Plasma kinetics of vitamin A in humans after a single oral dose of [8,9,19-13C]retinyl palmitate

Abstract

The kinetics of vitamin A and its major metabolites were investigated in humans. Eleven healthy male subjects ingested 105 mumol (100,000 IU) of [8,9,19-13C]retinyl palmitate in an oily solution. Twenty-seven blood samples were collected during the 1-week study. Plasma samples were analyzed for retinyl esters and for [12C]- and [8,9,19-13C]retinol. Retinol isotopes were quantified using a newly developed GC-MS method. Total retinyl esters peaked at about 4.45 mumol/L from 3.5 to 12 h after dosing. As a result of the perturbation of the tracee system, the plasma concentration of [12C]retinol increased and then decreased as the concentration of [8,9,19-13C]retinol increased, indicating rapid distribution kinetics. A broad single peak (1.16 +/- 0.32 mumol/L) was observed for [8,9,19-13C]retinol at about 10 to 24 h postdose; this likely reflects hepatic secretion of [8,9,19-13C]retinol associated with retinol-binding protein. Then, declining levels of the tracer and increasing levels of the tracee were observed. At its peak, the ingested [8,9,19-13C]retinol reached about 51% of the observed total plasma retinol concentration. This percentage dropped to 13.4% on day 7 indicating slow final elimination from plasma. Our data support the concept that the liver follows the principle “last in/first out' in maintaining vitamin A homeostasis.