Interactions on record — worth a quick check against your medications. Based on 9 of 10 ingredients. Check your meds →
Dietary supplement

CirculEnz Ingredients & Drug Interactions

by ProEnzol

CirculEnz label
See full label image
Capsule Category: Other Combinations
Most serious interaction: Moderate
Clinical methodology reviewed by · Updated Sep 16, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking CirculEnz 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

CirculEnz is a dietary supplement by ProEnzol with 10 active ingredients. Its ingredients are commonly taken for inflammation and swelling, sinus and nasal congestion, digestion support.Based on those ingredients, 1,509 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are Citrus Bioflavonoids, Grape Seed Extract, Diosmin. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against CirculEnz by ProEnzol

Ask about any prescription or over-the-counter medication and we check it for interactions with CirculEnz by ProEnzol — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of CirculEnz by ProEnzol

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

Low disclosure
Ingredient Transparency · database check
Low

Most active ingredients don't disclose an individual amount — you can't tell how much of each you're getting.

Why this rating?
  • The label discloses an exact amount for 0 of its 10 active ingredients.
  • “Therapeutic Enzyme Blend” is a proprietary blend — the label gives one combined amount (148 mg) without saying how much of each component you get.
  • “Modulating Botanical Blend” is a proprietary blend — the label gives one combined amount (810 mg) without saying how much of each component you get.

CirculEnz contains 10 active ingredients designed to support circulation. Bromelain is a digestive enzyme from pineapple; citrus bioflavonoids (derived from quercetin) are plant compounds; grape seed extract, blueberry fruit extract, horse chestnut seed extract, diosmin, butcher's broom root extract, gotu kola whole herb extract, and nattokinase are herbal and enzyme ingredients targeting vascular and blood flow function.

A therapeutic enzyme blend and modulating botanical blend serve as compound delivery systems. The product also contains inactive ingredients: plant fiber and water.

Does it work?

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

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

Why this rating?
  • The label markets this product for: support healthy veins and capillary blood flow.
  • We looked for evidence on: Chronic venous insufficiency, Chronic venous insufficiency (CVI), Hemorrhoids, varicose veins, leg swelling, spider veins.
  • The strongest evidence on file: Butcher's Broom is rated "Possibly Effective" for Chronic venous insufficiency (CVI) (Natural Medicines).
  • Also on file: Grape is rated "Possibly Effective" for Chronic venous insufficiency (CVI).
  • Also on file: Gotu Kola is rated "Possibly Effective" for Venous insufficiency.

Evidence for these ingredients is mixed. Grape seed extract and horse chestnut are rated Possibly Effective for chronic venous insufficiency (poor circulation in the legs).

Diosmin is Possibly Effective for chronic venous insufficiency and venous leg ulcers, and Gotu kola is Possibly Effective for venous insufficiency and burns. For most other uses listed on this product—such as general circulation support, blood vessel health, and cardiovascular function—the evidence we hold is insufficient to rate effectiveness, meaning it hasn't been reliably established in the studies available to us.

Bromelain, citrus bioflavonoids, blueberry, butcher's broom, and nattokinase all lack reliable evidence for the conditions they're marketed to address in this formula.

The evidence, ingredient by ingredient Bromelain Nattokinase Quercetin Grape Blueberry Horse Chestnut Diosmin Butcher's Broom

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 9 of the 9 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 9 of 9.
  • General safety write-ups exist for 9 of 9.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most ingredients are generally well tolerated short-term. Bromelain may cause digestive upset (diarrhea, gas, nausea) or allergic reactions in sensitive people.

Citrus bioflavonoids and blueberry extract are generally well tolerated; blueberry's freeze-dried form caused gastrointestinal complaints in about 26 percent of trial participants in one study. Grape seed extract is generally well tolerated, though rare anaphylaxis to grape skin has been reported.

Horse chestnut, diosmin, butcher's broom, and gotu kola can cause nausea, diarrhea, and stomach upset. Gotu kola raises liver-function concerns—while a 6-month study at 120 mg daily showed no changes in liver function, at least four cases of hepatotoxicity have been reported, though causation isn't certain.

Nattokinase carries a documented case of brain hemorrhage when combined with aspirin. Pregnancy safety: bromelain, citrus bioflavonoids, horse chestnut, butcher's broom, gotu kola, and nattokinase lack sufficient data and are best avoided in pregnancy.

Diosmin is rated Likely or Possibly Safe in pregnancy. Grape seed extract and blueberry are rated Likely Safe, though concentrated grape supplements are best avoided.

Breastfeeding data is unavailable for most ingredients; grape seed extract and blueberry are rated Likely Safe, but the others carry insufficient data to recommend their use.

Side effects, ingredient by ingredient Bromelain Nattokinase Quercetin Grape Blueberry Horse Chestnut Diosmin Butcher's Broom

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?
  • 9 of the 9 matched ingredients can interact with medications — Quercetin, Butcher's Broom, Grape, Gotu Kola, Bromelain, among others.
  • The most serious interaction on file is rated Moderate.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; diabetes medications.
  • For scale: 1,510 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 CirculEnz, double-check with your pharmacist if you take any blood thinners or antiplatelet drugs (like warfarin, aspirin, or clopidogrel)—multiple ingredients increase bleeding risk. Also flag: blood pressure medications (losartan and antihypertensive drugs), cholesterol drugs (pravastatin), cyclosporine, antibiotics (tetracycline and quinolone types), muscle relaxants (chlorzoxazone), seizure medications (carbamazepine), sedating drugs, diabetes medications, and any hepatotoxic (liver-damaging) drugs.

The scope and severity of interactions are Moderate across most categories.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFormula with limited ingredient disclosure with some supporting evidence for its stated purpose. Moderate medication interactions have been identified, and safety information is well characterized.

CirculEnz may help with leg circulation if you have chronic venous insufficiency, but it's essential to check your medications first—especially blood thinners, blood pressure drugs, cholesterol medications, and sedatives. If you're pregnant or breastfeeding, talk with your pharmacist before starting.

Anyone with a bleeding disorder or scheduled surgery should get medical clearance.

