Interactions on record — worth a quick check against your medications. Based on 12 of 13 ingredients. Check your meds →
Dietary supplement

2-in-1 Cleanse & Flush Ingredients & Drug Interactions

by Irwin Naturals

2-in-1 Cleanse & Flush label
See full label image
Softgel 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 2-in-1 Cleanse & Flush 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

2-in-1 Cleanse & Flush is a dietary supplement by Irwin Naturals with 13 active ingredients. Its ingredients are commonly taken for nausea and vomiting, motion sickness, morning sickness in pregnancy.Based on those ingredients, 2,215 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are Marshmallow Root Extract, Turmeric Root Extract, 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 2-in-1 Cleanse & Flush by Irwin Naturals

Ask about any prescription or over-the-counter medication and we check it for interactions with 2-in-1 Cleanse & Flush by Irwin Naturals — 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 2-in-1 Cleanse & Flush by Irwin Naturals

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 Jul 11, 2026

What’s inside

Partial disclosure
Ingredient Transparency · database check
Partial

Most active ingredients list an amount, but at least one is hidden in a blend or missing.

Why this rating?
  • The label discloses an exact amount for 10 of its 12 active ingredients.
  • “BioPerine Complex” is a proprietary blend — the label gives one combined amount (3 mg) without saying how much of each component you get.
  • “Turmeric Root Extract” is listed as a grouped ingredient — the label gives one combined amount (50 mg) without saying how much of each component you get.

2-in-1 Cleanse & Flush contains 12 active ingredients designed to support digestive function. The main components are cascara sagrada bark extract (a stimulant laxative), marshmallow root extract, ginger rhizome extract, and gymnema leaf extract — each with traditional digestive or metabolic roles.

You'll also find chromium, milk thistle seed extract, black pepper/BioPerine (which boosts absorption of other ingredients), turmeric root extract, lemon balm aerial extract, cinnamon bark extract, cardamom fruit extract, and extra virgin olive oil. Several inactive ingredients are present as fillers and binders, including gelatin, glycerin, titanium dioxide, and silicon dioxide.

Does it work?

Not established
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
Not established

The graded evidence we hold for these ingredients covers different conditions than the ones this product is marketed for, so there's no established rating for its stated use.

Why this rating?
  • The label markets this product for: digestive cleansing and waste elimination support.
  • We looked for evidence on: Bowel preparation, Constipation, Diarrhea, regularity, bloating, digestive tract health.
  • The closest evidence on file: Cascara Sagrada is rated "Possibly Ineffective" for Bowel preparation (Natural Medicines).
  • Also on file: Turmeric is rated "Insufficient Reliable Evidence To Rate" for Chemotherapy-induced diarrhea, Chemotherapy-induced constipation.
  • Also on file: Cascara Sagrada is rated "Insufficient Reliable Evidence To Rate" for Constipation.

The evidence for effectiveness varies by ingredient. Cascara sagrada shows insufficient reliable evidence for constipation and is considered possibly ineffective for bowel preparation.

Ginger has possibly effective evidence for pregnancy-induced nausea and vomiting, dysmenorrhea, and osteoarthritis. Chromium is likely effective for chromium deficiency and possibly effective for diabetes, but possibly ineffective for prediabetes.

Milk thistle is possibly effective for diabetes. Lemon balm is possibly effective for cold sores, stress, and depression.

For other ingredients — gymnema, black pepper, cinnamon, marshmallow, cardamom, and olive oil — the evidence in our data is insufficient to rate their effectiveness, or they lack ratings altogether.

The evidence, ingredient by ingredient Ginger Black Pepper Cascara Sagrada Marshmallow Chromium Gymnema Turmeric Olive

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 11 of the 12 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 12 of 12.
  • General safety write-ups exist for 12 of 12.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Cascara sagrada is generally well tolerated for short-term use but carries real risks with long-term use; it should be avoided during pregnancy and breastfeeding. Ginger is generally well tolerated in typical amounts for healthy adults, though higher doses (over 5 grams daily) increase the risk of side effects like heartburn and diarrhea.

Chromium is usually well tolerated at typical doses; pregnancy and breastfeeding safety data are limited, so extra supplement doses should be avoided unless a doctor recommends them. Marshmallow has limited human safety data; it is best avoided during pregnancy and breastfeeding.

Milk thistle is generally well tolerated but should be avoided during pregnancy; breastfeeding safety is not well studied. Lemon balm is generally well tolerated for short-term use; it should be avoided during pregnancy unless a doctor advises otherwise.

Black pepper is generally safe as a food spice; concentrated supplements should be used more cautiously. Cinnamon in food amounts is generally safe, but high-dose supplements may harm the liver over time and should be avoided in pregnancy.

Cardamom in food amounts is generally well tolerated. Gymnema and olive oil safety data are limited for concentrated supplements.

Side effects, ingredient by ingredient Ginger Black Pepper Cascara Sagrada Marshmallow Chromium Gymnema Turmeric Olive

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?
  • 10 of the 12 matched ingredients can interact with medications — Milk Thistle, Lemon Balm, Turmeric, Cascara Sagrada, Marshmallow, 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; heart-rhythm medications; lithium.
  • For scale: 2,216 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.

Before taking this product, double-check if you use blood thinners or anticoagulants (warfarin, phenprocoumon, other antiplatelet drugs), antidiabetes medications (including insulin), heart or blood pressure drugs (propranolol, nifedipine, losartan), thyroid replacement (levothyroxine), corticosteroids, diuretics, lithium, or any drugs metabolized by liver enzymes — especially CYP3A4, CYP2C9, CYP1A2, and CYP2B6 substrates. Ginger, cascara sagrada, chromium, and several other ingredients in this product interact with these drug classes at Moderate or Minor severity.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glancePartially disclosed formula with no established evidence rating for its marketed use. Moderate medication interactions have been identified, and safety information is well characterized.

This product is best suited for short-term digestive support in people without medications that interact with its ingredients — especially those not on blood thinners, diabetes drugs, or thyroid replacement. If you take any prescription medications, check them against this product's interactions before starting.

Long-term use of cascara sagrada is not recommended. Talk to your pharmacist or doctor before starting, particularly if you're pregnant, breastfeeding, or have liver, kidney, or blood sugar concerns.

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

Assessment coverage: 12 of 12 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Jan 23, 2025.

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 2-in-1 Cleanse & Flush, straight from the product label.

