy · How we use AI
Assessment coverage: 1 of 1 active ingredient matched to our full ingredient reviews (monographs). Based on the product label dated Jun 24, 2020.
This Scorecard evaluates available label information, ingredient evidence, and known medication-safety considerations. It does not independently verify product identity, purity, potency, contamination, or manufacturing quality. How these ratings are computed
General information
Key facts about Milk Thistle, straight from the product label.
| Brand | Higher Nature |
|---|---|
| Net contents | 30 Hard Capsule(s) |
| Market status | On market |
| Date entered into DSLD | Jun 24, 2020 |
| DSLD ID | 224717 |
| Product type | Botanical |
| Supplement form | Capsule |
| Dietary claims / uses | All Other, Structure/Function |
| Intended target group(s) | Adult (18 - 50 Years), Women (not pregnant or lactating), Seniors/Mature (>50 Years) |
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.
Supplement Facts
The label details for Milk Thistle by Higher Nature, sourced from the NIH Dietary Supplement Label Database.
Supplement Facts
| Ingredient | Amount | % DV |
|---|---|---|
| Milk Thistle fruits (Silybum marianum (L.) Gaetn.) standardised extract | 0 NP | -- |
| Milk Thistle | 0 NP | -- |
Other ingredients: Acetone
Tap any ingredient to jump to its full detail below.
These statements are the manufacturer’s wording, reproduced from the product label — the label is saying it, not HelloPharmacist. We don’t verify or endorse them.
Formulation
A traditional herbal medicinal product used to relieve the symptoms associated with occasional over indulgence of drink and food, based on traditional use only.
Traditionally used for: Over-indulgence Indigestion Upset stomach
THR 23056/0010 THR certification mark
Formula
Milk Thistle standardised fruit extract
Suggested/Recommended/Usage/Directions
Dosage: For oral use. Adults and the elderly. Take 1 capsule up to twice daily. The capsules should be swallowed whole with some water or other liquid. The capsules should not be chewed.
Precautions
Warning: Do not exceed stated dose.
Do not use if you are: Under 18 years Pregnant or breastfeeding Allergic to any of the ingredients
Do not use if you are: Under 18 years Pregnant or breastfeeding Allergic to any of the ingredients
Do not use if you are: Under 18 years Pregnant or breastfeeding Allergic to any of the ingredients
Keep out of sight and reach of children
Please read the enclosed Patient Information Leaflet carefully before taking these capsules.
Do not use if you are allergic to Milk Thistle or other members of the daisy (Asteraceae/Compositae) family.
Storage
Storage: Do not store above 25 degrees C. Store in the original packaging.
General Statements
Expiry date: see base
Is this label outdated? Report a formula or label change and our pharmacy team will review it.
Milk Thistle by Higher Nature label
The label scan from the NIH Dietary Supplement Label Database. Tap to enlarge.
Label images are published by the NIH Dietary Supplement Label Database for the version of this product on file. Always read your actual product label.
View the full label (PDF)The Ingredients in Milk Thistle by Higher Nature
This is the 1 active ingredient this product is made of. Select it to open its full monograph.
Serving size1 Capsule(s) Dosage formCapsule Amounts shown are per serving.
Milk Thistle fruits (Silybum marianum (L.) Gaetn.) standardised extract
Interacts with954 drugs
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....
Milk Thistle fruits (Silybum marianum (L.) Gaetn.) standardised extract monograph & interactionsOther (inactive) ingredients: Acetone. These complete the product’s ingredient list but are not active constituents.
Milk Thistle by Higher Nature Drug Interactions
HelloPharmacist Interaction Report
Higher Nature's Milk Thistle contains one active ingredient — milk thistle extract — and it does interact with a number of medications.
The most serious concern is with blood thinners like warfarin (Coumadin): a case report showed that milk thistle increased warfarin's effects enough to raise bleeding risk, so your INR (a measure of blood thickness) needs monitoring if you're on it.
Read the full breakdown — every affected drug type, severity by severity
Milk thistle also affects how your body processes several other drug types. It may increase blood sugar-lowering effects with antidiabetes drugs, raising the risk of low blood sugar (hypoglycemia).
It can slow the clearance of drugs processed through glucuronidation (a major liver pathway), potentially raising their levels. It may affect morphine levels — either increasing or decreasing them — and might decrease the effectiveness of sofosbuvir (Sovaldi), an antiviral.
