Metabolism of Carotenoids in Mammals.

Pathways for xanthophyll metabolism have been proposed on the basis of several oxidation products of dietary xanthophylls detected in the tissues of fish, birds, and human subjects. No enzyme reaction had been characterized as responsible for the pathways until a mouse liver homogenate was found to oxidize the 3-hydroxy β-end of xanthophylls to a 3-oxo ε-end in the presence of a cofactor, NAD. This oxidation consists of dehydrogenation to an unstable intermediate having a 3-oxo β-end group and the subsequent migration of a double bond.

3'-hydroxy-ε,ε-caroten-3-one inhibits the differentiation of 3T3-L1 cells to adipocytes.

An oxidative metabolite of lutein, 3'-hydroxy-ε,ε-caroten-3-one, inhibited the differentiation of 3T3-L1 cells to adipocytes and the subsequent triacylglycerol production, but lutein did not. The α,β-unsaturated carbonyl structure of 3'-hydroxy-ε,ε-caroten-3-one was considered to participate in the inhibitory effect, suggesting that this lutein metabolite has the potential to prevent metabolic syndrome.

Lysoglyceroglycolipids Improve the Intestinal Absorption of Micellar Fucoxanthin by Caco-2 Cells.

To improve the intestinal absorption of fucoxanthin, we evaluated the effects of dietary glyceroglycolipids on the uptake and secretion of fucoxanthin solubilized in mixed micelles by human intestinal Caco-2 cells. Although digalactosyldiacylglycerol and sulfoquinovosyldiacylglycerol suppressed fucoxanthin uptake and secretion, their lyso-types, digalactosylmonoacylglycerol and sulfoquinovosylmonoa cylglycerol, remarkably enhanced them. Thus, some dietary glyceroglycolipids may be potential enhancers of fucoxanthin bioavailability in humans.

Glyceroglycolipids Affect Uptake of Carotenoids Solubilized in Mixed Micelles by Human Intestinal Caco-2 Cells.

We previously reported that phospholipids markedly affected the uptake of carotenoids solubilized in mixed micelles by human intestinal Caco-2 cells. In the present study, we found that two classes of dietary glyceroglycolipids and the corresponding lysoglyceroglycolipids affected uptake of β-carotene and lutein by differentiated Caco-2 cells. The levels of carotenoid uptake from micelles containing digalactosyldiacylglycerol or sulfoquinovosyldiacylglycerol were significantly lower than that from control micelles.

A 3-hydroxy β-end group in xanthophylls is preferentially oxidized to a 3-oxo ε-end group in mammals.

We previously found that mice fed lutein accumulated its oxidative metabolites (3'-hydroxy-ε,ε-caroten-3-one and ε,ε-carotene-3,3'-dione) as major carotenoids, suggesting that mammals can convert xanthophylls to keto-carotenoids by the oxidation of hydroxyl groups. Here we elucidated the metabolic activities of mouse liver for several xanthophylls. When lutein was incubated with liver postmitochondrial fraction in the presence of NAD(+), (3'R,6'R)-3'-hydroxy-β,ε-caroten-3-one and (6RS,3'R,6'R)-3'-hydroxy-ε,ε-caroten-3-one were produced as major oxidation products.

Effects of fats and oils on the bioaccessibility of carotenoids and vitamin E in vegetables.

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.

Effects of mixed micellar lipids on carotenoid uptake by human intestinal Caco-2 cells.

We reported previously that lysophosphatidylcholine remarkably enhanced β-carotene uptake from bile acid-mixed micelles by human intestinal Caco-2 cells. In the present study, we evaluated how mixed micelle components other than phospholipids, viz., fatty acids, monoolein, and cholesterol, affect carotenoid uptake by Caco-2 cells.

Absorption and metabolism of xanthophylls.

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.

Absorption and metabolism of dietary carotenoids.

A number of carotenoids with diverse structures are present in foods and have beneficial effects on human health due to their common antioxidant activity and their respective biological activities. The major carotenoids found in human tissues, however, are limited to several including such as β-carotene, lycopene, and lutein. We have little knowledge of whether carotenoids are selectively absorbed in intestine and metabolized discriminately in the body.

Keto-carotenoids are the major metabolites of dietary lutein and fucoxanthin in mouse tissues.

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.

Effect of glycerophospholipid class on the beta-carotene uptake by human intestinal Caco-2 cells.

The effects were evaluated of various glycerophospholipids on the uptake of beta-carotene solubilized in mixed micelles by human intestinal Caco-2 cells. Phosphatidylethanolamine markedly enhanced the transfer of beta-carotene from the micelles to the cells, whereas phosphatidylcholine suppressed it. All the lysoglycerophospholipids enhanced the transfer, irrespective of the polar head group.

Absorption and function of dietary carotenoids.

Carotenoids are highly hydrophobic pigments with yellow to red color and their major dietary sources are fruits and vegetables. They have an essential physiological function as a vitamin A precursor and also have antioxidant, anticancer, immune enhancement and antiobesity activities related to prevention of degenerative diseases. The release of carotenoids from food matrix, their dispersion within the digestive tract, and their solubilization in mixed micelles are important steps for carotenoid bioaccessibility.

Soluble fibers inhibit carotenoid micellization in vitro and uptake by Caco-2 cells.

We evaluated the effects of soluble fibers on beta-carotene and lutein micellization during simulated digestion in vitro, and on carotenoid uptake from mixed micelles by Caco-2 cells. Medium- and high-viscosity alginates and pectins inhibited carotenoid micellization and cellular uptake relative to the fiber-free control. Alginates, carboxy-methylcelluloses, and methylcelluloses inhibited beta-carotene uptake mainly by increasing medium viscosity, but pectins might inhibit carotenoid uptake by additional mechanisms.

