Drug & supplement interaction

Ligandrol + Methotrexate

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

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Ligandrol has a moderate interaction with Methotrexate. Theoretically, concomitant use might have additive hepatotoxic effects.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Ligandrol and Methotrexate

Here is the interaction we found between these two, with the evidence behind it.

Moderate

HEPATOTOXIC DRUGS

Why this applies to Methotrexate

Methotrexate falls under HEPATOTOXIC DRUGS — the group Ligandrol interacts with.

Theoretically, concomitant use might have additive hepatotoxic effects.
In case reports, patients were diagnosed with liver injury thought to be related to the use of products containing ligandrol.
Severity Moderate Likelihood Possible Evidence D

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.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the main concern with putting these two together: both can be hard on your liver. Methotrexate is well known for stressing liver cells, which is why your doctor checks your liver blood tests regularly while you're on it. Ligandrol has been tied to cases of liver injury too, so stacking them could add up and raise your risk.

I want to be honest that this is based on case reports and theory, not solid studies, so we can't say exactly how often it happens. Still, watch for warning signs like yellowing of your eyes or skin, dark urine, belly pain, or unusual tiredness. Honestly, Ligandrol is an unapproved SARM I wouldn't recommend at all. Please talk with your doctor or pharmacist before combining anything with your methotrexate.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Barbara M, Dhingra S, Mindikoglu AL. Drug-induced liver injury associated with alpha bolic (RAD-140) and alpha elite (RAD-140 and LGD-4033). ACG Case Rep J 2020;7(6):e00409. PubMed
  2. Barbara M, Dhingra S, Mindikoglu AL. Ligandrol (LGD-4033)-Induced Liver Injury. ACG Case Rep J 2020;7(6):e00370. PubMed
  3. Koller T, Vrbova P, Meciarova I, et al. Liver injury associated with the use of selective androgen receptor modulators and post-cycle therapy: Two case reports and literature review. World J Clin Cases 2021;9(16):4062-4071. PubMed
  4. Flores JE, Chitturi S, Walker S. Drug-induced liver injury by selective androgenic receptor modulators. Hepatol Commun. 2020;4(3):450-452. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction 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.
  • PossibleInteraction 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.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Ligandrol Also Interacts With Other Medications

Ligandrol has 369 moderate known drug interactions in our database — the Methotrexate one above is one of them. If you take anything else, check it against the full list below.

Moderate 369 No known interaction 2,461 (incl. Methotrexate)
Taking anything else?

Check Another of Your Medications Against Ligandrol

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

From our Q&A

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

We hold 26 real supplement products containing Ligandrol, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Ligandrol. Your product may carry other ingredients that interact with Methotrexate too, on top of Ligandrol — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Ligandrol 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 Ligandrol
Top half

#553 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.

Supplement

About Ligandrol

What is Ligandrol?

  • Muscle building
  • Athletic performance and strength
  • Body recomposition
  • Bodybuilding cycles

Ligandrol (LGD-4033) is a synthetic selective androgen receptor modulator (SARM), not a natural herb or approved dietary supplement. It is not approved for human use, is banned in sports, and has been linked to liver injury and hormonal disruption, so it should not be taken as a supplement.

Read the full Ligandrol 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.

See full Methotrexate drug information
Keep checking

Other Drugs & Ligandrol

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

0Major
369Moderate
0Minor
2,460No known interaction
369 Moderate 2,460 No interaction
Moderate

369 interactions

Showing 60 of 369 moderate interactions — see all 369 on the Ligandrol page.

No interaction 2,460 drugs checked — show the list

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

Showing the 60 most looked-up of 2,460 medications checked with no known interaction — see the full Ligandrol list.

See the full Ligandrol interactions page
See every supplement checked against Methotrexate, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Ligandrol monograph › Uses, safety, and every drug interaction in one place Methotrexate supplement interactions › Every supplement checked against Methotrexate, ranked by severity Methotrexate drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Ligandrol and Methotrexate Together: Common Questions

Can you take Ligandrol with Methotrexate?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Ligandrol and Methotrexate interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

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

Still Have a Question About Methotrexate and Ligandrol?

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.