Stahl 1 reviews L-methylfolate as a possibly helpful adjunctive antidepressant agent, 1 and Mischoulon and Fava 2 briefly review the evidence that folates, including folic acid, a stable synthetic substance, could be useful augmenting antidepressant agents. However, there is some evidence of possibly harmful or, at the least, disappointing effects of folate supplementation. 1. There has long been a concern that folate supplementation might mask, or even worsen, the manifestations of B 12-deficiency anemia. L-Methylfolate may be less likely to do this than folic acid. 3 2. Folates are growth-promoting substances and therefore may in fact be dangerous at the early stage of tumor growth in colon cancer. 4-6 3. Since folate deficiency has been linked with elevated homocysteine levels, which in turn are linked to vascular pathology, there was hope that folate supplementation might be beneficial in promoting vascular health and slowing the rate of cognitive decline. Folate supplementation has been disappointing in prevention of cardiovascular morbidity in recent studies. 7,8 In one community study, 9 higher intake of folate was associated with a decline in cognition, and B vitamin administration has not been associated with a decrease in dementia. 10,11 4. A recent study 12 showed that administration of B vitamins, including B 12 and folic acid, led to a decrease in homocysteine levels without decreasing depression severity or incidence. 5. The use of synthetic folic acid may result in unmetabolized folic acid in the serum. The consequences of this are unknown. 3,4 It is not yet clear that folates will be safe and effective adjunctive agents in treating depression, particularly if the patient is B 12 deficient.
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