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

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.

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

“…To simulate TBS over time in young children, we used recently published VA intake and kinetic data for children in 4 countries. Specifically, we used data for groups of 1 ) Bangladeshi infants (mean age: 12 mo; n = 87) with an average VA intake of 1.23 μmol RAE/d and TBS of 198 μmol ( 13 ); 2 ) Filipino infants (mean age: 14 mo; n = 120) with a mean intake of 2.54 μmol RAE/d and VA TBS of 533 μmol ( 13 ); 3 ) Guatemalan children (mean age: 50 mo; n = 135) with an average VA intake of 2.67 μmol RAE/d and TBS of 1062 μmol ( 13 ); and 4 ) Mexican infants (mean age: 26 mo; n = 15) ( 9 ) and children (mean age: 58 mo; n = 24) ( 12 ) estimated to consume ∼1.4 μmol RAE/d with VA TBS of 844 and 1097 μmol, respectively. As detailed later, to obtain estimates of reported VA intake from birth to 5 y, we collected additional information from the literature for infants and children from these 4 countries.…”

“…For TBS predictions based on reported VA intakes, we used data for infants and children from Bangladesh ( 32 – 38 ), the Philippines ( 39 – 42 ), Guatemala ( 13 , 43 – 46 ), and Mexico ( 6 , 9 , 12 , 47 ). For each group, breast milk VA consumption was estimated based on the average daily consumption of breast milk ( 1 , 48 ), using measured volumes of milk consumed in Bangladeshi ( 38 ) and Mexican children ( 6 ), and estimates reported for Guatemalan and Filipino children ( 39 ), as well as the VA content in breast milk at various stages of lactation ( 6 , 32 , 38 , 39 ).…”

“…Values for FCR at different ages were obtained from references ( 9 , 12 , 13 ). Based on the rationale that FCR is inversely correlated with TBS ( 56 , 57 ) and infants are born with very limited VA stores that, with adequate intake, increase with age ( 19 , 23 , 58 ), we hypothesized that FCR would decrease exponentially with age.…”

“…However, in the years since the VA DRIs were developed, a substantial amount of new information has been published on VA intake, VA total body stores (TBS), and retinol kinetics in children. For example, using a deuterium oxide dilution technique, the volume of breast milk, and thus the amount of VA, consumed by infants has been determined ( 5 , 6 ); TBS over a wide range (∼100–1100 μmol) has been estimated in children with various VA intakes [100–900 retinol activity equivalents (RAE)/d] using retinol isotope dilution equations ( 7 – 12 ) and model-based compartmental analysis ( 9 , 12 , 13 ); and compartmental modeling using a population-based (super-child) design has been successfully applied to quantify whole-body VA kinetics in children ( 9 , 12 , 13 ). In addition, numerous studies have been carried out to assess children's VA intake from breast milk, foods, and other sources, including VA supplements, micronutrient powders (MNPs), and fortified foods (for reviews, see references 14 – 18 ).…”

“…We adapted these methods here to integrate current knowledge and hypotheses related to VA consumed in breast milk, foods, and supplements by children from birth to age 5 y and to predict changes in VA TBS and liver VA concentrations that would be expected to result from these intakes. To develop these predictions, we used information in the literature for VA intakes as well as recently published data on retinol kinetics in infants and preschool-aged children from Bangladesh ( 13 ), the Philippines ( 13 ), Guatemala ( 13 ), and Mexico ( 9 , 12 ). Our results indicate that the current VA DRIs [specifically, Adequate Intake (AI) from birth to age 12 mo and RDA from 1 to 5 y] are sufficient to build and maintain VA stores during infancy and early childhood in these groups.…”