Development of a Compartmental Model for Studying Vitamin A Kinetics and Status in Theoretical Lactating Women

Background Low vitamin A status and suboptimal milk vitamin A concentrations are problems in many populations worldwide. However, limited research has been done on whole-body vitamin A kinetics in women of reproductive age, especially during lactation. Objectives Goals were to develop compartmental models describing retinol kinetics in theoretical nonlactating (NL) and lactating (L) women and to determine whether the retinol isotope dilution (RID) method accurately predicted vitamin A total body stores (TBS) in the groups and individuals. Methods We adapted 12 previously-used theoretical females with assigned values for retinol kinetic parameters and TBS (225-1348 mu mol); subjects were NL or L (nursing one 3- to 6-mo-old infant) during 49-d kinetic studies after isotope dosing. We used an established compartmental model, adding a compartment for chylomicrons and, for L, another for mammary gland milk with inputs from holo-retinol-binding protein and chylomicron retinyl esters and output to milk. Using compartmental analysis, we simulated tracer responses in compartments of interest and calculated TBS using the RID equation TBS = FaS/SA(p) [Fa, fraction of dose in stores; S, retinol specific activity in plasma/specific activity in stores; SA(p), specific activity of retinol in plasma]. Results Models for both groups were well identified. Simulated plasma tracer responses were similar for NL and L, with L always below NL; milk tracer paralleled plasma from 10 d postdosing. Geometric mean FaS ratios (L/NL) were similar to 0.75 during days 2-30. Using appropriate group FaS, RID provided accurate TBS predictions for >80% of NL and L subjects after day 18 when CV% for FaS was similar to 10%. Conclusions These new physiologically-based models for vitamin A kinetics may be useful for future research in women of reproductive age. Results indicate that, in groups like these, RID to assess an individual's vitamin A status should be done at 21-28 d after isotope dosing.