Principal Investigator: Jacob Selhub
Abstract: In 1996, the U.S. Food and Drug Administration published a regulation to be effective by January 1998 that all enriched fluor, breads, rive, pasta, corn meal, and other grain products would contain 140 micrograms of folic acid per 100 grams. The main purpose of this proposed study is to examine the impact of fortification on folate status in the Framingham Offspring Study cohort. We have measured plasma folate and homocysteine concentrations at the 5th examination cycle (January 1991-December 1994), and have preliminary data on a subset of subjects from the 6th examination cycle (January 1995-September 1998). We propose to measure folate and homocysteine status at the 7th examination cycle (September 1998-August 2001) so that we can establish post-fortification concentrations of plasma folate and homocysteine in the entire cohort. We plan to test the following hypotheses: 1) Current folic acid fortification levels are adequate to virtually eliminate low folate status and elevated homocysteine concentrations associated with inadequate folate status in relatively healthy, non- institutionalized adults. 2) Folic acid fortification at current levels will largely remove the methylenetetrahydrofolate reductase (MTHFR) C677T mutation as a risk factor for elevated homocysteine concentrations. 3) The increase in folate intake due to fortification will increase the prevalence of low vitamin B12 status in association with folate intakes above 1 microgram/day. 4) The important sources of folate in the diet are dramatically changed in the area of folic acid fortification. The following specific aims address each of these hypotheses in the Framingham Offspring cohort, a population-based sample of adults, in which three serial blood samples will be obtained between the years 1991 and 2001 (with at least one sample obtained before and after implementation of fortification) in combination with members of the Framingham Omni minority cohort, which was established between 1994 and 1998: 1) To assess the change in plasma and RBC folate and plasma homocysteine concentrations associated with the FDA-RBC folate at the 7th examination cycle, and RBC folate at the 6th examination. 2) To determine if the relation between homocysteine and MTHFR C677T genotype is weakened after implementation of folic acid fortification, we will determine MTHFR genotype for the C677T mutation in the Offspring cohort. 3) To evaluate the potential for an increased prevalence of low vitamin B12 status in the presence of high folic acid intakes after fortification, we will measure plasma vitamin B12 and dietary supplemental nutrient intake using the Willett food frequency questionnaire at examination 7. 4) To determine the contribution of folic acid from fortification of folic acid from fortification to total dietary folate and the change in percent contribution for each source before and after fortification so that we can characterize the most important sources of folate in the era of fortification, we will measure dietary and supplemental nutrient intake using the Willett food frequency questionnaire at examination 7.
Funding Period: 1999-08-01 - 2003-07-31
more information: NIH RePORT