Milk Thistle Extract Ingredients & Drug Interactions
What is this page for?
First and foremost: checking Milk Thistle Extract 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 Extract is a dietary supplement by Nature's Answer 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 seed extract. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.
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HelloPharmacist Scorecard of Milk Thistle Extract by Nature's Answer
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
Full disclosure
This product contains one active ingredient: milk thistle seed extract. Milk thistle has been studied for liver health and blood sugar control, and its active compounds — particularly silybin — are what researchers believe drive its effects.
The liquid form also contains purified water, vegetable glycerin, and alcohol as inactive ingredients.
Does it work?
Insufficient evidence
Milk thistle is possibly effective for type 2 diabetes based on clinical evidence that it can lower blood sugar and HbA1c levels. For acne, alcohol-related liver disease, hay fever, gambling disorder, and poisoning from Amanita mushrooms, the evidence we hold is insufficient to rate it — meaning the studies are either too small, too few, or their results are unclear.
How safe is it?
Well-documented data
Milk thistle is generally well tolerated in most adults. The most common side effects are mild gut symptoms — bloating, diarrhea, indigestion, gas, and nausea — but they don't typically happen more often than with a placebo.
Rarely, allergic reactions including anaphylaxis have been reported. Some people have also reported headache, dizziness, and sleep problems.
There isn't enough reliable safety data to recommend it during pregnancy, so it's best avoided then. During breastfeeding, safety hasn't been well studied, so caution is warranted — talk with your doctor or pharmacist for personalized advice.
Meds to double-check
Moderate interaction found
Double-check this product with your doctor or pharmacist before taking it if you're on a blood thinner like warfarin, a diabetes medication, ledipasvir (for hepatitis C), the immunosuppressant sirolimus, morphine or other opioids, sofosbuvir, or any drug that your liver breaks down using the CYP2B6 enzyme or glucuronidation pathways. All of these are Moderate-severity concerns.
The bottom line
Scorecard at a glanceFully disclosed formula with insufficient evidence for its stated purpose. Moderate medication interactions have been identified, and safety information is well characterized.
Milk thistle may be worth considering if you have type 2 diabetes and want to explore a herbal approach alongside your regular care — but it can lower blood sugar on its own, so you'll need to coordinate with your doctor to avoid lows. It's not right for anyone taking a blood thinner, ledipasvir, sirolimus, or morphine without checking first.
Before you start, go over your full medication list with your doctor or pharmacist, since milk thistle affects how your liver processes many drugs.
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 16, 2022.
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 Extract, straight from the product label.
| Brand | Nature's Answer |
|---|---|
| Barcode (UPC) | 083000004049 |
| Net contents | 1 fl. Oz.; 30 mL |
| Market status | On market |
| Date entered into DSLD | Jun 16, 2022 |
| DSLD ID | 264082 |
| Product type | Botanical |
| Supplement form | Liquid |
| Dietary claims / uses | All Other, Structure/Function |
| Intended target group(s) | Adult (18 - 50 Years), Kosher, Women (not pregnant or lactating) |
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 Extract by Nature's Answer, sourced from the NIH Dietary Supplement Label Database.
Supplement Facts
| Ingredient | Amount | % DV |
|---|---|---|
| Milk Thistle seed extract | 210 mg | -- |
Other ingredients: purified Water, Vegetable Glycerin, Alcohol
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.
FDA Disclaimer Statement
This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease.
Seals/Symbols
K Parve (Kosher)
Bio-Chelated Cold Extraction Process
Formula
K Parve (Kosher)
Silybum marianum Made from 2,000mg Milk Thistle Seeds
Low Alcohol
Brand IP Statement(s)
Nature's Answer Since 1972
Discover Nature's Answer
Copyright 2019 Nature's Answer
Formulation
Promotes healthy liver function
12-15% Certified Organic Alcohol.
Our alcohol extracts are produced using our cold Bio-Chelated proprietary extraction process, yielding a Holistically Balanced Advanced Botanical Fingerprint extract in the same synergistic ratios as in the plant.
