Folic acid is the synthetic form of folate (vitamin B9) — arguably the most important supplement for women planning pregnancy. Our research, from 19 meta-analyses and 147,000+ participants, confirms it prevents neural tube defects, reduces homocysteine, and may adjunctively improve depression when added to antidepressants. The critical safety concern: folic acid can mask vitamin B12 deficiency, allowing irreversible nerve damage to progress silently.
Reduces drug effectiveness
Avoid high-dose folic acid during malaria treatment.
Reduces drug levels
Monitor phenytoin levels when adding folic acid.
Reduces drug effectiveness
Avoid with cancer-dose methotrexate. USE with low-dose methotrexate.
Enhances drug toxicity
Do not supplement during fluorouracil-based chemotherapy.
L-methylfolate supplements show wild variation: 0-280% of labeled amount in one study. Folic acid is more stable and reliable.
Not Prohibited.
L-methylfolate supplements show wild variation: 0-280% of labeled amount in one study. Folic acid is more stable and reliable.
Reviewed by the Scan Dose Research Team and Clinical Advisory Board | Last updated: April 5, 2026
Not medical advice. Based on published clinical research and systematic reviews.
Safety
Moderate interactions. Monitoring, timing separation, or dose adjustment may be required.
Methotrexate
Folic acid competes with methotrexate for folate receptors.
Source: FDA label
Phenytoin (Dilantin)
Folic acid may reduce phenytoin levels.
Source: Clinical pharmacology
5-Fluorouracil (5-FU)
Folic acid (as leucovorin) is sometimes given with 5-FU to enhance its effect.
Source: Oncology standard
Educational information only. This is not medical advice. These statements have not been evaluated by the FDA. Talk to your prescriber before starting, stopping, or combining any supplement with prescription medication.