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Dietary supplement

Circulation & Vein Support for Healthy Legs Ingredients & Drug Interactions

by ProCaps

Circulation & Vein Support for Healthy Legs 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 Circulation & Vein Support for Healthy Legs 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

Circulation & Vein Support for Healthy Legs is a dietary supplement by ProCaps with 8 active ingredients. Its ingredients are commonly taken for varicose veins and chronic venous insufficiency, hemorrhoids, easy bruising and fragile capillaries.Based on those ingredients, 1,434 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are Grape Seed Extract, Diosmin, Hesperidin. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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HelloPharmacist Scorecard of Circulation & Vein Support for Healthy Legs by ProCaps

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 12, 2026

What’s inside

Full disclosure
Ingredient Transparency · database check
Full

Every active ingredient lists its own amount on the label.

Why this rating?
  • The label discloses an exact amount for 8 of its 8 active ingredients.
  • No proprietary blends here — you can verify the dose of every single component.

This product contains 8 active ingredients chosen to support healthy leg circulation and vein function. Rutin, Hesperidin, Diosmin, Grape Seed Extract, Butcher's Broom extract, Horse Chestnut extract, and Pine Bark extract are plant-derived compounds with a long history in traditional circulation support.

Vitamin C is included as an antioxidant. The capsule itself is made from gelatin.

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: promote healthy circulation in legs and veins.
  • We looked for evidence on: Chronic venous insufficiency (CVI), Varicose veins, Leg swelling and heaviness, Hemorrhoids.
  • 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: Maritime Pine is rated "Possibly Effective" for Chronic venous insufficiency (CVI).

The evidence for most of these ingredients is limited or mixed. For Chronic Venous Insufficiency (CVI)—a condition involving poor blood flow in the legs—Grape Seed Extract, Diosmin, Butcher's Broom, Horse Chestnut, and Pine Bark Extract are all rated Possibly Effective, meaning there's some clinical evidence but it's not definitive.

Vitamin C is Effective for vitamin C deficiency and Possibly Effective for a handful of other conditions, but the data we hold don't establish it as proven for circulation. Rutin and Hesperidin lack sufficient reliable evidence to rate them for any condition.

The evidence, ingredient by ingredient Rutin Hesperidin Vitamin C Grape Diosmin Butcher's Broom Horse Chestnut Maritime Pine

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 8 of the 8 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 8 of 8.
  • General safety write-ups exist for 8 of 8.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most ingredients are generally well tolerated in short-term use, but long-term safety data are limited for several of them. Common side effects reported include gastrointestinal complaints (nausea, diarrhea, heartburn, stomach upset) with Vitamin C, Grape Seed, Diosmin, Butcher's Broom, and Horse Chestnut.

Vitamin C can cause kidney stones in people prone to them and is safest below 2 grams daily. Horse Chestnut seed extract must be processed to remove a toxic constituent; raw plant parts are dangerous.

During pregnancy, safety varies by ingredient: Rutin and Diosmin are likely safe, Hesperidin is possibly safe, but Butcher's Broom and Horse Chestnut should be avoided, and Pine Bark Extract is possibly safe. During breastfeeding, the picture is murkier—Rutin, Hesperidin, and Vitamin C lack enough safety data, and Butcher's Broom, Horse Chestnut, and Pine Bark should be avoided.

Side effects, ingredient by ingredient Rutin Hesperidin Vitamin C Grape Diosmin Butcher's Broom Horse Chestnut Maritime Pine

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?
  • 8 of the 8 matched ingredients can interact with medications — Rutin, Butcher's Broom, Grape, Vitamin C, Maritime Pine, 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.
  • For scale: 1,435 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, check with your pharmacist if you're on blood thinners or antiplatelet drugs (warfarin, aspirin, clopidogrel); diabetes medications; blood pressure drugs; estrogen-based medications like birth control or hormone therapy; verapamil or diltiazem for your heart; levothyroxine for thyroid; or any medications processed by liver enzymes. Vitamin C at the doses in this product is unlikely to cause significant interactions, but the combination of multiple interactive ingredients means a medication review is wise.

Check your own medication Run your meds through the checker above

The bottom line

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

This blend is designed for people seeking circulation support, particularly for leg health and vein function. If you're on any medications—especially blood thinners, diabetes drugs, blood pressure medications, birth control, heart drugs, or drugs processed by the liver—check your specific medications with the tool on this page before starting.

Pregnant or breastfeeding? Talk to your pharmacist first, as safety data are incomplete for several ingredients.

