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 mg/g; n = 52; VA study), VA + 10% retinoic acid (6mg/g; n= 42; VARA study), or placebo (canola oil; n= 94; both studies), all of which contained ;2 mCi [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 VARAcompared 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. Curr Dev Nutr