Does the Amount of Stable Isotope Dose Influence Retinol Kinetic Responses and Predictions of Vitamin A Total Body Stores by the Retinol Isotope Dilution Method in Theoretical Children and Adults?

Abstract

Background: To minimize both cost and perturbations to the vitamin A system, investigators limit the amount of stable isotope administered when estimating vitamin A total body stores (TBS) by retinol isotope dilution (RID).

Objectives: We hypothesized that reasonable increases in the mass of stable isotope administered to theoretical subjects would have only transient impacts on vitamin A kinetics and minimal effects on RID-predicted TBS.

Methods: We adapted previously used theoretical subjects (3 children, 3 adults) with low, moderate, or high assigned TBS and applied compartmental analysis to solve a steady state model for tracer and tracee using assigned values for retinol kinetic parameters and plasma retinol. To follow retinol trafficking when increasing amounts of stable isotope were administered [1.39-7 (children) and 2.8-14 μmol retinol (adults)], we added assumptions to an established compartmental model so that plasma retinol homeostasis was maintained. Using model-simulated data, we plotted retinol kinetics versus time and applied the RID equation TBS = FaS/SAp [Fa, fraction of dose in stores; S, retinol specific activity (SA) in plasma/SA in stores; SAp, SA in plasma] to calculate vitamin A stores.

Results: The model predicted that increasing the stable isotope dose caused transient early increases in hepatocyte total retinol; increases in plasma tracer were accompanied by decreases in tracee to maintain plasma retinol homeostasis. Despite changes in kinetic responses, RID accurately predicted assigned TBS (98-105%) at all loads for all theoretical subjects from 1 to 28 d postdosing.

Conclusions: Results indicate that, compared with doses of 1.4-3.5 μmol used in recent RID field studies, doubling the stable isotope dose should not affect the accuracy of TBS predictions, thus allowing for experiments of longer duration when including a super-subject design (Ford et al., J Nutr 2020;150:411-8) and/or studying retinol kinetics.

Keywords: model-based compartmental analysis; retinol isotope dilution method; retinol kinetics; theoretical humans; vitamin A status.