Drug & supplement interaction

Glutamine + 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 Glutamine 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

Glutamine 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 Glutamine 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.

Glutamine safety at a glance

Glutamine overall Use caution Generally well tolerated in healthy adults, but people with kidney or liver disease should use it only under medical supervision.
Pregnancy Likely Safe When consumed in amounts commonly found in foods. There is insufficient reliable information available about the safety of glutamine when used in larger amounts... Read the full pregnancy detail
Breastfeeding Likely Safe When consumed in amounts commonly found in foods. There is insufficient reliable information available about the safety of glutamine when used in larger amounts... 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 Glutamine? 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. Glutamine has documented interactions with 1 drug class — the most serious being anticonvulsants (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

Glutamine Does Interact With Other Medications

Glutamine has 50 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 50 No known interaction 2,780 (incl. Methotrexate)
Taking anything else?

Check Another of Your Medications Against Glutamine

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

What to actually watch for

No Interaction Found — But Data Suggests Glutamine 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.

  • Chest pain Worth acting on Additional detail

    Glutamine

    “Orally, glutamine 30 grams daily has been associated with cases of musculoskeletal pain and non-cardiac chest pain in clinical trials for patients with sickle cell disease.”

    Glutamine · Natural Medicines adverse-effect record, reported in pain.

    1 source cited
    1. 99414. Niihara Y, Miller ST, Kanter J, et al. A Phase 3 Trial of l-Glutamine in Sickle Cell Disease. N Engl J Med 2018;379(3):226-35. doi: 10.1056/NEJMoa1715971.

    Methotrexate

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

  • Cough Additional detail

    Glutamine

    “Orally, glutamine has been associated with cough when a powdered formulation is used. It is unclear if this was due to accidental inhalation. One case of a burning sensation and one case of hypersplenism has been reported in a patient taking glutamine 5-15 grams twice daily orally for up to 1 year.”

    Glutamine · Natural Medicines adverse-effect record, reported in cough.

    1 source cited
    1. 96520. Endari (l-glutamine) [package insert]. Torrance, CA: Emmaus Medical,Inc; 2017.

    Methotrexate

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

  • Muscle pain Additional detail

    Glutamine

    Recorded for Glutamine in the same Natural Medicines adverse-effect record shown under Cough above.

    Methotrexate

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

  • Stomach upset / Stomach pain Additional detail

    Glutamine

    “Orally, glutamine has been associated with belching, bloating, constipation, flatulence, nausea, vomiting, diarrhea, and gastrointestinal (GI) pain. Nausea, vomiting, constipation, diarrhea, and GI pain have been reported in clinical trials using high-dose glutamine 10-30 grams (0.3 grams/kg) in two divided doses daily to treat sickle cell disease.”

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

    3 sources cited
    1. 99414. Niihara Y, Miller ST, Kanter J, et al. A Phase 3 Trial of l-Glutamine in Sickle Cell Disease. N Engl J Med 2018;379(3):226-35. doi: 10.1056/NEJMoa1715971.
    2. 96520. Endari (l-glutamine) [package insert]. Torrance, CA: Emmaus Medical,Inc; 2017.
    3. 105013. Ogden HB, Child RB, Fallowfield JL, et al. Gastrointestinal Tolerance of Low, Medium and High Dose Acute Oral l-Glutamine Supplementation in Healthy Adults: A Pilot Study. Nutrients. 2020;12(10):2953. PubMed

    Methotrexate

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

  • Dizziness Additional detail

    Glutamine

    “Orally, glutamine has been associated with dizziness and headache. A single case of dizziness has been reported in a patient treated with oral glutamine 0.5 grams/kg. However, the symptom resolved after reducing the dose to 0.25 grams/kg. Mania and hypomania have been reported in 2 patients with bipolar disorder taking commercially purchased glutamine up to 4 grams daily.”

    Glutamine · Natural Medicines adverse-effect record, reported in bipolar disorder.

    3 sources cited
    1. 91356. Laviano A, Molfino A, Lacaria MT, Canelli A, De Leo S, Preziosa I, Rossi Fanelli F. Glutamine supplementation favors weight loss in nondieting obese female patients. A pilot study. Eur J Clin Nutr. 2014 Nov;68(11):1264-6. PubMed
    2. 7291. Mebane AH. L-Glutamine and mania. Am J Psychiatry 984;141:1302-3.
    3. 7293. Garlick PJ. Assessment of the safety of glutamine and other amino acids. J Nutr 2001;131:2556S-61S.. PubMed

    Methotrexate

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

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

    Glutamine

    Recorded for Glutamine in the same Natural Medicines adverse-effect record shown under Cough above.

    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 ›

  • Headache Additional detail

    Glutamine

    Recorded for Glutamine in the same Natural Medicines adverse-effect record shown under Cough above.

