Measurement of carotenoid levels in human serum and a catalog of the lutein conformation populations from semi-empirical calculations

Lutein is a principal constituent of the human macular pigment. This study is composed of two projects. The first studies the conformational geometries of lutein and its potential adaptability in biological systems. The second is a study of the response of human subjects to lutein supplements. Using semi-empirical parametric method 3 (PM3) and density functional theory with the B3LYP/6-31G* basis set, the relative energies of s- cis conformers of lutein were determined. All 512 s-cis conformers were calculated with PM3. A smaller, representative group was also studied using density functional theory. PM3 results were correlated systematically to B3LYP values and this enables the results to be calibrated. The relative energies of the conformers range from 1-30 kcal/mole, and many are dynamically accessible at normal temperatures. Four commercial formulations containing lutein were studied. The serum and macular pigment (MP) responses of human subjects to these lutein supplements with doses of 9 or 20 mg/day were measured, relative to a placebo, over a six month period. In each instance, lutein levels in serum increased and correlated with MP increases. The results demonstrate that responses are significantly dependent upon formulation and that components other than lutein have an important influence serum response.

Calculations on the end-group conformational barrier in carotenoids and a study of the bioavailability of xanthophyll esters in humans

The present study measures the increase in serum carotenoid concentration in 30 healthy individuals after supplementation with a low dose xanthophyll ester (3 and 6 mg of lutein equivalent/per day) when compared to a placebo. Serum levels of carotenoids were measured using HPLC and showed an increase in the concentration of lutein, zeaxanthin and four lutein metabolites proportional to dose. In order to further assess the importance of the end-group structure in carotenoids we have investigated the influence of the end-group type and functionality on the conformational energy barrier. We used the density functional method implemented on GAUSSIAN 98 to calculate the conformational energy curves for rotation of the P-ring or the E-ring relative to short polyene chains around the C6-C7 single bond. A large barrier is observed for the interconversion of conformers in the E-rings (8 kcal/mol) when compared to beta rings (2.3-3 kcal/mol).