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Advanced Theoretical Applications of Mathematical Modeling and Compartmental Analysis in Vitamin A and Provitamin A Carotenoid Research: Validation of Prediction Methods.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Advanced Theoretical Applications of Mathematical Modeling and Compartmental Analysis in Vitamin A and Provitamin A Carotenoid Research: Validation of Prediction Methods./
Author:	Ford, Jennifer Lynn.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	286 p.
Notes:	Source: Dissertations Abstracts International, Volume: 80-12, Section: B.
Contained By:	Dissertations Abstracts International80-12B.
Subject:	Applied Mathematics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13917904
ISBN:	9781392318379

Advanced Theoretical Applications of Mathematical Modeling and Compartmental Analysis in Vitamin A and Provitamin A Carotenoid Research: Validation of Prediction Methods.
Ford, Jennifer Lynn.

Advanced Theoretical Applications of Mathematical Modeling and Compartmental Analysis in Vitamin A and Provitamin A Carotenoid Research: Validation of Prediction Methods. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 286 p.

Source: Dissertations Abstracts International, Volume: 80-12, Section: B.

Thesis (Ph.D.)--The Pennsylvania State University, 2019.

Vitamin A is an essential nutrient that is required for vision, growth, immune function, reproduction and cellular communication. Vitamin A deficiency continues to be a public health concern in many areas worldwide. To combat deficiency, numerous intervention strategies, including vitamin A supplementation and food fortification, are being implemented in at-risk populations. While these strategies have been shown to be effective for relieving the consequences of vitamin A deficiency, some concerns have been raised that the overlap in these programs may lead to vitamin A excess. Thus, accurate and feasible methods are needed for assessing vitamin A status from deficiency through excess and for evaluating the efficacy of interventions. Of the available methods, two are considered accurate for estimating vitamin A total body stores (TBS) across the range of statuses: retinol isotope dilution (RID) and model-based compartmental analysis. Because provitamin A carotenoids (primarily β-carotene) are a significant dietary source of vitamin A for many populations and can be used in vitamin A interventions, assessment methods are also needed to evaluate the efficiency of absorption and conversion of provitamin A carotenoids to vitamin A (i.e., bioefficacy), processes that are influenced by numerous factors and which vary greatly among individuals.Evaluating the accuracy of assessment methods requires appropriate data for testing and ideally, known reference values for the prediction of interest. Both of these can be obtained theoretically by model-based compartmental analysis and model simulation using the Windows version of the Simulation, Analysis and Modeling software. Specifically, a physiologically-based compartmental model that represents the system under study (e.g., vitamin A or provitamin A carotenoid metabolism) can be constructed and values for model parameters, related variables and the outcomes of interest (e.g., vitamin A TBS or provitamin A carotenoid bioefficacy) can be assigned a priori to theoretical subjects. Then the model can be applied to simulate data that can be used to test the method and predictions can be compared to the known (assigned) reference values for evaluation. In the current work, this theoretical modeling approach was applied to investigate the accuracy of methods for assessing vitamin A status and provitamin A carotenoid bioefficacy.First, a simple plasma retinol isotope ratio (RIR) for estimating β-carotene relative bioefficacy was validated (see Chapter 2). Using compartmental models describing whole-body β-carotene and retinol metabolism, plasma tracer response data for retinol derived from oral doses of labeled β-carotene and retinyl acetate were simulated for 10 theoretical human subjects with a wide range of known values for bioefficacy and ratios of the 2 isotopes were calculated at various times after dosing. The RIR accurately predicted relative bioefficacy based on analysis of a single plasma sample collected at 14 d or later and it provided information about the extent of post-absorptive bioconversion if an additional sample was obtained at 1 d.In addition, the contribution of dietary vitamin A to plasma retinol turnover and the impact of vitamin A restriction on RID predictions were investigated (see Chapter 3). Using compartmental analysis, steady state retinol tracer and tracee response data were generated for 3 theoretical subjects with known values for vitamin A TBS. Then, various levels of restriction were simulated while mathematically invoking homeostatic control over plasma retinol. Results indicated that dietary vitamin A intake was only a minor contributor to total retinol input into plasma each day. When a steady state RID equation was applied, restriction led to an underestimation of TBS indicating that, contrary to common belief, subjects should consume their normal, balanced diet during RID studies.Finally, compartmental analysis was used to evaluate a population-based (super-child) modeling approach for estimating population vitamin A TBS and retinol kinetics and for predicting TBS for individual children using RID (see Chapter 4). A database for 50 theoretical children with known values for vitamin A TBS and retinol kinetics was generated. Mean datasets for subjects at extensive and reduced sampling times plus 5 datasets with reduced subject numbers and times were analyzed using compartmental analysis. Overall, the super-child approach accurately predicted population vitamin A TBS, adequately estimated population retinol kinetics, and using a 4 d RID equation, predicted TBS in individual children reasonably well.In summary, results from these analyses provide compelling evidence that model-based compartmental analysis can be effectively applied to evaluate the accuracy of prediction methods for assessing vitamin A status and provitamin A carotenoid bioefficacy using theoretical data. As evidenced by these applications, theoretical modeling approaches can enable researchers to improve current methods as well as validate new techniques. The approach can potentially be applied to other nutrients.

