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Plasma kinetics of zeaxanthin and 3'-dehydro-lutein after multiple oral doses of synthetic zeaxanthin^1,2,3,4

¹ From the Department of Human Nutrition and Health, Roche Vitamins Ltd, Basel, Switzerland (DH, VS, WS, and WC), and the Institute of Clinical Pharmacology, HELIOS Klinikum Wuppertal, University of Witten/Herdecke, Wuppertal, Germany (PAT and BM).

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 possible influence of other carotenoids on plasma zeaxanthin concentrations.

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 µmol) or 10 mg (17.6 µmol) zeaxanthin for 42 d. Plasma concentration-time profiles on days 1 and 42, concentrations immediately before zeaxanthin intake during the dosing period, and concentrations after the last dose until day 76 were monitored.

Results: all-E-Zeaxanthin concentrations increased from 0.048 ± 0.026 µmol/L at baseline to 0.20 ± 0.07 and 0.92 ± 0.28 µmol/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 compatible with an effective half-life for accumulation of 5 d. The terminal 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.

Key Words: Xanthophyll • carotenoids • zeaxanthin • multiple oral dose kinetics • beadlet formulation • all-E-3'-dehydro-lutein • lutein

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