Esterification of xanthophylls by human intestinal Caco-2 cells.

We recently found that peridinin, which is uniquely present in dinoflagellates, reduced cell viability by inducing apoptosis in human colon cancer cells. Peridinin is also found in edible clams and oysters because the major food sources of those shellfish are phytoplanktons such as dinoflagellates. Little is known, however, about the fate of dietary peridinin and its biological activities in mammals.

Low bioavailability of dietary epoxyxanthophylls in humans.

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.

Induction of apoptosis in DLD-1 human colon cancer cells by peridinin isolated from the dinoflagellate, Heterocapsa triquetra.

Peridinin, which is uniquely present in dinoflagellates, is one of the most abundant carotenoids found in nature. We evaluated the apoptotic effect of peridinin on DLD-1 human colorectal cancer cells. Peridinin significantly reduced the cell viability in a dose-dependent manner (0-20 microM) and induced apoptosis by activating both caspase-8 and caspase-9.

Intestinal absorption of dietary carotenoids.

The assessment of carotenoid bioavailability has long been hampered by the limited knowledge of their absorption mechanisms. However, recent reports have elucidated important aspects of carotenoid digestion and absorption. Disruption of food matrix and increasing amounts of fat seem to enhance the absorption of carotenes to a larger extent than that of xanthophylls.

A highly polar xanthophyll of 9'-cis-neoxanthin induces apoptosis in HCT116 human colon cancer cells through mitochondrial dysfunction.

Highly polar xanthophylls of 9'-cis-neoxanthin (neoxanthin) and fucoxanthin, which have the characteristic structure of an epoxy group and an allenic bond, were previously found to induce apoptosis in human prostate cancer cells. In the present study, we found apoptosis induction by neoxanthin in HCT116 human colon cancer cells and examined the induction mechanism. The cells exposed to 20 microM neoxanthin clearly showed chromatin condensation, DNA fragmentation, and an increase in hypodiploid cells.

Acyl moieties modulate the effects of phospholipids on beta-carotene uptake by Caco-2 cells.

The intestinal absorption of carotenoids is thought to be mediated by the carotenoid assembly in mixed micelles, followed by its transfer into the enterocytes and subsequent secretion to the lymph as chylomicron particles. In the present study we investigated the effects of phospholipids and lysophospholipids with diverse fatty acyl moieties on the uptake of beta-carotene solubilized in mixed micelles by Caco-2 cells. Compared with phospholipid-free mixed micelles (NoPL), those containing long-chain PC inhibited beta-carotene uptake (16:0,18:1-PC approximately equal to 16:0,18:2-PC < 14:0,14:0-PC approximately equal to 16:0, 14:0-PC < 16:0,16:0-PC < NoPL).

The homeostasis model assessment-insulin resistance index is inversely associated with serum carotenoids in non-diabetic subjects.

Background: Carotenoids may reduce the risk for diabetes mellitus, but little is known about the association of insulin resistance with serum carotenoids in non-diabetic subjects. This study aimed to investigate whether the homeostasis model assessment-insulin resistance (HOMA-IR) index would be lower in the presence of high serum carotenoid concentrations in non-diabetic subjects.

Methods: A total of 812 subjects (256 males and 556 females) who had received health examinations in 2003 participated in the study.

High serum carotenoids are inversely associated with serum gamma-glutamyltransferase in alcohol drinkers within normal liver function.

Background: Many studies have reported that the consumption of alcohol induces the generation of free radicals. Moreover, recent studies suggest that serum gamma-glutamyltransferase (gamma-GTP) within its normal range might be an early marker of oxidative stress. In this study, we tested the hypothesis that serum antioxidant carotenoids would be inversely associated with serum gamma-GTP in alcohol drinkers within normal liver function.

Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice.

A series of crocetin glycosides (crocins) are the main pigment of the stigmas of saffron (Crocussativus L.) and the fruits of gardenia (Gardenia jasminoides Ellis). Although numerous studies have demonstrated that crocetin and crocins have a variety of biological functions, the metabolism of dietary crocetin and crocins remains unknown.

Serum carotenoid concentrations are inversely associated with serum aminotransferases in hyperglycemic subjects.

Hyperglycemia increases the generation of free radicals by glucose auto-oxidation, and the increment of free radicals may lead to liver cell damage. In this study, we tested the hypothesis that hyperglycemia-induced increases of serum liver enzymes among its physiological concentration would be inversely associated with serum antioxidant carotenoid level. Study subjects were 857 male and female Japanese who had received health examinations in 2003.

Seasonal changes in the relationship between serum concentration of beta-cryptoxanthin and serum lipid levels.

Beta-cryptoxanthin (beta-CRX) is a carotenoid pigment found especially in Satsuma mandarin (Citrus unshiu Marc.) fruit, which is mainly produced in Japan. Previously, we found that serum beta-CRX concentrations rose to extreme levels as the frequency of consumption of Satsuma mandarin increases.

Neoxanthin and fucoxanthin induce apoptosis in PC-3 human prostate cancer cells.

Neoxanthin and fucoxanthin, which have the characteristic structure of 5,6-monoepoxide and an allenic bond, were previously found to reduce the viability of human prostate cancer cells most intensively among 15 dietary carotenoids tested. In the present study, the induction of apoptosis in PC-3 cells by these two carotenoids was characterized by morphological changes, DNA fragmentation, an increased percentage of hypodiploid cells, and cleavages of caspase-3 and PARP. The ratio of apoptotic cells reached more than 30% after treatment for 48 h with 20 microM carotenoids.