Drug & supplement interaction

Equol + Methotrexate

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

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Oct 4, 2026
The bottom line No known interaction

We found no known interaction between Equol and Methotrexate in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first.

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Interaction report

Equol and Methotrexate

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Methotrexate and Equol in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Equol safety at a glance

Equol overall Use caution Generally well tolerated in studies, but long-term safety and effects on hormone-sensitive conditions are not well established.
Pregnancy Avoid Not enough safety data and possible hormone-like effects, so it is best avoided.
Breastfeeding Avoid There is no reliable safety information, so avoid use while breastfeeding.

Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Methotrexate and Equol? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Methotrexate

Interactions in our licensed database are recorded against drug classes, not just single drug names. Methotrexate is filed under 6 classifications — including organic anion-transporting polypeptide substrates (oatp), organic anion transporter 3 (oat3) substrates, hepatotoxic drugs. Equol has documented interactions with 4 drug classes — the most serious being contraceptive drugs (moderate), estrogens (moderate) and testosterone (moderate) — and none of Methotrexate’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Equol Does Interact With Other Medications

Equol has 58 moderate, 75 minor known drug interactions in our database — Methotrexate isn’t one of them. If you take anything else, check it against the full list below.

Moderate 58 Minor 75 No known interaction 2,697 (incl. Methotrexate)
Taking anything else?

Check Another of Your Medications Against Equol

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

What to actually watch for

What Equol Itself Has Been Linked To

This is not an interaction — nothing below involves Methotrexate. It is the side-effect record for Equol on its own, from the licensed Natural Medicines monograph. If something new turns up after you add Equol, this list is the first place to look. One entry is worth acting on rather than waiting out — marked below.

  • Low mood Worth acting on Additional detail

    “Orally, equol has been rarely reported to cause depression.”

    Equol · Natural Medicines adverse-effect record, reported in depression.

    1 source cited
    1. 19075. Jenks BH, Iwashita S, Nakagawa Y, et al. A pilot study on the effects of S-equol compared to soy isoflavones on menopausal hot flash frequency. J Womens Health (Larchmt) 2012;21:674-82.
  • Bloating or gas Additional detail

    Recorded for Equol in the same Natural Medicines adverse-effect record shown under Low mood above.

  • Constipation Additional detail

    “Orally, equol has been reported to cause abdominal distention and constipation.”

    Equol · Natural Medicines adverse-effect record, reported in constipation.

    1 source cited
    1. 19075. Jenks BH, Iwashita S, Nakagawa Y, et al. A pilot study on the effects of S-equol compared to soy isoflavones on menopausal hot flash frequency. J Womens Health (Larchmt) 2012;21:674-82.

Everything above comes from the Natural Medicines adverse-effect record for Equol — expand a row for the licensed statement it rests on. We read the ADVERSE REACTIONS section of Methotrexate’s FDA label too, and the two lists don’t meaningfully overlap — which is why no Methotrexate column appears here.

Overlapping uses

What Methotrexate Is Prescribed For, and What Equol Has Been Studied For

These two come up together because they touch the same health topic — not because they do the same job. Methotrexate is a prescription medicine with approved uses on its FDA label. Equol is a supplement: what follows is what researchers have looked at it for, and how strong that evidence is.

Methotrexate is prescribed for: Methotrexate treats several kinds of cancer, plus rheumatoid arthritis, polyarticular juvenile idiopathic arthritis (pJIA, a form of arthritis in children that affects many joints), and severe psoriasis. Which uses apply depends on the specific product. Methotrexate tablets, Trexall and Jylamvo (oral solution) are used for acute lymphoblastic leukemia (ALL), mycosis fungoides, relapsed or refractory non-Hodgkin lymphoma, rheumatoid arthritis, pJIA and severe psoriasis. Xatmep (oral solution) is only for ALL and pJIA in children.

Read the rest of what Methotrexate is prescribed for

Methotrexate injection products cover a wider list of cancers. Otrexup and Rasuvo (subcutaneous auto-injectors) are for rheumatoid arthritis, pJIA and psoriasis only, and are not for cancer.

Equol has been studied for:

  • Breast cancer studied, not established Equol has been studied for this. Natural Medicines rates the evidence: Insufficient Reliable Evidence To Rate Read what the research shows

    Equol for breast cancer

    Although there has been interest in using oral equol for breast cancer, there is insufficient reliable information about the clinical effects of equol for this purpose.

Effectiveness ratings and the research summaries above are the verbatim record from the Natural Medicines database, which grades evidence from “Effective” down to “Insufficient Reliable Evidence To Rate”. A rating below the top of that scale means researchers have looked at it — not that it works, and never that it can stand in for a prescribed medicine. Do not stop or replace Methotrexate on your own; if you are taking Equol for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

From our Q&A

Questions About Equol 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 Equol 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 Equol 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

How much people look this up

Where Equol 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 Equol
Top half

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

29 days ago today
Medication Methotrexate
Top 5%

#37 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.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Equol reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified October 4, 2026. The Equol and Methotrexate records this page draws on were last updated July 10, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
Supplement

About Equol

What is Equol?

