What is the recommended dose of Methylfolate?

- **Look for:** L-5-MTHF (the L isomer specifically); Quatrefolic® (most stable, best bioavailability); Metafolin® (calcium L-5-MTHF); dose in mcg or mg clearly stated - **Avoid:** Folic acid (for ...

Is Methylfolate safe to take daily?

Methylfolate is rated "Generally Safe" based on clinical evidence. Always consult your healthcare provider before starting any supplement.

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Ingredient Research

Graded against 173,636 supplements + 177 published clinical interactions, sourced from PubMed, FDA CAERS, openFDA, NIH DSLD

Methylfolate

MODERATE EVIDENCEVitaminLast updated

AVELOR SUMMARY

Methylfolate is the biologically active form of folate (vitamin B9) — the form your body actually uses. This matters because approximately 40% of the population has at least one copy of the MTHFR C677T polymorphism, reducing their ability to convert folic acid to methylfolate by 30-70%. Our research shows methylfolate supplementation bypasses this genetic bottleneck entirely. L-methylfolate (Deplin®) is also FDA-approved as a medical food for depression (15mg/day as SSRI adjunct), making it one of the very few supplements that has crossed into prescription territory. For pregnancy, adequate folate prevents 70% of neural tube defects — and methylfolate ensures those with MTHFR variants are protected.

WHAT IT DOES

Methylfolate (5-MTHF) is the final active form of folate that donates methyl groups in one-carbon metabolism. Its primary function: (1) remethylating homocysteine to methionine (via methionine synthase + B12), reducing cardiovascular-toxic homocysteine; (2) methionine → S-adenosylmethionine (SAMe) → methyl donor for DNA methylation, neurotransmitter synthesis (serotonin, dopamine, norepinephrine), and 200+ methylation reactions; (3) thymidylate synthesis for DNA replication (critical in pregnancy). The MTHFR enzyme converts folic acid → dihydrofolate → tetrahydrofolate → 5-MTHF. Variants (C677T, A1298C) reduce this enzyme's efficiency, creating a bottleneck that supplemental 5-MTHF bypasses entirely.

OPTIMAL DOSAGE

Look for: L-5-MTHF (the L isomer specifically); Quatrefolic® (most stable, best bioavailability); Metafolin® (calcium L-5-MTHF); dose in mcg or mg clearly stated
Avoid: Folic acid (for known MTHFR carriers); DL-5-MTHF (contains inactive D-isomer — 50% wasted); "folate" without specifying form; products relying solely on folic acid labeled as "methylfolate"
Minimum effective dose: 400mcg/day (RDA); 1-5mg for depression adjunct; 15mg for treatment-resistant depression (Deplin)
Third-party tested brands: Thorne (5-MTHF), Seeking Health (Optimal Methylate), Life Extension, Pure Encapsulations

Scan a supplement containing Methylfolate

SAFETY PROFILE

Critical Interactions (Do Not Combine Without Medical Supervision)

Moderate Interactions (Monitor Closely)

Theoretical/Low-Risk Interactions

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Quality Testing Intelligence

Based on independent third-party laboratory analysis

Category pass rate: ~75%. Dose accuracy and dissolution are the main issues.

Scan Your Methylfolate Supplement Browse all ingredients

Independently graded against 173,636 indexed supplements with 177 published clinical interactions, sourced from PubMed, FDA CAERS, openFDA, and NIH DSLD | Last updated:

Not medical advice. Based on published clinical research and systematic reviews.

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Ingredient Research

Graded against 173,636 supplements + 177 published clinical interactions, sourced from PubMed, FDA CAERS, openFDA, NIH DSLD

Methylfolate

MODERATE EVIDENCEVitaminLast updated

AVELOR SUMMARY

WHAT IT DOES

OPTIMAL DOSAGE

Look for: L-5-MTHF (the L isomer specifically); Quatrefolic® (most stable, best bioavailability); Metafolin® (calcium L-5-MTHF); dose in mcg or mg clearly stated
Avoid: Folic acid (for known MTHFR carriers); DL-5-MTHF (contains inactive D-isomer — 50% wasted); "folate" without specifying form; products relying solely on folic acid labeled as "methylfolate"
Minimum effective dose: 400mcg/day (RDA); 1-5mg for depression adjunct; 15mg for treatment-resistant depression (Deplin)
Third-party tested brands: Thorne (5-MTHF), Seeking Health (Optimal Methylate), Life Extension, Pure Encapsulations

Scan a supplement containing Methylfolate

SAFETY PROFILE

Critical Interactions (Do Not Combine Without Medical Supervision)

Moderate Interactions (Monitor Closely)

Theoretical/Low-Risk Interactions

RELATED RESEARCH

Acerola Cherry

Amla

BiotinBiotin is a cofactor for five carboxylase enzymes critical to metabolism: pyruva

Amla

Quality Testing Intelligence

Based on independent third-party laboratory analysis

Category pass rate: ~75%. Dose accuracy and dissolution are the main issues.

Scan Your Methylfolate Supplement Browse all ingredients

Independently graded against 173,636 indexed supplements with 177 published clinical interactions, sourced from PubMed, FDA CAERS, openFDA, and NIH DSLD | Last updated:

Not medical advice. Based on published clinical research and systematic reviews.

Discover More

Explore

Browse All 834 Ingredients Browse All 20 Conditions