**2.3. Astaxanthin**

Astaxanthin is a xanthophyll (C40H52O4 ) that is principally responsible for the dark-red color in various microalgae and marine animals [1, 72]. Astaxanthin shows an especially strong antioxidant activity among carotenoids [6] and can significantly reduce the risk of cancer, eye disease, and cardiovascular disease [73, 74]. For instance, astaxanthin protected mice from carcinogenesis of the urinary bladder by reducing the incidence of chemically induced bladder carcinoma and further, astaxanthin supplementation in rats inhibited the stress-induced suppression of tumor-fighting natural killer cells [73]. In addition, astaxanthin is frequently used as an animal and fish feed additive to improve their body colors [75]. Data from several studies have demonstrated that the bioavailability and antioxidant activity of astaxanthin were changed by *Z*-isomerization.

In terms of the bioavailability, an *in vitro* test using a simulated digestion model and human intestinal Caco-2 cells [76] and human oral-dosing studies [16, 77] have shown that *Z*-isomers have higher bioavailability than the all-*E*-isomer. For example, Yang et al. [76] reported that (13*Z*)-astaxanthin showed higher bioaccessibility than (9*Z*)- and (all-*E*)-astaxanthins using an *in vitro*-digestion model, and (9*Z*)-astaxanthin exhibited higher cellular-transport efficiency than (all-*E*)- and (13*Z*)-astaxanthin in Caco-2 cell monolayers. However, oral-dosing studies in rainbow trout (*Oncorhynchus mykiss*) have shown a "negative" effect of astaxanthin *Z*-isomerization on bioavailability [78, 79]. These results suggest that the bioavailability of carotenoid isomers differs among species. Thus, future studies should seek to establish the biochemical basis for species-specific differences in the utilization of carotenoid isomers.

Although the antioxidant activity measured depends on the assay method employed, many studies have shown "positive" effects. Namely, assay that measure antioxidant enzyme activities, DPPH radical scavenging, oxygen radical-absorption capacity (ORAC), photochemiluminescence (PLC) and peroxidation have shown higher antioxidant activities of astaxanthin *Z*-isomers than detected for the all-*E*-isomer [76, 80, 81]. In contrast, when the antioxidant activity was evaluated by a cellular antioxidant activity (CAA) assay, the order of the antioxidant activity was 13*Z*-isomer > all-*E*-isomer > 9*Z*-isomer [81]. The results of these studies suggest that *Z*-isomers of astaxanthin, especially the 13*Z*-isomer, have higher antioxidant activity than the all-*E*-isomer.

Most investigators have concluded that "positive" effects on the bioavailability and antioxidant activity occurred following astaxanthin *Z*-isomerization. Thus, the ingestion of astaxanthin *Z*-isomers could be effective in these terms. As with other carotenoids, *Z*-isomers of astaxanthin could be obtained by heating [81, 82] and catalytic treatment [76, 81, 83] of the all-*E*-isomer.

#### **2.4. Canthaxanthin**

[59, 60] than the all-*E*-isomer. On the other hand, there are other "negative" effects. Namely, β-carotene is a very important retinol precursor with a high conversion rate. The (all-*E*)- and (9*Z*)-β-carotene can be metabolized respectively to (all-*E*)-retinoic acid and (9*Z*)-retinoic acid [61, 62], both of which are active in gene regulation [63, 64]. However, the rates of cleavage of β-carotene isomers to vitamin A and the composition of the respective isomer metabolites vary, that is, (all-*E*)-β-carotene was the preferred substrate for cleavage to vitamin A when

