A Retinol Isotope Dilution Equation Predicts Both Group and Individual Total Body Vitamin A Stores in Adults Based on Data from an Early Postdosing Blood Sample

Green, Michael H.; Ford, Jennifer Lynn; Green, Joanne Balmer; Berry, Philip; Boddy, Alan V.; Oxley, Anthony

doi:10.3945/jn.116.233676

Cited by 38 publications

(42 citation statements)

References 25 publications

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“…In conclusion, the application of model-based compartmental analysis has the potential to provide unique information and insights into vitamin A and β-carotene kinetics and metabolism as well as practical results with the potential for application in the field. For example, in the accompanying article in this issue ( 26 ), we used modeling results to modify the original retinol isotope dilution equation ( 27 ) for predicting total body vitamin A stores on the basis of a single, early blood sample. Similarly, our current modeling results confirm graphical methods for estimating β-carotene bioefficacy and may lead to a simpler method that will be useful in the field.…”

Section: Discussionmentioning

confidence: 99%

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

Green

Ford

Oxley

et al. 2016

The Journal of Nutrition

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Background: Model-based compartmental analysis of data on plasma retinol kinetics after administration of labeled retinol provides unique information about whole-body vitamin A metabolism. If labeled β-carotene is coadministered, its bioefficacy relative to the retinol reference dose can also be estimated.Objectives: The objectives were to model plasma retinol kinetics after administration of labeled preformed vitamin A and provitamin A β-carotene and to determine relative β-carotene bioefficacy.Methods: We used the Simulation, Analysis and Modeling software (WinSAAM version 3.0.8; http://www.WinSAAM.org) to analyze previously collected data on plasma [13C10]- and [13C5]retinol kinetics for 14 d after oral administration of 1 mg [13C10]retinyl acetate and 2 mg [13C10]β-carotene in oil to 30 healthy young adults of European ancestry [13 men, 17 women; mean ± SD age: 24.5 ± 4.2 y; mean ± SD body weight: 65.2 ± 10 kg; mean ± SD body mass index (in kg/m2): 22.5 ± 1.9] with moderate vitamin A intakes.Results: A 6-component model provided the best fit to the data, including compartments for initial metabolism of vitamin A, plasma retinol, and extravascular vitamin A storage. The disposal rate was 6.7 ± 3.1 μmol/d, fractional catabolic rate was 6.0% ± 2.3%/d, and vitamin A stores were 123 ± 71 μmol. Relative β-carotene bioefficacy, based on the ratio of the areas under the fraction of dose curves calculated by WinSAAM, averaged 13.5% ± 6.02% (retinol activity equivalents = 7.7:1.0 μg). Interindividual variation in relative β-carotene bioefficacy was high (CV: 44%).Conclusions: Vitamin A kinetics in these young adults were best described by essentially the same model that had been previously developed by using data for older adults with higher vitamin A stores; differences in parameter values reflected differences in vitamin A status. Estimated β-carotene bioefficacy was relatively low but similar to previously reported estimates obtained by graphical methods. This trial was registered at the UK Clinical Research Network as UKCRN 7413.

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Section: Discussionmentioning

confidence: 99%

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

Green

Ford

Oxley

et al. 2016

The Journal of Nutrition

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“…In addition to SA p , RID equations include coefficients that account for absorption and retention of the dose and mixing of tracer with the body pool. Here we used the RID equation presented by Green et al ( 21 ), shown below as Equation 2 , to predict TBS for individual subjects: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} }{}\begin{eqnarray*} {\rm{TBS}}\left( {\rm{\mu}} {\rm{mol}} \right) = Fa \times S \times 1/{\rm{S}}{{\rm{A}}_{\rm{p}}} \end{eqnarray*}\end{document} where Fa is the fraction of dose of labeled vitamin A absorbed and found in the body's storage pool at time t , S is the ratio of retinol specific activity in plasma to that in the storage pool at time t , and SA p was calculated as FD p ÷ plasma retinol pool size (µmol) at time t . In empirical studies, one would calculate SA p as [tracer ÷ (tracer + tracee)] ÷ dose (µmol) in plasma at time t .…”

Section: Methodsmentioning

confidence: 99%

“…We used Equation 2 as follows to predict TBS in individual children at the time (4 d) that is currently being used in the ongoing field studies. First, for each protocol, we simulated values for the time-variant coefficients Fa and S at 4 d using the population model (for details on the calculation of equation coefficients by the model, see references 14 and 21 and Supplemental Methods). Population estimates for the composite coefficient Fa × S were then used in Equation 2 , along with each theoretical child's SA p at 4 d, to predict TBS.…”

Section: Methodsmentioning

confidence: 99%

“…In studies in Bangladesh, Guatemala, Morocco, Nigeria, Philippines, and Zambia, children ( n = 50) ingest a dose of stable isotope–labeled retinyl acetate; a blood sample is collected from all children 4 d later, and a second sample is obtained from each child at 1 of 10 additional times between 6 h and 28 d. Model-based compartmental analysis [specifically, WinSAAM, the Windows version of the Simulation, Analysis and Modeling software ( 19 , 20 )] will then be applied to each study's composite data set for plasma retinol isotope response versus time to estimate vitamin A TBS and retinol kinetics for the population. Modeling results will also be used to generate population-specific estimates for the coefficients used in the 4-d RID equation ( 21 ) and vitamin A TBS will be calculated for individual children.…”

