Interactions on record — worth a quick check against your medications. Check your meds →
Dietary supplement

Liv-R Support Ingredients & Drug Interactions

by Highland Laboratories

Liv-R Support label
See full label image
Capsule Category: Other Combinations
Most serious interaction: Moderate
Clinical methodology reviewed by · Updated Sep 9, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Liv-R Support 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

The interaction bottom line Most serious interaction: Moderate

Liv-R Support is a dietary supplement by Highland Laboratories with 16 active ingredients. Its ingredients are commonly taken for morning sickness in pregnancy, premenstrual syndrome (pms), preventing or treating b6 deficiency.Based on those ingredients, 1,497 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are Oregon Grape, Curcumin C3 Complex, BioPerine. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Liv-R Support by Highland Laboratories

Ask about any prescription or over-the-counter medication and we check it for interactions with Liv-R Support by Highland Laboratories — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
Prefer a human? Send your question to our licensed pharmacists — free, answered by email within 24 hours.

HelloPharmacist Scorecard of Liv-R Support by Highland Laboratories

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.

From our pharmacy team — supplement deep dive

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Aug 13, 2026

What’s inside

Full disclosure
Ingredient Transparency · database check
Full

Every active ingredient lists its own amount on the label.

Why this rating?
  • The label discloses an exact amount for 16 of its 16 active ingredients.
  • “Choline” is listed as a grouped ingredient — the label gives one combined amount (600 mg) without saying how much of each component you get.

Liv-R Support contains 16 active ingredients. Vitamin B6 supports red blood cell formation and metabolism.

L-methionine is an amino acid. Inositol plays a role in cell signaling.

Dandelion root and leaf support digestive and liver function. Choline (as Choline Bitartrate) is essential for nerve and brain function.

BioPerine (black pepper extract) aids nutrient absorption. L-carnitine supports energy production.

Schisandra (Schizandra) is a traditional adaptogenic herb. Gotu Kola, Bromelain (a pineapple enzyme), Artichoke leaf extract, Oregon Grape root, Turmeric (Curcumin C3 Complex), Chromium, Milk Thistle standardized extract, and Boldo leaf round out the formula.

The capsules also contain inactive ingredients including vegetable cellulose, magnesium trisilicate, silica, magnesium stearate, and cellulose.

Does it work?

Moderate evidence
Evidence for Intended Use · database check
By FDA rules, dietary supplements can’t claim to treat, cure, or prevent disease — so labels speak in careful marketing language. We discern each product’s intended use from its name, label claims, and label statements, then grade the clinical evidence for that use. How these ratings are computed
Moderate

Some clinical evidence supports this product's ingredients for its stated purpose, but it isn't conclusive.

Why this rating?
  • The label markets this product for: liver health and support.
  • We looked for evidence on: Alcohol-related liver disease, Biliary disorders, hepatitis, cirrhosis, fatty liver disease.
  • The strongest evidence on file: Turmeric is rated "Possibly Effective" for Nonalcoholic fatty liver disease (NAFLD) (Natural Medicines).
  • Also on file: Milk Thistle is rated "Insufficient Reliable Evidence To Rate" for Alcohol-related liver disease, Hepatitis, Hepatitis B, Hepatitis C, and more.
  • Also on file: Inositol is rated "Insufficient Reliable Evidence To Rate" for Nonalcoholic fatty liver disease (NAFLD).

The evidence for these ingredients varies. Vitamin B6 is effective for sideroblastic anemia and vitamin B6 deficiency, and likely effective for elevated homocysteine (hyperhomocysteinemia); it's possibly effective for pregnancy-related nausea and vomiting.

L-methionine is possibly effective for neural tube birth defects. Inositol is possibly effective for polycystic ovary syndrome (PCOS) and metabolic syndrome.

Artichoke leaf is possibly effective for high cholesterol (hyperlipidemia) and indigestion (dyspepsia). Turmeric is possibly effective for depression, high cholesterol, and hay fever.

L-carnitine is possibly effective for high cholesterol, congestive heart failure, and angina. Chromium is possibly effective for diabetes.

Milk thistle is possibly effective for diabetes. For dandelion, gotu kola, bromelain, schisandra, Oregon grape, choline, and boldo, the data we hold shows insufficient reliable evidence or does not establish effectiveness for their listed uses.

The evidence, ingredient by ingredient Vitamin B6 Methionine Inositol Dandelion Choline Black Pepper L-carnitine Schisandra

How safe is it?

Well-documented data
Safety Information · database check
Well characterized

Adverse-effect, pregnancy, and general safety data are on file for most of these ingredients.

Why this rating?
  • We hold adverse-effect (side-effect) data for 16 of the 16 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 16 of 16.
  • General safety write-ups exist for 16 of 16.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most ingredients are generally well tolerated at standard doses. Vitamin B6 is safe at normal food and supplement amounts, but high doses over time can damage nerves (sensory neuropathy); common side effects include headache and nausea.

L-methionine is well tolerated in food amounts but high-dose supplements may cause dizziness, drowsiness, and low blood pressure (hypotension). Inositol typically causes only mild digestive effects (diarrhea, gas, nausea).

Dandelion is generally well tolerated but may cause diarrhea, heartburn, or stomach discomfort; allergic reactions including anaphylaxis are rare. Choline is safe in food amounts but high doses (over 3.5 grams daily) can cause fishy body odor and gastrointestinal upset.

Black pepper is well tolerated as a food spice. L-carnitine may cause abdominal cramps, diarrhea, nausea, and a fish-like body odor.

Schisandra is generally well tolerated short-term but may cause decreased appetite, heartburn, or hives. Gotu kola is generally well tolerated but rare cases of liver toxicity have been reported.

Bromelain is generally well tolerated but may cause diarrhea and flatulence. Artichoke may cause abdominal pain, diarrhea, or allergy.

Oregon grape applied topically may cause itching and burning. Turmeric is generally safe as a food but concentrated supplements have been linked to rare liver injury.

Chromium is usually well tolerated but may cause headaches or mood changes. Milk thistle is well tolerated but may cause mild digestive upset.

Boldo may cause nausea and vomiting, and its ascaridole content poses a liver toxicity risk.

Side effects, ingredient by ingredient Vitamin B6 Methionine Inositol Dandelion Choline Black Pepper L-carnitine Schisandra

Meds to double-check

Moderate interaction found
Known Interaction Concern · database check
Moderate identified

The most serious documented interaction for these ingredients is Moderate. Check your medications for a personalized result.

Why this rating?
  • 15 of the 16 matched ingredients can interact with medications — Milk Thistle, Inositol, Schisandra, Choline, Oregon Grape, among others.
  • The most serious interaction on file is rated Moderate.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; cancer treatments; diabetes medications; lithium; Parkinson's medications.
  • For scale: 1,498 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Check with your doctor or pharmacist before taking Liv-R Support if you take tacrolimus (especially serious — schisandra may increase levels dramatically). Also clear it if you take seizure medications (phenytoin or phenobarbital), blood thinners or antiplatelet drugs (warfarin, clopidogrel), antidiabetes medications, or heart/blood pressure drugs.

Several liver enzymes are affected (CYP2D6, CYP2C9, CYP3A4, CYP1A2, CYP2C19, CYP2B6), so any medication that relies on these for breakdown needs review. If you take lithium, ask first.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with some supporting evidence for its stated purpose. Moderate medication interactions have been identified, and safety information is well characterized.

Liv-R Support is a multi-ingredient formula aimed at liver support, containing herbs and nutrients with varying levels of evidence. Because this product contains 16 active ingredients with multiple documented interactions affecting 1,498 individual medications—most notably a serious interaction between schisandra and tacrolimus—it is critical to check your specific medications before starting.

If you take any prescription drugs, especially blood thinners, seizure medications, diabetes drugs, immunosuppressants, or heart medications, discuss this product with your doctor or pharmacist before use.

Educational only — not medical advice; always confirm with your pharmacist. Our editorial policy · How we use AI

Assessment coverage: 16 of 16 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Nov 20, 2017.

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

At a glance

General information

Key facts about Liv-R Support, straight from the product label.

Brand Highland Laboratories
Barcode (UPC) 768305115217
Net contents 120 Vegetarian Capsule(s)
Market status On market
Date entered into DSLD Nov 20, 2017
DSLD ID 79969
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other
Intended target group(s) Adult (18 - 50 Years), Gluten Free, Dairy Free, Sugar Free
From the label
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 Liv-R Support by Highland Laboratories, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
4 Vegetarian Capsule(s)
Maximum serving Sizes:
4 Vegetarian Capsule(s)
Servings per container
30
UPC/BARCODE
768305115217
IngredientAmount% DV
Vitamin B610 mg500%
L-Methionine300 mg--
Inositol300 mg--
Dandelion30 mg--
Choline Bitartrate1310 mg--
Choline600 mg--
BioPerine1 mg--
L-Carnitine500 mg--
Schizandra30 mg--
Gotu Kola25 mg--
Bromelain25 mg--
Artichoke30 mg--
Oregon Grape30 mg--
Curcumin C3 Complex30 mg--
Chromium100 mcg83%
Milk Thistle standardized extract50 mg--
Boldo30 mg--

Other ingredients: Vegetable Cellulose, Magnesium Trisilicate, Silica, Magnesium Stearate, Cellulose

Tap any ingredient to jump to its full detail below.

Label statements
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.
Formula

Milk Thistle, Boldo leaf, etc.

Curcumin C3 Complex is a standardized extract of Curcuma Longa which contains a minimum of 95% concentration of Curcumin, Bisdemethoxy curcumin, and Demethoxy curcumin.

FDA Statement of Identity

Dietary Supplement

Seals/Symbols

GMP Quality Assured Earth Friendly

General Statements

% Daily Value

Formulation

No corn, soy, yeast, gluten, milk & egg products, sugar, starch, or preservatives.

Suggested/Recommended/Usage/Directions

Two capsules, twice daily with meals, as a dietary supplement.

Brand IP Statement(s)

Curcumin C3 Complex and Bioperine are registered trademarks of Sabinsa Corporation.

General

PR 1152

Is this label outdated? Report a formula or label change and our pharmacy team will review it.

See for yourself

Liv-R Support by Highland Laboratories label

The label scan from the NIH Dietary Supplement Label Database. Tap to enlarge.

Liv-R Support label

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)
What’s inside

The Ingredients in Liv-R Support by Highland Laboratories

These are the 16 active ingredients this product is made of. Select any to open its full monograph.

Serving size4 Vegetarian Capsule(s) Dosage formCapsule Servings per container30 Amounts shown are per serving.

Most supplement products combine several ingredients, and a medication can interact with the product through any one of them. Each ingredient below shows whether it has known drug interactions.

Vitamin B6

Interacts with
210 drugs
10 mg per serving Form: Pyridoxine Hydrochloride

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is b...

Vitamin B6 monograph & interactions

L-Methionine

No known
interactions
300 mg per serving

Methionine is an essential amino acid that your body needs for protein building and many basic chemical reactions. Most people get enough from a norma...

L-Methionine monograph & interactions

Inositol

Interacts with
86 drugs
300 mg per serving

Inositol is a sugar alcohol made naturally in the body and found in many foods, and it is sold as a supplement (often myo-inositol) mainly for PCOS, m...

Inositol monograph & interactions

Dandelion

Interacts with
457 drugs
30 mg per serving

Dandelion is a common plant used in food and traditional medicine, often promoted as a natural 'water pill' and digestive aid. Human evidence for thes...

Dandelion monograph & interactions

Choline

Interacts with
16 drugs
600 mg per serving

Choline is an essential nutrient your body needs for liver function, brain health, and nerve signaling, and many people get enough from foods like egg...

Choline monograph & interactions

BioPerine

Interacts with
1,019 drugs
1 mg per serving

Black pepper is a common kitchen spice that is generally safe in the amounts used in food. Its extract, piperine, is mostly added to supplements to he...

BioPerine monograph & interactions

L-Carnitine

Interacts with
19 drugs
500 mg per serving Form: L-Carnitine Tartrate

L-carnitine is a compound your body makes naturally and also gets from foods like meat. It helps cells turn fat into energy, and supplements are most...

L-Carnitine monograph & interactions

Schizandra

Interacts with
803 drugs
30 mg per serving

Schisandra is a traditional Chinese medicine berry used as an adaptogen for stress, fatigue, and liver support. Human evidence is limited and most cla...

Schizandra monograph & interactions

Gotu Kola

Interacts with
579 drugs
25 mg per serving

Gotu kola is a traditional Ayurvedic and Asian herb that people use for wound healing, circulation, skin problems, and as a calming or memory-supporti...

Gotu Kola monograph & interactions

Bromelain

Interacts with
141 drugs
25 mg per serving Form: Ananas comosus

Bromelain is a group of protein-digesting enzymes from pineapple that people take mainly for inflammation, swelling, and sinus problems. Some early st...

Bromelain monograph & interactions

Artichoke

Interacts with
363 drugs
30 mg per serving

Artichoke leaf extract is a generally well-tolerated supplement that may have a mild cholesterol-lowering effect and is often used for indigestion, th...

Artichoke monograph & interactions

Oregon Grape

Interacts with
1,218 drugs
30 mg per serving

Oregon grape is a shrub whose root contains berberine and related compounds. The strongest (though still modest) evidence is for topical creams that m...

Oregon Grape monograph & interactions

Curcumin C3 Complex

Interacts with
1,133 drugs
30 mg per serving

Turmeric is a popular spice whose main active compounds, curcuminoids, are studied mostly for inflammation and joint pain. Some research is promising,...

Curcumin C3 Complex monograph & interactions

Chromium

Interacts with
178 drugs
100 mcg per serving Form: Chromium Picolinate

Chromium is an essential trace mineral involved in how the body handles sugar and fat. Some studies suggest it may modestly help blood sugar control i...

Chromium monograph & interactions

Milk Thistle standardized extract

Interacts with
954 drugs
50 mg per serving Form: Silymarin

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 standardized extract monograph & interactions

Boldo

Interacts with
482 drugs
30 mg per serving

Boldo is a South American shrub whose leaves are traditionally used for digestive and gallbladder complaints, but good human evidence is very limited....

Boldo monograph & interactions

Other (inactive) ingredients: Vegetable Cellulose, Magnesium Trisilicate, Silica, Magnesium Stearate, Cellulose. These complete the product’s ingredient list but are not active constituents.

Interaction report

Liv-R Support by Highland Laboratories Drug Interactions

Want to check YOUR meds against Liv-R Support?

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 checker
1,497Drugs
1,460 Moderate 37 Minor

Ingredients driving the most interactions

Oregon Grape 1,218
Curcumin C3 Complex 1,133
BioPerine 1,019
Milk Thistle standardized extract 954
Schizandra 803

Individual Drug Interactions

The ingredients in Liv-R Support interact with 1,497 drugs. Click any drug to see the details.

15 of the 16 ingredients in Liv-R Support interact with drugs. Each result below shows which ingredient is responsible. Oregon Grape Curcumin C3 Complex BioPerine Milk Thistle standardized extract Schizandra Gotu Kola Boldo Dandelion Artichoke Vitamin B6 Chromium Bromelain Inositol L-Carnitine Choline

Each ingredient & the kinds of drugs it affects

For each ingredient in Liv-R Support with known interactions, here are the types of medications they can affect. Open any type for the detail — or search your exact drug in the checker above.

Oregon Grape9 drug types · 1,218 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, Oregon grape might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
In vitro and in vivo research suggests that berberine, a constituent of Oregon grape, can inhibit platelet aggregation.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, Oregon grape might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Clinical research suggests that berberine, a constituent of Oregon grape, can lower blood glucose levels.

Likelihood Possible Evidence A
Antihypertensive Drugs

Theoretically, Oregon grape might increase the risk of hypotension when taken with antihypertensive drugs.
Animal research suggests that berberine, a constituent of Oregon grape, can have hypotensive effects. Also, an analysis of clinical evidence suggests that taking berberine in combination with amlodipine (Norvasc) can lower systolic and diastolic blood pressure when compared with taking amlodipine alone.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, Oregon grape might increase the sedative effects of CNS depressants.
Animal research suggests that berberine, a constituent of Oregon grape, can have sedative effects.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Theoretically, Oregon grape might increase the effects and adverse effects of cyclosporine.
Berberine, a constituent of Oregon grape, can reduce metabolism of cyclosporine and increase serum levels. It might inhibit cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporine.

Likelihood Possible Evidence D
Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP2C9.
Preliminary clinical evidence suggests that berberine, a constituent of Oregon grape, can inhibit cytochrome P450 2C9 (CYP2C9).

Likelihood Possible Evidence B
Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP2D6.
In vitro research and preliminary clinical evidence suggest that berberine, a constituent of Oregon grape, can inhibit cytochrome P450 2D6 (CYP2D6).

Likelihood Possible Evidence B
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP3A4.
In vitro research and preliminary clinical evidence suggest that berberine, a constituent of Oregon grape, moderately inhibits cytochrome P450 3A4 (CYP3A4).

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, Oregon grape might increase serum levels of drugs that are P-glycoprotein (P-gp) substrates.
In vitro research suggests that Oregon grape extracts inhibit P-gp efflux.

Likelihood Possible Evidence D
Oregon Grape full monograph & interactions

Curcumin C3 Complex24 drug types · 1,133 drugs

Alkylating Agents

Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
In vitro research suggests that curcumin, a constituent of turmeric, inhibits mechlorethamine-induced apoptosis of breast cancer cells by up to 70%. Also, animal research shows that curcumin inhibits cyclophosphamide-induced tumor regression. However, some in vitro research shows that curcumin does not affect the apoptosis capacity of etoposide. Also, other laboratory research suggests that curcumin might augment the cytotoxic effects of alkylating agents. Reasons for the discrepancies may relate to the dose of curcumin and the specific chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects. More evidence is needed to determine what effect, if any, turmeric might have on alkylating agents.

Likelihood Possible Evidence D
Amlodipine (Norvasc)

Taking turmeric with amlodipine may increase levels of amlodipine.
Animal research shows that giving amlodipine 1 mg/kg as a single dose following the use of turmeric extract 200 mg/kg daily for 2 weeks increases the maximum concentration and area under the curve by 53% and 56%, respectively, when compared with amlodipine alone. Additional animal research shows that taking amlodipine 1 mg/kg with a curcumin 2 mg/kg pretreatment for 10 days increases the maximum concentration and area under the curve by about 2-fold when compared with amlodipine alone.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Turmeric may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
Curcumin, a constituent of turmeric, has demonstrated antiplatelet effects in vitro. Furthermore, two case reports have found that taking turmeric along with warfarin or fluindione was associated with an increased international normalized ratio (INR). However, one clinical study in healthy volunteers shows that taking curcumin 500 mg daily for 3 weeks, alone or with aspirin 100 mg, does not increase antiplatelet effects or bleeding risk. It is possible that the dose of turmeric used in this study was too low to produce a notable effect.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, taking turmeric with antidiabetes drugs might increase the risk of hypoglycemia.
Animal research and case reports suggest that curcumin, a turmeric constituent, can reduce blood glucose levels in patients with diabetes. Furthermore, clinical research in adults with type 2 diabetes shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg decreased postprandial glucose levels for up to 24 hours when compared with glyburide alone, despite the lack of a significant pharmacokinetic interaction. Other clinical studies in patients with diabetes show that taking curcumin daily can reduce blood glucose levels when compared with placebo.

