Medication interaction hub

What Supplements Interact with Methotrexate?

Methotrexate brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex, Xatmep. Every interaction below applies to the brands too.

82 Interactions 7 Major 60 Moderate 15 Minor
Curated & coded by · Clinical Pharmacist · Updated September 24, 2026

Drug–supplement interaction data sourced from Natural Medicines Pro, the licensed clinical database from TRC Healthcare / Therapeutic Research, with additional analysis by the HelloPharmacist Pharmacist Team. Our sources · Editorial policy

What is this page for?

One answer, for one medication: what supplements and herbal products interact with Methotrexate? Every vitamin, herb, and supplement ingredient we’ve checked against it is on this page, ranked by severity, each linking to the full report for that exact pair.

This page covers supplement interactions only — to check Methotrexate against your other medications, use the drug–drug interaction checker. Educational information from our licensed clinical databases, not medical advice. Our editorial policy

HelloPharmacist Bottom Line
Our Pharmacist Explains
What is this? The interaction data in the HelloPharmacist supplement database is licensed from Natural Medicines Pro by TRC Healthcare (Therapeutic Research). HelloPharmacist pharmacists often add our own analysis and context on top of that licensed data — such as this Bottom Line summary and the notes on individual interaction pages — and any such commentary is noted as ours.

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 with real care. Seven entries are rated major, and not all of them are exotic: grapefruit and apple juice can block the gut transporter that moves oral methotrexate into the bloodstream, cutting how much of a dose actually gets absorbed.

The remaining 60 moderate and 15 minor entries mostly echo those same two patterns with less force, adding liver strain or interfering with absorption. Folic acid is the outlier worth understanding. Many people take it alongside methotrexate for arthritis, but when methotrexate is treating cancer, folic acid may blunt its effect, a question worth putting directly to your pharmacist.

— , Clinical Pharmacist · July 18, 2026

Major 7 Moderate 60 Minor 15 No known interaction 1,370

This box checks one ingredient at a time (like turmeric or magnesium). Taking a supplement product with a whole label of ingredients? Search the product instead — we check every ingredient on it ↓

Most Viewed Ingredient Interactions

Methotrexate: Top Interactions at a Glance

The Methotrexate supplement & herbal interactions people checked most in the last 24 hours, colored by severity. Tap any ingredient to open the full report for that pair.

Showing the 12 highest-ranked of 82 interacting ingredients — plus 1,370 more checked with no known interaction. See the complete ranked list.

Start here

The Most-Checked Methotrexate Combinations Today

The Methotrexate + supplement pages people viewed most in the last 24 hours (resets at midnight). Open any card for the full report.

Major Likelihood Probable Beer + Methotrexatei

Concomitant use of alcohol with hepatotoxic drugs may increase the risk of hepatotoxicity.

Read the full interaction Major Likelihood Probable Wine + Methotrexatei

Concomitant use of alcohol with hepatotoxic drugs may increase the risk of hepatotoxicity.

Read the full interaction Moderate Likelihood Probable Coffee Charcoal + Methotrexatei

Coffee charcoal can reduce the absorption of orally administered drugs and should be separated from oral drug administration by at least two hours.

Read the full interaction Major Likelihood Likely Apple + Methotrexatei

Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of OATP substrates.

Read the full interaction Major Likelihood Likely Grapefruit + Methotrexatei

Grapefruit juice can decrease levels of drugs that are substrates of OATP.

Read the full interaction Major Likelihood Likely Siberian Cocklebur + Methotrexatei

Siberian cocklebur can adversely affect the liver.

Read the full interaction
The complete list

Every Supplement Checked Against Methotrexate

All 1,452 ingredients in our database, ranked by severity — 82 with a Methotrexate interaction on file and 1,370 with none found. Filter by severity or search any ingredient; hover the for what each ingredient is.

Looking for an interaction with a specific supplement product? Search products instead ↓

Straight answers

Can You Take It With Methotrexate?

One-line answers, one card per combination — scroll through today’s 20 and tap any card for the full report. A different set rotates in daily until every combination has had its turn.

Can you take Beer with Methotrexate?

Major Use real caution — this is a major-rated interaction, generally best avoided or used only under close supervision. Concomitant use of alcohol with hepatotoxic drugs may increase the risk of hepatotoxicity.

Full Beer + Methotrexate answer

Can you take Wine with Methotrexate?

Major Use real caution — this is a major-rated interaction, generally best avoided or used only under close supervision. Concomitant use of alcohol with hepatotoxic drugs may increase the risk of hepatotoxicity.

Full Wine + Methotrexate answer

Can you take Coffee Charcoal with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. Coffee charcoal can reduce the absorption of orally administered drugs and should be separated from oral drug administration by at least two...

Full Coffee Charcoal + Methotrexate answer

Can you take Apple with Methotrexate?

Major Use real caution — this is a major-rated interaction, generally best avoided or used only under close supervision. Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of OATP substrates.

Full Apple + Methotrexate answer

Can you take Padang Cassia with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. There is some concern that ingesting large amounts of Padang cassia might cause hepatotoxicity in some people.

