Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 6/5/2008
Publication Date: 11/24/2009
Citation: Morris, M.S., Jacques, P. 2009. Folate and neurological function: epidemiology perspective. In: Baily, L.B., editor. Folate in Health and Disease. 2nd edition. Boca Raton, FL: CRC Press. p. 1733-1744. Interpretive Summary:
Technical Abstract: This book chapter reviews and summarizes published literature on the relationship between folate status and Alzheimer’s disease, age-related cognitive impairment, and depression. Much of this research was motivated by the hypothesis that high circulating levels of the sulfur-containing amino acid homocysteine, which results from low folate status, was a direct cause of these mental health problems. For this reason, studies that considered the association between circulating homocysteine levels and the three outcomes are included. The largest group of studies considered folate and/or homocysteine status in relation to performance on cognitive function tests. Publications were added to this subgroup very gradually from the 1980s through the early years of the 21st century, and early reviewers concluded that results were mixed. However, a large number of studies were published in 2005, and when these and later studies were added to the rest, results overwhelmingly supported the existence of an association between low folate status, high circulating homocysteine levels, and poor cognitive test performance. Few studies have considered the independent effects of folate and homocysteine, but those that have tended to suggest that folate does not operate in cognition through homocysteine alone. Although folate deficiency and depression have long been thought to be related, this association has been addressed in relatively few epidemiological studies, and drawing conclusions from them is hampered by variation among them in the age group studied and the methods used to evaluate depression. Important considerations include the possibility that depression in young people has different causes than depression in the elderly and the additional complexity of diagnosing depression in the elderly, whose somatic complaints may be misinterpreted as depressive symptoms. Of course, correlations do not always equate with cause and effect relationships, and only a very few relevant clinical trials have been completed. Because these trials were conducted only recently, their results are complicated by the unprecedented folic acid intakes achievable through food folic acid fortification and the possibility that folic acid itself, or the very high folate levels that supplementation and fortification produce, are actually harmful to mental health.