Functional properties of carotenoids in human health

International Journal of Food Properties

Volumn 10, Issue 2, 2007, Pages 201-230

  Perera, Conrad O ^a,b   Yen, Gan Mei ^a  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b NONE   (New Zealand)

Author keywords

Absorption and transport; Bioavailability; Carotenoids; Human health; Nutrition; Toxicity

Indexed keywords

BIOACTIVITY; EPIDEMIOLOGY; NUTRITION; TOXICITY; TUMORS;

BIOAVAILABILITY; CAROTENOIDS; DEGENERATIVE DISEASES; HUMAN HEALTH;

PIGMENTS;

LYCOPERSICON ESCULENTUM;

EID: 34247638950     PISSN: 10942912     EISSN: 15322386     Source Type: Journal    
DOI: 10.1080/10942910601045271     Document Type: Article

References (181)

1. Britton, G. Structure and Properties of Carotenoids in Relation to Function. FASEB J. 1995, 9, 1551-1558.
2. Gerster, H. Anticarcinogenic Effect of Common Carotenoids. Int. J. Vitam. Nutr. Res. 1993, 63, 93-121.
3. Bowen, P.E.; Mobarhan, S. Evidence from Cancer Intervention and Biomarker Studies and the Development of Biochemical Markers. Am. J. Clin. Nutr. 1995, 62, 1403S-1409S.
4. Benedich, A. Recent Advances in Clinical Research Involving Carotenoids. Pure Appl. Chem. 1994, 66, 1017-1024.
5. Mayne, S.T. Beta-Carotene, Carotenoids and Disease Prevention in Humans. FASEB J. 1996, 10, 690-701.
6. Seddon, J.M.; Ajani, U.A.; Sperduto, R.D.; Hiller, R.; Blair, N.; Burton, T.C.; Farber, M.D.; Gragoudas, E.S.; Haller, J.; Miller, D.T. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration: Eye disease case-control study group. J. Am. Medical Assoc. 1994, 272 (18), 1413-20.
7. (Erratum in: JAMA 1995 Feb 22; 273 (8):622.).
8. Snodderly, D.M. Evidence for Protection Against Age-Related Macular Degeration by Carotenoids and Antioxidant Vitamins. Am. J. Clin. Nutr. 1995, 62, 1448S-1461S.
9. Chew, B.P. Antioxidant Vitamins Affect Food Animal Immunity and Health. J Nutr. 1995, 125, 1804S-1808S.
10. Meydani, S.N.; Wu, D.; Santos, M.S.; Hayek, M.G.. Antioxidants and Immune Response in Aged Persons: Overview of Present Evidence. Am. J. Clin. Nutr. 1995, 62, 1462S-1476S.
11. Walfisch, Y.; Walfisch, S.; Agbaria, R.; Levy, J.; Sharoni, Y. Lycopene in Serum, Skin and Adipose Tissues after Tomato-Oleoresin Supplementation in Patients Undergoing Haemorrhoidectomy or Peri-Anal Fistulotomy. Br. J. Nutr. 2003, 90 (4), 759-766.
12. Stahl, W.; Schwarz, W.; Sundquist, A.R.; Sies, H. Cis-Trans Isomers of Lycopene and Beta-Carotene in Human Serum and Tissues. Arch. Biochem. Biophys. 1992, 294, 173-177.
13. Boileau, T.W.M.; Boileau, A.C.; Erdman, Jr. J.W. Bioavailability of All-Trans and Cis-Isomers of Lycopene. Experimental Biology and Medicine 2002, 227, 914-919.
14. McEligot, A.J.; Rock, C.L.; Shanks, T.G.; Flatt, S.W.; Newman, V.; Faerber, S.; Pierce, J.P. Comparison of Serum Carotenoid Responses between Women Consuming Vegetable Juice and Women Consuming Raw or Cooked Vegetables. Cancer Epidemiol. Biomarkers Prev. 1999, 8, 227-231.
15. van het Hof, K.H.; Brouwer, I.A.; West, C.E.; Haddeman, E.; Steegers-Theunissen, R.P.M.; van Dusseldorp, M.; Weststrate, J.A.; Eskes, T.K.A.B.; Hautvast, J.G.A.J. Bioavailability of Lutein is Five Times Higher than that of β-Carotene. Am. J. Clin. Nutr. 1999, 70, 261-268.
16. Alves-Rodrigues, A.; Shao, A. The Science Behind Lutein. Toxicological Letters. 2004, 50, 57-83.
17. Olson, J.A. Carotenoids. In Modern Nutrition in Health and Disease. Shils, M.E.; Olson, J.A.; Shike, M.; Ross, A.C. Eds.; Williams and Wilkins: Baltimore, MD, 1999; 525-541.
18. Britton, G. Structure and Nomenclature. In Carotenoids in Photosynthesis; Young, A.; Britton; Eds.; Chapman and Hall: London, 1993; 1-15.
19. Weedon, B.C.L.; Moss, G.P. Structure and Nomenclature. In Carotenoids Vol. 1A: Isolation and Analysis; Britton, G.; Liaaen-Jensen, S.; Pfander, H.; Eds.; Birkhäuser Verlag: Basel, Switzerland, 1995; 27-70.
20. Davies, B.H.; Matthews, S.; Kirk, J.T.O. The Nature and Biosynthesis of the Carotenoids of Different Colour Varieties of Capsicum Annuum. Phytochemistry 1970, 9, 797-805.
21. Goodwin, T.W. Distribution of Carotenoids. In Chemistry and Biochemistry of Plant Pigments, Vol 1; Goodwin, T.W.; Ed.; Academic Press: New York. 1976; 225-261.
22. Farin, D.; Ikan, R.; Gross, J. The Carotenoid Pigments in the Juice and Flavedo of Mandarin Hybrid (Citrus Reticulate) cv Michal during Ripening. Phytochemistry 1983, 22, 403-408.