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

Assessment coverage: 9 of 10 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 CirculEnz, straight from the product label.

Brand ProEnzol
Barcode (UPC) 707636122716
Net contents 60 Vegan Capsule(s)
Market status On market
Date entered into DSLD Jan 23, 2025
DSLD ID 322819
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Vegan, Vegetarian, Adult (18 - 50 Years), Gluten Free, Dairy Free, Sugar Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for CirculEnz by ProEnzol, 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 Vegan Capsule(s)
Maximum serving Sizes:
2 Vegan Capsule(s)
Servings per container
30
UPC/BARCODE
707636122716
IngredientAmount% DV
Bromelain0 NP--
Citrus Bioflavonoids0 NP--
Grape Seed Extract0 NP--
Blueberry Fruit Extract0 NP--
Therapeutic Enzyme Blend148 mg--
Horse Chestnut seed extract0 NP--
Diosmin0 NP--
Butcher's Broom root extract0 NP--
Gotu Kola Whole Herb Extract0 NP--
Nattokinase0 NP--
Modulating Botanical Blend810 mg--
pHysioProtease0 NP--

Other ingredients: Plant Fiber, Water

Tap any ingredient to jump to its full detail below.

Label statements
These statements are the manufacturer’s wording, reproduced from the product label — the label is saying it, not HelloPharmacist. We don’t verify or endorse them.
Formula

ProEnzol CirculEnz provides a modulating blend of potent botanical extracts including Horse Chestnut and Diosmin, plus powerful systemic enzymes from non-animal sources to support healthy structure and function of veins and capillaries, helping to maintain adequate peripheral blood flow.

Suggested/Recommended/Usage/Directions

Directions: take two (2) capsules one to two (1-2) times daily on an empty stomach, or as directed by your healthcare professional.

Precautions

Caution: if you are pregnant, nursing, have a serious medical condition, or take any medications, consult your healthcare professional before use.

Use only if tamper-evident seal is unbroken.

Keep out of reach of children.

Exclusively for professionals

Allergen warning: contains soy

Storage

Store tightly closed in a cool, dry place.

FDA Disclaimer Statement

This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, mitigate, cure, or prevent any disease.

Formulation

Assists in maintaining healthy venous and capillary blood flow

Contains no: sugar, soy, wheat, yeast, gluten, peanuts, tree nuts, eggs, dairy, animal products, artificial colors, flavors and sweeteners or genetically modified organisms (GMOs).

FDA Statement of Identity

Dietary Supplement

Brand IP Statement(s)

pHysioProtease is a registered trademark of Enzymes Inc.

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

See for yourself

CirculEnz by ProEnzol label

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

CirculEnz 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 CirculEnz by ProEnzol

These are the 10 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Vegan Capsule(s) Dosage formCapsule Servings per container30 Amounts shown are per serving.

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

Therapeutic Enzyme Blend

148 mg per serving

Other (inactive) ingredients: Plant Fiber, Water. These complete the product’s ingredient list but are not active constituents.

Interaction report

CirculEnz by ProEnzol Drug Interactions

Want to check YOUR meds against CirculEnz?

Ask about interactions with your drugs in plain English — “Can I take it with lisinopril?” — and we find you the answer in seconds, ingredient by ingredient.

 Go to the checker
1,509Drugs
1,507 Moderate 2 Minor

Ingredients driving the most interactions

Citrus Bioflavonoids 1,169
Grape Seed Extract 910
Diosmin 884
Gotu Kola Whole Herb Extract 579
Nattokinase 289

Individual Drug Interactions

The ingredients in CirculEnz interact with 1,509 drugs. Click any drug to see the details.

9 of the 10 ingredients in CirculEnz interact with drugs. Each result below shows which ingredient is responsible. Citrus Bioflavonoids Grape Seed Extract Diosmin Gotu Kola Whole Herb Extract Nattokinase Butcher's Broom root extract Bromelain Horse Chestnut seed extract Blueberry Fruit Extract

Each ingredient & the kinds of drugs it affects

For each ingredient in CirculEnz 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.

Citrus Bioflavonoids21 drug types · 1,169 drugs

Antidiabetes Drugs

Theoretically, concomitant use of quercetin and antidiabetes drugs might increase the risk of hypoglycemia.

Clinical research suggests that a combination of quercetin, myricetin, and chlorogenic acid reduce levels of fasting glucose in patients with type 2 diabetes, including those already taking antidiabetes agents. The effect of quercetin alone is unknown.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, taking quercetin with antihypertensive drugs might increase the risk of hypotension.

Quercetin can modestly decrease blood pressure in people with mild hypertension. Theoretically, it might have additive blood pressure lowering effects when used with antihypertensive drugs.

Likelihood Possible Evidence B
Cyclosporine (Neoral, Sandimmune)

Theoretically, concomitant use might increase the levels and adverse effects of cyclosporine.

A small study in healthy volunteers shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of a single dose of cyclosporine, possibly due to inhibition of p-glycoprotein or cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporin.

Likelihood Possible Evidence B
Cytochrome P450 2C8 (Cyp2C8) Substrates

Theoretically, concomitant use might increase the levels and adverse effects of CYP2C8 substrates.

In vitro research shows that quercetin inhibits CYP2C8. Inhibition of paclitaxel (Taxol) metabolism via CYP2C8 has been reported in vitro. However, a small study in humans found no effect of quercetin on rosiglitazone (Avandia), which is also a CYP2C8 substrate.

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

Theoretically, concomitant use might increase the levels and adverse effects of CYP2C9 substrates.

A small clinical study in healthy volunteers shows that taking quercetin 500 mg twice daily for 10 days prior to taking diclofenac, a CYP2C9 substrate, increases diclofenac plasma levels by 75% and prolongs the half-life by 32.5%. Animal research also shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of losartan (Cozaar), a substrate of CYP2C9. Furthermore, laboratory research shows that quercetin inhibits CYP2C9.

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

Theoretically, concomitant use might increase the levels and adverse effects of CYP2D6 substrates.