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

Assessment coverage: 8 of 8 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Aug 23, 2021.

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 Circulation & Vein Support for Healthy Legs, straight from the product label.

Brand ProCaps
Barcode (UPC) 702942
Net contents 360 Easy-To-Swallow Capsule(s)
Market status On market
Date entered into DSLD Aug 23, 2021
DSLD ID 248426
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten Free, Dairy Free, Sugar Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Circulation & Vein Support for Healthy Legs by ProCaps, 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 Capsule(s)
Maximum serving Sizes:
2 Capsule(s)
Servings per container
180
UPC/BARCODE
702942
IngredientAmount% DV
Rutin10 mg--
Hesperidin50 mg--
Vitamin C30 mg33%
Grape Seed Extract10 mg--
Diosmin600 mg--
Butcher's Broom extract80 mg--
Horse Chestnut extract80 mg--
Pine Bark extract10 mg--

Other ingredients: Gelatin Capsule

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.
Suggested/Recommended/Usage/Directions

Suggested use consume two capsules each day or as recommended by your physician. This product is most effective as part of a healthy diet and active lifestyle. For questions about the use of this product call 800.332.7799.

Precautions

Note: Not intended for use during pregnancy without physician's approval.

Formulation

For over 40 years unsurpassed purity, quality and efficacy 100% solar production Zero carbon footprint

Andrew Lessman's Circulation and Vein Support is a blend of the most effective, clinically studied natural ingredients to promote healthy circulation in the legs and provide relief to their challenged tissues and veins. This unique formula is designed to combat the natural swelling of the veins and tissues of our legs that occur with aging, overweight and our daily activities.

Contains no additives of any kind Contains no milk, soy, yeast, wheat, gluten, sodium, salt, sugar, fat, cholesterol, color, preservative, common allergens or manufacturing additives.

General Statements

We remain uniquely committed to you and the planet. You have my unwavering promise. Andrew Lessman, founder Questions?/reorders? 800.800.1200 www.ProCapsLabs.com HSN www.HSN.com 800.944.9999 www.QVC.com 800.345.1515

The blood vessels in our legs are perhaps the most challenged in our body and, as a result, our feet, ankles and calves can swell, enlarge and experience discomfort. This normal process is intensified by aging, overweight and prolonged sitting or standing.

Formula

Diosmin, Butcher broom, Horse Chestnut, Hesperidin, Rutin, Grape seed, Pine bark

Our primary ingredient, Diosmin is the most researched natural ingredient for promoting healthy leg circulation. It has been recommended by physicians in Europe for over 70 years for swollen, heavy, uncomfortable legs, as well as to promote the healthy function and appearance of leg veins. We also add extracts of both Butcher's Broom and Horse Chestnut - two natural ingredients utilized traditionally for centuries in Europe. Both ingredients have been clinically shown to relieve tired, heavy legs and promote optimum leg vein health and appearance. We also add the protective benefits of Hesperidin, Rutin, Pine Bark and Grape seed. In short, Circulation and Vein Support is designed to provide a visible, tangible difference to the circulation, tissues and veins of our legs. Its unique proprietary blend of Diosmin, Butcher's Broom and Horse Chestnut provide a natural, clinically validated response to the enormous demands we place on the already challenged circulation in our legs.

FDA Statement of Identity

Dietary Supplement

FDA Disclaimer Statement

These statements have not been evaluated by the Food and 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

Circulation & Vein Support for Healthy Legs by ProCaps label

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

Circulation & Vein Support for Healthy Legs 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 Circulation & Vein Support for Healthy Legs by ProCaps

These are the 8 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Capsule(s) Dosage formCapsule Servings per container180 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.

Rutin

Interacts with
86 drugs
10 mg per serving

Rutin is a plant flavonoid (often taken from buckwheat or citrus) that people use mainly for blood vessel and circulation problems like varicose veins...

Rutin monograph & interactions

Hesperidin

Interacts with
702 drugs
50 mg per serving

Hesperidin is a flavonoid found in citrus fruits that is often combined with diosmin and used for vein and circulation problems like hemorrhoids and v...

Hesperidin monograph & interactions

Vitamin C

Interacts with
207 drugs
30 mg per serving Form: Ascorbyl Palmitate, Calcium Ascorbate

Vitamin C (ascorbic acid) is an essential nutrient your body needs but cannot make, so you must get it from food or supplements. It's important for im...

Vitamin C monograph & interactions

Grape Seed Extract

Interacts with
910 drugs
10 mg per serving Form: Polyphenols

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and b...

