Is there an anti-inflammatory potential beyond the antioxidant power of cocoa?

Chocolate, Fast Foods and Sweeteners: Consumption and Health

Volumn , Issue , 2011, Pages 85-104

  Pérez Cano, Francisco J ^a,b   Pérez Berezo, Teresa ^a   Ramos Romero, Sara ^a   Ramiro Puig, Emma ^c   Castellote, Cristina ^a,b,d   Franch, Àngels ^a,b,d   Castell, Margarida ^a,b  

^a UNIVERSITY OF BARCELONA   (Spain)

^b Institut de Recerca en Nutrició i Seguretat Alimentària   (Spain)

^c INSERM   (France)

^d CIBER EPIDEMIOLOGÍA Y SALUD PÚBLICA CIBERESP   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84881595401     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (117)

1. Alía, M., Mateos, R., Ramos, S., Lecumberri, E., Bravo, L. & Goya, L. (2006). Influence of quercetin and rutin on growth and antioxidant defense system of a human hepatoma cell line (HepG2). Eur. J. Nutr., 45, 19-28.
2. Anonymous. (1993). The Cocoa Manual: A Guide to De Zaan's Cocoa Products. Holland De Zaan Pub.
3. Azam, S., Hadi, N., Khan, U. N. & Hadi, S. M. (2003). Antioxidant and prooxidant properties of caffeine, theobromine and xanthine. Med. Sci. Monit., 9, 325-330.
4. Baba, S., Osakabe, N., Natsume, M., Yasuda, A., Takizawa, T., Nakamura, T. & Terao, J. (2000). Cocoa powder enhances the level of antioxidative activity in rat plasma. Br. J. Nutr., 84, 673-680.
5. Baba, S., Osakabe, N., Natsume, M., Muto, Y., Takizawa, T. & Terao, J. (2001). Absorption and urinary excretion of (-)-epicatechin after administration of different levels of cocoa powder or (-)-epicatechin in rats. J. Agric. Food Chem., 49, 6050-6056.
6. Baba, S., Osakabe, N., Natsume, M. & Terao, J. (2002). Absorption and urinary Free Radic. Biol. Med., 33, 142-148.
7. Baba, S., Osakabe, N., Kato, Y., Natsume, M., Yasuda, A., Kido, T., Fukuda, K., Muto, Y. & Kondo, K. (2007). Continuous intake of polyphenolic compounds Am. J. Clin. Nutr., 85, 709-717.
8. Belščak, A., Komes, D., Horžić, D., Ganić, K. K. & Karlović, D. (2009). Comparative study of commercially available cocoa products in terms of their bioactive composition. Food Res. Int., 42, 707-716.
9. Borchers, A. T., Keen, C. L., Hannum, S. M. & Gershwin, M. E. (2000). Cocoa and chocolate: composition, bioavailability and health implications. J. Med. Food, 3, 77-105.
10. Buijsse, B., Feskens, E. J. M., Kok, F. J. & Kromhout, D. (2006). Cocoa intake, blood pressure, and cardiovascular mortality: the Zutphen Elderly Study. Arch. Int. Med., 166, 411-417.
11. Bureau, G., Longpré, F. & Martinoli, M. G. (2008). Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation. J. Neurosci. Res., 86, 403-410.
12. Castell, M., Franch, A., Ramos-Romero, S., Ramiro-Puig, E., Pérez-Cano, F. J. & Castellote, C. (2009) Effect of a diet rich in cocoa flavonoids on experimental acute inflammation. In Flavonoids: biosynthesis, biological effects and dietary sources, Nova Science Publishers, 213-229.
13. Cho, E. S., Jang, Y. J., Kang, N. J., Hwang, M. K., Kim, Y. T., Lee, K. W. & Lee, H. J. (2009). Cocoa procyanidins Free Radic. Biol. Med., 46, 1319-1327.
14. Comalada, M., Camuesco, D., Sierra, S., Ballester, I., Xaus, J., Gálvez, J. & Zarzuelo, A. (2005). In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kB pathway. Eur. J. Immunol., 35, 584-592.