23. Hornero-Méndez, D.; Mínguez-Mosquera, M.I.. Xanthophyll Esterification Accompanying Carotenoid Overaccumulation in Chromoplast of Capsicum Annuum Ripening Fruits is a Constitutive Process and Useful for Ripening Index. J. Agric. Food Chem. 2000, 48, 1617-1622.
24. Reboul, E.; Abou, L.; Mikail, C.; Ghiringhelli, O.; André, M.; Gleize, B.; Kaloustian, J.; Portugal, H.; Amiot, M-J.; Borel, P. Lutein is Apparently Absorbed by a Carrier-Mediated Transport Process in Caco-2 cells. Clin. Nutr. 2003, 22, S103.
25. Reboul, E.; Abou, L.; Mikail, C.; Ghiringhelli, O.; André, M.; Portugal, H.; JourdheuilRahmani, D.; Amiot, M-J.; Lairon, D.; Borel, P. Lutein Transport by Caco-2 TC-7 Cells occurs Partly by a Facilitated Process Involving the Scavenger Receptor Class B Type I (SR-BI). Biochem. J. 2005, 387, 455-461.
26. Konta, T.; Xu, Q.; Furusu, A.; Nakayama, K.; Kitamura, M. Selectives Roles of Retinoic Acid Receptor and Retinoid X Receptor in the Suppression of Apoptosis by All-Trans-Retinoic Acid. J. Biol. Chem. 2001, 276, 12697-12701.
27. Costet, P.; Lalanne, F.; Gerbod-Giannone, M.C.; Molina, J.R.; Fu, X.; Lund, E.G.; Gudas, L.J.; Tall, A.R. Retinoic Acid Receptor-Mediated Induction of ABCA1 in Macrophages. Mol. Cell Biol. 2003, 23 (21), 7756-66.
28. Li, E.; Tso, P. Vitamin A Uptake from Foods. Current Opinion in Lipidology. 2003, 14 (3), 241-247.
29. Borel, P.; Drai, J.; Faure, H.; Fayol, V.; Galabert, C.; Laromiguière, M.; Le Moël, G. Données Récentes Sur l'absorption et le Catabolisme des Caroténoïdes. Annales de Biologie Clinique. 2005, 63 (2), 165-177.
30. Wyss, A.; Wirtz, G.M.; Woggon, W-D.; Brugger, R.; Wyss, M.; Friedlein, A.; Riss, G.; Bachmann, H.; Hunziker, W. Expression Pattern and Localization of Beta,Beta-Carotene 15,15′-Dioxygenase in Different Tissues. Biochem. J. 2001, 354, 521-529.
31. Wyss, A. Carotene Oxygenases: A New Family of Double Bond Cleavage Enzymes. J. Nutr. 2004, 134, 246S-250S.
32. Khachik, F.; Beecher, G.R.; Goli, M.B.; Lusby, W.R. Separation, Identification and Quantification of Carotenoids in Fruits, Vegetables and Human Plasma by HPLC. Pure Appl. Chem. 1991, 63,71-80.
33. Khachik, F.; Beecher, G.R.; Goli, M.B.; Lusby, W.R. Separation and Quantification of Carotenoids in Foods. Methods Enzymol. 1992, 213A, 347-359.
34. Steghens, J.P.; Van Kappel, A.L.; Riboli, E.; Collombel, C. Simultaneous Measurement of Seven Carotenoids, Retinol and Alpha-Tocopherol in Serum by High-Performance Liquid Chromatography. J. Chromatogr. B Biomed. Sc. Appl. 1997, 694, 71-81.
35. Lyan, B.; Azais-Braesco, V.; Cardinault, N. Simple Method for Clinical Determination of 13 Carotenoids in Human Plasma Using an Isocratic High-Performance Liquid Chromatographic Method. J. Chromatogr. B. 2001, 25, 297-303.
36. Erdman, J.W. Jr.; Bierer, T.L.; Gugger, E.T. Absorption and Transport of Carotenoids. Annals of the New York Academy of Sciences 1993, 691, 76-85.
37. Tyssandier, V.; Reboul, E.; Dumas, J.F. Processing of Vegetable-Borne Carotenoids in the Human Stomach and Duodenum. Am. J. Physiol. Gastrointest. Liver Physiol. 2003, 284, G913-G923.
38. Rich, G.T.; Fillery-Travis, A.; Parker, M.L. Low pH Enhances the Transfer of Carotene from Carrot Juice to Olive Oil. Lipids 1998, 33, 985-992.
39. Carey, M.C.; Hernell, O. Digestion and Absorption of Fat. Semin. Gastrointest. Dis. 1992, 3, 189-208.
40. Tso, P. Intestinal Lipid Absorption. In Physiology of the Gatrointestinal Tract; Johnson, L.R.; Ed; Raven Press: New York, 1994; 1867-1907.
41. Borel, P.; Grolier, P.; Armand, M.; Partier, A.; Lafont, H.; Lairon, D.; Azais-Braesco, V. Carotenoids in Biological Emulsions: Solubility, Surface-to-Core Distribution and Release from Lipid Droplets. J. Lipid Res. 1996, 37, 250-261.
42. Leo, M.A.; Ahmed, S.; Aleynik, S.; Siegel, J.H.; Kasmin, F.; Lieber, C.S. Carotenoids and Tocopherols in Various Hepatobiliary Conditions. J. Hepatol. 1995, 23, 550-556.
43. El-Gorab, M.; Underwood, B.A.; Loerch, J.D. The Roles of Bile Salts in the Uptake of Beta-Carotene and Retinol by Rat Everted Gut Sacs. Biochim. Biophys. Acta. 1975, 401, 265-277.
44. Hollander, D.; Ruble, P.E. Jr. Beta-Carotene Intestinal Absorption: Bile, Fatty Acid, pH and Flow Rate Effects on Transport. Am. J. Physiol. 1978, 235, E686-E691.
45. Canfield, L.M.; Fritz, T.A.; Tarara, T.E.. Incoporation of Beta-Carotene into Mixed Micelles. Methods Enzymol. 1990, 189, 418-422.
