Drug & supplement interaction

Malic Acid + Methotrexate

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

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 13, 2026
The bottom line No known interaction

We found no known interaction between Malic Acid 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. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

Malic Acid 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 Malic Acid 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.

Malic Acid safety at a glance

Malic Acid overall Use caution Generally well tolerated in food amounts, but supplement safety is not well studied.
Pregnancy Likely Safe When used orally in amounts commonly found in foods. There is insufficient reliable information available about the safety of using malic acid in medicinal amou... Read the full pregnancy detail
Breastfeeding Likely Safe When used orally in amounts commonly found in foods. There is insufficient reliable information available about the safety of using malic acid in medicinal amou... Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center) — the full detail is in the Special populations card below. Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Methotrexate and Malic Acid? 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. Malic Acid has documented interactions with 1 drug class — the most serious being antihypertensive drugs (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

Malic Acid Does Interact With Other Medications

Malic Acid has 172 moderate 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 172 No known interaction 2,658 (incl. Methotrexate)
Taking anything else?

Check Another of Your Medications Against Malic Acid

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

What to actually watch for

No Interaction Found — But Data Suggests Malic Acid and Methotrexate May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do. One of them is worth acting on rather than waiting out — marked below.

  • Hives Worth acting on Additional detail

    Malic Acid

    “Topically, malic acid may cause moderate to strong skin irritation and peeling. In patients first patch tested with malic acid, next instructed to avoid foods containing malic or citric acid, and then challenged with foods containing high amounts of malic and citric acid, skin reactions including immediate hives and delayed contact dermatitis occurred.”

    Malic Acid · Natural Medicines adverse-effect record, reported in dermatitis.

    3 sources cited
    1. 26968. Fiume, Z. Final report on the safety assessment of malic acid and sodium malate. Int J Toxicol 2001;20 Suppl 1:47-55. PubMed
    2. 95564. Chiriac A, Brzezinski P. Topical malic acid in combination with citric acid: an option to treat recalcitrant warts. Dermatol Ther. 2015;28(6):336-8. PubMed
    3. 95595. Amended Safety Assessment of Malic Acid and Sodium Malate as Used in Cosmetics. Cosmetic Ingredient Review Expert Panel. Updated May 19, 2017. http://www.cir-safety.org/sites/default/files/malic%20acid.pdf. Accessed January 24, 2018.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • Nausea / Diarrhea reported in 5.9% of FDA reports for Methotrexate Additional detail

    Malic Acid

    “Orally, diarrhea and nausea have been reported for patients taking a specific combination product (Super Malic) containing malic acid1200 mg and magnesium 300 mg twice daily. However, it is unclear if the adverse effect is due to malic acid, since it is known that magnesium can have a laxative effect at this dose.”

    Malic Acid · Natural Medicines adverse-effect record, reported in diarrhea.

    1 source cited
    1. 3262. Russell IJ, Michalek JE, Flechas JD, Abraham GE. Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study. J Rheumatol 1995;22:953-8.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate, and in voluntary FDA adverse-event reports. Read the label on DailyMed ›

  • A skin rash Additional detail

    Malic Acid

    Recorded for Malic Acid in the same Natural Medicines adverse-effect record shown under Hives above.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

Reported for Malic Acid but not commonly for Methotrexate: eye irritation or redness.

Effects for Methotrexate come from the ADVERSE REACTIONS section of its FDA label; effects for Malic Acid come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 489,806 voluntary FDA FAERS reports for Methotrexate that mention that effect — a reporting proportion, not an incidence rate and not evidence the drug caused it. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

Special populations

Malic Acid in Pregnancy & Breastfeeding

Pregnancy And Lactation Likely Safe

When used orally in amounts commonly found in foods. There is insufficient reliable information available about the safety of using malic acid in medicinal amounts during pregnancy or lactation.

DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.© 2026 Therapeutic Research Center

Overlapping uses

What Methotrexate Is Prescribed For, and What Malic Acid 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. Malic Acid 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 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.

Malic Acid has been studied for:

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

    Malic Acid for psoriasis

    Although there has been interest in using topical malic acid for psoriasis, there is insufficient reliable information about the clinical effects of malic acid 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 Malic Acid for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

From our Q&A

Questions About Malic Acid 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 Malic Acid 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 Malic Acid 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 Malic Acid as Part of a Dietary Supplement Product? Check It for Interactions

We hold 678 real supplement products containing Malic Acid, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Malic Acid. Even though Malic Acid itself has no known interaction with Methotrexate, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Malic Acid 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 Malic Acid
Top 25%

#206 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.

