L-Methylfolate and Antidepressants: Can This Complement Increase Your Therapy?

Up to date March 7, 2025

Unique article: January 6, 2008

I do loads of psychopharmacology analysis — greater than most individuals would contemplate regular. I attempt to share solely essentially the most fascinating and related findings whereas sparing you the extra technical particulars. However at the moment, you’re in for a deeper dive.

This matter is just too necessary to disregard, particularly in case you’re combating treatment-resistant melancholy.

What Is L-Methylfolate (MTHF)?

L-methylfolate (MTHF) is the biologically energetic type of folate, a B vitamin essential for mind perform and neurotransmitter manufacturing. Your physique converts dietary folate into MTHF, however this course of requires particular enzymes — and never everybody produces sufficient of them effectively.

You’ve in all probability heard of folic acid, the artificial model of folate generally present in dietary supplements and prenatal nutritional vitamins. Whereas folic acid can enhance MTHF ranges, the conversion course of isn’t all the time efficient, significantly for folks with sure genetic variations.

Why Does L-Methylfolate Matter for Psychological Well being?

Low ranges of MTHF are linked to melancholy, and a few folks don’t synthesize sufficient of it, even with a folate-rich weight-reduction plan or dietary supplements. That is the place issues get fascinating:

MTHF is important for producing serotonin, dopamine, and norepinephrine, the mind chemical substances most antidepressants goal.
Some analysis suggests MTHF can improve the effectiveness of antidepressants, even in folks with out a deficiency.
Sure medicines, together with anticonvulsants (temper stabilizers like lamotrigine [Lamictal]), might be able to deplete MTHF ranges, doubtlessly decreasing the effectiveness of antidepressants over time.

Can L-Methylfolate Assist When Antidepressants Aren’t Working?

Rising analysis signifies that L-methylfolate supplementation could enhance antidepressant response (see under) in folks with melancholy. Not like customary antidepressants, which instantly affect neurotransmitters, MTHF works by supporting their pure manufacturing. (Be aware: The analysis under means that it’d work even higher for these with irritation or a better physique mass index [BMI], weight problems.) L-methylfolate has even been proven to assist these with treatment-resistant melancholy.

The Meals and Drug Administration (FDA) regulates L-methylfolate as a medical meals, which means it requires a prescription however is just not categorized as a drug. This implies it’s unlikely to contribute to your facet impact load.

My Expertise with L-Methylfolate

My physician — who’s about as no-nonsense as they arrive — launched me to L-methylfolate. She respects the researchers learning it and felt it was value making an attempt. After being on anticonvulsants for years (eight, to be precise), it’s not surprising that I could be low on key vitamins.

Might this clarify why antidepressants typically cease working? Might MTHF be the lacking piece for some folks? Presumably.

Closing Ideas: Ought to You Attempt L-Methylfolate?

L-methylfolate isn’t a miracle treatment, and the analysis remains to be evolving. But when antidepressants aren’t working — or in the event that they’ve stopped working — it could be value discussing along with your physician. Because it’s comparatively low-risk in comparison with different psychiatric therapies, it might be an choice value exploring.

As all the time, don’t begin any new complement with out medical supervision, particularly in case you’re on different medicines.

Current L-Methylfolate Analysis

Listed below are some latest research that present that L-methylfolate could profit these taking an antidepressant for melancholy:

Maruf, A. A., Poweleit, E. A., Brown, L. C., Strawn, J. R., & Bousman, C. A. (2021). Systematic Overview and Meta-Evaluation of L-Methylfolate augmentation in depressive Issues. Pharmacopsychiatry, 55(03), 139–147. https://doi.org/10.1055/a-1681-2047
Maletic, V., Shelton, R., & Holmes, V. (2023). A assessment of L-Methylfolate as adjunctive remedy within the remedy of main depressive dysfunction. The Main Care Companion for CNS Issues, 25(3). https://doi.org/10.4088/pcc.22nr03361
Macaluso, M. (2022). L-Methylfolate in antidepressant non-responders: the influence of physique weight and irritation. Frontiers in Psychiatry, 13. https://doi.org/10.3389/fpsyt.2022.840116