A Low Molar Ratio of Retinol Binding Protein to Transthyretin Indicates Vitamin A Deficiency during Inflammation: Studies in Rats and A Posteriori Analysis of Vitamin A–Supplemented Children with Measles

Abstract

To assess whether the molar ratio of retinol-binding protein (RBP) to transthyretin (TTR) is of utility in detecting vitamin A (VA) deficiency during inflammation, we analyzed data from a rat model of endotoxin-induced inflammation and from a previously reported randomized, placebo-controlled trial of VA supplementation in children with acute measles. In rats, both marginal VA deficiency and inflammation were independent causes of low plasma RBP (two-way ANOVA, P < 0.001), whereas plasma TTR concentration was reduced only by inflammation (P < 0.001). The molar ratio of plasma RBP to TTR was reduced (by ∼50%) only in rats with marginal VA deficiency and inflammation (two-way ANOVA interaction, P < 0.01). Serum retinol concentration, C-reactive protein (CRP, an indicator of inflammation) and the RBP:TTR molar ratio were determined in children with acute measles at baseline and 2 wk after subgroups received a placebo or a 210 μmol VA supplement. The ratio of RBP:TTR was selectively reduced in children in the placebo group with low plasma retinol (<0.35 μmol/L) and elevated CRP (>40 mg/L). In children with a low RBP:TTR molar ratio (<0.30) at baseline, the RBP:TTR ratio increased significantly 2 wk later only in the VA-treated subgroup. These analyses provide evidence that, because RBP is differentially reduced in comparison to TTR during VA deficiency, the combined determination of the concentrations of serum RBP and TTR may provide a promising means of detecting VA deficiency during inflammation.