OnePin Peptide Library · Metabolic
Methylfolate
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.
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.
How it works
Methylfolate functions in the methylation cycle:
Direct Bioactive Form
5-MTHF is the active form used in DNA methylation, neurotransmitter synthesis (serotonin, dopamine, norepinephrine), and homocysteine recycling. No conversion needed.
Bypasses MTHFR
Standard folic acid requires MTHFR enzyme conversion to 5-MTHF; MTHFR polymorphisms (C677T, A1298C) reduce this. Methylfolate provides direct active form.
SAMe Production
5-MTHF donates methyl groups to homocysteine, producing methionine and ultimately SAMe (universal methyl donor).
Neurotransmitter Synthesis
Folate cycle is required for tetrahydrobiopterin (BH4) regeneration - cofactor for serotonin, dopamine, NE synthesis. Methylfolate supports neurotransmitter production.
Homocysteine Reduction
Lowers serum homocysteine - cardiovascular risk marker.
Avoids Unmetabolized Folic Acid
Some individuals accumulate unmetabolized folic acid on high-dose synthetic folic acid - theoretical concerns for cancer and immune function. Methylfolate avoids this.
What to expect
Days 1-14: subtle effects.
Weeks 2-6: peak depression effects.
Long-term sustained.
Evidence
Interactions & stacking
What's safe to combine, and what belongs in a separate pin.
Keep separate
Side effects & safety
Commonly reported
- Generally well-tolerated
- Mild headache (rare)
Less common & notes
- Mania in bipolar at high doses.
- Methotrexate antagonism.
- Long-term safety good.
Pharmacokinetics
Storage. Capsule. Cool dry location, light-sensitive.
Regulatory status
Dietary supplement (US, DSHEA). Deplin (L-methylfolate) is FDA medical food for depression.
Put it to work
Calculate, log & track
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 guide & community
The complete Methylfolate walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.
Join the community ↗