46. El-Gorab, M.; Underwood, B.A. Solubilization of Beta-Carotene and Retinol into Aqueous Solutions of Mixed Micelles. Biochim. Biophys. Acta. 1973, 306, 58-66.
47. Westergaard, H.; Dietschy, J.M. The Mechanism Whereby Bile Acid Micelles Increase the Rate of Fatty Acid and Cholesterol Uptake into the Intestinal Mucosal Cells. J. Clin. Invest. 1976, 58, 97-108.
48. During, A.; Nagao, A.; Junji Terao, J. β-Carotene 15,15′-Dioxygenase Activity and Cellular Retinol-Binding Protein Type II Level Are Enhanced by Dietary Unsaturated Triacylglycerols in Rat Intestines. The Journal of Nutr. 1998, 128 (10), 1614-1619.
49. Gugger, E.T., Bierer, T.L., Henze, T.M., White, W.S.; Erdman, J.W. Jr. β-Carotene Uptake and Tissue Distribution in the Ferret (mustela putorius furo). J. Nutr. 1992, 112, 115-119.
50. Poor, C.L.; Bierer, T.L.; Merchen, N.R.; Fahey, G.C. Jr.; Murphy, M.R.; Erdman, J.W. Jr. Evaluation of the Preruminant Calf as a Model for Study of Human Carotenoid Metabolism. J. Nutr. 1992, 122, 262-268.
51. Furr, H.C.; Clark, R.M. Intestinal Absorption and Tissue Distribution of Carotenoids. Nutritional Biochem. 1997, 8, 364-377.
52. Yeum, K.J.; Russell, R.M.. Carotenoid Bioavailability and Bioconversion. Annu. Rev. Nutr. 2002, 22, 483-504.
53. Krinsky, N.I.; Cornwell, D.G.; Oncley, J.I. The Transport of Vitamin A and Carotenoids in Human Plasma. Arch. Biochem. Biophys. 1958, 73, 233-246.
54. Johnson, E.J.; Russell, R.M. Distribution of Orally Administered Beta-Carotene among Lipoproteins in Healthy Men. Am. J. Clinical Nutr. 1992, 56, 128-135.
55. Kostic, D.; White, W.S.; Olson, J.A. Intestinal Absorption, Serum Clearance and Interactions Between Lutein and Beta-Carotene When Administered to Human Adults in Separate or Combined Oral Doses. Am. J. Clinical Nutr. 1995, 62, 604-610.
56. Gartner, C.; Stahl, W.; Sies, H. Preferential Increase in Chylomicron Levels of the Xanthophylls Lutein and Zeaxanthin Compared to Beta-Carotene in the Human. Int. J. Vit. Nutr. Res. 1996, 66, 119-125.
57. Parker, R.S. Absorption, Metabolism and Transport of Carotenoids. FASED J. 1996, 10, 542-551.
58. Yao, L.; Burn, B.J.; Furr, H.C. Carotenoid Distribution Among Human Plasma Lipoproteins During Dietary Depletion. FASEB J. 1995, 9, A458 (Abstract).
59. Romanchik, J.E.; Morel, D.W.; Harrison, E.H. Distributions of Carotenoids and Alpha-Tocopherol among Lipoproteins do not change when Human Plasma is Incubated In-Vitro. J. Nutrition. 1995, 125 (10), 2610-2617.
60. Willstaedt, H.; Lindqvist, T. Uber die Carotenoide des Serums und der Leber beim Menschen I. (About the Carotenoids of Serum and Liver in Humans). Hoppe Seylers. Z.Physiol. Chem. 1936, 240, 10-18.
61. Daudu, P.A.; Kelley, D.S.; Taylor, P.C.; Burri, B.J.; Wu, M.M. Effect of a Low Beta-Carotene Diet on the Immune Functions of Adult Women. Am. J. Clin. Nutr. 1994, 60, 969-972.
62. Barua, A.B.; Kostic, D.; Olson, J.A. New Simplified Procedures for the Extraction and Simultaneous High-Perfonnance Liquid Chromatographic Analysis of Retinol, Tocopherols and Carotenoids in Human Serum. J. Chromatography B. 1993, 617 (2), 257-264.
63. Olson, J.A. Absorption, Transport, and Metabolism of Carotenoids in Humans. Pure & Appl. Chem. 1994, 66 (5), 1011-1016.
64. Hata, T.R.; Scholz, T.A.; Ermakov, I.V.; McClane, R.W.; Khachik, F.; Gellermann, W.; Pershing, L.K. Non-Invasive Raman Spectroscopic Detection of Carotenoids in Human Skin. J. Invest Dermatol. 2000, 115 (3), 441-448.
65. Maharshak, N.; Shapiro, J.; Trau, H. Carotenoderma - A Review of the Current Literature. Int. J. Dermatol. 2003, 42 (3), 178-81.
66. Kaplan, L.A.; Miller, J.A.; Stein, E.A.; Stampfer, M.J. Simultaneous, High-Performance Liquid Chromatographic Analysis of Retinol, Tocopherols, Lycopene, and Alpha- and Beta-Carotene in Serum and Plasma. Methods Enzymol. 1990, 189, 155-167.
67. Schmitz, H.H.; Poor, C.L.; Wellman, R.B.; Erdman, J.W. Jr. Concentrations of Selected Carotenoids and Vitamin A in Human Liver, Kidney and Lung Tissue. J. Nutr. 1991, 121 (10), 1613-1621.
68. Clinton, S.K.; Emenhiser, C.; Schwartz, S.J.; Bostwick, D.G.; Williams, A.W.; Moore, B.J.; Erdman, J.W. Cis-Trans Lycopene Isomers, Carotenoids, and Retinal in the Human Prostate. Cancer Epidemiol Biomarkers Prev. 1996, 5, 823-833.
69. Shi, H.L.; Furr, H.C.; Olson, J.A. Retinoids and Carotenoids in Bovine Pineal Gland. Brain Res. Bull. 1991, 26 (2), 235-239.
