L-methylfolate (5-MTHF) has 4 documented interactions in Magellan’s curated dataset, covering Anti-seizure medications, Chemotherapy and cancer therapy, Pyrimethamine, Sulfasalazine. Each entry below gives the mechanism as the cited reference states it, the direction the risk runs, how serious that reference treats it, and what to actually do about it — which is, in every case, a conversation with the clinician or pharmacist who manages the prescription rather than a decision you make alone.
What it is. L-Methylfolate (also called 5-methyltetrahydrofolate, 5-MTHF, or levomefolic acid) is the biologically active, circulating form of the B-vitamin folate and the form that enters cells and the brain without further conversion. Unlike synthetic folic acid, it does not require reduction by dihydrofolate reductase or activation by methylenetetrahydrofolate reductase (MTHFR), so its bioavailability is not reduced by common MTHFR gene polymorphisms.
Where it sits on the evidence. Magellan grades the supplement itself as Moderate evidence, with a typical studied dose of 15 mg/day as antidepressant adjunct (7.5 mg was ineffective). That grade is about whether it works, not about whether it is safe alongside your medication — the two questions are independent, and this page answers only the second.
Products this covers: L-Methylfolate (5-MTHF).
How the risks cluster. The entries split across 2 different mechanisms — nutrient level; opposing — and they are not managed the same way, so read each one rather than assuming a single rule covers all of them.
Safety and efficacy are separate questions, and this page only answers the first. For the second, the study Magellan’s coverage of L-methylfolate rests on is:
“Adjunctive L-methylfolate modestly improved antidepressant response versus placebo (RR 1.25 for HAMD-17 response; SMD −0.38), supporting the 15 mg/day trial findings.”
A strong result does not make a supplement safe alongside your prescription, and a documented interaction does not mean the supplement does not work. Magellan grades those two things separately, and neither grade moves for a commission.
Magellan’s Medication Safety Check runs entirely on your device — type the medicines you take and it flags every documented interaction in this dataset. Nothing you type is sent anywhere.
Open the Medication Safety Check →These medications can lower serum folate levels, while folate supplementation can in turn lower blood levels of the antiepileptic drug itself, potentially reducing seizure control; patients on these drugs should consult their provider before taking folate/methylfolate supplements.
Medicines in this group include: Phenytoin (Dilantin), Carbamazepine (Tegretol), Valproic acid (Depakote, Valproate), Phenobarbital (Luminal), Levetiracetam (Keppra), Lamotrigine (Lamictal), Gabapentin (Neurontin), Topiramate (Topamax).
Folate is a methotrexate antagonist; when methotrexate is used for cancer, folate supplements could interfere with its anticancer effect and should only be used under oncologist guidance (when methotrexate is used at low doses for rheumatoid arthritis or psoriasis, folate is sometimes co-prescribed, so the clinical impact depends on the indication).
Medicines in this group include: Methotrexate (Trexall, Otrexup), Tamoxifen (Nolvadex), Cisplatin, Doxorubicin (Adriamycin), Vincristine (Oncovin), Bortezomib (Velcade), Cyclophosphamide (Cytoxan).
Folic acid/folate can interfere with pyrimethamine's effectiveness; since pyrimethamine is used for malaria prevention/treatment and toxoplasmosis, this interaction is considered clinically significant.
Medicines in this group include: Pyrimethamine (Daraprim).
Sulfasalazine inhibits intestinal absorption of folate and can contribute to folate deficiency; this is generally a reason clinicians may recommend folate rather than a dangerous interaction, but patients should discuss supplementation with their provider.
Medicines in this group include: Sulfasalazine (Azulfidine).
These are the warning signs that go with the medication classes on this page. They are general safety-netting, not a prediction that any supplement will cause them.
If something feels seriously wrong, do not wait for an appointment. Call 911 (US) or your local emergency number.
Severity describes the interaction as the cited reference frames it, not how a specific person will react. A “minor” entry in someone with kidney disease, on five other drugs, can matter more than a “major” one in someone on nothing else.
This is a curated set of interactions with citations — not an exhaustive pharmacology database. An interaction that is absent here has not been ruled out; it may simply not be documented in the references Magellan curates from. Supplements are also not batch-tested for identity or contamination the way prescription drugs are, so what is on the label is a claim rather than a guarantee. And most of these entries come from case reports and mechanistic work rather than randomized trials, which is exactly why the sensible response is a pharmacist review rather than either alarm or dismissal.
43 documented interactions across 24 supplements.
9 documented interactions across 9 supplements.
7 documented interactions · shares a drug class with L-methylfolate.
8 documented interactions · shares a drug class with L-methylfolate.
4 documented interactions · shares a drug class with L-methylfolate.
3 documented interactions · shares a drug class with L-methylfolate.
The mechanism and the research behind the compound itself.
A–Z of every supplement and drug class in this dataset, plus how to read an interaction.
What the research actually shows, graded independently of affiliate commissions.
Not without checking with the prescriber or pharmacist first. Magellan's dataset grades this as a moderate interaction: These medications can lower serum folate levels, while folate supplementation can in turn lower blood levels of the antiepileptic drug itself, potentially reducing seizure control; patients on these drugs should consult their provider before taking folate/methylfolate supplements. (Source: Folate - Health Professional Fact Sheet.)
4 interactions are documented in Magellan's curated dataset: 3 moderate, 1 minor. They cover Anti-seizure medications, Chemotherapy and cancer therapy, Pyrimethamine, Sulfasalazine. Absence from this list is not proof of safety — it means no interaction is documented in the references we curate from.
Magellan lists the typical studied dose as: 15 mg/day as antidepressant adjunct (7.5 mg was ineffective). Dose matters for interactions — several of the entries on this page describe effects that only appear at supplemental rather than dietary intakes.