Absolutely no preservatives
FDA Statement of Identity
Herbal Supplement
Suggested/Recommended/Usage/Directions
Suggested use: As a dietary supplement, take 2 mL (56 drops) three (3) times a day in a small amount of water. Shake well.
Precautions
Keep out of reach of children.
Warning: Do not use if pregnant or nursing.
Do not use if safety seal is damaged or missing.
Storage
Store in a cool, dry place.
Is this label outdated? Report a formula or label change and our pharmacy team will review it.
Milk Thistle Extract by Nature's Answer 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 Extract by Nature's Answer
This is the 1 active ingredient this product is made of. Select it to open its full monograph.
Serving size2 mL Dosage formLiquid Servings per container15 Amounts shown are per serving.
Milk Thistle seed 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 seed extract monograph & interactionsOther (inactive) ingredients: Purified Water, Vegetable Glycerin, Alcohol. These complete the product’s ingredient list but are not active constituents.
Milk Thistle Extract by Nature's Answer Drug Interactions
HelloPharmacist Interaction Report
Nature's Answer Milk Thistle Extract contains milk thistle seed extract, which has documented interactions with a number of medications.
The most serious concern is a Moderate-severity interaction with blood thinners like warfarin (Coumadin) — milk thistle may increase their effects and raise your bleeding risk. One case report showed a patient's clotting measure (INR) jump significantly after starting a product containing milk thistle.
Read the full breakdown — every affected drug type, severity by severity
Milk thistle also interacts with diabetes drugs, the hepatitis C medication ledipasvir, the immunosuppressant sirolimus, morphine and other opioids, and drugs that are cleared from your body by glucuronidation — all at Moderate severity. It can lower blood sugar on its own, which adds to the risk if you're already taking diabetes medication.
For ledipasvir and sirolimus, milk thistle may raise their blood levels and effects. It may also affect how your body metabolizes sofosbuvir (Sovaldi).
Additionally, milk thistle may interfere with CYP2B6 substrates — a group of drugs your liver processes using this enzyme.
Altogether, these interactions span 955 individual medications. Check your exact prescriptions with the tool on this page before you start, especially if you take a blood thinner, diabetes medication, or any drug metabolized by your liver.
Check your own medications below · Editorial policy · How we use AI
Want to check YOUR meds against Milk Thistle Extract?
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 Extract interact with 954 drugs. Click any drug to see the details.
1 of the 1 ingredient in Milk Thistle Extract interact with drugs. Each result below shows which ingredient is responsible. Milk Thistle seed extract
Ado-trastuzumab EmtansineKadcyla
How Ado-trastuzumab Emtansine interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Ado-trastuzumab Emtansine interactionAbemaciclibVerzenio
How Abemaciclib interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Abemaciclib interactionAbiraterone
How Abiraterone interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Abiraterone interactionAbiraterone AcetateYonsa, Zytiga
How Abiraterone Acetate interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Abiraterone Acetate interactionAbrocitinibCibinqo
How Abrocitinib interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 2c9 (cyp2c9) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
Read the full Milk Thistle Seed Extract + Abrocitinib interactionAcalabrutinibCalquence
How Acalabrutinib interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome 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 Seed Extract + Acalabrutinib interactionAdagrasibKrazati
How Adagrasib interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Adagrasib interactionAerosphere Budesonide, Formoterol Fumarate, GlycopyrrolateBreztri
How Aerosphere Budesonide, Formoterol Fumarate, Glycopyrrolate interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 2c9 (cyp2c9) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
Read the full Milk Thistle Seed Extract + Aerosphere Budesonide, Formoterol Fumarate, Glycopyrrolate interactionAfatinib DimaleateGilotrif
How Afatinib Dimaleate interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractP-glycoprotein Substrates Minor
Interaction Summary
Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates.
