Drug & supplement interaction

Pomegranate + Amitriptyline

Amitriptyline brand name: Elavil.

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

Amitriptyline falls into 3 drug categories that Pomegranate can interact with; the most serious is rated moderate. Theoretically, pomegranate might increase levels of drugs metabolized by CYP2D6.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Pomegranate and Amitriptyline

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Pomegranate interacts with whole categories of medication. Amitriptyline falls into 3 of those categories, so it can interact with Pomegranate in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

1 of 3

Why this applies to Amitriptyline

Amitriptyline falls under CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES — the group Pomegranate interacts with.

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.
Severity Moderate Likelihood Possible Evidence D

Interaction 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.

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

Here's the gist: your body uses an enzyme called CYP2D6 to help break down amitriptyline. In lab (test tube) studies, pomegranate seemed to slow that enzyme down. If that happened in real life, amitriptyline could clear a bit more slowly and build up, which might mean stronger effects and more side effects like drowsiness, dry mouth, constipation, blurry vision, or a faster heartbeat.

That said, I want to be straight with you: this is only a theoretical concern based on lab data, not on real patients, so we honestly don't know if it matters in everyday life. Enjoying pomegranate as a fruit or normal juice is very unlikely to cause trouble. Before using concentrated pomegranate extracts, just run it by your pharmacist or doctor.

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

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 3

Amitriptyline also falls under 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.
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 gist for amitriptyline (Elavil) and pomegranate. On paper, pomegranate can slow an enzyme called CYP2C9, which is one of the pathways that helps your body break down amitriptyline. If that pathway were blocked, the drug could build up a bit, which in theory might mean more of its usual side effects, things like drowsiness, dry mouth, constipation, dizziness when standing, or a faster heartbeat.

The good news is that this is mostly a lab and animal finding. In actual human studies, pomegranate juice and extract did not meaningfully change CYP2C9 activity. So enjoying pomegranate as a food or normal juice is very unlikely to cause a problem. If you're considering concentrated pomegranate extract pills, just run it by your pharmacist or doctor first.

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

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

3 of 3

Amitriptyline also falls under 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.
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 gist: amitriptyline is partly broken down by a liver enzyme called CYP3A4, and pomegranate has compounds that can block that enzyme in a test tube. In theory, slowing that breakdown could let more amitriptyline build up, which might mean more of its usual side effects like drowsiness, dry mouth, constipation, blurred vision, or feeling lightheaded when you stand up.

The reassuring part is that real human studies don't back this up. When people actually drank pomegranate juice, it didn't meaningfully change levels of other CYP3A4 drugs. So enjoying pomegranate as a fruit or juice is very unlikely to cause a problem. If you're thinking about concentrated pomegranate extracts, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. 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
  2. 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
  3. 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.
  4. 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.
  5. 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
  6. 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

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 354 moderate, 567 minor known drug interactions in our database — the Amitriptyline one above is among them. If you take anything else, check it against the full list below.

Moderate 354 Minor 567 No known interaction 1,909 (incl. Amitriptyline)
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 Amitriptyline

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 Amitriptyline, 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 Amitriptyline

This page covers Pomegranate only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Amitriptyline page lists 296 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), American Hellebore (major), Arsenic (major) and Beer (major).

By severity: 17 major · 228 moderate · 51 minor.

From our pharmacist’s overview on the Amitriptyline page

“Amitriptyline (Elavil), an older antidepressant now often prescribed for nerve pain, migraines, and sleep, is one of the drugs I genuinely want patients to be careful with, and 17 of the 296 supplement and herbal ingredients on this list carry a major rating. Most of the serious ones deepen the drowsiness amitriptyline already causes,…”

Reviewed by 2 · Jul 18, 2026

Open the Amitriptyline 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 Amitriptyline 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 Amitriptyline 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 Amitriptyline
Top 5%

#50 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 Amitriptyline

What Is Amitriptyline Used For?

Brand name: Elavil

Amitriptyline HCL and Amitriptyline Hydrochloride tablets are used to relieve symptoms of depression. Depression that originates from within the body (called endogenous depression) tends to respond better than other types of depression.

See full Amitriptyline 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
354Moderate
567Minor
1,908No known interaction
354 Moderate 567 Minor 1,908 No interaction
Moderate

354 interactions

Showing 60 of 354 moderate interactions — see all 354 on the Pomegranate page.

Minor

567 interactions

Showing 60 of 567 minor interactions — see all 567 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 Amitriptyline, 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 Amitriptyline supplement interactions › Every supplement checked against Amitriptyline, ranked by severity Amitriptyline 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 Amitriptyline Together: Common Questions

Can you take Pomegranate with Amitriptyline?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Pomegranate and Amitriptyline?
Amitriptyline 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 Amitriptyline interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

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

Still Have a Question About Amitriptyline 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.