Brand Irwin Naturals
Barcode (UPC) 710363597115
Net contents 60 Liquid Softgel(s)
Market status On market
Date entered into DSLD Jan 23, 2025
DSLD ID 323273
Product type Other Combinations
Supplement form Softgel Capsule
Dietary claims / uses Nutrient, All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Women (not pregnant or lactating)
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 2-in-1 Cleanse & Flush by Irwin Naturals, 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:
2 Liquid Soft-Gel(s)
Maximum serving Sizes:
2 Liquid Soft-Gel(s)
Servings per container
30
UPC/BARCODE
710363597115
IngredientAmount% DV
Calories20 Calorie(s)--
Total Carbohydrates1 Gram(s)1%
Total Fat1 Gram(s)1%
Protein1 Gram(s)--
BioPerine Complex3 mg--
Cascara Sagrada Bark Extract200 mg--
Marshmallow Root Extract50 mg--
Chromium100 mcg286%
Ginger Rhizome Extract0 NP--
Gymnema leaf extract67.5 mg--
BioPerine0 NP--
Turmeric Root Extract50 mg--
Extra Virgin Olive Oil1100 mg--
Cardamom Fruit Extract50 mg--
Milk Thistle Seed Extract222.5 mg--
Curcuminoids47.5 mg--
Lemon Balm Aerial Extract50 mg--
Cinnamon Bark Extract100 mg--

Other ingredients: Gelatin, Water, Purified, Glycerin, Beeswax, Dextrin, Soy Lecithin, Turmeric, Maltodextrin, Titanium Dioxide, Riboflavin, Silicon Dioxide, Sodium Copper Chlorophyllin

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.
Formulation

2-in-1 Cleanse & Flush Weight Loss Support is a multi-pronged formula that is designed to cleanse your digestive tract and eliminate excess matter from the body. In just days, you can safely experience increased regularity, reduced bloating, and a flatter abdomen.

What makes us different: Liquid soft-gels - The nutrients in these easy-to-swallow liquid soft-gels are released fast. Other forms of delivery can contain binders and fillers that may cause stomach upset and offer no nutritional value. Advanced liquid soft-gels provide an optimum delivery system. Quality assurance - Irwin Naturals is committed to providing the highest quality products for your health. We employ compliance testing to ensure purity and potency.

Weight loss support Flush up to 2-to-3 pounds of backed-up matter Reduce excess water weight

No preservatives added.

Formula

Cleanse & Flush: This powerful formula features Cascara Sagrada, a valuable botanical that is traditionally used to stimulate the bowels and gently flush excess waste from the digestive tract. We've combined this unique action with soothing Lemon Balm, as well as Marshmallow Root and Cardamom which have been used in traditional digestive formulas. Advanced cleansing support is supplied by potent milk thistle extract revered for its liver supporting benefits, and by concentrated Turmeric which exhibits powerful antioxidant activity. Weight management nutrition: Additional nutrition is delivered with 200 mcg of Chromium per day, along with Cinnamon Extract, and concentrated gymnema extract used traditionally to support energy balance and to eliminate excess water from the body. Patented BioPerine - Our special BioPerine Complex enhances the bioavailability, absorption and potency of many nutrients.

2-in-1 Cleanse & Flush plus gymnema extract

Seals/Symbols

Pass Quality Tested Guaranteed

Precautions

Usage warnings: Do not use if safety seal is broken. Do not use if you have an intestinal obstruction, bile duct obstruction, hemorrhoids or other intestinal disorders. Do not use if you are taking any other product concurrently that has laxative effects. Do not exceed recommended daily intake. Note: This product is not intended to be used without breaks. Cascara Sagrada belongs to a family of plants containing compounds with laxative effects. Can lead to dehydration and electrolyte loss. With long-term use without breaks, these ingredients may interfere with diagnostic imaging procedures of the colon. Taking a break of 30 or more days between use cycles will help maintain natural regularity. Not intended for long-term use.

Check with your doctor before using this product if you are using medication, including diuretics, heart medications, and corticosteroids, or have any medical conditions, including but not limited to diabetes or blood sugar disorders. Do not use if you may become pregnant, are pregnant or nursing.

Not intended for use by persons under 18. Keep out of reach of children.

Notice: This product contains Cascara Sagrada. Read and follow the directions carefully. Do not use if you have or develop diarrhea, loose stools, or abdominal pain because Cascara Sagrada may worsen these conditions and be harmful to your health.

Consult your physician if you have frequent diarrhea or if you are pregnant, nursing, taking medication, or have a medical condition.

Contains: Soy

Storage

Store in a cool, dry place.

General Statements

Questions: Contact consume affairs 1-800-297-3273 - Weekdays 8:00 AM to 5:00 PM (PST) 100+ Highly specialized products: www.IrwinNaturals.com

Full disclosure ingredient panel

FDA Statement of Identity

Dietary Supplement

Suggested/Recommended/Usage/Directions

Dictions: Take two (2) liquid soft-gels in the morning prior to breakfast and two (2) liquid soft-gels in the evening, prior to bedtime. Drink a full glass (8oz) of water with each serving. Do not exceed four (4) liquid soft-gels per day. If stools are loose, reduce intake to three (3) liquid soft-gels per day.

Brand IP Statement(s)

BioPerine is a registered trademark of Sabinsa Corporation.

FDA Disclaimer Statement

These statements have not been evaluated by the Food & Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

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

See for yourself

2-in-1 Cleanse & Flush by Irwin Naturals label

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

2-in-1 Cleanse & Flush 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 2-in-1 Cleanse & Flush by Irwin Naturals

These are the 13 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Liquid Soft-Gel(s) Dosage formSoftgel Capsule 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.

Protein

1 Gram(s) per serving

BioPerine Complex

3 mg per serving

Cascara Sagrada Bark Extract

Interacts with
745 drugs
200 mg per serving

Cascara sagrada is a stimulant laxative made from the aged bark of a Pacific Northwest tree, used mainly for short-term relief of constipation. Becaus...

Cascara Sagrada Bark Extract monograph & interactions

Marshmallow Root Extract

Interacts with
2,040 drugs
50 mg per serving

Marshmallow root is a traditional herb rich in soothing, gel-like fibers called mucilage, which is why it has long been used for coughs, sore throats,...

Marshmallow Root Extract 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

Gymnema leaf extract

Interacts with
851 drugs
67.5 mg per serving

Gymnema is an Ayurvedic herb best known for possibly helping lower blood sugar and reducing the taste of sweetness on the tongue. Some early human stu...

Gymnema leaf extract monograph & interactions

Turmeric Root Extract

Interacts with
1,133 drugs
50 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,...

Turmeric Root Extract monograph & interactions

Extra Virgin Olive Oil

No known
interactions
1100 mg per serving

Olive comes from the same tree that gives us olives and olive oil, and its leaf and fruit contain antioxidant compounds like oleuropein and hydroxytyr...

Extra Virgin Olive Oil monograph & interactions

Cardamom Fruit Extract

No known
interactions
50 mg per serving

Cardamom is a popular cooking spice that has long been used in traditional medicine for digestion and fresh breath. As a food, it is generally safe fo...

Cardamom Fruit Extract monograph & interactions

Milk Thistle Seed Extract

Interacts with
954 drugs
222.5 mg per serving

Milk thistle is a popular herbal supplement most often used for liver health, and its main active component is a group of compounds called silymarin....

Milk Thistle Seed Extract monograph & interactions

Lemon Balm Aerial Extract

Interacts with
264 drugs
50 mg per serving

Lemon balm is a gentle, lemon-scented mint-family herb traditionally used to ease stress, support sleep, and calm digestion, and topically for cold so...

Lemon Balm Aerial Extract monograph & interactions

Cinnamon Bark Extract

Interacts with
442 drugs
100 mg per serving Form: Cinnamomum zeylanicum Bark Extract

Cassia cinnamon is the common, inexpensive cinnamon used in cooking, and it is also taken as a supplement, most often for blood sugar support. The evi...