Read the full Milk Thistle Seed Extract + Afatinib Dimaleate interactionAgomelatineValdoxan
How Agomelatine interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 2c9 (cyp2c9) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
Read the full Milk Thistle Seed Extract + Agomelatine interactionAlfentanilAlfenta
How Alfentanil interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Alfentanil interactionAlfuzosinUroxatral
How Alfuzosin interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Alfuzosin interactionAliskirenTekturna
How Aliskiren interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Aliskiren interactionAlmotriptanAlmogran, Axert
How Almotriptan interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Almotriptan interactionAlpelisibPiqray
How Alpelisib interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Alpelisib interactionAlprazolamNiravam, Xanax
How Alprazolam interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Alprazolam interactionAlvimopanEntereg
How Alvimopan interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractP-glycoprotein Substrates Minor
Interaction Summary
Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates.
Read the full Milk Thistle Seed Extract + Alvimopan interactionAmbrisentanLetairis, Volibris
How Ambrisentan interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractP-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 Seed Extract + Ambrisentan interactionAmiodaroneCordarone, Pacerone
How Amiodarone interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Amiodarone interactionAmitriptylineElavil
How Amitriptyline interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome 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 Seed Extract + Amitriptyline interactionAmitriptyline, ChlordiazepoxideLimbitrol DS
How Amitriptyline, Chlordiazepoxide interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome 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 Seed Extract + Amitriptyline, Chlordiazepoxide interactionAmitriptyline, PerphenazineEtrafon, Etrafon-A, Etrafon-Forte, Triavil
How Amitriptyline, Perphenazine interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome 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 Seed Extract + Amitriptyline, Perphenazine interactionAmlodipineNorliqva
How Amlodipine interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Amlodipine interactionAmlodipine BenzoateKaterzia
How Amlodipine Benzoate interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Amlodipine Benzoate interactionAmlodipine BesilateIstin
How Amlodipine Besilate interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Amlodipine Besilate interactionAmlodipine BesylateNorvasc
How Amlodipine Besylate interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Amlodipine Besylate interactionAmlodipine Besylate, BenazeprilLotrel
How Amlodipine Besylate, Benazepril interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome P450 3a4 (cyp3a4) Substrates Minor
Interaction Summary
It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
Read the full Milk Thistle Seed Extract + Amlodipine Besylate, Benazepril interactionAmlodipine, CelecoxibConsensi
How Amlodipine, Celecoxib interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome 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 Seed Extract + Amlodipine, Celecoxib interactionAmoxicillin, Omeprazole Magnesium, RifabutinTalicia
How Amoxicillin, Omeprazole Magnesium, Rifabutin interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractCytochrome 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 Seed Extract + Amoxicillin, Omeprazole Magnesium, Rifabutin interactionAmphotericin, TetracyclineMysteclin-F
How Amphotericin, Tetracycline interacts with Milk Thistle Extract — through 1 ingredient. Tap an ingredient for the detail:
Milk Thistle Seed ExtractP-glycoprotein Substrates Minor
Interaction Summary
Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates.
Read the full Milk Thistle Seed Extract + Amphotericin, Tetracycline interactionEach ingredient & the kinds of drugs it affects
For each ingredient in Milk Thistle Extract 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 seed 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 Extract, from the product label.
Nature's Answer
See all Nature's Answer products- Name
- Nature's Answer
- Street Address
- 85 Commerce Drive
- City
- Hauppauge
- State
- NY
- ZipCode
- 11788
- Phone Number
- (800) 439-2324
- Web Address
- www.naturesanswer.com
Milk Thistle Extract by Nature's Answer: Common Questions
Does Milk Thistle Extract by Nature's Answer interact with any medications?
How can one product interact with so many drugs?
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Is milk thistle safe to take while breastfeeding?
What are the side effects of milk thistle?
Can milk thistle lower my blood sugar?
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The Full Monographs Behind Milk Thistle Extract’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 Extract'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
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- 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
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- 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
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- 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.
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- 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
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- 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.
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- 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
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- Lash DB, Ward S. CYP2C9-mediated warfarin and milk thistle interaction. J Clin Pharm Ther. 2019. PubMed
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- 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
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- 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
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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