Effects of Supplemental Vitamin A on Retinoic Acid Concentrations in the Plasma of Preruminant Calves

Abstract

Neonatal calves are fed frequently milk replacers with vitamin A concentrations exceeding those recommended by the National Research Council. The vitamin A metabolite, retinoic acid (RA), affects profoundly cellular differentiation and homeostasis. For this reason, effects of dietary vitamin A on plasma concentrations of RA isomers in milk replacer-fed calves were examined. Male, Holstein calves (n = 24) were fed colostrum within 12 hours after birth and, thereafter, a custom-formulated low vitamin A milk replacer providing 0, 1700 [National Research Council (NRC) daily requirement for young growing calves] (controls), 34000 (industry standard in the United States) or 68000 IU of vitamin A daily. Concentrations of retinol and RA isomers in plasma samples collected from birth to 27 days of age were determined by HPLC. Retinol was affected by dietary vitamin A with higher concentrations occurring in calves supplemented with >= 34000 IU of vitamin A/day than in control (1700 IU of vitamin daily) and unsupplemented calves. Relative to controls, concentrations of all isomers of RA were higher in calves supplemented with >= 34000 of vitamin A daily during the experimental period. The predominant isomer in all calves was 9,13-dicis-RA. In control calves, 9,13-dicis-RA and 9-cis-RA were maximal at 1 to 6 days of age and then decreased progressively. In calves fed >= 34000 IU of vitamin A daily, concentrations of these isomers were markedly higher at 6 days of age, relative to controls, and remained elevated for the duration of the study. In all calves, retinol was correlated positively with 9,13-dicis- and 9-cis-RA from 9 to 27 day of age. 9,13-cis-Retinoic acid was correlated positively with 9-cis- and 13-cis-RA from 13 to 27 days of age. It is concluded that supplementing milk replacer-fed calves with vitamin A at levels exceeding current NRC recommendations by >= 20-fold causes an elevation in plasma concentrations of retinol and retinoic acids. 9,13-dicis- and 9-cis-Retinoic acids were most affected by supplemental vitamin A. Physiologic consequences of increased plasma RA concentrations induced by high dietary levels of vitamin A warrant investigation.