title: 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 IU VA in oil within 12 h of birth when mean ± 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 VA maintained 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. Body weight was 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-term impacts of retinoid signaling on weight gain remain to be elucidated, and longer follow-up studies are needed.
authors.affiliation: Department of Nutritional Sciences, Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI.
authors.forename: Bryan M
authors.identifier: 0000-0003-1781-9242
authors.initials: BM
authors.lastname: Gannon
authors.affiliation: Department of Nutritional Sciences, Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Davis
authors.affiliation: Department of Nutritional Sciences, Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI.
authors.forename: Nivedita
authors.initials: N
authors.lastname: Nair
authors.affiliation: Department of Nutritional Sciences, Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI.
authors.forename: Michael
authors.initials: M
authors.lastname: Grahn
authors.affiliation: Department of Nutritional Sciences, Interdepartmental Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI sherry@nutrisci.wisc.edu.
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Tanumihardjo
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D019587:Dietary Supplements; D004952:Esters / Q000097:blood; D005260:Female; D006801:Humans; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D013154:Spleen / Q000378:metabolism; D013552:Swine; D014018:Tissue Distribution; D014801:Vitamin A / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014802:Vitamin A Deficiency / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D004952:Esters; D014801:Vitamin A
keywords: adrenal; kidney; lung; retinol; spleen