Cinnamon Bark Extract monograph & interactions

Other (inactive) ingredients: Gelatin, Water, Purified, Glycerin, Beeswax, Dextrin, Soy Lecithin, Turmeric, Maltodextrin, Titanium Dioxide, Riboflavin, Silicon Dioxide, Sodium Copper Chlorophyllin. These complete the product’s ingredient list but are not active constituents.

Interaction report

2-in-1 Cleanse & Flush by Irwin Naturals Drug Interactions

Want to check YOUR meds against 2-in-1 Cleanse & Flush?

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
2,215Drugs
1,412 Moderate 803 Minor

Ingredients driving the most interactions

Marshmallow Root Extract 2,040
Turmeric Root Extract 1,133
BioPerine 1,019
Ginger Rhizome Extract 1,007
Milk Thistle Seed Extract 954

Individual Drug Interactions

The ingredients in 2-in-1 Cleanse & Flush interact with 2,215 drugs. Click any drug to see the details.

10 of the 13 ingredients in 2-in-1 Cleanse & Flush interact with drugs. Each result below shows which ingredient is responsible. Marshmallow Root Extract Turmeric Root Extract BioPerine Ginger Rhizome Extract Milk Thistle Seed Extract Gymnema leaf extract Cascara Sagrada Bark Extract Cinnamon Bark Extract Lemon Balm Aerial Extract Chromium

Each ingredient & the kinds of drugs it affects

For each ingredient in 2-in-1 Cleanse & Flush 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.

Marshmallow Root Extract3 drug types · 2,040 drugs

Lithium

Theoretically, due to potential diuretic effects, marshmallow might reduce excretion and increase levels of lithium.
Marshmallow is thought to have diuretic properties. To avoid lithium toxicity, the dose of lithium might need to be decreased when used with marshmallow.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, marshmallow flower might have antiplatelet effects.
Animal research suggests that marshmallow flower extract has antiplatelet effects. However, the root and leaf of marshmallow, not the flower, are the plant parts most commonly found in dietary supplements. Theoretically, use of marshmallow flower with anticoagulant/antiplatelet drugs can have additive effects, and might increase the risk for bleeding in some patients.

Likelihood Unlikely Evidence D
Oral Drugs

Theoretically, mucilage in marshmallow might impair absorption of oral drugs.
Marshmallow contains mucilage which can affect oral drug absorption. To avoid changes in absorption, take marshmallow 30-60 minutes after oral medications.

Likelihood Possible Evidence D
Marshmallow Root Extract full monograph & interactions

Turmeric Root Extract24 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
Turmeric Root Extract 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

Ginger Rhizome Extract14 drug types · 1,007 drugs

Anticoagulant/Antiplatelet Drugs

Ginger may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
Laboratory research suggests that ginger inhibits thromboxane synthetase and decreases platelet aggregation. However, this has not been demonstrated unequivocally in humans, with mixed results from clinical trials. Theoretically, excessive amounts of ginger might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, taking ginger with antidiabetes drugs might increase the risk of hypoglycemia.
Animal and human research suggests that ginger might increase insulin levels and/or decrease blood glucose levels.

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

Ginger might increase or decrease the levels of CYP3A4 substrates.
In vitro research and some case reports suggest that ginger inhibits CYP3A4 activity. Three case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are CYP3A4 substrates (imatinib, dabrafenib, and crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration.
Conversely, other in vitro research suggests that ginger induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Losartan (Cozaar)

Theoretically, ginger might increase levels of losartan and the risk of hypotension.
In animal research, ginger increased the levels and hypotensive effects of a single dose of losartan. It is not clear if ginger alters the concentration or effects of losartan when taken continuously. Additionally, this interaction has not been shown in humans.

Likelihood Possible Evidence D
Nifedipine (Procardia)

Ginger may have antiplatelet effects and increase the risk of bleeding if used with nifedipine.
Clinical research shows that combined treatment with ginger 1 gram plus nifedipine 10 mg significantly inhibits platelet aggregation when compared to nifedipine or ginger alone.

Likelihood Possible Evidence B
P-Glycoprotein Substrates

Ginger might increase the absorption and blood levels of P-glycoprotein (P-gp) substrates.
In vitro research and case reports suggest that ginger inhibits drug efflux by P-gp, potentially increasing absorption and serum levels of P-gp substrates. Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are P-gp substrates (trametinib, crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration.

Likelihood Possible Evidence D
Phenprocoumon (Marcoumar, Others)

Ginger might increase the risk of bleeding with phenprocoumon.
Phenprocoumon, a warfarin-related anticoagulant, might increase the international normalized ratio (INR) when taken with ginger. There is one case report of a 76-year-old woman with a stable INR on phenprocoumon that increased to greater than 10 when she began consuming dried ginger and ginger tea.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Ginger might increase the risk of bleeding with warfarin.
Laboratory research suggests that ginger might inhibit thromboxane synthetase and decrease platelet aggregation. In one case report, ginger increased the INR when taken with phenprocoumon, which has similar pharmacological effects as warfarin. In another case report, ginger increased the INR when taken with a combination of warfarin, hydrochlorothiazide, and acetaminophen. A longitudinal analysis suggests that taking ginger increases the risk of bleeding in patients taking warfarin for at least 4 months. However, research in healthy people suggests that ginger has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin. Until more is known, monitor INRs closely in patients taking large amounts of ginger.

Likelihood Possible Evidence B
Calcium Channel Blockers

Theoretically, taking ginger with calcium channel blockers might increase the risk of hypotension.
Some animal and in vitro research suggests that ginger has hypotensive and calcium channel-blocking effects. Another animal study shows that concomitant administration of ginger and the calcium channel blocker amlodipine leads to greater reductions in blood pressure when compared with amlodipine alone.

Likelihood Unlikely Evidence D
Cyclosporine (Neoral, Sandimmune)

Theoretically, when taken prior to cyclosporine, ginger might decrease cyclosporine levels.
In an animal model, ginger juice taken 2 hours prior to cyclosporine administration reduced the maximum concentration and area under the curve of cyclosporine by 51% and 40%, respectively. This effect was not observed when ginger juice and cyclosporine were administered at the same time.

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

Theoretically, ginger might increase the levels of CYP1A2 substrates.
In vitro research shows that ginger inhibits CYP1A2 activity. However, this interaction has not been reported in humans.

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

Theoretically, ginger might increase the levels of CYP2B6 substrates.
In vitro research shows that ginger inhibits CYP2B6 activity. However, this interaction has not been reported in humans.

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

Theoretically, ginger might increase the levels of CYP2C9 substrates.
In vitro research shows that ginger inhibits CYP2C9 activity. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Metronidazole (Flagyl)

Theoretically, ginger might increase levels of metronidazole.
In an animal model, ginger increased the absorption and plasma half-life of metronidazole. In addition, the elimination rate and clearance of metronidazole was significantly reduced.

Likelihood Possible Evidence D
Ginger Rhizome Extract full monograph & interactions

Milk Thistle Seed 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 Seed Extract full monograph & interactions

Gymnema leaf extract6 drug types · 851 drugs

Antidiabetes Drugs

Theoretically, taking gymnema with antidiabetes drugs might increase the risk of hypoglycemia.
Gymnema reduces blood glucose levels in some human and animal research. In human studies, it has been shown to enhance the blood glucose lowering effects of hypoglycemic drugs. However, other research in adults with prediabetes or metabolic syndrome suggests that gymnema does not reduce fasting levels of blood glucose. Until more is known, monitor blood glucose levels closely.