Full Padang Cassia + Methotrexate answer

Can you take Quercetin with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. Theoretically, concomitant use might increase the effects and adverse effects of OAT3 substrates.

Full Quercetin + Methotrexate answer

Can you take Rauwolscine with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. Theoretically, taking rauwolscine with seizure threshold lowering drugs might increase the risk of adverse convulsant effects.

Full Rauwolscine + Methotrexate answer

Can you take Red Clover with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. Theoretically, red clover might increase the risk of methotrexate toxicity.

Full Red Clover + Methotrexate answer

Can you take Red Yeast Rice with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. Theoretically, concomitant use might increase the risk of liver damage.

Full Red Yeast Rice + Methotrexate answer

Can you take Rhubarb with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. Theoretically, concomitant use of rhubarb with potentially hepatotoxic drugs might increase the risk of developing liver damage.

Full Rhubarb + Methotrexate answer

Can you take Saigon Cinnamon with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. Theoretically, Saigon cinnamon might cause additive effects when used with hepatotoxic drugs.

Full Saigon Cinnamon + Methotrexate answer

Can you take Slippery Elm with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. Theoretically, slippery elm may slow the absorption and reduce serum levels of oral drugs.

Full Slippery Elm + Methotrexate answer

Can you take Sorrel with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. Sorrel might reduce the effectiveness of OATP substrates by reducing their absorption from the gut.

Full Sorrel + Methotrexate answer

Can you take Spearmint with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. Theoretically, high doses of spearmint might increase the risk of liver damage when taken with hepatotoxic drugs.

Full Spearmint + Methotrexate answer

Can you take Sweet Annie with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. Theoretically, concomitant use might have additive adverse hepatotoxic effects.

Full Sweet Annie + Methotrexate answer

Can you take Sweet Clover with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. Theoretically, concomitant use of sweet clover with hepatoxic drugs might increase the risk of hepatotoxicity.

Full Sweet Clover + Methotrexate answer

Can you take Syrian Rue with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. Theoretically, high doses of Syrian rue might increase the risk of liver damage when taken with hepatotoxic drugs.

Full Syrian Rue + Methotrexate answer

Can you take Testolone with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. Theoretically, concomitant use might have additive hepatotoxic effects.

Full Testolone + Methotrexate answer

Can you take Theaflavin with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. In vitro, theaflavin inhibits organic anion-transporting polypeptide (OATP)2B1.

Full Theaflavin + Methotrexate answer

Can you take Thuja with Methotrexate?

Moderate Possibly, but carefully — this moderate-rated combination may need monitoring, a dose adjustment, or separated timing. Thuja products can contains significant amounts of thujone, a neurotoxin.

Full Thuja + Methotrexate answer
Read the list like a pharmacist

What Severity, Likelihood & Evidence Mean

Severity — How Serious It Can Be

  • Major. Clinically significant; generally best avoided, or used only under direct professional supervision.
  • Moderate. May need monitoring, a dose adjustment, or separating the times you take each one.
  • Minor. Generally not clinically significant, but still worth noting and mentioning to your pharmacist.
  • No known interaction. Checked against our sources with nothing documented — not the same as proven safety.

Likelihood — How Well It’s Documented

  • Likely. Well-controlled human studies have demonstrated the likely existence of this interaction
  • Probable. Interaction 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.
  • Possible. 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
  • Unlikely. Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans.

Where This Data Comes From

  • Interaction records are evidence-graded and sourced from the Natural Medicines database (TRC Healthcare), the same reference used by pharmacists and hospitals.
  • Each entry links to a full report with the clinical detail, likelihood, evidence level, and citations for that exact combination.
  • Content is reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

How Does Our Interaction Checker Work?

Behind every verdict on this page is a category system. Our source database doesn’t document supplement interactions drug-by-drug — it documents them against groups of medications that behave the same way (for example, “drugs processed by the CYP3A4 liver enzyme” or “blood-thinning medications”).

So the check works in three steps: (1) Methotrexate is classified into the pharmacology categories it belongs to, (2) every supplement interaction documented against any of those categories is inherited by Methotrexate, and (3) each ingredient keeps its own severity, likelihood, and evidence grades from the underlying record. That’s why one supplement can carry several records for one drug — it may interact through more than one category.

Methotrexate sits in 6 interaction categories. Open any one to see what the group means:

Hepatotoxic Drugs 38 ingredients

Medications with known liver considerations. Supplements that can stress the liver add to the load.

38 of the supplement ingredients on this page reach Methotrexate through this category.

Oral Drugs 17 ingredients

A pharmacology grouping from our source database: medications in this group share a property that certain supplements are known to interact with, so an interaction documented for the group applies to every drug in it.

17 of the supplement ingredients on this page reach Methotrexate through this category.

Organic Anion-Transporting Polypeptide Substrates (Oatp) 17 ingredients

A pharmacology grouping from our source database: medications in this group share a property that certain supplements are known to interact with, so an interaction documented for the group applies to every drug in it.

