TY - JOUR
T1 - Duration of retinol isotope dilution studies with compartmental modeling affects model complexity, kinetic parameters, and calculated Vitamin A stores in US women
AU - Gannon, Bryan M.
AU - Valentine, Ashley R.
AU - Davis, Christopher R.
AU - Howe, Julie A.
AU - Tanumihardjo, Sherry A.
N1 - Funding Information:
This work ranked first in the Emerging Leaders Competition for the Carotenoids and Retinoids Interactive Group at the ASN meeting in 2017. Supported by NIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 61973 and the National Research Initiative of the USDA Cooperative State Research, Education, and Extension Service (grant 2003-35200-05377). Author disclosures: BMG, ARV, CRD, JAH, and SAT, no conflicts of interest. Supplemental Figure 1 and Supplemental Tables 1–3 are available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/jn/. Present address for BMG: Cornell University, Division of Nutritional Sciences, 244 Garden Ave. Ithaca, NY 14853. Present address for ARV: Oregon Health and Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239. Present address for JAH: Texas A&M University, Soil and Crop Sciences, 2474 TAMU Soil & Crop Sciences Dept., College Station, TX 77843. Address correspondence to SAT (e-mail: sherry@nutrisci.wisc.edu) or BMG (e-mail: bryan.gannon@cornell.com). Abbreviations used: EAR, Estimated Average Requirement; RAE, retinol activity equivalent; RID, retinol isotope dilution; TBS, total body stores; TLR, total liver reserve; TTR, tracer-to-tracee ratio; UW, University of Wisconsin; VA, vitamin A.
Publisher Copyright:
© 2018 American Society for Nutrition. All rights reserved.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Background: Retinol isotope dilution (RID) indirectly estimates vitamin A (VA) status. Multicompartment modeling of RID data is used to refine study designs and equations to calculate VA stores. Previous studies suggest that VA in slowly turning over pools is not traced if follow-up is not long enough; however, shorter RID studies are being investigated. Few long-term models have been published. Objective: We determined the effect of time on mathematical models of VA kinetics, model parameters, and outcomes. Methods: In this longitudinal study, women (mean ± SD age: 22 ± 3 y; n = 7) were given 2.0 µmol [14,15]-13C2-retinyl acetate. Blood samples were staggered from 4 h to 152 d; the fraction of dose in serum was modeled with compartmental models. Four model-time categories were created: full models that used all data (median: 137 d; range 97-152 d) and truncated shorter studies of 14, 27, and 52 d (range: 42-62 d). Outcomes included number of compartments to adequately model serum data, kinetic parameters, total traced VA mass, and time-to-dose equilibration. To gain insight into longer follow-up, an additional participant was given 17.5 µmol13C4-VA, and data were modeled as long as enrichment was above baseline (5 y). Results: Longer follow-up times affected kinetic parameters and outcomes. Compared with the 14-d models, long-term full models required an additional compartment for adequate fit (14.3% compared with 100%; P= 0.0056) and had longer [median (quartile 1, quartile 3)] whole-body half-life [15.0 d (10.5, 72.6 d) compared with 135 d (115, 199 d); P = 0.0006], time-to-dose equilibration [3.40 d (3.14, 6.75 d) compared with 18.9 d (11.2, 25.7 d); P < 0.0001], and total traced mass [166 µmol VA (162, 252 µmol VA) compared with 476 µmol VA (290, 752 µmol VA); P = 0.0031]. Conclusions: Extended RID sampling alters numerous mathematically modeled, time-dependent outcomes in women. Length of study should be considered when using mathematical models for calculating total-body VA stores or kinetic parameters related to VA turnover.
AB - Background: Retinol isotope dilution (RID) indirectly estimates vitamin A (VA) status. Multicompartment modeling of RID data is used to refine study designs and equations to calculate VA stores. Previous studies suggest that VA in slowly turning over pools is not traced if follow-up is not long enough; however, shorter RID studies are being investigated. Few long-term models have been published. Objective: We determined the effect of time on mathematical models of VA kinetics, model parameters, and outcomes. Methods: In this longitudinal study, women (mean ± SD age: 22 ± 3 y; n = 7) were given 2.0 µmol [14,15]-13C2-retinyl acetate. Blood samples were staggered from 4 h to 152 d; the fraction of dose in serum was modeled with compartmental models. Four model-time categories were created: full models that used all data (median: 137 d; range 97-152 d) and truncated shorter studies of 14, 27, and 52 d (range: 42-62 d). Outcomes included number of compartments to adequately model serum data, kinetic parameters, total traced VA mass, and time-to-dose equilibration. To gain insight into longer follow-up, an additional participant was given 17.5 µmol13C4-VA, and data were modeled as long as enrichment was above baseline (5 y). Results: Longer follow-up times affected kinetic parameters and outcomes. Compared with the 14-d models, long-term full models required an additional compartment for adequate fit (14.3% compared with 100%; P= 0.0056) and had longer [median (quartile 1, quartile 3)] whole-body half-life [15.0 d (10.5, 72.6 d) compared with 135 d (115, 199 d); P = 0.0006], time-to-dose equilibration [3.40 d (3.14, 6.75 d) compared with 18.9 d (11.2, 25.7 d); P < 0.0001], and total traced mass [166 µmol VA (162, 252 µmol VA) compared with 476 µmol VA (290, 752 µmol VA); P = 0.0031]. Conclusions: Extended RID sampling alters numerous mathematically modeled, time-dependent outcomes in women. Length of study should be considered when using mathematical models for calculating total-body VA stores or kinetic parameters related to VA turnover.
KW - C-retinol
KW - Mathematical modeling
KW - Retinol kinetics
KW - Stable isotopes
KW - Vitamin A status
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U2 - 10.1093/jn/nxy095
DO - 10.1093/jn/nxy095
M3 - Article
C2 - 30137477
AN - SCOPUS:85055536678
VL - 148
SP - 1387
EP - 1396
JO - Journal of Nutrition
JF - Journal of Nutrition
SN - 0022-3166
IS - 8
ER -