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

Theoretically, gymnema might increase levels of drugs metabolized by CYP1A2.
Animal and in vitro research shows that gymnema can inhibit the CYP1A2 enzyme. In one animal study, oral administration of gymnema for 7 days increased the plasma concentrations of phenacetin, a CYP1A2 substrate, by about 1.4-fold and reduced the clearance of phenacetin by about 29%.

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

Theoretically, gymnema might increase or decrease levels of drugs metabolized by CYP2C9.
Animal research shows that gymnema can induce the CYP2C9 enzyme. In one animal study, gymnema caused a 2.4-fold increase in the clearance of tolbutamide, a CYP2C9 substrate, in rats. In vitro research also shows that gymnema can inhibit CYP2C9.

Likelihood Possible Evidence D
Phenacetin

Theoretically, taking gymnema with phenacetin might increase the levels of phenacetin.
Animal research shows that gymnema, administered orally for 7 days, decreases the clearance of phenacetin in a dose-dependent manner by about 21% to 29% and increases plasma levels about 1.3- to 1.4-fold when compared to control.

Likelihood Possible Evidence D
Tolbutamide (Orinase)

Theoretically, taking gymnema with tolbutamide might the decrease levels of tolbutamide.
Animal research shows that gymnema, administered orally for 7 days, increases the clearance of tolbutamide by 2.4-fold when compared to control.

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

Theoretically, gymnema might increase levels of drugs metabolized by CYP3A4.
One in vitro study using rat liver microsomes shows that gymnema can modestly inhibit the CYP3A4 enzyme. However, other in vitro research using human liver microsomes shows that gymnema does not affect CYP3A4 activity. Animal research also shows that gymnema does not alter the function of CYP3A4. In one study in rats, oral administration of gymnema for 7 days did not alter the clearance of amlodipine, a CYP3A4 substrate.

Likelihood Unlikely Evidence D
Gymnema leaf extract full monograph & interactions

Cascara Sagrada Bark Extract6 drug types · 745 drugs

Corticosteroids

Theoretically, cascara sagrada might increase the risk of hypokalemia when taken with corticosteroids.
Cascara sagrada has stimulant laxative effects, and long-term use has been associated with hypokalemia.

Likelihood Possible Evidence D
Digoxin (Lanoxin)

Theoretically, cascara sagrada might cause hypokalemia, potentially increasing the risk of digoxin toxicity.
Cascara sagrada has stimulant laxative effects, and long-term use has been associated with hypokalemia.

Likelihood Possible Evidence D
Diuretic Drugs

Theoretically, cascara sagrada might increase the risk of hypokalemia when taken with diuretic drugs.
Cascara sagrada has stimulant laxative effects, and long-term use has been associated with hypokalemia.

Likelihood Possible Evidence D
Stimulant Laxatives

Theoretically, cascara sagrada might have additive adverse effects when taken with stimulant laxatives.
Cascara sagrada has stimulant laxative effects and might compound fluid and electrolyte losses when taken with stimulant laxatives.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, cascara sagrada might increase the risk of bleeding when taken with warfarin.
Cascara sagrada has stimulant laxative effects. In some people, cascara sagrada can cause diarrhea. Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding.

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

Theoretically, cascara sagrada might decrease the effects of CYP3A4 substrates.
In vitro research suggests that cascara sagrada can induce CYP3A4 enzymes, albeit to a much lower degree than rifampin, a known CYP3A4 inducer.

Likelihood Possible Evidence D
Cascara Sagrada Bark Extract full monograph & interactions

Cinnamon Bark Extract2 drug types · 442 drugs

Antidiabetes Drugs

Theoretically, cassia cinnamon may have additive effects with antidiabetes drugs.
Cassia cinnamon may lower blood glucose levels, and have additive effects in patients treated with antidiabetic agents. Dose adjustments to diabetes medications might be necessary.

Likelihood Possible Evidence B
Hepatotoxic Drugs

Theoretically, large doses of cassia cinnamon might cause additive effects when used with hepatotoxic drugs.
There is some concern that ingesting large amounts of cassia cinnamon for an extended duration might cause hepatotoxicity in some people. Cassia cinnamon contains coumarin, which can cause hepatotoxicity in animal models. In humans, very high doses of coumarin from 50-7000 mg/day can result in hepatotoxicity that resolves when coumarin use is discontinued. Lower amounts might also cause liver problems in sensitive people, such as those with liver disease or those taking potentially hepatotoxic agents.

Likelihood Possible Evidence D
Cinnamon Bark Extract full monograph & interactions

Lemon Balm Aerial Extract2 drug types · 264 drugs

Cns Depressants

Theoretically, concomitant use of lemon balm might have additive effects with CNS depressant drugs.
Lemon balm seems to have CNS depressant activity in animals and in humans.

Likelihood Possible Evidence B
Thyroid Hormone

Theoretically, lemon balm might interfere with thyroid hormone replacement therapy.
In vitro, constituents of lemon balm extract bind to thyroid stimulating hormone (TSH), preventing TSH receptor-binding and leading to the inhibition of TSH-stimulated adenylate cyclase activity. In animals, lemon balm extract has been shown to decrease levels of circulating TSH and inhibit thyroid secretion.

Likelihood Possible Evidence D
Lemon Balm Aerial Extract 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
The maker

Brand information

Manufacturer and brand details for 2-in-1 Cleanse & Flush, from the product label.

Irwin Naturals

See all Irwin Naturals products
Name
Irwin Naturals
Street Address
5310 Beethoven Street
City
Los Angeles
State
CA
ZipCode
90066
Phone Number
1-800-297-3273
Web Address
www.IrwinNaturals.com
Pharmacist Counseling Corner

2-in-1 Cleanse & Flush by Irwin Naturals: Common Questions

Does 2-in-1 Cleanse & Flush by Irwin Naturals interact with any medications?
Yes. Based on its ingredients, 2-in-1 Cleanse & Flush has a known interaction with 2,215 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
2-in-1 Cleanse & Flush contains 13 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 this safe to use while pregnant or breastfeeding?
No — cascara sagrada should be avoided during pregnancy and breastfeeding, as stimulant laxatives are generally not recommended and its active compounds may pass into breast milk. Marshmallow, gymnema, milk thistle, and lemon balm also lack sufficient safety data in pregnancy and breastfeeding. Talk to your doctor before using this product if you are pregnant or nursing.
Can I take this every day, or is it just for occasional constipation?
Long-term daily use of cascara sagrada — a key ingredient — carries real risks, especially the loss of potassium (hypokalemia) and damage to the colon lining. This product is designed for short-term use. If you need ongoing digestive support, talk to your pharmacist or doctor about safer alternatives.
What does ginger do in this formula?
Ginger rhizome extract is included for its traditional digestive and anti-inflammatory properties. Research shows it is possibly effective for pregnancy-related nausea, period pain, and osteoarthritis. In this cleanse product, it likely supports digestive comfort.
Why is black pepper in a digestive supplement?
Black pepper (BioPerine) is a bioavailability enhancer — it helps your body absorb and use the other active ingredients more effectively. It doesn't directly support digestion itself but makes the formula work better.
Will this product interfere with my blood sugar control?
Yes — several ingredients (chromium, ginger, gymnema, cinnamon, and milk thistle) may lower blood sugar. If you take antidiabetes drugs or insulin, this product could increase your risk of low blood sugar (hypoglycemia). Check with your pharmacist before using it.
What are the most common side effects?
From cascara sagrada, expect mild abdominal cramps and discomfort. Ginger may cause heartburn, diarrhea, or a peppery mouth sensation — especially at higher doses. Chromium can cause headache, irritability, or stomach upset. Most side effects are mild if you use the product short-term as directed.

