Plasma appearance of unesterified astaxanthin geometrical E/Z and optical R/S isomers in men given single doses of a mixture of optical 3 and 3′R/S isomers of astaxanthin fatty acyl diesters

Appearance, pharmacokinetics and distribution of astaxanthin all-E-, 9Z- and 13Z-geomettical and (3R,3R)-, (3R,3S)- and (3S,3S)-optical isomers in plasma fractions were studied in three middle-aged male volunteers (41-50 years) after ingestion of a single meal containing first a 10 mg dose equivalent of astaxanthin from astaxanthin diesters, followed by a dose of 100 mg astaxanthin equivalents after 4 weeks. Direct resolution of geometrical isomers and optical isomers of astaxanthin dicamphanates by HPLC after saponification showed that the astaxanthin consisted of 95.2% all-E-, 1.2% 9Z- and 3.6% 13Z-astaxanthin, of (3R,3R)-, (3R,3S; meso)- and (3S,3S)-astaxanthin in a 31:49:20 ratio. The plasma astaxanthin concentration-time curves were measured during 76 h. Astaxanthin esters were not detected in plasma. Maximum levels of astaxanthin (C-max=0.28+/-0.1 mg/1) were reached 11.5 h after administration and the plasma astaxanthin elimination half-life was 52+/-40 h. The C-max at the low dose was 0.08 mg/l and showed that, the dose response was non-linear. The (3R,P)-astaxanthin optical isomer accumulated selectively in plasma compared to the (3R,35)- and (3S,3S)-isomers, and comprised 54% of total astaxanthin in the blood and only 31% of total astaxanthin in the administered dose. The astaxanthin Z-isomers were absorbed selectively into plasma and comprised similar to32% of total astaxanthin 6-7.5 h postprandially. The proportion of all-E-astaxanthin was significantly higher in the very low density lipoproteins and chylomicrons (VLDL/CM) plasma lipoprotein fraction than in the high density lipoproteins (HDL) and low density lipoproteins (LDL) fractions (P<0.05). The results indicate that a selective process increase the relative proportion of astaxanthin Z-isomers compared to the all-E-astaxanthin before uptake in blood and that the astaxanthin esters are hydrolyzed selectively during absorption. (C) 2004 Elsevier Inc. All rights reserved.