Antioxidant effect of astaxanthin on phospholipid peroxidation in human erythrocytes

Abstract

Phospholipid hydroperoxides (PLOOH) accumulate abnormally in the erythrocytes of dementia patients, and dietary xanthophylls (polar carotenoids such as astaxanthin) are hypothesised to prevent the accumulation. In the present study, we conducted a randomised, double-blind, placebo-controlled human trial to assess the efficacy of 12-week astaxanthin supplementation (6 or 12 mg/d) on both astaxanthin and PLOOH levels in the erythrocytes of thirty middle-aged and senior subjects. After 12 weeks of treatment, erythrocyte astaxanthin concentrations were higher in both the 6 and 12 mg astaxanthin groups than in the placebo group. In contrast, erythrocyte PLOOH concentrations were lower in the astaxanthin groups than in the placebo group. In the plasma, somewhat lower PLOOH levels were found after astaxanthin treatment. These results suggest that astaxanthin supplementation results in improved erythrocyte antioxidant status and decreased PLOOH levels, which may contribute to the prevention of dementia. Key words: Astaxanthin: Phospholipid hydroperoxides: Erythrocytes: DementiaWe have previously confirmed that higher levels of phospholipid hydroperoxides (PLOOH), the primary oxidation products of phospholipids (PL) (1,2) , accumulate abnormally in the erythrocytes of dementia patients (3) . Such erythrocytes with high levels of lipid hydroperoxides have been postulated to have a decreased ability to transport oxygen to the brain, which may impair blood rheology, thus facilitating dementia (4 -8) . Recently, we have developed an HPLC method to determine erythrocyte carotenoid content (9) . Using this method, we gathered evidence that accumulation of polar oxygenated carotenoids (xanthophylls) occurs predominantly in human erythrocytes (9) , and that a decrease in xanthophylls and an increase in PLOOH levels in erythrocytes correlate with the severity of dementia (10) . These findings led to the hypothesis that xanthophyll supplementation may minimise the accumulation of erythrocyte PLOOH, and that xanthophylls could be used therapeutically as drugs or functional foods to prevent the disease. Although there is still scarce information on whether orally administered xanthophylls are distributed to human erythrocytes and actually inhibit erythrocyte PLOOH formation, our recent human study has revealed antioxidant properties of the xanthophyll lutein towards erythrocyte PLOOH formation (11) . Animal studies have also supported this hypothesis (12,13) .Among xanthophylls, astaxanthin has recently received attention for its potent antioxidant activity (14,15) . Astaxanthin is naturally synthesised by plants and algae, and is now commercially available as a food supplement from Haematococcus alga (16) . The recommended daily intake is estimated to be 1 -12 mg/d; however, there is not much information regarding the bioavailability of astaxanthin in humans. To the best of our knowledge, the occurrence and antioxidant roles of astaxanthin in human erythrocytes have not been reported.In this investigation of whether admini...

Kinetics of plasma and erythrocyte-astaxanthin in healthy subjects following a single and maintenance oral dose

“…The median percentage astaxanthin found in RBC throughout the 17 days maintenance dose (with the plasma concentration set at 100%) was 49% (range of individual medians: 28-71%). This value is in agreement with the median of 44% (range of individual medians: 26-56%) of the study group throughout the 72 h observation period following the single 40 mg dose (see above), and comparable to the median of 43% (range: 35-48%) that we estimated from the data from Nakagawa et al 9 Large intra-and inter-individual variations were observed for plasma-and RBC-astaxanthin, notably for the latter, during the 17 days supplementation period. This may be partly due to the low dose compared with the background intakes (from food).…”

“…The median percentage astaxanthin found in RBC throughout the 72 h observation period (with the plasma concentration set at 100%) amounted to 44% (range of individual medians: 26-56%). These RBC-plasma ratios, subject to a large variation, are comparable to the median of 43% (range: 35-48%) that we estimated from the data from Nakagawa et al 9 who supplemented healthy adults with 6 and 12 mg oral astaxanthin/day for 12 weeks.…”

“…8 Orally administered astaxanthin incorporates into both plasma and erythrocytes (red blood cell [RBC]) of healthy subjects, improves RBC antioxidant status and decreases membrane phospholipid peroxidation after a 12-week daily supplementation. 9 Following its ingestion, astaxanthin has been shown to reach a peak in plasma at about 7 h and to decline with a median half-life of about 21 h. 10 The kinetics of astaxanthin in RBC are currently unknown. We investigated the kinetics of astaxanthin in both plasma and RBC after a single oral 40 mg dose and its distribution in both compartments during a 17-day 8 mg/day maintenance dose.…”

Erythrocytes Carotenoids after Astaxanthin Supplementation in Middle-Aged and Senior Japanese Subjects

“…Supplementation of astaxanthin for 12 weeks 12 mg/day also resulted in a signifi cant decrease in erythrocyte phospholipid hydroperoxide PLOOH concentrations in senior subjects 7 .…”

“…Little is known regarding the bioavailability of astaxanthin in humans, especially for Japanese middleaged and senior subjects. Recently, we conducted a randomized, double-blind human trial to assess the effi cacy of 12-week astaxanthin supplementation 6 or 12 mg/day 7 .…”