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Folic Acid's Role in Cognition & Depression Highlighted in Review

Homocysteine Link Expands to Depression

A recent review in the British Medical Journal outlined the evidence that suggests folic acid can prevent depression, dementia and perhaps even Alzheimers disease.

The reviewer noted that folate deficiency has been reported in up to one third of psychiatric outpatients or inpatients. He also noted that depressed patients with folate deficiency had higher depression scores and a poorer response to standard treatment with antidepressants. Other studies have indicated that plasma homocysteine is raised in 20-30% of depressed patients.

The reviewer also highlighted a number of studies showing folic acid can benefit patients with depression. In a double-blind, placebo controlled trial in depressive patients treated with lithium, the addition of 200 µg of folic acid for one year significantly improved affective morbidity. Similarly, depressed patients treated with both 500 µg folic acid and the drug Prozac for 10 weeks experienced a significantly improved antidepressant response, especially in women. In another double-blind, placebo controlled study, researchers combined 15 mg of methylfolate to standard psychotropic medication and reported significant improvement in depressed and schizophrenic patients over six months. In an earlier controlled study, folic acid alone (15 mg daily) improved both mood and neuropsychological function in depressed patients treated for four months.

In addition, the reviewer points out, there is a clear link between Alzheimers disease and high levels of the amino acid homocysteine. In a case-control study of 164 Alzheimers disease patients, cognitive decline was significantly associated with raised plasma homocysteine and lowered serum folate and vitamin B12 concentrations. In the Framingham study, a raised plasma homocysteine concentration doubled the risk of developing Alzheimers and non-Alzheimers dementia. Folic acid, vitamin B6, vitamin B12 and/or betaine have been shown to lower high homocysteine levels.

Researchers believe folic acid works in the same way as SAMe (S-adenosylmethionine). Both folic acid and SAMe affect methylation in the brain, a process linked to mood and cognitive function. Methylation also plays a role in the metabolism of homocysteine, the amino acid linked to heart conditions and other diseases. Folic acid and SAMe also both influence monoamine metabolism, a process linked to depression. In numerous studies, low levels of folate in serum, red cells, and cerebrospinal fluid and high levels of plasma homocysteine are linked to depression and dementia.


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