The rise and fall of blood folate in the United States emphasizes the need to identify all sources of folic acid 1 , 2

Folic acid–containing supplements and fortified foods, including enriched cereal–grain products and ready-to-eat (RTE) cereals, are the primary sources of folic acid intake in the United States (1). Changes in the intake of any of these sources may significantly affect blood folate concentrations. To effectively monitor how changes in folic acid intake are influencing trends in folate status, it is important to characterize the sources of folic acid, as illustrated in the recent publications by Yang et al (1) and Berry et al (2). During the past decade, as blood folate concentrations have first increased and then decreased, the assumption was that the blood folate changes were due solely to changes in folic acid intake from enriched cereal–grain products. A report by Pfeiffer et al (3) in this issue of the Journal provides the first opportunity to evaluate trends in blood folate concentrations in the US population that extend beyond the early postfortification phase (ie, 1999–2000) by encompassing the more recent periods of 2001–2002 and 2003–2004. In these 2 survey periods, serum and RBC folate concentrations declined significantly from those seen in 1999–2000. The observed decreases are of a magnitude much smaller than that of the initial increase that occurred in the wake of fortification. Detailed analysis of the sources of folic acid intake will be necessary before it is possible to ascertain whether the observed changes in blood folate concentrations could be attributed to changes in folic acid intakes from enriched cereal–grain products, folic acid–containing supplements, or RTE cereals. It is important to consider that changes in the use of folic acid–containing supplements may have affected blood folate concentrations in the years since fortification was implemented. Supplement use in the United States previously was reported to be greater during the first postfortification period (NHANES 1999–2000) than during the prefortification period (NHANES 1988–1994); considerable variation was seen, depending on race-ethnicity (4). The reported use of folic acid–containing supplements in predominantly white women of childbearing age across all time intervals fluctuated from 30% of that population before fortification (1995–1998), rising to 40% in 2004 and returning to prefortification proportions in 2005 (5). Differences in supplement use should also be considered as a potential explanation for observed differences in blood folate concentrations between different racial-ethnic groups. Yang et al (1) estimated that non-Hispanic white women in the United States obtained 48% of their folic acid intake from supplements, whereas non-Hispanic black and Hispanic women obtained only 26%, according to data from NHANES 2001–2002. No supplement use data are provided in the report by Pfeiffer et al (3); however, the rank order of blood folate concentrations among racialethnic groups—ie, non-Hispanic white Mexican American non-Hispanic black—likely is due in part to differences in the proportions of each of these groups who used folic acid– containing supplements (1, 6). Because the blood folate data were not analyzed separately for supplement users and nonusers, it is not possible to estimate the potential influence of supplement use on observed changes in blood folate concentrations (3). In future investigations of trends in blood folate concentrations, it would be of interest to determine whether folate status differs between supplement users and nonusers and whether supplement use is affected by race-ethnicity in each sex and age group. A potential explanation for the most recent observed decreases in blood folate concentrations may be that industry has reduced the amount of folic acid it adds to enriched cereal–grain products. In an analysis of a number of enriched foods during the early postfortification period (1998–1999), Rader et al (7) found that the total folate content of many of the analyzed foods far exceeded the amount required by federal regulations. Although there has been no systemic examination of changes in folate content of enriched cereal–grain products, 2 research groups have reported data supporting the conclusion that the amount of folic acid added to the food supply has been reduced (8, 9). Johnston and Tamura (8) found that, in 2002 and 2003, the folate content of white breads containing enriched flour was significantly lower than that observed in 2001. Poo-Prieto et al (9) used a new affinity/HPLC method to measure the quantity of folic acid in numerous folic acid–enriched foods. In their study, no evidence was found of folic acid overages in enriched products. An ongoing systematic evaluation of the folic acid content of enriched food products is needed to track changes that may be associated with observed fluctuations in blood folate concentrations in the US population, such as those reported by Pfeiffer et al (3). This evaluation will be a daunting task, considering the fact that there are thousands of food products—including such