Green Michael H, Green Joanne Balmer
Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, PA, USA.
J Nutr. 2022 Mar 3;152(3):707-713. doi: 10.1093/jn/nxab441.
We review recent work in which model-based compartmental analysis has been applied to data for theoretical human subjects in order to study questions related to vitamin A kinetics and metabolism. Using model simulations in this way, one can validate experimental designs, evaluate or improve vitamin A assessment methods, study the influence of perturbations on assessment methods, and/or advance information related to retinol kinetics. We also provide some information on the rationale for assigning physiologically appropriate values for specified characteristics [e.g., plasma retinol concentration, vitamin A total body stores (TBS), vitamin A intake] to hypothetical individuals, and in addition, we outline how one might first select an appropriate compartmental model for whole-body vitamin A metabolism and then specify physiologically reasonable values for the associated retinol kinetic parameters. In the studies discussed here, the Simulation, Analysis, and Modeling software was used to simulate responses in key model compartments for hypothetical subjects so that model predictions could be compared to assigned values or projected outcomes. For example, in the case of the retinol isotope dilution (RID) method that is used to assess vitamin A status, application of this approach has provided a way to evaluate the accuracy of TBS predictions under different steady state and non-steady state conditions, thus increasing confidence about the validity of RID results obtained in the field. Although datasets for theoretical subjects have been used to evaluate protocols in pharmacokinetics, to our knowledge, other nutrition researchers have not previously used approaches such as those described here. Our results to date indicate that this strategy has the potential to provide useful information related not only to vitamin A but perhaps to other nutrients as well.
我们回顾了最近的一些研究工作，其中基于模型的房室分析已应用于理论人体受试者的数据，以研究与维生素A动力学和代谢相关的问题。通过这种方式使用模型模拟，可以验证实验设计、评估或改进维生素A评估方法、研究扰动对评估方法的影响，和/或推进与视黄醇动力学相关的信息。我们还提供了一些关于为假设个体的特定特征[例如血浆视黄醇浓度、维生素A全身储存量（TBS）、维生素A摄入量]指定生理合适值的基本原理的信息，此外，我们概述了如何首先为全身维生素A代谢选择合适的房室模型，然后为相关的视黄醇动力学参数指定生理合理值。在这里讨论的研究中，使用了模拟、分析和建模软件来模拟假设受试者关键模型房室中的反应，以便将模型预测与指定值或预测结果进行比较。例如，在用于评估维生素A状态的视黄醇同位素稀释（RID）方法的情况下，这种方法的应用提供了一种在不同稳态和非稳态条件下评估TBS预测准确性的方法，从而增加了对现场获得的RID结果有效性的信心。尽管理论受试者的数据集已用于评估药代动力学方案，但据我们所知，其他营养研究人员以前尚未使用过此处描述的方法。我们目前的结果表明，这种策略不仅有可能提供与维生素A相关的有用信息，而且可能也与其他营养素相关。