Regarding β-carotene, considering that "positive" and "negative" effects are associated with *Z*-isomerization, it is considered important to use them properly depending on the situation. Besides, as the *Z*-isomerization method for (all-*E*)-β-carotene, heating [67, 68], light irradiation with photosensitizers [69], and catalytic treatment [70, 71] were well documented. Moreover, *Dunaliella salina* and *Dunaliella bardawil*, which contain a large amount of (9*Z*)-β-carotene,

in various microalgae and marine animals [1, 72]. Astaxanthin shows an especially strong antioxidant activity among carotenoids [6] and can significantly reduce the risk of cancer, eye disease, and cardiovascular disease [73, 74]. For instance, astaxanthin protected mice from carcinogenesis of the urinary bladder by reducing the incidence of chemically induced bladder carcinoma and further, astaxanthin supplementation in rats inhibited the stress-induced suppression of tumor-fighting natural killer cells [73]. In addition, astaxanthin is frequently used as an animal and fish feed additive to improve their body colors [75]. Data from several studies have demonstrated that the bioavailability and antioxidant activity of astaxanthin

In terms of the bioavailability, an *in vitro* test using a simulated digestion model and human intestinal Caco-2 cells [76] and human oral-dosing studies [16, 77] have shown that *Z*-isomers have higher bioavailability than the all-*E*-isomer. For example, Yang et al. [76] reported that (13*Z*)-astaxanthin showed higher bioaccessibility than (9*Z*)- and (all-*E*)-astaxanthins using an *in vitro*-digestion model, and (9*Z*)-astaxanthin exhibited higher cellular-transport efficiency than (all-*E*)- and (13*Z*)-astaxanthin in Caco-2 cell monolayers. However, oral-dosing studies in rainbow trout (*Oncorhynchus mykiss*) have shown a "negative" effect of astaxanthin *Z*-isomerization on bioavailability [78, 79]. These results suggest that the bioavailability of carotenoid isomers differs among species. Thus, future studies should seek to establish the biochemical basis for species-specific differences in the utilization of carotenoid isomers.

Although the antioxidant activity measured depends on the assay method employed, many studies have shown "positive" effects. Namely, assay that measure antioxidant enzyme activities, DPPH radical scavenging, oxygen radical-absorption capacity (ORAC), photochemiluminescence (PLC) and peroxidation have shown higher antioxidant activities of astaxanthin *Z*-isomers than detected for the all-*E*-isomer [76, 80, 81]. In contrast, when the antioxidant activity was evaluated by a cellular antioxidant activity (CAA) assay, the order of

) that is principally responsible for the dark-red color

compared with the *Z*-isomers [61, 65, 66].

Astaxanthin is a xanthophyll (C40H52O4

were changed by *Z*-isomerization.

**2.3. Astaxanthin**

144 Progress in Carotenoid Research

have been used as *Z*-isomer-rich materials [43–48].

Canthaxanthin is a xanthophyll (C40H52O2 ) that is principally responsible for the orangepink color found abundantly in egg yolk and various microbes such as *Bradyrhizobium* sp. and *Halobacterium* sp. [84, 85]. Canthaxanthin can significantly reduce the risk of cancer and neurodegenerative disorder [86, 87] and shows strong antioxidant activity [88], that is, canthaxanthin administration decreased mammary tumor volumes in mice [86] and exhibited antiinflammatory activities by increasing the activity of GPX and catalase, thereby reducing the production of IL-1, IL-6, and TNF-α [87]. Furthermore, canthaxanthin is widely used as feed for hens and fish to improve the egg yolk color and the body color, respectively [84, 89]. A few reports have shown the effect of canthaxanthin *Z*-isomerization on antioxidant activity and functionality. Venugopalan et al. [88] reported that (9*Z*)-canthaxanthin isolated from *Dietzia* sp. had higher antioxidant activity, as evaluated by performing DPPH radicalscavenging assay, superoxide radical-scavenging assay and fluorescence assay to detect reactive oxygen species generated in THP-1 cells. Moreover, the (9*Z*)-isomer exhibited higher pro-apoptotic activity than the all-*E*-isomer, which was evaluated in THP-1 macrophages [90]. The above literature indicates that *Z*-isomerization of canthaxanthin has "positive" effects. Canthaxanthin *Z*-isomerization can be achieved by heating and catalytic treatment [91, 92], and *Dietzia* sp. can serve as a source of (9*Z*)-canthaxanthin [88, 89].