In vitro research show that quercetin inhibits CYP2D6. This effect has not been reported in humans.

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

Theoretically, concomitant use might alter the effects and adverse effects of CYP3A4 substrates.
A small clinical study in healthy volunteers shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of a single dose of cyclosporine (Neoral, Sandimmune), a substrate of CYP3A4. Animal research also shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of losartan (Cozaar) and quetiapine (Seroquel), substrates of CYP3A4. Other laboratory research also shows that quercetin inhibits CYP3A4. However, one clinical study shows that quercetin can increase the metabolism of midazolam, a substrate of CYP3A4, and decrease serum concentrations of midazolam by about 24% in some healthy individuals, suggesting possible induction of CYP3A4.

Likelihood Possible Evidence D
Diclofenac (Voltaren, Others)

Theoretically, concomitant use might increase the levels and adverse effects of diclofenac.

A small clinical study in healthy volunteers shows that taking quercetin 500 mg twice daily for 10 days prior to taking diclofenac increases diclofenac plasma levels by 75% and prolongs the half-life by 32.5%. This is thought to be due to inhibition of CYP2C9 by quercetin.

Likelihood Probable Evidence B
Losartan (Cozaar)

Theoretically, concomitant use might increase the effects and adverse effects of losartan and decrease the effects of its active metabolite.

Animal research shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of losartan (Cozaar) while decreasing plasma levels of losartan's active metabolite. This metabolite, which is around 10-fold more potent than losartan, is the result of cytochrome P450 (CYP) 2C9- and CYP3A4-mediated transformation of losartan. Additionally, in vitro research shows that quercetin may inhibit P-glycoprotein-mediated efflux of losartan from the intestines, resulting in increased absorption of losartan. These results suggest that concomitant use of quercetin and losartan might increase systemic exposure to losartan while also decreasing plasma concentrations of losartan's active and more potent metabolite.

Likelihood Possible Evidence D
Midazolam (Versed)

Theoretically, concomitant use might decrease the levels and effects of midazolam.

A small clinical study in healthy volunteers shows that quercetin can increase the metabolism of midazolam, with a decrease in AUC of about 24%.

Likelihood Possible Evidence B
Mitoxantrone

Theoretically, quercetin might increase the effects and adverse effects of mitoxantrone.
In vitro research shows that quercetin increases the intracellular accumulation and cytotoxicity of mitoxantrone, possibly through inhibition of breast cancer resistance protein (BCRP), of which mitoxantrone is a substrate. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Organic Anion Transporter 1 (Oat1) Substrates

Theoretically, concomitant use might increase the effects and adverse effects of OAT1 substrates.

In vitro research shows that quercetin is a strong non-competitive inhibitor of OAT1, with half-maximal inhibitory concentration (IC50) values less than 10 mcM. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Organic Anion Transporter 3 (Oat3) Substrates

Theoretically, concomitant use might increase the effects and adverse effects of OAT3 substrates.

In vitro research shows that quercetin is a strong non-competitive inhibitor of OAT3, with half-maximal inhibitory concentration (IC50) values as low as 0.75 mcM. So far, this interaction has not been reported in humans.

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

Theoretically, concomitant use might increase the effects and adverse effects of OATP substrates.

In vitro evidence shows that quercetin can inhibit organic anion-transporting peptide (OATP) 1B1-mediated uptake of estrone-3-sulfate and pravastatin. Furthermore, clinical research in healthy males shows that intake of quercetin along with pravastatin increases the AUC of pravastatin by 24%, prolongs its half-life by 14%, and decreases its apparent clearance by 18%, suggesting that quercetin modestly inhibits the uptake of pravastatin in hepatic cells.

Likelihood Possible Evidence B
P-Glycoprotein Substrates

Theoretically, concomitant use might alter the effects and adverse effects of P-glycoprotein substrates.

There is preliminary evidence that quercetin inhibits the gastrointestinal P-glycoprotein efflux pump, which might increase the bioavailability and serum levels of drugs transported by the pump. A small study in healthy volunteers reported that pretreatment with quercetin increased bioavailability and plasma levels after a single dose of cyclosporine (Neoral, Sandimmune). Also, two small studies have shown that quercetin might decrease the absorption of talinolol, a substrate transported by the gastrointestinal P-glycoprotein efflux pump. However, in another small study, several days of quercetin treatment did not significantly affect the pharmacokinetics of saquinavir (Invirase). The reason for these discrepancies is not entirely clear. Until more is known, use quercetin cautiously in combination with P-glycoprotein substrates.

Likelihood Possible Evidence B
Pravastatin (Pravachol)

Theoretically, concomitant use might increase the effects and adverse effects of pravastatin.
In vitro evidence shows that quercetin can inhibit OATP 1B1-mediated uptake of pravastatin. Also, preliminary clinical research in healthy males shows that intake of quercetin along with pravastatin increases the maximum concentration of pravastatin by 24%, prolongs its half-life by 14%, and decreases its apparent clearance by 18%, suggesting that quercetin modestly inhibits the uptake of pravastatin in hepatic cells.

Likelihood Possible Evidence B
Prazosin (Minipress)

Theoretically, quercetin might increase the effects and adverse effects of prazosin.
In vitro research shows that quercetin inhibits the transcellular efflux of prazosin, possibly through inhibition of breast cancer resistance protein (BCRP), of which prazosin is a substrate. BCRP is an ATP-binding cassette efflux transporter in the intestines, kidneys, and liver. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Quetiapine (Seroquel)

Theoretically, concomitant use might increase the effects and adverse effects of quetiapine.
Animal research shows that pretreatment with quercetin can increase plasma levels of quetiapine and prolong its clearance, possibly due to inhibition of cytochrome P450 3A4 (CYP3A4) by quercetin. Additionally, the brain-to-plasma ratio of quetiapine concentrations increased, possibly due to inhibition of P-glycoprotein at the blood-brain barrier. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Quinolone Antibiotics

Theoretically, concomitant use might inhibit the effects of quinolone antibiotics.
In vitro, quercetin binds to the DNA gyrase site on bacteria, which may interfere with the activity of quinolone antibiotics.

