scholarly journals Updated Estimates of Vitamin a Total Body Stores in Healthy Young Adults Determined by Compartmental Modeling with Vitamin a Intake Added as Data (FS06-07-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Jennifer Ford ◽  
Georg Lietz ◽  
Anthony Oxley ◽  
Joanne Green ◽  
Michael Green
Keyword(s):  
Young Adults ◽  
Vitamin A ◽  
Model Prediction ◽  
Simulation Analysis ◽  
Geometric Mean ◽  
Compartmental Analysis ◽  
Science Research ◽  
European Ancestry ◽  
Retinyl Acetate ◽  
Total Body

Abstract Objectives We applied a new modeling approach to generate estimates of vitamin A total body stores (TBS) for previously-studied subjects (Green et al. J Nutr 2016;146:2129–36) who were consuming moderate amounts of preformed vitamin A. Based on recent work, we hypothesized that inclusion of an estimate of vitamin A dietary intake (DI) during modeling would help compensate for the less-than-optimal study duration (14 d). Methods We reanalyzed retinol kinetic data collected after ingestion of [13C10]retinyl acetate by 26 young adults of European ancestry for whom estimates of DI were available. To predict TBS by compartmental analysis, geometric mean (GM) data on fraction of dose in plasma versus time plus estimated intake (2.9 µmol retinol activity equivalents/d) were analyzed using the Simulation, Analysis and Modeling software in light of previously-established models. We also used modeling to estimate coefficients (“FaS”) used in retinol isotope dilution (RID) equations and calculated TBS for the group and individuals. Results TBS predicted by the model without DI data included was 98 µmol; when the GM DI was included in the modeling data stream, predicted TBS was 273 µmol. Including DI data during modeling also resulted in lower predictions of intake [2.9 versus 8.7 µmol/d without DI, compared with the average RDA for adults (2.8 µmol/d)] and longer predicted days of vitamin A stores (125 versus 15 d). Using the FaS at 7 d (0.90) predicted by the model with DI, RID-predicted TBS agreed with the model prediction (GM, 274 µmol, range 106–889 µmol). Conclusions Results indicate that including an estimate of DI during modeling provides more realistic predictions of TBS for studies of short duration and improves confidence in model prediction of vitamin A status. Funding Sources Original human studies were supported by Biotechnology and Biological Science Research Council (grant BB/G004056/1 to GL) and Cancer Research UK; current analyses were supported by College of Health and Human Development, Penn State University.

scholarly journals The “Super-Child” Approach Is Applied To Estimate Retinol Kinetics and Vitamin A Total Body Stores in Mexican Preschoolers

2020 ◽  
Vol 150 (6) ◽  
pp. 1644-1651 ◽  
Author(s):  
Veronica Lopez-Teros ◽  
Jennifer L Ford ◽  
Michael H Green ◽  
Brianda Monreal-Barraza ◽  
Lilian García-Miranda ◽  
...  
Keyword(s):  
Vitamin A ◽  
Corn Oil ◽  
Compartmental Analysis ◽  
Whole Body ◽  
Retinyl Acetate ◽  
Data Set ◽  
Mexican Children ◽  
Model Predictions ◽  
Total Body ◽  
Composite Data