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

Not sure if 2-in-1 Cleanse & Flush 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.

2-in-1 Cleanse & Flush label
Go deeper

The Full Monographs Behind 2-in-1 Cleanse & Flush’s Ingredients

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

Herb & supplement monograph

Ginger

Interacts with 1,007 drugs

Ginger is a widely used culinary spice with a long history in traditional medicine, and it has the strongest evidence for helping with nausea and vomiting, including from motion sickness, pr...

Read the full Ginger 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

Cascara Sagrada

Interacts with 745 drugs

Cascara sagrada is a stimulant laxative made from the aged bark of a Pacific Northwest tree, used mainly for short-term relief of constipation. Because it can cause cramping, dehydration, an...

Read the full Cascara Sagrada monograph → Herb & supplement monograph

Marshmallow

Interacts with 2,040 drugs

Marshmallow root is a traditional herb rich in soothing, gel-like fibers called mucilage, which is why it has long been used for coughs, sore throats, and stomach irritation. Evidence for th...

Read the full Marshmallow 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

Gymnema

Interacts with 851 drugs

Gymnema is an Ayurvedic herb best known for possibly helping lower blood sugar and reducing the taste of sweetness on the tongue. Some early human studies are encouraging for blood sugar sup...

Read the full Gymnema 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

Olive

Olive comes from the same tree that gives us olives and olive oil, and its leaf and fruit contain antioxidant compounds like oleuropein and hydroxytyrosol. Olive oil as part of a Mediterrane...

Read the full Olive monograph → Herb & supplement monograph

Cardamom

Cardamom is a popular cooking spice that has long been used in traditional medicine for digestion and fresh breath. As a food, it is generally safe for most people, but high-dose supplements...

Read the full Cardamom 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

Lemon Balm

Interacts with 264 drugs

Lemon balm is a gentle, lemon-scented mint-family herb traditionally used to ease stress, support sleep, and calm digestion, and topically for cold sores. Early studies are promising but gen...

Read the full Lemon Balm monograph → Herb & supplement monograph

Cassia Cinnamon

Interacts with 442 drugs

Cassia cinnamon is the common, inexpensive cinnamon used in cooking, and it is also taken as a supplement, most often for blood sugar support. The evidence for its health benefits is mixed a...

Read the full Cassia Cinnamon monograph →
Sources

Sources & How We Checked

2-in-1 Cleanse & Flush'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 379 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.

Cascara Sagrada 9 references
  1. Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Trans. S. Klein. Boston, MA: American Botanical Council, 1998.
  2. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  3. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  4. Covington TR, et al. Handbook of Nonprescription Drugs. 11th ed. Washington, DC: American Pharmaceutical Association, 1996.
  5. Nusko G, Schneider B, Schneider I, et al. Anthranoid laxative use is not a risk factor for colorectal neoplasia: results of a prospective case control study. Gut 2000;46:651-5. PubMed
  6. Nadir A, Reddy D, Van Thiel DH. Cascara-sagrada induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity. Am J Gastroenterol 2000;95:3634-7. PubMed
  7. Nakasone ES, Tokeshi J. A serendipitous find: a case of cholangiocarcinoma identified incidentally after acute liver injury due to cascara sagrada ingestion. Hawaii J Med Public Health 2015;74(6):200-2.
  8. Cirillo C, Capasso R. Constipation and botanical medicines: an overview. Phytother Res 2015;29(10):1488-93. PubMed
  9. Mazzari ALDA, Lacerda MG, Milton FA, et al. In vitro effects of European and Latin-American medicinal plants in CYP3A4 gene expression, glutathione levels, and P-glycoprotein activity. Front Pharmacol 2022;13:826395. PubMed

See these in context on the Cascara Sagrada monograph →

Marshmallow 5 references
  1. Monographs on the medicinal uses of plant drugs. Exeter, UK: European Scientific Co-op Phytother, 1997.
  2. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  3. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  4. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  5. Hage-Sleiman R, Mroueh M, Daher CF. Pharmacological evaluation of aqueous extract of Althaea officinalis flower grown in Lebanon. Pharm Biol 2011;49(3):327-33.

See these in context on the Marshmallow 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 →