Likelihood Possible Evidence B
Antitumor Antibiotics

Turmeric has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
In vitro and animal research shows that curcumin, a constituent of turmeric, inhibits doxorubicin-induced apoptosis of breast cancer cells by up to 65%. However, curcumin does not seem to affect the apoptosis capacity of daunorubicin. In fact, some research shows that curcumin might augment the cytotoxic effects of antitumor antibiotics, increasing their effectiveness. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agent. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects. More evidence is needed to determine what effects, if any, antioxidants such as turmeric have on antitumor antibiotics.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Turmeric might increase or decrease levels of drugs metabolized by CYP3A4.
In vitro and animal research show that turmeric and its constituents curcumin and curcuminoids inhibit CYP3A4. Also, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking turmeric and cancer medications that are CYP3A4 substrates, including everolimus, ruxolitinib, ibrutinib, and palbociclib, and bortezomib. In another case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels after consuming turmeric powder at a dose of 15 or more spoonfuls daily for ten days prior. It was thought that turmeric increased levels of tacrolimus due to CYP3A4 inhibition.
Conversely, other in vitro research suggests that turmeric induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates. An animal model suggests that induction of CYP3A4 occurs after daily curcumin use for 1 week. However, the induction of CYP3A4 by turmeric has not been reported in humans.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, turmeric might increase the risk of liver damage when taken with hepatotoxic drugs.
There is concern that turmeric might cause hepatotoxicity, especially when highly bioavailable formulations are used in high doses.

Likelihood Possible Evidence D
Methotrexate (Trexall, Others)

Theoretically, turmeric might have additive effects when used with hepatotoxic drugs such as methotrexate.
In one case report, a 39-year-old female taking methotrexate, turmeric, and linseed oil developed hepatotoxicity.

Likelihood Possible Evidence D
Organic Anion-Transporting Polypeptide Substrates (Oatp)

Theoretically, turmeric might increase blood levels of OATP4C1 substrates.
In vitro research shows that the turmeric constituent curcumin competitively inhibits OATP4C1 transport. This transporter is expressed in the kidney and facilitates the renal excretion of certain drugs. Theoretically, taking turmeric might decrease renal excretion of OATP substrates.

Likelihood Possible Evidence D
Sulfasalazine (Azulfidine)

Turmeric might increase the effects and adverse effects of sulfasalazine.
Clinical research shows that taking the turmeric constituent, curcumin, can increase blood levels of sulfasalazine by 3.2-fold.

Likelihood Probable Evidence B
Tacrolimus (Prograf)

Turmeric might increase the effects and adverse effects of tacrolimus.
In one case report, a transplant patient presented with acute nephrotoxicity and elevated tacrolimus levels of 29 ng/mL. The patient previously had tacrolimus levels within the therapeutic range at 9.7 ng/mL. Ten days prior to presenting at the emergency room the patient started consumption of turmeric powder at a dose of 15 or more spoonfuls daily. It was thought that turmeric increased levels of tacrolimus due to cytochrome P450 3A4 (CYP3A4) inhibition. In vitro and animal research show that turmeric and its constituent curcumin inhibit CYP3A4.

Likelihood Possible Evidence D
Talinolol

Turmeric may reduce the absorption of talinolol in some situations.
Clinical research shows that taking curcumin for 6 days decreases the bioavailability of talinolol when taken together on the seventh day. The clinical significance of this effect is unclear.

Likelihood Probable Evidence B
Tamoxifen (Nolvadex)

Theoretically, turmeric might reduce the levels and clinical effects of tamoxifen.
In a small clinical trial in patients with breast cancer taking tamoxifen 20-30 mg daily, adding curcumin 1200 mg plus piperine 10 mg three times daily reduces the 24-hour area under the curve of tamoxifen and the active metabolite endoxifen by 12.8% and 12.4%, respectively, as well as the maximum concentrations of tamoxifen, when compared with tamoxifen alone. However, in the absence of piperine, the area under the curve for endoxifen and the maximum concentration of tamoxifen were not significantly reduced. Effects were most pronounced in patients who were extensive cytochrome P450 (CYP) 2D6 metabolizers.

Likelihood Possible Evidence B
Topoisomerase I Inhibitors

Turmeric has antioxidant effects. There is some concern that this may reduce the activity of chemotherapy drugs that generate free radicals. However, research is conflicting.
In vitro research shows that curcumin, a constituent of turmeric, inhibits camptothecin-induced apoptosis of breast cancer cells by up to 71%. However, other in vitro research shows that curcumin augments the cytotoxic effects of camptothecin. Reasons for the discrepancies may relate to the dose of curcumin and the chemotherapeutic agents. Lower doses of curcumin might have antioxidant effects while higher doses might have pro-oxidant effects. More evidence is needed to determine what effect, if any, turmeric might have.

Likelihood Possible Evidence D
Tramadol (Ultram)

Theoretically, turmeric might increase or decrease levels of tramadol.
Animal research suggests that a single dose of curcumin, a constituent of turmeric, may increase tramadol's maximum concentration (Cmax) by inhibiting metabolism, while continued daily use for 7 days may reduce the area under the curve (AUC) due to the induction of drug-metabolizing enzymes such as cytochrome P450 3A4 (CYP3A4). However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Turmeric might increase the risk of bleeding with warfarin.
One case of increased international normalized ratio (INR) has been reported for a patient taking warfarin who began taking turmeric. Prior to taking turmeric, the patient had stable INR measurements. Within a few weeks of starting turmeric supplementation, the patient's INR increased to 10. Additionally, curcumin, the active constituent in turmeric, has demonstrated antiplatelet effects in vitro, which may produce additive effects when taken with warfarin.

Likelihood Possible Evidence D
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, turmeric might increase levels of drugs metabolized by CYP1A2. However, research is conflicting.
In vitro and animal research show that the turmeric constituent, curcumin, inhibits CYP1A2. However, other in vitro research suggests that curcumin does not significantly affect CYP1A2.

Likelihood Possible Evidence D
Docetaxel (Taxotere)

Theoretically, turmeric might increase blood levels of oral docetaxel.
Animal research suggests that the turmeric constituent, curcumin, enhances the oral bioavailability of docetaxel. However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

Likelihood Possible Evidence D
Estrogens

Theoretically, large amounts of turmeric might interfere with hormone replacement therapy through competition for estrogen receptors.
In vitro research shows that curcumin, a constituent of turmeric, displaces the binding of estrogen to its receptors.

Likelihood Possible Evidence D
Glyburide (Diabeta, Others)

Theoretically, taking turmeric and glyburide in combination might increase the risk of hypoglycemia.
Clinical research shows that taking curcumin 475 mg daily for 10 days prior to taking glyburide 5 mg increases blood levels of glyburide by 12% at 2 hours after the dose in patients with type 2 diabetes. While maximal blood concentrations of glyburide were not affected, turmeric modestly decreased postprandial glucose levels for up to 24 hours when compared to glyburide alone, possibly due to the hypoglycemic effect of turmeric demonstrated in animal research.

Likelihood Possible Evidence B
Losartan (Cozaar)

Theoretically, turmeric might increase the effects of losartan.
Research in hypertensive rats shows that taking turmeric can increase the hypotensive effects of losartan.

Likelihood Possible Evidence D
Norfloxacin (Noroxin)

Theoretically, turmeric might increase the effects and adverse effects of norfloxacin.
Animal research shows that taking curcumin, a turmeric constituent, can increase blood levels of orally administered norfloxacin.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, turmeric might increase the absorption of P-glycoprotein substrates.
In vitro and animal research shows that curcuminoids and other constituents found in turmeric can inhibit P-glycoprotein expression and activity.

Likelihood Possible Evidence D
Paclitaxel (Abraxane, Onxol)

Theoretically, turmeric might alter blood levels of paclitaxel, although any effect may not be clinically relevant.
Clinical research in adults with breast cancer receiving intravenous paclitaxel suggests that taking turmeric may modestly alter paclitaxel pharmacokinetics. Patients received paclitaxel on day 1, followed by either no treatment or turmeric 2 grams daily from days 2-22. Pharmacokinetic modeling suggests that turmeric reduces the maximum concentration and area under the curve of paclitaxel by 12.1% and 7.7%, respectively. However, these changes are not likely to be considered clinically relevant. Conversely, animal research suggests that curcumin, a constituent of turmeric, enhances the oral bioavailability of paclitaxel. However, the significance of this interaction is unclear, as this drug is typically administered intravenously in clinical settings.

Likelihood Possible Evidence D
Curcumin C3 Complex full monograph & interactions

BioPerine17 drug types · 1,019 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, black pepper might increase the risk of bleeding when taken with antiplatelet or anticoagulant drugs.
In vitro research shows that piperine, a constituent of black pepper, seems to inhibit platelet aggregation. This has not been reported in humans.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, black pepper might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal research shows that piperine, a constituent of black pepper, can reduce blood glucose levels. Monitor blood glucose levels closely. Dose adjustments might be necessary.

Likelihood Possible Evidence D
Atorvastatin (Lipitor)

Theoretically, black pepper might increase blood levels of atorvastatin.
Animal research shows that taking piperine, a constituent of black pepper, 35 mg/kg can increase the maximum serum concentration of atorvastatin three-fold. This has not been reported in humans.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Theoretically, black pepper might increase the effects and side effects of cyclosporine.
In vitro research shows that piperine, a constituent of black pepper, increases the bioavailability of cyclosporine. This has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.
In vitro research suggests that some constituents of black pepper inhibit CYP2D6. This has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.
In vitro research and pharmacokinetic simulation data suggest that piperine, a constituent of black pepper, as well as the pepper fruit seem to inhibit CYP3A4. This has not been reported in humans.

Likelihood Possible Evidence D
Lithium

Theoretically, black pepper might increase blood levels of lithium due to its diuretic effects. The dose of lithium might need to be reduced.
Black pepper is thought to have diuretic properties.

Likelihood Probable Evidence D
Nevirapine (Viramune)

Black pepper might increase blood levels of nevirapine.
Clinical research shows that piperine, a constituent of black pepper, increases the plasma concentration of nevirapine. However, no adverse effects were observed in this study.

Likelihood Probable Evidence D
P-Glycoprotein Substrates

Theoretically, black pepper might increase levels of P-glycoprotein substrates.
In vitro research shows that piperine, a constituent of black pepper, seems to inhibit P-glycoprotein.

Likelihood Possible Evidence D
Pentobarbital (Nembutal)

Theoretically, black pepper might increase the sedative effects of pentobarbital.
Animal research shows that piperine, a constituent of black pepper, increases pentobarbital-induced sleeping time.

Likelihood Possible Evidence D
Phenytoin (Dilantin)

Black pepper might increase blood levels of phenytoin.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption, slow elimination, and increase levels of phenytoin. Taking a single dose of black pepper 1 gram along with phenytoin seems to double the serum concentration of phenytoin. Consuming a soup with black pepper providing piperine 44 mg/200 mL of soup along with phenytoin also seems to increase phenytoin levels when compared with consuming the same soup without black pepper.

Likelihood Possible Evidence B
Propranolol (Inderal)

Black pepper might increase blood levels of propranolol.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of propranolol.

Likelihood Possible Evidence B
Rifampin (Rifadin)

Black pepper might increase blood levels of rifampin.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and serum levels of rifampin.

Likelihood Possible Evidence B
Theophylline

Black pepper might increase blood levels of theophylline.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of theophylline.

Likelihood Possible Evidence D
Amoxicillin (Amoxil, Trimox)

Theoretically, black pepper might increase the effects and side effects of amoxicillin.
Animal research shows that taking piperine, a constituent of black pepper, with amoxicillin increases plasma levels of amoxicillin. This has not been reported in humans.

Likelihood Possible Evidence D
Carbamazepine (Tegretol)

Theoretically, black pepper might increase blood levels of carbamazepine, potentially increasing the effects and side effects of carbamazepine.
One clinical study in patients taking carbamazepine 300 mg or 500 mg twice daily shows that taking a single 20 mg dose of purified piperine, a constituent of black pepper, increases carbamazepine levels. Piperine may increase carbamazepine absorption by increasing blood flow to the GI tract, increasing the surface area of the small intestine, or inhibiting cytochrome P450 3A4 (CYP3A4) in the gut wall. Absorption was significantly increased by 7-10 mcg/mL/hour. The time to eliminate carbamazepine was also increased by 4-8 hours. Although carbamazepine levels were increased, this did not appear to increase side effects. In vitro research also shows that piperine can increase carbamazepine levels by 11% in a time-dependent manner.

Likelihood Possible Evidence B
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, black pepper might decrease levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research suggests that black pepper induces CYP1A2. This has not been reported in humans.

Likelihood Possible Evidence D
BioPerine full monograph & interactions

Milk Thistle standardized extract17 drug types · 954 drugs

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
Milk Thistle standardized extract full monograph & interactions

Schizandra12 drug types · 803 drugs

Cyclophosphamide

Theoretically, schisandra might increase the levels and clinical effects of cyclophosphamide.
In vitro research shows that schisandra increases the concentration of cyclophosphamide, likely through inhibition of cytochrome P450 3A4. After multiple doses of the schisandra constituents schisandrin A and schisantherin A, the maximum concentration of cyclophosphamide was increased by 7% and 75%, respectively, while the overall exposure to cyclophosphamide was increased by 29% and 301%, respectively.

Likelihood Probable Evidence D
Cyclosporine (Neoral, Sandimmune)

Schisandra can increase the levels and clinical effects of cyclosporine.
A small observational study in children with aplastic anemia found that taking schisandra with cyclosporine increased cyclosporine trough levels by 93% without increasing the risk of adverse events. However, the dose of cyclosporine was reduced in 9% of children to maintain appropriate cyclosporine blood concentrations.

Likelihood Probable Evidence B
Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, schisandra might increase the levels and clinical effects of CYP2C19 substrates.
In vitro research shows that schisandra inhibits CYP2C19, and animal research shows that schisandra increases the concentration of voriconazole, a CYP2C19 substrate. Theoretically, schisandra may also inhibit the metabolism of other CYP2C19 substrates. This effect has not been reported in humans.

Likelihood Probable Evidence D
Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, schisandra might decrease the levels and clinical effects of CYP2C9 substrates.
In vitro and animal research suggests that schisandra induces CYP2C9 enzymes. This effect has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Schisandra can increase the levels and clinical effects of drugs metabolized by CYP3A4.
Most clinical and laboratory research shows that schisandra, administered either as a single dose or up to twice daily for 14 days, inhibits CYP3A4 and increases the concentration of CYP3A4 substrates such as cyclophosphamide, midazolam, tacrolimus, and talinolol. Although one in vitro and animal study shows that schisandra may induce CYP3A4 metabolism, this effect appears to be overpowered by schisandra's CYP3A4 inhibitory activity and has not been reported in humans.

Likelihood Probable Evidence D
Midazolam (Versed)

Schisandra can increase the levels and clinical effects of midazolam.
A small pharmacokinetic study in healthy adults shows that taking schisandra extract (Hezheng Pharmaceutical Co.) containing deoxyschizandrin 33.75 mg twice daily for 8 days and a single dose of midazolam 15 mg on day 8 increases the overall exposure to midazolam by about 119%, increases the peak plasma level of midazolam by 86%, and decreases midazolam clearance by about 52%. This effect has been attributed to inhibition of CYP3A4 by schisandra.

Likelihood Probable Evidence B
P-Glycoprotein Substrates

Schisandra might increase the levels and clinical effects of P-glycoprotein substrates.
In vitro research shows that schisandra extracts and constituents such as schisandrin B inhibit P-glycoprotein mediated efflux in intestinal cells and in P-glycoprotein over-expressing cell lines. Additionally, a small clinical study shows that schisandra increases the peak concentration and overall exposure to talinolol, a P-glycoprotein probe substrate. Theoretically, schisandra might inhibit the efflux of other P-glycoprotein substrates.

Likelihood Possible Evidence D
Sirolimus (Rapamune)

Schisandra can increase the levels and clinical effects of sirolimus.
A small pharmacokinetic study in healthy volunteers shows that taking 3 capsules of schisandra (Hezheng Pharmaceutical Company) containing a total of 33.75 mg deoxyschizandrin twice daily for 13 days and then taking a single dose of sirolimus 2 mg increases the overall exposure and peak level of sirolimus by two-fold. This effect is thought to be due to inhibition of cytochrome P450 3A4 by schisandra, as well as possible inhibition of the P-glycoprotein drug transporter.

Likelihood Probable Evidence B
Tacrolimus (Prograf)

Schisandra can increase the levels and clinical effects of tacrolimus.
Clinical research in healthy children and adults, transplant patients, and patients with nephrotic syndrome and various rheumatic immunologic disorders shows that taking schisandra with tacrolimus increases tacrolimus peak levels by 183% to 268%, prolongs or delays time to peak tacrolimus concentrations, increases overall exposure to tacrolimus by 126% to 343%, and decreases tacrolimus clearance by 19% to 73%. This effect is thought to be due to inhibition of P-glycoprotein drug transporter and CYP3A4 and CYP3A5 by schisandra. Some clinical and observational studies suggest that schisandra increases tacrolimus levels similarly in both expressors and non-expressors of CYP3A5, while other studies suggest it does so to a greater degree in CYP3A5 expressors than non-expressors. Animal research suggests that the greatest increase in tacrolimus levels occurs when schisandra is taken either concomitantly or up to 2 hours before tacrolimus, and clinical and observational research in humans suggests that schisandra may increase whole blood levels of tacrolimus and decrease clearance of tacrolimus in a dose-dependent manner.

Likelihood Probable Evidence B
Talinolol

Schisandra can increase the levels and clinical effects of talinolol.
A small pharmacokinetic study in healthy volunteers shows that taking schisandra extract 300 mg twice daily for 14 days with a single dose of talinolol 100 mg on day 14 increases the peak talinolol level by 51% and the overall exposure to talinolol by 47%. This effect is thought to be due to the possible inhibition of cytochrome P450 3A4 and P-glycoprotein by schisandra. tly.

