MTHFR is an enzyme needed for the body to break down vitamin B9, also known as folate or folic acid. It also helps convert the toxic amino acid homocysteine into the antidepressant amino acid s-adenysl-methionine. However, a significant segment of the population (some estimate 40%) have a genetic mutation in the MTHFR gene that interferes with the body’s ability to break down B vitamins and is linked to higher levels of homocysteine. MTHFR mutations are also linked to depression.
A 2016 study by Arnold W. Mech and Andrew Farah in the Journal of Clinical Psychiatry found that treating people with major depression and a MTHFR deficiency using a combination of micronutrients and already-broken-down B vitamins improved their depression and reduced their homocysteine levels compared to placebo.
The study included 330 adult patients with major depression and one of two genetic variants in the MTHFR gene—C677T or A1298C. Of those who received the metabolized vitamins, 82.4% showed reduced homocysteine levels. Those who received placebo showed a small average increase in homocysteine. The vitamin group also saw a large drop in depression symptoms on average after 8 weeks, with 42% achieving full remission. There were no side effects.
These findings suggest that homocysteine levels play a role in depression and that metabolized B vitamins can be an effective treatment for depression, particularly in those with a MTHFR deficiency. A metabolized form of folate that is commercially available is called L-methylfolate.