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

Nattosyn Ingredients & Drug Interactions

by Douglas Laboratories

Nattosyn 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 Nattosyn 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

Nattosyn is a dietary supplement by Douglas Laboratories with 3 active ingredients. Its ingredients are commonly taken for hemorrhoids, varicose veins and poor circulation, leg swelling (venous insufficiency).Based on those ingredients, 1,157 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are Standardized Pomegranate extract, Hesperidin Methyl Chalcone, Nattokinase. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Nattosyn by Douglas Laboratories

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

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HelloPharmacist Scorecard of Nattosyn by Douglas Laboratories

Our pharmacy team’s full take, with four database checks built into the cards below — a summary of what is known, not a grade of the product itself.

From our pharmacy team — supplement deep dive

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Aug 27, 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 3 of its 3 active ingredients.
  • No proprietary blends here — you can verify the dose of every single component.

Nattosyn contains three active ingredients. Hesperidin methyl chalcone is a flavonoid (a plant compound) derived from citrus.

Nattokinase is an enzyme extracted from natto, a fermented soybean food, believed to have fibrin-breaking (thrombolytic) properties. Standardized pomegranate extract comes from the pomegranate fruit and is standardized to a measured level of active compounds.

The capsules also contain inactive ingredients: microcrystalline cellulose, hydroxypropyl methylcellulose, silica, and vegetable stearate—these are fillers, thickeners, and flow agents typical of supplement capsules.

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

This product doesn't appear to be marketed for a specific use, so we graded its ingredients' overall clinical evidence instead.

Moderate

Some clinical evidence supports its ingredients for:

Why this rating?
  • We looked at the product name, claims, and label statements and couldn't find a stated purpose to grade.
  • Since the label doesn't commit to one use, we graded the ingredients' overall clinical evidence instead.
  • On file: Hypertension — rated "Possibly Effective" (Pomegranate) (Natural Medicines).

The evidence for Nattosyn's ingredients is limited. Hesperidin methyl chalcone is rated possibly ineffective for obesity and high cholesterol (hypercholesterolemia), and there is insufficient reliable evidence for nonalcoholic fatty liver disease.

Nattokinase has insufficient reliable evidence for angina, atherosclerosis, cancer, cardiovascular disease, and chronic fatigue syndrome—meaning we don't have enough quality studies to say whether it works for any of these. Pomegranate extract is rated possibly effective for high blood pressure (hypertension) but possibly ineffective for high cholesterol and diabetes, with insufficient evidence for fatty liver disease.

Overall, the data supporting this product's use for its intended purposes is sparse.

The evidence, ingredient by ingredient Hesperidin Nattokinase Pomegranate

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 3 of the 3 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 3 of 3.
  • General safety write-ups exist for 3 of 3.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Hesperidin methyl chalcone is generally well tolerated in food amounts and short-term use, though long-term safety data is limited. One case of allergic skin reaction was reported.

The safety facts advise against it in pregnancy and while breastfeeding due to insufficient data. Nattokinase is generally tolerated short-term but carries a blood-thinning effect, so caution is warranted if you have any bleeding risk.

Rare cases of bleeding, including the serious intracranial hemorrhage mentioned above, have been reported. Hypersensitivity reactions (including anaphylaxis) have occurred in people sensitive to natto or its components.

The safety data advises against nattokinase in pregnancy and recommends avoiding it while breastfeeding. Pomegranate extract is generally well tolerated as a food, though concentrated supplements warrant caution.

Mild gastrointestinal side effects—diarrhea, flatulence, nausea, abdominal pain—occurred in a small to modest percentage of trial participants at higher doses. The facts rate pomegranate possibly safe in pregnancy and lactation.