70. Sauberlich, H.E.; Hodges, R.E.; Wallace, D.L.; Kolder, H.; Canham, J.E.; Hood, J.; Raica, N. Jr.; Lowry, L.K. Vitamin A Metabolism and Requirements in the Human Studied with the Use of Labeled Retinol. Vitam. Horm. 1974, 32, 251-275.
71. de Pee, S.; West, C.E. Dietary Carotenoids and their Role in Combating Vitamin A Deficiency: A Review of the Literature. Eur. J. Clin. Nutr. 1996, 50 (Supplement) 3:S38-S53.
72. FAO/WHO. Requirements of Vitamin A, Thiamin, Riboflavine and Niacin. FAO Nutr Rep Ser no. 41, WHO Tech Rep Ser no. 360. WHO Press: Geneva, 1967, 1-86.
73. Parker, R.S.; Swanson, J.E.; Cha, S.Y.; Edwards, A.J.; Huang, T. Bioavailability of Carotenoids in Human Subjects. Proceed. Nutrition Society 1999, 58, 155-162.
74. During, A.; Harrison, E.H. Intestinal Absorption And Metabolism Of Carotenoids: Insights From Cell Culture. Archives Of Biochemistry And Biophysics 2004, 430, 77-88.
75. Johnson, E.J.; Hammond, B.R.; Yeum, K.J.; Qin, J.; Wang, X.D. Relation among Serum and Tissue Concentrations of Lutein and Zeaxanthin and Mascular Pigment Density. Am. J. Clin. Nutr. 2000, 71, 1555-1562.
76. 30 Reversed-Phase High-Performance Liquid Chromatography Coupled to UV and Atmospheric Pressure Chemical Ionization Mass Spectrometric Detection. Journal of Chromatography A 1999, 854 (1-2), 37-44.
77. Coral-Hinostroza, G.N.; Ytrestøyl, T.; Ruyter, B.; Bjerkeng, B. Plasma Appearance of Unesterified Astaxanthin Geometrical E/Z and Optical R/S Isomers in Men Given Single Doses of a Mixture of Optical 3 and 3′R/S Isomers of Astaxanthin Fatty Acyl Diesters. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 2004, 139 (1-3); 99-110.
78. You, C.S.; Parker, R.S.; Goodman, K.J. Evidence of Cis-Trans Isomerization of 9-Cis-Beta-Carotene during Absorption in Humans. Am. J. Clin. Nutr. 1996, 64, 177-183.
79. Breithaupt, D.E.; Weller, P.; Wolters, M.; Hahn, A. Plasma Response to a Single Dose of Dietary β-cryptoxanthin Esters from Papaya (Carica papaya L.) or Non-Esterified β-cryptoxanthin in Adult Human Subjects: A Comparative Study. British J. Nutrn. 2003, 90 (4), 795-801.
80. Bone, R.A.; Landrum, J.T.; Guerra, L.H.; Ruiz, C.A. Lutein and Zeaxanthin Dietary Supplements Raise Macular Pigment Density and Serum Concentrations of these Carotenoids in Humans J. Nutr. 2003, 133, 992-998.
81. Roodenburg, A.J.C.; Leenen, R.; van het Hof, K.H.; Weststrate, J.A.; Tijburg, L.B.M. Amount of Fat in the Diet Affects Bioavailability of Lutein Esters but not of α-carotene, β-carotene, and Vitamin E in Humans. Am. J. Clin. Nutr. 2000, 71, 1187-1193.
82. Bowen, P.E.; Herbst-Espinosa, S.M.; Hussain, E.A.; Stacewicz-Sapuntzakis, M. Esterification Does not Impair Lutein Bioavailability in Humans. J. Nutr. 2002, 132 (12), 3668-3673.
83. Higdon, J. Vitamin A. Linus Pauling Institute Micronutrient Information Centre. 2003. http://lpi.oregonstate.edu/infocenter/vitaminA/ (accessed May 19, 2005).
84. Castenmiller, J.J.; West, C.E.; van het Hoff, K.H.; Voragen, A.G. The Food Matrix of Spinach is a Limiting Factor in Determining the Bioavailability of Beta-Carotene and to a Lesser Extent of Lutein in Humans. J. Nutr. 1999, 129 (2), 349-355.
85. Riedl, J.; Linseisen, J.; Hoffmann, J.; Wolfram, G. Some Dietary Fibers Reduce the Absorption of Carotenoids in Women. J. Nutr. 1999, 129 (12), 2170-2176.
86. van het Hof, K.H.; Tijburg, L.B.; Pietrzik, K.; Weststrate, J.A. Influence of Feeding Different Vegetables on Plasma Levels of Carotenoids, Folate and Vitamin C. Effect of Disruption of the Vegetable Matrix. Br. J. Nutr. 1999, 82, 203-212.
87. Rock, C.L.; Lovalvo, J.L.; Emenhiser, C.; Ruffin, M.T.; Flatt, SW.; Schwartz, S.J. Bioavailability of β-Carotene Is Lower in Raw than in Processed Carrots and Spinach in Women. The Journal of Nutrition. 1998, 128 (5), 913-916.
88. Dietz, J.M.; Sri Kantha, S.; Erdman, J.W. Jr. Reversed Phase HPLC Analysis of Alpha- and Beta-Carotene from Selected Raw and Cooked Vegetables. Plant Foods Hum. Nutr. 1988, 38, 333-341.
89. Castenmillern, J.J.M.; West, C.E. Bioavailability of Carotenoids. J. Pure & Applied. Chem. 1997, 69 (10), 2145-2150.
90. Moise, A.R.; von Lintig, J.; Palczewski, K. Related Enzymes Solve Evolutionarily Recurrent Problems in the Metabolism of Carotenoids. Trends in Plant Sci. 2005, 10 (4), 178-186.
91. Moore, T. Vitamin A and Carotene. Biochem. J. 1930, 24, 692-702.
92. Camara, B.; Bouvier, F. Oxidative Remodeling of Plastid Carotenoids. Archives of Biochem. and Biophys. 2004, 430 (1), 16-21.
