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Elevated plasma folate in older adults is associated with more pronounced evidence of vitamin B12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin

Recent reports based on NHANES data showed that in older adults exposed to folic acid fortification, the combination of low B12 and elevated folate is associated with higher homocysteine (Hcy) and methylmalonic acid (MMA) and higher odds ratios for cognitive impairment and anemia than the combination of low B12 and non‐elevated folate. These findings await confirmation in other populations. We compared indicators of B12 status and cognitive function among elderly Latinos (Sacramento Area Latino Study on Aging: n=1535, age≥60y) with elevated and non‐elevated plasma folate. Subjects were divided into 4 groups based on plasma B12 (< or ≥148 pmol/L) and folate (≤ or >45.3 nmol/L). Hcy, MMA, holotranscobalamin (holoTC), holoTC/B12 ratio, modified mini‐mental state examination (3MSE) and delayed recall scores were compared among the groups. Hcy and MMA were highest and holoTC and holoTC/B12 ratio were lowest in individuals with low B12/elevated folate (n=22) compared with all other groups (p≤0.003). No differences in cognitive function scores were observed between the low B12/elevated folate group and the other groups. Low B12 is associated with more pronounced metabolic evidence of B12 deficiency when folate is elevated than when folate is not elevated. These data should be considered when assessing the costs, risks, and benefits of folic acid and B12 fortification programs.