Direct Use of Plasma or Milk Vitamin A Specific Activity Data to Model Retinol Kinetics and Predict Vitamin A Stores in Theoretical Lactating Women

Background: Many applications of the Simulation, Analysis and Modeling software use data on the fraction of an orally administered tracer dose (FD) in plasma; thus, researchers must scale-up measured analyte concentration to the total plasma pool. For studies in lactating women, estimating breast milk pool size is challenging. Objectives: The objectives were to determine whether the standard vitamin A modeling approach using FD data could be modified to use vitamin A specific activity in milk (SA_m) and/or plasma (SA_p) for compartmental analysis of vitamin A kinetics and status in theoretical lactating women. Methods: Using 12 previously studied theoretical subjects with a wide range of assigned values for vitamin A total body stores (TBS) and the coefficient (“FaS”) needed to predict TBS using a retinol isotope dilution equation, we simulated data for SA_p and SA_m for 49 d after oral administration of labeled vitamin A. Then we modeled datasets for SA_p and SA_m, as well as only SA_p or SA_m, incorporating a linear scaling factor to automatically convert SA to FD and including several physiologically reasonable constraints as input data. As outcomes, we compared model-predicted TBS and FaS to assigned values. Results: Scaling factors effectively adjusted SA data to adequately predict vitamin A mass in plasma and breast milk pools. Data for SA_p and SA_m provided model predictions of TBS that were comparable to assigned values (range: 85–107%); using only SA_p, ratios ranged from 92% to 108% and for SA_m from 85% to 108%. Parallel results were obtained for simulated FaS. Conclusions: Results show that SA data from plasma and/or milk can be used directly for modeling vitamin A during lactation in theoretical subjects, providing accurate estimates of TBS and FaS. Results suggest that, in free-living lactating women, researchers might measure only SA_p or only SA_m and adequately describe whole-body vitamin A metabolism and status.