Vitamin A and retinoic acid combined have a more potent effect compared to 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 vs. 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 two prior kinetic studies of Sprague-Dawley neonatal rats nursed by mothers fed a VA-marginal diet (0.35 mg retinol equivalents/kg diet). On postnatal d 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 containing ~2 μCi of [3 H]retinol as the tracer for VA. Total retinol concentrations and tracer levels had been measured in plasma and tissues from 1 h to 14 d after dosing. Control group data from both studies were merged prior to 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 vs. 288 times in VARA- vs. VA-treated group). Although the 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.

Conclusions: 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 levels in the extrahepatic organs that continue to develop postnatally.