Drug & supplement interaction

Red Clover + Methotrexate

Methotrexate brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex.

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

Red Clover has a moderate interaction with Methotrexate. Theoretically, red clover might increase the risk of methotrexate toxicity.

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

Red Clover and Methotrexate

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

Moderate

METHOTREXATE (Trexall, others)

Theoretically, red clover might increase the risk of methotrexate toxicity.
In a case report, a 52-year-old female receiving weekly methotrexate injections for psoriasis developed symptoms of methotrexate toxicity, including severe vomiting and epigastric pain, after three days of taking red clover 430 mg daily. Toxicity resolved after red clover was discontinued. However, no liver function tests or methotrexate levels were reported.
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 short version: there's a chance that pairing red clover with your methotrexate could nudge methotrexate levels higher in your body, which can mean more of its side effects. Methotrexate isn't a prodrug, so this isn't about boosting a benefit, it's about the drug potentially building up and causing trouble like severe nausea, vomiting, mouth sores, stomach pain, fatigue, or in bigger picture terms, strain on the liver or blood counts.

I want to be honest with you, though: this is based on a single case report, not strong studies, and we don't even have lab values to confirm it. So it's more of a theoretical, be-cautious flag than a proven danger. Methotrexate is a drug where small changes can matter, so before you add red clover, please run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Orr A and Parker R. Red clover causing symptoms suggestive of methotrexate toxicity in a patient on high-dose methotrexate. Menopause Int. 2013;19(3):133-134. 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

Red Clover Also Interacts With Other Medications

Red Clover has 43 moderate, 823 minor known drug interactions in our database — the Methotrexate one above is one of them. If you take anything else, check it against the full list below.

Moderate 43 Minor 823 No known interaction 1,964 (incl. Methotrexate)
Taking anything else?

Check Another of Your Medications Against Red Clover

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

From our Q&A

Questions About Red Clover or Methotrexate

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

This page covers Red Clover only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Methotrexate page lists 82 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Apple (major), Beer (major), Grapefruit (major) and Siberian Cocklebur (major).

By severity: 7 major · 60 moderate · 15 minor.

From our pharmacist’s overview on the Methotrexate page

“The liver is where methotrexate and supplements clash most. Methotrexate (Rheumatrex, Otrexup, Rasuvo), used for rheumatoid arthritis, psoriasis, and certain cancers, can strain the liver on its own, and 38 of the 82 interacting ingredients on this list add liver risk of their own, alcohol included, which makes this a list to approach…”

Reviewed by 2 · Jul 18, 2026

Open the Methotrexate interaction page

One more smart check

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

We hold 1,480 real supplement products containing Red Clover, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Red Clover. Your product may carry other ingredients that interact with Methotrexate too, on top of Red Clover — 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 Red Clover and Methotrexate 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 Red Clover
Top 25%

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

29 days ago today
Medication Methotrexate
Top 5%

#49 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 Red Clover

What is Red Clover?

Red Clover
  • Menopause symptoms (hot flashes)
  • High cholesterol
  • Bone health/osteoporosis
  • Skin and hair concerns
  • Women's health

Red clover is a plant rich in isoflavones (plant compounds with weak estrogen-like activity) that is most often used for menopause symptoms like hot flashes. The evidence is mixed and generally weak, with some studies showing modest benefit and others showing none. Because of its hormone-like effects, it's not for everyone—talk with your pharmacist or doctor before trying it, especially if you have a hormone-sensitive condition.

Read the full Red Clover monograph & all interactions
Medication

About Methotrexate

What Is Methotrexate Used For?

Brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex

Methotrexate treats a wide range of serious conditions. In cancer care, it is used for acute lymphoblastic leukemia, non-Hodgkin lymphoma, osteosarcoma, breast cancer, head and neck cancer, and gestational trophoblastic neoplasia (a rare tumor related to pregnancy). It is also used to prevent and treat meningeal leukemia (cancer affecting the lining of the brain and spinal cord).

Outside of cancer, methotrexate is prescribed for adults with rheumatoid arthritis (RA), children with polyarticular juvenile idiopathic arthritis (a form of childhood arthritis), and adults with severe psoriasis that hasn't responded well to other treatments.

See full Methotrexate drug information
Keep checking

Other Drugs & Red Clover

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

0Major
43Moderate
823Minor
1,963No known interaction
43 Moderate 823 Minor 1,963 No interaction
Moderate

43 interactions

Minor

823 interactions

Showing 60 of 823 minor interactions — see all 823 on the Red Clover page.

No interaction 1,963 drugs checked — show the list

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

Showing the 60 most looked-up of 1,963 medications checked with no known interaction — see the full Red Clover list.

See the full Red Clover interactions page
See every supplement checked against Methotrexate, 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
Red Clover monograph › Uses, safety, and every drug interaction in one place Methotrexate supplement interactions › Every supplement checked against Methotrexate, ranked by severity Methotrexate drug information › The full plain-English guide to this medication 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 Red Clover and Methotrexate Together: Common Questions

Can you take Red Clover with Methotrexate?
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 Red Clover and Methotrexate 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 Methotrexate and Red Clover?

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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.