Use of the Paired Retinol Isotope Dilution Test, but with a Single Isotope Dose, to Assess the Impact of a Vitamin A Intervention on Vitamin A Stores in Theoretical Children with Low Stores

Background: As currently applied, the paired retinol isotope dilution (RID) test, which is used to assess the impact of a vitamin A intervention on vitamin A total body stores (TBS), requires 2 doses of stable isotope-labeled vitamin A.

Objectives: The objectives of this study were to evaluate use of a single isotope dose (4 μmol) to assess TBS by RID before and after intervention in theoretical children with low/moderate TBS.

Methods: We selected 6 theoretical children with assigned values for TBS ranging from 82 to 281 μmol. Using Simulation, Analysis and Modeling software, we simulated the variable [plasma retinol specific activity (SA_p)] and coefficients (Fa and S) used in the RID equation TBS (μmol) = FaS × 1/SA_p in both the unsupplemented steady state at day 14 postdosing and during the subsequent 4 mo without or with vitamin A supplementation [2.8 μmol retinol/d (801 μg retinol activity equivalents/d)].

Results: Fraction of dose in plasma on day 150 compared with day 14 was similar in the unsupplemented and supplemented conditions [geometric mean, 32% (range, 20%-48%) and 30% (20%-48%), respectively] and simulated values for FaS were similar under the 2 conditions. After 2 and 4 mo of daily vitamin A supplementation with 2.8 μmol/d, TBS was 78% and 128% higher, respectively, than without supplementation.

Conclusions: Results indicate that the paired RID method can successfully be done using a single 4 μmol dose of stable isotope. Furthermore, because values for the RID coefficient FaS were similar in the unsupplemented and vitamin A-supplemented conditions, these results in theoretical children indicate that FaS determined by population ("super-subject") modeling of steady state vitamin A kinetic data could be used to predict TBS by RID after a vitamin A intervention in individuals from the same or a similar group.