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 [C-13(5)] AND [H-2(2)]FOLIC ACID

Stable isotopic protocols for the study of folate absorption were cond ucted to determine the following: (1) the equivalence of the [C-13(5)] and [H-2(2)] forms of folic acid, and (2) the merits of short-term pl asma kinetics from injected and oral doses vs. urinary excretion of [C -13(5)] and [H-2(2)]folates. Another objective was to evaluate the mer its of protocols not involving ''saturation'' of subjects with nonlabe led folate. Oral administration of [C-13(5)] and [H-2(2)]folic acid (s imilar to 500 nmol each) to adult subjects (n = 4) yielded an equivale nt 24-h urinary excretion of similar to 2% of each dose (molar ratio o f urinary [C-13(5)]/[H-2(2)]folates = 0.96 +/- 0.055; mean +/- SEM). E xpression of urinary excretion as a ratio of [C-13(5)]/[H-2(2)]folates yielded less within-group variability than seen for absolute excretio n of each form of labeled folate. In the second study, subjects receiv ed 226 nmol of [H-2(2)]folic acid intravenously and 1010 nmol of [C-13 (5)]folic acid orally. Isotopic enrichment of plasma [H-2(2)]folates r ose rapidly and returned to near basal values by similar to 2 h postdo se. In contrast, enrichment of plasma [C-13(5)]folates was detected un til 4 h after dose, whereas enrichment values were far lower than seen with [H-2(2)]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 limite d short-term plasma response even with a relatively large oral dose, p resumably due to hepatic first-pass uptake, these findings suggest tha t plasma kinetics would be of limited usefulness in assessing the rela tive bioavailability of nutritionally relevant oral doses of labeled f olate.