15. Cooper, K. A., Donovan, J. L., Waterhouse, A. L. & Williamson, G. (2008) Cocoa and health: a decade of research. Br. J. Nutr., 99, 1-11.
16. Corti, R., Flammer, A. J., Hollenberg, N. K. & Lüscher, T. H. (2009). Cocoa and cardiovascular health. Circulation, 119, 1433-1441.
17. Cotelle, N. (2001). Role of flavonoids in oxidative stress. Curr. Top. Med. Chem., 1, 569-590.
18. Counet, C. & Collin, S. (2003). Effect of the number of flavanol units on the antioxidant activity of procyanidin fractions isolated from chocolate. J. Agric. Food Chem., 51, 6816-6822.
19. de Boer, V. C., Dihal, A. A., van der Woude, H., Arts, I. C., Wolffram, S., Alink, G. M., Rietjens, I. M., Keijer, J. & Hollman, P. C. (2005). Tissue distribution of quercetin in rats and pigs. J. Nutr., 135, 1718-1725.
20. de Pascual-Teresa, S., Johnston, K. L., DuPont, M. S., O'Leary, K. A., Needs, P. W., Morgan, L. M., Clifford, M. N., Bao, Y. & Williamson, G. (2004). Quercetin J. Nutr., 134, 552-557.
21. Deprez, S., Brezillon, C., Rabot, S., Philippe, C., Mila, I., Lapierre, C. & Scalbert, A. (2000). Polymeric proanthocyanidins are catabolized by human colonic microflora into low-molecular-weight phenolic acids. J. Nutr., 130, 2733-2738.
22. di Giuseppe, R., di Castelnuovo, A., Centritto, F., Zito, F., de Curtis, A., Costanzo, S., Vohnout, B., Sieri, S., Krogh, V., Donati, M. B., de Gaetano, G. & Iacoviello, L. (2008). Regular consumption of dark chocolate is associated with low serum concentrations of C-reactive protein in a healthy Italian population. J. Nutr., 138, 1939-1945.
23. Dillinger, T. L., Barriga, P., Escarcega, S., Jimenez, M., Salazar Lowe, D. & Grivetti, L. E. (2000). Food of the gods: cure for humanity? A cultural history of the medicinal and ritual use of chocolate. J. Nutr., 130, 2057S-2072S.
24. Erlejman, A. G., Fraga, C. G. & Oteiza, P. I. (2006). Procyanidins protect Caco-2 cells from bile acid- and oxidant-induced damage. Free Radic. Biol. Med., 41, 1247-1256.
25. Erlejman, A. G., Jaggers, G., Fraga, C. G. & Oteiza, P. I. (2008). TNFα-induced NF-kB activation and cell oxidant production are modulated by hexameric procyanidins in Caco-2 cells. Arch. Biochem. Biophys., 476, 186-195.
26. Fraga, C. G., Actis-Goretta, L., Ottaviani, J. I., Carrasquedo, F., Lotito, S. B., Lazarus, S., Schmitz, H. H. & Keen, C. L. (2005). Regular consumption of a flavanol-rich chocolate can improve oxidant stress in young soccer players. Clin. Dev. Immunol., 12, 11-17.
27. Galati, G. & O'Brien, P. J. (2004). Potential toxicity of flavonoids and other dietary phenolics: significance for chemoprotective anti-cancer properties. Free Radic. Biol. Med., 37, 287-303.
28. García-Mediavilla, V., Crespo, I., Collado, P. S., Esteller, A., Sánchez-Campos, S., Tuñón, M. J. & González-Gallego, J. (2007). The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cycloxygenase-2 and reactive C-protein, and down-regulation f the nuclear factor kappaB pathway in Chang Liver cells. Eur. J. Pharmacol., 557, 221-229.
29. Ghosh, D. & Scheepens, A. (2009). Vascular action of polyphenols. Mol. Nutr. Food Res., 53, 322-331.
30. Granado-Serrano, A. B., Martín, M. A., Izquierdo-Pulido, M., Goya, L., Bravo, L. & Ramos, S. (2007). Molecular mechanisms of (-)-epicatechin and chlorogenic acid on the regulation of the apoptotic and survival/proliferation pathways in a human hepatoma cell line. J. Agric. Food Chem., 55, 2020-2027.
