Methylfolate is the active form of folic acid – which is an essential B vitamin.
Methylfolate is essential for the brain to make the neurotransmitters that prevent depression (norepinephrine, serotonin, and dopamine).
In other words, a low level of depression can cause or worsen depression because it leads to lower levels of serotonin, norepinephrine and dopamine.
Most of us are able to get plenty of folate (from typical vitamins) and dihydrofolate (from foods) and most of us can then convert these two forms into the active L Methyl Folate.
The brain uses a specific enzyme in order to convert folic acid and folate to methylfolate.
Methylenetetrahydrofolate reductase (MTHFR) is the enzyme responsible for activating folic acid and folate. A gene significantly reduces the activity of MTHFR,and therefore reduces the brain’s ability to convert folic acid and folate (the dietary sources of the vitamin) to methylfolate.
Many people with depression may not be aware that they lack the gene that allows their brain to use folate and folic acid from their diet and from typical vitamin supplements, and may not be aware that taking the active form of folate (L methyl folate) may be essential to getting a good response to common antidepressants like Lexapro, Zoloft, Prozac and Paxil.
A number of studies have shown that people with the lower activity gene for MTHFR have a greater risk of developing depression. In addition, several randomized controlled trials have demonstrated that methylfolate supplements can be effective in boosting the response of people with depression to antidepressants. .
Methylfolate is available both as an over-the-counter supplement, and as a medical food requiring a prescription. The prescribed form of methylfolate (Deplin) is much more expensive.
You can find Metabolic Maintenance L Methyl Folate and Life Extension Optimized Folate as well as Jarrow Formulas Methylfolate at Amazon.com
1. Robinson, D.M., Vitamins, Monoamines, and Depression. Primary Psychiatry, 2009. 16(2): p. 19-21.
2. Bredy, T.W., Y.E. Sun, and M.S. Kobor, How the epigenome contributes to the development of psychiatric disorders. Developmental Psychobiology, 2010. 52(4): p. 331-342.
3. Gilbody, S., S. Lewis, and T. Lightfoot, Methylenetetrahydrofolate Reductase (MTHFR) Genetic Polymorphisms and Psychiatric Disorders: A HuGE Review. American Journal of Epidemiology, 2007. 165(1): p. 1-13.
4. Wu, Y.L., et al., Association between MTHFR C677T polymorphism and depression: An updated meta-analysis of 26 studies. Prog Neuropsychopharmacol Biol Psychiatry, 2013. 46: p. 78-85.
5. Lok, A., et al., Interaction between the MTHFR C677T polymorphism and traumatic childhood events predicts depression. Transl Psychiatry, 2013. 3: p. e288.
6. Shelton, R.C., et al., Assessing Effects of l-Methylfolate in Depression Management: Results of a Real-World Patient Experience Trial. Prim Care Companion CNS Disord, 2013. 15(4).
7. Papakostas, G.I., et al., L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry, 2012. 169(12): p. 1267-74.
8. Farah, A., The role of L-methylfolate in depressive disorders. CNS Spectr, 2009. 14(1 Suppl 2): p. 2-7.
9. Nahas, R. and O. Sheikh, Complementary and alternative medicine for the treatment of major depressive disorder. Can Fam Physician, 2011. 57(6): p. 659-63.
10. LD, G., O. AY, and D. YA, L-methylfolate Plus SSRI or SNRI from Treatment Initiation Compared to SSRI or SNRI Monotherapy in a Major Depressive Episode. Innov Clin Neurosci, 2011. 8(1): p. 19-28.