Section: Introductionmentioning

confidence: 99%

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A Population-Based (Super-Child) Approach for Predicting Vitamin A Total Body Stores and Retinol Kinetics in Children Is Validated by the Application of Model-Based Compartmental Analysis to Theoretical Data

Ford

Green

2018

Current Developments in Nutrition

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BackgroundPublic health nutritionists need accurate and feasible methods to assess vitamin A status and to evaluate efficacy of interventions, especially in children. The application of population-based designs to tracer kinetic data is an effective approach that reduces sample burden for each child.ObjectivesObjectives of the study were to use theoretical data to validate a population-based (super-child) approach for estimating group mean vitamin A total body stores (TBS) and retinol kinetics in children and to use population-based data to improve individual TBS predictions using retinol isotope dilution (RID).MethodsWe generated plasma retinol kinetic data from 6 h to 56 d for 50 theoretical children with high vitamin A intakes, assigning values within physiologically reasonable ranges for state variables and kinetic parameters (“known values”). Mean data sets for all subjects at extensive (n = 36) and reduced (n = 11) sampling times, plus 5 data sets for reduced numbers (5/time, except all at 4 d) and times, were analyzed using Simulation, Analysis and Modeling software. Results were compared with known values; population RID coefficients were used to calculate TBS for individuals.ResultsFor extensive and reduced data sets including all subjects, population TBS predictions were within 1% of the known value. For 5 data sets reflecting numbers and times being used in ongoing super-child studies, predictions were within 1–17% of the known group value. Using RID equation coefficients from population modeling, TBS predictions at 4 d were within 25% of the known value for 66–80% of subjects and reflected the range of assigned values; when ranked, predicted and assigned values were significantly correlated (Rs = 0.93, P < 0.0001). Results indicate that 7 d may be better than 4 d for applying RID in children. For all data sets, predictions for kinetic parameters reflected the range of known values.ConclusionThe population-based (super-child) approach provides a feasible experimental design for quantifying retinol kinetics, accurately estimating group mean TBS, and predicting TBS for individuals reasonably well.

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“…The changing fraction of the dose in the serum is mathematically modeled by constructing several theoretical compartments within the body by using kinetic constants that describe the movement of retinol throughout the body and its irreversible degradation. Attempts have been made to use this model to develop RID equations that could be applied as early as 3–5 d postdose by estimating the ratio of isotopic enrichment of retinol in plasma and stores reached in the body at any given time ( 47 † , 48 † ). Some studies make use of a composite model (i.e., “super child” or “super woman”) in which data points from multiple subjects, who each contribute to a fraction of the total number of time points, are combined to form a population-level compartmental model ( 49 † , 50 ).…”

Section: Current Status Of Knowledgementioning

confidence: 99%

Use of Stable Isotopes to Evaluate Bioefficacy of Provitamin A Carotenoids, Vitamin A Status, and Bioavailability of Iron and Zinc

Sheftel

Loechl

Mokhtar

et al. 2018

Advances in Nutrition

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The ability of nutrition scientists to measure the status, bioavailability, and bioefficacy of micronutrients is affected by lack of access to the parts of the body through which a nutrient may travel before appearing in accessible body compartments (typically blood or urine). Stable isotope–labeled tracers function as safe, nonradioactive tools to follow micronutrients in a quantitative manner because the absorption, distribution, metabolism, and excretion of the tracer are assumed to be similar to the unlabeled vitamin or mineral. The International Atomic Energy Agency (IAEA) supports research on the safe use of stable isotopes in global health and nutrition. This review focuses on IAEA's contributions to vitamin A, iron, and zinc research. These micronutrients are specifically targeted by the WHO because of their importance in health and worldwide prevalence of deficiency. These 3 micronutrients are included in food fortification and biofortification efforts in low- and middle-income regions of the world. Vitamin A isotopic techniques can be used to evaluate the efficacy and effectiveness of interventions. For example, total body retinol stores were estimated by using 13C2-retinol isotope dilution before and after feeding Zambian children maize biofortified with β-carotene to determine if vitamin A reserves were improved by the intervention. Stable isotopes of iron and zinc have been used to determine mineral bioavailability. In Thailand, ferrous sulfate was better absorbed from fish sauce than was ferrous lactate or ferric ammonium citrate, determined with the use of different iron isotopes in each compound. Comparisons of one zinc isotope injected intravenously with another isotope taken orally from a micronutrient powder proved that the powder increased total absorbed zinc from a meal in Pakistani infants. Capacity building by the IAEA with appropriate collaborations in low- and middle-income countries to use stable isotopes has resulted in many advancements in human nutrition.

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A Retinol Isotope Dilution Equation Predicts Both Group and Individual Total Body Vitamin A Stores in Adults Based on Data from an Early Postdosing Blood Sample

Cited by 38 publications

References 25 publications

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

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

A Population-Based (Super-Child) Approach for Predicting Vitamin A Total Body Stores and Retinol Kinetics in Children Is Validated by the Application of Model-Based Compartmental Analysis to Theoretical Data

Use of Stable Isotopes to Evaluate Bioefficacy of Provitamin A Carotenoids, Vitamin A Status, and Bioavailability of Iron and Zinc

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