31. Granado-Serrano, A. B., Martín M. A., Goya, L., Bravo, L. & Ramos, S. (2009). Time-course regulation J. Nutr. Biochem., 20, 115-124.
32. Gu, L., House, S. E., Wu, X., Ou, B. & Prior, R. L. (2006). Procyanidin and catechin contents and antioxidant capacity of cocoa and chocolate products. J. Agric. Food Chem., 54, 4057-4061.
33. Hämäläinen, M., Nieminen, R., Vuorela, P., Heinonen, M. & Moilanen, E. (2007). Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm., 2007, 45673-45683.
34. Hatano, T., Miyatake, H., Natsume, M., Osakabe, N., Takizawa, T., Ito, H. & Yoshida, T. (2002). Proanthocyanidin glycosides and related polyphenols from cacao liquor and their antioxidant effects. Phytochemistry, 59, 749-758.
35. Heptinstall, S., May, J., Fox, S., Kwik-Uribe, C. & Zhao, L. (2006). Cocoa flavanols and platelet J. Cardiovasc. Pharmacol., 47, S197-S205.
36. Holt, R. R., Lazarus, S. A., Sullards, M. C., Zhu, Q. Y., Schramm, D. D., Hammerstone, J. F., Fraga, C. G., Schmitz, H. H. & Keen, C. L. (2002). Procyanidin dimer Am. J. Clin. Nutr., 76, 798-804.
37. Hurst, W. J., Tarka, S. M. Jr., Powis, T. G., Valdez, F. Jr. & Hester, T. R. (2002). Cacao usage by the earliest Maya civilization. Nature, 418, 289-290.
38. Jalil, A. M. & Ismail, A. (2008a). Polyphenols in cocoa and cocoa products: is there a link between antioxidant properties and health?. Molecules, 13, 2190-2219.
39. Jalil, A. M., Ismail, A., Pei, C. P., Hamid, M. & Kamaruddin, S. H. (2008b). Effect of cocoa extract on glucometabolism, oxidative stress, and antioxidant enzymes in obese-diabetic rats. J. Agric. Food Chem., 56, 7877-7884.
40. Jenny, M., Saner, E., Klein, A., Ledochowski, M., Schennach H., Ueberall, F. & Fuchs, D. (2009). Cacao extracts suppress tryptophan degradation of mitogen-stimulated peripheral blood mononuclear cells. J. Ethnopharmacol., 122, 261-267.
41. Jonfia-Essien, W. A., West, G., Alderson, P. G. & Tucker, G. (2008). Phenolic content and antioxidant capacity of hybrid variety cocoa beans. Food Chem., 108, 1155-1159.
42. Kang, N. J., Lee, K. W., Lee, D. E., Rogozin, E. A., Bode, A. M., Lee, H. J., Dong, Z. (2008). Cocoa procyanidins suppress transformation by inhibiting mitogen-activated protein kinase kinase. J. Biol. Chem., 283, 20664-20673.
43. Kenny, T. P., Keen, C. L., Schmitz, H. H. & Gershwin, M. E. (2007). Immune effects of cocoa procyanidin oligomers on peripheral blood mononuclear cells. Exp. Biol. Med. (Maywood), 232, 293-300.
44. Kurosawa, T., Itoh, F., Nozaki, A., Nakano, Y., Katsuda, S., Osakabe, N., Tsubone, H., Kondo, K. & Itakura, H. (2005). Suppressive effects of cacao liquor polyphenols (CLP) on LDL oxidation and the development of atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic rabbits. Atherosclerosis, 179, 237-246.
45. Kwon, D. Y., Choi, K. H., Kim, S. J., Choi, D. W., Kim, Y. S., Kim, Y. C. (2009). Comparison of peroxyl radical scavenging capacity of commonly consumed beverages. Arch. Pharm. Res. 32, 283-287.
