Drug & supplement interaction

Pomegranate + Tolbutamide

Tolbutamide brand name: Orinase.

Minor Interaction
Medically reviewed by · Updated September 2026
The bottom line Minor

Tolbutamide falls into 2 drug categories that Pomegranate can interact with; the most serious is rated minor. Theoretically, pomegranate might increase levels of drugs metabolized by CYP2C9.

Read the full interaction report
SeverityMinor
LikelihoodUnlikely
Interactions2
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Pomegranate and Tolbutamide

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Pomegranate interacts with whole categories of medication. Tolbutamide falls into 2 of those categories, so it can interact with Pomegranate in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Minor).

Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

1 of 2

Why this applies to Tolbutamide

Tolbutamide falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES — the group Pomegranate interacts with.

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.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the short version: your body clears tolbutamide using a liver enzyme called CYP2C9, and pomegranate has been looked at for possibly slowing that enzyme down. If it did, tolbutamide could linger longer and push your blood sugar lower than expected, which might show up as shakiness, sweating, dizziness, or feeling unusually hungry.

The reassuring part is that this is mostly a theoretical concern. Lab and animal studies hinted at it, but actual human studies found that pomegranate juice and extract did not meaningfully change CYP2C9. Enjoying pomegranate as a food or juice is very unlikely to cause a problem. If you plan to use a concentrated pomegranate extract regularly, just give your pharmacist or doctor a quick heads-up.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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
  2. 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
Minor

TOLBUTAMIDE (Orinase)

2 of 2
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.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist with pomegranate and your tolbutamide (Orinase). Tolbutamide is cleared by an enzyme called CYP2C9, and in animal studies pomegranate juice slowed that enzyme a bit, nudging tolbutamide levels up by about 1.2 times. In theory, slightly higher levels could mean a touch more blood-sugar lowering, with the main thing to watch being low blood sugar (shakiness, sweating, dizziness, hunger).

The reassuring part: in actual human studies, neither pomegranate juice nor pomegranate extract meaningfully changed this enzyme, so this interaction isn't expected to cause real problems. Enjoying pomegranate as food or juice should be fine. If you're thinking about concentrated extract supplements, just run it by your pharmacist or doctor first, and keep checking your sugars as usual.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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
  2. 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

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Pomegranate Also Interacts With Other Medications

Pomegranate has 355 moderate, 566 minor known drug interactions in our database — the Tolbutamide one above is among them. If you take anything else, check it against the full list below.

Moderate 355 Minor 566 No known interaction 1,909 (incl. Tolbutamide)
Taking anything else?

Check Another of Your Medications Against Pomegranate

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

From our Q&A

Questions About Pomegranate or Tolbutamide

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Pomegranate or Tolbutamide, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Tolbutamide

This page covers Pomegranate 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

One more smart check

Taking Pomegranate as Part of a Dietary Supplement Product? Check It for Interactions

We hold 4,607 real supplement products containing Pomegranate, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Pomegranate. Your product may carry other ingredients that interact with Tolbutamide too, on top of Pomegranate — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Pomegranate 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 Pomegranate
Top 5%

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

29 days ago today
Medication Tolbutamide
Steady interest

#1,619 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.

Supplement

About Pomegranate

What is Pomegranate?

Pomegranate
  • Heart and blood vessel health
  • Antioxidant support
  • High blood pressure
  • Inflammation
  • Digestive upset
  • Skin health

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 evidence is still limited and not strong enough to call it a proven treatment. As a food it is generally safe, but talk to your pharmacist or doctor before using concentrated extracts, especially if you are pregnant, breastfeeding, or take medications.

Read the full Pomegranate 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 & Pomegranate

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

0Major
355Moderate
566Minor
1,908No known interaction
355 Moderate 566 Minor 1,908 No interaction
Moderate

355 interactions

Showing 60 of 355 moderate interactions — see all 355 on the Pomegranate page.

Minor

566 interactions

Showing 60 of 566 minor interactions — see all 566 on the Pomegranate page.

No interaction 1,908 drugs checked — show the list

We also checked Pomegranate against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,908 medications checked with no known interaction — see the full Pomegranate list.

See the full Pomegranate interactions page
See every supplement checked against Tolbutamide, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

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

© 2021 Therapeutic Research Center, LLC

Keep exploring
Pomegranate monograph › Uses, safety, and every drug interaction in one place Tolbutamide supplement interactions › Every supplement checked against Tolbutamide, ranked by severity Tolbutamide drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Pomegranate and Tolbutamide Together: Common Questions

Can you take Pomegranate with Tolbutamide?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Pomegranate and Tolbutamide?
Tolbutamide belongs to more than one drug category, and Pomegranate interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Pomegranate and Tolbutamide interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

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

Still Have a Question About Tolbutamide and Pomegranate?

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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.