Updated on October 27, 2023.
I see a lot of people with depression in my practice. My experience treating it has been similar to what is discussed in medical literature. In about 70 percent of patients there has been some improvement with antidepressants, but a full remission has occurred in only 40 to 50 percent. In the interest of boosting this disappointing remission rate, I have been searching for something that will either augment antidepressants or that could be used alone.
I have found a supplement considered to be medicinal food. It is safe, and it really does work. It is a vitamin that is a form of folic acid known as L-methylfolate.
Folic acid is an essential B vitamin. It is found in green leafy vegetables, eggs, cereals, and fortified foods, to name a few. (When it appears in whole foods it’s known as folate.) When you take in folate or folic acid in your diet, it is absorbed by the small intestine, where it is converted by an enzyme into L-methylfolate. This metabolite is used to make serotonin, norepinephrine, and dopamine, which are all important brain chemicals for mood regulation.
Scientists have identified 40 mutations on the gene responsible for making the enzyme that converts folic acid into L-methylfolate. If there is one mutation on this gene—known as MTHFR—your ability to convert folic acid is reduced by a sizable amount. If you have two mutations, it is reduced even further.
If you have a defective enzyme, you cannot convert folic acid to L-methylfolate properly. This can potentially lead to lower levels of serotonin, norepinephrine, and dopamine. As it turns out, these gene mutations are quite common.
The treatment is simple: a prescription of L-methylfolate. If given in the proper amounts (7.5 to 15 milligrams) it can improve mild depression relatively quickly. One 2011 study of people with major depression found that adding L-methylfolate improved depression symptoms over a period of 60 days from 7 percent for those taking an antidepressant alone to 18.5 percent with the addition of L-methylfolate.
A 2013 study published in The Primary Care Companion for CNS Disorders reported on the results of a survey conducted among patients with major depression disorder who were treated with L-methylfolate as an addition to their ongoing antidepressant. The participants reported significant improvements in their depressive symptoms and functioning, with 45.7 percent of patients achieving remission from their symptoms over 12 weeks.
Other published case studies have shown similarly promising results. Interestingly, some research has shown that patients with depression who also have elevated levels of inflammation and/or obesity show an even greater response to L-methylfolate.
L-methylfolate is generally well-tolerated with no more side effects than placebo. It tends not to interact with other medications. In my experience, if an antidepressant has produced a positive response but the patient is still somewhat depressed, L-methylfolate can help.
The results I have seen are impressive. When I treat people with MTHFR mutations (with or without mild depression) with L-methylfolate, their mood improves and often they sleep better. Related problems such as irritable bowel syndrome will often get better as well. If you are depressed and/or on medication for depression, consider asking your healthcare provider for more information about MTHFR genetic mutations.
Taking L-methylfolate to help with depression may not work for everyone. But if your serotonin levels are genetically low, it may be a healthy way to boost them.