#### **2.5. Fucoxanthin**

Fucoxanthin is an allenic xanthophyll (C42H58O6 ) that is found abundantly in edible shellfish and brown seaweeds such as *Mactra chinensis* and *Undaria pinnatifida* [1, 93]. Fucoxanthin has high antioxidant capacity [94] and shows anticancer and antiangiogenic activities [95, 96]. For example, fucoxanthin remarkably reduced the viability of human colon cancer cell lines, such as Caco-2, HT-29, and DLD-1 cells [95]. In addition, fucoxanthin has antiobesity and antidiabetic effects [97–99], for example, administration of Wakame (*Undaria pinnatifida*) (which is rich in fucoxanthin) significantly suppressed body weight and white adipose tissue weight gain induced by the high fat diet in an obese murine model [98], which has attracted much attention recently in the food industry. The *Z*-isomerization of (all-*E*)-fucoxanthin can induce changes in the antioxidant and anticancer activities. Namely, Zhang et al. [19] reported that when the antioxidant activity of fucoxanthin isomers was evaluated by performing DPPH radical-scavenging and superoxide-detection assay, the following relative activities were observed: 13*Z*-isomer ≈ 13′*Z*-isomer > all-*E*-isomer > 9′*Z*-isomer. Evaluation by performing 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydroxyl radical-scavenging assay revealed the following relative activities: 9′*Z*-isomer > all-*E*-isomer >13*Z*-isomer ≈ 13′*Z*-isomer. Moreover, Kawee-ai et al. [100] showed that when the ratio of the *Z*-isomer of fucoxanthin increased by 2% from 11 to 13% by heating, the scavenging activities against DPPH, hydrogen peroxide, and superoxide anions, and the reducing power decreased by 21.0, 10.3, 16.0 and 19.7%, respectively. Hence, it is considered that the *Z*-isomerization of fucoxanthin negatively affects the antioxidant activity. However, Nakazawa et al. [13] demonstrated that *Z*-isomers of fucoxanthin had higher anticancer activity than the all-*E*-isomer, as evaluated by measuring the potent inhibitory effects on human promyelocytic leukemia cells (HL-60) and colon cancer cells (Caco-2). To the best of our knowledge, only fucoxanthin was investigated in terms of the effect of *Z*-isomerization on anticancer activity. Thus, it is expected that such investigation will extend to other carotenoids in the future. *Z*-isomerization of (all-*E*)-fucoxanthin has been achieved by heating and light irradiation [100, 101].

**Carotenoid Evaluation Overview of results Effect\* Reference**

micelles and lymph-cannulated ferrets

*Z*-Isomers > all-*E*-isomer, evaluated using a diffusion

*Z*-Isomers > all-*E*-isomer, evaluated using bile acid

*Z*-Isomers > all-*E*-isomer, evaluated in human oral-dosing

*Z*-Isomers > all-*E*-isomer, evaluated in PSC and MbFeIII-LP

All-*E*-isomer ≈ *Z*-isomers, evaluated in TEAC and FRAP

13′*Z*-Isomer > all-*E*-isomer ≈ 9′*Z*-isomer > 9*Z*-isomer ≈

All-*E*-isomer > *Z*-isomers, evaluated in Caco-2 cells, HSC-

All-*E*-isomer > *Z*-isomers, evaluated in ferret oral-dosing

All-*E*-isomer > *Z*-isomers, evaluated in gerbil oral-dosing

All-*E*-isomer > 9*Z*-isomer, evaluated in human oral-dosing

9*Z*-Isomer > all-*E*-isomer, evaluated in the small intestines

9*Z*-Isomer > all-*E*-isomer, evaluated by measuring the

9*Z*-Isomer > all-*E*-isomer, evaluated by determining the

All-*E*-isomer > 9*Z*-isomer, evaluated by measuring LDL

All-*E*-isomer ≈ 9*Z*-isomer ≈ 13*Z*-isomer ≈ 15*Z*-isomer,

All-*E*-isomer ≈ 9*Z*-isomer ≈ 13*Z*-isomer > 15*Z*-isomer,

9*Z*-Isomer > all-*E*-isomer, evaluated in female LDLR−/−

9*Z*-Isomer > all-*E*-isomer, evaluated in Caco-2 cells + [52]