    Methotrexate

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

Reported for Glutamine but not commonly for Methotrexate: constipation, bloating or gas, heartburn and mania or an unusually elevated mood.

Effects for Methotrexate come from the ADVERSE REACTIONS section of its FDA label; effects for Glutamine 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

Glutamine in Pregnancy & Breastfeeding

Pregnancy And Lactation Likely Safe

When consumed in amounts commonly found in foods. There is insufficient reliable information available about the safety of glutamine when used in larger amounts as medicine 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 Glutamine 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. Glutamine 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.

Glutamine has been studied for:

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

    Glutamine for lung cancer

    It is unclear if oral glutamine improves survival in patients with advanced lung cancer.

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 Glutamine for the same health topic, tell your prescriber, especially if the medicine is being adjusted to a target.

From our Q&A

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

We hold 5,253 real supplement products containing Glutamine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Glutamine. Even though Glutamine 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 Glutamine 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 Glutamine
Top 5%

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

What is Glutamine?

  • Muscle recovery and sports performance
  • Gut health and 'leaky gut'
  • Recovery from severe illness or injury
  • Immune support
  • Side effects of cancer treatment (mucositis)
  • Sickle cell disease (prescription form)

Glutamine is the most abundant amino acid in the body and is usually made in your muscles. A prescription form is FDA-approved to help reduce sickle cell disease complications, but for most popular uses such as muscle building, gut health, and immunity the evidence is limited or mixed. It is generally well tolerated in healthy people, but anyone with serious liver or kidney problems should check with a doctor first.

Amino acid (made in the body and found in protein-rich foods) · Powder, capsules, tablets, prescription oral powder (for sickle cell disease)

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

Glutamine: dosing

There is no single standardized dose of glutamine for general supplement use, and the right amount depends on why it is being used. Doses studied in research and used in hospitals vary widely and are often individualized.The prescription product for sickle cell disease is dosed by body weight and prescribed by a doctor, so it should only be used as directed by your healthcare team.For over-the-counter products, follow the directions on the label and do not exceed the recommended amount.

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

Read the full Glutamine 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 & Glutamine

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

0Major
50Moderate
0Minor
2,779No known interaction
50 Moderate 2,779 No interaction
Moderate

50 interactions

No interaction 2,779 drugs checked — show the list

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

Showing the 60 most looked-up of 2,779 medications checked with no known interaction — see the full Glutamine list.

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

Glutamine References

The 11 references that drive our Glutamine 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. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev 1999;4:239-48..
  2. Bozzetti F, Biganzoli L, Gavazzi C, et al. Glutamine supplementation in cancer patients receiving chemotherapy: a double-blind randomized study. Nutrition 1997;13:748-51.. PubMed
  3. Mebane AH. L-Glutamine and mania. Am J Psychiatry 984;141:1302-3.
  4. Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr 2000;130:1007S-15S.. PubMed
  5. Garlick PJ. Assessment of the safety of glutamine and other amino acids. J Nutr 2001;131:2556S-61S.. PubMed
  6. Chapman AG. Glutamate and epilepsy. J Nutr 2000;130:1043S-5S.. PubMed
  7. Ziegler TR. Glutamine supplementation in cancer patients receiving bone marrow transplantation and high dose chemotherapy. J Nutr 2001;131:2578S-84S.. PubMed
  8. Laviano A, Molfino A, Lacaria MT, Canelli A, De Leo S, Preziosa I, Rossi Fanelli F. Glutamine supplementation favors weight loss in nondieting obese female patients. A pilot study. Eur J Clin Nutr. 2014 Nov;68(11):1264-6. PubMed
  9. Endari (l-glutamine) [package insert]. Torrance, CA: Emmaus Medical,Inc; 2017.
  10. Niihara Y, Miller ST, Kanter J, et al. A Phase 3 Trial of l-Glutamine in Sickle Cell Disease. N Engl J Med 2018;379(3):226-35. doi: 10.1056/NEJMoa1715971.
  11. Ogden HB, Child RB, Fallowfield JL, et al. Gastrointestinal Tolerance of Low, Medium and High Dose Acute Oral l-Glutamine Supplementation in Healthy Adults: A Pilot Study. Nutrients. 2020;12(10):2953. 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 Glutamine and Methotrexate Together: Common Questions

Is it safe to take Glutamine with Methotrexate?
We do not list a known interaction between Glutamine 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 Glutamine and Methotrexate have any of the same side effects?
Yes — our sources link each of them separately to 10 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 Glutamine 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 Glutamine in each. That is a conversation for your prescriber, especially if Methotrexate is being adjusted to a target.
How was the Glutamine and Methotrexate combination checked?
Interactions in our licensed database are recorded against drug classes. Methotrexate is filed under 6 classifications, and Glutamine 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 Glutamine interact with any other medications?
Yes. Glutamine has 50 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 — Glutamine 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

Glutamine 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 11 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Methotrexate and Glutamine?

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.