Drug & supplement interaction

L-tryptophan + 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 L-tryptophan 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.

Know someone taking this? Share
Facebook Post Reddit Email
On this page
Interaction report

L-tryptophan 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 L-tryptophan 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.

L-tryptophan safety at a glance

L-tryptophan overall Use caution May cause mild side effects and has a past history of a contaminated-product safety scare.
Pregnancy Likely Safe When used orally in amounts commonly found in foods. 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 larger medicinal amounts; avoid us... 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 L-tryptophan? 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. L-tryptophan has documented interactions with 2 drug classes — the most serious being cns depressants (major) and serotonergic 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

L-tryptophan Does Interact With Other Medications

L-tryptophan has 248 major, 146 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.

Major 248 Moderate 146 No known interaction 2,436 (incl. Methotrexate)
Taking anything else?

Check Another of Your Medications Against L-tryptophan

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

What to actually watch for

No Interaction Found — But Data Suggests L-tryptophan 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.

  • Hair loss Additional detail

    L-tryptophan

    “Orally, L-tryptophan can cause headache, lightheadedness, and ataxia.

    In 1989, more than 1500 cases of the neurological disorder EMS were associated with oral L-tryptophan use in the US. About 95% of all EMS cases were traced to contaminated L-tryptophan produced by a single manufacturer in Japan. In 1990, L-tryptophan was recalled in the U.S.”

    L-tryptophan · Natural Medicines adverse-effect record, reported in alopecia.

    6 sources cited
    1. 10853. Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev 2002;(1):CD003198. PubMed
    2. 99884. Ullrich SS, Fitzgerald PCE, Giesbertz P, Steinert RE, Horowitz M, Feinle-Bisset C. Effects of intragastric administration of tryptophan on the blood glucose response to a nutrient drink and energy intake, in lean and obese men. Nutrients 2018;10(4). pii: PubMed
    3. 8054. Philen RM, Hill RH, Flanders WD, et al. Tryptophan contaminants associated with eosinophilia-myalgia syndrome. Am J Epidemiol 1993;138:154-9. PubMed
    4. 10288. Klein R, Berg PA. A comparative study on antibodies to nucleoli and 5-hydroxytryptamine in patients with fibromyalgia syndrome and tryptophan-induced eosinophilia-myalgia syndrome. Clin Investig 1994;72:541-9.. PubMed
    5. 10289. Simat TJ, Kleeberg KK, Muller B, Sierts A. Synthesis, formation, and occurrence of contaminants in biotechnologically manufactured L-tryptophan. Adv Exp Med Biol 1999;467:469-80.. PubMed
    6. 11475. Horwitz RI, Daniels SR. Bias or biology: evaluating the epidemiologic studies of L-tryptophan and the eosinophilia-myalgia syndrome. J Rheumatol Suppl 1996;46:60-72.

    “Orally, L-tryptophan has been associated with eosinophilia-myalgia syndrome (EMS), which can include dermatological symptoms such as sclerodermiform skin changes, alopecia, and rash.”

    L-tryptophan · Natural Medicines adverse-effect record, reported in alopecia.

    2 sources cited
    1. 8053. Sullivan EA, Kamb ML, Jones JL, et al. The natural history of eosinophilia-myalgia syndrome in a tryptophan-exposed cohort in South Carolina. Arch Intern Med 1996;156:973-9. DOI
    2. 11477. Mayeno AN, Gleich GJ. The eosinophilia-myalgia syndrome: lessons from Germany. Mayo Clin Proc 1994;69:702-4. PubMed

    Methotrexate

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

  • Cough Additional detail

    L-tryptophan

    “Orally, L-tryptophan has been associated with eosinophilia-myalgia syndrome (EMS), which can include respiratory symptoms such as dyspnea and cough.”

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

    2 sources cited
    1. 8053. Sullivan EA, Kamb ML, Jones JL, et al. The natural history of eosinophilia-myalgia syndrome in a tryptophan-exposed cohort in South Carolina. Arch Intern Med 1996;156:973-9. DOI
    2. 11477. Mayeno AN, Gleich GJ. The eosinophilia-myalgia syndrome: lessons from Germany. Mayo Clin Proc 1994;69:702-4. PubMed

    Methotrexate

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

  • Drowsiness Additional detail

    L-tryptophan

    “Orally, L-tryptophan is generally well tolerated.

