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Am J Clin Nutr. 2009 Mar;89(3):844-52. doi: 10.3945/ajcn.2008.26878. Epub 2009 Jan 21.

Steady state folate concentrations achieved with 5 compared with 1.1 mg folic acid supplementation among women of childbearing age.

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  • 1Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.



Synthetic folic acid (0.4-1.0 mg) consumed during the periconceptional period has been shown to reduce the risk of neural tube defects. Women with poor supplement adherence or a previous pregnancy affected by a neural tube defect may need to take higher doses of folic acid (4-5 mg). However, there are limited data on the pharmacokinetics of higher folic acid doses.


Our aim was to compare steady state folate concentrations in women of childbearing age who took 5 or 1.1 mg folic acid daily for 30 wk.


Forty nonpregnant women aged between 18 and 45 y, who did not take folic acid supplements, were enrolled in the study. Subjects were randomly assigned to take either 5 or 1.1 mg folic acid daily for 30 wk. Plasma and red blood cell (RBC) folate concentrations were measured at baseline and at weeks 2, 4, 6, 12, and 30.


There was no significant difference in baseline RBC folate concentrations between the 2 groups (1121 +/- 410 and 1035 +/- 273 nmol/L for the 5- and 1.1-mg folic acid groups, respectively). Significant differences in RBC folate were detected between groups at weeks 4, 6, 12, and 30. RBC folate concentrations by week 30 were 2339 +/- 782 and 1625 +/- 339 nmol/L for the 5- and 1.1-mg folic acid groups, respectively.


The use of 5 mg folic acid among women of childbearing age produced higher blood folate concentrations, with a faster rate of folate accumulation, compared with 1.1 mg folic acid.

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