9*Z*-Isomer > all-*E*-isomer, evaluated in rat oral-dosing tests + [55]

9*Z*-Isomer > all-*E*-isomer, evaluated in knockout mice + [58]

13*Z*-isomer, evaluated in TEAC assay

T6 cells, and rat liver microsomes

sensitivity to external oxidants

antiperoxidative activity

evaluated in TEAC assay

and apoE-deficient mice

evaluated in TEAC and PSC assay

*Z*-Isomers > all-*E*-isomer, evaluated in Caco-2 cells + [23]

Effects of *Z*-Isomerization on the Bioavailability and Functionality of Carotenoids: A Review

*Z*-Isomers > all-*E*-isomer, evaluated in TEAC assay + [10]

+ [20]

http://dx.doi.org/10.5772/intechopen.78309

+ [21, 22]

147

+ [12, 24–26]

+ [11]

± [11]

± [10]

− [14]

− [41]

− [42]

+ [53]

+ [54]

+ 18

− [17]

− [10]

− [56,57]

+ [59, 60]

− [43–48]

Lycopene Bioavailability/

α-Carotene Antioxidant

β-Carotene Bioavailability/

activity

bioaccessibility

Antioxidant activity

Atherogenesis activity

Atherosclerosis activity

bioaccessibility

Antioxidant activity

model

tests

assay

assay

test

test

tests

of ferrets

oxidation

#### **2.6. Lutein**

Lutein is a xanthophyll (C40H56O2 ) that is principally responsible for the yellow-orange color found abundantly in vegetables, for example, corn, carrots, kale, and peas, and in egg yolks [102]. Lutein has preventive effects against various diseases such as eye diseases and cardiovascular diseases [102–104]. In particular, several studies have addressed the role of lutein in reducing the risk of the two most common eye diseases in older people, that is, cataracts and macular degeneration [102–104]. Only a few reports have shown the effect of lutein *Z*-isomerization on bioavailability and antioxidant activity [15, 105]. *In vitro* tests using a digestion model have shown a higher bioaccessibility of *Z*-isomers of lutein than the all-*E*-isomer, and a Caco-2 cell monolayer model has shown a lower bioavailability. These results indicated that *Z*-isomers of lutein are more efficiently incorporated into bile acid micelles, but they have lower transport efficiency in enterocytes via the activities of carotenoid-transport proteins like β-carotene, as described above [15, 27, 49–51].

In terms of antioxidant activity, the *Z*-isomers, especially the 13′*Z*-isomer, have shown higher antioxidant activities than the all-*E*-isomer in FRAP, DPPH, and ORAC assay, but no significant differences in the activities of the isomers were observed in CAA assay [15]. Since few reports are available regarding the effects of *Z*-isomerization on lutein bioavailability and functionality, and no such studies have been conducted in humans, further studies are needed to clarify whether *Z*-isomerization shows "positive" or "negative" effects. Several studies have reported that (all-*E*)-lutein can be isomerized to the *Z*-isomers by heating [106, 107] and catalytic treatment [15].

