Validity of the relative-dose-response test and the modified-relative-dose-response test as indicators of vitamin A stores in liver.

BACKGROUND Our group and many others have used the relative-dose-response (RDR) test and the modified-RDR (MRDR) test as proxy indicators of liver stores of vitamin A. However, we have become concerned about the validity of these indicators. OBJECTIVE Simulation models were used to assess effects of random variations in serum retinol concentration on the RDR and to assess effects of group differences in serum retinol concentration on the distribution of RDR and MRDR values. DESIGN Random and independent samples were drawn from normally distributed, computer-generated numbers whose distributions simulated serum concentrations of retinol and 3,4-didehydroretinol as obtained from published reports. The resulting data sets were used to compute surrogate RDR or MRDR values. In model 1, the relation between serum concentrations of retinol and RDR was examined within a fictitious population. In models 2 and 3, fictitious populations with different distributions of serum retinol concentration were compared with respect to their RDR and MRDR values. RESULTS Simulated RDR values and serum retinol concentrations were negatively related. Models 2 and 3 showed that group differences in serum retinol concentrations necessarily produced group differences in mean RDR or MRDR values. A mathematical artifact may explain the negative relation reported between MRDR and serum retinol concentration, and it dictates that this relation will necessarily vary between populations with different degrees of vitamin A deficiency. CONCLUSION A continued search for alternative blood indicators of liver stores of vitamin A is needed.