Additionally, it theoretically inhibits CYP2B6, an enzyme that breaks down certain medications, and may reduce the clearance of sirolimus (Rapamune), a transplant immunosuppressant. It may also affect ledipasvir, an antiviral for hepatitis C.
Altogether, these interactions span 940 individual medications. Before you start milk thistle, run your exact medications through the checker below — especially if you take blood thinners, diabetes drugs, antivirals, morphine, or any transplant medication.
Check your own medications below · Editorial policy · How we use AI
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Ask about interactions with your drugs in plain English — “Can I take it with lisinopril?” — and we find you the answer in seconds, ingredient by ingredient.
Go to the checkerIngredients driving the most interactions
Individual Drug Interactions
The ingredients in Milk Thistle interact with 954 drugs. Click any drug to see the details.
1 of the 1 ingredient in Milk Thistle interact with drugs. Each result below shows which ingredient is responsible. Milk Thistle fruits (Silybum marianum (L.) Gaetn.) standardised extract
Ado-trastuzumab EmtansineKadcyla
How Ado-trastuzumab Emtansine interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Ado-trastuzumab Emtansine interactionAbemaciclibVerzenio
How Abemaciclib interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Abemaciclib interactionAbiraterone
How Abiraterone interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Abiraterone interactionAbiraterone AcetateYonsa, Zytiga
How Abiraterone Acetate interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Abiraterone Acetate interactionAbrocitinibCibinqo
How Abrocitinib interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 2c9 (cyp2c9) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
Read the full Milk Thistle + Abrocitinib interactionAcalabrutinibCalquence
How Acalabrutinib interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates, P-glycoprotein Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Acalabrutinib interactionAdagrasibKrazati
How Adagrasib interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Adagrasib interactionAerosphere Budesonide, Formoterol Fumarate, GlycopyrrolateBreztri
How Aerosphere Budesonide, Formoterol Fumarate, Glycopyrrolate interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 2c9 (cyp2c9) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
Read the full Milk Thistle + Aerosphere Budesonide, Formoterol Fumarate, Glycopyrrolate interactionAfatinib DimaleateGilotrif
How Afatinib Dimaleate interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleP-glycoprotein Substrates Minor
Interaction Summary
Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates.
Read the full Milk Thistle + Afatinib Dimaleate interactionAgomelatineValdoxan
How Agomelatine interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 2c9 (cyp2c9) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
Read the full Milk Thistle + Agomelatine interactionAlfentanilAlfenta
How Alfentanil interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Alfentanil interactionAlfuzosinUroxatral
How Alfuzosin interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Alfuzosin interactionAliskirenTekturna
How Aliskiren interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Aliskiren interactionAlmotriptanAlmogran, Axert
How Almotriptan interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Almotriptan interactionAlpelisibPiqray
How Alpelisib interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Alpelisib interactionAlprazolamNiravam, Xanax
How Alprazolam interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Alprazolam interactionAlvimopanEntereg
How Alvimopan interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleP-glycoprotein Substrates Minor
Interaction Summary
Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates.
Read the full Milk Thistle + Alvimopan interactionAmbrisentanLetairis, Volibris
How Ambrisentan interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleP-glycoprotein Substrates, Cytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates.
Read the full Milk Thistle + Ambrisentan interactionAmiodaroneCordarone, Pacerone
How Amiodarone interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Amiodarone interactionAmitriptylineElavil
How Amitriptyline interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates, Cytochrome P450 2c9 (cyp2c9) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Amitriptyline interactionAmitriptyline, ChlordiazepoxideLimbitrol DS
How Amitriptyline, Chlordiazepoxide interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 2c9 (cyp2c9) Substrates, Cytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
Read the full Milk Thistle + Amitriptyline, Chlordiazepoxide interactionAmitriptyline, PerphenazineEtrafon, Etrafon-A, Etrafon-Forte, Triavil
How Amitriptyline, Perphenazine interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 2c9 (cyp2c9) Substrates, Cytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
Read the full Milk Thistle + Amitriptyline, Perphenazine interactionAmlodipineNorliqva
How Amlodipine interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Amlodipine interactionAmlodipine BenzoateKaterzia
How Amlodipine Benzoate interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Amlodipine Benzoate interactionAmlodipine BesilateIstin
How Amlodipine Besilate interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Amlodipine Besilate interactionAmlodipine BesylateNorvasc
How Amlodipine Besylate interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Amlodipine Besylate interactionAmlodipine Besylate, BenazeprilLotrel
How Amlodipine Besylate, Benazepril interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Amlodipine Besylate, Benazepril interactionAmlodipine, CelecoxibConsensi
How Amlodipine, Celecoxib interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 2c9 (cyp2c9) Substrates, Cytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
Read the full Milk Thistle + Amlodipine, Celecoxib interactionAmoxicillin, Omeprazole Magnesium, RifabutinTalicia
How Amoxicillin, Omeprazole Magnesium, Rifabutin interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleCytochrome P450 3a4 (cyp3a4) Substrates, Cytochrome P450 2c9 (cyp2c9) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle + Amoxicillin, Omeprazole Magnesium, Rifabutin interactionAmphotericin, TetracyclineMysteclin-F
How Amphotericin, Tetracycline interacts with Milk Thistle — through 1 ingredient. Tap an ingredient for the detail:
Milk ThistleP-glycoprotein Substrates Minor
Interaction Summary
Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates.
