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Title: 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

Author
item MILLER, JOSHUA - University Of California
item GARROD, MAJORIES - University Of California
item Allen, Lindsay - A
item HAAN, MARY - University Of California
item GREEN, RALPH - University Of California

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/2/2009
Publication Date: 9/2/2009
Citation: Miller, J.W., Garrod, M.G., Allen, L.H., Haan, M.N., Green, R. 2009. 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. American Journal of Clinical Nutrition. 90:1586-1592.

Interpretive Summary: Previous analysis of data from the National Health and Nutrition Examination Survey, conducted after folic acid fortification of flour, indicated that the combination of low serum vitamin B12 and elevated serum folate was associated with higher serum homocysteine (Hcy) and methylmalonic acid (MMA), and greater risk of cognitive impairment and anemia, compared to the combination of low serum B12 and normal serum folate. To test these associations in another population, data from 1535 subjects from the Sacramento Area Latino Study on Aging (age equal or greater than 60 years) were divided into four groups; plasma B-12 (< or equal or greater than 148 pmol/L) and folate (equal or less than or >45.3 pmol/L). Individuals with low B12 and elevated folate (n=22) had the highest serum Hcy and MMA (metabolic evidence of more pronounced vitamin B12 deficiency) compared to the other 3 groups (P<0.003). There were no differences in the Modified Mini-Mental State Examination, delayed recall, or depressive symptom scores between the low vitamin B-12 and elevated folate group and the other groups. The data support the possibility that elevated folate status may exacerbate metabolic symptoms of vitamin B12 deficiency. These results should be tested in other population groups, with clarification of possible mechanisms involved, to confirm this apparently adverse effect of high folate status on vitamin B12 metabolism.

Technical 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: greater than or less than 60y) from the Sacramento Area Latino Study on Aging. Subjects were divided into 4 groups on the basis of plasma vitamin B-12 (< or greater than or less than 148 pmol/L) and folate (less than or equal to 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 less than or equal to 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 and vitamin B-12 fortification programs.