**Eiichi Kotake-Nara and Akihiko Nagao \***

National Food Research Institute, National Agriculture and Food Research Organization, 

2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan; E-Mail: ekotake@affrc.go.jp 

\* Author to whom correspondence should be addressed; E-Mail: nagao@affrc.go.jp; Tel.: +81-29-838-8039; Fax: +81-29-838-7996.

*Received: 1 April 2011; in revised form: 3 June 2011 / Accepted: 7 June 2011 / Published: 10 June 2011* 

**Abstract:** 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 Ά-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. 

**Keywords:** absorption; bioavailability; carotenoid; metabolism; xanthophyll 

## **1. Introduction**

Carotenoids, which are synthesized *de novo* by microorganisms and plants, accumulate in various biological tissues throughout the food chain. More than 700 carotenoids, including the metabolites in animals, are present in nature. Most of the carotenoids contain oxygen functions in the molecules, and these carotenoids are referred to as xanthophylls. In recent years, a great deal of attention has been focused on biological activities of dietary xanthophylls such as lutein, zeaxanthin, Άcryptoxanthin, capsanthin, astaxanthin, and fucoxanthin. 

Lutein is one of the major xanthophylls present in green leafy vegetables. Lutein and zeaxanthin are known to selectively accumulate in the macula of the human retina. They have been thought to work as antioxidants [1,2] and as blue light filters [3] to protect the eyes from such oxidative stresses as cigarette smoking and sunlight exposure, which can lead to age-related macular degeneration and cataracts. Ά-Cryptoxanthin, a major xanthophyll in fruits such as papaya and mandarin orange, was reported to decrease the gene expression of interleukin-1 Ά in mouse macrophage RAW264 cells [4], to promote osteoblastic differentiation of mouse MC3T3 cells [5], and to prevent the decrease of calcium content in the bone of ovariectomized rat [6]. Capsanthin, a major xanthophyll in paprika, was reported to increase high-density lipoprotein (HDL)-cholesterol in rat plasma [7]. 

Astaxanthin and fucoxanthin are abundant in green algae and brown algae, respectively. Numerous studies have reported that astaxanthin has the potential to prevent cancers, diabetes, and inflammatory and cardiovascular diseases [8,9]. Fucoxanthin has been shown to inhibit the growth of various cancer cell lines [10– 14] and chemically induced mouse carcinogenesis [15]. Furthermore, the antiallergic and anti-obese activities of fucoxanthin were recently shown in rodent mast cells [16] and in mice [17], respectively. Neoxanthin, which has a structure similar to that of fucoxanthin, is present in green leafy vegetables. These two xanthophylls have a 5,6-monoepoxide and an allenic bond as the common characteristic functional groups (Figure 1). We found that fucoxanthin and neoxanthin showed the highest inhibitory effect on the proliferation of human prostate cancer cells among the fifteen carotenoids tested [13]. 

**Figure 1.** Chemical structures of various epoxy xanthophylls. The geometrical configuration of neoxanthin in nature was recognized as 9<sup>ȝ</sup>*cis*. 

Thus, the characteristic biological activities of several xanthophylls have attracted a great deal of attention. Although no less than forty carotenoids are ingested from common foods, only six major carotenoids ( Ά-carotene, ΅-carotene, lycopene, Άcryptoxanthin, lutein, and zeaxanthin), their proposed metabolites, and several acyclic carotenes such as phytoene, phytofluene, and Ί-carotene have been found in the plasma of human subjects under usual dietary habits [18,19]. For example, neoxanthin and violaxanthin are ingested together with lutein from green leafy vegetables, but the accumulation of the former two xanthophylls was not confirmed in human plasma [18]. Carotenoids are thought to be selectively absorbed in the human intestine. Moreover, carotenoid accumulations in the biological tissues are known to differ greatly among animal species [20]. However, the mechanisms underlying these phenomena have not been determined. 

After intestinal absorption of dietary carotenoids, conversion from Ά-carotene to vitamin A is well known in animals. In fishes and birds, oxidative and reductive metabolisms of the end group in xanthophylls were also proposed by the identification of the metabolic products, but details as to the mechanism of their metabolic transformation are yet to be elucidated. In mammals, several proposed metabolites of xanthophylls have been detected in the tissues, but the metabolic pathway is still uncertain. It is necessary to reveal the carotenoid metabolism after intestinal absorption in order to elucidate not only the mechanism of the biological activities but also the exact bioavailability. Here, we describe the absorption and metabolism of xanthophylls in mammals. 
