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.
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 ( approximately 500 nmol each) to adult subjects (n = 4) yielded an equivalent 24-h urinary excretion of approximately 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 approximately 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.
Rogers
L M
LM
Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA.
Pfeiffer
C M
CM
Bailey
L B
LB
Gregory
J F
JF
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002247:Carbon Isotopes; D003903:Deuterium; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006801:Humans; D007275:Injections, Intravenous; D007553:Isotope Labeling; D008297:Male
D002247:Carbon Isotopes; D005492:Folic Acid; D003903:Deuterium