#### **2.7. Other carotenoids**

The effects of *Z*-isomerization on the antioxidant activities of other carotenoids, such as α-carotene and zeaxanthin, were investigated by Böhm et al. [10] by performing TEAC assay. The following relative antioxidant activities of α-carotene stereoisomers were found: 13′*Z*-isomer > all-*E*-isomer ≈ 9′*Z*-isomer > 9*Z*-isomer ≈ 13*Z*-isomer, whereas those for zeaxanthin were as follows: all-*E*-isomer ≈ 13*Z*-isomer > 9*Z*-isomer. It is difficult to discern whether


2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydroxyl radical-scavenging assay revealed the following relative activities: 9′*Z*-isomer > all-*E*-isomer >13*Z*-isomer ≈ 13′*Z*-isomer. Moreover, Kawee-ai et al. [100] showed that when the ratio of the *Z*-isomer of fucoxanthin increased by 2% from 11 to 13% by heating, the scavenging activities against DPPH, hydrogen peroxide, and superoxide anions, and the reducing power decreased by 21.0, 10.3, 16.0 and 19.7%, respectively. Hence, it is considered that the *Z*-isomerization of fucoxanthin negatively affects the antioxidant activity. However, Nakazawa et al. [13] demonstrated that *Z*-isomers of fucoxanthin had higher anticancer activity than the all-*E*-isomer, as evaluated by measuring the potent inhibitory effects on human promyelocytic leukemia cells (HL-60) and colon cancer cells (Caco-2). To the best of our knowledge, only fucoxanthin was investigated in terms of the effect of *Z*-isomerization on anticancer activity. Thus, it is expected that such investigation will extend to other carotenoids in the future. *Z*-isomerization of (all-*E*)-fucoxanthin

found abundantly in vegetables, for example, corn, carrots, kale, and peas, and in egg yolks [102]. Lutein has preventive effects against various diseases such as eye diseases and cardiovascular diseases [102–104]. In particular, several studies have addressed the role of lutein in reducing the risk of the two most common eye diseases in older people, that is, cataracts and macular degeneration [102–104]. Only a few reports have shown the effect of lutein *Z*-isomerization on bioavailability and antioxidant activity [15, 105]. *In vitro* tests using a digestion model have shown a higher bioaccessibility of *Z*-isomers of lutein than the all-*E*-isomer, and a Caco-2 cell monolayer model has shown a lower bioavailability. These results indicated that *Z*-isomers of lutein are more efficiently incorporated into bile acid micelles, but they have lower transport efficiency in enterocytes via the activities of carotenoid-transport proteins like

In terms of antioxidant activity, the *Z*-isomers, especially the 13′*Z*-isomer, have shown higher antioxidant activities than the all-*E*-isomer in FRAP, DPPH, and ORAC assay, but no significant differences in the activities of the isomers were observed in CAA assay [15]. Since few reports are available regarding the effects of *Z*-isomerization on lutein bioavailability and functionality, and no such studies have been conducted in humans, further studies are needed to clarify whether *Z*-isomerization shows "positive" or "negative" effects. Several studies have reported that (all-*E*)-lutein can be isomerized to the *Z*-isomers by heating [106,

The effects of *Z*-isomerization on the antioxidant activities of other carotenoids, such as α-carotene and zeaxanthin, were investigated by Böhm et al. [10] by performing TEAC assay. The following relative antioxidant activities of α-carotene stereoisomers were found: 13′*Z*-isomer > all-*E*-isomer ≈ 9′*Z*-isomer > 9*Z*-isomer ≈ 13*Z*-isomer, whereas those for zeaxanthin were as follows: all-*E*-isomer ≈ 13*Z*-isomer > 9*Z*-isomer. It is difficult to discern whether

) that is principally responsible for the yellow-orange color

has been achieved by heating and light irradiation [100, 101].

**2.6. Lutein**

146 Progress in Carotenoid Research

Lutein is a xanthophyll (C40H56O2

β-carotene, as described above [15, 27, 49–51].

107] and catalytic treatment [15].

