Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of synthetic zeaxanthin

Background: Zeaxanthin is hypothesized to reduce the risk of age-related macular degeneration; however, kinetic information is limited. Objectives: The objective was to investigate the plasma kinetics of synthetic zeaxanthin after repeated oral doses and to assess the pos-sible influence of other carotenoids on plasma zeaxanthin concen-trations. Design: After a run-in of 3 d, 20 healthy volunteers assigned to 2 parallel dose groups received once daily oral doses of either 1 mg (1.76 mol) or 10 mg (17.6 mol) zeaxanthin for 42 d. Plasma concentration-time profiles on days 1 and 42, concentrations imme-diately before zeaxanthin intake during the dosing period, and con-centrations after the last dose until day 76 were monitored. Results: all-E-Zeaxanthin concentrations increased from 0.048 0.026 mol/L at baseline to 0.20 0.07 and 0.92 0.28 mol/L with 1 and 10 mg zeaxanthin, respectively. The dose-normalized bioavailability of all-E-zeaxanthin after the10-mg dose was 40% lower (P 0.001) than after the 1-mg dose. Other kinetic parameters did not differ significantly between groups. After 17 d of dosing, 90 % of steady state concentrations were reached, which was com-patible with an effective half-life for accumulation of 5 d. The ter-minal elimination half-life was 12 7 d (n 20). The time course of plasma all-E-3'-dehydro-lutein concentrations resembled that of all-E-zeaxanthin. The data provided evidence that all-E-3'-dehydro-lutein was derived from all-E-zeaxanthin. Concentrations of other carotenoids were not affected. Zeaxanthin was well tolerated. Conclusion: Long-term oral intake of 1 and 10 mg zeaxanthin as beadlets increases plasma zeaxanthin concentrations 4- and 20-fold, respectively. Evidence that all-E-3'-dehydro-lutein is formed from zeaxanthin was strong. Am J Clin Nutr 2004;79:410–7. KEY WORDS Xanthophyll, carotenoids, zeaxanthin, multi-ple oral dose kinetics, beadlet formulation, all-E-3'-dehydro-lutein, lutei