A Compartmental Model Describing the Kinetics of β-Carotene and β-Carotene-Derived Retinol in Healthy Older Adults

Abstract

ABSTRACT Background Descriptive and quantitative information on β-carotene whole-body kinetics in humans is limited. Objectives 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. Methods 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. Results 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. Conclusions 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.