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...