93. Barua, T.; Olson, J.A. Beta-Carotene is Converted Primarily to Retinoids in Rats in Vivo. J. Nutr. 2000, 130 (8), 1996-2001.
94. Khachik, F.; Englert, G.; Beecher, G.R.; Smith, J.C. Jr. Isolation, Structural Elucidation and Partial Synthesis of Lutein Dehydration Products in Extracts from Human Plasma. J. Chromatogr. Biomed. Appl. 1995, 670, 219-233.
95. Khachik, F.; Spangler, C.J.; Smith, J.C. Jr.; Canfield, L.M.; Steck, A.; Pfander, H. Identification, Quantification and Relative Concentrations of Carotenoids and Their Metabolites in Human Milk and Serum. Anal. Chem. 1997, 69, 1873-1881.
96. Khachik, F.; Bernstein, P.S.; Garland, G.L. Identification of Lutein and Zeaxanthin Oxidation Products in Human and Monkey Retinas. Investigative Ophthalmology & Visual Science 1997, 38, 1802-1811.
97. th Int. Congr. Nutr. Montreal, Canada, July 27-Aug 1, 1997; 127.
98. Stahl, W.; Sies, H. Lycopene: A Biologically Important Carotenoid for Humans? Arch Biochem. Biophys. 1996, 336 (1), 1-9.
99. White, W.S.; Stacewicz-Sapuntzakis, M.; Erdman, J.W.; Bowen, P.E. Pharmacokinetics of β-Carotene and Canthaxanthin after Ingestion of Individual and Combined Doses by Human Subjects. J. Am. Coll. Nutr. 1994, 13, 665-671.
100. Tyczkowski, J.K.; Yagen, B.; Hamilton, P.B. Metabolism of Canthaxanthin, a Red Diketocarotenoid, by Chickens. Poult. Sci. 1988, 67 (5), 787-793.
101. Oshima, S.; Sakamoto, H.; Ishiguro, Y.; Teraro, J. Accumulation and Clearance of Capzanthin in Blood Plasma after the Ingestion of Paprika Juice in Men. J. Nutr. 1997, 127 (8), 1475-1479.
102. Perez-Galvez, A.; Martin, H.D.; Sies, H.; Stahl, W. Incorporation of Carotenoids from Paprika Oleoresin into Human Chylomicrons. Br. J. Nutr. 2003, 89 (6), 787-793.
103. Levy, L.W.; Regalado, E.; Navarrete, S.; Watkins, R.H. Bixin and Norbixin in Human Plasma: Determination and Study of the Absorption of a Single Dose of Annatto Food Color. Analyst 1997, 122 (9), 977-980.
104. Czeczuga-Semeniuk, E.; Wolczynski, S.; Markiewicz, W. Preliminary Identification of Carotenoids in Malignant and Benign Neoplasms of the Breast and Surrounding Fatty Tissue. Neoplasma 2003, 50 (4), 280-286.
105. Bonzongo, J-C. J.; Donkor, A.K. Increasing UV-B Radiation at the Earth's Surface and Potential Effects on Aqueous Mercury Cycling and Toxicity. Chemosphere 2003, 52 (8), 1263-1273.
106. Young, T.A.; Cunningham, C.C.; Bailey, S.M. Reactive Oxygen Species Production by the Mitochondrial Respiratory Chain in Isolated Rat Hepatocytes and Liver Mitochondria: Studies using Myxothiazol. Arch Biochem. Biophys, 2002, 405, 65-72.
107. Afanas'ev, I.B. On Mechanism of Superoxide Signaling under Physiological and Pathophysiological Conditions. Medical Hypotheses 2005, 64(1): 127-129.
108. Ames, B.N.; Shigenaga, M.K.; Hagen, T.M. Oxidants, Antioxidants and the Degenerative Diseases of Aging. Proc. Natl. Acad. Sci. USA 1993, 90, 7915-7922.
109. Halliwell, B.; Gutteridge, J.M.C. Oxidative Stress and Antioxidant Protection: Some Special Cases. In Free Radicals in Biology and Medicine, 3rd Ed.; Halliwell, B.; Gutteridge, J.M.C.; Eds.; Clarendon Press: Oxford, 1999; 530-533.
110. Stahl, W.; Sies, H. Bioactivity and Protective Effects of Natural Carotenoids. Biochimica et Biophysica Acta (BBA) -Molecular Basis of Disease 2005, 1740 (2), 101-107.
111. Stahl, W.; Sies, H. Antioxidant Activity of Carotenoids. Molecular Aspects of Medicine 2003, 24 (6), 345-351.
112. Piette, J. Biological Consequences Associated with DNA Oxidation Mediated by Singlet Oxygen. J. Photochem. Photobiol. 1991, 11, 241-260.
113. Epe, B. Genotoxicity of Singlet Oxygen. Chem. Biol. Interact. 1991, 80, 239-260.
114. Ouedraogo, G.D.; Redmond, R.W. Secondary Reactive Oxygen Species Extend the Range of Photosensitization Effects in Cells: DNA Damage Produced via Initial Membrane Photosensitization. Photochem. Photobiol. 2003, 77 (2), 192-203.
115. Honda, S.; Hjelmeland, L.M.; Handa, J.T. Oxidative Stress-Induced Single-Strand Breaks in Chromosomal Telomeres of Human Retinal Pigment Epithelial Cells in Vitro. Investigative Ophthalmology and Visual Science 2001, 42, 2139-2144.
116. Kathe, S.D.; Shen, G.P.; Wallace, S.S. Single-Stranded Breaks in DNA but Not Oxidative DNA Base Damages Block Transcriptional Elongation by RNA Polymerase II in HeLa Cell Nuclear Extracts. J. Biol. Chem. 2004, 279 (18), 18,511-18,520.
117. Cui, J.; Liu, P.K. Neuronal NOS Inhibitor that Reduces Oxidative DNA Lesions and Neuronal Sensitivity Increases the Expression of Intact c-fos Transcripts after Brain Injury. Journal of Biomedical Sci. 2001, 8, 336-341.
