Nutrition and Depression: The Role of Folate

Jonathan E. Alpert, MD, PhD, Maurizio Fava, MD


Medscape Psychiatry & Mental Health eJournal. 1997;2(1) 

In This Article

The Basis for Folate Deficiency in Depression

How folate interrelates with depression is unclear. A wide variety of factors and conditions are associated with folate deficiency states, including drugs (particularly certain anticonvulsants, antibiotics, oral contraceptives, and antifolate cancer chemotherapeutics); malabsorption syndromes; chronic diseases (including autoimmune disorders such as rheumatoid arthritis); inborn errors of folate metabolism such as 5,10-methylene tetrahydrofolate reductase deficiency; alcoholism; increased utilization states such as pregnancy; and dietary folate deficiency.[1,23] Does a primary folate deficiency produce depression and its symptoms, or does poor nutrition as a symptom of depression cause a decrease in folate level?

Consistent with the latter hypothesis--that poor nutrition in depression leads to low folate levels--is the finding that when measured across depressive subtypes, low folate appears to predominate in melancholic depression, and anorexia and weight loss are common features of this type.[10] Nevertheless, efforts to prove that low folate in depression is the result of poor diet have so far been inconclusive.[8,11] Mixed results may, in part, reflect the difficulty of obtaining an accurate dietary record among depressed patients. In addition, they may suggest a multifactorial etiology. Abou-Saleh and Coppen[23] hypothesized that it is a combination of decreased appetite, decreased absorption, and increased utilization of folate that results in folate depletion and eventually produces a CNS effect. In addition, as appears to be true of depression itself, the etiology of folate deficiency in depressive disorders and the temporal relationship between low folate levels and depression are likely to reflect considerable heterogeneity across patient populations. Among medical and alcohol-dependent populations, in particular, it is plausible to suggest that folate deficiency may be a predisposing factor to the development of depression. For other individuals with persistent depression, loss of appetite or poor food selection may contribute to the secondary development of low folate levels, which then seems likely to exacerbate the depression and produce greater refractoriness to standard antidepressant therapies.


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