ABSTRACT Background Retinol isotope dilution (RID) and model-based compartmental analysis are recognized techniques for assessing vitamin A (VA) status. Recent studies have shown that RID predictions of VA total body stores (TBS) can be improved by using modeling and that VA kinetics and TBS in children can be effectively studied by applying population modeling (“super-child” approach) to a composite data set. Objectives The objectives were to model whole-body retinol kinetics and predict VA TBS in a group of Mexican preschoolers using the super-child approach and to use model predictions of RID coefficients to estimate TBS by RID in individuals. Methods Twenty-four healthy Mexican children (aged 3–6 y) received an oral dose (2.96 μmol) of [13C10]retinyl acetate in corn oil. Blood samples were collected from 8 h to 21 d after dosing, with each child sampled at 4 d and at 1 other time. Composite data for plasma labeled retinol compared with time were analyzed using a 6-component model to obtain group retinol kinetic parameters and pool sizes. Model-predicted TBS was compared with mean RID predictions at 4 d; RID estimates at 4 d were compared with those calculated at 7–21 d. Results Model-predicted TBS was 1097 μmol, equivalent to ∼2.4 y-worth of VA; using model-derived coefficients, group mean RID-predicted TBS was 1096 μmol (IQR: 836–1492 μmol). TBS at 4 d compared with a later time was similar (P = 0.33). The model predicted that retinol spent 1.5 h in plasma during each transit and recycled to plasma 13 times before utilization. Conclusions The super-child modeling approach provides information on whole-body VA kinetics and can be used with RID to estimate TBS at any time between 4 and 21 d postdose. The high TBS predicted for these children suggests positive VA balance, likely due to large-dose VA supplements, and warrants further investigation.

scholarly journals Inclusion of Vitamin A Intake Data Provides Improved Compartmental Model-Derived Estimates of Vitamin A Total Body Stores and Disposal Rate in Older Adults

2019 ◽  
Vol 149 (7) ◽  
pp. 1282-1287 ◽  
Author(s):  
Michael H Green ◽  
Jennifer Lynn Ford ◽  
Joanne Balmer Green
Keyword(s):  
Vitamin A ◽  
Simulation Analysis ◽  
Compartmental Analysis ◽  
Published Data ◽  
Study Duration ◽  
Additional Input ◽  
Modeling Software ◽  
Ev Model ◽  
Plasma Retinol ◽  
Total Body

ABSTRACT Background Sampling times and study duration impact estimates of kinetic parameters and variables including total body stores (TBS) and disposal rate (DR) when compartmental analysis is used to analyze vitamin A kinetic data. Objective We hypothesized that inclusion of dietary intake (DI) of vitamin A as an additional input would improve confidence in predictions of TBS and DR when modeling results appear to indicate that studies are not long enough to accurately define the terminal slope of the plasma retinol isotope response curve. Methods We reanalyzed previously published data on vitamin A kinetics monitored over 52 d in 7 US and 6 Chinese adults (means: 56 y, BMI 26.6 kg/m2, 38% males), adding an estimate for vitamin A intake [2.8 µmol/d (mean RDA)] as an input during application of the Simulation, Analysis and Modeling software. Results Use of a model with 1 extravascular compartment (1 EV), as in the original analysis, resulted in predictions of vitamin A intake that were higher than physiologically reasonable; inclusion of intake data in a model with 2 extravascular compartments (2 EV DI) resulted in more realistic estimates of intake and DR. Specifically, predictions of DR by the 2 EV DI (versus 1 EV) model were 2.10 compared with 12.2 µmol/d (US) and 2.21 compared with 5.13 µmol/d (Chinese). Predictions of both TBS [2056 compared with 783 µmol (US) and 594 compared with 219 µmol (Chinese)] and days of vitamin A stores [981 compared with 64 d (US) and 269 compared with 43 d (Chinese)] were higher using the new approach. Conclusions Inclusion of vitamin A intake as additional data input when modeling vitamin A kinetics can compensate for less-than-optimal study duration, providing more realistic predictions of vitamin A TBS and DR. This approach advances the application of compartmental analysis to the study of vitamin A and, potentially, other nutrients.

scholarly journals Use of Model-Based Compartmental Analysis and a Super-Child Design to Study Whole-Body Retinol Kinetics and Vitamin A Total Body Stores in Children from 3 Lower-Income Countries

2019 ◽  
Vol 150 (2) ◽  
pp. 411-418 ◽  
Author(s):  
Jennifer Lynn Ford ◽  
Joanne Balmer Green ◽  
Marjorie J Haskell ◽  
Shaikh M Ahmad ◽  
Dora Inés Mazariegos Cordero ◽  
...  
Keyword(s):  
Vitamin A ◽  
Compartmental Analysis ◽  
The Philippines ◽  
Whole Body ◽  
Retinyl Acetate ◽  
Data Set ◽  
Blood Samples ◽  
Model Based ◽  
Vitamin A Status ◽  
Total Body

