Drug & supplement interaction

Sulforaphane + 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 3 drug categories that Sulforaphane can interact with; the most serious is rated moderate. Theoretically, sulforaphane might alter the levels and clinical effects of CYP1A2 substrates.

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

Sulforaphane and Acetaminophen, Aspirin, Caffeine

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

Why Are There 3 Interactions?

Sulforaphane interacts with whole categories of medication. Acetaminophen, Aspirin, Caffeine falls into 3 of those categories, so it can interact with Sulforaphane 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 1A2 (CYP1A2) SUBSTRATES

1 of 3

Why this applies to Acetaminophen, Aspirin, Caffeine

Acetaminophen, Aspirin, Caffeine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Sulforaphane interacts with.

Theoretically, sulforaphane might alter the levels and clinical effects of CYP1A2 substrates.
Animal and in vitro research shows that sulforaphane inhibits CYP1A2 enzyme activity. However, its precursor glucoraphanin also appears to increase the expression of the CYP1A2 enzyme, which could lead to increased metabolism of CYP1A2 substrates. These effects have 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 combo product, the piece that interacts is the caffeine. Your body clears caffeine mainly through a liver enzyme called CYP1A2, and lab and animal studies suggest sulforaphane can slow that enzyme down. If that happened in people, caffeine could hang around a little longer and feel stronger, meaning more jitteriness, a racing heart, or trouble sleeping. The acetaminophen and aspirin parts aren't really affected here.

Here's the reassuring part: this is only theoretical, based on test-tube and animal research, and it hasn't been shown in actual humans. Broccoli on your dinner plate is not a concern. If you take a concentrated sulforaphane supplement and notice extra caffeine buzz, just check in with your pharmacist or doctor.

References
  1. Barcelo S, Mace K, Pfeifer AM, Chipman JK. Production of DNA strand breaks by N-nitrosodimethylamine and 2-amino-3-methylimidazo[4,5-f]quinoline in THLE cells expressing human CYP isoenzymes and inhibition by sulforaphane. Mutat Res 1998;402:111-20. PubMed
  2. Fimognari C, Lenzi M, Hrelia P. Interaction of the isothiocyanate sulforaphane with drug disposition and metabolism: pharmacological and toxicological implications. Curr Drug Metab. 2008;9(7):668-78. PubMed
  3. Chinnappan SM, George A, Evans M, Anthony J. Efficacy of Labisia pumila and Eurycoma longifolia standardised extracts on hot flushes, quality of life, hormone and lipid profile of peri-menopausal and menopausal women: a randomised, placebo-controlled stud
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

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

Theoretically, sulforaphane might increase the levels and effects of CYP3A4 substrates.
Animal and in vitro research shows that sulforaphane inhibits CYP3A4 enzyme activity and downregulates its expression. 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 honest take on combining sulforaphane with Excedrin (acetaminophen, aspirin, and caffeine). The concern on file is that sulforaphane might block an enzyme called CYP3A4, which could in theory let certain drugs build up. But I want to keep this in perspective: the three ingredients in Excedrin aren't really cleared by CYP3A4 in a meaningful way. Acetaminophen and aspirin go through different pathways, and caffeine is mainly handled by CYP1A2.

On top of that, this whole concern comes only from lab and animal studies, never confirmed in people. Eating broccoli is no worry at all. If you take a concentrated sulforaphane supplement and have any questions, just run it by your pharmacist or doctor to be safe.

References
  1. Fimognari C, Lenzi M, Hrelia P. Interaction of the isothiocyanate sulforaphane with drug disposition and metabolism: pharmacological and toxicological implications. Curr Drug Metab. 2008;9(7):668-78. PubMed
  2. Mahéo K, Morel F, Langouët S, et al. Inhibition of cytochromes P-450 and induction of glutathione S-transferases by sulforaphane in primary human and rat hepatocytes. Cancer Res. 1997;57(17):3649-52.
  3. Yoxall V, Kentish P, Coldham N, Kuhnert N, Sauer MJ, Ioannides C. Modulation of hepatic cytochromes P450 and phase II enzymes by dietary doses of sulforaphane in rats: Implications for its chemopreventive activity. Int J Cancer. 2005;117(3):356-62. PubMed
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

3 of 3

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

Theoretically, sulforaphane might increase the levels and effects of CYP2E1 substrates.
In vitro evidence shows that sulforaphane inhibits CYP2E1 enzymes. 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 piece that matters for Excedrin: the acetaminophen part of this combo is partly handled by a liver enzyme called CYP2E1. In lab (test tube) studies, sulforaphane appears to slow that enzyme down. In theory, slowing CYP2E1 could shift how acetaminophen is processed. The good news is this is one route where CYP2E1 actually makes a harmful byproduct of acetaminophen, so blocking it isn't an obvious recipe for trouble. Bottom line, this interaction is theoretical and has never been documented in real people.

Eating broccoli won't be a problem. If you take a concentrated sulforaphane supplement and use Excedrin regularly, just mention it to your pharmacist or doctor so they can keep an eye on things.

References
  1. Fimognari C, Lenzi M, Hrelia P. Interaction of the isothiocyanate sulforaphane with drug disposition and metabolism: pharmacological and toxicological implications. Curr Drug Metab. 2008;9(7):668-78. 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

Sulforaphane Also Interacts With Other Medications

Sulforaphane has 721 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 Sulforaphane

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

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Aspirin, Caffeine

This page covers Sulforaphane 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 Sulforaphane as Part of a Dietary Supplement Product? Check It for Interactions

We hold 167 real supplement products containing Sulforaphane, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sulforaphane. Your product may carry other ingredients that interact with Acetaminophen, Aspirin, Caffeine too, on top of Sulforaphane — 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 Sulforaphane 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 Sulforaphane
Top 25%

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

29 days ago today
Medication Acetaminophen, Aspirin, Caffeine
Top 25%

#330 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 Sulforaphane

What is Sulforaphane?

  • Antioxidant support
  • General cellular health
  • Detoxification support
  • Inflammation
  • Skin and aging concerns

Sulforaphane is a natural compound found in broccoli and other cruciferous vegetables that has shown promising antioxidant and anti-inflammatory effects in lab studies, but strong human evidence for most specific health claims is still limited. It is generally well tolerated as part of a vegetable-rich diet, but if you take a concentrated supplement, talk to your pharmacist or doctor first.

Read the full Sulforaphane monograph & all interactions
Keep checking

Other Drugs & Sulforaphane

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

0Major
721Moderate
0Minor
2,108No known interaction
Moderate

721 interactions

Showing 60 of 721 moderate interactions — see all 721 on the Sulforaphane page.

No interaction 2,108 drugs checked — show the 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

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Pharmacist Counseling Corner

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

Can you take Sulforaphane 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 3 interactions listed for Sulforaphane and Acetaminophen, Aspirin, Caffeine?
Acetaminophen, Aspirin, Caffeine belongs to more than one drug category, and Sulforaphane 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 Sulforaphane 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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