Retinol homeostasis in lambs given low and high intakes of vitamin A

Four groups of lambs were fed on a low-carotene basal diet. One group received no supplemental vitamin A (mildly deficient). Remaining groups were supplemented daily with vitamin A acetate equivalent to 100 (control) 9000 (mildly intoxicated) and 18000 (severely intoxicated) microgram retinol/kg body-weight. After 16 weeks lambs received a bolus of [15-3H]retinol intravenously; blood, urine and faeces were sampled for 48 h. Plasma retinol was complexed to a protein of 20000 molecular weight (MW), which in turn was complexed to a protein of 65000 MW; these proteins correspond respectively to retinol-binding protein and prealbumin. Plasma retinol concentration reached plateau values in intoxicated lambs, but plasma retinyl ester concentrations increased rapidly when liver contents of both retinol and retinyl esters exceeded approximately 10 and 100 mg respectively and kidney contents of both retinol and retinyl esters exceeded 30 micrograms. Labelled compounds, more polar than retinol, were found in plasma; their concentration increased tenfold in intoxicated lambs within 48 h. Plasma retinol transport rates were 0.1, 10.5 and 11.8 times control values, and clearance rates were 0.3, 14.1 and 14.3 times control values in mildly-deficient, and mildly- or severely-intoxicated lambs respectively. Turnover of retinol increased rapidly when liver contents of retinol and retinyl esters exceeded approximately 10 and 100 mg respectively and kidney contents of both retinol and retinyl esters exceeded approximately 30 micrograms. Plasma clearance of retinyl esters was unchanged with intake. Faecal excretion of tracer increased linearly with plasma retinol clearance. Our findings identify several variables that appear to be involved in retinol homeostasis, including plasma retinol clearance and excretion.