**2.7. Other carotenoids**


*Z*-isomers of both carotenoids have higher antioxidant activity than the all-*E*-isomer based on the TEAC assay results alone; thus, further evaluations by multiple testing methods are

Effects of *Z*-Isomerization on the Bioavailability and Functionality of Carotenoids: A Review

http://dx.doi.org/10.5772/intechopen.78309

149

To the best of our knowledge, the effect of *Z*-isomerization of other important carotenoids such as capsanthin and β-cryptoxanthin (which have large markets and high functionalities) on the bioavailability and functionality has not been reported. Among the over 1100 reported carotenoids found in nature, only the eight carotenoids mentioned above have been characterized in terms of the effects of *Z*-isomerization, as summarized in **Table 1**. Thus, further

Changes in the bioavailability and functionality of carotenoids after *Z*-isomerization should have strong correlations with changes in their physicochemical properties. Several reports have shown that the *Z*-isomerization of carotenoids can induce changes in various properties such as the stability, solubility, and crystallinity. Some computational approaches using a Gaussian program have revealed that the *Z*-isomerization of carotenoids affected the Gibbs free energy [34, 35, 108, 109], that is, the relative stability of all-*E*- and mono-*Z*-isomers were in the following order: all-*E*-isomer ≈ 5*Z*-isomer > 9*Z*-isomer > 13*Z*-isomer > 15*Z*-isomer > 7*Z*-isomer ≈ 11*Z*-isomer for lycopene [34, 35, 108]; all-*E*-isomer > 9*Z*-isomer > 13*Z*-isomer > 15*Z*-isomer > 7*Z*-isomer ≈ 11*Z*-isome for β-carotene [109]. Thus, (all-*E*)-carotenoids should be more stable than the *Z*-isomers, which was confirmed experimentally by Murakami et al. [36] using lycopene isomers. Changes in the Gibbs free energy, stability, of carotenoids following *Z*-isomerization would affect their antioxidant activities. In addition, there is limited experimental evidence that the *Z*-isomers of carotenoids such as lycopene, β-carotene, and

**3. Changes in the physicochemical properties of carotenoids by** 

astaxanthin have higher solubility in vegetable oil, organic solvents and SC-CO2

*E*-isomer [28–32, 110, 111], for example, the solubility of lycopene *Z*-isomers in ethanol was over 4000 times higher than that of the all-*E*-isomer [29]. These properties should affect the bioavailability of carotenoids. Namely, *Z*-isomerization of carotenoids could enhance uptake into bile acid micelles due to an increased solubility; thus, the bioavailability of lycopene and astaxanthin was improved [20–22]. On the other hand, regarding β-carotene and lutein, whose *Z*-isomers showed lower bioavailability [15, 41–48, 105], the uptake into bile acid micelles could potentially be improved by *Z*-isomerization, but they might have lower transport efficiency in enterocytes due to the activities of several carotenoids transport proteins, which are temporarily present at the apical membrane [27, 49–51]. *In vitro* tests of lutein support this hypothesis, that is, the *Z*-isomers showed higher bioaccessibility than the all-*E*-isomers in a digestion model [15, 105], whereas the opposite result was obtained in Caco-2 cells [15]. It has been predicted that *Z*-isomers of lycopene and astaxanthin can be efficiently internalized via carotenoid transporters, based on the results of testing conducted using Caco-2 cells [23, 76]. The abovementioned theory is strongly supported by the observations that, in human blood, over 50% of total lycopene exists in the *Z*-form, but only 5% of total β-carotene exists in the *Z*-form [112]. To attain a better understanding of the underlying mechanisms, further study

than the all-

progress in this research area is expected in the future.

necessary.

*Z***-isomerization**

\* Expected effect of carotenoid *Z*-isomerization on humans: +, "positive" effect; −, "negative" effect; ±, no change or indetermine.

**Table 1**. Summary of the effects of *Z*-isomerization of different carotenoids on the bioavailability and functionality.

*Z*-isomers of both carotenoids have higher antioxidant activity than the all-*E*-isomer based on the TEAC assay results alone; thus, further evaluations by multiple testing methods are necessary.