ABSTRACT Background Model-based compartmental analysis has been used to describe and quantify whole-body vitamin A metabolism and estimate total body stores (TBS) in animals and humans. Objectives We applied compartmental modeling and a super-child design to estimate retinol kinetic parameters and TBS for young children in Bangladesh, Guatemala, and the Philippines. Methods Children ingested [13C10]retinyl acetate and 1 or 2 blood samples were collected from each child from 6 h to 28 d after dosing. Temporal data for fraction of dose in plasma [13C10]retinol were modeled using WinSAAM software and a 6-component model with vitamin A intake included as weighted data. Results Model-predicted TBS was 198, 533, and 1062 μmol for the Bangladeshi (age, 9–17 mo), Filipino (12–18 mo), and Guatemalan children (35–65 mo). Retinol kinetics were similar for Filipino and Guatemalan groups and generally faster for Bangladeshi children, although fractional transfer of plasma retinol to a larger exchangeable storage pool was the same for the 3 groups. Recycling to plasma from that pool was ∼2.5 times faster in the Bangladeshi children compared with the other groups and the recycling number was 2–3 times greater. Differences in kinetics between groups are likely related to differences in vitamin A stores and intakes (geometric means: 352, 727, and 764 μg retinol activity equivalents/d for the Bangladeshi, Filipino, and Guatemalan children, respectively). Conclusions By collecting 1 or 2 blood samples from each child to generate a composite plasma tracer data set with a minimum of 5 children/time, group TBS and retinol kinetics can be estimated in children by compartmental analysis; inclusion of vitamin A intake data increases confidence in model predictions. The super-child modeling approach is an effective technique for comparing vitamin A status among children from different populations. These trials were registered at www.clinicaltrials.gov as NCT03000543 (Bangladesh), NCT03345147 (Guatemala), and NCT03030339 (Philippines).

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

2016 ◽  
Vol 146 (10) ◽  
pp. 2129-2136 ◽  
Author(s):  
Michael H Green ◽  
Jennifer Lynn Ford ◽  
Anthony Oxley ◽  
Joanne Balmer Green ◽  
Hyunjin Park ◽  
...  
Keyword(s):  
Young Adults ◽  
Vitamin A ◽  
Compartmental Analysis ◽  
Model Based ◽  
Plasma Retinol ◽  
Β Carotene

Does the Amount of Stable Isotope Dose Influence Retinol Kinetic Responses and Predictions of Vitamin A Total Body Stores by the Retinol Isotope Dilution Method in Theoretical Children and Adults?

2021 ◽  
Author(s):  
Michael H Green ◽  
Veronica Lopez-Teros ◽  
Joanne Balmer Green
Keyword(s):  
Stable Isotope ◽  
Vitamin A ◽  
Isotope Dilution ◽  
Specific Activity ◽  
Simulated Data ◽  
Compartmental Analysis ◽  
Isotope Dilution Method ◽  
Dilution Method ◽  
Plasma Retinol ◽  
Total Body