Side effects, ingredient by ingredient Hesperidin Nattokinase Pomegranate

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?
  • 3 of the 3 matched ingredients can interact with medications — Pomegranate, Hesperidin, Nattokinase.
  • The most serious interaction on file is rated Moderate.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs.
  • For scale: 1,158 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 Nattosyn, double-check the following medication types with your doctor or pharmacist, starting with the most serious: blood thinners and antiplatelet drugs (including aspirin)—nattokinase carries a Moderate risk of increased bleeding and has a case report of intracranial hemorrhage; blood pressure medications (antihypertensives and ACE inhibitors)—all three ingredients may lower your pressure further; sedatives and CNS depressants (from hesperidin); heart rhythm drugs like verapamil and diltiazem (from hesperidin); warfarin specifically (from pomegranate); cholesterol drugs, especially rosuvastatin (from pomegranate); and any medications metabolized by your liver's cytochrome P450 enzymes, a large group spanning many drug classes (from pomegranate and hesperidin).

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with some supporting evidence behind its ingredients' uses. Moderate medication interactions have been identified, and safety information is well characterized.

Nattosyn combines three ingredients with limited evidence of effectiveness and several documented or theoretical interactions with common medications, especially blood thinners and blood pressure drugs. If you take any prescription or over-the-counter medications, or have a bleeding disorder or cardiovascular condition, check with your doctor or pharmacist before starting this product.

The decision to take it belongs with your own healthcare provider, who can weigh the evidence and your individual health picture.

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

Assessment coverage: 3 of 3 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Oct 23, 2020.

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 Nattosyn, straight from the product label.

Brand Douglas Laboratories
Barcode (UPC) 310539022405
Net contents 60 Vegetarian Capsule(s)
Market status On market
Date entered into DSLD Oct 23, 2020
DSLD ID 237131
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Women (not pregnant or lactating), Gluten 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 Nattosyn by Douglas Laboratories, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
1 Vegetarian Capsule(s)
Maximum serving Sizes:
2 Vegetarian Capsule(s)
Servings per container
60
UPC/BARCODE
310539022405
IngredientAmount% DV
Hesperidin Methyl Chalcone100 mg--
Nattokinase50 mg--
Standardized Pomegranate extract50 mg--

Other ingredients: Microcrystalline Cellulose, Hydroxypropyl Methylcellulose, Silica, Vegetable Stearate

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 Usage: As a dietary supplement, adults take 1-2 capsule, 1-2 times daily or as directed by your health professional.

Precautions

Warning: Not to be taken by pregnant or lactating women. If you have any health condition or are taking any medication, consult your health professional before use.

Keep out of the reach of children.

Use only if safety seal is intact.

Contains: Soy

Brand IP Statement(s)

NSK-SD is a registered trademark of Japan BioScience Laboratories.

Storage

Store in a cool, dry place.

Formulation

Gluten-free, Non-GMO

Circulatory health

FDA Disclaimer Statement

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

General Statements

Scan to learn about our manufacturing excellence Contents may not fill package in order to accommodate required labeling. Please rely on stated quantity.

FDA Statement of Identity

Dietary Supplement

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

See for yourself

Nattosyn by Douglas Laboratories label

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

Nattosyn 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 Nattosyn by Douglas Laboratories

These are the 3 active ingredients this product is made of. Select any to open its full monograph.

Serving size1 Vegetarian Capsule(s) Dosage formCapsule Servings per container60 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.

Hesperidin Methyl Chalcone

Interacts with
702 drugs
100 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 Methyl Chalcone monograph & interactions

Nattokinase

Interacts with
289 drugs
50 mg per serving Form: Soy

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 be...

Nattokinase monograph & interactions

Standardized Pomegranate extract

Interacts with
922 drugs
50 mg per serving Form: Ellagic Acid

Pomegranate is a nutrient-rich fruit that is high in antioxidants and is widely enjoyed as food and juice. Early research suggests it may support hear...

Standardized Pomegranate extract monograph & interactions

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

Interaction report

Nattosyn by Douglas Laboratories Drug Interactions

Want to check YOUR meds against Nattosyn?

