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 β-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 β-carotene and to determine relative β-carotene bioefficacy. Methods: We used the Simulation, Analysis andModeling software (WinSAAMversion 3.0.8; http://www. WinSAAM.org) to analyze previously collected data on plasma [¹³C₁₀]- and [¹³C₅]retinol kinetics for 14 d after oral administration of 1 mg [¹³C₁₀] retinyl acetate and 2mg [¹³C₁₀]β-carotene in oil to 30 healthy young adults of European ancestry [13men, 17women; mean± SD age: 24.5 ± 4.2 y; mean ± SD body weight: 65.2 ± 10 kg; mean ± SD body mass index (in kg/m²): 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 μmol/d, fractional catabolic rate was 6.0% ± 2.3%/d, and vitamin A stores were 123 ± 71 μmol. Relative β-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 μg). Interindividual variation in relative β-carotene bioefficacy was high (CV: 44%). Conclusions: Vitamin A kinetics in these young adults were best described by essentially the samemodel 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 β-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.