Abstract Background To minimize both cost and perturbations to the vitamin A system, investigators limit the amount of stable isotope administered when estimating vitamin A total body stores (TBS) by retinol isotope dilution (RID). Objectives We hypothesized that reasonable increases in the mass of stable isotope administered to theoretical subjects would have only transient impacts on vitamin A kinetics and minimal effects on RID-predicted TBS. Methods We adapted previously-used theoretical subjects (3 children, 3 adults) with low, moderate, or high assigned TBS and applied compartmental analysis to solve a steady state model for tracer and tracee using assigned values for retinol kinetic parameters and plasma retinol. To follow retinol trafficking when increasing amounts of stable isotope were administered [1.39-7 (children) and 2.8-14 µmol retinol (adults)], we added assumptions to an established compartmental model so that plasma retinol homeostasis was maintained. Using model-simulated data, we plotted retinol kinetics versus time and applied the RID equation TBS = FaS/SAp [Fa, fraction of dose in stores; S, retinol specific activity (SA) in plasma/SA in stores; SAp, SA in plasma] to calculate vitamin A stores. Results The model predicted that increasing the stable isotope dose caused transient early increases in hepatocyte total retinol; increases in plasma tracer were accompanied by decreases in tracee to maintain plasma retinol homeostasis. Despite changes in kinetic responses, RID accurately predicted assigned TBS (98-105%) at all loads for all theoretical subjects from 1-28 d postdosing. Conclusions Results indicate that, compared with doses of 1.4–3.5 µmol used in recent RID field studies, doubling the stable isotope dose should not affect accuracy of TBS predictions, thus allowing for experiments of longer duration when including a super-subject design (Ford et al., J Nutr 2020;150:411–8) and/or studying retinol kinetics.

scholarly journals Plasma kinetics of an oral dose of [2H4]retinyl acetate in human subjects with estimated low or high total body stores of vitamin A

1998 ◽  
Vol 68 (1) ◽  
pp. 90-95 ◽  
Author(s):  
M J Haskell ◽  
M A Islam ◽  
G J Handelman ◽  
J M Peerson ◽  
A D Jones ◽  
...  
Keyword(s):  
Vitamin A ◽  
Oral Dose ◽  
Human Subjects ◽  
Retinyl Acetate ◽  
Plasma Kinetics ◽  
Total Body ◽  
Kinetics Of

scholarly journals Validation of a Method for Estimating Vitamin A Absorption Efficiency Based on Compartmental Analysis of Post-Prandial Plasma Retinyl Ester Kinetics

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 108-108
Author(s):  
Michael Green ◽  
Jennifer Ford ◽  
Joanne Green
Keyword(s):  
Vitamin A ◽  
Simulation Analysis ◽  
Compartmental Analysis ◽  
Population Based ◽  
Absorption Efficiency ◽  
Average Error ◽  
Response Curves ◽  
Retinyl Ester ◽  
Free Data ◽  
Gates Foundation

Abstract Objectives Because good methods are not available to estimate vitamin A (VA) absorption, we evaluated an approach based on modeling retinyl ester response to an oral VA dose. Methods We generated data for 12 theoretical subjects, assigning values for VA absorption, stores, and kinetic parameters; we used WinSAAM (Simulation, Analysis and Modeling software) to simulate data (without and with 5% average error) for plasma chylomicron retinyl esters (RE) and retinol versus time (30 min to 8 h or 56 d, respectively) after ingestion of labeled VA; next we fit data to a previously-published 9-component model for VA metabolism to obtain “known” values for VA absorption. Then RE data only were modeled for each subject using a robust (n = 16 times) vs truncated sampling schedule (n = 10) and model-predicted absorptions were compared to known values. Areas under the plasma RE response curves (AUCs) were also calculated and compared to known absorption values. Results Known values for VA absorption based on modeling all data with error ranged from 54 – 92% (mean, 72%), VA stores from 160 – 1775 μmol, and chylomicron t1/2 from 6 – 12 min. Using the full sampling scheme for RE, the ratio of model-predicted to known absorption ranged from 0.927 – 1.06 (mean, 0.997); using the truncated scheme, the ratio was 0.814 – 1.13 (mean, 0.973). AUCs were not significantly correlated with known values for VA absorption (R2 = 0.112; P > 0.05), presumably because absorption and chylomicron catabolism are occurring simultaneously. Conclusions By modeling chylomicron RE tracer data after ingestion of labeled VA, absorption efficiency was estimated accurately using error-free data; using data with 5% error, estimates were within 10% of known values (full sampling) or within 20% (truncated). If subjects, after an overnight fast, consume a breakfast containing some fat and a known amount of VA, then no tracer is required to estimate VA absorption using this modeling approach. By incorporating a population-based design, the method could be used in children. Funding Sources Supported by Bill & Melinda Gates Foundation (Project Number OPP1115464) and HarvestPlus (BH183438).

