title: Circulating folic acid in plasma: relation to folic acid fortification.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Vitamin Metabolism and Aging Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
authors.forename: Renee D
authors.initials: RD
authors.lastname: Kalmbach
authors.forename: Silvina F
authors.initials: SF
authors.lastname: Choumenkovitch
authors.forename: Aron M
authors.initials: AM
authors.lastname: Troen
authors.forename: Ralph
authors.initials: R
authors.lastname: D'Agostino
authors.forename: Paul F
authors.initials: PF
authors.lastname: Jacques
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood*; D005527:Food, Fortified; D006331:Heart Diseases / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009511:New England
chemical_list: D005492:Folic Acid
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