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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #242168
Title: Circulating folic acid in plasma: relation to folic acid fortification

Author
item SELHUB, JACOB - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item KALMBACH, RENEE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item CHOUMENKOVITCH, SILVINA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item TROEN, ARON - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item JACQUES, PAUL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item D'AGOSTINO, RALPH - Boston University Medical School

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/30/2008
Publication Date: 9/8/2008
Citation: Selhub, J., Kalmbach, R., Choumenkovitch, S., Troen, A., Jacques, P., D'Agostino, R. 2008. Circulating folic acid in plasma: relation to folic acid fortification. American Journal of Clinical Nutrition. 88:763-768.

Interpretive Summary: Since mandatory folic acid (FA) fortification in 1998 numerous studies have reported a dramatic impact on folate status and related health outcomes. While there are benefits to improved folate status, there may be consequences of consuming high amounts of synthetic FA found in fortified foods and vitamin supplements. High FA intake can overwhelm the body’s absorptive capacity, resulting in the appearance of FA in circulation. The safety of this exposure is currently unknown and there are increasing concerns that high FA intake is associated with adverse effects. The objective was to characterize circulating FA status in the US population before and after fortification. To accomplish this, we determined the effect of FA fortification on plasma concentrations of circulating FA and identified determinants of high circulating FA. Our results indicated FA fortification and supplement use significantly increased the prevalence of having detectable FA. The prevalence of high circulating FA also significantly increased in non supplement users and in supplement users. FA intake and total plasma folate were positively and significantly related to the prevalence of high circulating FA. Thus, it appears almost all Americans are exposed to FA in circulation and that high FA intake increases serum FA concentrations.

Technical Abstract: 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. We assessed the effect of folic acid fortification on circulating concentrations of folic acid and 5-methyltetrahydrofolate in the Framingham Offspring Cohort. 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. 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). 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.