Folate (also known as B-9) 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). Similarly, having either a folate deficiency or problem with malabsorption is associated with poor response to antidepressant medications.
“Where Can I Find It, and Why Can’t I Use It?”
Folate is found naturally in grains, fruits, vegetables, beans, and other foods. For most people, the synthetic version, folic acid, is absorbed more rapidly than folate; however, it must be converted back to folate to be used by the body.
Although folic acid is routinely added to many processed foods, including cereals, energy bars, and breads, the inability to properly metabolize or absorb folate can result in a deficiency — even if one consumes the recommended amount (400 mcg) of folic acid.
Specifically, certain diseases, including gastrointestinal disorders like celiac disease, liver disease, and a genetic mutation (MTHFR); alcoholism or excessive alcohol consumption; taking certain medications; being on kidney dialysis; and being pregnant can lead to a deficiency. Frequent vomiting due to pregnancy or an eating disorder can also lead to deficiency.
Blood levels of folate may not accurately reflect the levels that are present in the central nervous system. In cases where a folate deficiency is pronounced or when a medical issue inhibits absorption of folic acid, the more bioavailable form, l-methylfolate, is recommended, and often at higher doses than the % Daily Value of 400 mcg.
L-Methylfolate for Treatment-Resistant Depression
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 to 7 percent of adults in a given year, and nearly twice as many women as men.
Approximately 50 to 70 percent 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 advocated 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.