Ginger 64 references
  1. Fischer-Rasmussen W, Kjaer SK, Dahl C, Asping U. Ginger treatment of hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol 1991;38:19-24. PubMed
  2. Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev 2000;(2):CD000145. PubMed
  3. Vutyavanich T, Kraisarin T, Ruangsri R. Ginger for nausea and vomiting in pregnancy: randomized, double-masked, placebo-controlled trial. Obstet Gynecol 2001;97:577-82. DOI
  4. Backon J. Ginger in preventing nausea and vomiting of pregnancy; a caveat due to its thromboxane synthetase activity and effect on testosterone binding. Eur J Obstet Gynecol Reprod Biol 1991;42:163-4. PubMed
  5. Srivastava KC. Effect of onion and ginger consumption on platelet thromboxane production in humans. Prostaglandins Leukot Essent Fatty Acids 1989;35:183-5. PubMed
  6. Stewart JJ, Wood MJ, Wood CD, Mims ME. Effects of ginger on motion sickness susceptibility and gastric function. Pharmacology 1991;42:111-20. PubMed
  7. Smith C, Crowther C, Willson K, et al. A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet Gynecol 2004;103:639-45. PubMed
  8. Portnoi G, Chng LA, Karimi-Tabesh L, et al. Prospective comparative study of the safety and effectiveness of ginger for the treatment of nausea and vomiting in pregnancy. Am J Obstet Gynecol 2003;189:1374-7.. PubMed
  9. Wigler I, Grotto I, Caspi D, Yaron M. The effects of Zintona EC (a ginger extract) on symptomatic gonarthritis. Osteoarthritis Cartilage 2003;11:783-9. PubMed
  10. Ghayur MN, Gilani AH. Ginger lowers blood pressure through blockade of voltage-dependent calcium channels. J Cardiovasc Pharmacol 2005;45:74-80. PubMed
  11. Thomson M, Al-Qattan KK, Al-Sawan SM, et al. The use of ginger (Zingiber officinale Rosc.) as a potential anti-inflammatory and antithrombotic agent. Prostaglandins Leukot Essent Fatty Acids 2002;67:475-8. PubMed
  12. Kanerva L, Estlander T, Jolanki R. Occupational allergic contact dermatitis from spices. Contact Dermatitis 1996;35:157-62. PubMed
  13. Akhani SP, Vishwakarma SL, Goyal RK. Anti-diabetic activity of Zingiber officinale in streptozotocin-induced type I diabetic rats. J Pharm Pharmacol 2004;56:101-5.
  14. Kruth P, Brosi E, Fux R, et al. Ginger-associated overanticoagulation by phenprocoumon. Ann Pharmacother 2004;38:257-60. PubMed
  15. Jiang X, Williams KM, Liauw WS, et al. Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2005;59:425-32. PubMed
  16. Borrelli F, Capasso R, Aviello G, et al. Effectiveness and safety of ginger in the treatment of pregnancy-induced nausea and vomiting. Obstet Gynecol 2005;105:849-56. PubMed
  17. Smith C, Crowther C, Wilson K et al. A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet Gynecol 2004;103:639-45. PubMed
  18. Jiang X, Blair EY, McLachlan AJ. Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach. J Clin Pharmacol 2006;46:1370-8. PubMed
  19. 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.
  20. Ozgoli G, Goli M, Moattar F. Comparison of effects of ginger, mefenamic acid, and ibuprofen on pain in women with primary dysmenorrhea. J Altern Complement Med 2009;15:129-32. PubMed
  21. Black CD, Herring MP, Hurley DJ, O'Connor PJ. Ginger (Zingiber officinale) reduces muscle pain caused by eccentric exercise. J Pain 2010;11:894-903. PubMed
  22. Heitmann K, Nordeng H, Holst L. Safety of ginger use in pregnancy: results from a large population-based cohort study. Eur J Clin Pharmacol 2012 Jun 17. PubMed
  23. Ryan JL, Heckler CE, Roscoe JA, et al. Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients. Support Care Cancer. 2012;20:1479-89. PubMed
  24. Backon J. Ginger as an antiemetic: possible side effects due to its thromboxane synthetase activity. Anaesthesia. 1991;46(8):705-6.. PubMed
  25. Abebe W. Herbal medication: potential for adverse interactions with analgesic drugs. J Clin Pharm Ther. 2002;27:391-401. PubMed
  26. Argento A, Tiraferri E, Marzaloni M. [Oral anticoagulants and medicinal plants. An emerging interaction]. Ann Ital Med Int. 2000;15:139-43.
  27. Young HY, Liao JC, Chang YS, et al. Synergistic effect of ginger and nifedipine on human platelet aggregation: a study in hypertensive patients and normal volunteers. Am J Chin Med. 2006;34:545-51. PubMed
  28. Greenway FL, Liu Z, Martin CK, et al. Safety and efficacy of NT, an herbal supplement, in treating human obesity. Int J Obes (Lond). 2006;30:1737-41. PubMed
  29. Shalansky S, Lynd L, Richardson K, et al. Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis. Pharmacotherapy. 2007;27:1237-47. PubMed
  30. Lesho EP, Saullo L, Udvari-Nagy S. A 76-year-old woman with erratic anticoagulation. Cleve Clin J Med. 2004;71:651-6. PubMed
  31. Okonta JM, Uboh M, Obonga WO. Herb-Drug Interaction: A Case Study of Effect of Ginger on the Pharmacokinetic of Metronidazole in Rabbit. Indian Journal of Pharmaceutical Sciences (India) 2008;70(230):232. PubMed
  32. Chiang HM, Chao PD, Hsiu SL, et al. Ginger significantly decreased the oral bioavailability of cyclosporine in rats. Am J Chin Med. 2006;34:845-55. PubMed
  33. Bhandari U, Kanojia R, Pillai KK. Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats. J Ethnopharmacol. 2005;97:227-30. PubMed
  34. Ojewole JA. Analgesic, antiinflammatory and hypoglycaemic effects of ethanol extract of Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats. Phytother Res. 2006;20:764-72.
  35. Al-Amin ZM, Thomson M, Al-Qattan KK, et al. Anti-diabetic and hypolipidaemic properties of ginger (Zingiber officinale) in streptozotocin-induced diabetic rats. Br J Nutr. 2006;96:660-6.
  36. Islam MS, Choi H. Comparative effects of dietary ginger (Zingiber officinale) and garlic (Allium sativum) investigated in a type 2 diabetes model of rats. J Med Food. 2008;11:152-9.
  37. Cady RK, Goldstein J, Nett R, et al. A double-blind placebo-controlled pilot study of sublingual feverfew and ginger (LipiGesic M) in the treatment of migraine. Headache 2011;51:1078-86.
  38. Futrell, J. M. and Rietschel, R. L. Spice allergy evaluated by results of patch tests. Cutis 1993;52(5):288-290.
  39. Sripramote, M. and Lekhyananda, N. A randomized comparison of ginger and vitamin B6 in the treatment of nausea and vomiting of pregnancy. J Med Assoc.Thai. 2003;86(9):846-853.
  40. Lohsiriwat, S., Rukkiat, M., Chaikomin, R., and Leelakusolvong, S. Effect of ginger on lower esophageal sphincter pressure. J.Med.Assoc.Thai. 2010;93(3):366-372.
  41. Liu, P. H. and Ho, H. L. Ginger and drug bezoar induced small bowel obstruction. J R.Coll.Surg.Edinb. 1983;28(6):397-398.
  42. Maghbooli M, Golipour F, Moghimi Esfandabadi A, Yousefi M. Comparison between the efficacy of ginger and sumatriptan in the ablative treatment of the common migraine. Phytother Res 2014;28(3):412-5. PubMed
  43. Mahluji S, Attari VE, Mobasseri M, Payahoo L, Ostadrahimi A, Golzari SE. Effects of ginger (Zingiber officinale) on plasma glucose level, HbA1c and insulin sensitivity in type 2 diabetic patients. Int J Food Sci Nutr 2013;64(6):682-6.
  44. Mozaffari-Khosravi H, Talaei B, Jalali BA, Najarzadeh A, Mozayan MR. The effect of ginger powder supplementation on insulin resistance and glycemic indices in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Complement PubMed
  45. Paramdeep G. Efficacy and tolerability of ginger (Zingiber officinale) in patients of osteoarthritis of knee. Indian J Physiol Pharmacol 2013;57(2):177-83.
  46. Rahnama P, Montazeri A, Huseini HF, Kianbakht S, Naseri M. Effect of Zingiber officinale R. rhizomes (ginger) on pain relief in primary dysmenorrhea: a placebo randomized trial. BMC Complement Altern Med 2012;12:92. PubMed
  47. Viljoen E, Visser J, Koen N, Musekiwa A. A systematic review and meta-analysis of the effect and safety of ginger in the treatment of pregnancy-associated nausea and vomiting. Nutr J 2014;13:20. PubMed
  48. Bartels EM, Folmer VN, Bliddal H, et al. Efficacy and safety of ginger in osteoarthritis patients: a meta-analysis of randomized placebo-controlled trials. Osteoarthritis Cartilage. 2015;23(1):13-21. PubMed
  49. Choi JS, Han JY, Ahn HK, et al. Assessment of fetal and neonatal outcomes in the offspring of women who had been treated with dried ginger (Zingiberis rhizoma siccus) for a variety of illnesses during pregnancy. J Obstet Gynaecol. 2015;35(2):125-30.
  50. Marx W, McKavanagh D, McCarthy AL, Bird R, Ried K, Chan A, Isenring L. The effect of ginger (Zingiber officinale) on platelet aggregation: A systematic literature review. PLoS One. 2015;10(10):e0141119. PubMed
  51. Crichton M, Marshall S, Marx W, McCarthy AL, Isenring E. Efficacy of ginger (Zingiber officinale) in ameliorating chemotherapy-induced nausea and vomiting and chemotherapy-related outcomes: A systematic review update and meta-analysis. J Acad Nutr Diet. 2 PubMed
  52. Martins LB, Rodrigues AMDS, Monteze NM, et al. Double-blind placebo-controlled randomized clinical trial of ginger (Zingiber officinale Rosc.) in the prophylactic treatment of migraine. Cephalalgia. 2020;40(1):88-95.
  53. Martins LB, Rodrigues AMDS, Rodrigues DF, Dos Santos LC, Teixeira AL, Ferreira AVM. Double-blind placebo-controlled randomized clinical trial of ginger (Zingiber officinale Rosc.) addition in migraine acute treatment. Cephalalgia. 2019;39(1):68-76.
  54. Ahad A, Raish M, Bin Jardan YA, Alam MA, Al-Mohizea AM, Al-Jenoobi FI. Effect of Hibiscus sabdariffa and Zingiber officinale on the antihypertensive activity and pharmacokinetic of losartan in hypertensive rats. Xenobiotica. 2020:1-11.
  55. Okuhira H, Nakatani Y, Furukawa F, Kanazawa N. Anaphylaxis to ginger induced by herbal medicine. Allergol Int. 2020;69(1):159-160. PubMed
  56. Yamprasert R, Chanvimalueng W, Mukkasombut N, Itharat A. Ginger extract versus Loratadine in the treatment of allergic rhinitis: a randomized controlled trial. BMC Complement Med Ther. 2020;20(1):116. PubMed
  57. Ebrahimzadeh A, Ebrahimzadeh A, Mirghazanfari SM, Hazrati E, Hadi S, Milajerdi A. The effect of ginger supplementation on metabolic profiles in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. PubMed
  58. Alam MA, Bin Jardan YA, Alzenaidy B, et al. Effect of Hibiscus sabdariffa and Zingiber officinale on pharmacokinetics and pharmacodynamics of amlodipine. J Pharm Pharmacol 2021;73(9):1151-60.
  59. Akbarzadeh E, Heydari M, Atarzadeh F, Jaladat AM. Chronic dysuria following ginger (Zingiber officinale) use: a case report. Galen Med J 2018;7:e1086. DOI
  60. 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
  61. Rostamkhani H, Veisi P, Niknafs B, Jafarabadi MA, Ghoreishi Z. The effect of zingiber officinale on prooxidant-antioxidant balance and glycemic control in diabetic patients with ESRD undergoing hemodialysis: a double-blind randomized control trial. BMC Co PubMed
  62. Husain I, Dale OR, Idrisi M, et al. Evaluation of the Herb-Drug Interaction (HDI) Potential of Zingiber officinale and Its Major Phytoconstituents. J Agric Food Chem. 2023;71(19):7521-7534.
  63. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. PubMed
  64. 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

