Increased Dietary Intake of Folate Reduces the Risk of Developing Alzheimer's Disease

Abstract & Commentary

By M. Flint Beal, MD Dr. Beal is Professor and Chairman, Department of Neurology, Cornell University Medical College and is Editor of Neurology Alert. Dr. Beal reports no consultant, stockholder, speaker's bureau, research, or other relationships related to this field of study.

Synopsis: An increased dietary intake of folate reduces the risk of developing AD.

Source: Corrada M, et al. Reduced Risk of Alzheimer's Disease with High Folate Intake: The Baltimore Longitudinal Study of Aging. Alzheimer's & Dementia. 2005;1:11-18

The present report comes from the Baltimore Longitudinal Study of Aging. This is a large study prospectively following patients for development of Alzheimer's disease (AD). The study was initiated in 1958 by the National Institute of Aging to prospectively examine the normal aging process. It was originally limited to men, but the study began enrolling women in 1978. The study cohort comprises well-educated, predominantly white community-dwelling volunteers who return every 2 years for 2.5 days of multidisciplinary tests. These include medical, physiological, and biomedical examinations, as well as cognitive evaluations. The present study was based on a dietary intake report, which previously has been determined to be an accurate assessment of vitamin intake. Corrada and colleagues evaluated whether total intake from diet plus supplements of antioxidant vitamins including vitamin E, C, carotenoids, and B vitamins, including folate, B6, and B12 were associated with a reduced risk of developing AD. The participants were 579 non-demented elderly volunteers who recorded their dietary supplement intake for a 7-day period. After a mean follow-up of 9.3 years, 57 participants developed AD, as assessed by standard criteria. A higher intake of folate resulted in a relative risk of developing AD of 0.41, and vitamin E with a relative risk of 0.56. Vitamin B6 had a relative risk of 0.41. These were individual associations of decreased risk of developing AD after adjusting for age, gender, education, and caloric intake. When the 3 vitamins were analyzed together, however, only intake of folate at or above the recommended dietary allowance was associated with significant decreased risk of AD. These findings suggest that an increased dietary intake of folate reduces the risk of developing AD.


In previous columns, the association of increased homocysteine levels with AD has been discussed. This appears to be independent of the increased risk of vascular diseases associated with elevated homocysteine levels. This prospective study provides evidence of a reduced risk of AD among people with high intake of folate. This may very well be an effect on homocysteine levels. Some studies of antioxidant supplements have found effects of vitamin C or vitamin E with vitamin C; however, this was not observed in the present study. The present results were obtained before mandatory folate fortification of green products began in the United States in 1998. This was done with the intention of reducing neural tube defects. It is, therefore, as yet unclear, whether folate supplementation will be beneficial. Corrada et al, however, felt that almost half of the participants would have been deficient regardless of the increased folate fortification in present diets. These results provide further evidence that modulation of diet may have a major effect on risk of developing AD. As noted, some but not all prior studies of antioxidant vitamins have shown a reduced risk of developing AD. Furthermore, diets with high amounts of omega 3 fatty acids also reduce the risk of developing AD. The present results provide further evidence that intake of folate may also have a major effect on risk of developing AD.