Methotrexate — Nutrient Depletion & Health Patterns
Also known as: Methotrexate (Rheumatrex, Trexall, Otrexup)
Drug Class: Disease-modifying antirheumatic drug (DMARD) / Chemotherapy agent
Folate antagonist used at low weekly doses for rheumatoid arthritis, psoriasis, and psoriatic arthritis — and at higher doses for certain cancers. At rheumatologic doses (7.5–25mg weekly), works as an immunomodulator. At cancer doses (much higher), is cytotoxic. The most prescribed DMARD for RA worldwide. Folate supplementation is universally co-prescribed to reduce toxicity — but must be timed away from the dose to avoid reducing efficacy.
Nutrients That Methotrexate May Deplete
Long-term use of Methotrexate is associated with lower levels of the following nutrients based on peer-reviewed clinical research. WePattern surfaces these patterns from its clinical Knowledge Graph.
- Folic acid
- Vitamin B12
- Choline
- Magnesium
- Zinc
- CoQ10
Common Side Effects of Methotrexate
- Nausea and vomiting (very common — often on day-of and day-after weekly dose)
- Fatigue ('methotrexate hangover' the day after weekly dose)
- Mouth sores (oral mucositis — folate depletion)
- Liver fibrosis and cirrhosis (cumulative dose risk — requires liver monitoring)
- Pulmonary toxicity (rare but serious — dry cough, shortness of breath)
- Bone marrow suppression (immunosuppression)
- Hair thinning
- Megaloblastic anemia (folate and B12 depletion)
Key Drug Interactions — Methotrexate
Methotrexate has 9 documented drug-drug interactions in WePattern's Pattern Health Intelligence database. Key interactions include:
- NSAIDs (reduce methotrexate clearance — toxicity risk at rheumatologic doses)
- Aspirin (raises methotrexate levels — bleeding and toxicity)
- Penicillin antibiotics including amoxicillin (reduce methotrexate clearance — toxicity)
- Proton pump inhibitors (raise methotrexate levels — reduce clearance)
- Trimethoprim/sulfamethoxazole (additive folate antagonism — dangerous megaloblastic anemia)
- Live vaccines (methotrexate is immunosuppressive — no live vaccines)
Frequently Asked Questions
Does Methotrexate deplete nutrients?
Yes. Methotrexate has been associated with depletion of Folic acid, Vitamin B12, Choline, Magnesium, Zinc, CoQ10 based on clinical research. WePattern maps these relationships from peer-reviewed sources.
What nutrients does Methotrexate deplete?
Methotrexate is associated with lower levels of: Folic acid, Vitamin B12, Choline, Magnesium, Zinc, CoQ10. These depletions can develop over weeks to months of regular use.
What are the side effects of Methotrexate?
Common side effects associated with Methotrexate include: Nausea and vomiting (very common — often on day-of and day-after weekly dose); Fatigue ('methotrexate hangover' the day after weekly dose); Mouth sores (oral mucositis — folate depletion); Liver fibrosis and cirrhosis (cumulative dose risk — requires liver monitoring); Pulmonary toxicity (rare but serious — dry cough, shortness of breath).