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 Malic Acid reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Malic Acid 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 Malic Acid

What is Malic Acid?

Malic Acid
  • Fibromyalgia symptoms
  • Muscle pain and fatigue
  • Dry mouth (used in some lozenges)
  • Skin exfoliation (topical)
  • Flavoring and food additive

Malic acid is a natural acid found in apples and other fruits, often combined with magnesium in supplements marketed for fibromyalgia and muscle pain. The evidence for its health benefits is weak and limited, and it is mostly used as a food flavoring. It is generally well tolerated in food amounts, but talk to your pharmacist or doctor before using supplement doses.

Naturally found in fruits like apples; also made synthetically · Tablets, capsules, powders, combination products (often with magnesium), topical skincare products, and as a food additive

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

Malic Acid: dosing

There is no official or standardized dose of malic acid for any health condition. Supplement products vary widely, especially those that combine malic acid with magnesium.The best approach is to follow the directions on the product label and not exceed the recommended amount.

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

Read the full Malic Acid 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.

Most-Reported Side Effects for Methotrexate

From FAERS, the FDA’s public side-effect reporting system (489,806 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Rheumatoid arthritis 42,798 reports
Arthralgia 40,830 reports
Fatigue 33,049 reports
Nausea 28,999 reports
Joint swelling 25,026 reports
See full Methotrexate drug information
Keep checking

Other Drugs & Malic Acid

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

0Major
172Moderate
0Minor
2,657No known interaction
172 Moderate 2,657 No interaction
Moderate

172 interactions

Showing 60 of 172 moderate interactions — see all 172 on the Malic Acid page.

No interaction 2,657 drugs checked — show the list

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

Showing the 60 most looked-up of 2,657 medications checked with no known interaction — see the full Malic Acid list.

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

Malic Acid References

The 7 references that drive our Malic Acid 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. Russell IJ, Michalek JE, Flechas JD, Abraham GE. Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study. J Rheumatol 1995;22:953-8.
  2. Fiume, Z. Final report on the safety assessment of malic acid and sodium malate. Int J Toxicol 2001;20 Suppl 1:47-55. PubMed
  3. Electronic Code of Federal Regulations. Title 21. Part 184 - Direct Food Substances Affirmed as Generally Recognized as Safe. Available at: http://www.ecfr.gov/cgi-bin/text-idx?c=ecfr&sid=786bafc6f6343634fbf79fcdca7061e1&rgn=div5&view=text&node=21:3.0.1.1
  4. Saleem R, Ahmad M, Naz A, et al. Hypotensive and toxicological study of citric acid and other constituents from Tagetes patula roots. Arch Pharm Res 2004;27(10):1037-42.
  5. Chiriac A, Brzezinski P. Topical malic acid in combination with citric acid: an option to treat recalcitrant warts. Dermatol Ther. 2015;28(6):336-8. PubMed
  6. CFR - Code of Federal Regulations Title 21 SUBCHAPTER B. 184.1069 Malic Acid. Food and Drug Administration Department Of Health And Human Services. Updated April 1, 2017. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1069.
  7. Amended Safety Assessment of Malic Acid and Sodium Malate as Used in Cosmetics. Cosmetic Ingredient Review Expert Panel. Updated May 19, 2017. http://www.cir-safety.org/sites/default/files/malic%20acid.pdf. Accessed January 24, 2018.

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 Malic Acid and Methotrexate Together: Common Questions

Is it safe to take Malic Acid with Methotrexate?
We do not list a known interaction between Malic Acid 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.
Do Malic Acid and Methotrexate have any of the same side effects?
Yes — our sources link each of them separately to 4 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
Are Malic Acid 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 Malic Acid in each. That is a conversation for your prescriber, especially if Methotrexate is being adjusted to a target.
How was the Malic Acid and Methotrexate combination checked?
Interactions in our licensed database are recorded against drug classes. Methotrexate is filed under 6 classifications, and Malic Acid has documented interactions with 1 drug class — 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 Malic Acid interact with any other medications?
Yes. Malic Acid has 172 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 — Malic Acid 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

Malic Acid 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 Malic Acid?

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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.