Likelihood Probable Evidence B
Voriconazole (Vfend)

Theoretically, schisandra might increase the levels and clinical effects of voriconazole.
Animal research shows that oral schisandra given daily for 1 or 14 days increases levels of intravenously administered voriconazole, a cytochrome P450 (CYP) 2C19 substrate. This effect is thought to be due to inhibition of CYP2C19 by schisandra. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, schisandra might decrease the levels and clinical effects of warfarin.
Animal research suggests that oral schisandra extract, given daily for 6 days, reduces levels of intravenously administered warfarin. This effect might be due to the induction of cytochrome P450 (CYP) 2C9 metabolism by schisandra. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Schizandra full monograph & interactions

Gotu Kola2 drug types · 579 drugs

Cns Depressants

Theoretically, taking gotu kola might increase the sedative effects of CNS depressants.
In vitro research suggests that gotu kola may have sedative effects via binding of GABA receptors.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, taking gotu kola with hepatotoxic drugs might have additive adverse effects.
There are at least four case reports of hepatotoxicity associated with the use of gotu kola. However, more information is needed to determine if gotu kola was the causative factor in these cases.

Likelihood Possible Evidence D
Gotu Kola full monograph & interactions

Boldo5 drug types · 482 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, taking boldo with anticoagulant/antiplatelet drugs might increase the risk of bleeding.
Animal and in vitro research shows that boldine, a constituent of boldo, has antiplatelet activity. In one case report, an adult taking a combination of boldo and fenugreek with warfarin experienced an increase in international normalized ratio (INR); however, it is unclear if this effect was due to boldo, fenugreek, the combination, or another factor.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, taking boldo with hepatotoxic drugs might increase the risk of hepatic injury and disease.
Boldo leaf contains ascaridole, a known liver toxin. Many cases of hepatotoxicity, including elevated liver transaminase levels and jaundice, have been reported in patients taking boldo.

Likelihood Possible Evidence D
Lithium

Theoretically, taking boldo with lithium might increase the levels and clinical effects of lithium.
Boldo is believed to have diuretic effects. Theoretically, these diuretic effects might reduce the excretion of lithium. The dose of lithium might need to be decreased.

Likelihood Probable Evidence D
Tacrolimus (Prograf)

Taking boldo with tacrolimus may decrease the levels and clinical effects of tacrolimus, potentially increasing the risk of transplant rejection.
In one case report, a patient with a long-term history of stable tacrolimus levels developed subtherapeutic levels after taking boldo 300 mg twice daily orally for several weeks. Tacrolimus levels returned to normal after discontinuing boldo. However, the mechanism of this interaction is unclear.

Likelihood Possible Evidence D
Warfarin (Coumadin)

A combination of boldo and fenugreek was thought to be associated with an increased international normalized ratio (INR) in a female on warfarin. It is not clear if boldo, fenugreek, or the combination played a role in this interaction. Therefore, boldo may have additive effects with warfarin.

Likelihood Possible Evidence D
Boldo full monograph & interactions

Dandelion7 drug types · 457 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, taking dandelion root along with anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding.
In vitro research suggests that dandelion root inhibits platelet aggregation.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, dandelion might increase the risk for hypoglycemia when used with antidiabetes drugs.
Laboratory research suggests that dandelion extract may have moderate alpha-glucosidase inhibitor activity and might also increase insulin secretion. Also, in a case report, a 58-year-old woman with type 2 diabetes who was being treated with insulin developed hypoglycemia 2 weeks after beginning to eat salads containing dandelion.

Likelihood Possible Evidence D
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, dandelion might increase levels of drugs metabolized by CYP1A2.
Laboratory research suggests that dandelion might inhibit CYP1A2. So far, this interaction has not been reported in humans. However, until more is known, watch for an increase in the levels of drugs metabolized by CYP1A2 in patients taking dandelion.

Likelihood Possible Evidence D
Glucuronidated Drugs

Theoretically, dandelion might increase the clearance of drugs that are UDP-glucuronosyltransferase substrates.
There is some preliminary evidence that dandelion might induce UDP-glucuronosyltransferase, a phase II enzyme.

Likelihood Possible Evidence D
Lithium

Theoretically, through diuretic effects, dandelion might reduce excretion and increase levels of lithium.
Animal research suggests that dandelion has diuretic properties. As diuretics can increase serum lithium levels, the dose of lithium might need to be decreased when taken with dandelion.

Likelihood Probable Evidence D
Potassium-Sparing Diuretics

Theoretically, dandelion might increase the risk of hyperkalemia when taken with potassium-sparing diuretics.
Dandelion contains significant amounts of potassium.

Likelihood Possible Evidence D
Quinolone Antibiotics

Theoretically, dandelion might lower fluoroquinolone levels.
Animal research shows that dandelion reduces absorption of ciprofloxacin and can lower levels by 73%. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Dandelion full monograph & interactions

Artichoke4 drug types · 363 drugs

Antidiabetes Drugs

Theoretically, artichoke leaf extract may increase the risk of hypoglycemia when taken with antidiabetes drugs.
A meta-analysis of small clinical studies shows that taking artichoke leaf extract for 8-12 weeks can modestly reduce fasting plasma glucose when compared with placebo.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, artichoke leaf extract may increase the risk of hypotension when taken with antihypertensive drugs.
A meta-analysis of small clinical studies in patients with hypertension shows that taking artichoke can reduce systolic blood pressure by around 3 mmHg and diastolic blood pressure by around 2 mmHg when compared with placebo.

Likelihood Possible Evidence D
Cytochrome P450 2B6 (Cyp2B6) Substrates

Theoretically, artichoke might increase serum levels of drugs metabolized by CYP2B6.
In vitro research shows that artichoke leaf extract inhibits CYP2B6 activity. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, artichoke might increase serum levels of drugs metabolized by CYP2C19.
In vitro research shows that artichoke leaf extract inhibits CYP2C19 activity. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Artichoke full monograph & interactions

Vitamin B65 drug types · 210 drugs

Amiodarone (Cordarone)

Theoretically, vitamin B6 might increase the photosensitivity caused by amiodarone.
Despite initial case reports suggesting that pyridoxine may have a protective effect against amiodarone-induced photosensitivity, preliminary clinical research suggests that pyridoxine may actually exacerbate this adverse effect.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, vitamin B6 may have additive effects when used with antihypertensive drugs.
Research in hypertensive rats shows that vitamin B6 can decrease systolic blood pressure. Similarly, clinical research in patients with hypertension shows that taking high doses of vitamin B6 may reduce systolic and diastolic blood pressure, possibly by reducing plasma levels of epinephrine and norepinephrine.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenobarbital, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenobarbital to avoid high doses of vitamin B6.

Likelihood Possible Evidence D
Phenytoin (Dilantin)

High doses of vitamin B6 may reduce the levels and clinical effects of phenytoin.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenytoin, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenytoin to avoid high doses of vitamin B6.

Likelihood Possible Evidence D
Levodopa

Vitamin B6 may increase the metabolism of levodopa when taken alone, but not when taken in conjunction with carbidopa.
Vitamin B6 (pyridoxine) enhances the metabolism of levodopa, reducing its clinical effects. However, this interaction does not occur when carbidopa is used concurrently with levodopa (Sinemet). Therefore, it is not likely to be a problem in most people.

Likelihood Unlikely Evidence D
Vitamin B6 full monograph & interactions

Chromium5 drug types · 178 drugs

Antidiabetes Drugs

Theoretically, chromium may have additive effects with antidiabetic agents and increase the risk of hypoglycemia.
Some research shows that taking chromium might lower blood glucose levels, especially in patients with poorly controlled type 2 diabetes.

Likelihood Possible Evidence A
Insulin

Theoretically, concomitant use of chromium and insulin might increase the risk of hypoglycemia.
In clinical research, chromium has been shown to increase insulin sensitivity,

Likelihood Possible Evidence B
Levothyroxine (Synthroid, Others)

Chromium might bind levothyroxine in the intestinal tract and decrease levothyroxine absorption.
Clinical research in healthy volunteers shows that taking chromium picolinate 1000 mcg with levothyroxine 1 mg decreases serum levels of levothyroxine by 17% when compared to taking levothyroxine alone. Advise patients to take levothyroxine at least 30 minutes before or 3-4 hours after taking chromium.

Likelihood Probable Evidence B
Aspirin

Theoretically, aspirin might increase chromium absorption.
Animal research suggests that aspirin may increase chromium absorption and chromium levels in the blood.

Likelihood Possible Evidence D
Nonsteroidal Anti-Inflammatory Drugs (Nsaids)

NSAIDs might increase chromium levels in the body.
Drugs that are prostaglandin inhibitors, such as NSAIDs, seem to increase chromium absorption and retention.

Likelihood Possible Evidence D
Chromium full monograph & interactions

Bromelain2 drug types · 141 drugs

Anticoagulant/Antiplatelet Drugs

Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
There is one case report of a patient experiencing minor bruising while taking bromelain with naproxen. Bromelain is thought to have antiplatelet activity. Whether this interaction is of concern with topical bromelain is unclear. Interference with coagulation of burn wounds has been reported in a patient receiving bromelain-based enzymatic debridement. However, observational research has found that topical bromelain debridement is not associated with increases or decreases in laboratory markers of coagulation when compared with surgical debridement.

Likelihood Possible Evidence D
Tetracycline Antibiotics

Theoretically, bromelain might increase levels of tetracycline antibiotics.
Laboratory research suggests that bromelain might increase the absorption of tetracycline antibiotics. However, a study in healthy adults reported no difference in tetracycline plasma levels when a 500 mg dose was taken with or without bromelain 80 mg.

Likelihood Possible Evidence B
Bromelain full monograph & interactions

Inositol1 drug type · 86 drugs

Antidiabetes Drugs

Theoretically, taking inositol with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research shows that inositol lowers blood glucose levels and glycated hemoglobin (HbA1c) levels in patients with diabetes.

Likelihood Possible Evidence A
Inositol full monograph & interactions

L-Carnitine3 drug types · 19 drugs

Acenocoumarol (Sintrom)

Theoretically, L-carnitine might increase the anticoagulant effects of acenocoumarol.
L-carnitine might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant similar to warfarin, but shorter-acting. There are at least two case reports of INR elevation with concomitant use. In one case, a 33-year-old male with a previously stable INR had an elevated INR of 4.65 after L-carnitine was started and continued for 10 weeks. INR normalized after discontinuation of the L-carnitine-containing product.

Likelihood Possible Evidence D
Thyroid Hormone

Theoretically, L-carnitine might decrease the effectiveness of thyroid hormone replacement.
L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting entry of thyroid hormone into the nucleus of cells. Taking L-carnitine also seems to diminish some of the symptoms of hyperthyroidism.

Likelihood Probable Evidence B
Warfarin (Coumadin)

Theoretically, L-carnitine might increase the anticoagulant effects of warfarin.
L-carnitine might increase the anticoagulant effects of acenocoumarol, a shorter-acting oral anticoagulant similar to warfarin. There is not enough information to know whether this interaction occurs with L-carnitine and warfarin.

Likelihood Possible Evidence D
L-Carnitine full monograph & interactions

Choline1 drug type · 16 drugs

Atropine

Theoretically, choline might decrease the effects of atropine in the brain.
Animal research shows that administering choline one hour before administering atropine can attenuate atropine-induced decreases in brain levels of acetylcholine. Theoretically, concomitant use of choline and atropine may decrease the effects of atropine.

Likelihood Possible Evidence D
Choline full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Liv-R Support, from the product label.

Highland Laboratories

See all Highland Laboratories products
Name
Highland Laboratories
Pharmacist Counseling Corner

Liv-R Support by Highland Laboratories: Common Questions

Does Liv-R Support by Highland Laboratories interact with any medications?
Yes. Based on its ingredients, Liv-R Support has a known interaction with 1,497 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Liv-R Support contains 16 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Is Liv-R Support safe to take during pregnancy?
Safety varies by ingredient. Vitamin B6 is likely safe, L-methionine is likely safe, and inositol is possibly safe in pregnancy. However, schisandra, gotu kola, bromelain, artichoke, and boldo lack sufficient safety data or are considered possibly unsafe in pregnancy. Oregon grape is likely unsafe. Because this product contains multiple ingredients with limited or uncertain pregnancy data, talk with your doctor or pharmacist before using it during pregnancy.
Can I take this while breastfeeding?
Most safety data for breastfeeding is limited. Vitamin B6 is likely safe, and choline is likely safe while breastfeeding. However, schisandra, gotu kola, bromelain, artichoke, Oregon grape, and boldo have insufficient data or are considered unsafe during lactation. Since several ingredients lack breastfeeding safety information, check with your doctor or pharmacist before using this product while nursing.
What does this supplement actually do for my liver?
The data we hold shows insufficient reliable evidence for most ingredients' effects on liver health. Milk thistle is possibly effective for diabetes and has been traditionally used for liver support, but the product's effectiveness for overall liver support is not established in the evidence we have. Talk with your doctor about whether this product is right for your specific liver health goals.
Will this product cause side effects?
Most ingredients are generally well tolerated at standard doses, with common mild effects being digestive (diarrhea, nausea, stomach upset). However, vitamin B6 at high doses can cause nerve damage, and rare cases of liver injury have been reported with gotu kola, turmeric, and boldo. If you experience unusual symptoms, stop and contact your doctor or pharmacist.
Should I take this supplement if I have diabetes?
Several ingredients may lower blood sugar (inositol, dandelion, chromium, artichoke, and milk thistle), which could increase your risk of low blood sugar (hypoglycemia) if you're already on diabetes medication. Do not start this product without discussing it first with your doctor or pharmacist, especially if you take insulin or other diabetes drugs.
Is there a fishy body odor side effect from this supplement?
Yes. Both choline and L-carnitine in this product can cause a fishy body odor due to how your body metabolizes them, especially at higher doses. This is generally mild and reversible, but some people notice it. If this occurs, it does not mean the supplement isn't working — it's just a side effect of these ingredients.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Not sure if Liv-R Support is safe with your meds?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.

Liv-R Support label
Go deeper

The Full Monographs Behind Liv-R Support’s Ingredients

Every ingredient we hold a full HelloPharmacist monograph for — uses, evidence, safety, and the complete interaction list.

Herb & supplement monograph

Vitamin B6

Interacts with 210 drugs

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is best known for helping with pregnancy-rel...

Read the full Vitamin B6 monograph → Herb & supplement monograph

Methionine

Methionine is an essential amino acid that your body needs for protein building and many basic chemical reactions. Most people get enough from a normal diet, and supplements are generally no...

Read the full Methionine monograph → Herb & supplement monograph

Inositol

Interacts with 86 drugs

Inositol is a sugar alcohol made naturally in the body and found in many foods, and it is sold as a supplement (often myo-inositol) mainly for PCOS, mood, and metabolic concerns. The stronge...

Read the full Inositol monograph → Herb & supplement monograph

Dandelion

Interacts with 457 drugs

Dandelion is a common plant used in food and traditional medicine, often promoted as a natural 'water pill' and digestive aid. Human evidence for these uses is very limited, so its benefits...

Read the full Dandelion monograph → Herb & supplement monograph

Choline

Interacts with 16 drugs

Choline is an essential nutrient your body needs for liver function, brain health, and nerve signaling, and many people get enough from foods like eggs, meat, and fish. Supplements may help...

Read the full Choline monograph → Herb & supplement monograph

Black Pepper

Interacts with 1,019 drugs

Black pepper is a common kitchen spice that is generally safe in the amounts used in food. Its extract, piperine, is mostly added to supplements to help the body absorb other ingredients (li...

Read the full Black Pepper monograph → Herb & supplement monograph

L-carnitine

Interacts with 19 drugs

L-carnitine is a compound your body makes naturally and also gets from foods like meat. It helps cells turn fat into energy, and supplements are most clearly useful for people with a true ca...

Read the full L-carnitine monograph → Herb & supplement monograph

Schisandra

Interacts with 803 drugs

Schisandra is a traditional Chinese medicine berry used as an adaptogen for stress, fatigue, and liver support. Human evidence is limited and most claims are not well proven, but it appears...

Read the full Schisandra monograph → Herb & supplement monograph

Gotu Kola

Interacts with 579 drugs

Gotu kola is a traditional Ayurvedic and Asian herb that people use for wound healing, circulation, skin problems, and as a calming or memory-supporting herb. Some early studies suggest poss...

Read the full Gotu Kola monograph → Herb & supplement monograph

Bromelain

Interacts with 141 drugs

Bromelain is a group of protein-digesting enzymes from pineapple that people take mainly for inflammation, swelling, and sinus problems. Some early studies are promising, but the overall evi...

Read the full Bromelain monograph → Herb & supplement monograph

Artichoke

Interacts with 363 drugs

Artichoke leaf extract is a generally well-tolerated supplement that may have a mild cholesterol-lowering effect and is often used for indigestion, though the evidence is modest. It is not a...

Read the full Artichoke monograph → Herb & supplement monograph

Oregon Grape

Interacts with 1,218 drugs

Oregon grape is a shrub whose root contains berberine and related compounds. The strongest (though still modest) evidence is for topical creams that may slightly ease psoriasis; evidence for...

Read the full Oregon Grape monograph → Herb & supplement monograph

Turmeric

Interacts with 1,133 drugs

Turmeric is a popular spice whose main active compounds, curcuminoids, are studied mostly for inflammation and joint pain. Some research is promising, but quality is mixed and curcumin is po...

Read the full Turmeric monograph → Herb & supplement monograph

Chromium

Interacts with 178 drugs

Chromium is an essential trace mineral involved in how the body handles sugar and fat. Some studies suggest it may modestly help blood sugar control in certain people with type 2 diabetes, b...

Read the full Chromium monograph → Herb & supplement monograph

Milk Thistle

Interacts with 954 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. While it is generally well tolerated, th...

Read the full Milk Thistle monograph → Herb & supplement monograph

Boldo

Interacts with 482 drugs

Boldo is a South American shrub whose leaves are traditionally used for digestive and gallbladder complaints, but good human evidence is very limited. The leaves and oil contain ascaridole,...

Read the full Boldo monograph →
Sources

Sources & How We Checked

Liv-R Support'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.

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 503 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.