Likelihood Possible Evidence B
Sulfasalazine (Azulfidine)

Theoretically, quercetin might increase the effects and adverse effects of sulfasalazine.
Animal research shows that quercetin increases the maximum serum concentration (Cmax) and area under the curve (AUC) of sulfasalazine, possibly through inhibition of breast cancer resistance protein (BCRP), of which sulfasalazine is a substrate. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, quercetin may increase the risk of bleeding if used with warfarin.
Animal and in vitro studies show that quercetin might increase serum levels of warfarin. Quercetin and warfarin have the same human serum albumin (HSA) binding site, and in vitro research shows that quercetin has stronger affinity for the HSA binding site and can theoretically displace warfarin, causing higher serum levels of warfarin. Animal research shows that taking quercetin for 2 weeks before initiating warfarin increases the maximum serum level of warfarin by 30%, the half-life by 10%, and the overall exposure by 63% when compared with control. Concomitant administration of quercetin and warfarin, without quercetin pre-treatment, also increased these measures, but to a lesser degree. Researchers theorize that inhibition of CYP3A4 by quercetin may explain these effects. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Citrus Bioflavonoids full monograph & interactions

Grape Seed Extract9 drug types · 910 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, grape extracts may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro evidence suggests that grape extracts might decrease platelet aggregation.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Ingesting grape juice with cyclosporine can reduce cyclosporine absorption.
A small pharmacokinetic study in healthy young adults shows that intake of purple grape juice 200 mL along with cyclosporine can decrease the absorption of cyclosporine by up to 30% when compared with water. Separate doses of grape juice and cyclosporine by at least 2 hours to avoid this interaction.

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

Theoretically, grape juice might reduce the levels of CYP1A2 substrates.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2.

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

Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.
In vitro evidence suggests that grape seed extract might inhibit CYP2D6 enzymes. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2E1 (Cyp2E1) Substrates

Theoretically, grape seed extract might increase the levels of CYP2E1 substrates.
In vitro and animal research suggests that grape seed proanthocyanidin extract inhibits CYP2E1 enzymes. However, this interaction has not been reported in humans.

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

It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
In vitro evidence suggests that grape seed extract might inhibit CYP3A4 enzymes. However, evidence from animal research shows that grape seed extract may induce CYP3A4 in the liver. So far, these interactions have not been reported in humans.

Likelihood Possible Evidence D
Midazolam (Versed)

Theoretically, long-term intake of grape seed extract might decrease the effects of midazolam.
Animal research shows that subchronic ingestions of grape seed extract can increase the elimination of intravenous midazolam by increasing hepatic CYP3A4 activity. Single doses of grape seed extract do not appear to affect midazolam elimination.

Likelihood Possible Evidence D
Phenacetin

Grape juice might decrease phenacetin absorption.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of cytochrome P450 1A2 (CYP1A2).

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

It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.
In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes. However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism. The effects of continued grape juice consumption are unclear.

Likelihood Unlikely Evidence D
Grape Seed Extract full monograph & interactions

Diosmin9 drug types · 884 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, diosmin may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
A case of spontaneous intraventricular hemorrhage has been reported for a 77-year-old female after 6 weeks of warfarin therapy, despite an international normalized ratio (INR) of only 1.8. The patient had also been taking aspirin and diosmin for several years. Experts speculate that chronic intake of diosmin predisposed the patient to spontaneous intraventricular hemorrhage by inducing chronic microcirculatory hypertension and inhibiting platelet aggregation. The presence of aspirin was also thought to play a role in this event.

Likelihood Possible Evidence D
Carbamazepine (Tegretol)

Theoretically, diosmin might reduce the effects of carbamazepine and increase the risk for convulsions.
A pharmacokinetic study in humans shows that taking diosmin (Venex) 500 mg daily for 10 days prior to oral administration of carbamazepine 200 mg increases blood levels of carbamazepine by approximately 58% and decreases carbamazepine clearance by 42%. It also decreases the formation of carbamazepine's active metabolite. It is speculated that diosmin reduces the metabolism of carbamazepine by inhibiting cytochrome P450 3A4 (CYP3A4).

Likelihood Probable Evidence B
Chlorzoxazone (Parafon Forte, Paraflex)

Theoretically, diosmin might increase the levels and clinical effects of chlorzoxazone.
A pharmacokinetic study in humans shows that taking diosmin (Venex 500) 500 mg daily for 9 days prior to oral administration of chlorzoxazone 250 mg increases blood levels of chlorzoxazone by 53% and decreases chlorzoxazone clearance by 40%. It is speculated that diosmin reduces the metabolism of chlorzoxazone by inhibiting cytochrome P450 2E1 (CYP2E1).

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

Theoretically, diosmin might inhibit the metabolism of CYP2C9 substrates.
Diclofenac is metabolized by CYP2C9 enzymes. Clinical and laboratory research shows that diosmin inhibits the metabolism of diclofenac. A pharmacokinetic study in humans shows that taking diosmin (Venex 500) 500 mg daily for 9 days prior to oral administration of diclofenac 100 mg increases blood levels of diclofenac and decreases diclofenac clearance.

Likelihood Possible Evidence D
Cytochrome P450 2E1 (Cyp2E1) Substrates

Theoretically, diosmin might inhibit the metabolism of CYP2E1 substrates.
Chlorzoxazone is metabolized by CYP2E1 enzymes. A pharmacokinetic study in humans shows that taking diosmin (Venex 500) 500 mg daily for 9 days prior to oral administration of chlorzoxazone (Paraflex 250) 250 mg increases blood levels of chlorzoxazone by 34% and decreases chlorzoxazone clearance by 40%. It is speculated that diosmin reduces the metabolism of chlorzoxazone by inhibiting CYP2E1.

