Updated on March 7, 2025
Original article: January 6, 2008
I do a lot of psychopharmacology research, more than most people would consider normal. I try to share only the most interesting and relevant findings while saving the most technical details. But today, a deeper immersion awaits you.
This issue is too important to ignore, especially if you are struggling with treatment resistant.
What is L-methylpholate (MTHF)?
L-methylpholate (MTHF) is the biologically active folate form, a crucial vitamin B for brain function and neurotransmitter production. His body turns the folate into the diet in MTHF, but this process requires specific enzymes, and not all produce enough of them efficiently.
I have probably heard of folic acid, the synthetic version of the folate that is commonly found in supplements and prenatal vitamins. While folic acid can increase MTHF levels, the conversion process is not always effective, particularly for people with certain genetic variations.
Why is L-methylpholate important for mental health?
Low MTHF levels are linked to depression, and some people do not synthesize enough, even with a diet or supplements rich in folate. This is where things get interesting:
- MTHF is necessary to produce serotonin, dopamine and norepinenialineBrain chemicals are directed to most antidepressants.
- Some investigations suggest that MTHF can improve the effectiveness of antidepressants, even in people without deficiency.
- Certain medications, including anticonvulsions (mood stabilizers such as lamotrigine [Lamictal]), You can be able to exhaust MTHF levelspotentially reducing the effectiveness of antidepressants over time.
Can L-methylpholate help when antidepressants do not work?
Emerging research indicates that L-methylpholate supplementation can improve the antidepressant response (See below) in people with depression. Unlike standard antidepressants, which directly influence neurotransmitters, MTHF works by supporting their natural production. (Note: The following research suggests that it could work even better for those with inflammation or a higher body mass index [BMI]obesity.) It has been shown that L-methylpholate helps those with treatment resistant to treatment.
He Food and medication administration (FDA) regulates L-methylpholate as medical foodWhich means that it requires a recipe but is not classified as a medication. This means that it is unlikely to contribute to its secondary effect load.
My experience with L-methylpholate
My doctor, who makes no sense as it makes, introduced me to L-methylpholate. She respects the researchers who studied him and felt it was worth trying. After being anticonvulsive for years (eight, to be exact), it is not shocking that little key nutrients can have.
Could this explain why antidepressants sometimes stop working? Could MTHF be the missing piece for some people? Probably.
Final thoughts: Should you try L-methylpholate?
L-methylpholate is not a miraculous cure, and research is still evolving. But if antidepressants do not work, or if they have stopped working, it could be worth discussing with their doctor. Since it is a relatively low risk compared to other psychiatric treatments, it could be an option that is worth exploring.
As usual, Does not begin any new supplement without medical supervisionespecially if you are taking other medications.
Recent L-methylpholate research
Here are some recent studies that show that L-methylpholate can benefit those who take an antidepressant for depression:
- Maruf, AA, Poweleit, EA, Brown, LC, Strawn, JR and Bousman, CA (2021). Systematic review and meta-analysis of the increase in L-methylpholate in depressive disorders. Pharmacopopryatría, 55(03), 139–147. https://doi.org/10.1055/a-1681-2047
- Maletic, V., Shelton, R. and Holmes, V. (2023). A review of L-methylpholate as complementary therapy in the treatment of major depressive disorder. Primary Care Companion for CNC disorders, 25(3). https://doi.org/10.4088/pcc.22nr03361
- Macaluso, M. (2022). L-methylpholate in non-antidepressant responders: the impact of body weight and inflammation. Borders in psychiatry, 13. https://doi.org/10.3389/fpsyt.2022.840116
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