Use of Population-Based Compartmental Modeling and Retinol Isotope Dilution to Study Vitamin A Kinetics and Total Body Stores among Ghanaian Women of Reproductive Age

IF 3.8 Q2 NUTRITION & DIETETICS Current Developments in Nutrition Pub Date : 2024-11-01 DOI:10.1016/j.cdnut.2024.104484

Michael H Green , Veronica Lopez-Teros , Joanne Balmer Green , Georg Lietz , Sika M Kumordzie , Anthony Oxley , Ahmed D Fuseini , K Winifred Nyaaba , Emily Becher , Jennie N Davis , K Ryan Wessells , Seth Adu-Afarwuah , Reina Engle-Stone , Marjorie J Haskell

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Abstract

Background

Limited data are available on vitamin A kinetics and total body stores (TBS) in women. Such information can be obtained using compartmental modeling and retinol isotope dilution (RID).

Objectives

Objectives were to apply population-based (“super-subject”) modeling to determine retinol kinetics in nonpregnant Ghanaian women of reproductive age and to use RID to predict TBS in the group and its individuals.

Methods

Women (n = 89) ingested a dose of [²H₆]retinyl acetate and blood samples (3/woman) were collected from 6 h to 91 d, with all participants sampled at 14 d, about half at either 21 or 28 d, and each at one other time. Composite data (plasma retinol fraction of dose; FD_p) were analyzed using Simulation, Analysis and Modeling software to obtain kinetic parameters, TBS, and other state variables as well as model-derived values for the RID composite coefficient FaS. The latter were used in the RID equation TBS (μmol) = FaS × 1/SA_p (where SA_p is plasma retinol specific activity) to predict TBS at various times.

Results

Model-predicted TBS was 973 μmol (n = 87). Geometric mean RID-predicted TBS was 965, 926, and 1006 μmol at 14, 21, and 28 d, respectively, with wide ranges [for example, 252–3848 μmol on day 14 (n = 86)]; TBS predictions were similar at later times. Participants had a mean 2 y of vitamin A in stores and estimated liver vitamin A concentrations in the normal range. Model-predicted vitamin A disposal rate was 1.3 μmol/d and plasma recycling number was 37.

Conclusions

Super-subject modeling provides an estimate of group mean TBS as well as group-specific values for the RID coefficient FaS; the latter can be used to confidently predict TBS by RID for individual participants in the group under study or in similar individuals at 14 d or more after isotope ingestion.

Trial registration number

Trial is registered (NCT04632771) at https://clinicaltrials.gov.

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利用基于人群的区室模型和视黄醇同位素稀释研究加纳育龄妇女的维生素 A 动力学和体内总储量

背景有关女性维生素 A 动力学和体内总储量 (TBS) 的数据有限。目的应用基于人群（"超级受试者"）的模型来确定非怀孕的加纳育龄妇女的视黄醇动力学，并利用视黄醇同位素稀释（RID）来预测群体及其个体的总体内储存量。方法：妇女（n = 89）摄入一定剂量的[2H6]乙酸视黄醇，从 6 小时到 91 天采集血液样本（3 份/妇女），所有参与者在 14 天采样，约一半在 21 天或 28 天采样，每个人在其他时间采样。使用模拟、分析和建模软件对综合数据（血浆视黄醇剂量分数；FDp）进行分析，以获得动力学参数、TBS 和其他状态变量以及 RID 综合系数 FaS 的模型衍生值。后者用于 RID 公式 TBS (μmol) = FaS × 1/SAp（其中 SAp 为血浆视黄醇比活度），以预测不同时间的 TBS。RID预测的TBS在14天、21天和28天的几何平均值分别为965、926和1006 μmol，范围很广[例如，第14天为252-3848 μmol（n = 86）]；预测的TBS在之后的时间相近。参与者储存维生素 A 的平均时间为 2 y，估计肝脏中维生素 A 的浓度在正常范围内。模型预测的维生素 A 处置率为 1.3 μmol/d，血浆再循环次数为 37。结论超级受试者模型提供了群体平均 TBS 的估计值以及 RID 系数 FaS 的群体特异性值；后者可用于通过 RID 有把握地预测研究群体中个别参与者或类似个体在摄入同位素 14 天或更长时间后的 TBS。试验注册号试验已在 https://clinicaltrials.gov 注册 (NCT04632771)。

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