title: Folate-vitamin B-12 interaction in relation to cognitive impairment, anemia, and biochemical indicators of vitamin B-12 deficiency.
abstract: Previous reports on pernicious anemia treatment suggested that high folic acid intake adversely influences the natural history of vitamin B-12 deficiency, which affects many elderly individuals. However, experimental investigation of this hypothesis is unethical, and the few existing observational data are inconclusive. With the use of data from the 1999-2002 National Health and Nutrition Examination Survey (NHANES), we evaluated the interaction between high serum folate and low vitamin B-12 status [ie, plasma vitamin B-12 < 148 pmol/L or methylmalonic acid (MMA) > 210 nmol/L] with respect to anemia and cognitive impairment. With subjects having both plasma folate < or = 59 nmol/L and normal vitamin B-12 status as the referent category, odds ratios for the prevalence of anemia compared with normal hemoglobin concentration and impaired compared with unimpaired cognitive function were 2.1 (95% CI: 1.1, 3.7) and 1.7 (95% CI: 1.01, 2.9), respectively, for those with low vitamin B-12 status but normal serum folate and 4.9 (95% CI: 2.3, 10.6) and 5.0 (95% CI: 2.7, 9.5), respectively, for those with low vitamin B-12 status and plasma folate >59 nmol/L. Among subjects with low vitamin B-12 status, mean circulating vitamin B-12 was 228 pmol/L for the normal-folate subgroup and 354 pmol/L for the high-folate subgroup. We subsequently showed increases in circulating homocysteine and MMA concentrations with increasing serum folate among NHANES participants with serum vitamin B-12 < 148 pmol/L, whereas the opposite trends occurred among subjects with serum vitamin B-12 > or = 148 pmol/L. These interactions, which were not seen in NHANES III before fortification, imply that, in vitamin B-12 deficiency, high folate status is associated with impaired activity of the 2 vitamin B-12-dependent enzymes, methionine synthase and MMA-coenzyme A mutase.
authors.affiliation: Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA. jacob.selhub@tufts.edu
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
authors.forename: Martha Savaria
authors.initials: MS
authors.lastname: Morris
authors.forename: Paul F
authors.initials: PF
authors.lastname: Jacques
authors.forename: Irwin H
authors.initials: IH
authors.lastname: Rosenberg
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000378:metabolism; D000375:Aging / Q000097:blood; D000752:Anemia, Pernicious / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D003072:Cognition Disorders / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D004347:Drug Interactions; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood; D008765:Methylmalonyl-CoA Mutase / Q000378:metabolism; D008875:Middle Aged; D009749:Nutrition Surveys; D009752:Nutritional Status; D016017:Odds Ratio; D015995:Prevalence; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000097:blood*; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*
chemical_list: D006710:Homocysteine; D008764:Methylmalonic Acid; D005492:Folic Acid; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D008765:Methylmalonyl-CoA Mutase; D014805:Vitamin B 12