Grape Seed Extract monograph & interactions

Diosmin

Interacts with
884 drugs
600 mg per serving

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

Diosmin monograph & interactions

Butcher's Broom extract

Interacts with
158 drugs
80 mg per serving Form: Saponins

Butcher's broom is a plant extract most often used for circulation problems in the legs, such as chronic venous insufficiency, where some evidence sug...

Butcher's Broom extract monograph & interactions

Horse Chestnut extract

Interacts with
122 drugs
80 mg per serving Form: Aescin

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

Horse Chestnut extract monograph & interactions

Pine Bark extract

Interacts with
327 drugs
10 mg per serving Form: Polyphenols, Proanthocyanidins

Maritime pine bark extract (often sold as Pycnogenol) is a plant-based antioxidant most studied for circulation, vein, and skin health. Some research...

Pine Bark extract monograph & interactions

Other (inactive) ingredients: Gelatin Capsule. These complete the product’s ingredient list but are not active constituents.

Interaction report

Circulation & Vein Support for Healthy Legs by ProCaps Drug Interactions

Want to check YOUR meds against Circulation & Vein Support for Healthy Legs?

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
1,434Drugs
1,430 Moderate 4 Minor

Ingredients driving the most interactions

Grape Seed Extract 910
Diosmin 884
Hesperidin 702
Pine Bark extract 327
Vitamin C 207

Individual Drug Interactions

The ingredients in Circulation & Vein Support for Healthy Legs interact with 1,434 drugs. Click any drug to see the details.

8 of the 8 ingredients in Circulation & Vein Support for Healthy Legs interact with drugs. Each result below shows which ingredient is responsible. Grape Seed Extract Diosmin Hesperidin Pine Bark extract Vitamin C Butcher's Broom extract Horse Chestnut extract Rutin

Each ingredient & the kinds of drugs it affects

For each ingredient in Circulation & Vein Support for Healthy Legs 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.

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

Hesperidin7 drug types · 702 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, hesperidin may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Animal research suggests that hesperetin, a bioflavonoid aglycone derivative of hesperidin, may have antiplatelet activity.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, taking hesperidin with antihypertensive drugs might increase the risk of hypotension.
Some clinical and animal research shows that hesperidin can decrease blood pressure. However, other clinical research shows that hesperidin does not affect blood pressure.

Likelihood Possible Evidence D
Celiprolol (Celicard)

Theoretically, hesperidin may decrease the levels and clinical effects of celiprolol.
Animal research shows that concomitant use of hesperidin may reduce the plasma area under the curve of celiprolol by up to 75%. This effect has not been reported in humans.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, concomitant use with CNS depressants may cause additive sedative effects.
Animal studies show that hesperidin has sedative effects, due to opioid receptor activity and can increase sedation when used with diazepam. This effect has not been reported in humans.

Likelihood Possible Evidence D
Diltiazem (Cardizem, Others)

Theoretically, hesperidin may increase the levels and clinical effects of diltiazem.
Animal research suggests that hesperidin may enhance the bioavailability of diltiazem, increasing the plasma area under the curve of diltiazem by up to 65.3%. This effect has not been reported in humans.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, hesperidin might inhibit P-glycoprotein-mediated drug efflux and potentially increase levels of drugs that are substrates of P-glycoprotein.
In vitro research shows that hesperidin can inhibit P-glycoprotein efflux. This effect has not been reported in humans.

Likelihood Possible Evidence D
Verapamil (Calan, Others)

Theoretically, hesperidin might increase the levels and clinical effects of verapamil.
Animal research suggests that hesperidin may enhance the bioavailability of verapamil, increasing the plasma area under the curve of verapamil by 96.8%. This effect has not been reported in humans

Likelihood Possible Evidence D
Hesperidin full monograph & interactions

Pine Bark extract3 drug types · 327 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, maritime pine bark extract might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.
Clinical research suggests that maritime pine bark extract inhibits platelet aggregation. However, the clinical significance of this effect is unclear.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, maritime pine bark extract might increase the risk of hypoglycemia when used with antidiabetes drugs.
One clinical study shows that maritime pine bark extract decreases blood sugar in patients with diabetes being treated with antidiabetes agents. Monitor blood glucose levels closely. Dose adjustments might be necessary.

Likelihood Possible Evidence B
Immunosuppressants

Theoretically, maritime pine bark extract might decrease the effectiveness of immunosuppressant therapy.
In vitro and animal research suggests that maritime pine bark extract has immunostimulant activity. This effect has not been reported in humans.

