TY - JOUR
T1 - Use of model-based compartmental analysis and a super-child design to study whole-body retinol kinetics and Vitamin A total body stores in children from 3 lower-income countries
AU - Ford, Jennifer Lynn
AU - Green, Joanne Balmer
AU - Haskell, Marjorie J.
AU - Ahmad, Shaikh M.
AU - Cordero, Dora Inés Mazariegos
AU - Oxley, Anthony
AU - Engle-Stone, Reina
AU - Lietz, Georg
AU - Green, Michael H.
N1 - Funding Information:
Support for this work was provided by the Bill & Melinda Gates Foundation (Project Number OPP1115464). Author disclosures: JLF, JBG, MJH, SMA, DIMC, AO, RE-S, GL, and MHG, no conflicts of interest. Supplemental Methods, Supplemental Tables 1–3, Supplemental Discussion, Supplemental Figure 1, Supplemental WinSAAM Deck, and Supplemental References are available from the “Online Supporting Material” link in the online posting of the article and from the same link in the online table of contents at http://jn.nutrition.org. JLF and MHG contributed equally to this work. Data supporting this publication are openly available at https://doi.org/10.25405 /data.ncl.9771902.v1. Address correspondence to MHG (e-mail: mhg@psu.edu). Abbreviations used: DR, disposal rate; DT, delay time; FDp, fraction of administered dose in plasma; FSD, fractional standard deviation; GloVitAS, Global Vitamin A Safety Assessment; RAE, retinol activity equivalent(s); RID, retinol isotope dilution; TBS, total body store(s); WinSAAM, Windows version of the Simulation, Analysis and Modeling software.
Publisher Copyright:
Copyright © American Society for Nutrition 2019. All rights reserved.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Background: Model-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. Objectives: We applied compartmental modeling and a super-child design to estimate retinol kinetic parameters and TBS for young children in Bangladesh, Guatemala, and the Philippines. Methods: Children 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. Results: Model-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). 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.
AB - Background: Model-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. Objectives: We applied compartmental modeling and a super-child design to estimate retinol kinetic parameters and TBS for young children in Bangladesh, Guatemala, and the Philippines. Methods: Children 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. Results: Model-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). 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.
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U2 - 10.1093/jn/nxz225
DO - 10.1093/jn/nxz225
M3 - Article
C2 - 31535129
AN - SCOPUS:85079077893
VL - 150
SP - 411
EP - 418
JO - Journal of Nutrition
JF - Journal of Nutrition
SN - 0022-3166
IS - 2
ER -