J Food Bioact

Journal of Food Bioactives, ISSN 2637-8752 print, 2637-8779 online

Journal website www.isnff-jfb.com

Review

Volume 10, June 2020, pages 32-46

Chemistry and biochemistry of dietary carotenoids: bioaccessibility, bioavailability and bioactivities

Figure 1. Common dietary carotenoids and different isomeric structures in free and ester forms of carotenoids as represented by astaxanthin. R represents saturated or unsaturated alkyl chains.

Figure 2. The biosynthetic pathway of carotenoids in plants. The colors of the frames represent the appearance of different compounds. GAP represents glyceraldehyde 3-phosphate; MEP, methylerythritol 4-phosphate; IPP, isopentenyl pyrophosphate; DMAPP, dimethylallyl pyrophosphate; GGPP, geranylgeranyl pyrophosphate. CRTISO, carotenoid isomerase; LCYB, lycopene β-cyclase; LCYE, lycopene ε-cyclase; CYP97C, carotene ε-hydroxylase; CYP97A, cytochrome P450 carotene β-hydroxylase; ZEP, zeaxanthin epoxidase; VDE, violaxanthin de-epoxidase.

Figure 3. Schematic depiction of inflammatory signaling pathways and actions of carotenoids. Increased ROS causes the oxidative stress inside cells. During exposure to oxidants, IκB (inhibitors of NF-κB) proteins which are bound with NF-κB are rapidly degraded and release NF-κB protein to the nucleus. NF-κB could then bind to DNA sequences, and activate the expression of pro-inflammatory cytokines. The mitogen-activated protein kinase (MAPK) pathway activation begins with the activation of MAPKK-kinases (MAPKKKs). MAPKKKs phosphorylates MAPK-kinases (MAPKKs) subsequently, and the MAPKK further activates and phosphorylates MAPKs. Activated MAPKs then mediate the gene expression in nucleus. Certain carotenoids can inactivate the NF-κB pathway and MAPK signaling pathways to exhibit the anti-inflammatory effects.

**Table 1.** Quantitative distribution of common carotenoids and their predominant isomers in selected dietary foods
Carotenoid	Food sources (concentration)	Reference
FW, fresh weight; DW, dry weight.
all-E-lutein	Squash, Sweet Momma flesh (18.6μg/g FW); Spinach (37.4μg/g FW); Kale (123.1μg/g FW); Potato, Yukon Gold flesh (4.1μg/g FW); Tomato (6.41 μg/g DW)	Tsao and Yang (2006); Li et al. (2012)
13Z- or 13′Z-lutein	Tomato (0.76 μg/g DW)	Li et al. (2012)
9Z- or 9′Z-lutein	Tomato (0.53 μg/g DW)	Li et al. (2012)
all-E-β-carotene	Cassava root, sweet yellow (7.27 μg/g FW); Squash, Sweet Momma flesh (3.7 μg/g FW); Kale (23.8 μg/g FW); Tomato (81.29 μg/g DW)	Carvalho et al. (2012); Tsao and Yang (2006); Li et al. (2012)
9Z-β-carotene	Cassava root, sweet yellow (0.35μg/gFW); Tomato (2.15 μg/g DW)	Carvalho et al. (2012); Li et al. (2012)
13Z-β-carotene	Cassava root, sweet yellow (0.5μg/gFW); Tomato (1.85 μg/g DW)	Carvalho et al. (2012); Li et al. (2012)
15Z- or 15′Z-β-carotene	Tomato (1.15 μg/g DW)	Li et al. (2012)
all-E-lycopene	Tomato (145.85 μg/g DW)	Li et al. (2012)
5Z- or 5′Z-lycopene	Tomato (4.24 μg/g DW)	Li et al. (2012)
15Z- or 15′Z-lycopene	Tomato (2.79 μg/g DW)	Li et al. (2012)
13Z- or 13′Z-lycopene	Tomato (2.25 μg/g DW)	Li et al. (2012)
9Z- or 9′Z-lycopene	Tomato (1.75 μg/g DW)	Li et al. (2012)
all-E-astaxanthin	Antarctic krill, boiling (90.71μg/gDW)	Cong et al. (2019)
13Z-astaxanthin	Antarctic krill, boiling (15.65μg/gDW)	Cong et al. (2019)
9Z-astaxanthin	Antarctic krill, boiling (15.39μg/gDW)	Cong et al. (2019)

Table 1. Quantitative distribution of common carotenoids and their predominant isomers in selected dietary foods

Carotenoid

Food sources (concentration)

Reference

FW, fresh weight; DW, dry weight.

all-E-lutein

Squash, Sweet Momma flesh (18.6μg/g FW); Spinach (37.4μg/g FW); Kale (123.1μg/g FW); Potato, Yukon Gold flesh (4.1μg/g FW); Tomato (6.41 μg/g DW)

Tsao and Yang (2006); Li et al. (2012)

13Z- or 13′Z-lutein

Tomato (0.76 μg/g DW)

Li et al. (2012)

9Z- or 9′Z-lutein

Tomato (0.53 μg/g DW)