scholarly journals Better Predictions of Vitamin A Total Body Stores by the Retinol Isotope Dilution Method Are Possible with Deeper Understanding of the Mathematics and by Applying Compartmental Modeling

2019 ◽  
Vol 150 (5) ◽  
pp. 989-993 ◽  
Author(s):  
Michael H Green ◽  
Joanne Balmer Green ◽  
Jennifer Lynn Ford
Keyword(s):  
Vitamin A ◽  
Isotope Dilution ◽  
Theoretical Data ◽  
Compartmental Analysis ◽  
Whole Body ◽  
Optimal Time ◽  
Isotope Dilution Method ◽  
Dilution Method ◽  
Model Based ◽  
Total Body

ABSTRACT Retinol isotope dilution (RID) is a well-accepted technique for assessing vitamin A status [i.e., total body stores (TBS)]. Here, in an effort to increase understanding of the method, we briefly review RID equations and discuss their included variables and their coefficients (i.e., assumptions that account for the efficiency of absorption of an orally administered tracer dose of vitamin A, mixing of the dose with endogenous vitamin A, and loss due to utilization). Then, we focus on contributions of another technique, model-based compartmental analysis and especially the “super-person” approach, that advance the RID method. Specifically, we explain how adding this modeling component, which involves taking 1 additional blood sample from each subject, provides population-specific estimates for the RID coefficients that can be used in the equation instead of values derived from the literature; using model-derived RID coefficients results in improved confidence in predictions of TBS for both a group and its individuals. We note that work is still needed to identify the optimal time for applying RID in different groups and to quantify vitamin A absorption efficiency. Finally, we mention other contributions of modeling, including the use of theoretical data to verify the accuracy of RID predictions and the additional knowledge that model-based compartmental analysis provides about whole-body vitamin A kinetics.

scholarly journals Spirulina can increase total-body vitamin A stores of Chinese school-age children as determined by a paired isotope dilution technique

2012 ◽  
Vol 1 ◽  
Author(s):  
Lei Li ◽  
Xianfeng Zhao ◽  
Jie Wang ◽  
Tawanda Muzhingi ◽  
Paolo M. Suter ◽  
...  
Keyword(s):  
Vitamin A ◽  
Rural Areas ◽  
Enrichment Analysis ◽  
School Age Children ◽  
School Age ◽  
Serum Samples ◽  
Retinyl Acetate ◽  
Chinese School ◽  
Total Body ◽  
Β Carotene

AbstractSpirulina is an alga rich in high-quality protein and carotenoids. It is unclear whether spirulina can improve the total-body vitamin A stores of school-age children in China with a high prevalence of vitamin A malnutrition. We aimed to evaluate the efficacy of spirulina in improving the total-body vitamin A stores of school-age children in rural areas of China when they consumed spirulina in their daily meals. A total of 228 children (6–11 years) were recruited and randomly divided into three groups supplemented with 4 g (containing 4·18 µg β-carotene), 2 g (containing 2·54 µg β-carotene) or 0 g spirulina 5 d/week for 10 weeks, respectively. Before and after the intervention period, each child was given 0·5 mg [2H4]retinyl acetate and [2H8]retinyl acetate, respectively. To assess vitamin A stores, blood samples (3 ml) were collected on the third and the twenty-first day after each labelled retinyl acetate dose for a retinol enrichment analysis using a GC mass spectrometer. The concentrations of retinol and β-carotene in serum samples were also determined by using HPLC. After the 10-week intervention, serum β-carotene concentrations of children with 2 or 4 g spirulina supplement increased by 0·160 and 0·389 µmmol/l, respectively. Total-body vitamin A stores increased significantly, with a median increase of 0·160 mmol in children taking 2 g spirulina and of 0·279 mmol in children taking 4 g spirulina. Spirulina is a good dietary source of β-carotene, which may effectively increase the total-body vitamin A stores of Chinese school-age children.

Sign in / Sign up

Export Citation Format

Share Document