Single high-dose vitamin A supplementation to neonatal piglets results in a transient dose response in extrahepatic organs and sustained increases in liver stores

Abstract

Background: Neonatal vitamin A (VA) supplementation is being evaluated as a public health policy for preventing infant mortality, but inconsistencies in mortality trials demand mechanistic work to determine biological plausibility. Objectives: We investigated the absorption, distribution, and storage of single large oral VA doses administered shortly after birth. Methods: Fifty pregnant sows (Sus scrofas domesticas) were fed a VA-free diet.Male and female newborn piglets (n = 313) were orally administered 0, 25,000, 50,000, or 200,000 IUVA in oil within 12 h of birth whenmean ± SD weight was 1.56 ± 0.25 kg. Blood was drawn to determine absorption and storage 0.5-240 h after administration. Metabolic and postnatal dose-timing substudies were performed. Liver, lung, kidney, spleen, and adrenal VA concentrations were determined 7-240 h after administration. Results: Serum retinol and retinyl ester concentrations responded to treatment (P < 0.0001); however, differences between groups disappeared by 96 h. Liver VA concentrations responded to treatment (P < 0.0001), which persisted for 240 h. Liver VA for control piglets at 10 d (mean ± SD: 0.05 ± 0.02 μmol/g) was ≤0.1 μmol/g (deficiency), whereas groups that received VAmaintained concentrations > 0.1 μmol/g. Extrahepatic tissue VA concentrations displayed treatment effects (P ≤ 0.0077); groups that received treatments had higher VA concentrations than controls at early time points. Lung, kidney, and spleen VA did not differ between groups by 96 h,whereas adrenal glands did not differ by 240 h. Bodyweightwas affected by treatment (P = 0.0002); VA-deficient piglets weighed 23-29% more than all treated groups 240 h after administration. Conclusions: A high dose of VA administered to newborn piglets was well absorbed, appeared in serum primarily as retinyl esters, and was taken up dose-dependently in all tissues studied; however, enhancement did not persist in sera, lungs, kidneys, spleens, or adrenal glands. Short-termimpacts of retinoid signaling on weight gain remain to be elucidated, and longer follow-up studies are needed.