46. Lecumberri, E., Mateos, R., Ramos, S., Alía, M., Rúperez, P., Goya, L., Izquierdo-Pulido, M. & Bravo, L. (2006). Characterization of cocoa fiber and its effect on the antioxidant capacity of serum in rats. Nutr. Hosp. 21, 622-628.
47. Lecumberri, E., Goya, L., Mateos, R., Alía, M., Ramos, S., Izquierdo-Pulido, M. & Bravo, L. (2007). A diet rich in dietary fiber from cocoa improves lipid profile and reduces malondialdehyde in hypercholesterolemic rats. Nutrition, 23, 332-341.
48. Lee, J. K., Kim, S. Y., Kim, Y. S., Lee, W. H., Hwang, D. H. & Lee, J. Y. (2009). Suppression of the TRIF-dependent signaling pathway of Toll-like receptors by luteolin. Biochem. Pharmacol., 77, 1391-1400.
49. Lee, K. W., Kim, Y. J., Lee, H. J. & Lee, C. Y. (2003). Cocoa has more phenolic phytochemicals and a higher antioxidant capacity than teas and red wine. J. Agric. Food Chem., 51, 7292-7295.
50. Lee, K. W., Kundu, J. K., Kim, S. O., Chun, K. S., Lee, H. J. & Surh, Y. J. (2006). Cocoa polyphenols inhibit phorbol ester-induced superoxide anion formation in cultured HL-60 cells and expression of cyclooxygenase-2 and activation of NF-kappaB and MAPKs in mouse skin in vivo. J. Nutr., 136, 1150-1155.
51. Lin, S. K., Chang, H. H., Chen, Y. J., Wang, C. C., Galson, D. L., Hong, C. Y. & Kok, S. H. (2008). Epigallocatechin-3-gallate diminishes CCL2 expression in human osteoblastic cells via up-regulation of phosphatidylinositol 3-kinase/Akt/Raf-1 interaction: a potential therapeutic benefit for arthritis. Arthritis Rheum., 58, 3145-3156.
52. Mackenzie, G. G., Carrasquedo, F., Delfino, J. M., Keen, C. L., Fraga, C. G. & Oteiza, P. I. (2004). Epicatechin, catechin, and dimeric procyanidins inhibit PMA-induced NF-kappaB activation at multiple steps in Jurkat T cells. FASEB J., 18, 167-169.
53. Manach, C., Scalbert, A., Morand, C., Remesy, C. & Jimenez, L. (2004a). Polyphenols: food sources and bioavailability. Am. J. Clin. Nutr., 79, 727-747.
54. Manach, C. & Donovan, J. L. (2004b). Pharmacokinetics and metabolism of dietary flavonoids in humans. Free Radic. Res., 38, 771-785.
55. Manach, C., Williamson, G., Morand, C., Scalbert, A. & Remesy, C. (2005). Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am. J. Clin. Nutr., 81, 230-242.
56. Mao, T. K., van de Water, J., Keen, C. L., Schmitz, H. H. & Gershwin, M. E. (2002). Modulation of TNF-alpha secretion in peripheral blood mononuclear cells by cocoa flavanols and procyanidins. Dev. Immunol., 9, 135-141.
57. Martín, M. A., Ramos, S., Mateos, R., Granado-Serrano, A. B., Izquierdo-Pulido, M., Bravo, L. & Goya, L. (2008). Protection of human J. Agric. Food Chem., 56, 7765-7772.
58. Martín, M. A., Ramos, S., Mateos, R., Izquierdo-Pulido, M., Bravo, L. & Goya, L. Protection of human HepG2 cells against an oxidative stress by the flavonoid epicatechin. Phytotherapy Res., in press.
59. Martinon, F., Mayor, A. & Tschopp, J. (2009). The inflammasomes: guardians of the body. Annu. Rev. Immunol., 27, 229-265.
60. Mathur, S., Devaraj, S., Grundy, S. M. & Jialal, I. (2002). Cocoa products decrease low density lipoprotein oxidative susceptibility but do not affect biomarkers of inflammation in humans. J. Nutr., 132, 3663-3667.