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

Theoretically, diosmin might inhibit the metabolism of CYP3A4 substrates.
Laboratory research is conflicting with respect to the effects of diosmin on CYP3A4. Some research suggests that diosmin does not affect CYP3A4 activity. However, other research suggests that diosmin alters the metabolism of carbamazepine, a CYP3A4 substrate. Laboratory and animal research show that oral administration of diosmin for 7 days prior to oral administration of carbamazepine increases plasma concentrations of carbamazepine, decreases the clearance of carbamazepine, and decreases the formation of carbamazepine's active metabolite. Additionally, pharmacokinetic research in healthy male subjects shows that taking diosmin (Venex) 500 mg daily for 10 days prior to oral administration of carbamazepine 200 mg increases blood levels of carbamazepine by approximately 58% and decreases carbamazepine clearance by 42%. It is speculated that diosmin reduces the metabolism of carbamazepine by inhibiting CYP3A4. Diosmetin, a metabolite of diosmin, may also inhibit CYP3A4.

Likelihood Possible Evidence B
Diclofenac (Voltaren, Others)

Theoretically, diosmin might increase the levels and clinical effects of diclofenac.
Clinical and laboratory research shows that diosmin inhibits the metabolism of diclofenac. A pharmacokinetic study in humans shows that taking diosmin (Venex 500) 500 mg daily for 9 days prior to oral administration of diclofenac 100 mg increases blood levels of diclofenac and decreases diclofenac clearance. It is speculated that diosmin reduces the metabolism of diclofenac by inhibiting cytochrome P450 2C9 (CYP2C9).

Likelihood Probable Evidence B
Fexofenadine (Allegra)

Theoretically, diosmin might increase the levels and clinical effects of fexofenadine.
A pharmacokinetic study in humans shows that taking diosmin (Venex) 500 mg daily for 10 days prior to oral administration of fexofenadine 120 mg increases blood levels of fexofenadine by approximately 49% and decreases the apparent oral clearance of fexofenadine by 41%. The time taken to reach maximum plasma concentration, the half-life, and the apparent renal clearance of fexofenadine are not affected. For this reason, it is speculated that diosmin alters the pharmacokinetics of fexofenadine via inhibition of P-glycoprotein in the intestine, but not in the kidney or liver.

Likelihood Probable Evidence B
P-Glycoprotein Substrates

Theoretically, diosmin might increase levels of drugs that are substrates of P-glycoprotein (P-gp).
Preliminary laboratory research suggests that diosmin inhibits P-gp. Additionally, pharmacokinetic research in healthy male subjects shows that taking diosmin (Venex) 500 mg daily for 10 days prior to oral administration of fexofenadine 120 mg increases blood levels of fexofenadine, a P-gp substrate, by approximately 49% and decreases the apparent oral clearance of fexofenadine by 41%. The time taken to reach maximum plasma concentration, the half-life, and the apparent renal clearance of fexofenadine are not affected. For this reason, it is speculated that diosmin inhibits P-gp in the intestine, but not in the kidney or liver.

Likelihood Possible Evidence D
Diosmin full monograph & interactions

Gotu Kola Whole Herb Extract2 drug types · 579 drugs

Cns Depressants

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

Likelihood Possible Evidence D
Hepatotoxic Drugs

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

Likelihood Possible Evidence D
Gotu Kola Whole Herb Extract full monograph & interactions

Nattokinase2 drug types · 289 drugs

Anticoagulant/Antiplatelet Drugs

Nattokinase might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.
Nattokinase has thrombolytic and anticoagulant effects. There is a case report of intracranial hemorrhage in a patient who added nattokinase to aspirin therapy.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, nattokinase might increase the risk of hypotension when used with antihypertensive drugs.
Some clinical research suggests that nattokinase may reduce systolic and diastolic blood pressure.

Likelihood Possible Evidence D
Nattokinase full monograph & interactions

Butcher's Broom root extract2 drug types · 158 drugs

Alpha-Adrenergic Agonists

Theoretically, butcher's broom might increase the effects and adverse effects of alpha-adrenergic agonists.
Animal and in vitro studies show that butcher's broom has alpha-adrenergic agonist effects.

Likelihood Possible Evidence D
Alpha-Adrenergic Antagonists

Theoretically, butcher's broom might reduce the effects of alpha-adrenergic antagonists.
Animal and in vitro studies show that butcher's broom has alpha-adrenergic agonist effects.

Likelihood Possible Evidence D
Butcher's Broom root extract full monograph & interactions

Bromelain2 drug types · 141 drugs

Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Tetracycline Antibiotics

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

Likelihood Possible Evidence B
Bromelain full monograph & interactions

Horse Chestnut seed extract1 drug type · 122 drugs

Anticoagulant/Antiplatelet Drugs

Horse chestnut may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Horse chestnut contains the constituent esculin which has been shown to have antithrombotic effects. Therefore, horse chestnut might have antiplatelet effects. This has not been shown in humans.

Likelihood Possible Evidence D
Horse Chestnut seed extract full monograph & interactions

Blueberry Fruit Extract3 drug types · 88 drugs

Antidiabetes Drugs

Theoretically, blueberries or blueberry leaf extracts might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal and in vitro research suggests that blueberry and/or blueberry leaf extracts can lower blood glucose levels.

Likelihood Unlikely Evidence D
Buspirone (Buspar)

Theoretically, blueberry juice might increase blood levels of buspirone.
In vitro research shows that blueberry juice can inhibit the metabolism of buspirone, possibly by inhibiting cytochrome P450 3A (CYP3A) enzymes. However, pharmacokinetic research in humans shows that drinking 300 mL of blueberry juice 30 minutes before taking buspirone hydrochloride 10 mg does not significantly affect the concentration or clearance of buspirone.

Likelihood Unlikely Evidence B
Flurbiprofen (Ansaid, Others)

Theoretically, blueberry juice might increase blood levels of flurbiprofen.
In vitro research shows that blueberry juice can inhibit the metabolism of flurbiprofen, possibly by inhibiting cytochrome P450 2C9 (CYP2C9) enzymes. However, pharmacokinetic research in humans shows that drinking 300 mL of blueberry juice 30 minutes before taking flurbiprofen 100 mg does not significantly affect the concentration or clearance of flurbiprofen.

