Chronic ingestion of (3R,3'R,6'R)-lutein and (3R,3'R)-zeaxanthin in the female rhesus macaque.
OBJECTIVE
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.
Khachik
Frederick
F
Department of Chemistry and Biochemistry, Joint Institute for Food Safety and Applied Nutrition (JIFSAN), University of Maryland, College Park, Maryland 20742-2021, USA. khachik@umd.edu
London
Edra
E
de Moura
Fabiana F
FF
Johnson
Mary
M
Steidl
Scott
S
Detolla
Louis
L
Shipley
Steven
S
Sanchez
Rigoberto
R
Chen
Xue-Qing
XQ
Flaws
Jodi
J
Lutty
Gerard
G
McLeod
Scott
S
Fowler
Bruce
B
D000818:Animals; D002338:Carotenoids / Q000097:blood; D003404:Creatinine / Q000652:urine; D019587:Dietary Supplements; D004338:Drug Combinations; D005260:Female; D014975:Lutein / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D008253:Macaca mulatta; D009887:Ophthalmoscopy; D011507:Proteinuria / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D024341:Xanthophylls / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D065146:Zeaxanthins
D004338:Drug Combinations; D024341:Xanthophylls; D065146:Zeaxanthins; D002338:Carotenoids; D003404:Creatinine; D014975:Lutein