title: Plasma Retinol Kinetics and β-Carotene Bioefficacy Are Quantified by Model-Based Compartmental Analysis in Healthy Young Adults with Low Vitamin A Stores.
abstract: 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.
  
  
  OBJECTIVE
  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; 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 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.
authors: Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA; and.
authors: Michael H
authors: MH
authors: Green
authors: Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA; and.
authors: Jennifer Lynn
authors: JL
authors: Ford
authors: Human Nutrition Research Centre and.
authors: Anthony
authors: A
authors: Oxley
authors: Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA; and.
authors: Joanne Balmer
authors: JB
authors: Green
authors: Human Nutrition Research Centre and.
authors: Hyunjin
authors: H
authors: Park
authors: Northern Institute for Cancer Research, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors: Philip
authors: P
authors: Berry
authors: Northern Institute for Cancer Research, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors: Alan V
authors: AV
authors: Boddy
authors: Human Nutrition Research Centre and georg.lietz@ncl.ac.uk.
authors: Georg
authors: G
authors: Lietz
mesh_terms: D000284:Administration, Oral; D000328:Adult; D015992:Body Mass Index; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D004224:Diterpenes; D002149:Energy Intake; D005260:Female; D006801:Humans; D008297:Male; D008962:Models, Theoretical; D017711:Nonlinear Dynamics; D009752:Nutritional Status; D000084562:Retinyl Esters; D014280:Triglycerides / Q000097:blood; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D014802:Vitamin A Deficiency / Q000097:blood; D044465:White People; D055815:Young Adult; D019207:beta Carotene / Q000008:administration & dosage / Q000097:blood*
chemical_list: D004224:Diterpenes; D000084562:Retinyl Esters; D014280:Triglycerides; D019207:beta Carotene; D014801:Vitamin A; C009166:retinol acetate; D002784:Cholesterol
keywords: WinSAAM; area under the curve; bioconversion; bioefficacy; carotenoids; humans; isotope dilution; retinoids; retinol kinetics; vitamin A deficiency