17 of the supplement ingredients on this page reach Methotrexate through this category.

Methotrexate (Trexall, Others) 6 ingredients

A pharmacology grouping from our source database: medications in this group share a property that certain supplements are known to interact with, so an interaction documented for the group applies to every drug in it.

6 of the supplement ingredients on this page reach Methotrexate through this category.

Seizure Threshold Lowering Drugs 6 ingredients

A pharmacology grouping from our source database: medications in this group share a property that certain supplements are known to interact with, so an interaction documented for the group applies to every drug in it.

6 of the supplement ingredients on this page reach Methotrexate through this category.

Organic Anion Transporter 3 (Oat3) Substrates 4 ingredients

A pharmacology grouping from our source database: medications in this group share a property that certain supplements are known to interact with, so an interaction documented for the group applies to every drug in it.

4 of the supplement ingredients on this page reach Methotrexate through this category.

About Methotrexate

Methotrexate is an antimetabolite used to treat severe psoriasis, rheumatoid arthritis, and certain cancers.

Generic name: Methotrexate  ·  Brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex, Xatmep.

See the full Methotrexate drug information

Related: does Methotrexate deplete any nutrients?

Methotrexate has 4 reported nutrient associations in the research literature — see the Methotrexate nutrient depletion report.

Check a real product

Take a Supplement Product? Check the Whole Bottle Against Methotrexate

Most supplements are combination products — and the interaction may come from an ingredient you didn’t buy it for. Search any product below (or scan its label) and we’ll check every ingredient on it against Methotrexate.

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Grounded search over our product catalog — every verdict comes from our interaction database, never AI guesswork. How we use AI

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Pharmacist Counseling Corner

Methotrexate & Supplements: Common Questions

What supplements interact with Methotrexate?
Our database currently documents 82 ingredients with a known Methotrexate interaction (7 major, 60 moderate, 15 minor). The practical move: scan the major group first, then look up the exact supplements you take rather than reading all 82. The highest-ranked right now: Apple, Grapefruit, Siberian Cocklebur.
Which Methotrexate supplement interactions are the most serious?
Focus on the major group: Apple, Grapefruit, Siberian Cocklebur, Sweet Orange and Activated Charcoal, among others. A major rating means the combination can be clinically significant, not that harm is guaranteed — but it's exactly the kind of thing to run past your pharmacist before your next dose, not after. Jump to the ranked list.
Can I take vitamins or supplements while on Methotrexate?
Plenty of supplements coexist fine with Methotrexate; a shorter list does not. Rather than memorizing it, check the specific ingredients on your labels — the ranked list above covers every one we've checked, and multi-ingredient products can be checked label-by-label with our scanner. Try the label scanner or the interaction checker.
Do brands like Rheumatrex have the same supplement interactions as Methotrexate?
Yes — Rheumatrex, Otrexup, Rasuvo, Reditrex, Xatmep all contain Methotrexate, so everything on this page applies to them equally. Interactions belong to the active drug, never to the brand on the box; the same is true of generics.
Where do these interaction ratings come from?
Every rating comes from the Natural Medicines database — the same evidence-graded reference pharmacists and hospitals use — and each interaction carries three separate grades: severity (how bad it can be), likelihood (how well it's documented in studies and case reports), and an evidence level. Our pharmacists review the content; we never let an AI decide an interaction. See how to read the ratings and our editorial policy.
Does Methotrexate deplete any vitamins or nutrients?
It might — Methotrexate has 4 reported nutrient-depletion associations in the research literature, which is a different question from interactions: instead of a supplement changing the drug, the drug may lower a nutrient over time. See the Methotrexate nutrient depletion report for the specifics and what to discuss with your pharmacist.
What about Methotrexate and my other medications?
This page covers Methotrexate against supplements and herbal ingredients. Checking Methotrexate against your other prescription or OTC medications is a different tool — our drug interaction checker covers that side. Head to the drug–drug interaction checker, or read the full Methotrexate drug information.

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

Where next

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Sourcing

Where This Data Comes From — and Why You Can Trust It

🧪 Licensed clinical database

Every interaction verdict on this page comes from Natural Medicines Pro (TRC Healthcare / Therapeutic Research) — the same evidence-graded reference used by pharmacists and hospitals. We license this data directly; we do not scrape it, and no AI invents an interaction.

🧑‍⚕️ Pharmacist review

This page is curated and coded by , Clinical Pharmacist, with additional analysis by the HelloPharmacist Pharmacist Team. Editorial commentary is ours; the licensed interaction records are shown as sourced.

🔄 Kept current

Our interaction database refreshes on a weekly cycle, and this page re-checks the live database every time it’s rebuilt — what you see reflects the database as of September 24, 2026.

🔍 Full transparency

How every dataset on this site is sourced, licensed, and updated is documented publicly: our data sources · editorial policy · how we use AI.

Educational information, not medical advice. An interaction being on file does not mean it will happen to you — and absence of one is not proof of safety. Never start or stop a medication or supplement without talking to your pharmacist or doctor.