Likelihood Possible Evidence D
Pine Bark extract full monograph & interactions

Vitamin C13 drug types · 207 drugs

Alkylating Agents

Theoretically, antioxidant effects of vitamin C might reduce the effectiveness of alkylating agents.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin C have on chemotherapy.

Likelihood Possible Evidence D
Aluminum

Vitamin C can increase the amount of aluminum absorbed from aluminum compounds.
Research in animals and humans shows that vitamin C increases aluminum absorption, theoretically by chelating aluminum and keeping it in solution where it is available for absorption. In people with normal renal function, urinary excretion of aluminum will likely increase, making aluminum retention and toxicity unlikely. Patients with renal failure who take aluminum-containing compounds such as phosphate binders should avoid vitamin C supplements in doses above the recommended dietary allowances.

Likelihood Probable Evidence B
Antitumor Antibiotics

Theoretically, the antioxidant effects of vitamin C might reduce the effectiveness of antitumor antibiotics.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as doxorubicin. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on chemotherapy.

Likelihood Possible Evidence D
Estrogens

Vitamin C might increase blood levels of estrogens.
Increases in plasma estrogen levels of up to 55% occur under some circumstances when vitamin C is taken concurrently with oral contraceptives or hormone replacement therapy, including topical products. It is suggested that vitamin C prevents oxidation of estrogen in the tissues, regenerates oxidized estrogen, and reduces sulfate conjugation of estrogen in the gut wall. When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C does not have any effect on estrogen levels. Increases in plasma estrogen levels may occur when patients who are deficient in vitamin C take supplements. Monitor these patients for estrogen-related side effects.

Likelihood Probable Evidence B
Fluphenazine (Prolixin)

Theoretically, vitamin C might decrease levels of fluphenazine.
In one patient there was a clinically significant decrease in fluphenazine levels when vitamin C (500 mg twice daily) was started. The mechanism is not known, and there is no further data to confirm this interaction.

Likelihood Possible Evidence D
Indinavir (Crixivan)

Vitamin C can modestly reduce indinavir levels.
One pharmacokinetic study shows that taking vitamin C 1 gram orally once daily along with indinavir 800 mg orally three times daily reduces the area under the concentration-time curve of indinavir by 14%. The mechanism of this interaction is unknown, but it is unlikely to be clinically significant in most patients. The effect of higher doses of vitamin C on indinavir levels is unknown.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Vitamin C can increase levothyroxine absorption.
Two clinical studies in adults with poorly controlled hypothyroidism show that swallowing levothyroxine with a glass of water containing vitamin C 500-1000 mg in solution reduces thyroid stimulating hormone (TSH) levels and increases thyroxine (T4) levels when compared with taking levothyroxine alone. This suggests that vitamin C increases the oral absorption of levothyroxine, possibly due to a reduction in pH.

Likelihood Probable Evidence B
Warfarin (Coumadin)

High-dose vitamin C might reduce the levels and effectiveness of warfarin.
Vitamin C in high doses may cause diarrhea and possibly reduce warfarin absorption. There are reports of two people who took up to 16 grams daily of vitamin C and had a reduction in prothrombin time. Lower doses of 5-10 grams daily can also reduce warfarin absorption. In many cases, this does not seem to be clinically significant. However, a case of warfarin resistance has been reported for a patient who took vitamin C 500 mg twice daily. Cessation of vitamin C supplementation resulted in a rapid increase in international normalized ratio (INR). Tell patients taking warfarin to avoid taking vitamin C in excessively high doses (greater than 10 grams daily). Lower doses may be safe, but the anticoagulation activity of warfarin should be monitored. Patients who are stabilized on warfarin while taking vitamin C should avoid adjusting vitamin C dosage to prevent the possibility of warfarin resistance.

Likelihood Possible Evidence D
Acetaminophen (Tylenol, Others)

High-dose vitamin C might slightly prolong the clearance of acetaminophen.
A small pharmacokinetic study in healthy volunteers shows that taking high-dose vitamin C (3 grams) 1.5 hours after taking acetaminophen 1 gram slightly increases the apparent half-life of acetaminophen from around 2.3 hours to 3.1 hours. Ascorbic acid competitively inhibits sulfate conjugation of acetaminophen. However, to compensate, elimination of acetaminophen glucuronide and unconjugated acetaminophen increases. This effect is not likely to be clinically significant.

Likelihood Probable Evidence B
Aspirin

Acidification of the urine by vitamin C might increase aspirin levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction is not clinically significant.

