The Journal of Nutrition Vol. 127 No. 12 December 1997, pp. 2321-2327
Copyright ©1997 by the American Society for Nutritional Sciences

A Dual-Label Stable-Isotopic Protocol Is Suitable for Determination of Folate Bioavailability in Humans: Evaluation of Urinary Excretion and Plasma Folate Kinetics of Intravenous and Oral Doses of [¹³C₅] and [²H₂]Folic Acid

Lisa M. Rogers, Christine M. Pfeiffer, Lynn B. Bailey, and Jesse F. Gregory III

Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611

Stable isotopic protocols for the study of folate absorption were conducted to determine the following: (1) the equivalence of the [¹³C₅] and [²H₂] forms of folic acid, and (2) the merits of short-term plasma kinetics from injected and oral doses vs. urinary excretion of [¹³C₅] and [²H₂]folates. Another objective was to evaluate the merits of protocols not involving "saturation" of subjects with nonlabeled folate. Oral administration of [¹³C₅] and [²H₂]folic acid (~500 nmol each) to adult subjects (n = 4) yielded an equivalent 24-h urinary excretion of ~2% of each dose (molar ratio of urinary [¹³C₅]/[²H₂]folates = 0.96 ± 0.055; mean ± SEM). Expression of urinary excretion as a ratio of [¹³C₅]/[²H₂]folates yielded less within-group variability than seen for absolute excretion of each form of labeled folate. In the second study, subjects received 226 nmol of [²H₂]folic acid intravenously and 1010 nmol of [¹³C₅]folic acid orally. Isotopic enrichment of plasma [²H₂]folates rose rapidly and returned to near basal values by ~2 h postdose. In contrast, enrichment of plasma [¹³C₅]folates was detected until 4 h after dose, whereas enrichment values were far lower than seen with [²H₂]folate. Adjusting for the difference in dose, the molar response of plasma area under the curve for isotopic enrichment was 15- to 20-fold greater for injected folates. In view of this very limited short-term plasma response even with a relatively large oral dose, presumably due to hepatic first-pass uptake, these findings suggest that plasma kinetics would be of limited usefulness in assessing the relative bioavailability of nutritionally relevant oral doses of labeled folate.

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