Li et al. (2012)

all-E-β-carotene

Cassava root, sweet yellow (7.27 μg/g FW); Squash, Sweet Momma flesh (3.7 μg/g FW); Kale (23.8 μg/g FW); Tomato (81.29 μg/g DW)

Carvalho et al. (2012); Tsao and Yang (2006); Li et al. (2012)

9Z-β-carotene

Cassava root, sweet yellow (0.35μg/gFW); Tomato (2.15 μg/g DW)

Carvalho et al. (2012); Li et al. (2012)

13Z-β-carotene

Cassava root, sweet yellow (0.5μg/gFW); Tomato (1.85 μg/g DW)

Carvalho et al. (2012); Li et al. (2012)

15Z- or 15′Z-β-carotene

Tomato (1.15 μg/g DW)

Li et al. (2012)

all-E-lycopene

Tomato (145.85 μg/g DW)

Li et al. (2012)

5Z- or 5′Z-lycopene

Tomato (4.24 μg/g DW)

Li et al. (2012)

15Z- or 15′Z-lycopene

Tomato (2.79 μg/g DW)

Li et al. (2012)

13Z- or 13′Z-lycopene

Tomato (2.25 μg/g DW)

Li et al. (2012)

9Z- or 9′Z-lycopene

Tomato (1.75 μg/g DW)

Li et al. (2012)

all-E-astaxanthin

Antarctic krill, boiling (90.71μg/gDW)

Cong et al. (2019)

13Z-astaxanthin

Antarctic krill, boiling (15.65μg/gDW)

Cong et al. (2019)

9Z-astaxanthin

Antarctic krill, boiling (15.39μg/gDW)

Cong et al. (2019)

**Table 2.** Potential health effects of carotenoids and comparison among carotenoid isomers
	Summary of results	References
Antioxidant activities
ABTS+ assay	lycopene > β-carotene > lutein > α-tocopherol	Zanfini et al. (2010)
aTEAC assay	lycopene > β-carotene = α-carotene > neurosporene > phytofluene = phytoene	Müller et al. (2011)
ABTS+ assay	violaxanthin > lutein > β-carotene	Fu et al. (2011)
DPPH assay	β-carotene > lutein > violaxanthin	Fu et al. (2011)
ROO^• scavenging capacity	astaxanthin> lutein > zeaxanthin > α-tocopherol > fucoxanthin > β-carotene > lycopene	Rodrigues et al. (2012)
HO^• scavenging capacity	α-tocopherol > astaxanthin > zeaxanthin > fucoxanthin > lutein > β-carotene > lycopene	Rodrigues et al. (2012)
ORAC-L, PLC and CAA assays	13Z-astaxanthin > all-E-astaxanthin ≈ 9Z-astaxanthin	Yang et al. (2017)
DPPH assay	9Z-astaxanthin > 13Z-astaxanthin > all-E-astaxanthin	Liu and Osawa (2007)
Against oxidative stress in H₂O₂ induced Caco-2 cells	9Z-astaxanthin ≈ 13Z-astaxanthin > all-E-astaxanthin	Yang et al. (2017)
Extending the median lifespan of Caenorhabditis elegans	9Z-astaxanthin > all-E-astaxanthin > 13Z-astaxanthin	Liu et al. (2018)
DPPH and ORAC-L assays	9Z-astaxanthin ≈ 13Z-astaxanthin > all-E-astaxanthin ≈ 13′Z-lutein > 9Z-lutein ≈ all-E-lutein	Yang et al. (2018); Yang et al. (2017)
AAPH assay	5Z-lycopene > all-E-lycopene ≈other Z-lycopenes	Muller et al. (2011)
TEAC assay	all-E-zeaxanthin ≈ 13Z-zeaxanthin > 9Z-zeaxanthin	Böhm, et al. (2002)
Inhibiting LDL oxidation	all-E-β-carotene > 9Z-β-carotene	Lavy, et al. (1993)
Rat oral-dosing test	9Z-β-carotene > all-E-β-carotene	Levin, et al. (1997)
Chemical-based assays and CAA assay	3S,3′S-astaxanthin > 3R,3′R-astaxanthin > a mixture of different stereoisomers of astaxanthin (S: meso: R = 1:2:1)	Liu, Luo, et al. (2016)
Anti-inflammatory activity
Caco-2 monolayers treated with TNF-α	9Z-astaxanthin ≧ 13Z-astaxanthin ≧ all-E-astaxanthin	Yang et al. (2019)
Through inhibiting the nuclear NF-κB p50 subunit translocation and down-regulating the JNK activation	carotenoid extract rich in 9Z- or 9′Z-β-carotene and all-E-β-carotene	Yang et al. (2013)
Against LPS-induced inflammation in macrophages	meso-zeaxanthin [(3R, 3′S)- β, β-carotene-3, 3′-diol]	Firdous, Kuttan, and Kuttan (2015)
Lower the production of inflammatory mediators in UV-irradiated or IL-1-treated fibroblasts	phytoene and phytofluene	Fuller et al. (2006)
Through regulating pathways including Akt and MAPK pathways	fucoxanthin	Cho et al. (2018)
Anti-cancer effects
Benign prostate hyperplasia (BPH) treatment in mice	Z-lycopenes ≧ all-E-lycopene	Zou et al. (2014)
Inhibiting the colon cancer cell growth	3S,3′S-astaxanthin ≈ 3R,3′R-astaxanthin ≈ a mixture of different stereoisomers of astaxanthin (S: meso: R = 1:2:1)	Liu, Song, et al. (2016)
Controversial results	lycopene on prostate cancer	Woodside et al. (2015)
Controversial results	β-carotene on lung cancer	Woodside et al. (2015)
Macular degeneration
Protection against age-related macular degeneration (AMD)	lutein and zeaxanthin	Tsao, R. (2006)
Deposit in the retina of mammals	astaxanthin and lutein	Guerin et al. (2003)
Play an important role in retinal synthesis	β-carotene	Matos et al. (2017)

