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

Abstract

Appearance, pharmacokinetics and distribution of astaxanthin all- E-, 9 Z- and 13 Z-geometrical and (3 R,3′ R)-, (3 R,3′ S)- and (3 S,3′ S)-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% 9 Z- and 3.6% 13 Z-astaxanthin, of (3 R,3′ R)-, (3 R,3′ S; meso)- and (3 S,3′ S)-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/l) 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 (3 R,3′ R)-astaxanthin optical isomer accumulated selectively in plasma compared to the (3 R,3′ S)- and (3 S,3′ S)-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 ∼32% 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 denisty 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.