Read the full Milk Thistle + Amphotericin, Tetracycline interactionEach ingredient & the kinds of drugs it affects
For each ingredient in Milk Thistle with known interactions, here are the types of medications it can affect. Open any type for the detail — or search your exact drug in the checker above.
Milk Thistle fruits (Silybum marianum (L.) Gaetn.) standardised extract
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Brand information
Manufacturer and brand details for Milk Thistle, from the product label.
Higher Nature
See all Higher Nature products- Name
- Higher Nature
- City
- Burwash Common
- State
- East Sussex
- ZipCode
- TN19 7LX
Milk Thistle by Higher Nature: Common Questions
Does Milk Thistle by Higher Nature interact with any medications?
How can one product interact with so many drugs?
Where does this information come from?
Can I take this if I'm pregnant?
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Does milk thistle really help with blood sugar?
What are the most common side effects?
Is milk thistle safe to take with other supplements?
Why does the label say 'acetone'?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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Label information is sourced from the NIH Dietary Supplement Label Database and reflects the product version on file; always read your actual product label. This page is for education only and is not a substitute for professional medical advice. Confirm with your pharmacist or doctor before combining supplements and medications.
The Full Monographs Behind Milk Thistle’s Ingredients
Every ingredient we hold a full HelloPharmacist monograph for — uses, evidence, safety, and the complete interaction list.
Sources & How We Checked
Milk Thistle's label data comes from the NIH Dietary Supplement Label Database; the ingredient interaction data is from the Natural Medicines database, reviewed by our pharmacists.
- NIH Dietary Supplement Label Database (DSLD) — The official product label on file for this supplement.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference behind the ingredient interaction data.
Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.
The 69 references behind this product’s interaction data
Every citation that drives the interaction findings for this product’s ingredients, from the evidence-graded Natural Medicines (TRC Healthcare) database. Open an ingredient to browse its citations — links open the study on PubMed or the publisher’s site.
Milk Thistle 69 references
- Ferenci P, Dragosics B, Dittrich H, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 1989;9:105-13. PubMed
- Anon. Milk thistle: Effects on liver disease and cirrhosis and clinical adverse effects. Summary, Evidence Report/Technology Assessment: Number 21, September 2000. Agency for Healthcare Research and Quality, Rockville, MD. Available at: http://www.ahrq.g
- Beckmann-Knopp S, Rietbrock S, Weyhenmeyer R, et al. Inhibitory effects of silibinin on cytochrome P-450 enzymes in human liver microsomes. Pharmacol Toxicol 2000;86:250-6. PubMed
- Venkataramanan R, Ramachandran V, Komoroski BJ, et al. Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab Dispos 2000;28:1270-3. DOI
- Kim DH, Jin YH, Park JB, Kobashi K. Silymarin and its components are inhibitors of beta-glucuronidase. Biol Pharm Bull 1994;17:443-5. PubMed
- Pares A, Planas R, Torres M, et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 1998;28:615-21. PubMed
- Piscitelli SC, Formentini E, Burstein AH, et al. Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy 2002;22:551-6. PubMed
- Boerth J, Strong KM. The clinical utility of milk thistle (Silybum marianum) in cirrhosis of the liver. J Herb Pharmacother 2002;2:11-7.
- Tanamly MD, Tadros F, Labeeb S, et al. Randomised double-blinded trial evaluating silymarin for chronic hepatitis C in an Egyptian village: study description and 12-month results. Dig Liver Dis 2004;36:752-9. PubMed
- Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther 2004;76:428-40. .
- Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother Res 2006;20;1036-9.
