Drug & supplement interaction

Apple Polyphenols + Tolbutamide

Tolbutamide brand name: Orinase.

No Known Interaction
The bottom line No known interaction

We found no known interaction between Apple Polyphenols and Tolbutamide in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first.

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Interaction report

Apple Polyphenols and Tolbutamide

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Tolbutamide and Apple Polyphenols in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Apple Polyphenols safety at a glance

Apple Polyphenols overall Use caution Likely safe in food amounts; concentrated supplements are less studied for long-term use.
Pregnancy Use caution Apples as food are fine, but concentrated extracts have not been studied in pregnancy, so avoid supplements unless your doctor approves.
Breastfeeding Use caution There is not enough information on concentrated extracts during breastfeeding, so caution is advised.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Tolbutamide and Apple Polyphenols? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Tolbutamide

Interactions in our licensed database are recorded against drug classes, not just single drug names. Tolbutamide is filed under 5 classifications — including antidiabetes drugs, cytochrome p450 2c9 (cyp2c9) substrates, photosensitizing drugs. Apple Polyphenols has documented interactions with 1 drug class — the most serious being insulin (moderate) — and none of Tolbutamide’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Apple Polyphenols Does Interact With Other Medications

Apple Polyphenols has 13 moderate known drug interactions in our database — Tolbutamide isn’t one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Apple Polyphenols

Covers the 2,830 medications we’ve checked against Apple Polyphenols. Pick one to open its full report.

What to actually watch for

What Apple Polyphenols Itself Has Been Linked To

This is not an interaction — nothing below involves Tolbutamide. It is the side-effect record for Apple Polyphenols on its own, from the licensed Natural Medicines monograph. If something new turns up after you add Apple Polyphenols, this list is the first place to look.

  • Diarrhea Additional detail

    “Orally, taking 600 mg apple polyphenols was reported to cause diarrhea and loose stools in one clinical study.”

    Apple Polyphenols · Natural Medicines adverse-effect record, reported in diarrhea.

    1 source cited
    1. 94863. Nagasako-Akazome Y, Kanda T, Ohtake Y, Shimasaki H, Kobayashi T. Apple polyphenols influence cholesterol metabolism in healthy subjects with relatively high body mass index. J Oleo Sci. 2007;56(8):417-28. PubMed
  • Headache Additional detail

    “Orally, apple polyphenols seem to be well tolerated. Some clinical studies have reported no adverse effects with apple polyphenols, while mild gastrointestinal effects, nasopharyngitis, and headache have been reported in other studies.”

    Apple Polyphenols · Natural Medicines adverse-effect record, reported in cluster headache.

    4 sources cited
    1. 94855. Akazome Y, Kametani N, Kanda T, et al. Evaluation of safety of excessive intake and efficacy of long-term intake of beverages containing apple polyphenols. J Oleo Sci. 2010;59(6):321-38. PubMed
    2. 94863. Nagasako-Akazome Y, Kanda T, Ohtake Y, Shimasaki H, Kobayashi T. Apple polyphenols influence cholesterol metabolism in healthy subjects with relatively high body mass index. J Oleo Sci. 2007;56(8):417-28. PubMed
    3. 94869. Tenore GC, Caruso D, Buonomo G, et al. A Healthy Balance of Plasma Cholesterol by a Novel Annurca Apple-Based Nutraceutical Formulation: Results of a Randomized Trial. J Med Food. 2017;20(3):288-300. PubMed
    4. 102020. Saarenhovi M, Salo P, Scheinin M, et al. The effect of an apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers on brachial artery flow-mediated vasodilatory function in volunteers with elevated blood pressure. Nutr. J 2017;16(1):73. PubMed

    “Orally, taking apple polyphenols may cause headache in some patients. In one clinical trial, around 26% of patients taking apple polyphenols 330 mg daily for 4 weeks reported headaches, although this adverse effect was also reported in nearly 24% of patients taking placebo.”

