Circulating folic acid in plasma: relation to folic acid fortification.
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.
Kalmbach
Renee D
RD
Vitamin Metabolism and Aging Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
Choumenkovitch
Silvina F
SF
Troen
Aron M
AM
D'Agostino
Ralph
R
Jacques
Paul F
PF
Selhub
Jacob
J
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
D005492:Folic Acid
Am J Clin Nutr. 2005 Aug;82(2):279-80
16087969
Arch Neurol. 2005 Apr;62(4):641-5
15824266
J Nutr. 2002 Sep;132(9):2792-8
12221247
Am J Clin Nutr. 2006 Apr;83(4):895-904
16600944
BMC Public Health. 2007 Mar 22;7:41
17378936
J Nutr. 2006 Jan;136(1):189-94
16365081
Am J Clin Nutr. 1997 Jun;65(6):1790-5
9174474
Am J Clin Nutr. 2003 Jan;77(1):221-5
12499345
N Engl J Med. 1999 May 13;340(19):1449-54
10320382
Birth Defects Res A Clin Mol Teratol. 2004 Nov;70(11):844-5
15468072
Am J Public Health Nations Health. 1957 Apr;47(4 Pt 2):4-24
13411327
Clin Chem. 2004 Feb;50(2):423-32
14670827
Prev Med. 1975 Dec;4(4):518-25
1208363
Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1325-9
17626997
Circulation. 2006 Mar 14;113(10):1335-43
16534029
Am J Epidemiol. 2004 Aug 15;160(4):339-49
15286019
Am J Clin Nutr. 2007 Jan;85(1):193-200
17209196
Br J Nutr. 2007 Oct;98(4):667-75
17617936
JAMA. 2001 Jun 20;285(23):2981-6
11410096
Am J Epidemiol. 1992 May 15;135(10):1114-26; discussion 1127-36
1632423
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19995-20000
18056804
Clin Chem. 2000 Mar;46(3):404-11
10702529
Eur J Clin Nutr. 1989 Sep;43(9):631-5
2606094
N Engl J Med. 2003 Mar 6;348(10):891-9
12621133
Br J Nutr. 2006 Jan;95(1):145-51
16441927