Dietary carotenoids, especially xanthophylls, have attracted significant attention because of their characteristic biological activities, including anti-allergic, anti-cancer, and anti-obese actions. Although no less than forty carotenoids are ingested under usual dietary habits, only six carotenoids and their metabolites have been found in human tissues, suggesting selectivity in the intestinal absorption of carotenoids. Recently, facilitated diffusion in addition to simple diffusion has been reported to mediate the intestinal absorption of carotenoids in mammals. The selective absorption of carotenoids may be caused by uptake to the intestinal epithelia by the facilitated diffusion and an unknown excretion to intestinal lumen. It is well known that β-carotene can be metabolized to vitamin A after intestinal absorption of carotenoids, but little is known about the metabolic transformation of non provitamin A xanthophylls. The enzymatic oxidation of the secondary hydroxyl group leading to keto-carotenoids would occur as a common pathway of xanthophyll metabolism in mammals. This paper reviews the absorption and metabolism of xanthophylls by introducing recent advances in this field.

Epoxyxanthophylls (epoxide-containing xanthophylls), a group of carotenoids, are ubiquitously distributed in edible plants. Among them, neoxanthin in green leafy vegetables and fucoxanthin in brown algae have been reported to exhibit an antiproliferative effect on several human cancer cells in vitro. However, there is little information about the intestinal absorption and metabolic fate of dietary epoxyxanthophylls in humans. To estimate the intestinal absorption of neoxanthin and fucoxanthin in humans, we evaluated the plasma epoxyxanthophyll concentrations before and after 1-week dietary interventions with spinach (Spinacia oleracea) and wakame (Undaria pinnatifida). The epoxyxanthophylls and their metabolites in the plasma extracts were determined by HPLC after partial purification and concentration with solid-phase extraction cartridges. Even after 1 week of spinach intake (3·0 mg neoxanthin/d), the plasma concentrations of neoxanthin and its metabolites (neochrome stereoisomers) remained very low (about 1 nmol/l), whereas those of β-carotene and lutein were markedly increased. Similarly, the plasma concentration of fucoxanthinol, a gastrointestinal metabolite of fucoxanthin, was < 1 nmol/l after 1 week of wakame intake (6·1 mg fucoxanthin/d). These results indicated that the plasma response to dietary epoxyxanthophylls was very low in humans even after 1-week intake of epoxyxanthophyll-rich diets.

The low bioavailability of lipophilic micronutrients is mainly caused by their limited solubilization to an aqueous micelle, which hinders their ability to be taken up by the intestines. Bioaccessibility is the ratio of the solubilized portion to the whole amount ingested. We evaluated in this study the effects of individual fats and oils and their constituents on the bioaccessibility of carotenoids and vitamin E in vegetables by simulated digestion. Various fats and oils and long-chain triacylglycerols enhanced the bioaccessibility of β-carotene present in spinach, but not of lutein and α-tocopherol, which are less hydrophobic than β-carotene. Free fatty acid, monoacylglycerol, and diacylglycerol also enhanced the bioaccessibility of β-carotene present in spinach. In addition to the long-chain triacylglycerols, their hydrolyzates formed during digestion would facilitate the dispersion and solubilization of β-carotene into mixed micelles. Dietary fats and oils would therefore enhance the bioaccessibility of hydrophobic carotenes present in vegetables.

Fucoxanthin, a xanthophyll present in brown algae consumed in Eastern Asia, can suppress carcinogenesis and obesity in rodents. We investigated the metabolism, tissue distribution, and depletion of fucoxanthin in ICR mice by comparison with those of lutein. The experiments comprised 14-d dietary supplementation with lutein esters or fucoxanthin, followed by 41- or 28-d, respectively, depletion periods with carotenoid-free diets. After lutein ester supplementation, 3′-hydroxy-ε,ε-caroten-3-one and lutein were the predominant carotenoids in plasma and tissues, accompanied by ε,ε-carotene-3,3′-dione. The presence of these keto-carotenoids in mouse tissues is reported here for the first time, to our knowledge. Lutein and its metabolites accumulated most in the liver (7.51 μmol/kg), followed by plasma (2.11 μmol/L), adipose tissues (1.01–1.44 μmol/kg), and kidney (0.87 μmol/kg). The half-life of the depletion (t_1/2) of lutein metabolites varied as follows: plasma (1.16 d) < liver (2.63 d) < kidney (4.44 d) < < < adipose tissues (>41 d). Fucoxanthinol and amarouciaxanthin A were the main metabolites in mice fed fucoxanthin and partitioned more into adipose tissues (3.13–3.64 μmol/kg) than into plasma, liver, and kidney (1.29–1.80 μmol/kg). Fucoxanthin metabolites had shorter t_1/2 in plasma, liver, and kidneys (0.92–1.23 d) compared with those of adipose tissues (2.76–4.81 d). The tissue distribution of lutein and fucoxanthin metabolites was not associated with their lipophilicity, but depletion seemed to be slower for more lipophilic compounds. We concluded that mice actively convert lutein and fucoxanthin to keto-carotenoids by oxidizing the secondary hydroxyl groups and accumulate them in tissues.