Folate is a naturally occurring B vitamin (B9); its synthetic form is folic acid. When it is low during pregnancy, it can cause congenital neural tube defects in the developing fetus. Supplemental folic acid has been widely studied as a possible treatment for depression and cardiovascular disease. It is widely available in pharmacies, health food stores, and on the Internet; as in all such cases, the purity and potency of the compound may vary.

Mechanism of Action

Folate reduces the level of homocysteine, an amino acid thought to exacerbate some psychiatric symptoms. Folate is also involved in the synthesis of neurotransmitters and in many other metabolic pathways.

Use in Schizophrenia

In 1994, Goff et al. reported a correlation between low folate levels and negative symptoms in schizophrenia, thereby increasing interest in folate as a possible treatment.34 Five double-blind studies have been completed, three of which have been published. A study of 17 patients on methylfolate 15mg/day for 6 months reported “significantly improved clinical and social recovery.”35 A study of 42 patients given folic acid 2mg/day for 3 months reported significant improvement on PANSS positive and total, but not negative symptoms.36 Both of these studies used only patients with low serum folate levels. However, a study of 32 patients with normal serum folate levels, using folate 2mg/day for 3 months, reported no effect on negative symptoms.37 A study being submitted for publication of 100 patients treated with folic acid 5mg/day for 3 months found significant improvement in depression and in some cognitive function, but another unpublished study of 42 patients given folic acid 4mg/day for 3 months found no differences between patients taking folic acid and placebo. SMRI is supporting three other large, ongoing, double-blind trials.

Use in Bipolar Disorder

Although folate has been studied extensively for patients with depression, limited studies have been carried out for bipolar disorder. One study in bipolar patients demonstrated that elevated homocysteine levels were associated with impaired cognition (verbal learning, delayed memory, and executive function).38 SMRI is supporting two small studies: one using folate to improve cognition, and the other to retard the development of clinical disease in young adults with multiple risk factors for bipolar disorder.


If folate proves to be useful for serious psychiatric disorders, it is most likely to do so for depressive symptoms. Although widely used and relatively free of side effects, it is not entirely innocuous and at high doses has been suspected of possibly enhancing growth in developing cancers.