Table 2. Potential health effects of carotenoids and comparison among carotenoid isomers

Summary of results

References

Antioxidant activities

ABTS+ assay

lycopene > β-carotene > lutein > α-tocopherol

Zanfini et al. (2010)

aTEAC assay

lycopene > β-carotene = α-carotene > neurosporene > phytofluene = phytoene

Müller et al. (2011)

ABTS+ assay

violaxanthin > lutein > β-carotene

Fu et al. (2011)

DPPH assay

β-carotene > lutein > violaxanthin

Fu et al. (2011)

ROO^• scavenging capacity

astaxanthin> lutein > zeaxanthin > α-tocopherol > fucoxanthin > β-carotene > lycopene

Rodrigues et al. (2012)

HO^• scavenging capacity

α-tocopherol > astaxanthin > zeaxanthin > fucoxanthin > lutein > β-carotene > lycopene

Rodrigues et al. (2012)

ORAC-L, PLC and CAA assays

13Z-astaxanthin > all-E-astaxanthin ≈ 9Z-astaxanthin

Yang et al. (2017)

DPPH assay

9Z-astaxanthin > 13Z-astaxanthin > all-E-astaxanthin

Liu and Osawa (2007)

Against oxidative stress in H₂O₂ induced Caco-2 cells

9Z-astaxanthin ≈ 13Z-astaxanthin > all-E-astaxanthin

Yang et al. (2017)

Extending the median lifespan of Caenorhabditis elegans

9Z-astaxanthin > all-E-astaxanthin > 13Z-astaxanthin

Liu et al. (2018)

DPPH and ORAC-L assays

9Z-astaxanthin ≈ 13Z-astaxanthin > all-E-astaxanthin ≈ 13′Z-lutein > 9Z-lutein ≈ all-E-lutein

Yang et al. (2018); Yang et al. (2017)

AAPH assay

5Z-lycopene > all-E-lycopene ≈other Z-lycopenes

Muller et al. (2011)

TEAC assay

all-E-zeaxanthin ≈ 13Z-zeaxanthin > 9Z-zeaxanthin

Böhm, et al. (2002)

Inhibiting LDL oxidation

all-E-β-carotene > 9Z-β-carotene

Lavy, et al. (1993)

Rat oral-dosing test

9Z-β-carotene > all-E-β-carotene

Levin, et al. (1997)

Chemical-based assays and CAA assay

3S,3′S-astaxanthin > 3R,3′R-astaxanthin > a mixture of different stereoisomers of astaxanthin (S: meso: R = 1:2:1)

Liu, Luo, et al. (2016)

Anti-inflammatory activity

Caco-2 monolayers treated with TNF-α

9Z-astaxanthin ≧ 13Z-astaxanthin ≧ all-E-astaxanthin

Yang et al. (2019)

Through inhibiting the nuclear NF-κB p50 subunit translocation and down-regulating the JNK activation

carotenoid extract rich in 9Z- or 9′Z-β-carotene and all-E-β-carotene

Yang et al. (2013)

Against LPS-induced inflammation in macrophages

meso-zeaxanthin [(3R, 3′S)- β, β-carotene-3, 3′-diol]

Firdous, Kuttan, and Kuttan (2015)

Lower the production of inflammatory mediators in UV-irradiated or IL-1-treated fibroblasts

phytoene and phytofluene

Fuller et al. (2006)

Through regulating pathways including Akt and MAPK pathways

fucoxanthin

Cho et al. (2018)

Anti-cancer effects

Benign prostate hyperplasia (BPH) treatment in mice

Z-lycopenes ≧ all-E-lycopene

Zou et al. (2014)

Inhibiting the colon cancer cell growth

3S,3′S-astaxanthin ≈ 3R,3′R-astaxanthin ≈ a mixture of different stereoisomers of astaxanthin (S: meso: R = 1:2:1)

Liu, Song, et al. (2016)

Controversial results

lycopene on prostate cancer

Woodside et al. (2015)

Controversial results

β-carotene on lung cancer

Woodside et al. (2015)

Macular degeneration

Protection against age-related macular degeneration (AMD)

lutein and zeaxanthin

Tsao, R. (2006)

Deposit in the retina of mammals

astaxanthin and lutein

Guerin et al. (2003)

Play an important role in retinal synthesis

β-carotene

Matos et al. (2017)