Abstract
ABSTRACTBackgroundModel-based compartmental analysis has been used to describe and quantify whole-body vitamin A metabolism and estimate total body stores (TBS) in animals and humans.ObjectivesWe applied compartmental modeling and a super-child design to estimate retinol kinetic parameters and TBS for young children in Bangladesh, Guatemala, and the Philippines.MethodsChildren ingested [13C10]retinyl acetate and 1 or 2 blood samples were collected from each child from 6 h to 28 d after dosing. Temporal data for fraction of dose in plasma [13C10]retinol were modeled using WinSAAM software and a 6-component model with vitamin A intake included as weighted data.ResultsModel-predicted TBS was 198, 533, and 1062 μmol for the Bangladeshi (age, 9–17 mo), Filipino (12–18 mo), and Guatemalan children (35–65 mo). Retinol kinetics were similar for Filipino and Guatemalan groups and generally faster for Bangladeshi children, although fractional transfer of plasma retinol to a larger exchangeable storage pool was the same for the 3 groups. Recycling to plasma from that pool was ∼2.5 times faster in the Bangladeshi children compared with the other groups and the recycling number was 2–3 times greater. Differences in kinetics between groups are likely related to differences in vitamin A stores and intakes (geometric means: 352, 727, and 764 μg retinol activity equivalents/d for the Bangladeshi, Filipino, and Guatemalan children, respectively).ConclusionsBy collecting 1 or 2 blood samples from each child to generate a composite plasma tracer data set with a minimum of 5 children/time, group TBS and retinol kinetics can be estimated in children by compartmental analysis; inclusion of vitamin A intake data increases confidence in model predictions. The super-child modeling approach is an effective technique for comparing vitamin A status among children from different populations. These trials were registered at www.clinicaltrials.gov as NCT03000543 (Bangladesh), NCT03345147 (Guatemala), and NCT03030339 (Philippines).
Highlights
Over the past 35 y, application of model-based compartmental analysis to retinol kinetic data has led to important advances in our understanding of whole-body vitamin A metabolism and homeostasis in rats [for reviews, see [1, 2]]
Kinetic data and modeling analysis For modeling, each super-child data set was fit using the model shown in Figure 1, with all model parameters adjustable except that L(4,3) was fixed at 0.8 and L(0,3) at 0.2 to reflect an absorption efficiency of 80%, DT[8] was fixed at 75 min, and L(8,5) was fixed at the value calculated for each group to reflect 50% of the disposal rate (DR) leaving the system via the nonexchangeable tissue pool
Our analyses demonstrate the usefulness of the super-child modeling approach for quantifying vitamin A kinetics in children, in whom frequent and repeated blood sampling is generally not feasible
Summary
Over the past 35 y, application of model-based compartmental analysis to retinol kinetic data has led to important advances in our understanding of whole-body vitamin A metabolism and homeostasis in rats [for reviews, see [1, 2]]. The approach has been used to describe and quantify retinol kinetics and vitamin A total body stores (TBS), an indicator of vitamin A status [3], in humans [e.g., see [4, 5] and for reviews, see [2, 6, 7]]. Conclusions: By collecting 1 or 2 blood samples from each child to generate a composite plasma tracer data set with a minimum of 5 children/time, group TBS and retinol kinetics can be estimated in children by compartmental analysis; inclusion of vitamin A intake data increases confidence in model predictions. The super-child modeling approach is an effective technique for comparing vitamin A status among children from different populations These trials were registered at www.clinicaltrials.gov as NCT03000543 (Bangladesh), NCT03345147 (Guatemala), and NCT03030339 (Philippines).
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