Does the MTHFR 677C→T variant affect the Recommended Dietary Allowance for folate in the US population?

Background: The MTHFR 677C -> T variant is associated with reduced enzyme activity, abnormalities of folate metabolism, and potential increase in folate requirement. The effect of this variant on the Recommended Dietary Allowance (RDA) for folate is unclear. Objective: The aim of this study was to assess the effect of the MTHFR 677C -> T polymorphism on the current folate RDA for US adults aged >= 19 y (400 mu g/d) by race and ethnicity. Design: We calculated the projected RDA for folate for each racial and ethnic group according to the methods of the Institute of Medicine. We modeled the projected RDA with different hypothetical effect sizes ranging from 5% to 50%. The RDA value was then weighted according to the US prevalence of the TT (or the combined CT/TT) genotype in each racial and ethnic group. Results: The projected RDA ranges were based on TT genotype frequencies and on different effect sizes (5-50%) that ranged from 400 to 421 mu g/d for non-Hispanic whites, 401-436 mu g/d for Mexican Americans, and 400-402 mu g/d for non-Hispanic blacks. Conclusions: Our findings suggest that the current RDA for folate differs little for non-Hispanic whites, non-Hispanic blacks, and Mexican Americans irrespective of the MTHFR TT genotype, and, from a population perspective, the MTHFR 677C -> T variant does not warrant modifications to the current RDA for dietary folate at this time. Am J Clin Nutr 2009; 89: 1269-73.