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Metabolic evidence of vitamin B-12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin, is more pronounced in older adults with elevated plasma folate^1,2,3

¹ From the School of Medicine, Department of Medical Pathology and Laboratory Medicine (JWM, and RG), the US Department of Agriculture, Agricultural Research Service Western Human Nutrition Research Center (MGG and LHA), and the Department of Nutrition (LHA), University of California, Davis, CA, and the Department of Epidemiology, University of Michigan, Ann Arbor, MI (MNH).

² Supported by NIH grants AG12975, AG10129, and AG10220 and USDA grant 00-35200-9073.

³ Address correspondence to R Green, UC Davis Medical Center, Department of Medical Pathology and Laboratory Medicine, PATH Building, 4400 V Street, Sacramento, CA 95817. E-mail: ralph.green{at}ucdmc.ucdavis.edu.

ABSTRACT

Background: An analysis of data from the National Health and Nutrition Examination Survey indicated that in older adults exposed to folic acid fortification, the combination of low serum vitamin B-12 and elevated folate is associated with higher concentrations of homocysteine and methylmalonic acid and higher odds ratios for cognitive impairment and anemia than the combination of low vitamin B-12 and nonelevated folate. These findings await confirmation in other populations.

Objective: The purpose was to compare metabolic indicators of vitamin B-12 status, cognitive function, and depressive symptoms among elderly Latinos with elevated and nonelevated plasma folate.

Design: Cross-sectional data were analyzed for 1535 subjects (age: 60 y) from the Sacramento Area Latino Study on Aging. Subjects were divided into 4 groups on the basis of plasma vitamin B-12 (< or 148 pmol/L) and folate ( or >45.3 nmol/L). Homocysteine, methylmalonic acid, holotranscobalamin, ratio of holotranscobalamin to vitamin B-12, Modified Mini-Mental State Examination, delayed recall, and depressive symptom scores were compared between the groups.

Results: Individuals with low vitamin B-12 and elevated folate (n = 22) had the highest concentrations of homocysteine and methylmalonic acid and the lowest concentration of holotranscobalamin and ratio of holotranscobalamin to vitamin B-12 when compared with all other groups (P 0.003). No differences in Modified Mini-Mental State Examination, delayed recall, and depressive symptom scores were observed between the low vitamin B-12 and elevated-folate group compared with other groups.

Conclusions: Low vitamin B-12 is associated with more pronounced metabolic evidence of vitamin B-12 deficiency when folate is elevated than when folate is not elevated. These data should be considered when assessing the potential costs, risks, and benefits of folic acid and vitamin B-12 fortification programs.

Received for publication January 20, 2009. Accepted for publication July 31, 2009.

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				R. Carmel Does high folic acid intake affect unrecognized cobalamin deficiency, and how will we know it if we see it? Am. J. Clinical Nutrition, December 1, 2009; 90(6): 1449 - 1450. [Full Text] [PDF]