Additional Studies Confirm Folates Role in Preventing Depression

Two new studies provide further evidence that low folate levels may have a role to play in depression. In one study, high folate levels were linked to a greater success rate in treating depressed geriatric patients. In the other study, patients with depression had a more difficult time metabolizing folate.

Researchers undertook the one study because previous findings suggested that lower folate levels are associated with reduced responsiveness to treatment with selective serotonin reuptake inhibitors (SSRI). In addition, depressed geriatric patients have lower levels of folate than controls, and folate supplements have been found to reduce death related to depression.

In the current small, randomized, observational study, researchers with New York University Medical Center gave 12 geriatric patients the SSRI sertraline, while 10 patients received the SSRI nortriptyline for 12 weeks. The researchers measured folate levels at the beginning of the study and after treatment. At the beginning of the study, all patients had folate levels within the normal range. However, patients who had higher folate levels at the beginning of the study achieved greater improvement after treatment.

The reason why folate may help reduce depression is because deficiency of this important B vitamin causes brain levels of mood-boosting serotonin to fall. In addition, low levels of folate triggers a reduction of 5-hydroxyindoleacetic acid, which may contribute to depression in individuals with a predisposition to depression. Folate also plays a role in the metabolism of S-adenosylmethionine (SAMe), an action which also contributes to proper levels of brain serotonin. The researchers called for additional research to evaluate the role of folate supplements in patients with folate levels in the low normal range.

In the other study, researchers studied folate levels and levels of the amino acid homocysteine in 5,948 subjects aged 46 to 49 years and 70 to 74 years. The study authors found that subjects who had relatively high levels of homocysteine in their blood were almost twice as likely to be depressed, compared to people with the lowest homocysteine blood levels. Depressed subjects also were more likely to have impaired folate metabolism. Homocysteine is an amino acid implicated in heart disease. Folate is known to lower levels of homocysteine. The study authors concluded that folic acid supplements may help prevent depression.

In the middle-aged subjects, low levels of folate also were linked to depression. But even though markers of folate metabolism were altered in depression, actual levels of folate in the blood did not differ between the elderly subjects with and without depression. Researchers suggested that this may be because measuring folate in the blood may not be an accurate indication of how much folate actually resides in cells.

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How did we qualify them ?

Alpert M. Prediction of Treatment Response in Geriatric Depression From Baseline Folate Level: Interaction With an SSRI or a Tricyclic Antidepressant. J Clin Psychopharmacol. 2003;23:3:309-313.

Bjelland I, Tell GS, Vollset SE, Refsum H, Ueland PM. Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study. Arch Gen Psychiatry. 2003 Jun;60(6):618-26.

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