- Deng JW, Shon JH, Shin HJ, et al. Effect of silymarin supplement on the pharmacokinetics of rosuvastatin. Pharm Res 2008;25:1807-14. PubMed
- Kim CS, Choi SJ, Park CY, et al. Effects of silybinin on the pharmacokinetics of tamoxifen and its active metabolite, 4-hydroxytamoxifen in rats. Anticancer Res 2010;30:79-85.
- Sridar C, Goosen TC, Kent UM, et al. Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 2004;32:587-94. PubMed
- van Erp NP, Baker SD, Zhao M, et al. Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clin Cancer Res 2005;11:7800-6.
- Budzinski JW, Trudeau VL, Drouin CE, et al. Modulation of human cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) in Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal products. Can J Physiol Pharmacol 2007;85:966-78.
- Doehmer J, Weiss G, McGregor GP, Appel K. Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome-P450 activities. Toxicol In Vitro 2011;25:21-7. PubMed
- Jiao Z, Shi XJ, Li ZD, et al. Population pharmacokinetics of sirolimus in de novo Chinese adult renal transplant patients. Br.J.Clin.Pharmacol. 2009;68(1):47-60.
- Gurley, B. J., Barone, G. W., Williams, D. K., Carrier, J., Breen, P., Yates, C. R., Song, P. F., Hubbard, M. A., Tong, Y., and Cheboyina, S. Effect of milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa) supplementation on digoxin phar
- Allain, H., Schuck, S., Lebreton, S., Strenge-Hesse, A., Braun, W., Gandon, J. M., and Brissot, P. Aminotransferase levels and silymarin in de novo tacrine-treated patients with Alzheimer's disease. Dement.Geriatr.Cogn Disord. 1999;10(3):181-185. PubMed
- Angulo, P., Patel, T., Jorgensen, R. A., Therneau, T. M., and Lindor, K. D. Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid. Hepatology 2000;32(5):897-900. PubMed
- Bean, P. The use of alternative medicine in the treatment of hepatitis C. Am.Clin.Lab 2002;21(4):19-21.
- Hussain, S. A. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. J.Med.Food 2007;10(3):543-547. PubMed
- El-Kamary, S. S., Shardell, M. D., Abdel-Hamid, M., Ismail, S., El-Ateek, M., Metwally, M., Mikhail, N., Hashem, M., Mousa, A., Aboul-Fotouh, A., El-Kassas, M., Esmat, G., and Strickland, G. T. A randomized controlled trial to assess the safety and effic
- Gharagozloo, M., Moayedi, B., Zakerinia, M., Hamidi, M., Karimi, M., Maracy, M., and Amirghofran, Z. Combined therapy of silymarin and desferrioxamine in patients with beta-thalassemia major: a randomized double-blind clinical trial. Fundam.Clin.Pharmaco
- Ladas, E. J., Kroll, D. J., Oberlies, N. H., Cheng, B., Ndao, D. H., Rheingold, S. R., and Kelly, K. M. A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL PubMed
- Sayyah, M., Boostani, H., Pakseresht, S., and Malayeri, A. Comparison of Silybum marianum (L.) Gaertn. with fluoxetine in the treatment of Obsessive-Compulsive Disorder. Prog.Neuropsychopharmacol.Biol.Psychiatry 3-17-2010;34(2):362-365. PubMed
- Flaig, T. W., Glode, M., Gustafson, D., van, Bokhoven A., Tao, Y., Wilson, S., Su, L. J., Li, Y., Harrison, G., Agarwal, R., Crawford, E. D., Lucia, M. S., and Pollak, M. A study of high-dose oral silybin-phytosome followed by prostatectomy in patients w
- Ramirez-Santos, A., Perez-Bustillo, A., Gonzalez-Sixto, B., Suarez-Amor, O., and Rodriguez-Prieto, M. A. [Acute generalized exanthematous pustulosis due to milk thistle (Silybum marianum) tea]. Actas Dermosifiliogr. 2011;102(9):744-745. DOI
- Loguercio C, Andreone P, Brisc C, et al. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Free Radic Biol Med 2012;52(9):1658-65. PubMed
- Yakoot, M. and Salem, A. Spirulina platensis versus silymarin in the treatment of chronic hepatitis C virus infection. A pilot randomized, comparative clinical trial. BMC.Gastroenterol. 2012;12:32. PubMed
- Fallahzadeh, M. K., Dormanesh, B., Sagheb, M. M., Roozbeh, J., Vessal, G., Pakfetrat, M., Daneshbod, Y., Kamali-Sarvestani, E., and Lankarani, K. B. Effect of addition of silymarin to renin-angiotensin system inhibitors on proteinuria in type 2 diabetic
- Fried, M. W., Navarro, V. J., Afdhal, N., Belle, S. H., Wahed, A. S., Hawke, R. L., Doo, E., Meyers, C. M., and Reddy, K. R. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon t
- Fallah Huseini, H., Larijani, B., Fakhrzadeh, H., Rajabi Pour, B., Akhondzadeh, S., Toliat, T., and Heshmat, R. The clinical trial of Silybum Marianum seed extract (Silymarin) on type II diabetic patients with hyperlipidemia. Iran J.Diabetes Lipid Disord
- Mironets VI, Krasovskaia EA, and Polishchuk II. [A case of urticaria during Carsil treatment]. Vrach Delo 1990;7:86-87.
