In vitamin B 12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations

• Published in: Proceedings of the National Academy of Sciences - PNAS 2007-12, Vol.104 (50), p.19995-20000
• Main Authors: Selhub, Jacob, Morris, Martha Savaria, Jacques, Paul F.
• Format: Article
• Language: English
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0709487104

In a recent study of older participants (age ≥60 years) in the 1999–2002 National Health and Nutrition Examination Survey (NHANES), we showed that a combination of high serum folate and low vitamin B 12 status was associated with higher prevalence of cognitive impairment and anemia than other combinations of vitamin B 12 and folate status. In the present study, we sought to determine the joint influence of serum folate and vitamin B 12 concentrations on two functional indicators of vitamin B 12 status, total homocysteine (tHcy) and methylmalonic acid (MMA), among adult participants in phase 2 of the NHANES III (1991–1994) and the NHANES 1999–2002. Exclusion of subjects who were 148 pmol/liter (L), concentrations of both metabolites decreased significantly as serum folate increased. In subjects with lower serum vitamin B 12 , however, metabolite concentrations increased as serum folate increased starting at ≈20 nmol/L. These results suggest a worsening of vitamin B 12 's enzymatic functions as folate status increases in people who are vitamin B 12 -deficient.