61. Matsuoka, Y., Hasegawa, H., Okuda, S., Muraki, T., Uruno, T. & Kubota, K. (1995). Ameliorative effects of tea J. Pharmacol. Exp. Ther., 274, 602-608.
62. Mazzon, E., Muià, C., Paola, R. D., Genovese, T., Menegazzi, M., De Sarro, A., Suzuki, H. & Cuzzocrea, S. (2005). Green tea polyphenol extract attenuates colon injury induced by experimental colitis. Free Radic. Res., 39, 1017-1025.
63. McCarty, M. F. (2008). Scavenging of peroxynitrite-derived radicals by flavonoids may support endothelial NO synthase activity, contributing to the vascular protection associated with high fruit and vegetable intakes. Med. Hypotheses, 70, 170-181.
64. McShea, A., Ramiro-Puig, E., Munro, S. B., Casadesus, G., Castell, M. & Smith, M. A. (2008). Clinical benefit and preservation of flavonols in dark chocolate Nutr. Rev., 66, 630-641.
65. Medzhitov, R. (2008). Origin and physiological Nature 454, 428-435.
66. Miller, K. B., Stuart, D. A., Smith, N. L., Lee, C. Y., McHale, N. L., Flanagan, J. A., Ou, B. & Hurst, W. J. (2006). Antioxidant activity and polyphenol and procyanidin contents of selected commercially available cocoa-containing and chocolate products in the United States. J. Agric. Food Chem., 54, 4062-4068.
67. Miyake, M., Ide, K., Sasaki, K., Matsukura, Y., Shijima, K. & Fujiwara, D. (2008). Oral administration. Biosci. Biotechnol, Biochem., 72, 1781-1788.
68. Morel, I., Lescoat, G., Cogrel, P., Sergent, O., Pasdeloup, N., Brissot, P., Cillard, P. & Cillard, J. (1993). Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochem. Pharmacol., 45, 13-19.
69. Morikawa, K., Nonaka, M., Narahara, M., Torii, I., Kawaguchi, K., Yoshikawa, T., Kumazawa, Y., & Morikawa, S. (2003). Inhibitory effect of quercetin on carrageenan-induced inflammation in rats. Life Sci., 74, 709-721.
70. Morinobu, A., Biao, W., Tanaka, S., Horiuchi, M., Jun, L., Tsuji, G., Sakai, Y., Kurosaka, M. & Kumagai, S. (2008). (-)-Epigallocatechin-3-gallate suppresses osteoclast differentiation and ameliorates experimental arthritis in mice. Arthritis Rheum., 58, 2012-2018.
71. Muthian, G. & Bright, J. J. (2004). Quercetin, a flavonoid phytoestrogen, ameliorates experimental allergic encephalomyelitis by blocking IL-12 signaling through JAK-STAT pathway in T lymphocyte. J. Clin. Immunol., 24, 542-552.
72. Nair, M. P., Mahajan, S., Reynolds, J. L., Aalinkeel, R., Nair, H., Schwartz, S. A. & Kandaswami, C. (2006). The flavonoid quercetin inhibits proinflammatory cytokine (tumor necrosis factor alpha) gene expression in normal peripheral blood mononuclear cells via modulation of the NF-κβ system. Clin. Vaccine Immunol., 13, 319-328.
73. Nakao, M., Takio, S. & Ono, K. (1998). Alkyl peroxyl radical-scavenging activity of catechins. Phytochemistry, 49, 2379-2382.
74. Natsume, M., Osakabe, N., Yasuda, A., Baba, S., Tokunaga, T., Kondo, K., Osawa, T. & Terao, J. (2004). In vitro antioxidative activity of (-)-epicatechin glucuronide metabolites present in human and rat plasma. Free Radic. Res., 38, 1341-1348.
75. Nijveldt, R. J., van Nood, E., van Hoorn, D. E., Boelens, P. G., van Norren, K. & van Leeuwen, P. A. (2001). Flavonoids: a review of probable mechanisms of action and potential applications. Am. J. Clin. Nutr., 74, 418-425.