Likelihood Unlikely Evidence B
Blueberry Fruit Extract full monograph & interactions
The maker

Brand information

Manufacturer and brand details for CirculEnz, from the product label.

ProEnzol

See all ProEnzol products
Name
Enzymes Inc.
City
Kansas City
State
MO
ZipCode
64153
Phone Number
1-800-637-7893
Web Address
www.proenzol.com
Pharmacist Counseling Corner

CirculEnz by ProEnzol: Common Questions

Does CirculEnz by ProEnzol interact with any medications?
Yes. Based on its ingredients, CirculEnz has a known interaction with 1,509 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
CirculEnz contains 10 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.
Can I take CirculEnz if I'm on warfarin or another blood thinner?
No—not without talking to your pharmacist or doctor first. Citrus bioflavonoids, bromelain, grape seed extract, horse chestnut, diosmin, and nattokinase all may increase your bleeding risk when combined with blood thinners. There's even a case report of someone who had a serious bleed while on warfarin and diosmin together.
Does CirculEnz actually work for leg swelling or poor circulation?
Grape seed extract and horse chestnut are rated Possibly Effective for chronic venous insufficiency—that's the most solid evidence we have. Diosmin is Possibly Effective for leg circulation and venous ulcers. The other ingredients don't have reliable evidence for circulation support yet.
Is CirculEnz safe if I'm pregnant or planning to get pregnant?
Most of the ingredients lack enough safety data in pregnancy to recommend them. Diosmin is Likely or Possibly Safe, and grape seed extract and blueberry are rated Likely Safe, but bromelain, citrus bioflavonoids, horse chestnut, butcher's broom, gotu kola, and nattokinase are best avoided. Talk with your doctor or pharmacist before starting.
What side effects might I notice from CirculEnz?
Digestive complaints are most common—nausea, diarrhea, gas, stomach upset. Bromelain may cause allergic reactions in sensitive people. Gotu kola raises a small concern about liver function, though clinical trials at typical doses haven't shown problems. Nattokinase carries a rare risk of bleeding.
Does CirculEnz interact with my blood pressure or cholesterol medication?
Possibly. Citrus bioflavonoids may affect losartan (blood pressure) and pravastatin (cholesterol). Nattokinase and some other ingredients may lower blood pressure further. Check your exact medications with the tool on this page or ask your pharmacist.
Should I worry about the 'enzyme blend' and 'botanical blend' ingredients?
The enzyme and botanical blends are containers for other listed ingredients—those are the ones we focus on for interactions and safety. One ingredient, pHysioProtease, is listed separately and we hold no interaction data for it.

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

Not sure if CirculEnz 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.

CirculEnz label
Go deeper

The Full Monographs Behind CirculEnz’s Ingredients

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

Herb & supplement monograph

Bromelain

Interacts with 141 drugs

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

Read the full Bromelain monograph → Herb & supplement monograph

Nattokinase

Interacts with 289 drugs

Nattokinase is an enzyme from the fermented soybean food natto that may have mild blood-thinning and blood-flow effects. Some small studies hint at benefits for blood pressure and circulatio...

Read the full Nattokinase monograph → Herb & supplement monograph

Quercetin

Interacts with 1,169 drugs

Quercetin is a plant flavonoid with antioxidant and anti-inflammatory properties found in many common foods and sold as a supplement. While early research is interesting for allergies, blood...

Read the full Quercetin monograph → Herb & supplement monograph

Grape

Interacts with 910 drugs

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and blood vessel health. While the food is he...

Read the full Grape monograph → Herb & supplement monograph

Blueberry

Interacts with 88 drugs

Blueberries are a nutritious fruit rich in antioxidants called anthocyanins, and eating them as part of a balanced diet is healthy and safe for most people. Concentrated supplements are mark...

Read the full Blueberry monograph → Herb & supplement monograph

Horse Chestnut

Interacts with 122 drugs

Horse chestnut seed extract is most often used for chronic venous insufficiency, where standardized products may help reduce leg swelling, pain, and heaviness. Raw, unprocessed horse chestnu...

Read the full Horse Chestnut monograph → Herb & supplement monograph

Diosmin

Interacts with 884 drugs

Diosmin is a citrus-derived flavonoid most often used for vein-related problems such as chronic venous insufficiency and hemorrhoids, and it is usually combined with a related flavonoid call...

Read the full Diosmin monograph → Herb & supplement monograph

Butcher's Broom

Interacts with 158 drugs

Butcher's broom is a plant extract most often used for circulation problems in the legs, such as chronic venous insufficiency, where some evidence suggests it may help reduce swelling and di...

Read the full Butcher's Broom monograph → Herb & supplement monograph

Gotu Kola

Interacts with 579 drugs

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

Read the full Gotu Kola monograph →
Sources

Sources & How We Checked

CirculEnz'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 162 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.

