Evaluation of the “Olson Equation”, an Isotope Dilution Method for Estimating Vitamin A Stores

2014 ◽  
Vol 84 (Supplement 1) ◽  
pp. 9-15 ◽  
Author(s):  
Michael H. Green

Isotope dilution methods have been successfully used to estimate vitamin A status in human populations as well as to evaluate the impact of vitamin A interventions. The most commonly applied isotope dilution method is the retinol isotope dilution technique, which is based on the 1989 “Olson equation” for estimating total body vitamin A stores (sometimes equated to liver vitamin A) after an oral dose of labeled vitamin A. The equation relies on several factors related to absorption and retention of the dose, the equilibration of label in plasma vs. liver, and timing of a blood sample for measurement of labeled vitamin A. Here, the assumptions underlying these factors are discussed, and new results based on applying model-based compartmental analysis [specifically, the Simulation, Analysis and Modeling software (WinSAAM)] to data on retinol kinetics in humans are summarized. A simplification of the Olson equation, in which plasma tracer is measured 3 days after administration of the oral dose and several factors are eliminated, is presented. The potential usefulness of the retinol isotope dilution technique for setting vitamin A requirements and assessing vitamin A status in children, as well as the confounding effects of inflammation and likely variability in vitamin A absorption, are also discussed.

2002 ◽  
Vol 76 (2) ◽  
pp. 413-418 ◽  
Author(s):  
Guangwen Tang ◽  
Jian Qin ◽  
Lan-ying Hao ◽  
Shi-an Yin ◽  
Robert M Russell

2021 ◽  
Author(s):  
Veronica Lopez-Teros ◽  
Michael H Green ◽  
Marjorie J Haskell ◽  
Joanne Balmer Green

ABSTRACT Background Vitamin A status may influence the choice of a blood sampling time for applying the retinol isotope dilution (RID) equation to predict vitamin A total body stores (TBS) in children. Objectives We aimed to identify time(s) after administration of labeled vitamin A that provide accurate estimates of TBS in theoretical children with low or high TBS. Methods We postulated 2- to 5-y-old children (12/group) with low (<200 μmol) or high TBS (≥700 μmol) and used compartmental analysis to simulate individual subject values for the RID equation TBS =   FaS/SAp (Fa, fraction of dose in stores; S, retinol specific activity in plasma/in stores; SAp, retinol specific activity in plasma). Using individual SAp and group geometric mean FaS values from 1–28 d, we calculated individual and group mean TBS and compared them to assigned values. Results Mean TBS was accurately predicted for both groups at all times. For individuals, predicted and assigned TBS were closest when the CV% for FaS was low [12–14%; 4–13 d (low), 12–28 d (high)]. The mean percentage error for TBS was <10% from 2–19 d (low) and 7–28 d (high). Predicted TBS was within 25% of assigned TBS for ≥80% of children from 3–23 d (low) and 9–28 d (high). Within groups, RID tended to overestimate lower TBS and underestimate higher TBS. Conclusions Using a good estimate for FaS, accurate RID predictions of TBS for individuals will be obtained at many times. If vitamin A status is low, results indicate that early sampling (e.g., 4–13 d) is optimal; if vitamin A status is high, sampling at 12–28 d is indicated. When vitamin A status is unknown, sampling at 14 d is recommended, or a super-subject design can be used to obtain the group mean FaS at various times for RID prediction of TBS in individuals.


2014 ◽  
Vol 84 (Supplement 1) ◽  
pp. 40-51 ◽  
Author(s):  
Veronica Lopez-Teros ◽  
Justin Chileshe ◽  
Nicole Idohou-Dossou ◽  
Tetra Fajarwati ◽  
Gabriel Medoua Nama ◽  
...  

Inadequate vitamin A (VA) nutrition continues to be a major problem worldwide, and many interventions being implemented to improve VA status in various populations need to be evaluated. The interpretation of results after an intervention depends greatly on the method selected to assess VA status. To evaluate the effect of an intervention on VA status, researchers in Cameroon, India, Indonesia, Mexico, Senegal and Zambia have used serum retinol as an indicator, and have not always found improvement in response to supplementation. One problem is that homeostatic control of serum retinol may mask positive effects of treatment in that changes in concentration are observed only when status is either moderately to severely depleted or excessive. Because VA is stored mainly in the liver, measurements of hepatic VA stores are the “gold standard” for assessing VA status. Dose response tests such as the relative dose response (RDR) and the modified relative dose response (MRDR), allow a qualitative assessment of VA liver stores. On the other hand, the use of the vitamin A-labeled isotope dilution (VALID) technique, (using 13C or 2H-labeled retinyl acetate) serves as an indirect method to quantitatively estimate total body and liver VA stores. Countries including Cameroon, China, Ghana, Mexico, Thailand and Zambia are now applying the VALID method to sensitively assess changes in VA status during interventions, or to estimate a population’s dietary requirement for VA. Transition to the use of more sensitive biochemical indicators of VA status such as the VALID technique is needed to effectively assess interventions in populations where mild to moderate VA deficiency is more prevalent than severe deficiency.


1972 ◽  
Vol 27 (10) ◽  
pp. 1504-1507 ◽  
Author(s):  
Anselm Zänkert ◽  
Wilhelm Ackermann

Abstract Rubidium determinations of granites and biotites were performed by flamephotometric measurements and controlled by isotope dilution method. For isotope geological work the flamephotometric determination is not precise enough to replace the isotope dilution technique.


2021 ◽  
Author(s):  
Michael H Green ◽  
Veronica Lopez-Teros ◽  
Joanne Balmer Green

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.


2019 ◽  
Vol 150 (5) ◽  
pp. 989-993 ◽  
Author(s):  
Michael H Green ◽  
Joanne Balmer Green ◽  
Jennifer Lynn Ford

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.


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