Vitamin B6 32 references
  1. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Geerling BJ, Dagnelie PC, Badart-Smook A, et al. Diet as a risk factor for the development of ulcerative colitis. Am J Gastroenterol 2000;95:1008-13. PubMed
  4. South M. Neonatal seizures after pyridoxine use -- reply. Lancet 1999;354:2083. PubMed
  5. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  6. Baxter P, Aicardi J. Neonatal seizures after pyridoxine use. Lancet 1999;354:2082-3. PubMed
  7. Bendich A, Cohen M. Vitamin B6 safety issues. Ann N Y Acad Sci 1990;585:321-30.
  8. Schaumburg H, Kaplan J, Windebank A. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med 1983;309:445-8. PubMed
  9. Gordon N. Pyridoxine dependency: an update. Dev Med Child Neurol 1997;39:63-5. PubMed
  10. Lewis PJ. Pain in the hand and wrist. Pyridoxine supplements may help patients with carpal tunnel syndrome. BMJ 1995;310:1534. PubMed
  11. Kaufman G. Pyridoxine against amiodarone-induced photosensitivity (letter). Lancet 1984;1:51-2. PubMed
  12. Mulrow JP, Mulrow CD, McKenna WJ. Pyridoxine and amiodarone-induced photosensitivity. Ann Intern Med 1985;103:68-9. PubMed
  13. Kawada A, Kashima A, Shiraishi H, et al. Pyridoxine-induced photosensitivity and hypophosphatasia. Dermatology 2000;201:356-60.. PubMed
  14. Vasile A, Goldberg R, Kornberg B. Pyridoxine toxicity: report of a case. J Am Osteopath Assoc 1984;83:790-1. DOI
  15. Hansson O, Sillanpaa M. Pyridoxine and serum concentration of phenytoin and phenobarbitone. Lancet 1976;1:256. DOI
  16. Jansen T, Romiti R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol 2001;15:484-5..
  17. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai 2007;90:15-20.
  18. Hatzitolios, A., Iliadis, F., Katsiki, N., and Baltatzi, M. Is the anti-hypertensive effect of dietary supplements via aldehydes reduction evidence based? A systematic review. Clin Exp.Hypertens. 2008;30(7):628-639. PubMed
  19. Vasdev, S., Ford, C. A., Parai, S., Longerich, L., and Gadag, V. Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats. Mol.Cell Biochem. 1999;200(1-2):155-162.
  20. de, Vogel S., Dindore, V., van, Engeland M., Goldbohm, R. A., van den Brandt, P. A., and Weijenberg, M. P. Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectal cancer. J Nutr 2008;138(12):2372-2378. PubMed
  21. Hagen, I., Nesheim, B. I., and Tuntland, T. No effect of vitamin B-6 against premenstrual tension. A controlled clinical study. Acta Obstet.Gynecol.Scand. 1985;64(8):667-670. PubMed
  22. Aybak, M., Sermet, A., Ayyildiz, M. O., and Karakilcik, A. Z. Effect of oral pyridoxine hydrochloride supplementation on arterial blood pressure in patients with essential hypertension. Arzneimittelforschung. 1995;45(12):1271-1273.
  23. Lal, K. J., Dakshinamurti, K., and Thliveris, J. The effect of vitamin B6 on the systolic blood pressure of rats in various animal models of hypertension. J Hypertens. 1996;14(3):355-363. PubMed
  24. Lauritzen CH, Reuter HD, Repges R, Bohnert K, and Schmidt U. Treatment of premenstrual tension syndrome with Vitex agnus castus. Controlled, double-blind study versus pyridoxine. Phytomed 1997;4(3):183-189. PubMed
  25. Fonseca VA, Lavery LA, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: A randomized trial. Am J Med 2013;126(2):141-9. PubMed
  26. Hankey GJ, Eikelboom JW, Yi Q, et al. Treatment with B vitamins and incidence of cancer in patients with previous stroke or transient ischemic attack: Results of a randomized placebo-controlled trial. Stroke 2012;43(6):1572-7. PubMed
  27. Hoyer-Kuhn H, Kohbrok S, Volland R, Franklin J, Hero B, Beck BB, Hoppe B. Vitamin B6 in primary hyperoxaluria I: first prospective trial after 40 years of practice. Clin J Am Soc Nephrol. 2014 Mar;9(3):468-77. PubMed
  28. Mahmoud A, Tabassum S, Al Enazi S, et al. Amelioration of levetiracetam-induced behavioral side effects by pyridoxine. A randomized double blind controlled study. Pediatr Neurol 2021;119:15-21. PubMed
  29. Gupta M, Gallante B, Bamberger JN, et al. Prospective randomized evaluation of idiopathic hyperoxaluria treatments. J Endourol 2021;35(12):1844-1851. PubMed
  30. Li H, Chen M, Liang S, et al. Excessive vitamin B6 during treatment is related to poor prognosis of patients with nasopharyngeal carcinoma: A U-shaped distribution suggests low dose supplement. Clin Nutr 2021;40(4):2293-2300. PubMed
  31. Tanigawa J, Nabatame S, Tominaga K, et al. High-dose pyridoxine treatment for inherited glycosylphosphatidylinositol deficiency. Brain Dev 2021;43(6):680-687. PubMed
  32. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. PubMed

See these in context on the Vitamin B6 monograph →

Methionine 12 references
  1. La Vecchia C, Negri E, Franceschi S, Decarli A. Case-control study on influence of methionine, nitrite, and salt on gastric carcinogenesis in northern Italy. Nutr Cancer 1997;27:65-8. PubMed
  2. Btaiche IF, Khalidi N. Parenteral nutrition-associated liver complications in children. Pharmacotherapy 2002;22:188-211.. PubMed
  3. Cottington EM, LaMantia C, Stabler SP, et al. Adverse event associated with methionine loading test: a case report. Arterioscler Thromb Vasc Biol 2002;22:1046-50.. PubMed
  4. Anon. Should methionine be added to paracetamol formulations? Drug Ther Perspect 1997;10:11-3. DOI
  5. Smulders, Y. M., Rakic, M., Slaats, E. H., Treskes, M., Sijbrands, E. J., Odekerken, D. A., Stehouwer, C. D., and Silberbusch, J. Fasting and post-methionine homocysteine levels in NIDDM. Determinants and correlations with retinopathy, albuminuria, and c
  6. McAuley, D. F., Hanratty, C. G., McGurk, C., Nugent, A. G., and Johnston, G. D. Effect of methionine supplementation on endothelial function, plasma homocysteine, and lipid peroxidation. J.Toxicol.Clin.Toxicol. 1999;37(4):435-440. PubMed
  7. Hanratty, C. G., McGrath, L. T., McAuley, D. F., Young, I. S., and Johnston, G. D. The effects of oral methionine and homocysteine on endothelial function. Heart 2001;85(3):326-330. PubMed
  8. Ward, M., McNulty, H., McPartlin, J., Strain, J. J., Weir, D. G., and Scott, J. M. Effect of supplemental methionine on plasma homocysteine concentrations in healthy men: a preliminary study. Int.J.Vitam.Nutr.Res. 2001;71(1):82-86. PubMed
  9. Yaghmai, R., Kashani, A. H., Geraghty, M. T., Okoh, J., Pomper, M., Tangerman, A., Wagner, C., Stabler, S. P., Allen, R. H., Mudd, S. H., and Braverman, N. Progressive cerebral edema associated with high methionine levels and betaine therapy in a patient
  10. Talukdar R, Murthy HV, Reddy DN. Role of methionine containing antioxidant combination in the management of pain in chronic pancreatitis: a systematic review and meta-analysis. Pancreatology 2015;15(2):136-44. PubMed
  11. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press, 2005. Available at: https://doi.org/10.17226 DOI
  12. Khairan P, Sobue T, Eshak ES, et al. Association of B Vitamins and Methionine Intake with the Risk of Gastric Cancer: The Japan Public Health Center-based Prospective Study. Cancer Prev Res (Phila) 2022;15(2):101-110. PubMed

See these in context on the Methionine monograph →

Inositol 14 references
  1. Palatnik A, Frolov K, Fux M, Benjamin J. Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder. J Clin Psychopharmacol 2001;21:335-9.. PubMed
  2. Allan SJ, Kavanagh GM, Herd RM, Savin JA. The effect of inositol supplements on the psoriasis of patients taking lithium: a randomized, placebo-controlled trial. Br J Dermatol 2004;150:966-9. PubMed
  3. Machado-Vieira R, Viale CI, Kapczinski F. Mania associated with an energy drink: the possible role of caffeine, taurine, and inositol. Can J Psychiatry 2001;46:454-5. PubMed
  4. Kamenov Z, Kolarov G, Gateva A, Carlomagno G, Genazzani AD. Ovulation induction with myo-inositol alone and in combination with clomiphene citrate in polycystic ovarian syndrome patients with insulin resistance. Gynecol Endocrinol 2015;31(2):131-5. PubMed
  5. Matarrelli B, Vitacolonna E, D'Angelo M, et al. Effect of dietary myo-inositol supplementation in pregnancy on the incidence of maternal gestational diabetes mellitus and fetal outcomes: a randomized controlled trial. J Matern Fetal Neonatal Med 2013;26(1 PubMed
  6. Mukai T, Kishi T, Matsuda Y, Iwata N. A meta-analysis of inositol for depression and anxiety disorders. Hum Psychopharmacol 2014;29(1):55-63. PubMed
  7. Farren M, Daly N, McKeating A, Kinsley B, Turner MJ, Daly S. The Prevention of Gestational Diabetes Mellitus With Antenatal Oral Inositol Supplementation: A Randomized Controlled Trial. Diabetes Care. 2017;40(6):759-63. PubMed
  8. Zheng X, Liu Z, Zhang Y, et al. Relationship Between Myo-Inositol Supplementary and Gestational Diabetes Mellitus: A Meta-Analysis. Medicine (Baltimore). 2015;94(42):e1604. PubMed
  9. Crawford TJ, Crowther CA, Alsweiler J, Brown J. Antenatal dietary supplementation with myo-inositol in women during pregnancy for preventing gestational diabetes. Cochrane Database Syst Rev. 2015;(12):CD011507. PubMed
  10. Maurizi AR, Menduni M, Del Toro R, et al. A pilot study of D-chiro-inositol plus folic acid in overweight patients with type 1 diabetes. Acta Diabetol. 2017;54(4):361-65. PubMed
  11. Leppink EW, Redden SA, Grant JE. A double-blind, placebo-controlled study of inositol in trichotillomania. Int Clin Psychopharmacol. 2017;32(2):107-14. PubMed
  12. Lam S, Mandrekar SJ, Gesthalter Y. A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial Dysplasia. Cancer Prev Res (Phila). 2016;9(12):906-14.
  13. Wozniak J, Faraone SV, Chan J, et al. A randomized clinical trial of high eicosapentaenoic acid omega-3 fatty acids and inositol as monotherapy and in combination in the treatment of pediatric bipolar spectrum disorders: a pilot study. J Clin Psychiatry. PubMed
  14. Vitale SG, Corrado F, Caruso S, et al. Myo-inositol supplementation to prevent gestational diabetes in overweight non-obese women: bioelectrical impedance analysis, metabolic aspects, obstetric and neonatal outcomes - a randomized and open-label, placebo-

See these in context on the Inositol monograph →

Dandelion 27 references
  1. Maliakal PP, Wanwimolruk S. Effect of herbal teas on hepatic drug metabolizing enzymes in rats. J Pharm Pharmacol 2001;53:1323-9. PubMed
  2. Williams CA, Goldstone F, Greenham J. Flavonoids, cinnamic acids and coumarins from the different tissues and medicinal preparations of Taraxacum officinale. Phytochemistry 1996;42:121-7. PubMed
  3. Hussain Z, Waheed A, Qureshi RA, et al. The effect of medicinal plants of Islamabad and Murree region of Pakistan on insulin secretion from INS-1 cells. Phytother Res 2004;18:73-7. PubMed
  4. Racz-Kotilla E, Racz G, Solomon A. The action of Taraxacum officinale extracts on the body weight and diuresis of laboratory animals. Planta Med 1974;26:212-7. PubMed
  5. Zhu M, Wong PY, Li RC. Effects of taraxacum mongolicum on the bioavailability and disposition of ciprofloxacin in rats. J Pharm Sci 1999;88:632-4. PubMed
  6. Jovanovic M, Mimica-Dukic N, Poljacki M, Boza P. Erythema multiforme due to contact with weeds: a recurrence after patch testing. Contact Dermatitis 2003;48:17-25. PubMed
  7. Chivato T, Juan F, Montoro A, Laguna R. Anaphylaxis induced by ingestion of a pollen compound. J Investig Allergol Clin Immunol 1996;6:208-9.
  8. Cohen SH, Yunginger JW, Rosenberg N, Fink JN. Acute allergic reaction after composite pollen ingestion. J Allergy Clin Immunol 1979;64:270-4. PubMed
  9. Lovell CR, Rowan M. Dandelion dermatitis. Contact Dermatitis 1991;25:185-8. PubMed
  10. Agarwal SC, Crook JR, Pepper CB. Herbal remedies -- how safe are they? A case report of polymorphic ventricular tachycardia/ventricular fibrillation induced by herbal medication used for obesity. Int J Cardiol 2006;106:260-1. PubMed
  11. Martín-Muñoz MF, Bartolome B, Caminoa M, et al. Bee pollen: a dangerous food for allergic children. Identification of responsible allergens. Allergol Immunopathol (Madr) 2010;38:263-5. PubMed
  12. Neef H, Cilli F, Declerck PJ, et al. Platelet anti-aggregating activity of Taraxacum officinale Weber. Phytotherapy Research 1996;10:s138-s140.
  13. Cuzzolin L, Zaffani S, and Benoni G. Safety implications regarding use of phytomedicines. Eur.J Clin Pharmacol. 2006;62:37-42. PubMed
  14. Posadzki, P., Watson, L. K., and Ernst, E. Adverse effects of herbal medicines: an overview of systematic reviews. Clin Med 2013;13(1):7-12. PubMed
  15. Wakelin, S. H., Marren, P., Young, E., and Shaw, S. Compositae sensitivity and chronic hand dermatitis in a seven-year-old boy. Br J Dermatol 1997;137(2):289-291. PubMed
  16. Ingber, A. Seasonal allergic contact dermatitis from Taraxacum officinale (dandelion) in an Israeli florist. Contact Dermatitis 2000;43(1):49.
  17. Rodriguez, B., Rodriguez, A., de Barrio, M., Tornero, P., and Baeza, M. L. Asthma induced by canary food mix. Allergy Asthma Proc. 2003;24(4):265-268.
  18. Syhaieva, I. A. [Efficiency of specific immunotherapy in treatment of patients with seasonal allergic rhinitis]. Lik.Sprava. 2006;(1-2):51-53.
  19. Catania, M. A., Oteri, A., Caiello, P., Russo, A., Salvo, F., Giustini, E. S., Caputi, A. P., and Polimeni, G. Hemorrhagic cystitis induced by an herbal mixture. South.Med.J. 2010;103(1):90-92. PubMed
  20. Goksu, E., Eken, C., Karadeniz, O., and Kucukyilmaz, O. First report of hypoglycemia secondary to dandelion (Taraxacum officinale) ingestion. Am J Emerg.Med 2010;28(1):111-112. PubMed
  21. Fernandez-Gonzalez, D., Gonzalez-Parrado, Z., Vega-Maray, A. M., Valencia-Barrera, R. M., Camazon-Izquierdo, B., De, Nuntiis P., and Mandrioli, P. Platanus pollen allergen, Pla a 1: quantification in the atmosphere and influence on a sensitizing populati
  22. Liang, K. L., Su, M. C., Shiao, J. Y., Wu, S. H., Li, Y. H., and Jiang, R. S. Role of pollen allergy in Taiwanese patients with allergic rhinitis. J Formos.Med Assoc. 2010;109(12):879-885. PubMed
  23. Yang, Y., Zhao, Y., Wang, C. S., Wang, X. D., and Zhang, L. [Prevalence of sensitization to aeroallergens in 10 030 patients with allergic rhinitis]. Zhonghua Er.Bi Yan.Hou Tou.Jing.Wai Ke Za Zhi 2011;46(11):914-920.
  24. Davies, M. G. and Kersey, P. J. Contact allergy to yarrow and dandelion. Contact Dermatitis 1986;14(4):256-257. PubMed
  25. Collins JM and Miller DR. Dandelion green bezoar following antrectomy and vagotomy - case report. J Kansas Med Soc 1966;67(6):303-304.
  26. Moriarty B, Pinney JH, Owen-Casey MP, Rustin MH, Deroide F, Laing C, Davenport A. Digital necrosis from dandelion tea. Br J Dermatol. 2013 Jul;169(1):227-30. PubMed
  27. Onal S, Timur S, Okutucu B, Zihnioglu F. Inhibition of alphaglucosidase by aqueous extracts of some potent antidiabetic medicinal herbs. Prep Biochem Biotechnol 2005;35:29-36.

See these in context on the Dandelion monograph →

Choline 14 references
  1. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  2. Cho E, Willett WC, Colditz GA, et al. Dietary choline and betaine and the risk of distal colorectal adenoma in women. J Natl Cancer Inst 2007;99:1224-31. PubMed
  3. Schmidt, C., Abicht, A., Krampfl, K., Voss, W., Stucka, R., Mildner, G., Petrova, S., Schara, U., Mortier, W., Bufler, J., Huebner, A., and Lochmuller, H. Congenital myasthenic syndrome due to a novel missense mutation in the gene encoding choline acetyl
  4. Tamminga, C., Smith, R. C., Chang, S., Haraszti, J. S., and Davis, J. M. Depression associated with oral choline. Lancet 10-23-1976;2(7991):905. PubMed
  5. Wood, J. L. and Allison, R. G. Effects of consumption of choline and lecithin on neurological and cardiovascular systems. Fed.Proc. 1982;41(14):3015-3021.
  6. Growdon, J. H. and Gelenberg, A. J. Choline and lecithin administration to patients with tardive dyskinesia. Trans.Am.Neurol.Assoc. 1978;103:95-99.
  7. Smith, C. M., Swash, M., Exton-Smith, A. N., Phillips, M. J., Overstall, P. W., Piper, M. E., and Bailey, M. R. Choline therapy in Alzheimer's disease. Lancet 8-5-1978;2(8084):318. PubMed
  8. Morrison, L. M. and W. F. Gonzales. Choline in coronary atherosclerosis. Amer.Heart J. 1950;39:729.
  9. Christie, J. G. Blackburn 1. M. Glen A. I. M. Zeisel S. Shering A. & Yates C. M. Effects of choline and lecithin on CSF choline levels and on cognitive functioning in patients with presenile dementia of the Alzheimer type. Nutrition and the brain 1979;5
  10. Sidhu N, Davies S, Nadarajah A, et al. Oral choline supplementation for postoperative pain. Br J Anaesth 2013;111(2):249-55. PubMed
  11. Wozniak JR, Fuglestad AJ, Eckerle JK, et al. Choline supplementation in children with fetal alcohol spectrum disorders has high feasibility and tolerability. Nutr Res. 2013;33(11):897-904. PubMed
  12. Wozniak JR, Fuglestad AJ, Eckerle JK, et al. Choline supplementation in children with fetal alcohol disorders: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2015;102(5): 1113-25.
  13. Ross RG, Hunter SK, McCarthy L, et al. Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk. Am J Psychiatry. 2013;170(3):290-8. PubMed
  14. Food and Nutrition Board, Institute of Medicine. Choline. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington D.C.: National Academy Press; 1998:390-422.

