Abstract
Purpose: :
Lutein [(3R,3'R,6'R)–ß,ε–carotene–3,3'–diol] and zeaxanthin [a mixture of (3R,3'R)–ß,ß–carotene–3,3'diol and (3R,3'S–meso)–ß,ß–carotene–3,3'–diol] are found in substantial amounts in the retina of Japanese quail Coturnix japonica. This makes them an excellent model for studying the effect of dietary supplementation of these carotenoids. In this study, we used labeled lutein and zeaxanthin as dietary supplements to study the pharmacokinetics and metabolic transformations of macular pigments in serum, ocular, and non–ocular tissues.
Methods: :
Deuterated zeaxanthin and lutein were prepared from microbial sources. Japanese quails were orally fed with these deuterated carotenoids (0.3–0.4 mg perday) for 20 weeks. Birds were sacrificed at regular intervals and carotenoid contents were analyzed from ocular and nonocular tissues were determined by HPLC coupled with an in–line mass spectrometer (MS) in a positive ion atmospheric pressure chemical ionization (APCI) mode.
Results: :
The deuterated carotenoids were detected in serum and retinal tissue at weeks 8 and 12, respectively. The basal levels of zeaxanthin in the serum and retina of quail was 0.53 ±0.05 ng/ml and 20.18 ±3.1 ng /tissue respectively. After supplementation with deuterated zeaxanthin, the serum levels rose to 5.33 ±0.1 ng/ml in 10 weeks. After 16 weeks of supplementation, concentrations of zeaxanthin in the retina had increased by a factor of 8 (157.5 ±13.8 ng/tissue P < 0.001). The basal levels of lutein in the serum and retina of quail was 0.34 ±0.04 ng/ml and 9.2 ±2.2 ng /tissue, respectively. After supplementation with deuterated bacterial lutein, the serum levels rose to 2.3 ±0.1 ng/ml in 8 weeks. After 12 weeks of supplementation, concentrations of lutein in the retina had increased by a factor of 4.2 (38.1 ±5.7 ng/tissue P < 0.001). The presence of deuterated 3'–oxolutein and meso–zeaxanthin in the tissues demonstrated that precursors for 3'–oxolutein and meso–zeaxanthin are dietary zeaxanthin and lutein respectively.
Conclusions: :
These pharmacokinetic studies on Japanese quail show that uptake of carotenoids into the retina is a process that can take many weeks despite high–dose supplementation, a finding that correlates well with the time–course observed in most human clinical studies. Our studies demonstrate in an unambiguous manner in nondeficient vertebrates that dietary zeaxanthin is the precursor of 3'–oxolutein and that dietary lutein is the precursor for meso–zeaxanthin.
Keywords: carotenoids/carotenoid binding proteins • age-related macular degeneration • macular pigment