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

Lookup NU author(s): Dr Anthony OxleyORCiD, Philip Berry, Professor Georg Lietz



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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 and Modeling software (WinSAAM version 3.0.8; 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 2 mg [13C10]β-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/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 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 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.

Publication metadata

Author(s): Green MH, Ford JL, Oxley A, Green JB, Park H, Berry P, Boddy AV, Lietz G

Publication type: Article

Publication status: Published

Journal: Journal of Nutrition

Year: 2016

Volume: 146

Issue: 10

Pages: 2129-2136

Print publication date: 01/10/2016

Online publication date: 10/08/2016

Acceptance date: 23/06/2016

Date deposited: 25/08/2016

ISSN (print): 0022-3166

ISSN (electronic): 1541-6100

Publisher: American Society for Nutrition


DOI: 10.3945/jn.116.233486


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Funder referenceFunder name
Cancer Research UK
College of Health and Human Development, The Pennsylvania State University
Newcastle University
DSM Nutritional Products (Basel, Switzerland)
BB/G004056/1Biotechnology and Biological Science Research Council
BB/G004056/1Biotechnology and Biological Sciences Research Council