Abstract
BackgroundMathematical modeling of theoretical data has been used to validate experimental protocols and methods in several fields. ObjectiveWe hypothesized that adding dietary vitamin A intake data as an input during compartmental modeling of retinol kinetics would lead to accurate prediction of vitamin A total body stores (TBS) at 2 specified study lengths and would reduce study duration required to accurately define the system. MethodsWe generated reference values for state variables (including TBS and intake) and kinetic parameters for 12 theoretical individuals (4 each of children, younger adults, and older adults) based on modeling plasma retinol tracer data for 365 d. We compared TBS predictions using data to 28 d (children) or 56 d (adults) without and with intake included in the model to reference values for each subject. Then, by truncating data sets from 365 d, we determined the shortest study duration required to accurately define the system without and with inclusion of vitamin A intake. ResultsReference values for TBS ranged from 30 to 3023 µmol. Study durations of 28 and 56 d were sufficient to accurately predict TBS for 6 of the 12 subjects without intake; adding intake resulted in accurate predictions of TBS for all individuals. When intake was not included as a modeling input, durations of 35–310 d were required to define the system; inclusion of intake data substantially reduced the time required to 10–42 d. ConclusionsInclusion of vitamin A intake as additional data input when modeling vitamin A kinetics allows investigators to accurately predict TBS and define the vitamin A system in studies of reasonable length (4 wk in children and 8 wk in adults). Because it is generally possible to obtain estimates/measures of intake, including such data increases confidence in model predictions while also making studies more feasible.
Highlights
Since model-based compartmental analysis [1] was first applied to study vitamin A kinetics in rats [2], and later in humans [3], investigators have recognized the importance of study duration in the accurate prediction of model parameters
Shortest study durations required for accurate model predictions without and with vitamin A intake included as a modeling input the results described in the preceding section demonstrate that the specified times (28 and 56 d) provided accurate predictions of total body stores (TBS) when vitamin A intake was added to the model, it is possible that inclusion of diet would accurately define the system at even shorter study durations
The results of this study demonstrate that when vitamin A intake is included as a modeling input, study durations similar to those previously used for vitamin A kinetic studies (28 d for children and 56 d for adults) are long enough to accurately predict TBS and define the vitamin A system
Summary
Since model-based compartmental analysis [1] was first applied to study vitamin A kinetics in rats [2], and later in humans [3], investigators have recognized the importance of study duration in the accurate prediction of model parameters. Objectives: We hypothesized that adding dietary vitamin A intake data as an input during compartmental modeling of retinol kinetics would lead to accurate prediction of vitamin A total body stores (TBS) at 2 specified study lengths and would reduce study duration required to accurately define the system. Methods: We generated reference values for state variables (including TBS and intake) and kinetic parameters for 12 theoretical individuals (4 each of children, younger adults, and older adults) based on modeling plasma retinol tracer data for 365 d. Conclusions: Inclusion of vitamin A intake as additional data input when modeling vitamin A kinetics allows investigators to accurately predict TBS and define the vitamin A system in studies of reasonable length (4 wk in children and 8 wk in adults).
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