Plasma Retinol Kinetics and β-Carotene Bioefficacy Are Quantified by Model-Based Compartmental Analysis in Healthy Young Adults with Low Vitamin A Stores

Background: Model-based compartmental analysis of data on plasma retinol kinetics after administration of labeled retinol provides unique information about whole-body vitamin A metabolism. If labeled beta-carotene is coadministered, its bioefficacy relative to the retinol reference dose can also be estimated. Objectives: The objectives were to model plasma retinol kinetics after administration of labeled preformed vitamin A and provitamin A [3-carotene and to determine relative beta-carotene bioefficacy. Methods: We used the Simulation, Analysis and Modeling software (WinSAAM version 3.0.8; http://www.WinSAAM.org) to analyze previously collected data on plasma [C-13(10)]- and [C-13(5)]retinol kinetics for 14 d after oral administration of 1 mg [C-13(10)] retinyl acetate and 2 mg [C-13(10)]beta-carotene in oil to 30 healthy young adults of European ancestry [13 men, 17 women; mean SD age: 24.5 +/- 4.2 y; mean SD body weight: 65.2 +/- 10 kg; mean +/- SD body mass index (in kg/m(2)): 22.5 +/- 1.9] with moderate vitamin A intakes. Results: A 6-component model provided the best fit to the data, including compartments for initial metabolism of vitamin A, plasma retinol, and extravascular vitamin A storage. The disposal rate was 6.7 +/- 3.1 mu mol/d, fractional catabolic rate was 6.0% +/- 2.3%/d, and vitamin A stores were 123 +/- 71 mu mol. Relative pi-carotene bioefficacy, based on the ratio of the areas under the fraction of dose curves calculated by WinSAAM, averaged 13.5% +/- 6.02% (retinol activity equivalents = 7.7:1.0 mu g). Interindividual variation in relative (3-carotene bioefficacy was high (CV: 44%). Conclusions: Vitamin A kinetics in these young adults were best described by essentially the same model that had been previously developed by using data for older adults with higher vitamin A stores; differences in parameter values reflected differences in vitamin A status. Estimated beta-carotene bioefficacy was relatively low but similar to previously reported estimates obtained by graphical methods. This trial was registered at the UK Clinical Research Network as UKCRN 7413.