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Increased Study Length of Retinol Isotope Dilution with Compartmental Modeling Alters Kinetic Parameters and Calculated Vitamin A Stores
Author(s) -
Gan Bryan M,
Valentine Ashley R,
Davis Christopher R,
Howe Julie A,
Tanumihardjo Sherry A
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.32.1
Subject(s) - isotope dilution , dilution , isotope , chemistry , kinetic energy , compartment (ship) , biological system , mathematics , chromatography , thermodynamics , biology , physics , mass spectrometry , oceanography , quantum mechanics , geology
Background Retinol isotope dilution is considered an accurate, indirect measure of vitamin A (VA) status. Multi‐compartment mathematical modeling of isotope dilution data is used to refine study design and equations to calculate VA stores from isotope dilution. Previous studies suggest some VA may be in slowly turning over pools that is not traced if follow‐up is not long enough. Data and resulting models from long‐term studies are limited. Objectives Determine the effect of study duration on mathematical models of VA metabolism including kinetic parameters and model outcomes. Methods Adult females (22 ± 3 y; n = 7) were given 2 μmol 13 C‐VA and had blood sampled in a staggered serial design from 4 h to 152 d; fraction of dose in serum against time were modeled with compartmental models of VA metabolism. Four model time categories were created; full models were developed using all data (133 ± 23 d), and truncated data simulating shorter studies of 52 ± 6, 28, and 14 d to determine effect of study length on number of needed model compartments to adequately model the data, kinetic parameters, total traced VA mass, and time to dose equilibration. To gain insight into even longer follow‐up, an additional subject was given 17.5 μmol 13 C‐VA, and data were modeled as long as the dose was detectable above baseline enrichment (5 y). Results Increased follow‐up affected numerous kinetic parameters and modeling outcomes. Compared to the shortest 14 d model, full models required an additional compartment to adequately fit the model (14.3 vs. 100%, P = 0.0047) and had greater half‐life (30.8 ± 30.5 vs. 162 ± 80.2 d, P = 0.0006), time to dose equilibration (4.44 ± 2.08 vs. 19.8 ± 8.72 d, P < 0.0001), and total traced mass (209 ± 110 vs. 629 ± 490 μmol VA, P = 0.0031). Conclusions Extending the duration of isotope dilution and mathematical modeling studies alters numerous outcomes in a dose‐response fashion. It is important to consider these results when using mathematical models for calculating total body VA stores or kinetic parameters related to VA metabolism. Support or Funding Information Supported by NIHNIDDK 61973