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

See these in context on the Bromelain monograph →

Quercetin 26 references
  1. Shoskes DA, Zeitlin SI, Shahed A, Rajfer J. Quercetin in men with category III chronic prostatitis: A preliminary prospective, double-blind, placebo-controlled trial. Urol 1999;54:960-3. PubMed
  2. Starvic B. Quercetin in our diet: from potent mutagen to probable anticarcinogen. Clin Biochem 1994;27:245-8. PubMed
  3. Ferry DR, Smith A, Malkhandi J, et al. Phase I clinical trial of the flavonoid quercetin: Pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res 1996;2:659-67..
  4. Obach RS. Inhibition of human cytochrome P450 enzymes by constituents of St. John's wort, an herbal preparation used in the treatment of depression. J Pharmacol Exp Ther 2000;294:88-95. DOI
  5. Edwards RL, Lyon T, Litwin SE, et al. Quercetin reduces blood pressure in hypertensive subjects. J Nutr 2007;137:2405-11.
  6. Kim KA, Park PW, Kim HK, et al. Effect of quercetin on the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, in healthy subjects. J Clin Pharmacol 2005;45:941-6. PubMed
  7. DiCenzo R, Frerichs V, Larppanichpoonphol P, et al. Effect of quercetin on the plasma and intracellular concentrations of saquinavir in healthy adults. Pharmacotherapy 2006;26:1255-61. PubMed
  8. Choi JS, Choi BC, Choi KE. Effect of quercetin on the pharmacokinetics of oral cyclosporine. Am J Health Syst Pharm 2004;61:2406-9. PubMed
  9. Choi JS, Jo BW, Kim YC. Enhanced paclitaxel bioavailability after oral administration of paclitaxel or prodrug to rats pretreated with quercetin. Eur J Pharm Biopharm 2004;57:313-8. PubMed
  10. Vaclavikova R, Horsky S, Simek P, Gut I. Paclitaxel metabolism in rat and human liver microsomes is inhibited by phenolic antioxidants. Naunyn Schmiedebergs Arch Pharmacol 2003;368:200-9. PubMed
  11. Di Bari L, Ripoli S, Pradhan S, Salvadori P. Interactions between quercetin and warfarin for albumin binding: A new eye on food/drug interference. Chirality 2010;22:593-6. PubMed
  12. Lamson, D. W. and Brignall, M. S. Antioxidants and cancer, part 3: quercetin. Altern.Med.Rev. 2000;5(3):196-208.
  13. Duan KM, Wang SY, Ouyang W, Mao YM, Yang LJ. Effect of quercetin on CYP3A activity in Chinese healthy participants. J Clin Pharmacol 2012;52(6):940-6. PubMed
  14. Wang SY, Duan KM, Li Y, et al. Effect of quercetin on P-glycoprotein transport ability in Chinese healthy subjects. Eur J Clin Nutr 2013;67(4):390-4. PubMed
  15. Nguyen MA, Staubach P, Wolffram S, Langguth P. Effect of single-dose and short-term administration of quercetin on the pharmacokinetics of talinolol in humans - Implications for the evaluation of transporter-mediated flavonoid-drug interactions. Eur J Pha PubMed
  16. Wu LX, Guo CX, Chen WQ, et al. Inhibition of the organic anion-transporting polypeptide 1B1 by quercetin: an in vitro and in vivo assessment. Br J Clin Pharmacol 2012;73(5):750-7.
  17. Ahrens MJ, Thompson DL. Effect of emulin on blood glucose in type 2 diabetics. J Med Food. 2013;16(3):211-5. PubMed
  18. Larson A, Witman MA, Guo Y, et al. Acute, quercetin-induced reductions in blood pressure in hypertensive individuals are not secondary to lower plasma angiotensin-converting enzyme activity or endothelin-1: nitric oxide. Nutr Res. 2012;32(8):557-64. PubMed
  19. Bedada SK, Neerati P. Evaluation of the effect of quercetin treatment on CYP2C9 enzyme activity of diclofenac in healthy human volunteers. Phytother Res. 2018 Feb;32(2):305-311. doi: 10.1002/ptr.5978. PubMed
  20. Zhao Q, Wei J, Zhang H. Effects of quercetin on the pharmacokinetics of losartan and its metabolite EXP3174 in rats. Xenobiotica 2019;49(5):563-8. PubMed
  21. Bhutani P, Rajanna PK, Paul AT. Impact of quercetin on pharmacokinetics of quetiapine: insights from in-vivo studies in wistar rats. Xenobiotica. 2020:1-7.
  22. Li C, Wang X, Bi Y, et al. Potent Inhibitors of Organic Anion Transporters 1 and 3 From Natural Compounds and Their Protective Effect on Aristolochic Acid Nephropathy. Toxicol Sci. 2020;175(2):279-291. PubMed
  23. Ni Y, Duan Z, Zhou D, et al. Identification of Structural Features for the Inhibition of OAT3-Mediated Uptake of Enalaprilat by Selected Drugs and Flavonoids. Front Pharmacol. 2020;11:802. PubMed
  24. Song YK, Yoon JH, Woo JK, et al. Quercetin is a flavonoid breast cancer resistance protein inhibitor with an impact on the oral pharmacokinetics of sulfasalazine in rats. Pharmaceutics 2020;12(5):397. PubMed
  25. Ahmad E, Jahangir M, Ismail MA, et al. Influence of quercetin pretreatment on pharmacokinetics of warfarin in rats. Curr Drug Saf 2022. PubMed
  26. Nambiar A, Kellogg D 3rd, Justice J, et al. Senolytics dasatinib and quercetin in idiopathic pulmonary fibrosis: results of a phase I, single-blind, single-center, randomized, placebo-controlled pilot trial on feasibility and tolerability. EBioMedicine 20 PubMed