    Apple Polyphenols · Natural Medicines adverse-effect record, reported in cluster headache.

    1 source cited
    1. 102020. Saarenhovi M, Salo P, Scheinin M, et al. The effect of an apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers on brachial artery flow-mediated vasodilatory function in volunteers with elevated blood pressure. Nutr. J 2017;16(1):73. PubMed

Everything above comes from the Natural Medicines adverse-effect record for Apple Polyphenols — expand a row for the licensed statement it rests on. We haven’t matched Tolbutamide to its FDA label in our system yet, so we can’t compare its own side-effect list here — the leaflet that comes with your prescription is the authoritative list for Tolbutamide.

Everything else you take

See Every Supplement That Interacts With Tolbutamide

This page covers Apple Polyphenols only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tolbutamide page lists 305 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Siberian Cocklebur (major), Acai (moderate), Adrafinil (moderate) and African Wild Potato (moderate).

By severity: 2 major · 255 moderate · 48 minor.

From our pharmacist’s overview on the Tolbutamide page

“People take tolbutamide (Orinase) to lower blood sugar in type 2 diabetes, and diabetes is exactly the condition supplement shelves target, which is why this list runs to 305 ingredients and deserves real caution. Of those, 239 also push glucose around, most often downward, so combining them can drive sugar lower than intended.”

Reviewed by 2 · Jul 18, 2026

Open the Tolbutamide interaction page

How much people look this up

Where Apple Polyphenols and Tolbutamide Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Apple Polyphenols
Steady interest

#1,023 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Tolbutamide
Steady interest

#2,107 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Apple Polyphenols reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 20, 2026. The Apple Polyphenols and Tolbutamide records this page draws on were last updated July 10, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About Apple Polyphenols

What is Apple Polyphenols?

Apple Polyphenols
  • High cholesterol
  • High blood pressure
  • Weight management
  • Antioxidant support
  • Blood sugar support
  • Skin health (topical)

Apple polyphenols are antioxidant plant compounds taken from apples and marketed for heart, weight, and blood sugar health. Early research is interesting, but there is not enough reliable human evidence to confirm these benefits. They appear generally safe in food-like amounts, but talk with your pharmacist or doctor before using concentrated supplements.

Malus domestica · Rosaceae · Fruit, peel, and pomace (sometimes unripe apples) · Capsules, tablets, powders, and standardized extracts

An interaction check asks whether these two react with each other — it does not ask whether Apple Polyphenols is a good idea for someone in your situation. Here is what our Apple Polyphenols record says about it on its own.

Apple Polyphenols: dosing

There is no standardized, well-established dose for apple polyphenols. Products vary widely in how much polyphenol they contain.The best approach is to follow the directions on the product label and not exceed the suggested amount.

From our Apple Polyphenols monograph — the full record covers uses, side effects and every documented interaction.

Read the full Apple Polyphenols monograph & all interactions
Medication

About Tolbutamide

What Is Tolbutamide Used For?

Brand name: Orinase

  • Tolbutamide is used along with diet and exercise, and sometimes with other medications, to treat type 2 diabetes (condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood). Tolbutamide is in a class of medications called sulfonylureas. Tolbutamide lowers blood sugar by causing the pancreas to produce insulin (a natural substance that is needed to break down sugar in the body) and helping the body use insulin efficiently. This medication will only help lower blood sugar in people whose bodies produce insulin naturally. Tolbutamide is not used to treat type 1 diabetes (condition in which the body does not produce insulin and, therefore, cannot control the amount of sugar in the blood) or diabetic ketoacidosis (a serious condition that may occur if high blood sugar is not treated).

  • Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, including heart disease, stroke, kidney problems, nerve damage, and eye problems. Taking medication(s), making lifestyle changes (e.g., diet, exercise, quitting smoking), and regularly checking your blood sugar may help to manage your diabetes and improve your health. This therapy may also decrease your chances of having a heart attack, stroke, or other diabetes-related complications such as kidney failure, nerve damage (numb, cold legs or feet; decreased sexual ability in men and women), eye problems, including changes or loss of vision, or gum disease. Your doctor and other healthcare providers will talk to you about the best way to manage your diabetes.

