title: Pregnancy-induced changes in the long-term pharmacokinetics of 1.1 mg vs. 5 mg folic acid: a randomized clinical trial.
abstract: The objective of this randomized clinical trial was to compare steady-state gestational RBC and plasma folate concentrations in pregnant women supplementing daily with 1.1 mg (regular dose) vs. 5 mg (high dose) folic acid. Thirty-seven pregnant women, who were not previously taking folic acid, were enrolled in this open-label, 2-arm, randomized clinical trial after informed consent. Participants were randomly assigned either 1.1 or 5 mg of folic acid-containing prenatals until gestational age (g.a.) 30 weeks. Plasma and RBC folate concentrations were measured at baseline, g.a.6 weeks, g.a.12 weeks, and g.a.30 weeks using a chemiluminescent immunoassay. Results showed sustained significant increase in RBC folate in the 5 mg group between g.a.6 weeks and g.a.30 weeks (P < 0.001), and between g.a.12 weeks and g.a.30 weeks (P < 0.01), whereas a significant increase in RBC folate concentrations was observed in the 1.1 mg group only between g.a.12 weeks to g.a.30 weeks (P < 0.05). Plasma folate increased in both groups from baseline to g.a.6 weeks, and then decreased between g.a.6 weeks and g.a.30 weeks, but this was not statistically significant. Plasma concentrations at g.a.30 weeks in both groups were comparable to their respective baseline concentrations. Thus, physiological changes in pregnancy alter long-term folate pharmacokinetics. Despite supplementation over an extended period of time, steady-state does not seem to be achieved in either dose group within our study.
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; The Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Mahvash
authors.initials: M
authors.lastname: Shere
authors.forename: Patricia
authors.initials: P
authors.lastname: Nguyen
authors.forename: Carolyn
authors.initials: C
authors.lastname: Tam
authors.forename: Seth
authors.initials: S
authors.lastname: Stern
authors.forename: Bhushan
authors.initials: B
authors.lastname: Kapur
authors.forename: Deborah L
authors.initials: DL
authors.lastname: O'Connor
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
mesh_terms: D000328:Adult; D019587:Dietary Supplements; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D011247:Pregnancy / Q000378:metabolism*
chemical_list: D005492:Folic Acid
keywords: folic acid; periconceptional period; pharmacokinetics; pregnancy; prenatal supplementation; steady-state