76. Ono, K., Takahashi, T., Kamei, M., Mato, T., Hashizume, S., Kamiya, S. & Tsutsumi, H. (2003). Effects of an aqueous extract of cocoa on nitric oxide production of macrophages activated by lipopolysaccharide and interferon-gamma. Nutrition, 19, 681-685.
77. Orozco, T. J., Wang, J. F. & Keen, C. L. (2003). Chronic consumption of a flavanol- and procyanindin-rich diet is associated with reduced levels of 8-hydroxy-2'-deoxyguanosine in rat testes. J. Nutr. Biochem., 14, 104-110.
78. Osakabe, N., Baba, S., Yasuda, A., Iwamoto, T., Kamiyama, M., Takizawa, T., Itakura, H. & Kondo, K. (2001). Daily cocoa intake reduces the susceptibility of low-density lipoprotein to oxidation as demonstrated in healthy human volunteers. Free Radic. Res., 34, 93-99.
79. Pantano, C., Reynaert, N. L., van der Vliet, A. & Janssen-Heininger, Y. M. (2006). Redox-sensitive kinases of the nuclear factor-kappaB signaling pathway. Antioxid. Redox Signal., 8, 1791-1806.
80. Park, Y. C., Rimbach, G., Saliou, C., Valacchi, G. & Packer, L. (2000). Activity of monomeric, dimeric, and trimeric flavonoids on NO production, TNF-alpha secretion, and NF-kappaB-dependent gene expression in RAW 264.7 macrophages. FEBS Lett., 465, 93-97.
81. Pazos, M. & Ersen, M. L., Medina, I. & Skibsted, L. H. (2007). Efficiency of natural phenolic compounds regenerating alpha-tocopherol from alpha-tocopheroxyl radical. J. Agric. Food Chem., 55, 3661-3666.
82. Pétrilli, V., Dostert, C., Muruve, D. A. & Tschopp, J. (2007). The inflammasome: a danger. Curr. Opin. Immunol., 19, 615-622.
83. Pollard, S. E., Kuhnle, G. G., Vauzour, D., Vafeiadou, K., Tzounis, X., Whiteman, M., Rice-Evans, C. & Spencer, J. P. (2006). The reaction of flavonoid metabolites with peroxynitrite. Biochem. Biophys. Res. Commun., 350, 960-968.
84. Pucciarelli, D. L., Grivetti, L. E. (2008). The medicinal use of chocolate in Early North America. Mol. Nutr. Food Res., 52, 1215-1227.
85. Pura Naik, J. (2001). Improved high-performance liquid chromatography method to determine theobromine and caffeine in cocoa and cocoa products. J. Agric. Food Chem., 49, 3579-3583.
86. Ramiro, E., Franch, A., Castellote, C., Pérez-Cano, F., Permanyer, J., Izquierdo-Pulido, M. & Castell, M. (2005). Flavonoids from Theobroma cacao down-regulate inflammatory mediators. J. Agric. Food Chem., 53, 8506-8511.
87. Ramiro-Puig, E., Urpí-Sardà, M., Pérez-Cano, F. J., Franch, A., Castellote, C. Andrés-Lacueva, C., Izquierdo-Pulido, M. & Castell, M. (2007a). Cocoa-enriched diet enhances antioxidant enzyme activity and modulates lymphocyte composition in thymus from young rats. J. Agric. Food Chem., 55, 6431-6438.
88. Ramiro-Puig, E. & Castell, M. (2009a). Cocoa: antioxidant and immunomodulator. Br. J. Nutr. 101, 931-940.
89. Ramiro-Puig, E., Casadesús, G., Lee, H. G., Zhu, X., McShea, A., Perry, G., Pérez-Cano, F. J., Smith, M. A. & Castell, M. (2009b). Neuroprotective effect of cocoa flavonoids on in vitro oxidative stress. Eur. J. Nutr., 48, 54-61.
90. Ramos-Romero, S., Ramiro-Puig, E., Pérez-Cano, F. J., Castellote, C., Franch, A. & Castell, M. (2008). Anti-inflammatory Proc. Nutr. Soc., 67, E65.