Likelihood Possible Evidence B
Choline Magnesium Trisalicylate (Trilisate)

Acidification of the urine by vitamin C might increase choline magnesium trisalicylate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Likelihood Possible Evidence B
Niacin

Vitamin C might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.
A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease. It is not known whether this adverse effect is due to a single antioxidant such as vitamin C, or to the combination. It also is not known whether it will occur in other patient populations.

Likelihood Possible Evidence A
Salsalate (Disalcid)

Acidification of the urine by vitamin C might increase salsalate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams/day vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Likelihood Possible Evidence B
Vitamin C full monograph & interactions

Butcher's Broom 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 extract full monograph & interactions

Horse Chestnut 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 extract full monograph & interactions

Rutin1 drug type · 86 drugs

Antidiabetes Drugs

Theoretically, taking rutin with antidiabetes drugs might increase the risk of hypoglycemia.
Animal research suggests that rutin has hypoglycemic effects.

Likelihood Possible Evidence D
Rutin full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Circulation & Vein Support for Healthy Legs, from the product label.

ProCaps

See all ProCaps products
Name
ProCaps Labs
City
Henderson
State
NV
ZipCode
89011
Phone Number
800.800.1200
Web Address
www.ProCapsLabs.com
Pharmacist Counseling Corner

Circulation & Vein Support for Healthy Legs by ProCaps: Common Questions

Does Circulation & Vein Support for Healthy Legs by ProCaps interact with any medications?
Yes. Based on its ingredients, Circulation & Vein Support for Healthy Legs has a known interaction with 1,434 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Circulation & Vein Support for Healthy Legs contains 8 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.
Will this help my varicose veins or leg swelling?
Several ingredients here—Grape Seed, Diosmin, Butcher's Broom, Horse Chestnut, and Pine Bark—have some clinical evidence for Chronic Venous Insufficiency, a condition involving poor blood flow in the legs. The evidence is rated Possibly Effective, meaning it's not conclusive. Results vary, and you should discuss this with your doctor, especially if your leg problems are severe or worsening.
Can I take this if I'm on a blood thinner like warfarin or aspirin?
You need to check with your pharmacist before starting. Horse Chestnut, Grape Seed, Diosmin, and Pine Bark all have interactions with blood thinners and may increase bleeding risk. The interaction has not been confirmed in humans, but it's serious enough that your pharmacist needs to review your exact medication and dose.
Is this safe during pregnancy?
It depends on the ingredient. Rutin and Diosmin are likely safe, and Hesperidin is possibly safe. However, Butcher's Broom and Horse Chestnut should be avoided, and Pine Bark data aren't clear. Since this is a multi-ingredient product, talk with your doctor or pharmacist before using it during pregnancy.
Can I take this if I'm on diabetes medication?
Rutin and Pine Bark Extract both interact with diabetes drugs and may increase the risk of low blood sugar. If you take medication to lower your blood sugar, your pharmacist needs to review this product with you first. Your dose may need adjustment, or the combination may not be safe for you.
What are the most common side effects?
Gastrointestinal complaints are most common—nausea, diarrhea, heartburn, and stomach upset—reported with several of the plant extracts in this blend. Vitamin C at high doses can cause similar GI side effects and may cause kidney stones in people at risk. Headache has also been reported with a few ingredients.
Is this safe to take long-term?
Most ingredients are described as generally well tolerated short-term, but high-quality long-term safety data are limited for several of them, including Rutin, Hesperidin, Diosmin, Butcher's Broom, and Pine Bark. If you plan to use this for months, discuss it with your pharmacist or doctor first.

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

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Label information is sourced from the NIH Dietary Supplement Label Database and reflects the product version on file; always read your actual product label. This page is for education only and is not a substitute for professional medical advice. Confirm with your pharmacist or doctor before combining supplements and medications.

Circulation & Vein Support for Healthy Legs label
Go deeper

The Full Monographs Behind Circulation & Vein Support for Healthy Legs’s Ingredients

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

Herb & supplement monograph

Rutin

Interacts with 86 drugs

Rutin is a plant flavonoid (often taken from buckwheat or citrus) that people use mainly for blood vessel and circulation problems like varicose veins and hemorrhoids. The evidence is limite...

Read the full Rutin monograph → Herb & supplement monograph

Hesperidin

Interacts with 702 drugs

Hesperidin is a flavonoid found in citrus fruits that is often combined with diosmin and used for vein and circulation problems like hemorrhoids and varicose veins. Some evidence supports th...

