B-9, or Folate, is a vitamin that is necessary for, among other things, the formation of red blood cells, protein metabolism, cell growth and division, and prevention of neural tube defects. In addition to anemia and other health problems, folate deficiency may lead to the development of major depressive disorder (MDD). Likewise, having either a folate deficiency or problem with malabsorption is related with poor response to antidepressant medications.
Folate is found naturally in grains, fruits, vegetables, beans, and other foods. For most people, the synthetic version, folic acid, is absorbed faster than folate.
Researchers first began to link folate deficiency with depression in the 1960s. Although everyone feels down or sad at some point, major depressive disorder affects roughly 6–7% of adults in a given year, and nearly twice as many women as men. Approximately 50–70% of patients on antidepressants fail to have a remission of their depressive episode. For these patients, clinical trials and case studies suggest that l-methylfolate can improve response to antidepressants. Furthermore, although atypical antipsychotic medications are sometimes used to augment the effects of antidepressants, these drugs are associated with side effects such as weight gain and dyslipidemia (which can cause elevated triglycerides and LDL cholesterol). Some researchers have encouraged the use of L-methylfolate supplementation for those who don’t respond well to antidepressants alone because l-methylfolate has not been shown to cause the side effects associated with antipsychotics. In general, l-methylfolate is well-tolerated and over-the-counter brands are relatively inexpensive.
L-Methylfolate is the only form of folic acid that crosses the blood-brain barrier and plays a role in neurotransmitter synthesis. It indirectly facilitates the synthesis of serotonin, dopamine, and norepinephrine, three neurotransmitters involved in mood regulation and other important functions. L-methylfolate has been shown in several studies to enhance the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), two commonly prescribed classes of antidepressants.