Drug & supplement interaction

Resveratrol + Acetaminophen, Aspirin, Caffeine

Acetaminophen, Aspirin, Caffeine brand names: Excedrin Migraine, Excedrin, Excedrin Extra Strength.

Moderate Interaction
The bottom line Moderate

Acetaminophen, Aspirin, Caffeine falls into 4 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
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Resveratrol and Acetaminophen, Aspirin, Caffeine

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Resveratrol interacts with whole categories of medication. Acetaminophen, Aspirin, Caffeine falls into 4 of those categories, so it can interact with Resveratrol in 4 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 4

Why this applies to Acetaminophen, Aspirin, Caffeine

Acetaminophen, Aspirin, Caffeine 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

In this combination product (like Excedrin), the piece that matters here is the caffeine. Your body clears caffeine using a liver enzyme called CYP1A2. Lab studies suggest resveratrol can slow that enzyme down, which in theory could let caffeine linger a bit longer than usual. If that happened, you might notice more of caffeine's usual effects: feeling jittery, a racing heart, trouble sleeping, or an upset stomach.

Here's the reassuring part: this is only based on test-tube research, and it has never actually been reported in real people. The acetaminophen and aspirin parts aren't really affected. Still, if you take resveratrol and feel extra wired, mention it to your pharmacist or doctor before changing anything.

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 3A4 (CYP3A4) SUBSTRATES

2 of 4

Acetaminophen, Aspirin, Caffeine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, resveratrol might increase levels of drugs metabolized by CYP3A4.
In vitro research shows that resveratrol can inhibit the CYP3A4 enzyme. However, clinical research shows that taking resveratrol 3000 mg daily for 8 weeks does not necessitate dose adjustments to medications metabolized by CYP3A4.
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 with this combo product (acetaminophen, aspirin, and caffeine, like Excedrin). In test tube studies, resveratrol can block a liver enzyme called CYP3A4, and caffeine is partly handled by that enzyme family. In theory, that could let caffeine linger a bit longer, which might mean more jitteriness, a racing heart, or trouble sleeping. None of these three ingredients are prodrugs, so we're not worried about losing their effect.

Honestly, though, this is based only on lab data, not real people. A human study using a hefty 3000 mg of resveratrol daily found no need to adjust CYP3A4 medications. So for most folks this is unlikely to cause problems. If you take resveratrol regularly, just mention it to your pharmacist or doctor.

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. Chachay VS, Macdonald GA, Martin JH, Whitehead JP, O'Moore-Sullivan TM, Lee P, Franklin M, Klein K, Taylor PJ, Ferguson M, Coombes JS, Thomas GP, Cowin GJ, Kirkpatrick CM, Prins JB, Hickman IJ. Resveratrol does not benefit patients with nonalcoholic fatty
Moderate

ANTICOAGULANT/ANTIPLATELET DRUGS

3 of 4

Acetaminophen, Aspirin, Caffeine also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Resveratrol may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Resveratrol seems to have antiplatelet effects.
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

The piece of this combo that matters most here is the aspirin. Aspirin already thins the blood by making your platelets less sticky, which is exactly why it helps with headaches and heart protection. Resveratrol seems to do a mild version of the same thing, so stacking the two could add up and make bleeding or easy bruising a bit more likely. Think nosebleeds, bleeding gums, or a cut that takes longer to stop.

That said, this caution comes mostly from lab and test-tube studies, not strong human research, so the real-world risk is probably small for most people. Still, if you take Excedrin often or you're on any other blood thinner, it's worth a quick chat with your pharmacist or doctor before adding a resveratrol supplement.

