scholarly journals Addition of Vitamin A Intake Data during Compartmental Modeling of Retinol Kinetics in Theoretical Humans Leads to Accurate Prediction of Vitamin A Total Body Stores and Kinetic Parameters in Studies of Reasonable Duration

2019 ◽  
Vol 149 (11) ◽  
pp. 2065-2072 ◽  
Author(s):  
Jennifer Lynn Ford ◽  
Joanne Balmer Green ◽  
Michael H Green
Keyword(s):  
Vitamin A ◽  
Kinetic Parameters ◽  
Reference Values ◽  
Theoretical Data ◽  
Accurate Prediction ◽  
Dietary Vitamin ◽  
Compartmental Modeling ◽  
State Variables ◽  
Study Duration ◽  
Total Body

ABSTRACT Background Mathematical modeling of theoretical data has been used to validate experimental protocols and methods in several fields. Objectives We hypothesized that adding dietary vitamin A intake data as an input during compartmental modeling of retinol kinetics would lead to accurate prediction of vitamin A total body stores (TBS) at 2 specified study lengths and would reduce study duration required to accurately define the system. Methods We generated reference values for state variables (including TBS and intake) and kinetic parameters for 12 theoretical individuals (4 each of children, younger adults, and older adults) based on modeling plasma retinol tracer data for 365 d. We compared TBS predictions using data to 28 d (children) or 56 d (adults) without and with intake included in the model to reference values for each subject. Then, by truncating data sets from 365 d, we determined the shortest study duration required to accurately define the system without and with inclusion of vitamin A intake. Results Reference values for TBS ranged from 30 to 3023 µmol. Study durations of 28 and 56 d were sufficient to accurately predict TBS for 6 of the 12 subjects without intake; adding intake resulted in accurate predictions of TBS for all individuals. When intake was not included as a modeling input, durations of 35–310 d were required to define the system; inclusion of intake data substantially reduced the time required to 10–42 d. Conclusions Inclusion of vitamin A intake as additional data input when modeling vitamin A kinetics allows investigators to accurately predict TBS and define the vitamin A system in studies of reasonable length (4 wk in children and 8 wk in adults). Because it is generally possible to obtain estimates/measures of intake, including such data increases confidence in model predictions while also making studies more feasible.

scholarly journals Vitamin A Absorption Efficiency Determined by Compartmental Analysis of Postprandial Plasma Retinyl Ester Kinetics in Theoretical Humans

2020 ◽  
Vol 150 (8) ◽  
pp. 2223-2229 ◽  
Author(s):  
Michael H Green ◽  
Joanne Balmer Green ◽  
Jennifer Lynn Ford
Keyword(s):  
Vitamin A ◽  
Simulation Analysis ◽  
Theoretical Data ◽  
Absorption Efficiency ◽  
Compartmental Modeling ◽  
Dietary Recommendations ◽  
Response Curves ◽  
Stable Isotope Label ◽  
Sample Number ◽  
Retinyl Ester

ABSTRACT Background Better methods are needed for determining vitamin A absorption efficiency in humans to support development of dietary recommendations and to improve the accuracy of predictions of vitamin A status. Objectives We developed and evaluated a method for estimating vitamin A absorption efficiency based on compartmental modeling of theoretical data on postprandial plasma retinyl ester (RE) kinetics. Methods We generated data on plasma RE and retinol kinetics (30 min to 8 h or 56 d, respectively) after oral administration of labeled vitamin A for 12 theoretical adults with a range of values assigned for vitamin A absorption (55–90%); we modeled all data to obtain best-fit values for absorption and other parameters using Simulation, Analysis, and Modeling software. We then modeled RE data only (16 or 10 samples), with or without added random error, and compared assigned to predicted absorption values. We also compared assigned values to areas under RE response curves (RE AUCs). Results We confirmed that a unique value for vitamin A absorption cannot be identified by modeling plasma retinol tracer kinetics. However, when RE data were modeled, predicted vitamin A absorptions were within 1% of assigned values using data without error and within 12% when 5% error was included. When the sample number was reduced, predictions were still within 13% for 10 of the 12 subjects and within 23% overall. Assigned values for absorption were not correlated with RE AUC (P = 0.21). Conclusions We describe a feasible and accurate method for determining vitamin A absorption efficiency that is based on compartmental modeling of plasma RE kinetic data collected for 8 h after a test meal. This approach can be used in a clinical setting after fasting subjects consume a fat-containing breakfast meal with a known amount of vitamin A or a stable isotope label.