    Most Common Adverse Effects:

    Orally: Belching, diarrhea, drowsiness, dry mouth, flatulence, headache, heartburn, lightheadedness, nausea, stomach pain, visual blurring, and vomiting.

    Serious Adverse Effects (Rare):

    Orally: L-tryptophan has been associated with the neurological disorder eosinophilia-myalgia syndrome (EMS).”

    L-tryptophan · Natural Medicines adverse-effect record, reported in cluster headache.

    Methotrexate

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

  • Reduced appetite Additional detail

    L-tryptophan

    “Orally, L-tryptophan can cause gastrointestinal side effects such as heartburn, stomach pain, belching and flatulence, nausea, vomiting, diarrhea, dry mouth, and anorexia.”

    L-tryptophan · Natural Medicines adverse-effect record, reported in anorexia.

    2 sources cited
    1. 10853. Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev 2002;(1):CD003198. PubMed
    2. 99884. Ullrich SS, Fitzgerald PCE, Giesbertz P, Steinert RE, Horowitz M, Feinle-Bisset C. Effects of intragastric administration of tryptophan on the blood glucose response to a nutrient drink and energy intake, in lean and obese men. Nutrients 2018;10(4). pii: PubMed

    Methotrexate

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

  • Muscle pain / Dizziness Additional detail

    L-tryptophan

    Recorded for L-tryptophan in the same Natural Medicines adverse-effect record shown under Drowsiness above.

    Methotrexate

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

  • Tiredness reported in 6.7% of FDA reports for Methotrexate Additional detail

    L-tryptophan

    Recorded for L-tryptophan in the same Natural Medicines adverse-effect record shown under Hair loss 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 ›

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

    L-tryptophan

    Recorded for L-tryptophan in the same Natural Medicines adverse-effect record shown under Drowsiness 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 ›

Showing the 10 most notable of 13 shared effects — ranked by how unusual each one is, not just whether both lists mention it.

Reported for L-tryptophan but not commonly for Methotrexate: a fast or pounding heartbeat, bloating or gas, heartburn and dry mouth.

Effects for Methotrexate come from the ADVERSE REACTIONS section of its FDA label; effects for L-tryptophan 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

L-tryptophan in Pregnancy & Breastfeeding

Pregnancy Likely Safe

When used orally in amounts commonly found in foods.

Pregnancy Possibly Unsafe

When used orally in medicinal amounts because it may cause respiratory depression in utero. Avoid using in amounts greater than those found in foods.

Lactation Likely Safe

When used orally in amounts commonly found in foods. There is insufficient reliable information available about the safety of larger medicinal amounts; avoid using.

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

From our Q&A

Questions About L-tryptophan 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 L-tryptophan 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 L-tryptophan 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 L-tryptophan as Part of a Dietary Supplement Product? Check It for Interactions

We hold 5 real supplement products containing L-tryptophan, each one broken down to its full ingredient list — and combination products often carry several ingredients besides L-tryptophan. Even though L-tryptophan 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 L-tryptophan 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 L-tryptophan
Steady interest

#1,025 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 L-tryptophan reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The L-tryptophan and Methotrexate records this page draws on were last updated July 11, 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 L-tryptophan

What is L-tryptophan?

L-tryptophan
  • Sleep problems
  • Low mood and depression
  • Anxiety
  • Premenstrual symptoms
  • Appetite and food cravings

L-tryptophan is an essential amino acid the body uses to make serotonin and melatonin, and people take it to support sleep and mood. The evidence for supplement use is limited and mixed, and there are real safety concerns, so talk to a pharmacist or doctor before trying it.

Amino acid (made from dietary protein or by fermentation) · Capsules, tablets, powder

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

L-tryptophan: dosing

There is no official, standardized dose of L-tryptophan as a supplement. They can help you decide whether it is appropriate for you and whether it is safe with your other medicines and health conditions. Do not assume that taking more will work better, as higher amounts may increase side effects.

