Metabolism of lutein and zeaxanthin in rhesus monkeys: Identification of (3R,6′R)- and (3R,6′S)-3′-dehydro-lutein as common metabolites and comparison to humans

Abstract

Lutein and zeaxanthin are xanthophylls that can be found highly concentrated in the macula of the retina. They are thought to protect the macula through their role as blue-light filters and because of their antioxidant and singlet oxygen quenching properties. Examination of metabolites unique to lutein and zeaxanthin such as 3′-dehydro-lutein, and of their stereochemistry may provide insight to the mechanism by which they are formed and by which they exert protection. To evaluate the formation of such metabolites, eleven monkeys were raised on a xanthophyll-free diet, and supplemented with pure lutein or pure zeaxanthin (2.2 mg/kg body weight/d). The period of supplementation ranged between 12 to 92 weeks. At study start and throughout the study, serum samples were taken and analyzed for xanthophylls using different HPLC systems. Xanthophyll metabolites were identified using UV/VIS and HR-MS detection. Lutein and zeaxanthin metabolites were found in detectable amounts with 3′-dehydro-lutein being a common metabolite of both. Using chiral-phase HPLC, two diastereomers, (3R,6′R)-3′-dehydro-lutein and (3R, 6′S)-3′-dehydro-lutein, were identified and shown to be present in nearly equimolar amounts. A pathway for their formation from either lutein or zeaxanthin is proposed. These finding were comparable to results obtained with human plasma.

A 3-hydroxy %-end group in xanthophylls is preferentially oxidized to a 3-oxo ε-end group in mammals

“…This assumption is supported by the previous report that the plasma level of 3-hydroxy-␤ , -caroten-3 ′ -one was increased in humans and rhesus monkeys fed lutein ( 37,38 ). However, the oxidative activity of the ␤ -end group in zeaxanthin is suggested to be higher than that of the -end group in lutein, because the formation rate constant of 3-hydroxy-␤ , -caroten-3 ′ -one from zeaxanthin was found to be higher than that from lutein in Cohn and colleagues' kinetic study of lutein and zeaxanthin orally administered to human subjects ( 36,38 ).…”

“…Based on the metabolic activity of postmitochondrial fraction of mouse liver observed in the present study, we speculate in the plasma of humans and rhesus monkeys fed zeaxanthin ( 36,37 ). In particular, the presence of equal amounts of two diastereomers (3 R ,6 ′ R and 3 R ,6 ′ S ) of 3-hydroxy-␤ , -caroten-3 ′ -one in the plasma of rhesus monkeys was quite consistent with the oxidation of a ␤ -end group proposed in the present study.…”

Differential effects of testosterone, dihydrotestosterone and estradiol on carotenoid deposition in an avian sexually selected signal

“…In particular, this is one of the few studies that have detected dehydrolutein, an oxidized form of lutein and zeaxanthin (Gesa et al 2008), in the integument of birds (Costantini et al 2009). Interestingly, the eye ring contains very high amounts of carotenoid esters.…”

Dietary Sources of Lutein and Zeaxanthin Carotenoids and Their Role in Eye Health

“…It has been suggested that lutein and zeaxanthin are transported into retina in the same ratio as in plasma, and then transferred to macula where lutein is preferentially converted into meso -zeaxanthin [47,48,49,50,51]. These observations strongly suggest the importance of lutein, zeaxanthin and meso -zeaxanthin in the management of good eye health [51,52,53]. Several studies have shown that incidences of AMD can be reduced by consuming diets with high levels of lutein and zeaxanthin and supplementation by increasing their concentration in serum and parallel increase in macular pigment optical density (MPOD) [54,55,56,57,58].…”