Kinetics and interrelation of [beta]-carotene and canthaxanthin transport in human plasma lipoproteins
The kinetics of single equimolar oral doses of [beta]-carotene and canthaxanthin, a model oxycarotenoid, and the effects of a combined [beta]-carotene plus canthaxanthin dose on their individual kinetics in plasma and plasma lipoproteins were investigated and compared in 10 normolipidemic, premenopausal women. During three study periods the subjects ingested either an individual [beta]-carotene or canthaxanthin dose or a combined [beta]-carotene plus canthaxanthin dose. The lipoproteins were separated by cumulative rate ultracentrifugation into four subfractions of triglyceride-rich lipoproteins (TRL), i.e. chylomicron, very-low density lipoprotein A (VLDLA), VLDLB, and VLDLC, and also into intermediate density (IDL), and low density lipoproteins (LDL). Canthaxanthin concentrations in plasma increased rapidly with a single peak at 12 hours post-dosing, and thus showed kinetics similar to those reported for lutein, an oxycarotenoid prominent in human diets. The plasma appearance of canthaxanthin was significantly inhibited when canthaxanthin was administered concurrently with [beta]-carotene compared with the single oral dose of canthaxanthin. Underlying the monophasic canthaxanthin plasma response were coincident canthaxanthin peak increments in TRL and LDL. Canthaxanthin concentrations peaked 6 to 8 hours post-dosing in TRL. We observed a rapid accumulation of canthaxanthin in LDL which was not affected by coincident ingestion of [beta]-carotene. In contrast, in TRL, the appearance of canthaxanthin was significantly inhibited after the ingestion of the combined dose of [beta]-carotene and canthaxanthin. We observed significant reductions in the areas under the lipoprotein canthaxanthin concentration-time curves (AUC) for individual lipoprotein fractions of 30.3 ± 4.6%-43.0 ± 8.1%. The appearance of [beta]-carotene in plasma was biphasic showing a peak increment at 5 hours post-dosing and a larger sustained peak at 48 hours post-dosing. In TRL, [beta]-carotene peak increments occurred 6 hour post-dosing with a peak increment in VLDLA exceeding that in chylomicrons. Apolipoprotein B48 was absent from the VLDL fractions, excluding chylomicron remnants as a possible explanation for the observed large increment in VLDLA. In LDL, [beta]-carotene appearance was delayed. The appearance of [beta]-carotene in plasma and plasma lipoproteins was insignificantly affected by the concurrent administration of canthaxanthin. The findings from the current study extend earlier reports on the specific interactions of [beta]-carotene and the oxycarotenoids, canthaxanthin and lutein, during intestinal absorption.