118. Black, H.S. Radical Interception by Carotenoids and Effects on UV Carcinogenesis. Nutr. Cancer. 1998, 31, 212-217.
119. Edge, R.; McGarvey, D.J.; Truscott, T.G. The Carotenoids as Antioxidants: A Review. J. Photochem. Photobiol. B. Biology 1997, 41, 189-200.
120. Cantrell, A.; McGarvey, D.J.; Truscott, T.G.; Rancan, F.; Böhm, F. Singlet Oxygen Quenching by Dietary Carotenoids in a Model Membrane Environment. Archives of Biochemistry and Biophysics 2003, 412 (1), 47-54.
121. Palace, V.P.; Khaper, N.; Qin, Q.; Singal, P.K. Antioxidant Potentials of Vitamin A and Carotenoids and Their Relevance to Heart Disease. Free Radical Biology and Medicine 1999, 26 (5-6), 746-761.
122. Frei, B. Reactive Oxygen Species and Antioxidant Vitamins. Linus Pauling Institute, Fall Winter Newsletter. 1997. http://lpi.oregonstate.edu/f-w97/ reactive.html (accessed May 20, 2005).
123. Maoka, T.; Mochida, K.; Kozuka, M.; Ito, Y.; Fujiwara, Y.; Hashimoto, K.; Enjo, F.; Ogata, M.; Nobukuni, Y.; Tokuda, H.; Nishino, H. Cancer Chemopreventive Activity of Carotenoids in the Fruits of Red Paprika Capsicum Annuum L. Cancer Lett. 2001, 172 (2), 103-109.
124. Rühl, R.; Sczech, R.; Landes, N.; Pfluger, P.; Kluth, D.; Schweigert, F.J. Carotenoids and Their Metabolites are Naturally Occurring Activators of Gene Expression via the Pregnane X Receptor. European Journal of Nutr. 2004, 43 (6), 336-343.
125. Mecocci, P.; Polidori, M.C.; Churibini, A.; Ingegni, T.; Mattioli, P.; Catani, M.; Rinaldi, P.; Cecchetti, R.; Stahl, W.; Senin, U.; Beal, M.F. Lymphocyte Oxidative DNA Damage and Plasma Antioxidants in Alzheimer Disease. Arch. Neurol. 2002, 59 (5), 794-798.
126. Kim, M.K.; Ahn, S.H.; Lee-Kim, Y.C. Relationship of Serum α-Tocopherol, Carotenoids and Retinol with the Risk of Breast Cancer. Nutrition Research 2001, 21 (6), 797-809.
127. De Flora, S.; Bagnasco, M.; Vainio, H. Modulation of Genotoxic and Related Effects by Carotenoids and Vitamin A in Experimental Models: Mechanistic Issues. Mutagenesis 1999, 14 (2), 153-172.
128. Singh, V.N.; Gaby, S.K. Premalignant Lesions: Role of Antioxidant Vitamins and Beta-Carotene in Risk Reduction and Prevention of Malignant Transformation. Am. J. Clin. Nutr. 1991, 53, 386S-390S.
129. Nara, E.; Hayashi, H.; Kotake, M.; Miyashita, K.; Nagao, A. Acyclic Carotenoids and Their Oxidation Mixtures Inhibit the Growth of HL-60 Human Promyelocytic Leukemia Cells. Nutr. Cancer. 2001, 39, 273-283.
130. Livny, O.; Kaplan, I.; Reifen, R.; Polak-Charcon, S.; Madar, Z.; Schwartz, B. Lycopene Inhibits Proliferation and Enhances Gap-Junction Communication of KB-1 Human Oral Tumor Cells. J. Nutr. 2002, 132 (12), 3754-3759.
131. Zhang, L.X.; Cooney, R.V.; Bertram, J.S. Carotenoids Up-Regulate Connexin-43 Gene Expression Independent of Their Provitamin-A or Antioxidant Properties. Cancer Res. 1992, 52 (20), 5707-5712.
132. Levy, J.; Sharoni, Y. The Functions of Tomato Lycopene and its Role in Human Health. HerbalGram. 2004, 62, 49-56.
133. Krinsky, N. I. Carotenoids as Antioxidants. Nutrition 2001, 17, 815-817.
134. Hennekens, C.H.; Buring, J.E.; Manson, J.E.; Stampfer, M.; Rosner, B.; Cook, N.R.; Belanger, C.; LaMotte, F.; Gaziano, J.M.; Ridker, P.M. Lack of Effect of Long-Term Supplementation with α-Carotene on the Incidence of Malignant Neoplasms and Carduiovascular Disease. New Engl. J. Med. 1996, 334, 1145-1149.
135. Heinonen, O.P.; Huttunen, J.K.; Albanes, D.; Haapakoski, J.; Palmgren, J.; Pietinen, P.; Pikkarainen, J.; Rautalahti, M.; Virtamo, J.; Edwards, B.K. Effect of Vitamin E and β-Carotene on the Incidence of Lung Cancer and Other Cancers in Male Smokers. New Engl. J. Med. 1994, 330, 1029-1035.
136. Russell, R.M. The Enigma of β-Carotene in Carcinogenesis: What Can Be Learned from Animal Studies. J. Nutr. 2004, 134, 262S-268S.
137. Amir, H.; Karas, M.; Giat, J.; Danilenko, M.; Levy, R.; Yermiahu, T.; Levy, J.; Sharoni, Y. Lycopene and 1,25-Dihydroxyvitamin-D3 Cooperate in the Inhibition of Celly Cycle Progression and Induction of Differentiation in HL-60 Leukemic Cells. Nutr. Cancer. 1999, 33, 105-112.
138. Sharoni, Y.; Danilenko, M.; Dubi, N.; Ben-Dor, A.; Levy, J. Carotenoids and Transcription. Arch. Biochem. Biophys. 2004, 430 (1), 89-96.