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

Read the full L-tryptophan 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 & L-tryptophan

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

248Major
146Moderate
0Minor
2,435No known interaction
248 Major 146 Moderate 2,435 No interaction
Major

248 interactions

Showing 60 of 248 major interactions — see all 248 on the L-tryptophan page.

Moderate

146 interactions

Showing 60 of 146 moderate interactions — see all 146 on the L-tryptophan page.

No interaction 2,435 drugs checked — show the list

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

Showing the 60 most looked-up of 2,435 medications checked with no known interaction — see the full L-tryptophan list.

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

L-tryptophan References

The 18 references that drive our L-tryptophan 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. Messiha FS. Fluoxetine: adverse effects and drug-drug interactions. J Toxicol Clin Toxicol 1993;31:603-30. PubMed
  2. Devoe LD, Castillo RA, Searle NS. Maternal dietary substrates and human fetal biophysical activity. The effects of tryptophan and glucose on fetal breathing movements. Am J Obstet Gynecol 1986;155:135-9. DOI
  3. Lieberman HR, Corkin S, Spring BJ. The effects of dietary neurotransmitter precursors on human behavior. Am J Clin Nutr 1985;42:366-70. PubMed
  4. U. S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements. Information Paper on L-Tryptophan and 5-hydroxy-L-tryptophan, February 2001.
  5. Sullivan EA, Kamb ML, Jones JL, et al. The natural history of eosinophilia-myalgia syndrome in a tryptophan-exposed cohort in South Carolina. Arch Intern Med 1996;156:973-9. DOI
  6. Philen RM, Hill RH, Flanders WD, et al. Tryptophan contaminants associated with eosinophilia-myalgia syndrome. Am J Epidemiol 1993;138:154-9. PubMed
  7. Bohme A, Wolter M, Hoelzer D. L-tryptophan-related eosinophilia-myalgia syndrome possibly associated with a chronic B-lymphocytic leukemia. Ann Hematol 1998;77:235-8. PubMed
  8. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  9. Priori R, Conti F, Luan FL, et al. Chronic fatigue: a peculiar evolution of eosinophilia myalgia syndrome following treatment with L-tryptophan in four Italian adolescents. Eur J Pediatr 1994;153:344-6..
  10. Klein R, Berg PA. A comparative study on antibodies to nucleoli and 5-hydroxytryptamine in patients with fibromyalgia syndrome and tryptophan-induced eosinophilia-myalgia syndrome. Clin Investig 1994;72:541-9.. PubMed
  11. Simat TJ, Kleeberg KK, Muller B, Sierts A. Synthesis, formation, and occurrence of contaminants in biotechnologically manufactured L-tryptophan. Adv Exp Med Biol 1999;467:469-80.. PubMed
  12. Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev 2002;(1):CD003198. PubMed
  13. Kilbourne EM, Philen RM, Kamb ML, Falk H. Tryptophan produced by Showa Denko and epidemic eosinophilia-myalgia syndrome. J Rheumatol Suppl 1996;46:81-8.
  14. Horwitz RI, Daniels SR. Bias or biology: evaluating the epidemiologic studies of L-tryptophan and the eosinophilia-myalgia syndrome. J Rheumatol Suppl 1996;46:60-72.
  15. Shapiro S. Epidemiologic studies of the association of L-tryptophan with the eosinophilia-myalgia syndrome: a critique. J Rheumatol Suppl 1996;46:44-58.

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 L-tryptophan and Methotrexate Together: Common Questions

Is it safe to take L-tryptophan with Methotrexate?
We do not list a known interaction between L-tryptophan 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 L-tryptophan 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.
How was the L-tryptophan and Methotrexate combination checked?
Interactions in our licensed database are recorded against drug classes. Methotrexate is filed under 6 classifications, and L-tryptophan has documented interactions with 2 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 L-tryptophan interact with any other medications?
Yes. L-tryptophan has 394 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 — L-tryptophan 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

L-tryptophan 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 18 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Methotrexate and L-tryptophan?

Our pharmacists answer your medication & supplement questions — free.

Ask a pharmacist

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.