Drug & supplement interaction

Vitamin E + Tramadol

Tramadol brand names: Ultram, Zytram XL, Qdolo.

Moderate Interaction
The bottom line Moderate

Vitamin E has a moderate interaction with Tramadol. Theoretically, vitamin E might induce metabolism of CYP3A4, possibly reducing the levels CYP3A4 substrates.

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

Vitamin E and Tramadol

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Why this applies to Tramadol

Tramadol falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Vitamin E interacts with.

Theoretically, vitamin E might induce metabolism of CYP3A4, possibly reducing the levels CYP3A4 substrates.
Vitamin E appears to bind with the nuclear receptor, pregnane X receptor (PXR), which results in increased expression of CYP3A4. Although the clinical significance of this is not known, use caution when considering concomitant use of vitamin E and other drugs affected by these enzymes.
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 thing with tramadol: it's actually a prodrug. Your body has to convert it into its active form to give you most of its pain relief, and the CYP3A4 enzyme plays a part in handling it. The concern on file is that high-dose vitamin E might gently speed up that enzyme, which could shift how much tramadol is active in your system. With a pain medicine, that could mean it doesn't control your pain as well as expected.

But I want to keep this in perspective. This interaction is theoretical, based on lab pharmacology, not real patient reports, and ordinary food amounts of vitamin E are very unlikely to matter. If you're taking high-dose vitamin E supplements, just mention it to your pharmacist or doctor so they can keep an eye on your pain control.

References
  1. Landes N, Pfluger P, Kluth D, et al. Vitamin E activates gene expression via the pregnane X receptor. Biochem Pharmacol 2003;65:269-73. . PubMed
  2. Brigelius-Flohe R. Vitamin E and drug metabolism. Biochem Biophys Res Commun 2003;305:737-40. 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 E Also Interacts With Other Medications

Vitamin E has 762 moderate, 1 minor known drug interactions in our database — the Tramadol one above is one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Vitamin E

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

From our Q&A

Questions About Vitamin E or Tramadol

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 E or Tramadol, 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 Tramadol

This page covers Vitamin E only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tramadol page lists 223 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), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Grapefruit (major).

By severity: 10 major · 174 moderate · 39 minor.

From our pharmacist’s overview on the Tramadol page

“Tramadol (Ultram, Qdolo) is an opioid, and its supplement interactions worry me more than most because the worst of them compound the drug's most dangerous effects. Alcohol and dozens of calming herbs deepen its sedation, sometimes to the point of slowed breathing.”

Reviewed by 2 · Jul 18, 2026

Open the Tramadol interaction page

One more smart check

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

We hold 22,182 real supplement products containing Vitamin E, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Vitamin E. Your product may carry other ingredients that interact with Tramadol too, on top of Vitamin E — 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 E and Tramadol 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 E
Top 10

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

29 days ago today
Medication Tramadol
Top 25%

#341 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 E

What is Vitamin E?

Vitamin E
  • General antioxidant support
  • Skin and hair care
  • Heart health
  • Eye health (age-related conditions)
  • Immune support

Vitamin E is an essential fat-soluble vitamin and antioxidant that most people get in adequate amounts from a normal diet. Supplements can help correct a true deficiency, but high-dose vitamin E has not been clearly proven to prevent heart disease or cancer and may carry risks. Talk to your pharmacist or doctor before taking high doses.

Read the full Vitamin E monograph & all interactions
Medication

About Tramadol

What Is Tramadol Used For?

Brand names: Ultram, Zytram XL, Qdolo

Tramadol is used in adults for pain that is severe enough to need an opioid-strength medication and where non-opioid treatments haven't been enough. It's typically reserved for situations where milder options have failed or aren't expected to work.

It is not meant for everyday or long-term use unless the pain remains severe and alternatives continue to fall short. Prescribers carefully weigh the benefits against the real risks before starting tramadol.

See full Tramadol drug information
Keep checking

Other Drugs & Vitamin E

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

0Major
762Moderate
1Minor
2,066No known interaction
Moderate

762 interactions

Showing 60 of 762 moderate interactions — see all 762 on the Vitamin E page.

Minor

1 interaction

No interaction 2,066 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 Vitamin E and Tramadol Together: Common Questions

Can you take Vitamin E with Tramadol?
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.
How serious is the Vitamin E and Tramadol 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 Tramadol and Vitamin E?

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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.