Direct and indirect vitamin A supplementation strategies result in different plasma and tissue retinol kinetics in neonatal rats

Libo Tan,Amanda E Babbs,Michael H Green,A Catharine Ross

doi:10.1194/jlr.m067165

Libo Tan, Amanda E Babbs + Show 2 more

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https://doi.org/10.1194/jlr.m067165

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Abstract

Many questions remain regarding vitamin A (VA) supplementation of infants. Herein we compared direct oral VA supplementation of the neonate and indirect treatment through maternal dietary VA (M-VA) treatment on VA status and kinetics in neonatal rats. Treatments included direct VA combined with retinoic acid (RA) [D-VARA; VA (6 mg/kg) + 10% RA, given orally to neonates on postnatal day (P)2 and P3] and indirect VA supplementation through increased M-VA, compared with each other and oil-treated neonates. [3H]retinol was administered orally to all neonates on P4. Plasma and tissue [3H]retinol kinetics were determined from 1 h to 14 days post-dosing. D-VARA versus placebo dramatically increased liver and lung retinol, but only in the first 8–10 days. In M-VA neonates, liver and lung VA increased progressively throughout the study. Compartmental modeling of plasma [3H]retinol showed that both D-VARA and indirect M-VA reduced retinol recycling between plasma and tissues. Compartmental models of individual tissues predicted that D-VARA stimulated the uptake of VA in chylomicrons to extrahepatic tissues, especially intestine, while the uptake was not observed in M-VA neonates. In conclusion, indirect maternal supplementation had a greater sustained effect than D-VARA on neonatal VA status, while also differentially affecting plasma and tissue retinol kinetics.

Highlights

Many questions remain regarding vitamin A (VA) supplementation of infants
In maternal dietary VA (M-VA) pups, the liver total retinol concentration increased steadily with time until the end of the study and was significantly higher (4- to 8-fold) than that in the control group. Whereas both the direct vitamin A combined with retinoic acid (D-vitamin A combined with retinoic acid (VARA)) pretreatment of the neonate and indirect M-VA treatment improved liver VA content in the neonate, compared with the VA-marginal state, the kinetics were different, with DVARA resulting in only a transient increase in liver VA stores, while M-VA treatment resulted in a gradual steady accumulation of VA in the neonatal liver
We investigated how VA supplementation given directly to pups versus indirectly as increased dietary VA intake provided to dams affects VA status and retinol kinetics in neonatal rats by conducting tracer kinetic experiments and model-based compartmental analysis

Summary

Introduction

We compared direct oral VA supplementation of the neonate and indirect treatment through maternal dietary VA (M-VA) treatment on VA status and kinetics in neonatal rats. Treatments included direct VA combined with retinoic acid (RA) [D-VARA; VA (6 mg/kg) + 10% RA, given orally to neonates on postnatal day (P) and P3] and indirect VA supplementation through increased M-VA, compared with each other and oil-treated neonates. Indirect maternal supplementation had a greater sustained effect than D-VARA on neonatal VA status, while differentially affecting plasma and tissue retinol kinetics.—Tan, L., A. Direct and indirect vitamin A supplementation strategies result in different plasma and tissue retinol kinetics in neonatal rats. In one of our previous studies, we investigated VA kinetics from postnatal day 4 (P4) to P18 in neonatal rats that were either unsupplemented (oil-treated and nursed by VA-marginal dams; control group) or treated.

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