ISBN: 9781392318379Subjects--Topical Terms:

1669109
Applied Mathematics.

Advanced Theoretical Applications of Mathematical Modeling and Compartmental Analysis in Vitamin A and Provitamin A Carotenoid Research: Validation of Prediction Methods.
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520 $a Vitamin A is an essential nutrient that is required for vision, growth, immune function, reproduction and cellular communication. Vitamin A deficiency continues to be a public health concern in many areas worldwide. To combat deficiency, numerous intervention strategies, including vitamin A supplementation and food fortification, are being implemented in at-risk populations. While these strategies have been shown to be effective for relieving the consequences of vitamin A deficiency, some concerns have been raised that the overlap in these programs may lead to vitamin A excess. Thus, accurate and feasible methods are needed for assessing vitamin A status from deficiency through excess and for evaluating the efficacy of interventions. Of the available methods, two are considered accurate for estimating vitamin A total body stores (TBS) across the range of statuses: retinol isotope dilution (RID) and model-based compartmental analysis. Because provitamin A carotenoids (primarily β-carotene) are a significant dietary source of vitamin A for many populations and can be used in vitamin A interventions, assessment methods are also needed to evaluate the efficiency of absorption and conversion of provitamin A carotenoids to vitamin A (i.e., bioefficacy), processes that are influenced by numerous factors and which vary greatly among individuals.Evaluating the accuracy of assessment methods requires appropriate data for testing and ideally, known reference values for the prediction of interest. Both of these can be obtained theoretically by model-based compartmental analysis and model simulation using the Windows version of the Simulation, Analysis and Modeling software. Specifically, a physiologically-based compartmental model that represents the system under study (e.g., vitamin A or provitamin A carotenoid metabolism) can be constructed and values for model parameters, related variables and the outcomes of interest (e.g., vitamin A TBS or provitamin A carotenoid bioefficacy) can be assigned a priori to theoretical subjects. Then the model can be applied to simulate data that can be used to test the method and predictions can be compared to the known (assigned) reference values for evaluation. In the current work, this theoretical modeling approach was applied to investigate the accuracy of methods for assessing vitamin A status and provitamin A carotenoid bioefficacy.First, a simple plasma retinol isotope ratio (RIR) for estimating β-carotene relative bioefficacy was validated (see Chapter 2). Using compartmental models describing whole-body β-carotene and retinol metabolism, plasma tracer response data for retinol derived from oral doses of labeled β-carotene and retinyl acetate were simulated for 10 theoretical human subjects with a wide range of known values for bioefficacy and ratios of the 2 isotopes were calculated at various times after dosing. The RIR accurately predicted relative bioefficacy based on analysis of a single plasma sample collected at 14 d or later and it provided information about the extent of post-absorptive bioconversion if an additional sample was obtained at 1 d.In addition, the contribution of dietary vitamin A to plasma retinol turnover and the impact of vitamin A restriction on RID predictions were investigated (see Chapter 3). Using compartmental analysis, steady state retinol tracer and tracee response data were generated for 3 theoretical subjects with known values for vitamin A TBS. Then, various levels of restriction were simulated while mathematically invoking homeostatic control over plasma retinol. Results indicated that dietary vitamin A intake was only a minor contributor to total retinol input into plasma each day. When a steady state RID equation was applied, restriction led to an underestimation of TBS indicating that, contrary to common belief, subjects should consume their normal, balanced diet during RID studies.Finally, compartmental analysis was used to evaluate a population-based (super-child) modeling approach for estimating population vitamin A TBS and retinol kinetics and for predicting TBS for individual children using RID (see Chapter 4). A database for 50 theoretical children with known values for vitamin A TBS and retinol kinetics was generated. Mean datasets for subjects at extensive and reduced sampling times plus 5 datasets with reduced subject numbers and times were analyzed using compartmental analysis. Overall, the super-child approach accurately predicted population vitamin A TBS, adequately estimated population retinol kinetics, and using a 4 d RID equation, predicted TBS in individual children reasonably well.In summary, results from these analyses provide compelling evidence that model-based compartmental analysis can be effectively applied to evaluate the accuracy of prediction methods for assessing vitamin A status and provitamin A carotenoid bioefficacy using theoretical data. As evidenced by these applications, theoretical modeling approaches can enable researchers to improve current methods as well as validate new techniques. The approach can potentially be applied to other nutrients.
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