See these in context on the Choline monograph →

Black Pepper 29 references
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  2. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  3. Bano G, Amla V, Raina RK, et al. The effect of piperine on pharmacokinetics of phenytoin in healthy volunteers. Planta Med 1987;53:568-9. PubMed
  4. Bano G, et al. Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. Eur J Clin Pharmacol 1991;41;615-7. PubMed
  5. Cohle SD, Trestrail JD III, Graham MA, et al. Fatal pepper aspiration. Am J Dis Child 1988;142:633-6. PubMed
  6. Bhardwaj RK, Glaeser H, Becquemont L, et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50. PubMed
  7. Velpandian T, Jasuja R, Bhardwaj RK, et al. Piperine in food: interference in the pharmacokinetics of phenytoin. Eur J Drug Metab Pharmacokinet 2001;26:241-7. PubMed
  8. Pattanaik S, Hota D, Prabhakar S, et al. Pharmacokinetic interaction of a single dose of piperine with steady-state carbamazepine in epilepsy patients. Phytother Res 2009;23:1281-6.
  9. Munakata, M., Kobayashi, K., Niisato-Nezu, J., Tanaka, S., Kakisaka, Y., Ebihara, T., Ebihara, S., Haginoya, K., Tsuchiya, S., and Onuma, A. Olfactory stimulation using black pepper oil facilitates oral feeding in pediatric patients receiving long-term en
  10. Myers, B. M., Smith, J. L., and Graham, D. Y. Effect of red pepper and black pepper on the stomach. Am J Gastroenterol 1987;82(3):211-214.
  11. Raghavendra, R. H. and Naidu, K. A. Spice active principles as the inhibitors of human platelet aggregation and thromboxane biosynthesis. Prostaglandins Leukot.Essent.Fatty Acids 2009;81(1):73-78. PubMed
  12. Subehan, Usia, T., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of human liver microsomal cytochrome P450 2D6 (CYP2D6) by alkamides of Piper nigrum. Planta Med 2006;72(6):527-532.
  13. Kasibhatta, R. and Naidu, M. U. Influence of piperine on the pharmacokinetics of nevirapine under fasting conditions: a randomised, crossover, placebo-controlled study. Drugs R.D. 2007;8(6):383-391. PubMed
  14. Usia, T., Iwata, H., Hiratsuka, A., Watabe, T., Kadota, S., and Tezuka, Y. CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants. Phytomedicine. 2006;13(1-2):67-73. PubMed
  15. Mujumdar, A. M., Dhuley, J. N., Deshmukh, V. K., Raman, P. H., Thorat, S. L., and Naik, S. R. Effect of piperine on pentobarbitone induced hypnosis in rats. Indian J Exp.Biol. 1990;28(5):486-487.
  16. Panda, S. and Kar, A. Piperine lowers the serum concentrations of thyroid hormones, glucose and hepatic 5'D activity in adult male mice. Horm.Metab Res. 2003;35(9):523-526. PubMed
  17. Lawless, H. and Stevens, D. A. Effects of oral chemical irritation on taste. Physiol Behav. 1984;32(6):995-998. PubMed
  18. Hiwale, A. R., Dhuley, J. N., and Naik, S. R. Effect of co-administration of piperine on pharmacokinetics of beta-lactam antibiotics in rats. Indian J Exp.Biol. 2002;40(3):277-281.
  19. Han, Y., Chin Tan, T. M., and Lim, L. Y. In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression. Toxicol.Appl.Pharmacol. 8-1-2008;230(3):283-289. PubMed
  20. Sharma, P., Varma, M. V., Chawla, H. P., and Panchagnula, R. In situ and in vivo efficacy of peroral absorption enhancers in rats and correlation to in vitro mechanistic studies. Farmaco 2005;60(11-12):874-883. PubMed
  21. Aher, S., Biradar, S., Gopu, C. L., and Paradkar, A. Novel pepper extract for enhanced P-glycoprotein inhibition. J Pharm.Pharmacol. 2009;61(9):1179-1186. PubMed
  22. Zutshi, R. K., Singh, R., Zutshi, U., Johri, R. K., and Atal, C. K. Influence of piperine on rifampicin blood levels in patients of pulmonary tuberculosis. J Assoc.Physicians India 1985;33(3):223-224.
  23. Marotta, R. B. and Floch, M. H. Diet and nutrition in ulcer disease. Med Clin North Am 1991;75(4):967-979. PubMed
  24. Subehan, Usia, T., Iwata, H., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants. J Ethnopharmacol. 5-24-2006;105(3):449-455. PubMed
  25. Gimenez L, Zacharisen M. Severe pepper allergy in a young child. WMJ. 2011 Jun;110(3):138-9.
  26. Ren T, Yang M, Xiao M, Zhu J, Xie W, Zuo Z. Time-dependent inhibition of carbamazepine metabolism by piperine in anti-epileptic treatment. Life Sci. 2019;218:314-323. PubMed
  27. Thomas AB, Choudhary DC, Raje A, Nagrik SS. Pharmacokinetics and pharmacodynamic herb-drug interaction of piperine with atorvastatin in rats. J Chromatogr Sci 2021;59(4):371-80. PubMed
  28. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
  29. Lin F, Hu Y, Zhang Y, Zhao L, Zhong D, Liu J. Predicting Food-Drug Interactions between Piperine and CYP3A4 Substrate Drugs Using PBPK Modeling. Int J Mol Sci 2024;25(20):10955. PubMed

See these in context on the Black Pepper monograph →

L-carnitine 41 references
  1. Ellaway CM, Williams K, Leonard H, et al. Rett syndrome: randomized controlled trial of L-carnitine. J Child Neurol 1999;14:162-7. PubMed
  2. Anon. Carnitor (levocarnitine) package insert. Sigma-Tau Pharmaceuticals Inc, Gaithersburg, MD. December 1999.
  3. Cherchi A, Lai C, Angelino F, et al. Effects of L-carnitine on exercise tolerance in chronic stable angina: a multicenter, double-blind, randomized, placebo-controlled, crossover study. Int J Clin Pharmacol Ther Toxicol 1985;23:569-72.
  4. Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome. Neuropsychobiology 1997;35:16-23. PubMed
  5. Benvenga S, Ruggeri RM, Russo A, et al. Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Meta
  6. Martinez E, Domingo P, Roca-Cusachs A. Potentiation of acenocoumarol action by L-carnitine. J Intern Med 1993;233:94.
  7. Bachmann HU, Hoffmann A. Interaction of food supplement L-carnitine with oral anticoagulant acenocoumarol. Swiss Med Wkly 2004;134:385. PubMed
  8. Evans AM, Fornasini G. Pharmacokinetics of L-carnitine. Clin Pharmacokinet 2003;42:941-67. PubMed
  9. 12761 Benvenga S, Amato A, Calvani M, Trimarchi F. Effects of carnitine on thyroid hormone action. Ann N Y Acad Sci 2004;1033:158-67. PubMed
  10. Ciacci C, Peluso G, Iannoni E, et al. L-Carnitine in the treatment of fatigue in adult celiac disease patients: a pilot study. Dig Liver Dis 2007;39:922-8. PubMed
  11. Cruciani RA, Dvorkin E, Homel P, et al. Safety, tolerability and symptom outcomes associated with L-carnitine supplementation in patients with cancer, fatigue, and carnitine deficiency: a phase I/II study. J Pain Symptom Manage 2006;32:551-9. PubMed
  12. Lebrun C, Alchaar H, Candito M, et al. Levocarnitine administration in multiple sclerosis patients with immunosuppressive therapy-induced fatigue. Mult Scler 2006;12:321-4. PubMed
  13. Malaguarnera M, Cammalleri L, Gargante MP, et al. L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial. Am J Clin Nutr 2007;86:1738-44. PubMed
  14. Mantovani G, Maccio A, Madeddu C, et al. Randomized phase III clinical trial of five different arms of treatment in 322 patients with cancer cachexia. Oncologist 2010;15:200-11.
  15. Angelova-Fischer I, Rippke F, Fischer TW, Neufang G, Zillikens D. A double-blind, randomized, vehicle-controlled efficacy assessment study of a skin care formulation for improvement of mild to moderately severe acne. J Eur Acad Dermatol Venereol. 2013 Jul PubMed
  16. Hatamkhani S, Khalili H, Karimzadeh I, Dashti-Khavidaki S, Abdollahi A, Jafari S. Carnitine for prevention of antituberculosis drug-induced hepatotoxicity: a randomized, clinical trial. J Gastroenterol. Hepatol. 2014 May;29(5):997-1004. PubMed
  17. Boehm G, Stahl B. Oligosaccharides from milk. J Nutr 2007;137(3 Suppl 2):847S-849S.
  18. Van Oudheusden, L. J. and Scholte, H. R. Efficacy of carnitine in the treatment of children with attention-deficit hyperactivity disorder. Prostaglandins Leukot.Essent.Fatty Acids 2002;67(1):33-38. PubMed
  19. Derosa, G., Cicero, A. F., Gaddi, A., Mugellini, A., Ciccarelli, L., and Fogari, R. The effect of L-carnitine on plasma lipoprotein(a) levels in hypercholesterolemic patients with type 2 diabetes mellitus. Clin Ther 2003;25(5):1429-1439. PubMed
  20. Foitzik, K., Hoting, E., Heinrich, U., Tronnier, H., and Paus, R. Indications that topical L-carnitin-L-tartrate promotes human hair growth in vivo. J Dermatol.Sci 2007;48(2):141-144. PubMed
  21. Kumar, A., Singh, R. B., Saxena, M., Niaz, M. A., Josh, S. R., Chattopadhyay, P., Mechirova, V., Pella, D., and Fedacko, J. Effect of carni Q-gel (ubiquinol and carnitine) on cytokines in patients with heart failure in the Tishcon study. Acta Cardiol. 20
  22. Cruciani, R. A., Dvorkin, E., Homel, P., Culliney, B., Malamud, S., Lapin, J., Portenoy, R. K., and Esteban-Cruciani, N. L-carnitine supplementation in patients with advanced cancer and carnitine deficiency: a double-blind, placebo-controlled study. J Pa PubMed
  23. Malaguarnera, M., Vacante, M., Avitabile, T., Malaguarnera, M., Cammalleri, L., and Motta, M. L-Carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes. Am J Clin.Nutr 2009;89(1):71-76. PubMed
  24. Alvarez, T. M., Guardiola, P. D., Roldan, J. O., Elviro, R., Wevers, R., and Guijarro, G. [Primary trimethylaminuria: the fish odor syndrome]. Endocrinol.Nutr. 2009;56(6):337-340.
  25. Wu, Z. M., Lu, X., Wang, Y. W., Sun, J., Tao, J. W., Yin, F. H., and Cheng, H. J. [Short-term medication of L-carnitine before intracytoplasmic sperm injection for infertile men with oligoasthenozoospermia]. Zhonghua Nan.Ke.Xue 2012;18(3):253-256.
  26. Tarighat, Esfanjani A., Mahdavi, R., Ebrahimi, Mameghani M., Talebi, M., Nikniaz, Z., and Safaiyan, A. The effects of magnesium, L-carnitine, and concurrent magnesium-L-carnitine supplementation in migraine prophylaxis. Biol.Trace Elem.Res 2012;150(1-3): PubMed
  27. DiNicolantonio, J. J., Lavie, C. J., Fares, H., Menezes, A. R., and O'Keefe, J. H. L-carnitine in the secondary prevention of cardiovascular disease: systematic review and meta-analysis. Mayo Clin Proc. 2013;88(6):544-551. PubMed
  28. Huang, W. W., Wang, M. Y., Shi, H. M., Peng, Y., Peng, C. S., Zhang, M., Li, Y., Lu, J., and Li, X. B. Comparative study of bioactive constituents in crude and processed Glycyrrhizae radix and their respective metabolic profiles in gastrointestinal tract
  29. Madsen KL, Preisler N, Orngreen MC, Andersen SP, Olesen JH, Lund AM, Vissing J. Patients with medium-chain acyl-coenzyme a dehydrogenase deficiency have impaired oxidation of fat during exercise but no effect of L-carnitine supplementation. J Clin Endocri
  30. Prohaska ES, Muzyk AJ, Rivelli SK. Levocarnitine-induced hypophosphatemia in a hemodialysis patient with acute valproic acid toxicity. J Neuropsychiatry Clin Neurosci. 2012 Winter;24(1):E18-9. PubMed
  31. Shang R, Sun Z, Li H. Effective dosing of L-carnitine in the secondary prevention of cardiovascular disease: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2014 Jul 21;14:88. PubMed
  32. Zhang JJ, Wu ZB, Cai YJ, Ke B, Huang YJ, Qiu CP, Yang YB, Shi LY, Qin J. L-carnitine ameliorated fasting-induced fatigue, hunger, and metabolic abnormalities in patients with metabolic syndrome: a randomized controlled study. Nutr J. 2014 Nov 26;13:110. PubMed
  33. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Intestinal microbiota metabolism of L-carn
  34. Jun DW, Kim BI, Cho YK, Kim HJ, Kwon YO, Park SY, Han SY, Baek YH, Jung YJ, Kim HY, Kim W, Heo J, Woo HY, Hwang SG, Rim KS, Choi JY, Bae SH, Lee YS, Lim YS,Cheong JY, Cho SW, Lee BS, Kim SH, Sohn JH, Kim TY, Paik YH, Kim JK, Lee KS. Efficacy and safety of
  35. An JH, Kim YJ, Kim KJ, et al. L-carnitine supplementation for the management of fatigue in patients with hypothyroidism on levothyroxine treatment: a randomized, double-blind, placebo-controlled trial. Endocr J. 2016;63(10):885-95. PubMed
  36. Chen N, Yang M, Zhou M, Xiao J, Guo J, He L. L-carnitine for cognitive enhancement in people without cognitive impairment. Cochrane Database Syst Rev. 2017;3:CD009374. PubMed
  37. Khajeh B, Dashti-Khavidaki S, Nasiri-Toosi M, Mohammadi K, Jafari A. Effects of pre-transplant L-carnitine supplementation on primary graft dysfunction in liver transplant recipients: a pilot, randomized, placebo-controlled clinical trial. Res Pharm Sci. PubMed
  38. Kubota K, Uojima H, Shao X, et al. Additional L-carnitine Reduced the Risk of Hospitalization in Patients with Overt Hepatic Encephalopathy on Rifaximin. Dig Dis 2021. PubMed
  39. Amini L, Yaghini O, Ghazavi M, Aslani N. L-carnitine versus propranolol for pediatric migraine prophylaxis. Iran J Child Neurol 2021;15(2):77-86.
  40. Shakibaei F, Jelvani D. Effect of adding l -carnitine to risperidone on behavioral, cognitive, social, and physical symptoms in children and adolescents with autism: A randomized double-blinded placebo-controlled clinical trial. Clin Neuropharmacol 2023;4 PubMed
  41. Moustafa I, Connolly C, Anis M, Mustafa H, Oosthuizen F, Viljoen M. A prospective study to evaluate the efficacy and safety of vitamin E and levocarnitine prophylaxis against doxorubicin-induced cardiotoxicity in adult breast cancer patients. J Oncol Phar PubMed

See these in context on the L-carnitine monograph →

Schisandra 26 references
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  2. Iwata H, Tezuka Y, Kadota S, et al. Identification and characterization of potent CYP3A4 inhibitors in Schisandra fruit extract. Drug Metab Dispos 2004;32:1351-8. PubMed
  3. Mu Y, Zhang J, Zhang S, et al. Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. J Pharmacol Exp Ther 2006;316:1369-77. PubMed
  4. Xin HW, Wu XC, Li Q, et al. Effects of Schisandra sphenanthera extract on the pharmacokinetics of tacrolimus in healthy volunteers. Br J Clin Pharmacol 2007;64:469-75.
  5. Qin XL, Bi HC, Wang XD, et al. Mechanistic understanding of the different effects of Wuhzi Tablet (Schisandra sphenanthera extract) on the absorption and first-pass intestinal and hepatic metabolism of tacrolimus (FK506). Int J Pharm 2010;389:114-21.
  6. Makino, T., Mizuno, F., and Mizukami, H. Does a kampo medicine containing schisandra fruit affect pharmacokinetics of nifedipine like grapefruit juice? Biol.Pharm.Bull. 2006;29(10):2065-2069. PubMed
  7. Fan L, Mao XQ, Tao GY, Wang G, Jiang F, Chen Y, Li Q, Zhang W, Lei HP, Hu DL, Huang YF, Wang D, Zhou HH. Effect of Schisandra chinensis extract and Ginkgo biloba extract on the pharmacokinetics of talinolol in healthy volunteers. Xenobiotica. 2009 Mar;39(
  8. Jiang W, Wang X, Xu X, Kong L. Effect of Schisandra sphenanthera extract on the concentration of tacrolimus in the blood of liver transplant patients. Int J Clin Pharmacol Ther. 2010 Mar;48(3):224-9. PubMed
  9. Xin HW, Wu XC, Li Q, Yu AR, Xiong L. Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers. Br J Clin Pharmacol. 2009 May;67(5):541-6.
  10. Li J, Chen S, Qin X, et at. Wuzhi Tablet (<i>Schisandra sphenanthera</i> Extract) is a Promising Tacrolimus-Sparing Agent for Renal Transplant Recipients Who are CYP3A5 Expressers: a Two-Phase Prospective Study. Drug Metab Dispos. 2017;45(11):1114-1119.
  11. Qin XL, Li JL, Wang SH, Chen X, Huang M, Bi HC. Co-administration of Wuzhi tablet (Schisandra sphenanthera extract) alters tacrolimus pharmacokinetics in a dose- and time-dependent manner in rats. J Ethnopharmacol. 2020;263:113233. PubMed
  12. Yuan F, Liang X, Chen X, Qin X, Tan C, Wang L. CYP2C19 is involved in the effect of Wuzhi tablet (Schisandra sphenanthera extract) and its constituents on the pharmacokinetics of intravenous voriconazole. Pharmazie. 2020;75(11):559-564. DOI
  13. Zhang Z, Lu X, Dong L, Ma J, Fan X. Clinical observation on the effect of Wuzhi soft capsule on FK506 concentration in membranous nephropathy patients. Medicine (Baltimore). 2019;98(48):e18150. PubMed
  14. Yoo HH, Lee M, Lee MW, Lim SY, Shin J, Kim DH. Effects of Schisandra lignans on P-glycoprotein-mediated drug efflux in human intestinal Caco-2. Planta Med. 2007;73(5):444-50.
  15. Qiangrong P, Wang T, Lu Q, Hu X. Schisandrin B--a novel inhibitor of P-glycoprotein. Biochem Biophys Res Commun. 2005;335(2):406-11. PubMed
  16. Chen L, Ji N, Zhang M, Chen W. The influence of Wuzhi capsule on the pharmacokinetics of cyclophosphamide. Recent Pat Anticancer Drug Discov 2021. PubMed
  17. Cheng X, Ma J, Xu X, Zhang L, Wang X, Wu R. Effect of Wuzhi capsules on cyclosporine A concentration in children with aplastic anemia immunotherapy: a single-center observational study. Expert Rev Clin Pharmacol 2022:1-5. PubMed
  18. Cheng F, Li Q, Wang J, Zeng F, Zhang Y. Effects and safety evaluation of Wuzhi capsules combined with tacrolimus for the treatment of kidney transplantation recipients. J Clin Pharm Ther 2021;46(6):1636-49. PubMed
  19. Teng F, Wang W, Zhang W, et al. Effect of hepar-protecting Wuzhi capsule on pharmacokinetics and dose-effect character of tacrolimus in healthy volunteers. Biopharm Drug Dispos 2022.
  20. Kou K, Sun X, Li M, et al. Beneficial effects of Wuzhi capsule on tacrolimus blood concentrations in liver transplant patients with different donor-recipient CYP3A5 genotypes. J Clin Pharm Ther 2022;47(2):200-10. PubMed
  21. Peng Y, Jiang F, Zhou R, et al. Clinical evaluation of the efficacy and safety of co-administration of Wuzhi capsule and tacrolimus in adult Chinese patients with myasthenia gravis. Neuropsychiatr Dis Treat 2021;17:2281-9. PubMed
  22. Chen P, Dai R, She Y, et al. Prediction of tacrolimus and Wuzhi tablet pharmacokinetic interaction magnitude in renal transplant recipients. Clin Transplant 2022;36(12):e14807. PubMed
  23. Qu J, Bian R, Liu B, et al. The pharmacokinetic study of tacrolimus and Wuzhi capsule in Chinese liver transplant patients. Front Pharmacol 2022;13:956166. PubMed
  24. Zhou Y, Huang X, Liu L, et al. Effect of Wuzhi preparations on tacrolimus in CYP3A5 expressers during the early period after transplantation: A real-life experience from heart transplant recipients. Transpl Immunol 2023;76:101748. PubMed
  25. Huang Q, Lin X, Wang Y, et al. Tacrolimus pharmacokinetics in pediatric nephrotic syndrome: A combination of population pharmacokinetic modelling and machine learning approaches to improve individual prediction. Front Pharmacol 2022;13:942129. PubMed
  26. Wang CB, Zhang YJ, Zhao MM, Zhao LM. Population pharmacokinetic analyses of tacrolimus in non-transplant patients: a systematic review. Eur J Clin Pharmacol 2023;79(7):897-913. PubMed