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
1,157Drugs
795 Moderate 362 Minor

Ingredients driving the most interactions

Standardized Pomegranate extract 922
Hesperidin Methyl Chalcone 702
Nattokinase 289

Individual Drug Interactions

The ingredients in Nattosyn interact with 1,157 drugs. Click any drug to see the details.

3 of the 3 ingredients in Nattosyn interact with drugs. Each result below shows which ingredient is responsible. Standardized Pomegranate extract Hesperidin Methyl Chalcone Nattokinase

Each ingredient & the kinds of drugs it affects

For each ingredient in Nattosyn 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.

Standardized Pomegranate extract9 drug types · 922 drugs

Ace Inhibitors (Aceis)

Theoretically, taking pomegranate with ACEIs might increase the risk of adverse effects.
Pomegranate juice is thought to have ACE inhibitor-like effects.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, taking pomegranate with antihypertensive drugs might increase the risk of hypotension.
Consuming pomegranate juice can modestly lower blood pressure.

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

Theoretically, pomegranate might increase levels of drugs metabolized by CYP2D6.
In vitro, pomegranate juice inhibits CYP2D6. However, the clinical significance of this potential interaction in humans is not known.

Likelihood Possible Evidence D
Rosuvastatin (Crestor)

Theoretically, taking pomegranate with rosuvastatin might increase the risk of adverse effects.
In one case, a patient taking rosuvastatin 5 mg every other day in combination with ezetimibe 10 mg daily developed rhabdomyolysis after drinking pomegranate juice 200 mL twice weekly for 3 weeks. This patient had a history of elevated creatine kinase levels while not receiving any statin treatment. This suggests a possible underlying myopathy and predisposition to rhabdomyolysis.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, pomegranate might increase warfarin levels and increase the risk of bleeding. Also, discontinuing regular consumption of pomegranate juice might decrease warfarin levels.
In one case report, a patient had a stable, therapeutic bleeding time, as measured by international normalized ratio (INR), while taking warfarin in combination with pomegranate juice 2-3 times per week. The patient became subtherapeutic within about 10 days after discontinuing pomegranate juice, which required a warfarin dose increase. In another case report, a patient with a stable INR for over one year presented with an INR of 14. The patient noted no changes to medications or diet but did report consuming around 3 liters of pomegranate juice over the previous week. The patient's INR stabilized upon moderation of pomegranate juice consumption. The mechanism of this potential interaction is unclear.

Likelihood Possible Evidence D
Carbamazepine (Tegretol)

Theoretically, taking pomegranate with carbamazepine might increase the risk of adverse effects, although research suggests this interaction is unlikely to be clinically significant.
Animal research shows that pomegranate juice may inhibit cytochrome P450 3A4 (CYP3A4) metabolism of carbamazepine and increase levels of carbamazepine by 1.5 times without prolonging the elimination half-life. This suggests that pomegranate juice inhibits intestinal CYP3A4, but might not inhibit hepatic CYP3A4. However, some human research suggests that pomegranate does not significantly inhibit CYP3A4 drug metabolism in humans.

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

Theoretically, pomegranate might increase levels of drugs metabolized by CYP2C9.
Some animal and in vitro research shows that pomegranate juice inhibits intestinal, but not hepatic, CYP2C9 isoenzyme activity. However, clinical research shows that neither pomegranate juice nor pomegranate extract have a significant effect on CYP2C9 activity in humans.

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

Theoretically, pomegranate might increase levels of drugs metabolized by CYP3A4, but most research suggests this interaction is unlikely to be clinically significant.
Pomegranate contains several polyphenols that have individually been shown to inhibit CYP3A4. However, there is contradictory evidence about the effect of whole pomegranate juice on CYP3A4 activity. In vitro, pomegranate juice significantly inhibits the CYP3A4 enzyme, with comparable inhibition to grapefruit juice. In an animal model, pomegranate juice inhibits CYP3A4 metabolism of carbamazepine and increases levels of carbamazepine by 1.5 times; however, in human volunteers, drinking a single glass of pomegranate juice 240 mL or taking 200 mL daily for 2 weeks does not significantly affect levels of the CYP3A4 substrate midazolam after oral or intravenous administration. Another study in healthy volunteers shows that consuming pomegranate juice 300 mL three times daily for three days also does not significantly affect levels of simvastatin, a CYP3A4 substrate This suggests that pomegranate is unlikely to significantly affect levels of CYP3A4 substrates in humans.

