People suffering from depression often look for nondrug treatments. Who wouldn’t prefer to take a vitamin pill, for instance, over an antidepressant drug that often causes side effects? That’s why the idea of treating depression with the B vitamin folate is enticing.
For years researchers have noted an association between low blood levels of folate and depression. And it’s biochemically plausible that a folate deficiency could increase the risk of depression. 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 health.
Putting folate to the test
Many observational studies, mostly done before mandatory fortification of flour with folate went into effect in 1998, found that people with low dietary intakes or blood levels of folate have higher rates of depression.
But 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. Depressed people may also drink alcohol in excess, and alcohol interferes with folate absorption and increases its excretion.
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.
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.