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 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 Duration of Retinol Isotope Dilution Studies with Compartmental Modeling Affects Model Complexity, Kinetic Parameters, and Calculated Vitamin A Stores in US Women

2018 ◽  
Vol 148 (8) ◽  
pp. 1387-1396 ◽  
Author(s):  
Bryan M Gannon ◽  
Ashley R Valentine ◽  
Christopher R Davis ◽  
Julie A Howe ◽  
Sherry A Tanumihardjo
Keyword(s):  
Vitamin A ◽  
Kinetic Parameters ◽  
Isotope Dilution ◽  
Model Complexity ◽  
Compartmental Modeling

Research Recommendations for Applying Vitamin A-Labelled Isotope Dilution Techniques to Improve Human Vitamin A Nutrition

2014 ◽  
Vol 84 (Supplement 1) ◽  
pp. 52-59 ◽  
Author(s):  
Sherry A. Tanumihardjo ◽  
Anura V. Kurpad ◽  
Janet R. Hunt
Keyword(s):  
Public Health ◽  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Human Subjects ◽  
The Body ◽  
Pool Size ◽  
Serum Retinol ◽  
Vitamin A Status ◽  
Status Assessment ◽  
Total Body

The current use of serum retinol concentrations as a measurement of subclinical vitamin A deficiency is unsatisfactory for many reasons. The best technique available for vitamin A status assessment in humans is the measurement of total body pool size. Pool size is measured by the administration of retinol labelled with stable isotopes of carbon or hydrogen that are safe for human subjects, with subsequent measurement of the dilution of the labelled retinol within the body pool. However, the isotope techniques are time-consuming, technically challenging, and relatively expensive. There is also a need to assess different types of tracers and doses, and to establish clear guidelines for the use and interpretation of this method in different populations. Field-friendly improvements are desirable to encourage the application of this technique in developing countries where the need is greatest for monitoring the risk of vitamin A deficiency, the effectiveness of public health interventions, and the potential of hypervitaminosis due to combined supplement and fortification programs. These techniques should be applied to validate other less technical methods of assessing vitamin A deficiency. Another area of public health relevance for this technique is to understand the bioconversion of β-carotene to vitamin A, and its relation to existing vitamin A status, for future dietary diversification programs.

scholarly journals Dietary vitamin A supplementation in rats: suppression of leptin and induction of UCP1 mRNA

1999 ◽  
Vol 40 (5) ◽  
pp. 824-829 ◽  
Author(s):  
Monica V. Kumar ◽  
Gregory D. Sunvold ◽  
Philip J. Scarpace
Keyword(s):  
Vitamin A ◽  
Dietary Vitamin ◽  
Vitamin A Supplementation

scholarly journals The complexity of producing and interpreting dietary vitamin A statistics

2021 ◽  
pp. 103926
Author(s):  
Ana Moltedo ◽  
Cristina Álvarez-Sánchez ◽  
Fernanda Grande ◽  
Ruth Charrondiere
Keyword(s):  
Vitamin A ◽  
Dietary Vitamin

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 Maternal dietary intake of vitamin A during pregnancy was inversely associated with congenital diaphragmatic hernia: the Japan Environment and Children’s Study

2019 ◽  
Vol 122 (11) ◽  
pp. 1295-1302 ◽  
Author(s):  
Takehiro Michikawa ◽  
Shin Yamazaki ◽  
Makiko Sekiyama ◽  
Tatsuo Kuroda ◽  
Shoji F. Nakayama ◽  
...  
Keyword(s):  
Vitamin A ◽  
Congenital Diaphragmatic Hernia ◽  
Diaphragmatic Hernia ◽  
Dietary Habits ◽  
Daily Intake ◽  
First Trimester ◽  
Dietary Vitamin ◽  
Birth Cohort Study ◽  
Case Control Studies ◽  
Total Vitamin

AbstractThe pathogenesis of congenital diaphragmatic hernia (CDH) is largely unknown; however, vitamin A seems to play a role in diaphragmatic development. Previous case–control studies reported that maternal dietary vitamin A intake was inversely associated with the risk of CDH. To our knowledge, however, there is no prospective evidence regarding this association. Our aim was to examine whether maternal intake of vitamin A was associated with CDH occurrence. Baseline data, from the Japan nationwide birth cohort study (2011–2014) of 89 658 mothers (mean age at delivery = 31·2 years) who delivered singleton live births, were analysed. We assessed dietary habits using an FFQ focused on the first trimester and estimated the daily intake of total vitamin A (retinol activity equivalents), retinol, provitamin A carotenoids and vegetables. The occurrence of CDH was ascertained from medical records. A total of forty cases of CDH were documented. The adjusted OR of CDH occurrence for the high total vitamin A intake category (median = 468 μg/d) was 0·6 (95 % CI 0·3, 1·2) with reference to the low intake category (230 μg/d). When we restricted to mothers with a prepregnancy BMI of 18·5–24·9 kg/m2, vitamin A intake was inversely associated with the risk of their children being born with CDH (OR 0·5, 95 % CI 0·2, 1·0). Even given the limited number of cases in the study, our findings provide additional evidence to link vitamin A with CDH.

Sign in / Sign up

Export Citation Format

Share Document