**Carotenoid Evaluation Overview of results Effect\* Reference**

model and Caco-2 cells

enzyme-activity assay

peroxidation assay

PLC assay

power assay

Caco-2 cells

model

model

TEAC assay

DPPH and ORAC assay

assay

oral-dosing test

test

*Z*-Isomers > all-*E*-isomer, evaluated using a digestion

13*Z*-Isomer > all-*E*-isomer, 9*Z*-isomer, evaluated in human

*Z*-Isomers > all-*E*-isomer, evaluated in human oral-dosing

All-*E*-isomer > *Z*-isomers, evaluated in rainbow trout

*Z*-Isomers > all-*E*-isomer, evaluated in antioxidant

*Z*-Isomers > all-*E*-isomer, evaluated in DPPH and lipid-

*Z*-Isomers > all-*E*-isomer, evaluated in DPPH, ORAC, and

13*Z*-Isomer > all-*E*-isomer >9*Z*-isomer, evaluated in CAA

9*Z*-Isomer > all-*E*-isomer, evaluated in DPPH, superoxide

13*Z*-Isomer ≈ 13′*Z*-isomer > all-*E*-isomer > 9′*Z*-isomer, evaluated in DPPH and superoxide-detection assay

9′*Z*-Isomer > all-*E*-isomer > 13*Z*-isomer ≈ 13′*Z*-isomer, evaluated in ABTS and hydroxyl radical-scavenging assay

*Z*-Isomers > all-*E*-isomer, evaluated in DPPH, hydrogen peroxide-scavenging, superoxide anion, and reducing-

*Z*-Isomers > all-*E*-isomer, evaluated in HL-60 cells and

*Z*-Isomers > all-*E*-isomer, evaluated using a digestion

13*Z*-Isomer > all-*E*-isomer, evaluated using a digestion

13′*Z*-Isomer > all-*E*-isomer ≈ 9*Z*-isomer, evaluated in

All-*E*-isomer ≈ 13*Z*-isomer > 9*Z*-isomers, evaluated in

Expected effect of carotenoid *Z*-isomerization on humans: +, "positive" effect; −, "negative" effect; ±, no change or

**Table 1**. Summary of the effects of *Z*-isomerization of different carotenoids on the bioavailability and functionality.

9*Z*-Isomer > all-*E*-isomer, evaluated in THP-1 macrophages + [90]

All-*E*-isomer > *Z*-isomers, evaluated in Caco-2 cells − [15]

*Z*-Isomers > all-*E*-isomer, evaluated in FRAP assay + [15]

All-*E*-isomer ≈ *Z*-isomers, evaluated in CAA assay ± [15]

radical-scavenging, and fluorescence assay

(*Oncorhynchus mykiss*) oral-dosing tests

+ [76]

+ [77]

+ [16]

+ [76]

+ [80]

+ [81]

± [81]

+ [88]

± [19]

± [19]

− [100]

+ [13]

+ [15]

+ [105]

+ [15]

− [10]

− [78, 79]

Astaxanthin Bioavailability/

148 Progress in Carotenoid Research

Canthaxanthin Antioxidant

Fucoxanthin Antioxidant

Lutein Bioavailability/

Zeaxanthin Antioxidant

\*

indetermine.

activity

activity

Anticancer activity

bioaccessibility

Antioxidant activity

activity

Pro-apoptotic activity

bioaccessibility

Antioxidant activity

To the best of our knowledge, the effect of *Z*-isomerization of other important carotenoids such as capsanthin and β-cryptoxanthin (which have large markets and high functionalities) on the bioavailability and functionality has not been reported. Among the over 1100 reported carotenoids found in nature, only the eight carotenoids mentioned above have been characterized in terms of the effects of *Z*-isomerization, as summarized in **Table 1**. Thus, further progress in this research area is expected in the future.