See full Tolbutamide drug information
Keep checking

Other Drugs & Apple Polyphenols

Browse every other medication we’ve checked against Apple Polyphenols — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
13Moderate
0Minor
2,816No known interaction
Moderate

13 interactions

No interaction 2,816 drugs checked — show the list
Evidence & sources

Apple Polyphenols References

The 10 references that drive our Apple Polyphenols monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. Akazome Y, Kametani N, Kanda T, et al. Evaluation of safety of excessive intake and efficacy of long-term intake of beverages containing apple polyphenols. J Oleo Sci. 2010;59(6):321-38. PubMed
  2. Auclair S, Chironi G, Milenkovic D, et al. The regular consumption of a polyphenol-rich apple does not influence endothelial function: a randomised double-blind trial in hypercholesterolemic adults. Eur J Clin Nutr. 2010;64(10):1158-65. PubMed
  3. Deley G, Guillemet D, Allaert FA, Babault N. An Acute Dose of Specific Grape and Apple Polyphenols Improves Endurance Performance: A Randomized, Crossover, Double-Blind versus Placebo Controlled Study. Nutrients. 2017;9(8). pii: E917. PubMed
  4. Kamimura A, Takahashi T, Watanabe Y. Investigation of topical application of procyanidin B-2 from apple to identify its potential use as a hair growing agent. Phytomedicine. 2000;7(6):529-36. PubMed
  5. Kishi K, Saito M, Saito T, et al. Clinical efficacy of apple polyphenol for treating cedar pollinosis. Biosci Biotechnol Biochem. 2005;69(4):829-32. PubMed
  6. Nagasako-Akazome Y, Kanda T, Ohtake Y, Shimasaki H, Kobayashi T. Apple polyphenols influence cholesterol metabolism in healthy subjects with relatively high body mass index. J Oleo Sci. 2007;56(8):417-28. PubMed
  7. Takahashi T, Kamimura A, Kagoura M, et al. Investigation of the topical application of procyanidin oligomers from apples to identify their potential use as a hair-growing agent. J Cosmet Dermatol. 2005;4(4):245-9. PubMed
  8. Tenore GC, Caruso D, Buonomo G, et al. A Healthy Balance of Plasma Cholesterol by a Novel Annurca Apple-Based Nutraceutical Formulation: Results of a Randomized Trial. J Med Food. 2017;20(3):288-300. PubMed
  9. Saarenhovi M, Salo P, Scheinin M, et al. The effect of an apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers on brachial artery flow-mediated vasodilatory function in volunteers with elevated blood pressure. Nutr. J 2017;16(1):73. PubMed
  10. Prpa EJ, Corpe CP, Atkinson B, et al. Apple polyphenol-rich drinks dose-dependently decrease early-phase postprandial glucose concentrations following a high-carbohydrate meal: a randomized controlled trial in healthy adults and in vitro studies. J Nutr B PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Apple Polyphenols and Tolbutamide Together: Common Questions

Is it safe to take Apple Polyphenols with Tolbutamide?
We do not list a known interaction between Apple Polyphenols and Tolbutamide. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
How was the Apple Polyphenols and Tolbutamide combination checked?
Interactions in our licensed database are recorded against drug classes. Tolbutamide is filed under 5 classifications, and Apple Polyphenols has documented interactions with 1 drug class — none of Tolbutamide's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does Apple Polyphenols interact with any other medications?
Yes. Apple Polyphenols has 13 documented drug interactions in our database — Tolbutamide is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Tolbutamide interact with any supplements?
Yes. Tolbutamide has documented interactions with 305 supplements in our database — Apple Polyphenols is not one of them. The Tolbutamide interaction page linked on this page lists every one, ranked by severity.

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

Still Have a Question About Tolbutamide and Apple Polyphenols?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.