See these in context on the Schisandra monograph →

Gotu Kola 18 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. Pointel JP, Boccalon H, Cloarec M, et al. Titrated extract of Centella asiatica (TECA) in the treatment of venous insufficiency of the lower limbs. Angiol 1987;38:46-50. PubMed
  3. Brinkhaus B, Lindner M, Schuppan D, Hahn EG. Chemical, pharmacological and clinical profile of the east Asian medical plant Centella asiatica. Phytomedicine 2000;7:427-48.
  4. Eun HC, Lee AY. Contact dermatitis due to madecassol. Contact Dermatitis 1985;13:310-3.. PubMed
  5. Hausen BM. Centella asiatica (Indian pennywort), an effective therapeutic but a weak sensitizer. Contact Dermatitis 1993;29:175-9..
  6. Bilbao I, Aguirre A, Zabala R, et al. Allergic contact dermatitis from butoxyethyl nicotinic acid and Centella asiatica extract. Contact Dermatitis 1995;33:435-6.
  7. Cesarone MR, Incandela L, De Sanctis MT, et al. Evaluation of treatment of diabetic microangiopathy with total triterpenic fraction of Centella asiatica: a clinical prospective randomized trial with a microcirculatory model. Angiology 2001;52 Suppl 2 DOI
  8. Bradwejn J, Zhou Y, Koszycki D, Shlik J. A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects. J Clin Psychopharmacol 2000;20:680-4. PubMed
  9. Young GL, Jewell D. Creams for preventing stretch marks in pregnancy. Cochrane Database Syst Rev 2000;(2):CD000066. PubMed
  10. Jorge OA, Jorge AD. Hepatotoxicity associated with the ingestion of Centella asiatica. Rev Esp Enferm Dig 2005;97:115-24. PubMed
  11. Mallol J, Belda MA, Costa D, et al. Prophylaxis of striae gravidarum with a topical formulation. A double blind trial. Int J Cosmet Sci 1991;3:51-7.
  12. Izu, R., Aguirre, A., Gil, N., and Diaz-Perez, J. L. Allergic contact dermatitis from a cream containing Centella asiatica extract. Contact Dermatitis 1992;26(3):192-193.
  13. Santucci, B., Picardo, M., and Cristaudo, A. Contact dermatitis due to Centelase. Contact Dermatitis 1985;13(1):39. PubMed
  14. Vena, G. A. and Angelini, G. Contact allergy to Centelase. Contact Dermatitis 1986;15(2):108-109. PubMed
  15. Marastoni, F., Baldo, A., Redaelli, G., and Ghiringhelli, L. [Centella asiatica extract in venous pathology of the lower limbs and its evaluation as compared with tribenoside]. Minerva Cardioangiol. 1982;30(4):201-207.
  16. Danese, P., Carnevali, C., and Bertazzoni, M. G. Allergic contact dermatitis due to Centella asiatica extract. Contact Dermatitis 1994;31(3):201.
  17. Bilbao, I., Aguirre, A., Zabala, R., Gonzalez, R., Raton, J., and Diaz Perez, J. L. Allergic contact dermatitis from butoxyethyl nicotinic acid and Centella asiatica extract. Contact Dermatitis 1995;33(6):435-436.
  18. Dantuluri S, North-lewis P, Karthik SV. Gotu Kola induced hepatotoxicity in a child - need for caution with alternative remedies. Dig Liver Dis. 2011;43(6):500. PubMed

See these in context on the Gotu Kola monograph →

Bromelain 19 references
  1. Nettis E, Napoli G, Ferrannini A, Tursi A. IgE-mediated allergy to bromelain. Allergy 2001;56:257-8. PubMed
  2. Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol 1988;22:191-203.. PubMed
  3. Bradbrook ID, Morrison PJ, Rogers HJ. The effect of bromelain on the absorption of orally administered tetracycline. Br J Clin Pharmacol 1978;6:552-4. PubMed
  4. Bush TM, Rayburn KS, Holloway SW, et al. Adverse interactions between herbal and dietary substances and prescription medications: a clinical survey. Altern Ther Health Med 2007;13:30-5.
  5. Brien S, Lewith G, Walker AF, et al. Bromelain as an adjunctive treatment for moderate-to-severe osteoarthritis of the knee: a randomized placebo-controlled pilot study. QJM 2006;99:841-50. PubMed
  6. Mori S, Ojima Y, Hirose T, et al. The clinical effect of proteolytic enzyme containing bromelain and trypsin on urinary tract infection evaluated by double blind method. Acta Obstet Gynaecol Jpn 1972;19:147-53.
  7. Glaser D, Hilberg T. The influence of bromelain on platelet count and platelet activity in vitro. Platelets 2006;17:37-41. PubMed
  8. Heinicke R M, van der Wal L, Yokoyama M. Effect of bromelain (Ananase) on human platelet aggregation. Experientia 1972;28:844-5. PubMed
  9. Gailhofer, G., Wilders-Truschnig, M., Smolle, J., and Ludvan, M. Asthma caused by bromelain: an occupational allergy. Clin Allergy 1988;18(5):445-450. PubMed
  10. Mattei, O., Fabri, G., and Farina, G. [Occupational health experience regarding four cases of asthma due to bromelain (author's transl)]. Medicina del Lavoro 1979;70(5):404-409.
  11. Galleguillos, F. and Rodriguez, J. C. Asthma caused by bromelin inhalation. Clin Allergy 1978;8(1):21-24. PubMed
  12. Perez-Camo I, Quirce S, Duran MA, and et al. Latex allergy: evidence of cross-reactivity with papain and bromelain [abstract]. Allergy 1996;51(suppl 31):48.
  13. Martin GJ, Ehrenreich J, and Asbell N. Bromelain: pineapple proteases with anti-edema activity. Exp Med Surg 1962;20:227-247.
  14. Kasemsuk T, Saengpetch N, Sibmooh N, Unchern S. Improved WOMAC score following 16-week treatment with bromelain for knee osteoarthritis. Clin Rheumatol. 2016 Oct;35(10):2531-40. PubMed
  15. Kutlu Ö, DemirbaS A, Elmas ÖF, Güvenç U, Metin A. Fixed drug eruption: a new side effect of bromelain. Contact Dermatitis 2020. Online ahead of print. PubMed
  16. Shoham Y, Shapira E, Haik J, et al. Bromelain-based enzymatic debridement of chronic wounds: Results of a multicentre randomized controlled trial. Wound Repair Regen 2021;29(6):899-907. PubMed
  17. Pfister P, Garcia Wendel PD, Kim BS, et al. Coagulation side effects of enzymatic debridement in burned patients. Burns 2022. PubMed
  18. Hasham S, Riyat H, Fletcher A, O'Boyle CP, Alexander S. To bleed or not to bleed? Case series and discussion of haemorrhage risk with enzymatic debridement in burn injuries. Scars Burn Heal 2023;9:20595131231168333. PubMed
  19. Leelakanok N, Petchsomrit A, Janurai T, Saechan C, Sunsandee N. Efficacy and safety of bromelain: A systematic review and meta-analysis. Nutr Health 2023. PubMed

See these in context on the Bromelain monograph →

Artichoke 16 references
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  2. Walker AF, Middleton RW, Petrowicz O. Artichoke leaf extract reduces symptoms of irritable bowel syndrome in a post-marketing surveillance study. Phytother Res 2001;15:58-61. PubMed
  3. Pittler MH, White AR, Stevinson C, Ernst E. Effectiveness of artichoke extract in preventing alcohol-induced hangovers: a randomized controlled trial. CMAJ 2003;169:1269-73.
  4. Romano, C., Ferrara, A., and Falagiani, P. A case of allergy to globe artichoke and other clinical cases of rare food allergy. J Investig.Allergol.Clin Immunol. 2000;10(2):102-104.
  5. Miralles, J. C., Garcia-Sells, J., Bartolome, B., and Negro, J. M. Occupational rhinitis and bronchial asthma due to artichoke (Cynara scolymus). Ann Allergy Asthma Immunol. 2003;91(1):92-95. PubMed
  6. Franck, P., Moneret-Vautrin, D. A., Morisset, M., Kanny, G., Megret-Gabeaux, M. L., and Olivier, J. L. Anaphylactic reaction to inulin: first identification of specific IgEs to an inulin protein compound. Int Arch Allergy Immunol 2005;136(2):155-158. PubMed
  7. Meding, B. Allergic contact dermatitis from artichoke, Cynara scolymus. Contact Dermatitis 1983;9(4):314.
  8. Quirce, S., Tabar, A. I., Olaguibel, J. M., and Cuevas, M. Occupational contact urticaria syndrome caused by globe artichoke (Cynara scolymus). J Allergy Clin Immunol. 1996;97(2):710-711. PubMed
  9. Held C. Von der 1. Deutsche-Ungarischen Phytopharmakon-Konferenz, Budapest, 20. November 1991. Z Klin Med 1992;47:92-93.
  10. Barrat E, Zaïr Y, Ogier N, et al. A combined natural supplement lowers LDL cholesterol in subjects with moderate untreated hypercholesterolemia: a randomized placebo-controlled trial. Int J Food Sci Nutr. 2013;64(7):882-9. PubMed
  11. Huber R, Müller M, Naumann J, Schenk T, Lüdtke R. Artichoke leave extract for chronic hepatitis C - a pilot study. Phytomedicine. 2009 Sep;16(9):801-4. PubMed
  12. Caputo F, Barranco R, Bonsignore A, Fraternali Orcioni G, Ventura F. A rare case of fatal bowel obstruction secondary to a colonic bezoar. Am J Forensic Med Pathol. 2018;39(1):38-40. PubMed
  13. Elsebai MF, Abass K, Hakkola J, Atawia AR, Farag MA. The wild Egyptian artichoke as a promising functional food for the treatment of hepatitis C virus as revealed via UPLC-MS and clinical trials. Food Funct. 2016;7(7):3006-16. PubMed
  14. Moradi M, Sohrabi G, Golbidi M, et al. Effects of artichoke on blood pressure: a systematic review and meta-analysis. Complement Ther Med 2021;57:102668. PubMed
  15. Jalili C, Moradi S, Babaei A, et al. Effects of Cynara scolymus L. on glycemic indices: a systematic review and meta-analysis of randomized clinical trials. Complement Ther Med 2020;52:102496. PubMed
  16. Gallo R, Oddenino G, Trave I, Gasparini G, Guadagno A, Parodi A. Contact sensitivity to sesquiterpene lactone mix and artichoke in a patient with severe recurrent dermatitis: A puzzling case. Contact Dermatitis 2023;88(2):156-158. PubMed

See these in context on the Artichoke monograph →

Oregon Grape 21 references
  1. Wiesenauer M, Lydtke R. Mahonia aquifolium in patients with Psoriasis vulgaris; an intraindividual study. Phytomedicine 1996;3:231-5.
  2. Chan E. Displacement of bilirubin from albumin by berberine. Biol Neonate 1993;63:201-8. PubMed
  3. Janbaz KH, Gilani AH. Studies on preventive and curative effects of berberine on chemical-induced hepatotoxicity in rodents. Fitoterapia 2000;71:25-33.. PubMed
  4. Wu X, Li Q, Xin H, Yu A, Zhong M. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol 2005;61:567-72. PubMed
  5. Gulliver WP, Donsky HJ. A report on three recent clinical trials using Mahonia aquifolium 10% topical cream and a review of the worldwide clinical experience with Mahonia aquifolium for the treatment of plaque psoriasis. Am J Ther 2005;12:398-406. PubMed
  6. Zhang Y, Li X, Zou D, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab 2008;93:2559-65. PubMed
  7. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  8. Chatterjee P, Franklin MR. Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos 2003;31:1391-7. PubMed
  9. Shanbhag, S. M., Kulkarni, H. J., and Gaitonde, B. B. Pharmacological actions of berberine on the central nervous system. Jpn.J Pharmacol 1970;20(4):482-487. PubMed
  10. Wu, J. F. and Liu, T. P. [Effects of berberine on platelet aggregation and plasma levels of TXB2 and 6-keto-PGF1 alpha in rats with reversible middle cerebral artery occlusion]. Yao Xue.Xue.Bao. 1995;30(2):98-102.
  11. Peng, W. H., Hsieh, M. T., and Wu, C. R. Effect of long-term administration of berberine on scopolamine-induced amnesia in rats. Jpn J Pharmacol 1997;74(3):261-266. DOI
  12. Sabir M and Bhide NK. Study of some pharmacological actions of berberine. Ind J Physiol & Pharmac 1971;15(3):111-132.
  13. Tripathi YB and Shukla SD. Berberis artistata inhibits PAF induced aggregation of rabbit platelets. Phytotherapy Research 1996;10:628-630.
  14. Yin, J., Xing, H., and Ye, J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism 2008;57(5):712-717. PubMed
  15. Zhang, H., Wei, J., Xue, R., Wu, J. D., Zhao, W., Wang, Z. Z., Wang, S. K., Zhou, Z. X., Song, D. Q., Wang, Y. M., Pan, H. N., Kong, W. J., and Jiang, J. D. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin re
  16. Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. PubMed
  17. Wei, W., Zhao, H., Wang, A., Sui, M., Liang, K., Deng, H., Ma, Y., Zhang, Y., Zhang, H., and Guan, Y. A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndro
  18. Hermann, R. and von, Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med 2012;78(13):1458-1477. PubMed
  19. Chun YT, Yip TT, Lau KL, and et al. A biochemical study on the hypotensive effect of berberine in rats. Gen Pharmac 1979;10:177-182. PubMed
  20. Lan J, Zhao Y, Dong F, et al. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015;161:69-81. PubMed
  21. Fan Y, Zhou Z, Zhang L. Effect of Oregon grape root extracts on P-glycoprotein mediated transport in in vitro cell lines. J Pharm Pharm Sci 2024;26:11927. PubMed

