Use of Population-Based Compartmental Modeling and Retinol Isotope Dilution to Study Vitamin A Kinetics and Total Body Stores among Ghanaian Women of Reproductive Age.

Background: Limited data are available on vitamin A kinetics and total body stores (TBS) in women. Such information can be obtained using compartmental modeling and retinol isotope dilution (RID).
Objectives: Objectives were to apply population-based ("super-subject") modeling to determine retinol kinetics in nonpregnant Ghanaian women of reproductive age and to use RID to predict TBS in the group and its individuals.
Methods: Women ( n = 89) ingested a dose of [ ² H ₆ ]retinyl acetate and blood samples (3/woman) were collected from 6 h to 91 d, with all participants sampled at 14 d, about half at either 21 or 28 d, and each at one other time. Composite data (plasma retinol fraction of dose; FD _p ) were analyzed using Simulation, Analysis and Modeling software to obtain kinetic parameters, TBS, and other state variables as well as model-derived values for the RID composite coefficient FaS . The latter were used in the RID equation TBS (μmol) = FaS × 1/SA _p (where SA _p is plasma retinol specific activity) to predict TBS at various times.
Results: Model-predicted TBS was 973 μmol ( n = 87). Geometric mean RID-predicted TBS was 965, 926, and 1006 μmol at 14, 21, and 28 d, respectively, with wide ranges [for example, 252-3848 μmol on day 14 ( n = 86)]; TBS predictions were similar at later times. Participants had a mean 2 y of vitamin A in stores and estimated liver vitamin A concentrations in the normal range. Model-predicted vitamin A disposal rate was 1.3 μmol/d and plasma recycling number was 37.
Conclusions: Super-subject modeling provides an estimate of group mean TBS as well as group-specific values for the RID coefficient FaS ; the latter can be used to confidently predict TBS by RID for individual participants in the group under study or in similar individuals at 14 d or more after isotope ingestion.
Trial Registration Number: Trial is registered (NCT04632771) at https://clinicaltrials.gov.
(© 2024 The Author(s).)