Likelihood Unlikely Evidence B
Tolbutamide (Orinase)

Theoretically, pomegranate might increase levels of tolbutamide, although research suggests this interaction is unlikely to be clinically significant.
Animal research shows that pomegranate juice inhibits the cytochrome P450 2C9 (CYP2C9) metabolism of tolbutamide. Pomegranate juice increased tolbutamide levels by 1.2 times without prolonging the elimination half-life. This suggests that pomegranate juice inhibits intestinal CYP2C9, but might not inhibit hepatic CYP2C9. Despite this evidence, clinical research shows that neither pomegranate juice nor pomegranate extract have a significant effect on CYP2C9 activity in humans. This interaction does not appear to be clinically significant in humans.

Likelihood Unlikely Evidence D
Standardized Pomegranate extract full monograph & interactions

Hesperidin Methyl Chalcone7 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 Methyl Chalcone 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
The maker

Brand information

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

Douglas Laboratories

See all Douglas Laboratories products
Name
Douglas Laboratories
Street Address
600 Boyce Road
City
Pittsburgh
State
PA
ZipCode
15205
Phone Number
1.800.245.4440
Web Address
www.douglaslabs.com
Pharmacist Counseling Corner

Nattosyn by Douglas Laboratories: Common Questions

Does Nattosyn by Douglas Laboratories interact with any medications?
Yes. Based on its ingredients, Nattosyn has a known interaction with 1,157 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Nattosyn contains 3 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 this if I'm pregnant or breastfeeding?
The safety data advises against hesperidin methyl chalcone and nattokinase during pregnancy and lactation because there isn't enough information. Pomegranate extract is rated possibly safe in both periods, but there's not robust data. Talk with your doctor or pharmacist about whether this product is appropriate for you if you're pregnant or nursing.
What is nattokinase, and why is it in this product?
Nattokinase is an enzyme from natto, a fermented soybean food. It's included because some research suggests it may have effects on blood clotting and cardiovascular function, though the evidence is limited. The main concern is that it can thin your blood, which matters if you're already on blood thinners or have a bleeding risk.
Does this product actually help with high cholesterol or weight loss?
For cholesterol, hesperidin methyl chalcone is rated possibly ineffective, and pomegranate extract is also possibly ineffective—so the data doesn't support either one working well for that. For obesity, hesperidin is rated possibly ineffective. These aren't strong endorsements; the evidence is weak or absent.
What are the most common side effects?
Pomegranate extract can cause mild stomach upset—diarrhea, flatulence, nausea, abdominal pain, or constipation—in a small percentage of people at higher doses. Nattokinase may rarely cause serious bleeding. Hesperidin is generally well tolerated, though one allergic skin reaction has been reported.
Is this safe if I have no health conditions and take no medications?
Nattosyn hasn't been studied long-term, so we don't have a complete safety picture even in healthy people. Nattokinase's blood-thinning effect and the potential for allergic reaction to natto are still considerations. If you're thinking of starting it, a brief chat with your pharmacist or doctor is a good idea.
What happens if I stop taking pomegranate and I'm on warfarin?
One case report noted that discontinuing regular pomegranate juice affected warfarin levels, so stopping it could change how your blood thinner works. If you're on warfarin and consuming pomegranate regularly, any change to that needs to be discussed with your doctor, who may adjust your warfarin dose.

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.

