Folate and vitamin B12 status in relation to macrocytosis, anemia, and cognitive impairment in older Americans

Abstract

Fears of harm to seniors from food folate fortification are based on an age-related decrease in vitamin B12 status and historic case reports showing that folic acid therapy cured vitamin B12-deficiency anemia while neuropsychiatric effects persisted or worsened. Our objective was to assess interactions between folate and vitamin B12 status relative to macrocytosis (MC), anemia, and cognitive impairment (i.e., digit symbol-coding score<34) in Americans aged ≥ 60 y (N=1459). We excluded seniors reporting stroke, alcoholism, recent anemia therapy, or diseases of the kidneys, liver, thyroid, or coronary arteries. We defined low vitamin B12 status as serum B12<148 pmol/L or serum methylmalonic acid above the 90th percentile of subjects aged 30–39 y. Odds ratios (OR) (95% CI) relating low B12 status to MC, anemia, and cognitive impairment were 1.8 (1.01–3.3), 2.7 (1.7–4.3), and 2.4 (1.6–3.8), respectively, after control for demographics, smoking, alcohol use, diabetes, cancer, and serum levels of glucose, creatinine, and ferritin. Serum folate interacted with vitamin B12 status relative to anemia and cognitive impairment (P<0.05). In seniors with low B12 status, ORs (95% CI) relating serum folate>59 nmol/L (HSF) to anemia and cognitive impairment were 3.0 (95% CI, 1.4–6.9) and 2.7 (95% CI, 1.2–6.1), respectively. In seniors with normal B12 status, the OR (95% CI) relating HSF to cognitive impairment was 0.4 (0.2–0.9). HSF was unrelated to MC. In conclusion, when B12 status was normal, HSF was linked to protection from cognitive impairment. When B12 status was low, HSF was positively related to anemia and cognitive impairment.