Vitamin A and Retinoic Acid Combined Have a More Potent Effect Compared with Vitamin A Alone on the Uptake of Retinol into Extrahepatic Tissues of Neonatal Rats Raised under Vitamin A–Marginal Conditions

Background: Vitamin A (VA; retinol) supplementation is widely used to reduce child mortality in low-income countries. However, existing research suggests that supplementation with VA alone may not be optimal for infants. Objective: We compared the effect of VA with VA combined with retinoic acid (VARA) on retinol uptake and turnover in organs of neonatal rats raised under VA-marginal conditions. Methods: Secondary analysis was conducted on data obtained from 2 previous kinetic studies in Sprague-Dawley neonatal rats nursed by dams fed a VA-marginal diet (0.35 mg retinol equivalents/kg diet). On postnatal day 4, pups had been treated with a single dose of VA (6 μg/g; n = 52; VA study), VA + 10% retinoic acid (6 μg/g; n = 42; VARA study), or placebo (canola oil; n = 94; both studies), all of which contained ∼2 μCi [(3)H]retinol as the tracer for VA. Total retinol and tracer concentrations were measured in plasma and tissues from 1 h to 14 d after dosing. Control group data from both studies were merged before analysis. Kinetic parameters were re-estimated and compared statistically. Results: VARA supplementation administered to neonatal rats within a few days after birth resulted in a lower turnover of retinol in the lungs, kidneys, and carcass and less frequent recycling of retinol between plasma and organs (100 compared with 288 times in the VARA- compared with the VA-treated group). Although VA supplementation resulted in a higher concentration of retinol in the liver, VARA supplementation led to a higher uptake of postprandial retinyl esters into the lungs, intestines, and carcass. Conclusion: Given the relatively higher retinol uptake into several extrahepatic organs of neonates dosed orally with VARA, this form of supplementation may serve as a targeted treatment of low VA concentrations in extrahepatic organs that continue to develop postnatally.