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Calculation of red blood cell folate steady state conditions and elimination kinetics after daily supplementation with various folate forms and doses in women of childbearing age^1,2

¹ From the Institute of Nutrition and Food Sciences, Pathophysiology of Nutrition, University of Bonn, Bonn, Germany

Background: A maternal red blood cell (RBC) folate concentration > 906 nmol/L is thought to be optimal for lowering the risk of neural tube defects (NTDs) in pregnancy. Whereas the appearance of folate in RBCs has been followed during folic acid supplementation, data on elimination kinetics are not yet available.

Objective: The aim of our investigation was to estimate the steady state conditions and elimination kinetics of folate in RBCs.

Design: Data from 2 randomized, placebo-controlled, double-blind intervention trials were used for kinetic modeling. These studies were performed to investigate the appearance of folate in RBCs in healthy women of childbearing age after different supplementation strategies (study 1: n = 69; 400 µg folic acid/d and 416 µg [6S]-5-methyltetrahydrofolate/d for 24 wk; study 2: n = 21; 800 µg folic acid/d for 16 wk).

Results: For RBC folate concentrations, steady state conditions were not reached after 24 (study 1) and 16 (study 2) wk of folate supplementation. However, with the use of these data, we calculated the biological half-life (t_1/2) of RBC folate to be 8 wk. With the application of pharmacokinetic principles, steady state conditions for RBC folate should be reached after 40 wk (t_1/2 x 5).

Conclusion: With the use of pharmacokinetic principles, the appearance and elimination kinetics of RBC folate can be calculated on the basis of this t_1/2 value.

Key Words: Red blood cell folate • steady state • elimination • kinetics • neural tube defects

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