Nattosyn label
Go deeper

The Full Monographs Behind Nattosyn’s Ingredients

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

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

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

Pomegranate

Interacts with 922 drugs

Pomegranate is a nutrient-rich fruit that is high in antioxidants and is widely enjoyed as food and juice. Early research suggests it may support heart health and blood pressure, but the evi...

Read the full Pomegranate monograph →
Sources

Sources & How We Checked

Nattosyn'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 50 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.

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 →

Nattokinase 9 references
  1. Suzuki Y, Kondo K, Matsumoto Y, et al. Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery. Life Sci 2003;73:1289-98.. PubMed
  2. Sumi H, Hamada H, Nakanishi K, Hiratani H. Enchancement of fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol 1990;84:139-43.
  3. Chang, Y. Y., Liu, J. S., Lai, S. L., Wu, H. S., and Lan, M. Y. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med 2008;47(5):467-469. PubMed
  4. Kim, J. Y., Gum, S. N., Paik, J. K., Lim, H. H., Kim, K. C., Ogasawara, K., Inoue, K., Park, S., Jang, Y., and Lee, J. H. Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertens.Res 2008;31(8):1583-1588. PubMed
  5. <p>Maruyama M, Sumi H (eds): Effect of natto diet on blood pressure, in Basic and Clinical Aspects of Japanese Traditional Food Natto II. Japan Technology Transfer Association (JTTAS), 1998, pp 1–3.</p>
  6. Kurosawa Y, Nirengi S, Homma T, et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Sci Rep 2015;5:11601. PubMed
  7. Ramachandran L, Aqeel A, Jafri A, Sidhu Y, Mohamed Djirdeh T. Nattokinase-associated hemoperitoneum in an elderly woman. Cureus 2021;13(12):e20074. PubMed
  8. Awatani-Yoshidome K, Hashimoto T, Satoh T. Anaphylaxis from nattokinase in a patient with fermented soybean (natto) allergy. Allergol Int 2022;71(1):153-4. PubMed
  9. Suzuki K, Nakamura M, Sato N, Futamura K, Matsunaga K, Yagami A. Nattokinase, a subtilisin family serine protease, is a novel allergen contained in the traditional Japanese fermented food natto. Allergol Int 2022.