See these in context on the Oregon Grape monograph →

Turmeric 102 references
  1. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  2. Sharma RA, McLelland HR, Hill KA, et al. Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res 2001;7:1894-900..
  3. Shah BH, Nawaz Z, Pertani SA. Inhibitory effect of curcumin, a food spice from turmeric, on platelet-activating factor- and arachidonic acid-mediated platelet aggregation through inhibition of thromboxane formation and Ca2+ signaling. Biochem Pharmacol 1 PubMed
  4. Hata M, Sasaki E, Ota M, et al . Allergic contact dermatitis from curcumin (turmeric). Contact Dermatitis 1997;36:107-8. PubMed
  5. Kuttan R, Sudheeran PC, Josph CD. Turmeric and curcumin as topical agents in cancer therapy. Tumori 1987;73:29-31.. PubMed
  6. Thapliyal R, Deshpande SS, Maru GB. Mechanism(s) of turmeric-mediated protective effects against benzo(a)pyrene-derived DNA adducts. Cancer Lett 2002;175:79-88. PubMed
  7. Lee SW, Nah SS, Byon JS, et al. Transient complete atrioventricular block associated with curcumin intake. Int J Cardiol 2011;150:e50-2. PubMed
  8. Kuptniratsaikul V, Thanakhumtorn S, Chinswangwatanakul P, et al. Efficacy and safety of Curcuma domestica extracts in patients with knee osteoarthritis. J Altern Complement Med 2009;15:891-7.
  9. Carroll RE, Benya RV, Turgeon DK, et al. Phase IIa clinical trial of curcumin for the prevention of colorectal neoplasia. Cancer Prev Res (Phila) 2011;4:354-64. PubMed
  10. Junyaprasert, V. B., Soonthornchareonnon, N., Thongpraditchote, S., Murakami, T., and Takano, M. Inhibitory effect of Thai plant extracts on P-glycoprotein mediated efflux. Phytother.Res 2006;20(1):79-81. PubMed
  11. Ampasavate, C., Sotanaphun, U., Phattanawasin, P., and Piyapolrungroj, N. Effects of Curcuma spp. on P-glycoprotein function. Phytomedicine. 2010;17(7):506-512. PubMed
  12. Hou, X. L., Takahashi, K., Tanaka, K., Tougou, K., Qiu, F., Komatsu, K., Takahashi, K., and Azuma, J. Curcuma drugs and curcumin regulate the expression and function of P-gp in Caco-2 cells in completely opposite ways. Int.J Pharm 6-24-2008;358(1-2):224-2 PubMed
  13. Choi, B. H., Kim, C. G., Lim, Y., Shin, S. Y., and Lee, Y. H. Curcumin down-regulates the multidrug-resistance mdr1b gene by inhibiting the PI3K/Akt/NF kappa B pathway. Cancer Lett. 1-18-2008;259(1):111-118.
  14. Zhang, W., Tan, T. M., and Lim, L. Y. Impact of curcumin-induced changes in P-glycoprotein and CYP3A expression on the pharmacokinetics of peroral celiprolol and midazolam in rats. Drug Metab Dispos. 2007;35(1):110-115. PubMed
  15. Limtrakul, P., Chearwae, W., Shukla, S., Phisalphong, C., and Ambudkar, S. V. Modulation of function of three ABC drug transporters, P-glycoprotein (ABCB1), mitoxantrone resistance protein (ABCG2) and multidrug resistance protein 1 (ABCC1) by tetrahydrocu
  16. Holland, M. L., Panetta, J. A., Hoskins, J. M., Bebawy, M., Roufogalis, B. D., Allen, J. D., and Arnold, J. C. The effects of cannabinoids on P-glycoprotein transport and expression in multidrug resistant cells. Biochem.Pharmacol 4-14-2006;71(8):1146-1154 PubMed
  17. Tang, X. Q., Bi, H., Feng, J. Q., and Cao, J. G. Effect of curcumin on multidrug resistance in resistant human gastric carcinoma cell line SGC7901/VCR. Acta Pharmacol Sin. 2005;26(8):1009-1016. PubMed
  18. Nabekura, T., Kamiyama, S., and Kitagawa, S. Effects of dietary chemopreventive phytochemicals on P-glycoprotein function. Biochem.Biophys.Res Commun. 2-18-2005;327(3):866-870. PubMed
  19. Romiti, N., Tongiani, R., Cervelli, F., and Chieli, E. Effects of curcumin on P-glycoprotein in primary cultures of rat hepatocytes. Life Sci. 1998;62(25):2349-2358. PubMed
  20. Yue, G. G., Cheng, S. W., Yu, H., Xu, Z. S., Lee, J. K., Hon, P. M., Lee, M. Y., Kennelly, E. J., Deng, G., Yeung, S. K., Cassileth, B. R., Fung, K. P., Leung, P. C., and Lau, C. B. The role of turmerones on curcumin transportation and P-glycoprotein acti
  21. Shenouda, N. S., Zhou, C., Browning, J. D., Ansell, P. J., Sakla, M. S., Lubahn, D. B., and MacDonald, R. S. Phytoestrogens in common herbs regulate prostate cancer cell growth in vitro. Nutr.Cancer 2004;49(2):200-208. PubMed
  22. Appiah-Opong, R., Commandeur, J. N., Vugt-Lussenburg, B., and Vermeulen, N. P. Inhibition of human recombinant cytochrome P450s by curcumin and curcumin decomposition products. Toxicology 6-3-2007;235(1-2):83-91. PubMed
  23. Hou, X. L., Takahashi, K., Kinoshita, N., Qiu, F., Tanaka, K., Komatsu, K., Takahashi, K., and Azuma, J. Possible inhibitory mechanism of Curcuma drugs on CYP3A4 in 1alpha,25 dihydroxyvitamin D3 treated Caco-2 cells. Int.J Pharm 6-7-2007;337(1-2):169-177.
  24. Valentine, S. P., Le Nedelec, M. J., Menzies, A. R., Scandlyn, M. J., Goodin, M. G., and Rosengren, R. J. Curcumin modulates drug metabolizing enzymes in the female Swiss Webster mouse. Life Sci. 4-11-2006;78(20):2391-2398. PubMed
  25. Price, R. J., Scott, M. P., Giddings, A. M., Walters, D. G., Stierum, R. H., Meredith, C., and Lake, B. G. Effect of butylated hydroxytoluene, curcumin, propyl gallate and thiabendazole on cytochrome P450 forms in cultured human hepatocytes. Xenobiotica 2 PubMed
  26. Ganta, S., Devalapally, H., and Amiji, M. Curcumin enhances oral bioavailability and anti-tumor therapeutic efficacy of paclitaxel upon administration in nanoemulsion formulation. J Pharm Sci 2010;99(11):4630-4641. PubMed
  27. Lamb, S. R. and Wilkinson, S. M. Contact allergy to tetrahydrocurcumin. Contact Dermatitis 2003;48(4):227. PubMed
  28. Joshi, J., Ghaisas, S., Vaidya, A., Vaidya, R., Kamat, D. V., Bhagwat, A. N., and Bhide, S. Early human safety study of turmeric oil (Curcuma longa oil) administered orally in healthy volunteers. J Assoc.Physicians India 2003;51:1055-1060.
  29. Mahesh, T., Balasubashini, M. S., and Menon, V. P. Effect of photo-irradiated curcumin treatment against oxidative stress in streptozotocin-induced diabetic rats. J Med.Food 2005;8(2):251-255. PubMed
  30. Thompson, D. A. and Tan, B. B. Tetrahydracurcumin-related allergic contact dermatitis. Contact Dermatitis 2006;55(4):254-255. PubMed
  31. Patumraj, S., Wongeakin, N., Sridulyakul, P., Jariyapongskul, A., Futrakul, N., and Bunnag, S. Combined effects of curcumin and vitamin C to protect endothelial dysfunction in the iris tissue of STZ-induced diabetic rats. Clin Hemorheol.Microcirc. 2006;3
  32. Liddle, M., Hull, C., Liu, C., and Powell, D. Contact urticaria from curcumin. Dermatitis 2006;17(4):196-197. PubMed
  33. Juan, H., Terhaag, B., Cong, Z., Bi-Kui, Z., Rong-Hua, Z., Feng, W., Fen-Li, S., Juan, S., Jing, T., and Wen-Xing, P. Unexpected effect of concomitantly administered curcumin on the pharmacokinetics of talinolol in healthy Chinese volunteers. Eur.J Clin PubMed
  34. Murugan, P. and Pari, L. Influence of tetrahydrocurcumin on erythrocyte membrane bound enzymes and antioxidant status in experimental type 2 diabetic rats. J Ethnopharmacol. 9-25-2007;113(3):479-486. PubMed
  35. Seo, K. I., Choi, M. S., Jung, U. J., Kim, H. J., Yeo, J., Jeon, S. M., and Lee, M. K. Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice. Mol.Nutr.Food Res 2008;5
  36. Weisberg, S. P., Leibel, R., and Tortoriello, D. V. Dietary curcumin significantly improves obesity-associated inflammation and diabetes in mouse models of diabesity. Endocrinology 2008;149(7):3549-3558. PubMed
  37. Jain, S. K., Rains, J., Croad, J., Larson, B., and Jones, K. Curcumin supplementation lowers TNF-alpha, IL-6, IL-8, and MCP-1 secretion in high glucose-treated cultured monocytes and blood levels of TNF-alpha, IL-6, MCP-1, glucose, and glycosylated hemog
  38. Yu, Y., Hu, S. K., and Yan, H. [The study of insulin resistance and leptin resistance on the model of simplicity obesity rats by curcumin]. Zhonghua Yu Fang Yi.Xue.Za Zhi. 2008;42(11):818-822.
  39. Pavithra, B. H., Prakash, N., and Jayakumar, K. Modification of pharmacokinetics of norfloxacin following oral administration of curcumin in rabbits. J Vet.Sci. 2009;10(4):293-297. PubMed
  40. Yan, Y. D., Kim, D. H., Sung, J. H., Yong, C. S., and Choi, H. G. Enhanced oral bioavailability of docetaxel in rats by four consecutive days of pre-treatment with curcumin. Int J Pharm 10-31-2010;399(1-2):116-120. PubMed
  41. Epelbaum, R., Schaffer, M., Vizel, B., Badmaev, V., and Bar-Sela, G. Curcumin and gemcitabine in patients with advanced pancreatic cancer. Nutr Cancer 2010;62(8):1137-1141. PubMed
  42. Madkor, H. R., Mansour, S. W., and Ramadan, G. Modulatory effects of garlic, ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin-nicotinamide diabetic rats. Br J Nutr 2011;105(8):1210-1217. PubMed
  43. Pungcharoenkul, K. and Thongnopnua, P. Effect of different curcuminoid supplement dosages on total in vivo antioxidant capacity and cholesterol levels of healthy human subjects. Phytother Res 2011;25(11):1721-1726.
  44. Kusuhara, H., Furuie, H., Inano, A., Sunagawa, A., Yamada, S., Wu, C., Fukizawa, S., Morimoto, N., Ieiri, I., Morishita, M., Sumita, K., Mayahara, H., Fujita, T., Maeda, K., and Sugiyama, Y. Pharmacokinetic interaction study of sulphasalazine in healthy
  45. Mohammadi, A., Sahebkar, A., Iranshahi, M., Amini, M., Khojasteh, R., Ghayour-Mobarhan, M., and Ferns, G. A. Effects of supplementation with curcuminoids on dyslipidemia in obese patients: a randomized crossover trial. Phytother Res 2013;27(3):374-379. PubMed
  46. Chuengsamarn, S., Rattanamongkolgul, S., Luechapudiporn, R., Phisalaphong, C., and Jirawatnotai, S. Curcumin extract for prevention of type 2 diabetes. Diabetes Care 2012;35(11):2121-2127. PubMed
  47. Goh, C. L. and Ng, S. K. Allergic contact dermatitis to Curcuma longa (turmeric). Contact Dermatitis 1987;17(3):186. PubMed
  48. Srivastava, R., Puri, V., Srimal, R. C., and Dhawan, B. N. Effect of curcumin on platelet aggregation and vascular prostacyclin synthesis. Arzneimittelforschung. 1986;36(4):715-717.
  49. Srinivasan, M. Effect of curcumin on blood sugar as seen in a diabetic subject. Indian J Med Sci 1972;26(4):269-270.
  50. Srivastava, K. C., Bordia, A., and Verma, S. K. Curcumin, a major component of food spice turmeric (Curcuma longa) inhibits aggregation and alters eicosanoid metabolism in human blood platelets. Prostaglandins Leukot.Essent.Fatty Acids 1995;52(4):223-227 PubMed
  51. Oetari, S., Sudibyo, M., Commandeur, J. N., Samhoedi, R., and Vermeulen, N. P. Effects of curcumin on cytochrome P450 and glutathione S-transferase activities in rat liver. Biochem Pharmacol 1-12-1996;51(1):39-45. PubMed
  52. Kiec-Swierczynska, M. and Krecisz, B. Occupational allergic contact dermatitis due to curcumin food colour in a pasta factory worker. Contact Dermatitis 1998;39(1):30-31. PubMed
  53. Van Dau N, Ngoc Ham N, Huy Khac D, and et al. The effects of a traditional drug, tumeric (Curcuma longa), and placebo on the healing of duodenal ulcer. Phytomed 1998;5(1):29-34.
  54. Daveluy A, Géniaux H, Thibaud L, Mallaret M, Miremont-Salamé G, Haramburu F. Probable interaction between an oral vitamin K antagonist and turmeric (Curcuma longa). Therapie. 2014 Nov-Dec;69(6):519-20. PubMed
  55. Kuptniratsaikul V, Dajpratham P, Taechaarpornkul W, Buntragulpoontawee M, Lukkanapichonchut P, Chootip C, Saengsuwan J, Tantayakom K, Laongpech S. Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthrit
  56. Madhu K, Chanda K, Saji MJ. Safety and efficacy of Curcuma longa extract in the treatment of painful knee osteoarthritis: a randomized placebo-controlled trial. Inflammopharmacology 2013;21(2):129-36. PubMed
  57. Mali AM, Behal R, Gilda SS. Comparative evaluation of 0.1% turmeric mouthwash with 0.2% chlorhexidine gluconate in prevention of plaque and gingivitis: A clinical and microbiological study. J Indian Soc Periodontol 2012;16(3):386-91. PubMed
  58. Sanmukhani J, Satodia V, Trivedi J, Patel T, Tiwari D, Panchal B, Goel A, Tripathi CB. Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Phytother Res 2014;28(4):579-85. PubMed
  59. Nayeri A, Wu S, Adams E, et al. Acute Calcineurin Inhibitor Nephrotoxicity Secondary to Turmeric Intake: A Case Report. Transplant Proc. 2017;49(1):198-200. PubMed
  60. Mitchell TM. Correspondence re: Somasundaram et al., Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. 2003;63(16):5165-6; author reply 5166-7.
  61. Somasundaram S, Edmund NA, Moore DT, Small GW, Shi YY, Orlowski RZ. Dietary curcumin inhibits chemotherapy-induced apoptosis in models of human breast cancer. Cancer Res. 2002;62(13):3868-75.
  62. Haroyan A, Mukuchyan V, Mkrtchyan N, et al. Efficacy and safety of curcumin and its combination with boswellic acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled study. BMC Complement Altern Med. 2018;18(1):7. PubMed
  63. Al-Karawi D, Al Mamoori DA, Tayyar Y. The role of curcumin administration in patients with major depressive disorder: Mini meta-analysis of clinical trials. Phytother Res. 2016;30(2):175-83. PubMed
  64. Neerati P, Devde R, Gangi AK. Evaluation of the effect of curcumin capsules on glyburide therapy in patients with type-2 diabetes mellitus. Phytother Res. 2014;28(12):1796-800. PubMed
  65. Simental-Mendía LE, Pirro M, Gotto AM Jr, et al. Lipid-modifying activity of curcuminoids: A systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. 2017:1-10. PubMed
  66. Fung FY, Wong WH, Ang SK, et al. A randomized, double-blind, placebo- controlled study on the anti-haemostatic effects of Curcuma longa, Angelica sinensis and Panax ginseng. Phytomedicine. 2017;32:88-96. PubMed
  67. Small GW, Siddarth P, Li Z, et al. Memory and brain amyloid and tau effects of a bioavailable form of curcumin in non-demented adults: A double-blind, placebo-controlled 18-month trial. Am J Geriatr Psychiatry. 2018;26(3):266-277.
  68. Cruz-Correa M, Hylind LM, Marrero JH, et al. Efficacy and safety of curcumin in treatment of intestinal adenomas in patients with familial adenomatous polyposis. Gastroenterology. 2018 May 23. Pii:S0016-5085(18)34564-5. [Epub ahead of print] PubMed
  69. Rahmani S, Asgary S, Askari G, et al. Treatment of non-alcoholic fatty liver disease with curcumin: a randomized placebo-controlled trial. Phytother Res. 2016 Sep;30(9):1540-8. PubMed
  70. Lopez-Villafuerte L, CLores KH. Contact dermatitis caused by turmeric in a massage oil. Contact Dermatitis. 2016 Jul;75(1):52-3. PubMed
  71. Lukefahr AL, McEvoy S, Alfafara C, Funk JL. Drug-induced autoimmune hepatitis associated with turmeric dietary supplement use. BMJ Case Rep. 2018. pii: bcr-2018-224611. PubMed
  72. Medsafe Safety Communication- Turmeric/Curcumin Interaction with Warfarin. April 30, 2018. Accessed at: https://medsafe.govt.nz/safety/EWS/2018/Turmeric.asp.
  73. Imam Z, Khasawneh M, Jomaa D, Iftikhar H, Sayedahmad Z. Drug induced liver injury attributed to a curcumin supplement. Case Rep Gastrointest Med 2019 Oct 20;2019:6029403. doi: 10.1155/2019/6029403. PubMed
  74. Chand S, Hair C, Beswick L. A rare case of turmeric-induced hepatotoxicity. Intern Med J. 2020;50(2):258-259. PubMed
  75. Jiang N, Zhang M, Meng X, Sun B. Effects of Curcumin on the Pharmacokinetics of Amlodipine in Rats and Its Potential Mechanism. Pharm Biol. 2020;58(1):465-468. PubMed
  76. Lee BS, Bhatia T, Chaya CT, Wen R, Taira MT, Lim BS. Autoimmune Hepatitis Associated With Turmeric Consumption. ACG Case Rep J. 2020;7(3):e00320. PubMed
  77. Lombardi N, Crescioli G, Maggini V, et al. Acute liver injury following turmeric use in Tuscany: an analysis of the Italian Phytovigilance database and systematic review of case reports. Br J Clin Pharmacol. 2020. PubMed
  78. Suhail FK, Masood U, Sharma A, John S, Dhamoon A. Turmeric supplement induced hepatotoxicity: a rare complication of a poorly regulated substance. Clin Toxicol (Phila). 2020;58(3):216-217. PubMed
  79. Nakagawa Y, Mukai S, Yamada S, et al. The efficacy and safety of highly-bioavailable curcumin for treating knee osteoarthritis: a 6-month open-labeled prospective study. Clin Med Insights Arthritis Musculoskelet Disord. 2020;13:1179544120948471. PubMed
  80. Shafabakhsh R, Asemi Z, Reiner Z, Soleimani A, Aghadavod E, Bahmani F. The effects of nano-curcumin on metabolic status in patients with diabetes on hemodialysis, a randomized, double blind, placebo-controlled trial. Iran J Kidney Dis. 2020;14(4):290-9.
  81. Allegri P, Rosa R, Masala A, et al. Clinical effectiveness of a new oral curcumin formulation in acute non-infectious uveitic macular edema: a 12-month observational study. Eur Rev Med Pharmacol Sci 2022;26(1):46-53.
  82. Tsai IC, Hsu CW, Chang CH, Tseng PT, Chang KV. The effect of curcumin differs on individual cognitive domains across different patient populations: A systematic review and meta-analysis. Pharmaceuticals (Basel) 2021;14(12):1235. PubMed
  83. Alam MA, Bin Jardan YA, Raish M, Al-Mohizea AM, Ahad A, Al-Jenoobi FI. Herb-drug interaction: Pharmacokinetics and pharmacodynamics of anti-hypertensive drug amlodipine besylate in presence of lepidium sativum and curcuma longa. Xenobiotica 2022;1-9.
  84. Sohal A, Alhankawi D, Sandhu S, Chintanaboina J. Turmeric-induced hepatotoxicity: Report of 2 cases. Int Med Case Rep J 2021;14:849-852. PubMed
  85. Hussaarts KGAM, Hurkmans DP, Oomen-de Hoop E, et al. Impact of curcumin (with or without piperine) on the pharmacokinetics of tamoxifen. Cancers (Basel). 2019;11(3):403. PubMed
  86. Kalluru H, Mallayasamy SR, Kondaveeti SS, Chandrasekhar V, Kalachaveedu M. Effect of turmeric supplementation on the pharmacokinetics of paclitaxel in breast cancer patients: A study with population pharmacokinetics approach. Phytother Res 2022;36(4):1761 PubMed
  87. 109288 Halegoua-DeMarzio D, Navarro V, Ahmad J, et al. Liver injury associated with turmeric-A growing problem: Ten cases from the drug-induced liver injury network [DILIN]. Am J Med. 2022:S0002-9343(22)00740-9. PubMed
  88. Arzallus T, Izagirre A, Castiella A, Torrente S, Garmendia M, Zapata EM. Drug induced autoimmune hepatitis after turmeric intake. Gastroenterol Hepatol 2023. PubMed
  89. Gilad O, Rosner G, Ivancovsky-Wajcman D, et al. Efficacy of wholistic turmeric supplement on adenomatous polyps in patients with familial adenomatous polyposis-A randomized, double-blinded, placebo-controlled study. Genes (Basel) 2022;13(12):2182. PubMed
  90. Ahad A, Raish M, Abdelrahman IA, et al. Changes in pharmacokinetics and pharmacodynamics of losartan in experimental diseased rats treated with Curcuma longa and Lepidium sativum. Pharmaceuticals (Basel) 2022;16(1):33. PubMed
  91. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
  92. 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
  93. Kou H, Huang L, Jin M, He Q, Zhang R, Ma J. Effect of curcumin on rheumatoid arthritis: a systematic review and meta-analysis. Front Immunol 2023;14:1121655. PubMed
  94. Qiu L, Gao C, Wang H, et al. Effects of dietary polyphenol curcumin supplementation on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials. Front PubMed
  95. Sato T, Yagi A, Yamauchi M, et al. The use of an antioxidant enables accurate evaluation of the interaction of curcumin on organic anion-transporting polypeptides 4C1 by preventing auto-oxidation. Int J Mol Sci 2024;25(2):991. PubMed
  96. Washington O, Robinson E, Simh D, et al. Oxalate nephropathy and chronic turmeric supplementation: a case report. J Bras Nefrol 2024;46(1):99-106. PubMed
  97. Munshi R, Karande-Patil S, Kumbhar D, Deshmukh A, Hingorani L. A randomized, controlled, comparative, proof-of-concept study to evaluate the efficacy and safety of Nisha-Amalaki capsules in prediabetic patients for preventing progression to diabetes. J Ay PubMed
  98. Sharifi Razavi A, Mohajerani F, Niksolat F, Karimi N. Efficacy of topical curcumin on mild to moderate carpal tunnel syndrome: a randomized double-blind, placebo-controlled clinical trial. Pain Med 2024;25(5):327-333. PubMed
  99. Yaikwawong M, Jansarikit L, Jirawatnotai S, Chuengsamarn S. Curcumin Reduces Depression in Obese Patients with Type 2 Diabetes: A Randomized Controlled Trial. Nutrients 2024;16(15):2414. PubMed
  100. Tehrani SD, Hosseini A, Shahzamani M, et al. Evaluation of the effectiveness of curcumin and piperine co-supplementation on inflammatory factors, cardiac biomarkers, atrial fibrillation, and clinical outcomes after coronary artery bypass graft surgery. Cl PubMed
  101. Yaikwawong M, Jansarikit L, Jirawatnotai S, Chuengsamarn S. The Effect of Curcumin on Reducing Atherogenic Risks in Obese Patients with Type 2 Diabetes: A Randomized Controlled Trial. Nutrients 2024;16(15):2441. PubMed
  102. Dibaei M, Hosseini A, Lavasani H, Kiani-Dehkordi B, Rouini M. Assessment of metabolic interaction between curcumin and tramadol using the isolated perfused rat liver. Heliyon 2024;10(15):e35070. PubMed