139. Puduvalli, V.K.; Li, J.T.; Chen, L.; McCutcheon, I.E. Induction of Apoptosis in Primary Meningioma Cultures by Fenretinide. Cancer Res. 2005, 4, 1547-53.
140. Ramos-Gomez, M.; Kwak, M.K.; Dolan, P.M.; Itoh, K.; Yamamoto, M.; Talalay, P.; Kensler, T.W. Sensitivity to Carcinogenesis is Increased and Chemopreventive Efficacy of Enzyme Inducers is Lost in NrF2 Transcription Factor-Deficient Mice. Proc. Natl. Acad. Sci. USA. 2001, 98, 3410-3415.
141. Sharoni, Y.; Danilenko, M.; Walfisch, S.; Amir, H.; Nahum, A.; Ben-Dor, A.; Hirsch. K.; Khanin, M.; Steiner, M.; Agemy, L.; Zango, G.; Levy, J. Role of Gene Regulation in the Anti-canceractivity of Carotenoids. Pure Appl. Chem. 2002, 74 (8), 1469-1477.
142. Palozza, P. Carotenoids and Modulation of Cancer: Molecular Targets. Currtent Pharmacogenomics 2004, 2(1), 35-45.
143. Palozza, P.; Serini, S.; Torsello, A.; Di Nicuolo, F.; Maggiano, N.; Ranelletti, F.O.; Wolf, F.I.; Calviello, G. Mechanism of Activation of Caspase Cascade During β-Carotene-Induced Apoptosis in Human Tumor Cells. Nutrition and Cancer. 2003, 47 (1), 76-87.
144. Marchetti, P.; Zamzami, N.; Joseph, B.; Schraen-Maschke, S.; Mereau-Richard, C.; Costantini, P.; Metivier, D.; A. Susin, S.; Kroemer, G.; Formstecher, P. The Novel Retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2- naphtalene Carboxylic Acid Can Trigger Apoptosis through a Mitochondrial Pathway Independent of the Nucleus. Cancer Res. 1999, 59, 6257-6266.
145. Hail, N. Jr.; Youssef, E.M.; Lotan, R. Evidence Supporting a Role for Mitochondrial Respiration in Apoptosis Induction by the Synthetic Retinoid CD437/AHPN. Cancer Res. 2001, 61, 6698-6702.
146. Toba, T.; Shidoji, Y.; Fujii, J.; Moriwaki, H.; Muto, Y.; Suzuki, T. Growth Suppression and Induction of Heat-Shock Protein-70 by 9-cis-ß-Carotene in Cervical Dysplasia-Derived Cells. Life Sci. 1997, 61, 839-845.
147. Eberhart, C.E.; Coffey, R.J.; Radhika, A.; Giardiello, P.M.; Ferrenbach, S.; Dubois, R.N. Upregulation of Cyclooxygenase-2 Gene Expression in Human Colorectal Adenomas and Adenocarcinomas. Gastroenterology 1994, 107 (4), 1183-1188.
148. Collins, A.R. Carotenoids and Genomic Stability. Mutation Research/Fundamental and Molecular Mechanics of Mutagenesis 2001, 475 (1-2), 21-28.
149. Zhang, L.X.; Cooney, R.V.; Bertram, J.S. Carotenoids Enhance Gap Junctional Communication and Inhibit Lipid Peroxidation in C3H/10T1/2 Cells: Relationship to Their Cancer Chemopreventive Action. Carcinogenesis 1991, 12, 2109-2114.
150. Astorg, P. Food Carotenoids and Cancer Prevention: An Overview of Current Research. Trends Fd. Sci. Technol. 1997, 8 (12), 406-413.
151. Lee, I.M.; Cook, N.R.; Manson, J.E; Buring, J.E.; Hennekens, C.H. Beta-Carotene Supplementation and Incidence of Cancer and Cardiovascular Disease: the Women's Health Study. J. Natl. Cancer Inst. 1999, 91 (24), 2102-2106.
152. Pryor, W.A.; Stahl, W.; Rock, C.L. Beta Carotene: from Biochemistry to Clinical Trials. Nutr. Rev. 2000, 58, 39-53.
153. Omenn, G.S. Human Lung Cancer Chemoprevention Strategies. Chest. 2004, 125, 123S-127S.
154. Wright, M.E.; Mayne, S.T.; Swanson, C.A.; Sinha, R.; Alavcanja, M.C. Dietary Carotenoids, Vegetables, and Lung Cancer Risk in Women: the Missouri Women's Healty Study (United States). Cancer Causes Control 2003, 14 (1), 85-96.
155. Clavel-Chapelton, F.; Niravong, M.; Joseph, R.R. Diet and Breast Cancer: Review of the Epidemiologic Literature. Cancer Detect. Prev. 1977, 27 (5), 426-440.
156. Cooper, D.A.; Eldridge, A.L.; Peters, J.C. Dietary Carotenoids and Certain Cancers, Heart Disease, and Age-Related Macular Degeneration: A Review of Recent Research. Nutr. Rev. 1999, 57, 201-214.
157. Dorgan, J.F.; Sowell, A.; Swanson, C.A.; Potischman, N.; Miller, R.; Schussler, N.; Stephenson, H.E. Jr. Relationships of Serum Carotenoids, Retinol, Alpha-Tocopherol, and Selenium with Breast Cancer Risk: Results from a Prospective Study in Columbia, Missouri (United States). Cancer Causes Control 1998, 9 (1), 89-97.
158. Nahum, A.; Hirsch, K.; Danilenko, M.; Watts, C.K.W.; Prall, O.W.J.; Levy, J.; Sharoni Y. Lycopene Inhibition of Cell Cycle Progression in Breast and Endometrial Cancer Cells is Associated with Reduction in Cyclin D Levels and Retention of p27Kipl in the Cyclin E-cdk2 Complexes. Oncogene 2001, 20, 3428-3436.
