L-Methylfolate · 5-MTHF · L-5-MTHF · Active Folate
Methylfolate (5-methyltetrahydrofolate / 5-MTHF / L-methylfolate) is the bioactive form of folate (vitamin B9) - the form that crosses the blood-brain barrier and participates directly in methylation cycle reactions. Standard folic acid (synthetic, oxidized) requires conversion through dihydrofolate reductase and methylenetetrahydrofolate reductase (MTHFR) to become bioactive 5-MTHF.
Starting dose. 400-800mcg — Daily (general); 1-15mg (depression)
Morning preferred.
Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.
Methylfolate functions in the methylation cycle:
5-MTHF is the active form used in DNA methylation, neurotransmitter synthesis (serotonin, dopamine, norepinephrine), and homocysteine recycling. No conversion needed.
Standard folic acid requires MTHFR enzyme conversion to 5-MTHF; MTHFR polymorphisms (C677T, A1298C) reduce this. Methylfolate provides direct active form.
5-MTHF donates methyl groups to homocysteine, producing methionine and ultimately SAMe (universal methyl donor).
Folate cycle is required for tetrahydrobiopterin (BH4) regeneration - cofactor for serotonin, dopamine, NE synthesis. Methylfolate supports neurotransmitter production.
Lowers serum homocysteine - cardiovascular risk marker.
Some individuals accumulate unmetabolized folic acid on high-dose synthetic folic acid - theoretical concerns for cancer and immune function. Methylfolate avoids this.
Days 1-14: subtle effects.
Weeks 2-6: peak depression effects.
Long-term sustained.
Each reference below was re-fetched from its PubMed record, and the quoted sentence was confirmed to appear in that abstract and to support the claim it sits under. Follow any of them to read the source.
Evidence boundary from the checked abstract: The prescription of Deplin (L-methylfolate) greatly reduced the symptoms.
The prescription of Deplin (L-methylfolate) greatly reduced the symptoms.
Evidence scope. This entry supports only the exact statement quoted from the live abstract; it does not independently verify OnePin's displayed dose, route, frequency, formulation, population, or broader mechanism.
Claims we could not support
No abstract we checked supports these for this molecule at this route. That is not the same as saying they are false — it marks where the evidence is missing.
Dose/route: 400-800mcg daily (general); 1-15mg (depression); Oral capsule or sublingual; 1x daily. No checked live PubMed abstract verified this exact displayed dose, route, and frequency for the same molecule/formulation and relevant population.
Primary safety claim: No primary safety text present in source JSON. No checked live PubMed abstract directly verified this source-JSON safety claim at the displayed formulation, route, and regimen.
Plasma
Cumulative methylation cycle effects over weeks
Oral very high (no MTHFR conversion needed)
Daily dosing for sustained effects
Hepatic and renal
Storage. Capsule. Cool dry location, light-sensitive.
Dietary supplement (US, DSHEA). Deplin (L-methylfolate) is FDA medical food for depression.
Put it to work
Open Methylfolate straight into OnePin with your vial and dose pre-filled, then let it handle the syringe math and remind you before the vial runs out.
Open Methylfolate in the app →Go deeper
The complete Methylfolate walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.
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