The pharmacokinetics of dietary fucoxanthin, one of the xanthophylls in brown sea algae, is little understood. In the present study, mice were orally administered fucoxanthin, and the distribution and accumulation of fucoxanthin and its metabolites fucoxanthinol and amarouciaxanthin A were measured in the plasma, erythrocytes, liver, lung, kidney, heart, spleen and adipose tissue. In a single oral administration of 160 nmol fucoxanthin, fucoxanthinol and amarouciaxanthin A were detectable in all specimens tested in the present study, but fucoxanthin was not. The time at maximum concentration (T max ) of these metabolites in adipose tissue was 24 h, while the T max in the others was 4 h. The area under the curve to infinity (AUC 1 ) of fucoxanthinol in the liver was the highest value (4680 nmol/g £ h) among the tissues tested in the present study, while the AUC 1 of amarouciaxanthin A in adipose tissue was the highest value (4630 nmol/g £ h). In daily oral administration of 160 nmol fucoxanthin for 1 week, fucoxanthin was also detectable in the tissues even at a low concentration. The amount of fucoxanthinol was 123 nmol/g in the heart and 85·2 nmol/g in the liver. Amarouciaxanthin A in the adipose tissue was distributed at a concentration of 97·5 nmol/g. These results demonstrate that dietary fucoxanthin accumulates in the heart and liver as fucoxanthinol and in adipose tissue as amarouciaxanthin A. Fucoxanthin: Fucoxanthinol: Amarouciaxanthin A: MiceBrown algae are a traditional foodstuff of East Asians, and an epidemiological study (1) has shown that the consumption of brown sea algae is associated with a low risk of breast cancer. Brown alga powders or extracts have been reported to suppress chemical-induced carcinogenesis in animals (2 -5) . Fucoxanthin is one of the xanthophylls found in brown algae such as kombu (Laminaria japonica), hijiki (Sargassum fusiforme) and wakame (Undaria pinnatifida) (6) . The oral administration of fucoxanthin prevented carcinogenesis in several animal models (7,8) . Recent studies with cancer cell lines have suggested that the suppressive effect is due to the inhibitory effect of fucoxanthin on cell proliferation through the induction of apoptosis (9,10) and cell cycle arrest (11) . In addition to these activities, the compound also has anti-inflammatory and anti-obesity activities (12,13) . Interestingly, a recent study showed that dietary fucoxanthin stimulates the expression of uncoupling protein 1 in the mitochondria of white adipose tissue and facilitates the consumption of fats in rats (14) . Thus, fucoxanthin has various physiological activities and contributes to the beneficial effects of brown algae.Many studies (15 -20) have reported the metabolism of hydrocarbon carotenoids such as a-carotene and b-carotene; these carotenoids are absorbed in the small intestine and then converted to vitamin A. However, information on the metabolism of non-provitamin A-type carotenoids is insufficient to explain their bioavailability and safety, although some xanthophylls such as a...

Dietary fucoxanthin has been reported to exert several physiological functions, and fucoxanthinol is considered to be the primary active metabolite of fucoxanthin. However, there is no information about the pharmacokinetics of fucoxanthinol in human subjects. In the present study, eighteen human volunteers were orally administered kombu extract containing 31 mg fucoxanthin, and their peripheral blood was collected 5 min before and 0·5, 1, 2, 4, 8 and 24 h after the treatment. Plasma fucoxanthinol concentrations were measured by HPLC, and the pharmacokinetics of fucoxanthinol were as follows: maximum concentration, 44·2 nmol/l; time at maximum concentration, 4 h; terminal half-time, 7·0 h; area under the curve (AUC) for 1 -24 h, 578·7 nmol/l £ h; AUC (1) , 663·7 nmol/l £ h. In addition to fucoxanthinol, we also attempted to detect amarouciaxanthin A, a hepatic metabolite of fucoxanthinol, using HPLC, but it was not present in the volunteers' plasma. On the other hand, a peak that was suspected to represent the cis-isomer of fucoxanthinol was found in the HPLC chromatogram. By comparing the present results with those of a previous study using mice, we found that the bioavailability and metabolism of fucoxanthinol differ between human subjects and mice.

Fucoxanthin exhibits a preventative function with degenerative diseases such as cancer and metabolic syndrome without side effects. Therefore, commercial-scale preparation of fucoxanthin is needed, but it has been very difficult to find the required resources to do so. The aim of this study is to develop a preparation method of fucoxanthin using waste parts of cultured kombu (Laminalia japonica). Around 79,000 t of cultured kombu is discarded in Japan during thinning out and forming processes, which includes a high amount of fucoxanthin (21.3-17.8 mg/100 g fresh weight). Waste parts of kombu were examined to obtain better quality fucoxanthin. Heating increased fucoxanthin recovery, and additional washing with tap water reduced the salt content of the fucoxanthin extract. Cutting waste parts of kombu into 5-mm wide strips made extraction easier without the leakage of fucoxanthin during handling. After freezing and transportation to the extraction factory, kombu showed the best recovery of fucoxanthin and the lowest content of salt following two extractions with 3 volumes of absolute ethanol. To remove chlorophylls the extract was subjected to silica gel column chromatography. Finally, 1490 g fucoxanthin was obtained from 10 t of waste parts of kombu and the recovery ratio was 82%. The fucoxanthin obtained was stable and reduced by only 2% in 6 months storage at 4℃. Thus, waste parts of cultured kombu are a good bioresource for fucoxanthin extraction.