See these in context on the Ginger monograph →

Gymnema 12 references
  1. Shanmugasundaram ER, Rajeswari G, Baskaran K, et al. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol 1990;30:281-94. PubMed
  2. Baskaran K, Kizar Ahamath B, Radha Shanmugasundaram K, Shanmugasundaram ER. Antidiabetic effect of leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharmacol 1990;30:295-300.
  3. Kamble B, Gupta A, Moothedath I, Khatal L, Janrao S, Jadhav A, et al. Effects of Gymnema sylvestre extract on the pharmacokinetics and pharmacodynamics of glimepiride in streptozotocin induced diabetic rats. Chem Biol Interact. 2016;245:30-8. PubMed
  4. Tiwari P, Mishra BN, Sangwan NS. Phytochemical and pharmacological properties of Gymnema sylvestre: an important medicinal plant. Biomed Res Int. 2014; 2014:830285.
  5. Fabio GD, Romanucci V, De Marco A, Zarrelli A. Triterpenoids from Gymnema sylvestre and their pharmacological activities. Molecules. 2014;19(8):10956-81. PubMed
  6. Shiyovich A, Sztarkier I, Nesher L. Toxic hepatitis induced by Gymnema sylvestre, a natural remedy for type 2 diabetes mellitus. Am J Med Sci. 2010;340(6):514-7. PubMed
  7. Zuniga LY, Gonzalez-Ortiz M, Martinez-Abundis E. Effect of gymnema sylvestre administration on metabolic syndrome, insulin sensitivity, and insulin secretion. J Med Food. 2017 Aug;20(8):750-54.
  8. Rammohan B, Samit K, Chinmoy D, et al. Human cytochrome P450 enzyme modulation by gymnema sylvestre: a predictive safety evaluation by LC-MS/MS. Pharmacogn Mag. 2016 Jul;12(Suppl 4):S389-S394.
  9. Vaghela M, Sahu N, Kharkar P, Pandita N. In vivo pharmacokinetic interaction by ethanolic extract of gymnema sylvestre with CYP2C9 (tolbutamide), CYP3A4 (amlodipine) and CYP1A2 (phenacetin) in rats. Chem Biol Interact. 2017 Dec 25;278:141-151. PubMed
  10. Vaghela M, Iyer K, Pandita N. In vitro inhibitory effect of gymnema sylvestre extracts and total gymnemic acids fraction on select cytochrome P450 activities in rat liver microsomes. Eur J Drug Metab Pharmacokinet. 2017 Oct 10. PubMed
  11. Gaytán Martínez LA, Sánchez-Ruiz LA, Zuñiga LY, González-Ortiz M, Martínez-Abundis E. Effect of Gymnema sylvestre administration on glycemic control, insulin secretion, and insulin sensitivity in patients with impaired glucose tolerance. J Med Food. 2021;
  12. Philips CA, Theruvath AH, Ravindran R. Toxic hepatitis-associated aplastic anaemia after dual homeopathic remedies and Gymnema sylvestre use. BMJ Case Rep 2022;15(3):e247867. PubMed

See these in context on the Gymnema 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 →

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 →

Olive 2 references
  1. Liccardi G, D'Amato M, D'Amato G. Oleaceae pollinosis: a review. Int Arch Allergy Immunol 1996;111:210-7. PubMed
  2. Somerville V, Moore R, Braakhuis A. The effect of olive leaf extract on upper respiratory illness in high school athletes: A randomised control trial. Nutrients. 2019;11(2). pii: E358. PubMed

See these in context on the Olive monograph →

Cardamom 2 references
  1. Mobacken, H. and Fregert, S. Allergic contact dermatitis from cardamom. Contact Dermatitis 1975;1(3):175-176. PubMed
  2. Aghasi M, Koohdani F, Qorbani M, et al. Beneficial effects of green cardamom on serum SIRT1, glycemic indices and triglyceride levels in patients with type 2 diabetes mellitus: a randomized double-blind placebo controlled clinical trial. J Sci Food Agri PubMed