159. Sesso, H.D.; Buring, J.E.; Zhang, S.M.; Norkus, E.P.; Gaziano, J.M. Dietary and Plasma Lycopene and the Risk of Breast Cancer. Cancer Epidemiol Biomarkers Prev. 2005, 14 (5), 1074-1081.
160. Giovannucci, E., Ascherio, A.; Rimm, E.B.; Stampfer, M.J.; Coldtiz, G.A.; Willett, W.C. Intake of Carotenoids and Retinol in Relation to Risk of Prostate Cancer. J. Natl. Cancer Inst. 1995, 87, 1767-1776.
161. Giovannucci, E.; Rimm, E.; Liu, Y.; Stampfer, M.; Willet, W. A Prospective Study of Tomato Products, Lycopene and Prostate Cancer Risk. J. Natl. Cancer Inst. 2002, 94 (5), 391-398.
162. Amsellem-Ouazana, D.; Conquy, S. Diet and Prostate Cancer: From Prevention to Treatment. Prog. Urol. 2004, 14 (4), 573-576.
163. Miller, E.C.; Giovannucci, E.; Erdman, J.W.; Bahnson, R.; Schwartz, S.J.; Clinton, S.K. Tomato Products, Lycopene, and Prostate Cancer Risk. Urol. Clin. N. Am. 2002, 29, 83-93.
164. Chen, L.; Stacewicz-Sapuntzakis, M.; Duncan, C.; Sharifi, R.; Ghosh, L.; van Breemen, R.; Ashton, D.; Bowen, P.E. Oxidative DNA Damage in Prostate Cancer Patients Consuming Tomato Sauce-Based Entrees as a Whole-Food Intervention. J. Natl. Cancer Inst. 2001, 93, 1872-1879.
165. Potter, J.D.; Slattery, M.L.; Bostick, R.M.; Gapstur, S.M. Colon Cancer: A Review of the Epidemiology. Epidemiol. Rev. 1993, 15, 499-545.
166. Slattery, M.L.; Benson, J.; Curtin, K.; Ma, K-Ni.; Schaeffer, D.; Potter, J.D. Carotenoids and Colon Cancer. Am. J. Clin. Nutr. 2000, 71, 575-582.
167. Terry, P.; Jain, M.; Miller, A.B.; Howe, G.R.; Rohan, T.E. Dietary Carotenoid Intake and Colorectal Cancer Risk. Nutr. Cancer. 2002, 42 (2), 167-172.
168. Heinrich, U., Gartner, C., Wiebusch, M. Supplementation with Beta-Carotene or a Similar Amount of Mixed Carotenoids Protects Humans from UV-Induced Erythema. J. Nutr. 2003, 133 (1), 98-101.
169. Stahl, W.; Heinrich, U.; Wiseman, S.; Eichler, O.; Sies, H.; Tronnier, H. Dietary Tomato Paste Protects Against Ultraviolet Light-Induced Erythema in Humans. J. Nutr. 2001, 131 (5), 1449-1451.
170. Ribaya-Mercado, J.D.; Garmyn, M.; Gilchrest, B.A.; Russell, R.M. Skin Lycopene is Destroyed Preferentially over Beta-Carotene during Ultraviolet Irradiation in Humans. J. Nutr. 1995, 125 (7), 1854-1859.
171. Ferris, F.L. III; Fine, S.L.; Hyman, L.A. Age-Related Macular Degeneration and Blindness Due to Neovascular Maculopathy. Arch. Ophthalmol. 1984, 102, 1640-1642.
172. Bressler, N.M.; Bressler, S.B.; Fine, S.L. Age-Related Macular Degeneration. Surv. Ophthalmol. Vis. Sci. 1988, 32, 375.
173. Fuhrman, B.; Ben-Yaish, L.; Attias, J.; Hayek, T.; Aviram, M. Tomato Lycopene and Beta-Carotene Inhibit Low Density Lipoprotein Oxidation and this Effect Depends on Lipoprotein Vitamin E Content. Nutr. Metab. Cardiovasc. Dis. 1997, 7, 433-443.
174. Kohlmeier, L.; Kark, J.D.; Gomez-Gracia, E. Lycopene and Myocardial Infarction Risk in the EURAMIC Study. Am. J. Epidemiol. 1997, 146, 618-626.
175. Klipstein-Grobusch, K.; Launer, L.J.; Geleijnse, J.M.; Boeing, H.; Hofman, A.; Witteman, J.C. Serum Carotenoids and Atherosclerosis. The Rotterdam Study. Atherosclerosis 2000, 148 (1), 49-56.
176. Sesso, H.D.; Buring, J.E.; Norkus, E.P.; Gaziano, J.M. Plasma Lycopene, Other Carotenoids, and Retinol and the Risk of Cardiovascular Disease in Women. Am. J. Clin. Nutr. 2004, 79 (1), 47-53.
177. Watzl, B.; Bub, A.; Briviba, K.; Rechkemmer, G. Supplementation of a Low-Carotenoid Diet with Tomato or Carrot Juice Modulates Immune Functions in Healthy Men. Ann. Nutr. Metab. 2003, 47 (6), 255-261.
178. Chew, B.P.; Park, J.S. Carotenoid Action on the Immune Response. J. Nutr. 2004, 134 (1), 257S-261S.
179. Cser, M.A.; Majchrzak, D.; Rust, P.; Sziklai-Laszlo, I.; Kovacs, I.; Bocskai, E.; Elmadfa, I. Serum Carotenoid and Retinol Levels during Childhood Infections. Ann. Nutr. Metab. 2004, 48 (3), 156-162.
180. van der Horst-Graat, J.M.; Kok, F.J.; Schouten, E.G. Plasma Carotenoid Concentrations in Relation to Acute Respiratory Infections in Elderly People. Br. J. Nutr. 2004, 92 (1), 113-118.
181. Ruhl, R.; Garcia, A.; Schweigert, F.J.; Worm, M. Modulation of Cytokine Production by Low and High Retinoid Diets in Ovalbumin-Sensitized Mice. Int. J. Vitam. Nutr. Res. 2004, 74 (4), 279-284.