应用房室模型和视黄醇同位素稀释法评估镰状细胞病患儿补充维生素 A 前后维生素 A 储存量。

Use of Compartmental Modeling and Retinol Isotope Dilution to Determine Vitamin A Stores in Young People with Sickle Cell Disease Before and After Vitamin A Supplementation.

机构信息

Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, PA, United States.

出版信息

J Nutr. 2023 Sep;153(9):2762-2771. doi: 10.1016/j.tjnut.2023.07.004. Epub 2023 Jul 17.

DOI:10.1016/j.tjnut.2023.07.004

PMID:37468045

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10517228/

Abstract

BACKGROUND

Suboptimal plasma retinol concentrations have been documented in US children with sickle cell disease (SCD) hemoglobin SS type (SCD-HbSS), but little is known about vitamin A kinetics and stores in SCD.

OBJECTIVES

The objectives were to quantify vitamin A total body stores (TBS) and whole-body retinol kinetics in young people with SCD-HbSS and use retinol isotope dilution (RID) to predict TBS in SCD-HbSS and healthy peers as well as after vitamin A supplementation in SCD-HbSS subjects.

METHODS

Composite plasma [C]retinol response data collected from 22 subjects with SCD-HbSS for 28 d after isotope ingestion were analyzed using population-based compartmental modeling ("super-subject" approach); TBS and retinol kinetics were quantified for the group. TBS was also calculated for the same individuals using RID, as well as for healthy peers (n = 20) and for the subjects with SCD-HbSS after 8 wk of daily vitamin A supplements (3.15 or 6.29 μmol retinol/d [900 or 1800 μg retinol activity equivalents/d]).

RESULTS

Model-predicted group mean TBS for subjects with SCD-HbSS was 428 μmol, equivalent to ∼11 mo of stored vitamin A; vitamin A disposal rate was 1.3 μmol/d. Model-predicted TBS was similar to that predicted by RID at 3 d postdosing (mean, 389 μmol; ∼0.3 μmol/g liver); TBS predictions at 3 compared with 28 d were not significantly different. Mean TBS in healthy peers was similar (406 μmol). RID-predicted TBS for subjects with SCD-HbSS was not significantly affected by vitamin A supplementation at either dose.

CONCLUSIONS

Despite differences in plasma retinol concentrations, TBS was the same in subjects with SCD-HbSS compared with healthy peers. Because 56 d of vitamin A supplementation at levels 1.2 to 2.6 times the Recommended Dietary Allowance did not increase TBS in these subjects with SCD-HbSS, further work will be needed to understand the effects of SCD on retinol metabolism. This trial was registered as NCT03632876 at clinicaltrials.gov.

摘要

背景

已在患有镰状细胞病（SCD）血红蛋白 SS 型（SCD-HbSS）的美国儿童中发现血浆视黄醇浓度不理想，但对于 SCD 中的维生素 A 动力学和储存知之甚少。

目的

本研究的目的是定量研究 SCD-HbSS 青少年的维生素 A 全身总储存量（TBS）和全身视黄醇动力学，并使用视黄醇同位素稀释（RID）来预测 SCD-HbSS 和健康同龄人的 TBS 以及 SCD-HbSS 受试者接受维生素 A 补充后的 TBS。

方法

对 22 例 SCD-HbSS 患者在同位素摄入后 28 天内的复合血浆 [C]视黄醇反应数据进行基于群体的房室模型分析（“超级受试者”方法）；对该组进行 TBS 和视黄醇动力学的定量分析。还使用 RID 为相同个体计算 TBS，以及为健康同龄人（n=20）和 SCD-HbSS 患者在 8 周的每日维生素 A 补充后（3.15 或 6.29 μmol 视黄醇/天[900 或 1800 μg 视黄醇活性当量/天]）计算 TBS。

结果

模型预测 SCD-HbSS 患者的组平均 TBS 为 428 μmol，相当于约 11 个月的储存维生素 A；维生素 A 清除率为 1.3 μmol/d。在 3 天（平均 389 μmol，≈0.3 μmol/g 肝脏）和 28 天（平均 389 μmol，≈0.3 μmol/g 肝脏）的 RID 预测 TBS 与模型预测 TBS 相似，两者之间无显著差异。健康同龄人的平均 TBS 相似（406 μmol）。RID 预测的 SCD-HbSS 患者的 TBS 剂量在两种剂量下均不受维生素 A 补充的影响。

结论

尽管血浆视黄醇浓度存在差异，但 SCD-HbSS 患者的 TBS 与健康同龄人相似。由于 SCD-HbSS 患者 56 天的维生素 A 补充水平为推荐膳食允许量的 1.2 至 2.6 倍，并未增加 TBS，因此需要进一步研究以了解 SCD 对视黄醇代谢的影响。该试验在 clinicaltrials.gov 上注册为 NCT03632876。