A Simple Plasma Retinol Isotope Ratio Method for Estimating β-Carotene Relative Bioefficacy in Humans: Validation with the Use of Model-Based Compartmental Analysis

• Published in: The Journal of nutrition Vol. 147; no. 9; pp. 1806 - 1814
• Main Authors: Ford, Jennifer Lynn, Green, Joanne Balmer, Lietz, Georg, Oxley, Anthony, Green, Michael H
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2017
• Subjects: beta Carotene - metabolism; beta Carotene - pharmacokinetics; bioconversion; bioefficacy; Biological Availability; carotenoids; Diterpenes; Humans; Intestinal Absorption; isotope reference method; Isotopes - metabolism; model-based compartmental analysis; Models, Biological; Provitamins - metabolism; retinoids; retinol isotope ratio; Retinyl Esters; Vitamin A - analogs & derivatives; Vitamin A - biosynthesis; Vitamin A - blood; Vitamin A - metabolism; WinSAAM; β-carotene; carotenoids; IRM; bioconversion; β-carotene; model-based compartmental analysis; WinSAAM; isotope reference method; bioefficacy; FDp; retinol isotope ratio; RIR; humans; retinoids; AUCp
• ISSN: 0022-3166; 1541-6100; 1541-6100
• DOI: 10.3945/jn.117.252361

Provitamin A carotenoids are an important source of dietary vitamin A for many populations. Thus, accurate and simple methods for estimating carotenoid bioefficacy are needed to evaluate the vitamin A value of test solutions and plant sources. β-Carotene bioefficacy is often estimated from the ratio of the areas under plasma isotope response curves after subjects ingest labeled β-carotene and a labeled retinyl acetate reference dose [isotope reference method (IRM)], but to our knowledge, the method has not yet been evaluated for accuracy. Our objectives were to develop and test a physiologically based compartmental model that includes both absorptive and postabsorptive β-carotene bioconversion and to use the model to evaluate the accuracy of the IRM and a simple plasma retinol isotope ratio [(RIR), labeled β-carotene-derived retinol/labeled reference-dose-derived retinol in one plasma sample] for estimating relative bioefficacy. We used model-based compartmental analysis (Simulation, Analysis and Modeling software) to develop and apply a model that provided known values for β-carotene bioefficacy. Theoretical data for 10 subjects were generated by the model and used to determine bioefficacy by RIR and IRM; predictions were compared with known values. We also applied RIR and IRM to previously published data. Plasma RIR accurately predicted β-carotene relative bioefficacy at 14 d or later. IRM also accurately predicted bioefficacy by 14 d, except that, when there was substantial postabsorptive bioconversion, IRM underestimated bioefficacy. Based on our model, 1-d predictions of relative bioefficacy include absorptive plus a portion of early postabsorptive conversion. The plasma RIR is a simple tracer method that accurately predicts β-carotene relative bioefficacy based on analysis of one blood sample obtained at ≥14 d after co-ingestion of labeled β-carotene and retinyl acetate. The method also provides information about the contributions of absorptive and postabsorptive conversion to total bioefficacy if an additional sample is taken at 1 d.