Background: Mandatory folic acid fortification of cereal-grain products was introduced in the United States in 1998 to decrease the risk that women will have children with neural tube defects. Objective: The objective was to determine the effect of folic acid fortification on concentrations of serum and red blood cell (RBC) folate, serum vitamin B-12, and plasma total homocysteine (tHcy) and methylmalonic acid (MMA) in the US population. Design: Blood was collected from a nationally representative sample of approximate to 7300 participants aged >= 3 y in the National Health and Nutrition Examination Survey (NHANES) during 1999-2000 and was analyzed for these B vitamin-status indicators. The results were compared with findings from the prefortification survey NHANES III (1988-1994). Results: The reference ranges (5th-95th percentiles) were 13.1-74.3 nmol/L for serum folate, 347-1167 nmol/L for RBC folate, and 179-738 pmol/L for serum vitamin B-12. For plasma tHcy and MMA, the reference ranges for serum vitamin B-12-replete participants with normal serum creatinine concentrations were 3.2-10.7 mu mol/L and 60-210 nmol/L, respectively. The prevalence of low serum folate concentrations (< 6.8 nmol/L) decreased from 16% before to 0.5% after fortification. In elderly persons, the prevalence of high serum folate concentrations (> 45.3 nmol/L) increased from 7% before to 38% after fortification; 3% had marginally low serum vitamin B-12 concentrations (< 148 pmol/L) and 7% had elevated plasma MMA concentrations (> 370 nmol/L). Seventy-eight percent of the US population had plasma tHcy concentrations < 9 mu mol/L. Conclusions: Every segment of the US population appears to benefit from folic acid fortification. Continued monitoring of B vitamin concentrations in the US population is warranted.
