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(Investigative Ophthalmology and Visual Science. 2006;47:5476-5486.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.06-0194
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Chronic Ingestion of (3R,3'R,6'R)-Lutein and (3R,3'R)-Zeaxanthin in the Female Rhesus Macaque

Frederick Khachik,1 Edra London,1 Fabiana F. de Moura,1,2 Mary Johnson,3 Scott Steidl,3 Louis DeTolla,4,5 Steven Shipley,4 Rigoberto Sanchez,4 Xue-Qing Chen,5 Jodi Flaws,5 Gerard Lutty,6 Scott McLeod,6 and Bruce Fowler5,7

1From the Department of Chemistry and Biochemistry, Joint Institute for Food Safety and Applied Nutrition (JIFSAN), University of Maryland, College Park, Maryland; the 3Department of Ophthalmology and Visual Science, 4Comparative Medicine and Department of Pathology, the 5Department of Epidemiology and Preventive Medicine, School of Medicine, University of Maryland, Baltimore, Maryland; and the 6Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland.

PURPOSE. To investigate how supplementation of the monkey’s diet with high doses of lutein (L), zeaxanthin (Z), or a combination of the two affects the plasma levels and ocular tissue deposition of these carotenoids and their metabolites over time and to determine whether these high doses can cause ocular toxicity.

METHODS. Eighteen female rhesus monkeys were divided into groups of control (n = 3 control), L-treated (n = 5, 9.34 mg lutein/kg and 0.66 mg zeaxanthin/kg), Z-treated (n = 5, 10 mg zeaxanthin/kg), and L/Z-treated (n = 5, lutein and zeaxanthin, each 0.5 mg/kg). After 12 months of daily supplementation, one control animal, two L-treated animals, two Z-treated animals, and all the L/Z-treated animals were killed. The rest of the monkeys were killed after an additional six months without supplementation. Plasma and ocular tissue carotenoid analyses, fundus photography, and retina histopathology were performed on the animals.

RESULTS. Supplementation of monkeys with L and/or Z increased the mean plasma and ocular tissue concentrations of these carotenoids and their metabolites. The mean levels of L and Z in the retinas of the L- and Z-treated animals after 1 year increased significantly over baseline. High dose supplementation of monkeys with L or Z did not cause ocular toxicity and had no effect on biomarkers associated with kidney toxicity.

CONCLUSIONS. The mean levels of L and Z in plasma and ocular tissues of the rhesus monkeys increase with supplementation and in most cases correlate with the levels of their metabolites. Supplementation of monkeys with L or Z at high doses, or their combination does not cause ocular toxicity.






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