L-Methylfolate for Depression: What You Need to Know
This post explains how L-methylfolate may be used to support treatment for depression, especially if you have certain genetic traits that affect how your body processes folate (like the MTHFR gene variant).
L-methylfolate is the active form of folate (vitamin B9) that can easily enter the brain.
Why L-Methylfolate is Used
L-methylfolate helps your brain make important mood-related chemicals like serotonin, dopamine, and norepinephrine.
It can be especially helpful for people with treatment-resistant depression or MTHFR gene variants.
It may improve the way your current antidepressant works when taken together.
How to Take L-Methylfolate
Take with or without food
Watch for possible side effects like upset stomach, anxiety, or trouble sleeping
Let your provider know if you notice anything unusual
Starting dose:
- Begin with 5 mg once daily
- After 2–3 weeks, your provider may increase it to 10 mg
- If needed, the dose may go up to 15 mg daily
Where to buy L-Methylfolate
Prescription option:
Deplin® (available in 7.5 mg or 15 mg)
Effective, but often not covered by insurance
Can cost more than over-the-counter options
Over-the-counter (OTC) brands:
Thorne 5-MTHF
MethylPro
Carlyle Opti-Folate
These are usually much more affordable ($15–30/month)
Available online or at some supplement stores
Is L-Methylfolate Covered by Insurance? The Cost of L-Methylfolate
Deplin is usually not covered by insurance or Medicare. High-quality OTC versions are a good option and often more affordable. Ask your provider which option is best for you based on your needs and budget.
Please Note: If you're taking L-methylfolate, it's also important to ensure your body has enough vitamin B12.
Both nutrients work closely together to support brain and nervous system health.. Most people get enough B12 from multivitamins or a methylated B-complex supplement.
You can also check your B12 levels through a blood test
A level above 400 pg/mL is generally good for mental health
We’re here to help.
If you're navigating treatment-resistant depression or wondering whether a folate metabolism issue could be impacting your progress, we’re here to help. At New York Integrative Psychiatry, we take a personalized, integrative approach to mental health—considering biological factors like L-methylfolate alongside evidence-based therapies, including ketamine-assisted treatment. Schedule a Session to explore whether L-methylfolate can support your path to healing.