In 1996, the U.S. Food and Drug Administration issued a regulation requiring that all enriched cereal-grain products be fortified with folic acid by January 1998. An average increase in folic acid intake of 100 micro g/d was projected as a result of this fortification. The objective of the present study was to estimate the effect of this fortification on the intake of folic acid and total folate, and on the prevalence of individuals with inadequate folate intake and with high folic acid intake. We used data on food and nutrient intake from 1480 individuals who participated in the 5th and 6th examinations of the Framingham Offspring Cohort Study. Fortification was instituted during the 6th examination so that 931 participants were examined before its implementation (nonexposed) and 549 after implementation (exposed). Published data on total folate in enriched cereal-grain products were used to correct folate content in these foods to reflect fortification. Among nonsupplement users, folic acid intake increased by a mean of 190 [95% confidence interval (CI): 176, 204] micro g/d (P < 0.001) and total folate intake increased by a mean of 323 (95% CI: 296-350) micro g dietary folate equivalents (DFE)/d (P < 0.001) in the exposed participants. Similar increases were seen among supplement users exposed to fortification. The prevalence of exposed individuals with total folate intake below the estimated average requirement (320 micro g DFE/d) decreased from 48.6% (95% CI: 44.2-53.1%) before fortification to 7.0% (95% CI: 3.1-10.9%) after fortification in individuals who did not use folic acid supplements. This prevalence was approximately 1% or less for users of supplements both before and after fortification. Prevalence of individuals with folic acid intake above the upper tolerable intake level (1000 micro g folic acid/d) increased only among supplement users exposed to fortification (from 1.3 to 11.3%, P < 0.001). No changes in folic acid intake were observed over time in the nonexposed participants. By these estimations, folic acid fortification resulted in a mean increase in folic acid intake that was approximately twice as large as previously projected.

In recent years there has been growing interest in the vitamins folic acid and vitamin B12 because of the realization that the status of these vitamins in populations is less than adequate, and that such inadequacy may be linked to adverse public health outcomes. This concern has prompted the United States, Canada, and other countries to fortify grain products with folic acid, while additional countries are considering doing so in the near future. This presentation provides a new approach which relies on the combination of the concentrations in blood of vitamins and their respective functional indicators to establish cutoff points for assessing folate and vitamin B12 status in populations. The premise is based on the fact that the relationship between plasma vitamin concentrations and their respective functional indicators is inverse and biphasic, with a steep slope at low concentrations of the vitamin and a more moderate slope at higher plasma vitamin concentrations. We propose that the intersection of these two slopes be used as a guideline for assessing the status of these vitamins and the adequacy of fortification programs. The cutoff would be 10 nmol/L for serum folate and 340 nmol/L for red blood cell folate, based on lowest plasma homocysteine. For serum vitamin B12, the cutoff would be 150 pmol/L based on lowest methylmalonic acid and 300 pmol/L based on lowest homocysteine.

Background The implementation of folic acid fortification in the United States has resulted in unprecedented amounts of this synthetic form of folate in the American diet. Folic acid in circulation may be a useful measure of physiologic exposure to synthetic folic acid, and there is a potential for elevated concentrations after fortification and the possibility of adverse effects. Objective We assessed the effect of folic acid fortification on circulating concentrations of folic acid and 5-methyltetrahydrofolate in the Framingham Offspring Cohort. Design This is a cross-sectional study that used plasma samples from fasting subjects before and after fortification. Samples were measured for folate distribution with the use of an affinity-HPLC method with electrochemical detection. Results Among nonsupplement users, the median concentration of folic acid in plasma increased from 0.25 to 0.50 nmol/L (P < 0.001) after fortification, and among supplement users the median increased from 0.54 to 0.68 nmol/L (P = 0.001). Among nonsupplement users, the prevalence of high circulating folic acid (≥85th percentile) increased from 9.4% to 19.1% (P = 0.002) after fortification. Among supplement users, the prevalence of high circulating folic acid increased from 15.9% to 24.3% (P = 0.02). Folic acid intake and total plasma folate were positively and significantly related to high circulating folic acid after adjustment for potential confounding factors (P for trend < 0.001). Conclusions Folic acid fortification has resulted in increased exposure to circulating folic acid. The biochemical and physiologic consequences of this are unknown, but these findings highlight the need to understand the effects of chronic exposure to circulating folic acid.