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: Jacob Selhub, Martha Savaria Morris, Paul F Jacques, Irwin H Rosenberg
• Journal: The American journal of clinical nutrition (Am J Clin Nutr) Vol. 89 Issue 2 Pg. 702S-6S (Feb 2009) ISSN: 1938-3207 [Electronic] United States
• PMID: 19141696 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Homocysteine
• Methylmalonic Acid
• Folic Acid
• 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
• Methylmalonyl-CoA Mutase
• Vitamin B 12

Topics

• 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase (metabolism)
• Aging (blood)
• Anemia, Pernicious (blood, diagnosis, epidemiology)
• Cognition Disorders (blood, diagnosis, epidemiology)
• Drug Interactions
• Female
• Folic Acid (administration & dosage, 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, blood)
• Vitamin B 12 Deficiency (blood, diagnosis, epidemiology)