Folate affects levels of serotonin and other neurotransmitters that are linked to depression. It also helps lower homocysteine, an amino acid in the blood that may adversely affect brain and vascular health.
Many observational studies have found that people with low dietary intakes or blood levels of folate have higher rates of depression. Some studies testing the effects of supplemental folate (folic acid is the commonly used form) have found modest benefits in depressed people, especially those who are folate-deficient—but some have not found benefits.
Other research has shown that antidepressants tend to be less effective in folate-deficient people. A Cochrane Collaboration review found “limited” evidence for folate as an adjunct treatment for depression. But “the size of any potential benefit is uncertain and may be clinically insignificant,” it concluded.
It’s hard to tease apart the many biochemical, genetic, lifestyle and nutritional factors that can contribute to depression as well as to folate deficiency. Moreover, it’s possible that low blood levels of folate may be the result, rather than the cause, of depression. For instance, depressed people may have a poorer diet.
There is an expensive prescription “medical food” containing high-dose L-methylfolate (brand names Deplin or Metafolin) that’s marketed as a way to augment antidepressant therapy in folate-deficient people. This form of folate is supposed to be more readily absorbed than folic acid, but more research is needed to see if this is true.