No improvement in suboptimal vitamin A status with a randomized, double-blind, placebo-controlled trial of vitamin A supplementation in children with sickle cell disease

Background: Suboptimal vitamin A status is prevalent in children with type SS sickle cell disease (SCD-SS) and is associated with hospitalizations and poor growth and hematologic status. The supplemental vitamin A dose that optimizes suboptimal vitamin A status in this population is unknown. Objective: The efficacy of Recommended Dietary Allowance (RDA) doses (based on age and sex) of vitamin A (300, 400, or 600 μg retinyl palmitate/d) or vitamin A + zinc (10 or 20 mg zinc sulfate/d) compared with placebo to optimize vitamin A status was assessed in children aged 2.0-12.9 y with SCD-SS and a suboptimal baseline serum retinol concentration (<30 μg/dL). Design: In this randomized, double-blind, placebo-controlled trial, vitamin A status (serum retinol, prealbumin, retinol-binding protein, and relative-dose-response test) and disease-related illness events were assessed. Results: Twelve months of vitamin A supplementation at the doses recommended for healthy US children (based on age and sex) failed to improve serum retinol values in either group (vitamin A: n = 23; vitamin A + zinc: n = 18) compared with placebo (n = 21). By 12 mo, the increase (±SD) in serum retinol (3.6 ± 2.8 μg/dL) in those taking 600 μg vitamin A/d was significantly different from the decrease (±SD; -2.8 ± 2.4 μg/dL) in those taking 300 μg/d, which possibly suggests a dose-response relation (P < 0.05) with RDA doses. Conclusions: Compared with placebo, 12 mo of vitamin A supplementation at the RDA for healthy children did not improve serum retinol values in children with SCD-SS, which possibly suggests that higher doses are needed. However, the existence of alternative conclusions emphasizes the need for future research.