Drug & supplement interaction

Resveratrol + Acetaminophen, Diphenhydramine

Acetaminophen, Diphenhydramine brand names: Tylenol PM, Tylenol PM Ex Strength.

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

Acetaminophen, Diphenhydramine falls into 2 drug categories that Resveratrol can interact with; the most serious is rated moderate. Theoretically, resveratrol might increase levels of drugs metabolized by CYP1A2.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

Resveratrol and Acetaminophen, Diphenhydramine

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

Why Are There 2 Interactions?

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

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 2

Why this applies to Acetaminophen, Diphenhydramine

Acetaminophen, Diphenhydramine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Resveratrol interacts with.

Theoretically, resveratrol might increase levels of drugs metabolized by CYP1A2.
In vitro research shows that resveratrol can inhibit CYP1A2 enzymes. However, this interaction has not been reported in humans.
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 simple version. Tylenol PM combines acetaminophen (a pain and fever reliever) with diphenhydramine (the sleepy antihistamine in Benadryl). In test-tube studies, resveratrol can slow down a liver enzyme called CYP1A2, and the worry is that this could let certain drugs build up a bit higher than usual.

Honestly, though, this is mostly a theoretical concern. It has only been seen in lab dishes, not in real people, and these aren't drugs that lean heavily on CYP1A2 anyway. If anything tipped higher, you might feel a little extra drowsy, dry-mouthed, or foggy from the diphenhydramine. Food amounts of resveratrol (grapes, berries) won't matter. If you take both regularly, just give your pharmacist a quick heads-up.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Chang, T. K., Chen, J., and Lee, W. B. Differential inhibition and inactivation of human CYP1 enzymes by trans-resveratrol: evidence for mechanism-based inactivation of CYP1A2. J.Pharmacol.Exp.Ther. 2001;299(3):874-882.
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

2 of 2

Acetaminophen, Diphenhydramine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Resveratrol might increase levels of drugs metabolized by CYP2E1.
In vitro research suggests that resveratrol inhibits CYP2E1 isoenzyme. Also, a pharmacokinetic study shows that taking resveratrol 500 mg daily for 10 days prior to taking a single dose of chlorzoxazone 250 mg increases the maximum concentration of chlorzoxazone by about 54%, the area under the curve of chlorzoxazone by about 72%, and the half-life of chlorzoxazone by about 35%. Chlorzoxazone is used as a probe drug for CYP2E1.
Severity Moderate Likelihood Probable Evidence B

Interaction 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..

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

Here's the piece that matters with Tylenol PM, which combines acetaminophen with diphenhydramine. Acetaminophen is partly handled by an enzyme called CYP2E1, and resveratrol appears to slow that enzyme down. A human study using a different CYP2E1 test drug showed meaningfully higher levels when resveratrol was taken first, so the concern is that more of an acetaminophen dose could shift toward this pathway.

In practice, at normal acetaminophen doses this is usually a minor concern, but the worry is the toxic byproduct CYP2E1 makes, which can stress the liver if you take too much or use alcohol. The diphenhydramine side (drowsiness, dry mouth, grogginess) isn't affected by this. Don't change anything on your own, just keep acetaminophen at recommended doses and check with your pharmacist if you use resveratrol regularly.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Piver B, Berthou F, Dreano Y, Lucas D. Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components. Toxicol Lett 2001;125:83-91. PubMed
  2. Yu, C., Shin, Y. G., Kosmeder, J. W., Pezzuto, J. M., and van Breemen, R. B. Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate. Rapid Commun.Mass Spectro PubMed
  3. Bedada SK, Neerati P. Resveratrol Pretreatment Affects CYP2E1 Activity of Chlorzoxazone in Healthy Human Volunteers. Phytother Res. 2016;30(3):463-8. 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

Resveratrol Also Interacts With Other Medications

Resveratrol has 821 moderate known drug interactions in our database — the Acetaminophen, Diphenhydramine one above is among them. If you take anything else, check it against the full list below.

Moderate 821 No known interaction 2,009 (incl. Acetaminophen, Diphenhydramine)
Taking anything else?

Check Another of Your Medications Against Resveratrol

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

From our Q&A

Questions About Resveratrol or Acetaminophen, Diphenhydramine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Resveratrol or Acetaminophen, Diphenhydramine, 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 Acetaminophen, Diphenhydramine

This page covers Resveratrol only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Diphenhydramine page lists 254 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), Asarabacca (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 11 major · 204 moderate · 39 minor.

Open the Acetaminophen, Diphenhydramine interaction page

One more smart check

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

We hold 2,939 real supplement products containing Resveratrol, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Resveratrol. Your product may carry other ingredients that interact with Acetaminophen, Diphenhydramine too, on top of Resveratrol — 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 Resveratrol and Acetaminophen, Diphenhydramine 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 Resveratrol
Top 10%

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

29 days ago today
Medication Acetaminophen, Diphenhydramine
Top 25%

#302 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 Resveratrol

What is Resveratrol?

Resveratrol
  • Heart and blood vessel health
  • Antioxidant support
  • Anti-aging
  • Blood sugar and metabolic support
  • General anti-inflammatory support

Resveratrol is a plant compound found in red grapes, berries, and peanuts that is popular for heart health, anti-aging, and antioxidant support. While lab and animal studies are promising, strong human evidence for most uses is still limited. It appears generally well tolerated in supplement doses, but talk with your pharmacist or doctor before starting it.

Read the full Resveratrol monograph & all interactions
Keep checking

Other Drugs & Resveratrol

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

0Major
821Moderate
0Minor
2,008No known interaction
821 Moderate 2,008 No interaction
Moderate

821 interactions

Showing 60 of 821 moderate interactions — see all 821 on the Resveratrol page.

No interaction 2,008 drugs checked — show the list

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

Showing the 60 most looked-up of 2,008 medications checked with no known interaction — see the full Resveratrol list.

See the full Resveratrol interactions page
See every supplement checked against Acetaminophen, Diphenhydramine, 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
Resveratrol monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Diphenhydramine supplement interactions › Every supplement checked against Acetaminophen, Diphenhydramine, ranked by severity 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 Resveratrol and Acetaminophen, Diphenhydramine Together: Common Questions

Can you take Resveratrol with Acetaminophen, Diphenhydramine?
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 2 interactions listed for Resveratrol and Acetaminophen, Diphenhydramine?
Acetaminophen, Diphenhydramine belongs to more than one drug category, and Resveratrol 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 Resveratrol and Acetaminophen, Diphenhydramine 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 Acetaminophen, Diphenhydramine and Resveratrol?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.