Read the full Hesperidin monograph → Herb & supplement monograph

Vitamin C

Interacts with 207 drugs

Vitamin C (ascorbic acid) is an essential nutrient your body needs but cannot make, so you must get it from food or supplements. It's important for immune function, collagen, and acts as an...

Read the full Vitamin C 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

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

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

Maritime Pine

Interacts with 327 drugs

Maritime pine bark extract (often sold as Pycnogenol) is a plant-based antioxidant most studied for circulation, vein, and skin health. Some research is promising, but many studies are small...

Read the full Maritime Pine monograph →
Sources

Sources & How We Checked

Circulation & Vein Support for Healthy Legs'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 164 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.

Rutin 2 references
  1. Mehta DK (Ex Ed). British National Formulary, Number 37. British Medical Association and Royal Pharmaceutical Society of Great Britain: London, England, March 1999.
  2. Sun C, Wang L, Sun J, Wang Z, Tang Z. Hypoglycemic and hypolipidemic effects of rutin on hyperglycemic rats. J Tradit Chin Med. 2020;40(4):640-645.

See these in context on the Rutin monograph →

Hesperidin 14 references
  1. Fernandez, S. P., Wasowski, C., Paladini, A. C., and Marder, M. Synergistic interaction between hesperidin, a natural flavonoid, and diazepam. Eur.J.Pharmacol. 4-11-2005;512(2-3):189-198. PubMed
  2. Jin, Y. R., Han, X. H., Zhang, Y. H., Lee, J. J., Lim, Y., Chung, J. H., and Yun, Y. P. Antiplatelet activity of hesperetin, a bioflavonoid, is mainly mediated by inhibition of PLC-gamma2 phosphorylation and cyclooxygenase-1 activity. Atherosclerosis 200
  3. Loscalzo, L. M., Wasowski, C., Paladini, A. C., and Marder, M. Opioid receptors are involved in the sedative and antinociceptive effects of hesperidin as well as in its potentiation with benzodiazepines. Eur.J.Pharmacol. 2-12-2008;580(3):306-313. PubMed
  4. Yamamoto, M., Suzuki, A., Jokura, H., Yamamoto, N., and Hase, T. Glucosyl hesperidin prevents endothelial dysfunction and oxidative stress in spontaneously hypertensive rats. Nutrition 2008;24(5):470-476. PubMed
  5. El-Readi, M. Z., Hamdan, D., Farrag, N., El-Shazly, A., and Wink, M. Inhibition of P-glycoprotein activity by limonin and other secondary metabolites from Citrus species in human colon and leukaemia cell lines. Eur.J.Pharmacol. 1-25-2010;626(2-3):139-145 PubMed
  6. Buckshee, K., Takkar, D., and Aggarwal, N. Micronized flavonoid therapy in internal hemorrhoids of pregnancy. Int J Gynaecol Obstet 1997;57(2):145-151. PubMed
  7. Uesawa, Y. and Mohri, K. Hesperidin in orange juice reduces the absorption of celiprolol in rats. Biopharm Drug Dispos. 2008;29(3):185-188. PubMed
  8. Cho, YA, Choi, DH, and Choi, JS. Effect of hesperidin on the oral pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, in rats. J Pharm Pharmacol. 2009;61(6):825-829. PubMed
  9. Piao, YJ and Choi, JS. Enhanced bioavailability of verapamil after oral administration with hesperidin in rats. Arch Pharm Res. 2008;31(4):518-522. PubMed
  10. Andersen KE. Hesperidin methyl chalcone?-?a new cosmetic contact allergen. Contact Dermatitis. 2015;72(6):402-4. PubMed
  11. Morand C, Dubray C, Milenkovic D, et al. Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers. Am J Clin Nutr 2011;93(1):73-80. PubMed
  12. Homayouni F, Haidari F, Hedayati M, Zakerkish M, Ahmadi K. Blood pressure lowering and anti-inflammatory effects of hesperidin in type 2 diabetes; a randomized double-blind controlled clinical trial. Phytother Res. 2018;32(6):1073-1079. PubMed
  13. Mohammadi M, Ramezani-Jolfaie N, Lorzadeh E, Khoshbakht Y, Salehi-Abargouei A. Hesperidin, a major flavonoid in orange juice, might not affect lipid profile and blood pressure: A systematic review and meta-analysis of randomized controlled clinical trials PubMed
  14. Valls RM, Pedret A, Calderón-Pérez L, et al. Effects of hesperidin in orange juice on blood and pulse pressures in mildly hypertensive individuals: a randomized controlled trial (Citrus study). Eur J Nutr. 2021;60(3):1277-1288. PubMed

