A Comparison of Folic Acid Pharmacokinetics in Obese and Nonobese Women of Childbearing Age

Background: Although maternal folate deficiency during the periconceptional period represents a major risk factor for neural tube defects, obesity has been recognized as an additional risk factor. Studies have identified an increased risk for neural tube defect-affected births among obese mothers even after adjusting for folic acid supplementation. However, although folic acid intake may have been at the recommended dose in these samples, blood folate concentrations were not monitored to ensure that protective levels were reached. Hence, there is a need to compare folic acid pharmacokinetics in obese and nonobese women of childbearing age. Methods: Healthy obese (n = 12) and nonobese (n = 12) women of childbearing age volunteered to participate. Each obese participant was matched to a nonobese participant and assigned an equivalent dose of folic acid per kilogram body weight. Folic acid was orally administered after a 6-hour fast, and blood samples were taken over a 10-hour period to evaluate pharmacokinetic parameters. Results: Area under the time-concentration curve (AUC) was found to be significantly higher in the obese group (P = 0.008). Defining AUC as a function of dose per kilogram lean body weight (LBW) was found to be a stronger predictor than dose per kilogram total body weight (r(2) = 0.90 and 0.76, respectively). Conclusions: This indicates that the body tightly controls systemic exposure to folic acid, with 90% of the variability in AUC controlled by the dose per kilogram LBW. Periconceptional supplementation recommendations may need to be adjusted to account for LBW differences in the obese population.