See these in context on the Nattokinase monograph →

Pomegranate 27 references
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  2. Gaig P, Bartolome B, Lleonart R, et al. Allergy to pomegranate (Punica granatum). Allergy 1999;54:287-8.
  3. Aviram M, Dornfeld L. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Atherosclerosis 2001;158:195-8. PubMed
  4. Valsecchi R, Reseghetti A, Leghissa P, et al. Immediate contact hypersensitivity to pomegranate. Contact Dermatitis 1998;38:44-5. PubMed
  5. Esmaillzadeh A, Tahbaz F, Gaieni I, et al. Concentrated pomegranate juice improves lipid profiles in diabetic patients with hyperlipidemia. J Med Food 2004;7:305-8. PubMed
  6. Aviram M, Rosenblat M, Gaitini D, et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr 2004;23:423-33. DOI
  7. Hidaka M, Okumura M, Fujita K, et al. Effects of pomegranate juice on human cytochrome p450 3A (CYP3A) and carbamazepine pharmacokinetics in rats. Drug Metab Dispos 2005;33:644-8. PubMed
  8. Loren DJ, Seeram NP, Schulman RN, Holtzman DM. Maternal dietary supplementation with pomegranate juice is neuroprotective in an animal model of neonatal hypoxic-ischemic brain injury. Pediatr Res 2005;57:858-64. PubMed
  9. Kim ND, Mehta R, Yu W, et al. Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer. Breast Cancer Res Treat 2002;71:203-17. PubMed
  10. Sorokin AV, Duncan B, Panetta R, Thompson PD. Rhabdomyolysis associated with pomegranate juice consumption. Am J Cardiol 2006;98:705-6. PubMed
  11. Farkas D, Oleson LE, Zhao Y, et al. Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity: comparison with grapefruit juice. J Clin Pharmacol 2007;47:286-94. PubMed
  12. Yeo C, Shon J, Liu K, et al. The effects of pomegranate juice on the pharmacokinetics of simvastatin in healthy Korean subjects (PI-63). Clin Pharmacol Ther 2006;79:23.
  13. Farkas D, Greenblatt DJ. Influence of fruit juices on drug disposition: discrepancies between in vitro and clinical studies. Expert Opin Drug Metab Toxicol 2008;4:381-93.
  14. Nagata M, Hidaka M, Sekiya H, et al. Effects of pomegranate juice on human cytochrome P450 2C9 and tolbutamide pharmacokinetics in rats. Drug Metab Dispos 2007;35:302-5. PubMed
  15. Komperda KE. Potential interaction between pomegranate juice and warfarin. Pharmacotherapy 2009;29:1002-6. PubMed
  16. Gangemi S, Mistrello G, Roncarolo D, et al. Pomegranate-dependent exercise-induced anaphylaxis. J Investig Allergol Clin Immunol 2008;18:491-2.
  17. Misaka S, Nakamura R, Uchida S, et al. Effect of 2 weeks' consumption of pomegranate juice on the pharmacokinetics of a single dose of midazolam: an open-label, randomized, single-center, 2-period crossover study in healthy Japanese volunteers. Clin Ther PubMed
  18. Jarvis S, Li C, Bogle RG. Possible interaction between pomegranate juice and warfarin. Emerg Med J 2010;27:74-5. PubMed
  19. Esmaillzadeh, A., Tahbaz, F., Gaieni, I., Alavi-Majd, H., and Azadbakht, L. Cholesterol-lowering effect of concentrated pomegranate juice consumption in type II diabetic patients with hyperlipidemia. Int J Vitam.Nutr Res 2006;76(3):147-151. PubMed
  20. Forest, C. P., Padma-Nathan, H., and Liker, H. R. Efficacy and safety of pomegranate juice on improvement of erectile dysfunction in male patients with mild to moderate erectile dysfunction: a randomized, placebo-controlled, double-blind, crossover study PubMed
  21. Wright, H. and Pipkin F. B. Pomegranates (Punica granatum), kiwifruit (Actinidia deliciosa) and blood pressure: a pilot study. Proceedings of the Nutrition Society 2008;67(8):1.
  22. Sohrab G, Sotoodeh G, Siasi F, et al. Effect of pomegranate juice consumption on blood pressure in type 2 diabetic patients. Iranian Journal of Endocrinology and Metabolism 2008;9:399-405, 470.
  23. Enrique E, Utz M, De Mateo JA, et al. Allergy to lipid transfer proteins: cross-reactivity among pomegranate, hazelnut, and peanut. Ann Allergy Asthma Immunol 2006;96(1):122-3. PubMed
  24. Hanley MJ, Masse G, Harmatz JS, et al. Pomegranate juice and pomegranate extract do not impair oral clearance of flurbiprofen in human volunteers: divergence from in vitro results. Clin Pharmacol Ther 2012;92(5):651-7. PubMed
  25. Paller CJ, Ye X, Wozniak PJ, et al. A randomized phase II study of pomegranate extract for men with rising PSA following initial therapy for localized prostate cancer. Prostate Cancer Prostatic Dis 2013;16(1):50-5. PubMed
  26. Park SJ, Yeo CW, Shim EJ, et al. Pomegranate juice does not affect the disposition of simvastatin in healthy subjects. Eur J Drug Metab Pharmacokinet 2016;41(4):339-44. PubMed
  27. Ross MM, Cherkerzian S, Mikulis ND, et al. A randomized controlled trial investigating the impact of maternal dietary supplementation with pomegranate juice on brain injury in infants with IUGR. Sci Rep. 2021;11(1):3569. PubMed

See these in context on the Pomegranate monograph →

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DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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