See these in context on the Hesperidin monograph →

Vitamin C 51 references
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  2. Back DJ, Breckenridge AM, MacIver M, et al. Interaction of ethinyloestradiol with ascorbic acid in man. Br Med J (Clin Res Ed) 1981;282:1516.
  3. Morris JC, Beeley L, Ballantine N. Interaction of ethinyloestradiol with ascorbic acid in man [letter]. Br Med J (Clin Res Ed) 1981;283:503.
  4. Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.
  5. Dwyer JH, Merz NB, Shirocre AM, et al. Progression of early atherosclerosis and intake of vitamin C and vitamin E from supplements and food. The Los Angeles Atherosclerosis Study. 41st Annual Conference on Cardiovascular Disease Epidemiology and Prevent
  6. Levine M, Rumsey SC, Daruwala R, et al. Criteria and recommendations for vitamin C intake. JAMA 1999;281:1415-23. PubMed
  7. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  8. Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
  9. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.
  10. Houston JB, Levy G. Drug biotransformation interactions in man VI: Acetaminophen and ascorbic acid. J Pharm Sci 1976;65:1218-21. PubMed
  11. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93. DOI
  12. Rosenthal G. Interaction of ascorbic acid and warfarin. JAMA 1971;215:1671. DOI
  13. Hume R, Johnstone JM, Weyers E. Interaction of ascorbic acid and warfarin. JAMA 1972;219:1479. DOI
  14. Smith EC, Skalski RJ, Johnson GC, Rossi GV. Interaction of ascorbic acid and warfarin. JAMA 1972;221:1166. DOI
  15. Traxer O, Huet B, Poindexter J, et al. Effect of ascorbic acid consumption on urinary stone risk factors. J Urol 2003;170:397-401.. PubMed
  16. Domingo JL, Gomez M, Llobet JM, Richart C. Effect of ascorbic acid on gastrointestinal aluminum absorption (letter). Lancet 1991;338:1467.
  17. Domingo JL, Gomez M, Llobet JM, Corbella J. Influence of some dietary constituents on aluminum absorption and retention in rats. Kidney Int 1991;39:598-601. PubMed
  18. Partridge NA, Regnier FE, White JL, Hem SL. Influence of dietary constituents on intestinal absorption of aluminum. Kidney Int 1989;35:1413-7. PubMed
  19. Mc Leod DC, Nahata MC. Inefficacy of ascorbic acid as a urinary acidifier (letter). N Engl J Med 1977;296:1413. DOI
  20. Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharmacol 1980;20:326-31. PubMed
  21. Dysken MW, Cumming RJ, Channon RA, Davis JM. Drug interaction between ascorbic acid and fluphenazine. JAMA 1979;241:2008. DOI
  22. Vihtamaki T, Parantainen J, Koivisto AM, et al. Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Maturitas 2002;42:129-35. PubMed
  23. Slain D, Amsden JR, Khakoo RA, et al. Effect of high-dose vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers. Pharmacotherapy 2005;25:165-70. PubMed
  24. Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6. PubMed
  25. Feetam CL, Leach RH, Meynell MJ. Lack of a clinically important interaction between warfarin and ascorbic acid. Toxicol Appl Pharmacol 1975;31:544-7. PubMed
  26. Weintraub M, Griner PF. Warfarin and ascorbic acid: lack of evidence for a drug interaction. Toxicol Appl Pharmacol 1974;28:53-6. PubMed
  27. Lee DH, Folsom AR, Harnack L, et al. Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes? Am J Clin Nutr 2004;80:1194-200. PubMed
  28. Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol 2004;15:3225-32. PubMed
  29. 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
  30. Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S. PubMed
  31. Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S. PubMed
  32. Fairweather-Tait S, Hickson K, McGaw B, et al. Orange juice enhances aluminium absorption from antacid preparation. Eur J Clin Nutr. 1994;48(1):71-3.
  33. Gruenwald, J., Graubaum, H. J., Busch, R., and Bentley, C. Safety and tolerance of ester-C compared with regular ascorbic acid. Adv.Ther. 2006;23(1):171-178.
  34. Rahimi, R., Nikfar, S., Rezaie, A., and Abdollahi, M. A meta-analysis on the efficacy and safety of combined vitamin C and E supplementation in preeclamptic women. Hypertens.Pregnancy. 2009;28(4):417-434. PubMed
