Comparing folic acid pharmacokinetics among women of childbearing age: Single dose ingestion of 1.1 MG versus 5 MG folic acid

Background A 2001 study suggested that supplementation with 5 mg folic acid, among women of childbearing age, is needed to render maximum protection against neural tube defects (NTD). No human study is presently available which examined the pharmacokinetics of 5 mg folic acid. Objective To compare the pharmacokinetics of ingesting a single dose of 5 mg versus 1.1 mg folic acid contained in 2 prenatal multivitamins (PregVit® and PregVit-Folic 5®), and to estimate its contribution to steady-state folate levels. Method The pharmacokinetics of 1.1 mg folic acid was determined in a previously published study. The method was replicated among 6 healthy, non-pregnant women who were given 5 mg folic acid to ingest. Blood samples were drawn and serum folate concentrations were measured at various time points during 10 hours post-ingestion. Standard pharmacokinetic parameters were determined and compared with Student's t-test, when appropriate. Results The mean area under the curve (AUC) of 1.1 mg and 5 mg folic acid were 147.6 ± 52.8 (ng/mL)·;hr and 997.5 ± 271.9 (ng/mL)·hr, respectively (p<0.0002). An approximate 5-fold difference was detected in the peak concentrations (C_max) between the 2 groups (p<0.0005), alongside a slight difference in the times to peak (T_max) (p=0.02). The estimated steady-state serum folate concentrations produced by 1.1 mg and 5 mg folic acid were 6.2 ± 2.2 ng/mL and 41.6 ± 11.3 ng/mL, respectively (p<0.0002), prior to its summation with initial (baseline) steady-state levels. Conclusion Single dose administration between 1.1 mg and 5 mg folic acid demonstrated linear pharmacokinetics, with approximately a 5-fold difference between the 2 doses in serum folate contribution to steady-state levels, under ideal adherence.