Dataset Information

A Population-Based (Super-Child) Approach for Predicting Vitamin A Total Body Stores and Retinol Kinetics in Children Is Validated by the Application of Model-Based Compartmental Analysis to Theoretical Data.

ABSTRACT:

Background

Public health nutritionists need accurate and feasible methods to assess vitamin A status and to evaluate efficacy of interventions, especially in children. The application of population-based designs to tracer kinetic data is an effective approach that reduces sample burden for each child.

Objectives

Objectives of the study were to use theoretical data to validate a population-based (super-child) approach for estimating group mean vitamin A total body stores (TBS) and retinol kinetics in children and to use population-based data to improve individual TBS predictions using retinol isotope dilution (RID).

Methods

We generated plasma retinol kinetic data from 6 h to 56 d for 50 theoretical children with high vitamin A intakes, assigning values within physiologically reasonable ranges for state variables and kinetic parameters ("known values"). Mean data sets for all subjects at extensive (n = 36) and reduced (n = 11) sampling times, plus 5 data sets for reduced numbers (5/time, except all at 4 d) and times, were analyzed using Simulation, Analysis and Modeling software. Results were compared with known values; population RID coefficients were used to calculate TBS for individuals.

Results

For extensive and reduced data sets including all subjects, population TBS predictions were within 1% of the known value. For 5 data sets reflecting numbers and times being used in ongoing super-child studies, predictions were within 1-17% of the known group value. Using RID equation coefficients from population modeling, TBS predictions at 4 d were within 25% of the known value for 66-80% of subjects and reflected the range of assigned values; when ranked, predicted and assigned values were significantly correlated (R_s = 0.93, P < 0.0001). Results indicate that 7 d may be better than 4 d for applying RID in children. For all data sets, predictions for kinetic parameters reflected the range of known values.

Conclusion

The population-based (super-child) approach provides a feasible experimental design for quantifying retinol kinetics, accurately estimating group mean TBS, and predicting TBS for individuals reasonably well.

SUBMITTER: Ford JL

PROVIDER: S-EPMC6252344 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

A Population-Based (Super-Child) Approach for Predicting Vitamin A Total Body Stores and Retinol Kinetics in Children Is Validated by the Application of Model-Based Compartmental Analysis to Theoretical Data.

Ford Jennifer Lynn JL Green Joanne Balmer JB Green Michael H MH

Current developments in nutrition 20181124 11

<h4>Background</h4>Public health nutritionists need accurate and feasible methods to assess vitamin A status and to evaluate efficacy of interventions, especially in children. The application of population-based designs to tracer kinetic data is an effective approach that reduces sample burden for each child.<h4>Objectives</h4>Objectives of the study were to use theoretical data to validate a population-based (super-child) approach for estimating group mean vitamin A total body stores (TBS) and ...[more]

PMID: 30488046

Similar Datasets

Project description:BackgroundModel-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).

Project description:Background:Retinol isotope dilution (RID) indirectly estimates vitamin A (VA) status. Multicompartment modeling of RID data is used to refine study designs and equations to calculate VA stores. Previous studies suggest that VA in slowly turning over pools is not traced if follow-up is not long enough; however, shorter RID studies are being investigated. Few long-term models have been published. Objective:We determined the effect of time on mathematical models of VA kinetics, model parameters, and outcomes. Methods:In this longitudinal study, women (mean ± SD age: 22 ± 3 y; n = 7) were given 2.0 µmol [14,15]-13C2-retinyl acetate. Blood samples were staggered from 4 h to 152 d; the fraction of dose in serum was modeled with compartmental models. Four model-time categories were created: full models that used all data (median: 137 d; range 97-152 d) and truncated shorter studies of 14, 27, and 52 d (range: 42-62 d). Outcomes included number of compartments to adequately model serum data, kinetic parameters, total traced VA mass, and time-to-dose equilibration. To gain insight into longer follow-up, an additional participant was given 17.5 µmol 13C4-VA, and data were modeled as long as enrichment was above baseline (5 y). Results:Longer follow-up times affected kinetic parameters and outcomes. Compared with the 14-d models, long-term full models required an additional compartment for adequate fit (14.3% compared with 100%; P = 0.0056) and had longer [median (quartile 1, quartile 3)] whole-body half-life [15.0 d (10.5, 72.6 d) compared with 135 d (115, 199 d); P = 0.0006], time-to-dose equilibration [3.40 d (3.14, 6.75 d) compared with 18.9 d (11.2, 25.7 d); P < 0.0001], and total traced mass [166 µmol VA (162, 252 µmol VA) compared with 476 µmol VA (290, 752 µmol VA); P = 0.0031]. Conclusions:Extended RID sampling alters numerous mathematically modeled, time-dependent outcomes in women. Length of study should be considered when using mathematical models for calculating total-body VA stores or kinetic parameters related to VA turnover. This study is registered at www.clinicaltrials.gov as NCT03248700.

Project description:BackgroundVitamin A (VA) deficiency is a public health problem in some countries. Fortification, supplementation, and increased provitamin A consumption through biofortification are efficacious, but monitoring is needed due to risk of excessive VA intake when interventions overlap.ObjectivesTwo studies in 28-36-d-old male Mongolian gerbils simulated exposure to multiple VA interventions to determine the effects of provitamin A carotenoid consumption from biofortified maize and carrots and preformed VA fortificant on status.MethodsStudy 1 was a 2 × 2 × 2 factorial design (n = 85) with high-β-carotene maize, orange carrots, and VA fortification at 50% estimated gerbil needs, compared with white maize and white carrot controls. Study 2 was a 2 × 3 factorial design (n = 66) evaluating orange carrot and VA consumption through fortification at 100% and 200% estimated needs. Both studies utilized 2-wk VA depletion, baseline evaluation, 9-wk treatments, and liver VA stores by HPLC. Intestinal scavenger receptor class B member 1 (Scarb1), β-carotene 15,15'-dioxygenase (Bco1), β-carotene 9',10'-oxygenase (Bco2), intestine-specific homeobox (Isx), and cytochrome P450 26A1 isoform α1 (Cyp26a1) expression was analyzed by qRT-PCR in study 2.ResultsIn study 1, liver VA concentrations were significantly higher in orange carrot (0.69 ± 0.12 μmol/g) and orange maize groups (0.52 ± 0.21 μmol/g) compared with baseline (0.23 ± 0.069 μmol/g) and controls. Liver VA concentrations from VA fortificant alone (0.11 ± 0.053 μmol/g) did not differ from negative control. In study 2, orange carrot significantly enhanced liver VA concentrations (0.85 ± 0.24 μmol/g) relative to baseline (0.43 ± 0.14 μmol/g), but VA fortificant alone (0.42 ± 0.21 μmol/g) did not. Intestinal Scarb1 and Bco1 were negatively correlated with increasing liver VA concentrations (P < 0.01, r2 = 0.25-0.27). Serum retinol concentrations did not differ.ConclusionsBiofortified carrots and maize without fortification prevented VA deficiency in gerbils. During adequate provitamin A dietary intake, preformed VA intake resulted in excessive liver stores in gerbils, despite downregulation of carotenoid absorption and cleavage gene expression.

Dataset Information

A Population-Based (Super-Child) Approach for Predicting Vitamin A Total Body Stores and Retinol Kinetics in Children Is Validated by the Application of Model-Based Compartmental Analysis to Theoretical Data.

Background

Objectives

Methods

Results

Conclusion

Publications

A Population-Based (Super-Child) Approach for Predicting Vitamin A Total Body Stores and Retinol Kinetics in Children Is Validated by the Application of Model-Based Compartmental Analysis to Theoretical Data.

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