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

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: >or=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 >or=148 pmol/L) and folate (<or= 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 <or= 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.

FIGURE 1

Indicators of vitamin B-12 status in elderly Latinos. Subjects were grouped by low and nonlow plasma vitamin B-12 (< or ≥148 pmol/L) and nonelevated and elevated plasma folate (≤ or >45.3 nmol/L). Bars represent geometric means with 95% CIs for homocysteine (A), methylmalonic acid (B), holotranscobalamin (C), and the ratio of holotranscobalamin to total vitamin B-12 (holoTC/B12 ratio) (D). Sample sizes for each group are as follows: low vitamin B-12/nonelevated folate, n = 78; low vitamin B-12/elevated folate, n = 22; nonlow vitamin B-12/nonelevated folate, n = 1055; nonlow vitamin B-12/elevated folate, n = 380. Interactive effects of vitamin B-12 (low or nonlow) and folate (nonelevated or elevated) for all 4 dependent variables were detected, P < 0.001 (2-factor ANOVA). Differences between the groups were assessed by Scheffe test, controlled for age, sex, education, supplement use, and creatinine. Different letters represent significantly different values, P ≤ 0.001.

FIGURE 2

Geometric mean (with 95% CI) red blood cell (RBC) folate concentrations in elderly Latinos. Subjects were grouped by low and nonlow plasma vitamin B-12 (< or ≥148 pmol/L) and nonelevated and elevated plasma folate (≤ or >45.3 nmol/L). Sample sizes for each group are as follows: low vitamin B-12/nonelevated folate, n = 78; low vitamin B-12/elevated folate, n = 22; nonlow vitamin B-12/nonelevated folate, n = 1055; nonlow vitamin B-12/elevated folate, n = 380. No interactive effect of vitamin B-12 (low or nonlow) and folate (nonelevated or elevated) for RBC folate was detected (2-factor ANOVA). Differences among the groups were assessed by Scheffe test, controlled for age, sex, education, supplement use, and creatinine. Different letters represent significantly different values, P ≤ 0.001.