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 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 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 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 Feasibility study of volumetric modulated arc therapy with Halcyon™ linac for total body irradiation

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Takuya Uehara ◽  
Hajime Monzen ◽  
Mikoto Tamura ◽  
Masahiro Inada ◽  
Masakazu Otsuka ◽  
...  
Keyword(s):  
Total Body Irradiation ◽  
Organs At Risk ◽  
Volumetric Modulated Arc Therapy ◽  
Dose Calculation ◽  
Target Volume ◽  
The Body ◽  
Whole Body ◽  
Data Set ◽  
Arc Therapy ◽  
Total Body

Abstract Background The use of total body irradiation (TBI) with linac-based volumetric modulated arc therapy (VMAT) has been steadily increasing. Helical tomotherapy has been applied in TBI and total marrow irradiation to reduce the dose to critical organs, especially the lungs. However, the methodology of TBI with Halcyon™ linac remains unclear. This study aimed to evaluate whether VMAT with Halcyon™ linac can be clinically used for TBI. Methods VMAT planning with Halcyon™ linac was conducted using a whole-body computed tomography data set. The planning target volume (PTV) included the body cropped 3 mm from the source. A dose of 12 Gy in six fractions was prescribed for 50% of the PTV. The organs at risk (OARs) included the lens, lungs, kidneys, and testes. Results The PTV D98%, D95%, D50%, and D2% were 8.9 (74.2%), 10.1 (84.2%), 12.6 (105%), and 14.2 Gy (118%), respectively. The homogeneity index was 0.42. For OARs, the Dmean of the lungs, kidneys, lens, and testes were 9.6, 8.5, 8.9, and 4.4 Gy, respectively. The V12Gy of the lungs and kidneys were 4.5% and 0%, respectively. The Dmax of the testes was 5.8 Gy. Contouring took 1–2 h. Dose calculation and optimization was performed for 3–4 h. Quality assurance (QA) took 2–3 h. The treatment duration was 23 min. Conclusions A planning study of TBI with Halcyon™ to set up VMAT-TBI, dosimetric evaluation, and pretreatment QA, was established.

scholarly journals Prediction of Vitamin A Stores in Young Children Provides Insights into the Adequacy of Current Dietary Reference Intakes

2020 ◽  
Vol 4 (8) ◽  
Author(s):  
Jennifer Lynn Ford ◽  
Veronica Lopez-Teros
Keyword(s):  
Vitamin A ◽  
Intervention Programs ◽  
Limited Data ◽  
Adequate Intake ◽  
Mathematical Relationship ◽  
Middle Income ◽  
Mexican Children ◽  
Dietary Reference Intakes ◽  
Filipino Children ◽  
Total Body

ABSTRACT Background Limited data were available in infants and children when vitamin A (VA) DRIs were established; recommendations were developed based on average breast milk VA intake and extrapolation of data from adults. Objectives Our objective was to evaluate whether DRIs and reported intakes, with and without VA from intervention programs, would be sufficient to develop adequate VA stores from birth to age 5 y in Bangladeshi, Filipino, Guatemalan, and Mexican children. Methods A mathematical relationship was established, defined by a series of equations, to predict VA total body stores (TBS) as a function of age based on VA intake and utilization. TBS calculated using reported VA intakes, with and without additional VA from intervention programs, were compared to those predicted using DRIs (specifically, Adequate Intake and RDA). Liver VA concentrations were also estimated. Results Our predictions showed that for these 4 groups, DRIs were sufficient to attain liver VA concentrations >0.07 μmol/g by 1 wk of age and sustain positive VA balance for 5 y. Using reported intakes, which were lowest in Bangladeshis from 1 y on and highest in Guatemalans, predicted VA stores in Bangladeshi and Filipino children increased until ∼2–3 y, then TBS stabilized and liver VA concentrations decreased with age. When VA interventions were included, stores exceeded those predicted using DRIs by 12–18 mo. In contrast, reported intakes alone in Guatemalan and Mexican children resulted in VA stores that surpassed those calculated using DRIs. For all populations, reported intakes were sufficient to build liver concentrations >0.07 μmol/g by 3 mo. Conclusions Although more information is needed to better define dietary VA requirements in children, our results suggest that for an average, generally healthy child in a low- or middle-income country, current DRIs are sufficient to maintain positive VA balance during the first 5 y of life.

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 Use of a “Super-child” Approach to Assess the Vitamin A Equivalence ofMoringa oleiferaLeaves, Develop a Compartmental Model for Vitamin A Kinetics, and Estimate Vitamin A Total Body Stores in Young Mexican Children

2017 ◽  
Vol 147 (12) ◽  
pp. 2356-2363 ◽  
Author(s):  
Veronica Lopez-Teros ◽  
Jennifer Lynn Ford ◽  
Michael H Green ◽  
Guangwen Tang ◽  
Michael A Grusak ◽  
...  
Keyword(s):  
Vitamin A ◽  
Compartmental Model ◽  
Mexican Children ◽  
Total Body

scholarly journals A Compartmental Model Describing the Kinetics of β-Carotene and β-Carotene-Derived Retinol in Healthy Older Adults

2020 ◽  
Author(s):  
Michael H Green ◽  
Jennifer Lynn Ford ◽  
Joanne Balmer Green
Keyword(s):  
Vitamin A ◽  
Compartmental Model ◽  
Quantitative Information ◽  
Complex Model ◽  
Retinol Binding Protein ◽  
Whole Body ◽  
Published Data ◽  
Retinyl Acetate ◽  
Kinetics Of ◽  
Β Carotene

ABSTRACT Background Descriptive and quantitative information on β-carotene whole-body kinetics in humans is limited. Objectives Our objective was to advance the development of a physiologically based, working hypothesis compartmental model describing the metabolism of β-carotene and β-carotene-derived retinol. Methods We used model-based compartmental analysis (Simulation, Analysis and Modeling software) to analyze previously published data on plasma kinetics of [2H8]β-carotene, [2H4]β-carotene-derived retinol, and [2H8]retinyl acetate-derived retinol in healthy, older US adults (3 female, 2 male; 50–68 y); subjects were studied for 56 d after consuming doses of 11 μmol [2H8]β-carotene and, 3 d later, 9 μmol [2H8]retinyl acetate in oil. Results We developed a complex model for labeled β-carotene and β-carotene-derived retinol, as well as preformed vitamin A, using simulations to augment observed data during model calibration. The model predicts that mean (range) β-carotene absorption (bioavailability) was 9.5% (5.2–14%) and bioefficacy was 7.3% (3.6–14%). Of the absorbed β-carotene, 41% (25–58%) was packaged intact in chylomicrons and the balance was converted to retinol, with 58% (42–75%) transported as retinyl esters in chylomicrons and 0–2% by retinol-binding protein. Most (95%) chylomicron β-carotene was cleared by the liver. Later data revealed differences in the metabolism of retinyl acetate- versus β-carotene-derived retinol; data required that both β-carotene and derived retinol be recycled from extrahepatic tissues (e.g. adipose) in HDL. Of total bioconversion [73% (47–99%)], 82% occurred in the intestine, 17% in the liver, and 0.83% in other tissues. Conclusions Our model advances knowledge about whole-body β-carotene metabolism in healthy adults, including the kinetics of transport in all lipoprotein species, and suggests hypotheses to be tested in future studies, such as the possibility that retinol derived from hepatic conversion over a long period of time might contribute to plasma retinol homeostasis and total body vitamin A stores.

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