See these in context on the Cardamom 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 →

Lemon Balm 12 references
  1. Wolbling RH, Leonhardt K. Local therapy of herpes simplex with dried extract from Melissa officinalis. Phytomedicine 1994;1:25-31.
  2. Akhondzadeh S, Noroozian M, Mohammadi M, et al. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial. J Neurol Neurosurg Psychiatry 2003;74:863-6. PubMed
  3. Kennedy DO, Scholey AB, Tildesley NT, et al. Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacol Biochem Behav 2002;72:953-64. PubMed
  4. Albrecht M, Berger W, Laux P, Schmidt U, et al. Psychopharmaka und Verkehrssicherheit. Der Einfluß von Euvegal® - Dragees forte auf die Fahrtüchtigkeit und Kombinationswirkungen mit Alkohol Z Allg Med 1995;71:1215-25.
  5. Herberg, KW. Nebenwirkungen pflanzlicher Beruhigungsmittel/ Leistung und Befinden nach Einnahme einer Baldrian-Hopfen-Kombination. Z.Allg Med 1996;72:234-240.
  6. Soulimani R, Fleurentin J, Mortier F, et al. Neurotropic action of the hydroalcoholic extract of Melissa officinalis in the mouse. Planta Med. 1991 Apr;57:105-9.
  7. Sourgens H, Winterhoff H, Gumbinger HG, et al. Antihormonal effects of plant extracts. TSH- and prolactin-suppressing properties of Lithospermum officinale and other plants. Planta Med. 1982 Jun;45:78-86. DOI
  8. Auf'mkolk M, Ingbar JC, Amir SM, et al. Inhibition by certain plant extracts of the binding and adenylate cyclase stimulatory effect of bovine thyrotropin in human thyroid membranes. Endocrinology. 1984 Aug;115:527-34. PubMed
  9. Santini F, Vitti P, Ceccarini G, et al. In vitro assay of thyroid disruptors affecting TSH-stimulated adenylate cyclase activity. J Endocrinol Invest. 2003 Oct;26:950-5. PubMed
  10. Alijaniha F, et al. Heart palpitation relief with Melissa officinalis leaf extract: double blind, randomized, placebo controlled trial of efficacy and safety. J Ethnopharmacol. 2015;164:378-384. doi: 10.1016/j.jep.2015.02.007. Epub 2015 Feb 11. PubMed
  11. Araj-Khodaei M, Noorbala AA, Yarani R, et al. A double-blind, randomized pilot study for comparison of Melissa officinalis L. and Lavandula angustifolia Mill. with Fluoxetine for the treatment of depression. BMC Complement Med Ther. 2020;20(1):207. PubMed
  12. Kucuk U, Pham M, Raza Raja MH, Saad Shaukat MH, Clark R. Transient complete atrioventricular block associated with herbal supplement use. S D Med 2023;76(7):311-313.

See these in context on the Lemon Balm monograph →

Cassia Cinnamon 20 references
  1. Electronic Code of Federal Regulations. Title 21. Part 182 -- Substances Generally Recognized As Safe. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=182
  2. Khan A, Safdar M, Ali Khan M, et al. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003;26:3215-8. PubMed
  3. De Benito V, Alzaga R. Occupational allergic contact dermatitis from cassia (Chinese cinnamon) as a flavouring agent in coffee. Contact Dermatitis 1999;40:165. PubMed
  4. Drake TE, Maibach HI. Allergic contact dermatitis and stomatitis caused by a cinnamic aldehyde-flavored toothpaste. Arch Dermatol 1976;112:202-3.
  5. Press release. Cinnamon capsules to reduce blood sugar are medicinal products! Efficacy has not been scientifically proven - some products contain high levels of coumarin. Federal Institute of Risk Assessment (BfM), Germany, November 11, 2006. Available a
  6. Felter SP, Vassallo JD, Carlton BD, Daston GP. A safety assessment of coumarin taking into account species-specificity of toxicokinetics. Food Chem Toxicol 2006;44:462-75. PubMed
  7. Crawford P. Effectiveness of cinnamon for lowering hemoglobin A1C in patients with type 2 diabetes: a randomized, controlled trial. J Am Board Fam Med 2009;22:507-12. PubMed
  8. Akilen, R., Tsiami, A., Devendra, D., and Robinson, N. Glycated haemoglobin and blood pressure-lowering effect of cinnamon in multi-ethnic Type 2 diabetic patients in the UK: a randomized, placebo-controlled, double-blind clinical trial. Diabet.Med. 2010; PubMed
  9. Lu T, Sheng H Wu J Cheng Y Zhu J Chen Y. Cinnamon extract improves fasting blood glucose and glycosylated hemoglobin level in Chinese patients with type 2 diabetes. Nutr Res. 2012;32(6):408-412. PubMed
  10. Choi, J., Lee, K. T., Ka, H., Jung, W. T., Jung, H. J., and Park, H. J. Constituents of the essential oil of the Cinnamomum cassia stem bark and the biological properties. Arch Pharm Res 2001;24(5):418-423.
  11. Altschuler JA, Casella SJ, MacKenzie TA, Curtis KM. The effect of cinnamon on A1C among adolescents with type 1 diabetes. Diabetes Care 2007;30(4):813-6. PubMed
  12. Stoecker BR, Zhan Z, Luo R, et al. Cinnamon extract lowers blood glucose in hyperglycemic subjects. FASEB J. 2010;22:722.1 (Abstract only). DOI
  13. Admani S, Hill H, Jacob SE. Cinnamon Sugar Scrub Dermatitis: "Natural" Is Not Always Best. Pediatr Dermatol. 2017;34(1):e42-e43. PubMed
  14. Isaac-Renton M, Li MK, Parsons LM. Cinnamon spice and everything not nice: many features of intraoral allergy to cinnamic aldehyde. Dermatitis. 2015;26(3):116-21. PubMed
  15. Vandersall A, Katta R. Eyelid dermatitis as a manifestation of systemic contact dermatitis to cinnamon. Dermatitis. 2015 Jul-Aug;26(4):189. PubMed
  16. Wickenberg J, Lindstedt S, Nilsson J, Hlebowicz J. Cassia cinnamon does not change the insulin sensitivity or the liver enzymes in subjects with impaired glucose tolerance. Nutr J 2014 Sep 24;13:96. PubMed
  17. Brancheau D, Patel B, Zughaib M. Do cinnamon supplements cause acute hepatitis? Am J Case Rep 2015;16:250-4. PubMed
  18. Shekarchizadeh-Esfahani P, Heydarpour F, Izadi F, Jalili C. The effect of cinnamon supplementation on liver enzymes in adults: A systematic review and meta-analysis of randomized controlled trials. Complement Ther Med 2021;58:102699. PubMed
  19. Bernaola J, Valverde-Monge M, Otal-Buesa M, Cullen D, Heras-Mendaza F. Cinnamon allergic contact cheilitis. Contact Dermatitis 2023;88(5):418-419. PubMed
  20. Patel K, Howard M, Tate B. Cheilitis caused by allergic contact dermatitis to cinnamon in chai tea: A case report. Contact Dermatitis 2023;88(3):239-240. PubMed

See these in context on the Cassia Cinnamon 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