Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, PA, USA.
J Nutr. 2021 Feb 1;151(2):434-444. doi: 10.1093/jn/nxaa306.
Descriptive and quantitative information on β-carotene whole-body kinetics in humans is limited.
Our objective was to advance the development of a physiologically based, working hypothesis compartmental model describing the metabolism of β-carotene and β-carotene-derived retinol.
We used model-based compartmental analysis (Simulation, Analysis and Modeling software) to analyze previously published data on plasma kinetics of [2H8]β-carotene, [2H4]β-carotene-derived retinol, and [2H8]retinyl acetate-derived retinol in healthy, older US adults (3 female, 2 male; 50-68 y); subjects were studied for 56 d after consuming doses of 11 μmol [2H8]β-carotene and, 3 d later, 9 μmol [2H8]retinyl acetate in oil.
We developed a complex model for labeled β-carotene and β-carotene-derived retinol, as well as preformed vitamin A, using simulations to augment observed data during model calibration. The model predicts that mean (range) β-carotene absorption (bioavailability) was 9.5% (5.2-14%) and bioefficacy was 7.3% (3.6-14%). Of the absorbed β-carotene, 41% (25-58%) was packaged intact in chylomicrons and the balance was converted to retinol, with 58% (42-75%) transported as retinyl esters in chylomicrons and 0-2% by retinol-binding protein. Most (95%) chylomicron β-carotene was cleared by the liver. Later data revealed differences in the metabolism of retinyl acetate- versus β-carotene-derived retinol; data required that both β-carotene and derived retinol be recycled from extrahepatic tissues (e.g. adipose) in HDL. Of total bioconversion [73% (47-99%)], 82% occurred in the intestine, 17% in the liver, and 0.83% in other tissues.
Our model advances knowledge about whole-body β-carotene metabolism in healthy adults, including the kinetics of transport in all lipoprotein species, and suggests hypotheses to be tested in future studies, such as the possibility that retinol derived from hepatic conversion over a long period of time might contribute to plasma retinol homeostasis and total body vitamin A stores.
人体β-胡萝卜素全身动力学的描述性和定量信息有限。
我们的目标是推进一个基于生理学的、工作假说的房室模型的发展，该模型描述了β-胡萝卜素和β-胡萝卜素衍生的视黄醇的代谢。
我们使用基于模型的房室分析（Simulation、Analysis and Modeling 软件）来分析先前发表的关于健康的美国老年人（3 名女性，2 名男性；50-68 岁）血浆动力学的[2H8]β-胡萝卜素、[2H4]β-胡萝卜素衍生的视黄醇和[2H8]视黄基乙酸酯衍生的视黄醇的数据；在摄入 11 μmol [2H8]β-胡萝卜素剂量后，受试者被研究了 56 天，然后在 3 天后摄入 9 μmol [2H8]视黄基乙酸酯油。
我们使用模拟来增强模型校准期间的观察数据，为标记的β-胡萝卜素和β-胡萝卜素衍生的视黄醇以及预先形成的维生素 A 开发了一个复杂的模型。该模型预测，β-胡萝卜素吸收（生物利用度）的平均值（范围）为 9.5%（5.2-14%），生物效力为 7.3%（3.6-14%）。吸收的β-胡萝卜素中，41%（25-58%）完整地包装在乳糜微粒中，其余的转化为视黄醇，其中 58%（42-75%）以乳糜微粒中的视黄基酯的形式运输，0-2%通过视黄醇结合蛋白运输。大多数（95%）乳糜微粒β-胡萝卜素被肝脏清除。后来的数据显示，视黄基乙酸酯衍生的视黄醇与β-胡萝卜素衍生的视黄醇的代谢存在差异；数据要求β-胡萝卜素和衍生的视黄醇都从 HDL 中的肝外组织（如脂肪组织）中循环。总生物转化的[73%（47-99%）]，82%发生在肠道，17%发生在肝脏，0.83%发生在其他组织。
我们的模型推进了关于健康成年人全身β-胡萝卜素代谢的知识，包括所有脂蛋白种类中的运输动力学，并提出了在未来研究中进行测试的假设，例如，长期来自肝内转化的视黄醇可能有助于血浆视黄醇稳态和全身维生素 A 储存的可能性。