See these in context on the Quercetin monograph →

Grape 34 references
  1. Kiesewetter H, Koscielny J, Kalus U, et al. Efficacy of orally administered extract of red vine leaf AS 195 (folia vitis viniferae) in chronic venous insufficiency (stages I-II). A randomized, double-blind, placebo-controlled trial. Arzneimittelforschung
  2. Xiao Dong S, Zhi Ping Z, Zhong Xiao W, et al. Possible enhancement of the first-pass metabolism of phenacetin by ingestion of grape juice in Chinese subjects. Br J Clin Pharmacol 1999;48:638-40. PubMed
  3. Vaswani SK, Hamilton RG, Carey RN, et al. Anaphylaxis recurrent urticaria and angioedema from grape hypersensitivity. J Allergy Clin Immunol 1998;101:S31.
  4. Chevallier A. The Encyclopedia of Medicinal Plants. London, UK: Dorling Kindersley, Ltd., 1996.
  5. Bernstein DI, Bernstein CK, Deng C, et al. Evaluation of the clinical efficacy and safety of grapeseed extract in the treatment of fall seasonal allergic rhinitis: a pilot study. Ann Allergy Asthma Immunol 2002;88:272-8.. PubMed
  6. Greenblatt DJ, von Moltke LL, Perloff ES, et al. Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies. Clin Pharmacol Ther 2006;79:125-33. PubMed
  7. Ward NC, Hodgson JM, Croft KD, et al. The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial. J Hypertens 2005;23:427-34.. PubMed
  8. Ray, S. D., Parikh, H., Hickey, E., Bagchi, M., and Bagchi, D. Differential effects of IH636 grape seed proanthocyanidin extract and a DNA repair modulator 4-aminobenzamide on liver microsomal cytochrome 4502E1-dependent aniline hydroxylation. Mol Cell B PubMed
  9. O'Byrne, D. J., Devaraj, S., Grundy, S. M., and Jialal, I. Comparison of the antioxidant effects of Concord grape juice flavonoids alpha-tocopherol on markers of oxidative stress in healthy adults. Am J Clin.Nutr. 2002;76(6):1367-1374.
  10. Schaefer, E., Peil, H., Ambrosetti, L., and Petrini, O. Oedema protective properties of the red vine leaf extract AS 195 (Folia vitis viniferae) in the treatment of chronic venous insufficiency. A 6-week observational clinical trial. Arzneimittelforschun PubMed
  11. Nishikawa, M., Ariyoshi, N., Kotani, A., Ishii, I., Nakamura, H., Nakasa, H., Ida, M., Nakamura, H., Kimura, N., Kimura, M., Hasegawa, A., Kusu, F., Ohmori, S., Nakazawa, K., and Kitada, M. Effects of continuous ingestion of green tea or grape seed extra
  12. de Lange, D. W., Scholman, W. L., Kraaijenhagen, R. J., Akkerman, J. W., and van de Wiel, A. Alcohol and polyphenolic grape extract inhibit platelet adhesion in flowing blood. Eur.J Clin.Invest 2004;34(12):818-824. PubMed
  13. Samet, J. M. and Coultas, D. B. Reduced forced vital capacity in California grape workers. What does it mean? Am Rev.Respir.Dis 1992;145(2 Pt 1):255-256. PubMed
  14. Gamsky, T. E., McCurdy, S. A., Samuels, S. J., and Schenker, M. B. Reduced FVC among California grape workers. Am Rev.Respir.Dis 1992;145(2 Pt 1):257-262. PubMed
  15. de Lange, D. W., Verhoef, S., Gorter, G., Kraaijenhagen, R. J., van de Wiel, A., and Akkerman, J. W. Polyphenolic grape extract inhibits platelet activation through PECAM-1: an explanation for the French paradox. Alcohol Clin.Exp.Res 2007;31(8):1308-1314 PubMed
  16. Etheridge, A. S., Black, S. R., Patel, P. R., So, J., and Mathews, J. M. An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constitu
  17. Krikorian, R., Nash, T. A., Shidler, M. D., Shukitt-Hale, B., and Joseph, J. A. Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr. 2010;103(5):730-734. PubMed
  18. Ingersoll, G. L., Wasilewski, A., Haller, M., Pandya, K., Bennett, J., He, H., Hoffmire, C., and Berry, C. Effect of concord grape juice on chemotherapy-induced nausea and vomiting: results of a pilot study. Oncol.Nurs.Forum 2010;37(2):213-221. PubMed
  19. Oliveira-Freitas, V. L., Dalla, Costa T., Manfro, R. C., Cruz, L. B., and Schwartsmann, G. Influence of purple grape juice in cyclosporine bioavailability. J Ren Nutr. 2010;20(5):309-313. PubMed
  20. Hollis, J. H., Houchins, J. A., Blumberg, J. B., and Mattes, R. D. Effects of concord grape juice on appetite, diet, body weight, lipid profile, and antioxidant status of adults. J Am Coll.Nutr. 2009;28(5):574-582. PubMed
  21. Dohadwala, M. M., Hamburg, N. M., Holbrook, M., Kim, B. H., Duess, M. A., Levit, A., Titas, M., Chung, W. B., Vincent, F. B., Caiano, T. L., Frame, A. A., Keaney, J. F., Jr., and Vita, J. A. Effects of Concord grape juice on ambulatory blood pressure in
  22. Rabe, E., Stucker, M., Esperester, A., Schafer, E., and Ottillinger, B. Efficacy and tolerability of a red-vine-leaf extract in patients suffering from chronic venous insufficiency--results of a double-blind placebo-controlled study. Eur.J Vasc.Endovasc. PubMed
  23. Trotta, M., Cesaretti, M., Conzi, R., Derchi, L. E., and Borgonovo, G. Elderly male with mesogastric pain. Small bowel obstruction caused by an intact fresh grape. Ann.Emerg.Med 2011;58(4):e1-e2. PubMed
  24. McCurdy, S. A., Wiggins, P., Schenker, M. B., Munn, S., Shaieb, A. M., Weinbaum, Z., Goldsmith, D., McGillis, S. T., Berman, B., and Samuels, S. Assessing dermatitis in epidemiologic studies: occupational skin disease among California grape and tomato ha
  25. Winter, C. K. and Kurtz, P. H. Factors influencing grape worker susceptibility to skin rashes. Bull.Environ.Contam Toxicol. 1985;35(3):418-426. PubMed
  26. Yamasaki, R., Dekio, S., and Jidoi, J. Contact dermatitis from grape bud. Contact Dermatitis 1985;12(4):226-227. PubMed
  27. Cox, J. and Grigg, M. Small bowel obstruction by an intact grape. J Am Geriatr.Soc 1986;34(7):550. PubMed
  28. Faircloth, D. E. and Robison, W. J. Obstruction of the sigmoid colon by grape seeds. JAMA 11-27-1981;246(21):2430. PubMed
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  30. Brito, FF., Martinez, A., Palacios, R., Mur, P., Gomez, E., Galindo, P. A., Borja, J., and Martinez, J. Rhinoconjunctivitis and asthma caused by vine pollen: a case report. J Allergy Clin Immunol 1999;103(2 Pt 1):262-266. PubMed
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Blueberry 7 references
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Horse Chestnut 21 references
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Diosmin 20 references
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Butcher's Broom 8 references
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See these in context on the Butcher's Broom monograph →

Gotu Kola 18 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. Pointel JP, Boccalon H, Cloarec M, et al. Titrated extract of Centella asiatica (TECA) in the treatment of venous insufficiency of the lower limbs. Angiol 1987;38:46-50. PubMed
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Nattokinase 9 references
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DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

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