See these in context on the Turmeric monograph →

Chromium 53 references
  1. Cerulli J, Grabe DW, Gauthier I, et al. Chromium picolinate toxicity. Ann Pharmacother 1998;32:428-31. PubMed
  2. Urberg M, Zemel MB. Evidence for synergism between chromium and nicotinic acid in the control of glucose tolerance in elderly humans. Metabolism 1987;36:896-9. PubMed
  3. Mohamedshah FY, Moser-Veillon PB, Yamini S, et al. Distribution of a stable isotope of chromium (53Cr) in serum, urine, and breast milk in lactating women. Am J Clin Nutr 1998;67:1250-5. PubMed
  4. Wasser WG, Feldman NS, D'Agati VD. Chronic renal failure after ingestion of over-the-counter chromium picolinate. [letter]. Ann Intern Med 1997;126:410. PubMed
  5. Mertz W. Interaction of chromium with insulin: a progress report. Nutr Rev 1998;56:174-7. PubMed
  6. Anderson RA. Chromium, glucose intolerance and diabetes. J Am Coll Nutr 1998;17:548-55. PubMed
  7. McLeod MN, Gaynes BN, Golden RN. Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in 5 patients. J Clin Psych 1999;60:237-40. PubMed
  8. Fowler JF Jr. Systemic contact dermatitis caused by oral chromium picolinate. Cutis 2000;65:116. DOI
  9. Trent LK, Thieding-Cancel D. Effects of chromium picolinate on body composition. J Sports Med Phys Fitness 1995;35:273-80.
  10. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  11. Rabinovitz H, Friedensohn A, Leibovitz A, et al. Effect of chromium supplementation on blood glucose and lipid levels in type 2 diabetes mellitus elderly patients. Int J Vitam Nutr Res 2004;74:178-82. PubMed
  12. Lanca S, Alves A, Vieira AI, et al. Chromium-induced toxic hepatitis. Eur J Intern Med 2002;13:518-20. PubMed
  13. Kockler DR, McCarthy MW, Lawson CL. Seizure activity and unresponsiveness after hydroxycut ingestion. Pharmacotherapy 2001;21:647-51.. PubMed
  14. Davidson JR, Abraham K, Connor KM, McLeod MN. Effectiveness of chromium in atypical depression: a placebo-controlled trial. Biol Psychiatry 2003;53:261-4.. PubMed
  15. Food Standards Agency. Medicines and Healthcare products Regulatory Agency (MHRA). Expert Group on Vitamins and Minerals. Available at: http://cot.food.gov.uk/sites/default/files/vitmin2003.pdf.
  16. Mouser JF, Hak EB, Helms RA, et al. Chromium and zinc concentrations in pediatric patients receiving long-term parenteral nutrition. Am J Health Syst Pharm 1999;56:1950-6. PubMed
  17. Stevens T, Qadri A, Zein NN. Two patients with acute liver injury associated with use of the herbal weight-loss supplement hydroxycut. Ann Intern Med 2005;142:477-8. PubMed
  18. Wani S, Weskamp C, Marple J, Spry L. Acute tubular necrosis associated with chromium picolinate-containing dietary supplement. Ann Pharmacother 2006;40:563-6. PubMed
  19. Kleefstra N, Houweling ST, Jansman FG, et al. Chromium treatment has no effect in patients with poorly controlled, insulin-treated type 2 diabetes in an obese Western population: a randomized, double-blind, placebo-controlled trial. Diabetes Care 2006;29: PubMed
  20. Martin J, Wang ZQ, Zhang XH, et al. Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care 2006;29:1826-32. PubMed
  21. Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther 2006;8:636-43. PubMed
  22. John-Kalarickal J, Pearlman G, Carlson HE. New medications which decrease levothyroxine absorption. Thyroid 2007;17:763-5. PubMed
  23. Yazaki Y, Faridi Z, Ma Y, et al. A pilot study of chromium picolinate for weight loss. J Altern Complement Med 2010;16:291-9. PubMed
  24. Davis ML, Seaborn CD, and Stoecker BJ. Effects of over-the-counter drugs on chromium retention and urinary excretion in rats. Nutrition Research 1995;15(2):201-210.
  25. Young P, Turiansky G, Bonner M, and et al. Acute generalized exanthematous pustulosis induced by chromium picolinate. J.Am Acad.Dermatol. 1999;41(5 Pt 2):820-823. PubMed
  26. Gibb, H. J., Lees, P. S., Pinsky, P. F., and Rooney, B. C. Lung cancer among workers in chromium chemical production. Am J Ind.Med 2000;38(2):115-126. DOI
  27. Gibb, H. J., Lees, P. S., Pinsky, P. F., and Rooney, B. C. Clinical findings of irritation among chromium chemical production workers. Am J Ind.Med 2000;38(2):127-131. PubMed
  28. Pittler, M. H. and Ernst, E. Dietary supplements for body-weight reduction: a systematic review. Am.J.Clin Nutr. 2004;79(4):529-536. PubMed
  29. Pei, D., Hsieh, C. H., Hung, Y. J., Li, J. C., Lee, C. H., and Kuo, S. W. The influence of chromium chloride-containing milk to glycemic control of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Metabolism 2 PubMed
  30. Hisatomi, K., Ishii, H., Hashiguchi, K., Seki, M., Ide, M., Sugiyama, K., Ishimoto, H., Nakayama, S., Mukae, H., and Kohno, S. Interstitial pneumonia caused by inhalation of fumes of nickel and chrome. Respirology. 2006;11(6):814-817. PubMed
  31. Kleefstra, N., Houweling, S. T., Bakker, S. J., Verhoeven, S., Gans, R. O., Meyboom-de Jong, B., and Bilo, H. J. Chromium treatment has no effect in patients with type 2 diabetes in a Western population: a randomized, double-blind, placebo-controlled tri DOI
  32. Parsons, A., Ingram, J., Inglis, J., Aveyard, P., Johnstone, E., Brown, K., Franklin, M., and Bermudez, I. A proof of concept randomised placebo controlled factorial trial to examine the efficacy of St John's wort for smoking cessation and chromium to pr
  33. Bagdon RE and Hazen RE. Skin permeation and cutaneous hypersensitivity as a basis for making risk assessments of chromium as a soil contaminant. Environ.Health Perspect. 1991;92:111-119. PubMed
  34. Bharmal, S. V., Moyes, V., Ahmed, S., and Grossman, A. Hypoglycaemia: possible mediation by chromium salt medication. Hormones.(Athens.) 2010;9(2):181-183. PubMed
  35. Krol, E., Krejpcio, Z., Byks, H., Bogdanski, P., and Pupek-Musialik, D. Effects of chromium brewer's yeast supplementation on body mass, blood carbohydrates, and lipids and minerals in type 2 diabetic patients. Biol.Trace Elem.Res. 2011;143(2):726-737.
  36. Unisa, S., Jagannath, P., Dhir, V., Khandelwal, C., Sarangi, L., and Roy, T. K. Population-based study to estimate prevalence and determine risk factors of gallbladder diseases in the rural Gangetic basin of North India. HPB (Oxford) 2011;13(2):117-125. PubMed
  37. Noda, S., Asano, Y., and Sato, S. Lichen planus in a patient with long-term exposure to chrome. Eur.J.Dermatol. 2011;21(3):417-418. PubMed
  38. Xiang, J., Sun, Z., and Huan, J. N. Intensive chromic acid burns and acute chromium poisoning with acute renal failure. Chin Med.J.(Engl.) 7-5-2011;124(13):2071-2073.
  39. Chhabra, D., Oda, K., Jagannath, P., Utsunomiya, H., Takekoshi, S., and Nimura, Y. Chronic heavy metal exposure and gallbladder cancer risk in India, a comparative study with Japan. Asian Pac.J.Cancer Prev. 2012;13(1):187-190. PubMed
  40. Huszonek, J. Over-the-counter chromium picolinate. Am J Psychiatry 1993;150(10):1560-1561. PubMed
  41. Bunner S and McGinnis R. Chromium-induced hypoglycemia. Psychosomatics 1998;39(3):298-299. PubMed
  42. Martin, W. R. and Fuller, R. E. Suspected chromium picolinate-induced rhabdomyolysis. Pharmacotherapy 1998;18(4):860-862. DOI
  43. Proctor, D. M., Fredrick, M. M., Scott, P. K., Paustenbach, D. J., and Finley, B. L. The prevalence of chromium allergy in the United States and its implications for setting soil cleanup: a cost-effectiveness case study. Regul.Toxicol Pharmacol 1998;28(1 PubMed
  44. De Marchi S, Cecchin E, De Marchi SU. Systemic allergic dermatitis resulting from oral administration of chromium with a food supplement. Contact Dermatitis 2014;70(2):123-5. PubMed
  45. Hedberg YS, Gumulka M, Lind ML, Matura M, Lidén C. Severe occupational chromium allergy despite cement legislation. Contact Dermatitis. 2014;70(5):321-3. PubMed
  46. Thyssen JP, Jellesen MS, Møller P, Menné T, Johansen JD. Allergic chromium dermatitis from wearing 'chromium-free' footwear. Contact Dermatitis 2014;70(3):185-7. PubMed
  47. Liu Y, Cotillard A, Vatier C, et al. A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial. PLoS One.
  48. Jamilian M, Asemi Z. Chromium Supplementation and the Effects on Metabolic Status in Women with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Nutr Metab. 2015;67(1):42-8. PubMed
  49. Guimarães MM, Carvalho AC, Silva MS. Effect of chromium supplementation on the glucose homeostasis and anthropometry of type 2 diabetic patients: Double blind, randomized clinical trial: Chromium, glucose homeostasis and anthropometry. J Trace Elem Med Bi PubMed
  50. Paiva AN, Lima JG, Medeiros AC, et al. Beneficial effects of oral chromium picolinate supplementation on glycemic control in patients with type 2 diabetes: A randomized clinical study. J Trace Elem Med Biol. 2015;32:66-72. PubMed
  51. Yin RV, Phung OJ. Effect of chromium supplementation on glycated hemoglobin and fasting plasma glucose in patients with diabetes mellitus. Nutr J. 2015;14:14. PubMed
  52. Jamilian M, Zadeh Modarres S, Amiri Siavashani M, et al. The influences of chromium supplementation on glycemic control, markers of cardio-metabolic risk, and oxidative stress in infertile polycystic ovary syndrome women candidate for in vitro fertilizati
  53. Alinaghi F, Thyssen JP, Zachariae C, Johansen JD. No immediate effect of regulatory reduction of chromium in leather among adult patients with chromium allergy. Contact Dermatitis 2021;85(5):514-522. PubMed

See these in context on the Chromium monograph →

Milk Thistle 69 references
  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. Boerth J, Strong KM. The clinical utility of milk thistle (Silybum marianum) in cirrhosis of the liver. J Herb Pharmacother 2002;2:11-7.
  9. 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
  10. 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. .
  11. 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.
  12. Deng JW, Shon JH, Shin HJ, et al. Effect of silymarin supplement on the pharmacokinetics of rosuvastatin. Pharm Res 2008;25:1807-14. PubMed
  13. 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.
  14. 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
  15. 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.
  16. 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.
  17. 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
  18. 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.
  19. 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
  20. 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
  21. 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
  22. Bean, P. The use of alternative medicine in the treatment of hepatitis C. Am.Clin.Lab 2002;21(4):19-21.
  23. 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
  24. 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
  25. 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
  26. 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
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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
  35. Mironets VI, Krasovskaia EA, and Polishchuk II. [A case of urticaria during Carsil treatment]. Vrach Delo 1990;7:86-87.
  36. 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
  37. 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.
  38. 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.
  39. 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
  40. Grungreiff K, Albrecht M, and Strenge-Hesse A. Benefit of medicinal liver therapy in general practice. Med Welt 1995;46:222-227.
  41. Frerick F, Kuhn U, and Strenge-Hesse A. Silymarin--ein Phytopharmakon zur Behandlung toxischen Leberschaden: Anwendungsbeobachtung bei 2169 Patienten. Kassenarzt 1990;33:36-41.
  42. 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.
  43. Studlar M. Die Behandlung chronischer Leberkrankungen mit Silymarin und B-Vitaminen. Therapiewoche 1985;35:3375-3378.
  44. Anon. Adverse reaction: milk thistle-associated toxicity. Nurse Drug Alert 1999;23(7):51.
  45. 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
  46. 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
  47. 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
  48. 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
  49. 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
  50. 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
  51. 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
  52. 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
  53. 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
  54. 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
  55. 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
  56. 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
  57. Lash DB, Ward S. CYP2C9-mediated warfarin and milk thistle interaction. J Clin Pharm Ther. 2019. PubMed
  58. 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
  59. 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
  60. 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
  61. 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
  62. 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
  63. 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
  64. 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
  65. 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
  66. 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
  67. 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
  68. 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
  69. 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

See these in context on the Milk Thistle monograph →

Boldo 10 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. Lambert J, Cormier J. Potential interaction between warfarin and boldo-fenugreek. Pharmacotherapy 2001;21:509-12. PubMed
  3. Piscaglia F, Leoni S, Venturi A, et al. Caution in the use of boldo in herbal laxatives: a case of hepatotoxicity. Scand J Gastroenterol 2005;40:236-9. PubMed
  4. Agarwal SC, Crook JR, Pepper CB. Herbal remedies -- how safe are they? A case report of polymorphic ventricular tachycardia/ventricular fibrillation induced by herbal medication used for obesity. Int J Cardiol 2006;106:260-1. PubMed
  5. Teng, C. M., Hsueh, C. M., Chang, Y. L., Ko, F. N., Lee, S. S., and Liu, K. C. Antiplatelet effects of some aporphine and phenanthrene alkaloids in rabbits and man. J Pharm Pharmacol 1997;49(7):706-711. PubMed
  6. Carbajal R, Yisfalem A, Pradhan N, et al. Case report: Boldo (Peumus boldus) and tacrolimus interaction in a renal transplant patient. Transplant Proc 2014;46(7):2400-2. PubMed
  7. Almeida ER, Melo AM, Xavier H. Toxicological evaluation of the hydro-alcohol extract of the dry leaves of Peumus boldus and boldine in rats. Phytother Res 2000;14(2):99-102. DOI
  8. Ribeiro RJ, Silvestre C, Duarte C. Hidden risks of alternative medicines: a case of boldo-induced hepatotoxicity. J Diet Suppl 2017;14(2):186-90. PubMed
  9. Oliveira Sá A, Pimentel T, Oliveira N. Boldo-Induced Hepatotoxicity: A Case of Unexplained Jaundice. Eur J Case Rep Intern Med 2020;7(12):002116. PubMed
  10. Valdes R, Feuereisen A, Bellinghausen M. Allergic Contact Dermatitis to Boldo. Dermatitis 2021;32(2):e31-e32. PubMed

See these in context on the Boldo monograph →

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

Keep exploring
Supplement interaction checker › Check any supplement or product against your medications Drug–drug interactions › Check two or more of your medications against each other Browse medications A–Z › Every drug we've checked against herbs & supplements NDC & pricing lookup › Find a drug’s NDCs, packaging and costs Ask a pharmacist › Free, personal answer from our licensed team