(P01-006-24) Use of Theoretical Subjects and Compartmental Modeling to Evaluate the Paired Retinol Isotope Dilution Test With a Single Dose of Isotope to Assess a Vitamin A Intervention

Objectives: We used an emerging approach (compartmental modeling of theoretical datasets), which we have previously pioneered and that may eliminate the need for lengthy, expensive pilot studies, to investigate whether the paired retinol isotope dilution (RID) technique, which is done to determine vitamin A (VA) total body stores (TBS) before and after a period of VA supplementation, could be accomplished in theoretical children using a single dose of labeled VA (rather than two doses).

Methods: For 6 theoretical children with low VA status (assigned TBS = 81–281 µmol), we calculated TBS at 30 d after simulated ingestion of labeled VA tracer (4 µmol) (“RID1”) using this RID equation: TBS (µmol) = FaS x 1/SA_p where FaS is a correction factor and SA_p is plasma retinol specific activity [fraction of dose (FD)/µmol]. Then we simulated consumption or not of a daily VA supplement (2.8 µmol/d) for 4 mo for each subject and calculated RID2 with FaS and SA_p from d 150.  We used Simulation, Analysis and Modeling software to simulate FaS and SA_p over time.

Results: Simulations showed that SA_p decreased slowly after ~20 d postdosing and FD at 5 mo was 1/3 that at 1 mo with or without supplementation; thus, this isotope dose should still be detectable after a 4 mo intervention, assuming sensitive and accurate mass spectrometric methods for determining SA_p. Since simulated mean values for FaS were only 5.6% higher for supplemented vs non-supplemented conditions at RID2, use of the same coefficient can be justified.

Conclusions: If confirmed in community settings, this modified paired RID test is an improved approach for evaluating the impact of VA interventions, requiring only one dose of isotope and using the same FaS for the second RID for both non-supplemented and supplemented conditions. Since obtaining the most accurate FaS requires a full VA kinetic study, the latter result adds to the impact of our findings.

Funding Sources: Some meeting costs will be supported by an International Atomic Energy Agency grant to VL-T.