Folate-vitamin B-12 interaction in relation to cognitive impairment, anemia, and biochemical indicators of vitamin B-12 deficiency

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 d...

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Published in:The American journal of clinical nutrition Vol. 89; no. 2; p. 702S
Main Authors: Selhub, Jacob, Morris, Martha Savaria, Jacques, Paul F, Rosenberg, Irwin H
Format: Journal Article
Language:English
Published: United States 01.02.2009
Subjects:
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - metabolism
Aging - blood
Anemia, Pernicious - blood
Anemia, Pernicious - diagnosis
Anemia, Pernicious - epidemiology
Cognition Disorders - blood
Cognition Disorders - diagnosis
Cognition Disorders - epidemiology
Drug Interactions
Female
Folic Acid - administration & dosage
Folic Acid - blood
Homocysteine - blood
Humans
Male
Methylmalonic Acid - blood
Methylmalonyl-CoA Mutase - metabolism
Middle Aged
Nutrition Surveys
Nutritional Status
Odds Ratio
Prevalence
Vitamin B 12 - administration & dosage
Vitamin B 12 - blood
Vitamin B 12 Deficiency - blood
Vitamin B 12 Deficiency - diagnosis
Vitamin B 12 Deficiency - epidemiology
ISSN:1938-3207, 1938-3207
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Summary: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.
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ISSN:1938-3207
1938-3207
DOI:10.3945/ajcn.2008.26947C