- Velussi M, Cernigoi AM, Viezzoli L, and et al. Silymarin reduces hyperinsulinemia, malondialdehyde levels, and daily insulin need in cirrhotic diabetic patients. Curr Ther Res 1993;53(5):533-545. DOI
- Marcelli R, Bizzoni P, Conte D, and et al. Randomized controlled study of the efficacy and tolerability of a short course of IdB 1016 in the treatment of chronic persistent hepatitis. Eur Bull Drug Res 1992;1(3):131-135.
- Vailati A, Aristia L, Sozze E, and et al. Randomized open study of the dose-effect relationship of a short course of IdB 1016 in patients with viral or alcoholic hepatitis. Fitoterapia 1993;64(3):219-228.
- Marena C and Lampertico M. Preliminary clinical development of silipide: a new complex of silybin in toxic liver disorders. Planta Med 1991;57(2):A124-A125. DOI
- Grungreiff K, Albrecht M, and Strenge-Hesse A. Benefit of medicinal liver therapy in general practice. Med Welt 1995;46:222-227.
- Frerick F, Kuhn U, and Strenge-Hesse A. Silymarin--ein Phytopharmakon zur Behandlung toxischen Leberschaden: Anwendungsbeobachtung bei 2169 Patienten. Kassenarzt 1990;33:36-41.
- Schuppan D, Strosser W, Burkard G, and et al. Influence of Legalon(TM) 140 on the metabolism of collagen in patients with chronic liver disease--Review by measurement of PIIINP-values. Zeitschrift fur Allgemeinmedizin 1998;74:577-584.
- Studlar M. Die Behandlung chronischer Leberkrankungen mit Silymarin und B-Vitaminen. Therapiewoche 1985;35:3375-3378.
- Anon. Adverse reaction: milk thistle-associated toxicity. Nurse Drug Alert 1999;23(7):51.
- Gufford BT, Chen G, Vergara AG, et al. Milk Thistle Constituents Inhibit Raloxifene Intestinal Glucuronidation: A Potential Clinically Relevant Natural Product-Drug Interaction. Drug Metab Dispos. 2015;43(9):1353-9. PubMed
- El-Shitany NA, Hegazy S, El-Desoky K. Evidences for antiosteoporotic and selective estrogen receptor modulator activity of silymarin compared with ethinylestradiol in ovariectomized rats. Phytomedicine. 2010;17(2):116-25. PubMed
- Seidlová-Wuttke D, Becker T, Christoffel V, Jarry H, Wuttke W. Silymarin is a selective estrogen receptor beta (ERbeta) agonist and has estrogenic effects in the metaphysis of the femur but no or antiestrogenic effects in the uterus of ovariectomized (ovx
- Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
- Derosa G, Romano D, D'Angelo A, Maffioli P. Berberis aristata/Silybum marianum fixed combination (Berberol(®)) effects on lipid profile in dyslipidemic patients intolerant to statins at high dosages: a randomized, placebo-controlled, clinical trial. Phyto PubMed
- Luangchosiri C, Thakkinstian A, Chitphuk S, Stitchantrakul W, Petraksa S, Sobhonslidsuk A. A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury. BMC Complement Altern Med. 2015;15:334. PubMed
- Kawaguchi-Suzuki M, Frye RF, Zhu HJ, et al. The effects of milk thistle (Silybum marianum) on human cytochrome P450 activity. Drug Metab Dispos. 2014;42(10):1611-6. PubMed
- Rastegarpanah M, Malekzadeh R, Vahedi H, et al. A randomized, double blinded, placebo-controlled clinical trial of silymarin in ulcerative colitis. Chin J Integr Med. 2015;21(12):902-6. PubMed
- Di Pierro F, Bellone I, Rapacioli G, Putignano P. Clinical role of a fixed combination of standardized Berberis aristata and Silybum marianum extracts in diabetic and hypercholesterolemic patients intolerant to statins. Diabetes Metab Syndr Obes. 2015;8:8 PubMed