References
  1. Pace-Asciak CR, Rounova O, Hahn SE, et al. Wines and grape juices as modulators of platelet aggregation in healthy human subjects. Clin Chim Acta 1996;246:163-82. PubMed
  2. Bertelli AA, Giovannini L, Bernini W, et al. Antiplatelet activity of cis-resveratrol. Drugs Exp Clin Res 1996;22:61-3.
  3. Pace-Asciak CR, Hahn S, Diamandis EP, et al. The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Clin Chim Acta 1995;235:207-19.
  4. Bertelli A, Bertelli AA, Gozzini A, Giovannini L. Plasma and tissue resveratrol concentrations and pharmacological activity. Drugs Exp Clin Res 1998;24:133-8.
  5. Bertelli AA, Giovannini L, Giannessi D, et al. Antiplatelet activity of synthetic and natural resveratrol in red wine. Int J Tissue React 1995;17:1-3.
  6. Dobrydneva, Y., Williams, R. L., and Blackmore, P. F. trans-Resveratrol inhibits calcium influx in thrombin-stimulated human platelets. Br.J.Pharmacol. 1999;128(1):149-157.
  7. Kirk, R. I., Deitch, J. A., Wu, J. M., and Lerea, K. M. Resveratrol decreases early signaling events in washed platelets but has little effect on platalet in whole food. Blood Cells Mol.Dis. 2000;26(2):144-150.
  8. Zbikowska, H. M. and Olas, B. Antioxidants with carcinostatic activity (resveratrol, vitamin E and selenium) in modulation of blood platelet adhesion. J Physiol Pharmacol. 2000;51(3):513-520.
  9. Olas, B., Wachowicz, B., Saluk-Juszczak, J., and Zielinski, T. Effect of resveratrol, a natural polyphenolic compound, on platelet activation induced by endotoxin or thrombin. Thromb.Res 8-15-2002;107(3-4):141-145. PubMed
  10. Ma, Z. H. and Ma, Q. Y. Resveratrol: a medical drug for acute pancreatitis. World J Gastroenterol. 6-7-2005;11(21):3171-3174. PubMed
  11. Pendurthi, U. R., Williams, J. T., and Rao, L. V. Resveratrol, a polyphenolic compound found in wine, inhibits tissue factor expression in vascular cells : A possible mechanism for the cardiovascular benefits associated with moderate consumption of wine. PubMed
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

4 of 4

Acetaminophen, Aspirin, Caffeine 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 for products like Excedrin: the acetaminophen part is partly handled by a liver enzyme called CYP2E1. Resveratrol appears to slow that enzyme down. In one human study, blocking CYP2E1 raised levels of a test drug by about 50 to 70 percent. So in theory, taking concentrated resveratrol could let a bit more acetaminophen linger before your liver clears it.

Why I mention it: CYP2E1 helps create the byproduct of acetaminophen that can stress the liver. The aspirin and caffeine pieces aren't really affected here. For most people taking occasional, label-dose Excedrin, this is a low-key concern, and the grapes or berries in your diet won't matter. If you take acetaminophen often or drink alcohol regularly, check with your pharmacist before adding a resveratrol supplement.

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, Aspirin, Caffeine one above is among them. If you take anything else, check it against the full list below.

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, Aspirin, Caffeine

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, Aspirin, Caffeine, 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, Aspirin, Caffeine

This page covers Resveratrol only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Aspirin, Caffeine page lists 371 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Danshen (major) and Ephedra (major).

By severity: 13 major · 312 moderate · 46 minor.

From our pharmacist’s overview on the Acetaminophen, Aspirin, Caffeine page

“Excedrin (acetaminophen, aspirin, and caffeine) packs three drugs into one tablet, which multiplies the ways supplements can collide with it, so treat this list with real care. Most entries involve the aspirin: hundreds of herbs add to its blood-thinning effect and raise bleeding risk, and even beer or wine earns a major rating for sto…”

Reviewed by 2 · Jul 18, 2026

Open the Acetaminophen, Aspirin, Caffeine 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, Aspirin, Caffeine 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, Aspirin, Caffeine 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%

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

29 days ago today
Medication Acetaminophen, Aspirin, Caffeine
Top 1%

#20 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
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.

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
Pharmacist Counseling Corner

Taking Resveratrol and Acetaminophen, Aspirin, Caffeine Together: Common Questions

Can you take Resveratrol with Acetaminophen, Aspirin, Caffeine?
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 4 interactions listed for Resveratrol and Acetaminophen, Aspirin, Caffeine?
Acetaminophen, Aspirin, Caffeine 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, Aspirin, Caffeine 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

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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.