Background: There is a relationship between the etiology and management of clinical
depression and vitamin deficiencies.
Aim: To review the effect of dietary folic acid supplementation on cause, severity and treatment of
Methods: A narrative review of empirical and theoretical literature on the effect of folic acid supplementation
on the severity and treatment outcomes of depression.
Results: Many enzymes and neurotransmitters depend on folic acid for optimal functions. The
monoamine hypothesis of depression confirms the depletion of serotonin, dopamine, and norepinephrine.
The systemic level of methyl folate is dependent upon the enzyme methylenetetrahydrofolate
reductase [MTHFR], which is encoded by a polymorphic gene [C677T-MTHFR], as well as
being dependent on dietary folic acid intake. However, folate has procarcinogenic properties because
its coenzymes are involved in de novo purine and thymine nucleotide biosynthesis. Besides,
folate deficiency in normal tissues may also predispose to neoplastic transformation, while folate
supplementation may suppress the development of tumors in normal tissues. Epidemiological
studies revealed that low folate status is associated with depression; especially in terms of severity
and the outcome of antidepressant use.
Conclusion: The role of folic acid in the etiology and the management of depression cannot be
overemphasized. Folate supplementation has been yielding positive results in the management of