  35. Einerson, B., Nathorn, C., Kitiyakara, C., Sirada, M., and Thamlikitkul, V. The efficacy of ascorbic acid in suboptimal responsive anemic hemodialysis patients receiving erythropoietin: a meta-analysis. J Med.Assoc.Thai. 2011;94 Suppl 1:S134-S146.
  36. Li, G., Li, L., Yu, C., and Chen, L. Effect of vitamins C and E supplementation on Helicobacter pylori eradication: a meta-analysis. Br.J Nutr 2011;106(11):1632-1637.
  37. Chen X, Shen L, Gu X, et al. High-dose supplementation with vitamin C--induced pediatric urolithiasis: the first case report in a child and literature review. Urology. 2014;84(4):922-4. PubMed
  38. Sattar A, Willman JE, Kolluri R. Possible warfarin resistance due to interaction with ascorbic acid: case report and literature review. Am J Health Syst Pharm. 2013;70(9):782-6. PubMed
  39. Yaich S, Chaabouni Y, Charfeddine K, et al. Secondary oxalosis due to excess vitamin C intake: a cause of graft loss in a renal transplant recipient. Saudi J Kidney Dis Transpl. 2014;25(1):113-6. PubMed
  40. 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
  41. Rumbold A, Ota E, Nagata C, Shahrook S, Crowther CA. Vitamin C supplementation in pregnancy. Cochrane Database Syst Rev. 2015;(9):CD004072. PubMed
  42. Seo MS, Kim JK, Shim JY. High-dose vitamin C promotes regression of multiple pulmonary metastases originating from hepatocellular carcinoma. Yonsei Med J. 2015;56(5):1449-52. PubMed
  43. Skelin M, Lucijanic T, Amidzic Klaric D, et al. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017 Feb;39(2):378-403. PubMed
  44. Jiang K, Tang K, Liu H, Xu H, Ye Z, Chen Z. Ascorbic acid supplements and kidney stones incidence among men and women: a systematic review and meta-analysis. Urol J. 2019;16(2):115-120.
  45. Thomas S, Patel D, Bittel B, et al. Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial. JAMA Netw Open. 2 PubMed
  46. Giffen MA, McLemore JL. Hyperoxalosis Secondary to Intravenous Vitamin C Administration as a Non-Allopathic Treatment for Cancer. Acad Forensic Pathol 2019;9(1-2):118-126. PubMed
  47. Maike A, Sturgill D, Gallan A. Oxalate Nephropathy in a Renal Transplant Recipient After Receiving High Dose Ascorbic Acid. Am J Med Sci 2021. PubMed
  48. Shen ZY, Chen YR, Wang MC, Chang SS. High-dose vitamin C-induced acute oxalate nephropathy in a renal transplant recipient: a case report and literature review. Asian J Surg 2022. PubMed
  49. Yanase F, Spano S, Maeda A, et al. Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial. Crit Care 2023;27(1):371. PubMed
  50. Sharma Y, Sumanadasa S, Shahi R, et al. Efficacy and safety of vitamin C supplementation in the treatment of community-acquired pneumonia: a systematic review and meta-analysis with trial sequential analysis. Sci Rep 2024;14(1):11846. PubMed
  51. Pejcic AV, Petrovic NZ, Djordjic MD, Milosavljevic MN. Vitamin C Levels in Pregnant Women and the Efficacy of Vitamin C Supplements in Preventing Premature Rupture of Membranes: A Systematic Review and Meta-Analysis. Balkan Med J 2024;41(4):248-260. PubMed

See these in context on the Vitamin C 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
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Diosmin 20 references
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Butcher's Broom 8 references
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Horse Chestnut 21 references
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Maritime Pine 14 references
  1. Rice-Evans CA, Packer L, eds. Flavonoids in Health and Disease. Manhattan, NY: Marcel Dekker, Inc., 1998.
  2. Liu FJ, Zhang YX, Lau BH. Pycnogenol enhances immune and haemopoietic functions in senescence-accelerated mice. Cell Mol Life Sci 1998;54:1168-72. PubMed
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  12. Enseleit, F., Sudano, I., Periat, D., Winnik, S., Wolfrum, M., Flammer, A. J., Frohlich, G. M., Kaiser, P., Hirt, A., Haile, S. R., Krasniqi, N., Matter, C. M., Uhlenhut, K., Hogger, P., Neidhart, M., Luscher, T. F., Ruschitzka, F., and Noll, G. Effects
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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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