  • Menopause symptoms (hot flashes)
  • Bone health support
  • Skin aging
  • Prostate health
  • General hormone balance

Equol is a compound made in the gut when some people break down soy isoflavones, and it is also sold as a supplement. Early research links it to possible benefits for menopause symptoms and bone or skin health, but the evidence is still limited and far from proven. Talk with your pharmacist or doctor before using it, and avoid it during pregnancy and breastfeeding.

Not a plant part; a metabolite produced by gut bacteria from soy isoflavones (daidzein) · Capsules, tablets, and as a component of fermented soy or red clover supplements

An interaction check asks whether these two react with each other — it does not ask whether Equol is a good idea for someone in your situation. Here is what our Equol record says about it on its own.

Equol: dosing

There is no official or standardized dose of equol. Amounts used in research have varied, and supplement products differ in how much they contain.The best approach is to follow the directions on the product label and not take more than recommended.

From our Equol monograph — the full record covers uses, side effects and every documented interaction.

Read the full Equol monograph & all interactions
Medication

About Methotrexate

What Is Methotrexate Used For?

Brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex

Methotrexate treats several kinds of cancer, plus rheumatoid arthritis, polyarticular juvenile idiopathic arthritis (pJIA, a form of arthritis in children that affects many joints), and severe psoriasis. Which uses apply depends on the specific product.

Methotrexate tablets, Trexall and Jylamvo (oral solution) are used for acute lymphoblastic leukemia (ALL), mycosis fungoides, relapsed or refractory non-Hodgkin lymphoma, rheumatoid arthritis, pJIA and severe psoriasis. Xatmep (oral solution) is only for ALL and pJIA in children. Methotrexate injection products cover a wider list of cancers. Otrexup and Rasuvo (subcutaneous auto-injectors) are for rheumatoid arthritis, pJIA and psoriasis only, and are not for cancer.

See full Methotrexate drug information
Keep checking

Other Drugs & Equol

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

0Major
58Moderate
75Minor
2,696No known interaction
58 Moderate 75 Minor 2,696 No interaction
Moderate

58 interactions

Minor

75 interactions

Showing 60 of 75 minor interactions — see all 75 on the Equol page.

No interaction 2,696 drugs checked — show the list

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

Showing the 60 most looked-up of 2,696 medications checked with no known interaction — see the full Equol list.

See the full Equol interactions page
See every supplement checked against Methotrexate, ranked by severity
Evidence & sources

Equol References

The 7 references that drive our Equol monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. Aso T. Equol improves menopausal symptoms in Japanese women. J Nutr 2010;140:1386S-9S. PubMed
  2. Jenks BH, Iwashita S, Nakagawa Y, et al. A pilot study on the effects of S-equol compared to soy isoflavones on menopausal hot flash frequency. J Womens Health (Larchmt) 2012;21:674-82.
  3. Oyama A, Ueno T, Uchiyama S, et al. The effects of natural S-equol supplementation on skin aging in postmenopausal women: a pilot randomized placebo-controlled trial. Menopause 2012;19:202-10. PubMed
  4. Gimenez I, Lou M, Vargas F, et al. Renal and vascular actions of equol in the rat. J Hypertens 1997;15:1303-8. PubMed
  5. Martin ME, Haouriqui M, Pelissero C, et al. Interactions between phytoestrogens and human sex steroid binding protein. Life Sci 1996;58:429-36. PubMed
  6. Martinez RM, Gimenez I, Lou JM, et al. Soy isoflavonoids exhibit in vitro biological activities of loop diuretics. Am J Clin Nutr 1998;68:1354S-57S. PubMed
  7. Alda JO, Mayoral JA, Lou M, et al. Purification and chemical characterization of a potent inhibitor of the Na-K-Cl cotransport system in rat urine. Biochem Biophys Res Commun 1996;221:279-85. PubMed

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Equol and Methotrexate Together: Common Questions

Is it safe to take Equol with Methotrexate?
We do not list a known interaction between Equol and Methotrexate. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Are Equol and Methotrexate used for the same thing?
They overlap in purpose, which usually means the real question is whether you need both rather than whether they are safe together. This page lists the shared uses and how strong the evidence is for Equol in each. That is a conversation for your prescriber, especially if Methotrexate is being adjusted to a target.
How was the Equol and Methotrexate combination checked?
Interactions in our licensed database are recorded against drug classes. Methotrexate is filed under 6 classifications, and Equol has documented interactions with 4 drug classes — none of Methotrexate's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does Equol interact with any other medications?
Yes. Equol has 133 documented drug interactions in our database — Methotrexate is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Methotrexate interact with any supplements?
Yes. Methotrexate has documented interactions with 82 supplements in our database — Equol is not one of them. The Methotrexate interaction page linked on this page lists every one, ranked by severity.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Where next

Keep Exploring

Equol monograph Uses, safety profile, and every drug interaction in one place Methotrexate drug information The full plain-English guide to this medication Methotrexate supplement interactions Every supplement checked against Methotrexate, 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 References The 7 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Methotrexate and Equol?

Our pharmacists answer your medication & supplement questions — free.

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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.