- Di Pierro F, Villanova N, Agostini F, Marzocchi R, Soverini V, Marchesini G. Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients with suboptimal glycemic control. Diabetes Metab Syndr Obes. 2012;5:213-7. PubMed
- Guarino G, Strollo F, Carbone L, et al. Bioimpedance analysis, metabolic effects and safety of the association Berberis aristata/Bilybum marianum: a 52-week double-blind, placebo-controlled study in obese patients with type 2 diabetes. J Biol Regul Homeos
- Ebrahimpour-Koujan S, Gargari BP, Mobasseri M, Valizadeh H, Asghari-Jafarabadi M. Lower glycemic indices and lipid profile among type 2 diabetes mellitus patients who received novel dose of Silybum marianum (L.) Gaertn. (silymarin) extract supplement: A T
- Lash DB, Ward S. CYP2C9-mediated warfarin and milk thistle interaction. J Clin Pharm Ther. 2019. PubMed
- Malekshah RE, Khaleghian A. Influence of Silybum marianum on morphine addicted rats, biochemical parameters and molecular simulation studies on µ-opioid receptor. Drug Res (Stuttg). 2019;69(11):630-638. PubMed
- Soleymani S, Ayati MH, Mansourzadeh MJ, Namazi N, Zargaran A. The effects of Silymarin on the features of cardiometabolic syndrome in adults: A systematic review and meta-analysis. Phytother Res. 2022 Jan 11. doi: 10.1002/ptr.7364. PubMed
- Gamissans M, Expósito-Serrano V, López-Llunell C, Valdivieso L, Garbayo-Salmons P. Bullous pemphigoid triggered by Silybum marianum: an unexpected side effect of an herbal remedy. Int J Dermatol. 2021 Aug 7. doi: 10.1111/ijd.15822. PubMed
- Aboras SI, Korany MA, El-Yazbi AF, Ragab MAA, Abdine HH. In-depth investigation of the Silymarin effect on the pharmacokinetic parameters of sofosbuvir, GS-331007 and ledipasvir in rat plasma using LC-MS. Biomed Chromatogr 2022;36(9):e5427. PubMed
- Wattanakrai P, Nimmannitya K. A Randomized, Double-Blind, Split-Face Study of Topical Silymarin vs 2% Hydroquinone Cream in Melasmas. J Drugs Dermatol 2022;21(12):1304-1310. PubMed
- Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178. PubMed
- Zhang W, Zhang Y, Wen C, Jiang X, Wang L. In vitro Assessment of the Effects of Silybin on CYP2B6-mediated Metabolism. Planta Med 2023. PubMed
- Bechtold BJ, Lynch KD, Oyanna VO, et al. Rifampin- and Silymarin-Mediated Pharmacokinetic Interactions of Exogenous and Endogenous Substrates in a Transgenic OATP1B Mouse Model. Mol Pharm 2024;21(5):2284-2297. PubMed
- Mohammadi S, Asbaghi O, Afrisham R, et al. Impacts of Supplementation with Silymarin on Cardiovascular Risk Factors: A Systematic Review and Dose-Response Meta-Analysis. Antioxidants (Basel) 2024;13(4):390. PubMed
- Rustamzadeh A, Sadigh N, Vahabi Z, et al. Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer's patients: A double-blind placebo-controlled randomized clinical trial. IBRO Neurosci Rep 2024;17:108-121. PubMed
- Fatemi Shandiz A, Karimi G, Dayyani M, Hosseini S, Elyasi S. Evaluation of oral silymarin formulation efficacy in prevention of doxorubicin induced hepatotoxicity in patients with non-metastatic breast cancer. J Oncol Pharm Pract 2024. PubMed
- Duan X, Bai W, Hu J, et al. Inhibitory effect of flavonoids on multidrug and toxin extrusion protein 1 function: Implications for food/herb-drug interaction and drug-induced kidney injury. J Appl Toxicol 2024;44(9):1388-1402. PubMed
Parts of this content are provided by the Therapeutic Research Center, LLC.
DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.
© 2021 Therapeutic Research Center, LLC