Drug & supplement interaction

Vitamin D + Acetaminophen, Aspirin, Caffeine

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

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

Vitamin D has a minor interaction with Acetaminophen, Aspirin, Caffeine. Vitamin D might induce CYP3A4 enzymes and reduce the bioavailability of CYP3A4 substrates.

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

Vitamin D and Acetaminophen, Aspirin, Caffeine

Here is the interaction we found between these two, with the evidence behind it.

Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Acetaminophen, Aspirin, Caffeine

Acetaminophen, Aspirin, Caffeine falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Vitamin D interacts with.

Vitamin D might induce CYP3A4 enzymes and reduce the bioavailability of CYP3A4 substrates.
There is some concern that vitamin D might induce CYP3A4. In vitro research suggests that vitamin D induces CYP3A4 transcription. Additionally, observational research has found that increased UV light exposure and serum vitamin D levels are associated with decreased serum levels of CYP3A4 substrates such as tacrolimus and sirolimus, while no association between UV light exposure or vitamin D levels and levels of mycophenolic acid, a non-CYP3A4 substrate, was found. A small, low-quality clinical study shows that taking vitamin D reduces levels of the CYP3A4 substrate atorvastatin and its active metabolites by up to 55%; however, the clinical effects of atorvastatin were not reduced. While researchers theorized that vitamin D might induce CYP3A4, this proposed mechanism was not specifically studied.
Severity Minor 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: vitamin D might nudge a liver enzyme called CYP3A4 to work a little faster. In theory, that could clear certain drugs out of your body sooner. With a combo product like Excedrin (acetaminophen, aspirin, and caffeine), this really isn't something I'd lose sleep over. Caffeine is mostly handled by a different enzyme, and acetaminophen and aspirin don't lean heavily on CYP3A4 either.

The whole idea here is theoretical, based on lab studies, not real-world reports of this trio failing. In plain terms, taking vitamin D shouldn't meaningfully change how well your Excedrin works for a headache. If you have questions, your pharmacist is happy to double-check with you.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Schwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: A new drug interaction with an unexpected consequence. Clin Pharmacol Ther 2009;85:198-203. PubMed
  2. Wang Z, Schuetz EG, Xu Y, Thummel KE. Interplay between vitamin D and the drug metabolizing enzyme CYP3A4. J Steroid Biochem Mol Biol 2013;136:54-8. 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

Vitamin D Also Interacts With Other Medications

Vitamin D has 80 moderate, 634 minor known drug interactions in our database — the Acetaminophen, Aspirin, Caffeine one above is one of them. If you take anything else, check it against the full list below.

Moderate 80 Minor 634 No known interaction 2,116 (incl. Acetaminophen, Aspirin, Caffeine)
Taking anything else?

Check Another of Your Medications Against Vitamin D

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

From our Q&A

Questions About Vitamin D 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 Vitamin D 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 Vitamin D 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 Vitamin D as Part of a Dietary Supplement Product? Check It for Interactions

We hold 26,930 real supplement products containing Vitamin D, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Vitamin D. Your product may carry other ingredients that interact with Acetaminophen, Aspirin, Caffeine too, on top of Vitamin D — 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 Vitamin D 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 Vitamin D
Top 10

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

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

#383 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 Vitamin D

What is Vitamin D?

Vitamin D
  • Bone health and osteoporosis
  • Correcting vitamin D deficiency
  • Immune system support
  • Muscle strength in older adults
  • General supplementation when sun exposure is low

Vitamin D is a fat-soluble vitamin that helps your body absorb calcium and is important for healthy bones, muscles, and immune function. Many people, especially those with low sun exposure, benefit from supplementation, but more is not always better and very high doses can be harmful. Ask your pharmacist or doctor whether a blood test and supplement make sense for you.

Read the full Vitamin D monograph & all interactions
Keep checking

Other Drugs & Vitamin D

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

0Major
80Moderate
634Minor
2,115No known interaction
80 Moderate 634 Minor 2,115 No interaction
Moderate

80 interactions

Showing 60 of 80 moderate interactions — see all 80 on the Vitamin D page.

Minor

634 interactions

Showing 60 of 634 minor interactions — see all 634 on the Vitamin D page.

No interaction 2,115 drugs checked — show the list

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

Showing the 60 most looked-up of 2,115 medications checked with no known interaction — see the full Vitamin D list.

See the full Vitamin D interactions page
See every supplement checked against Acetaminophen, Aspirin, Caffeine, 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
Vitamin D monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Aspirin, Caffeine supplement interactions › Every supplement checked against Acetaminophen, Aspirin, Caffeine, 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 Vitamin D and Acetaminophen, Aspirin, Caffeine Together: Common Questions

Can you take Vitamin D with Acetaminophen, Aspirin, Caffeine?
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.
How serious is the Vitamin D and Acetaminophen, Aspirin, Caffeine 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 Acetaminophen, Aspirin, Caffeine and Vitamin D?

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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.