Folate and Vitamin B12 Deficiencies and Neurodegenerative Disease

Martha Clare Morris, ScD; Denis A. Evans, MD; Julia L. Bienias, ScD; Christine C. Tangney, PhD; Liesi E. Hebert, ScD; Paul A. Scherr, PhD, ScD; Julie A. Schneider, MD. Dietary Folate and Vitamin B12 Intake and Cognitive Decline Among Community-Dwelling Older Persons. Arch Neurol. 2005; 62: 641-645.
http://archneur.ama-assn.org/cgi/content/abstract/62/4/641

ABSTRACT
Background: Deficiencies in folate and vitamin B12 have been associated with neurodegenerative disease.

Objective: To examine the association between rates of age-related cognitive change and dietary intakes of folate and vitamin B12.

Design: Prospective study performed from 1993 to 2002.

Setting: Geographically defined biracial community in Chicago, Ill.

Participants: A total of 3718 residents, 65 years and older, who completed 2 to 3 cognitive assessments and a food frequency questionnaire.

Main Outcome Measure: Change in cognitive function measured at baseline and 3-year and 6-year follow-ups, using the average z score of 4 tests: the East Boston Tests of immediate and delayed recall, the Mini-Mental State Examination, and the Symbol Digit Modalities Test.

Results: High folate intake was associated with a faster rate of cognitive decline in mixed models adjusted for multiple risk factors. The rate of cognitive decline among persons in the top fifth of total folate intake (median, 742 痢/d) was more than twice that of those in the lowest fifth of intake (median, 186 痢/d), a statistically significant difference of 0.02 standardized unit per year (P = .002). A faster rate of cognitive decline was also associated with high folate intake from food (P for trend = .04) and with folate vitamin supplementation of more than 400 痢/d compared with nonusers (beta = -.03, P<.001). High total B12 intake was associated with slower cognitive decline only among the oldest participants.

Conclusions: High intake of folate may be associated with cognitive decline in older persons. These unexpected findings call for further study of the cognitive implications of high levels of dietary folate in older populations.

Author Affiliations: Rush Institute for Healthy Aging (Drs Morris, Evans, Bienias, and Hebert), Departments of Internal Medicine (Drs Morris, Evans, Bienias, and Hebert), Preventive Medicine (Dr Morris), and Clinical Nutrition (Dr Tangney), and Rush Alzheimer's Disease Center (Dr Schneider), Rush University Medical Center, Chicago, Ill; and Division of Adult and Community Health, Centers for Disease Control and Prevention, Atlanta, Ga (Dr Scherr).

COMMENT: Folic acid and Vitamin B-12 work together so this study, which shows a worsening of brain function with higher intakes of folic acid, but a better outcome with Vitamin B-12 is challenging.

I wonder if this outcome is because folic acid tends to be taken in isolation as a supplement or an addition to foods such as bread, whereas Vitmin B-12 tends to be obtained from natural foods? If this is the reason, then it strengthens the case for eating real food instead of relying on supplements to make good an inadequate diet.

This may be bad news for vegans and other extreme vegetarians whose intakes are likely to be unbalanced with higher than safe intakes of folic acid, and inadequate amounts of B-12.