91. Richard, T., Lefeuvre, D., Descendit, A., Quideau, S. & Monti, J. P. (2006). Recognition characters in peptide-polyphenol complex formation. Biochim. Biophys. Acta, 1760, 951-958.
92. Rios, L. Y., Gonthier, M. P., Remesy, C., Mila, I., Lapierre, C., Lazarus, S. A., Williamson, G. & Scalbert, A. (2003). Chocolate intake increases urinary excretion of polyphenol-derived phenolic acids in healthy human subjects. Am. J. Clin. Nutr., 77, 912-918.
93. Rössner, S. (1997). Chocolate-divine food, fattening junk or nutritious supplementation? Eur. J. Clin. Nutr., 51, 341-345.
94. Rotelli, A. E., Guardia, T., Juárez, A. O., de la Rocha, N. E. & Pelzer, L. E. (2003). Comparative study of flavonoids in experimental models of inflammation. Pharmacol. Res., 48, 601-606.
95. Sakakibara, H., Honda, Y., Nakagawa, S., Ashida, H. & Kanazawa, K. (2003). Simultaneous determination of all polyphenols in vegetables, fruits, and teas. J. Agric. Food Chem., 51, 571-581.
96. Sanbongi, C., Suzuki, N. & Sakane, T. (1997). Polyphenols in chocolate, which have antioxidant activity, modulate immune functions in humans in vitro. Cell Immunol., 177, 129-136.
97. Sánchez-Rabaneda, F., Jáuregui, O., Casals, I. Andrés-Lacueva, C., Izquierdo-Pulido, M. & Lamuela-Raventós, R. M. (2003). Liquid chromatographic/electrospray ionization tandem mass spectrometric study of the phenolic composition of cocoa (Theobroma cacao). J. Mass Spectrom., 38, 35-42.
98. Sano, A., Yamakoshi, J., Tokutake, S., Tobe, K., Kubota, Y. & Kikuchi, M. (2003). Procyanidin B1 is detected in human serum after intake of proanthocyanidin-rich grape seed extract. Biosci. Biotechnol. Biochem., 67, 1140-1143.
99. Shoji, T., Masumoto, S., Moriichi, N., Akiyama, H., Kanda, T., Ohtake, Y. & Goda, Y. (2006). Apple procyanidin oligomers absorption in rats after oral administration: analysis of procyanidins in plasma using the porter method and high-performance liquid chromatography/tandem mass spectrometry. J. Agric. Food Chem., 54, 884-892.
100. Sies, H., Schewe, T., Heiss, C. & Kelm, M. (2005). Cocoa polyphenols Am. J. Clin. Nutr., 81, 304S-312S.
101. Son, J., Pang, B., McFaline, J. L., Taghizadeh, K. & Dedon, P. C. (2008). Surveying the damage: the challenges of developing nucleic acid Mol. Biosyst., 4, 902-908.
102. Spencer, J. P., Schroeter, H., Rechner, A. R. & Rice-Evans, C. (2001). Bioavailability of flavan-3-ols and procyanidins: gastrointestinal tract influences and their relevance to bioactive forms in vivo. Antioxid. Redox Signal., 3, 1023-1039.
103. Tomás-Barberán, F. A., Cienfuegos-Jovellanos, E., Marín, A., Muguerza, B., Gil-Izquierdo, A., Cerda, B., Zafrilla, P., Morillas, J., Mulero, J., Ibarra, A., Pasamar, M. A., Ramón, D. & Espín, J. C. (2007). A new process to develop a cocoa powder with higher flavonoid monomer content and enhanced bioavailability in healthy humans. J. Agric. Food Chem., 55, 3926-3935.
104. Urpí-Sarda, M., Monagas, M., Khan, N., Lamuela-Raventós, R. M., Santos-Buelga, C., Sacanella, E., Castell, M., Permanyer, J. & Andrés-Lacueva, C. (2009). Epicatechin, procyanidins, and phenolic microbial metabolites after cocoa intake in humans and rats. Anal. Bioanal. Chem., 394, 1545-1556.
105. Van Dyke, T. E. & Kornman, K. S. (2008). Inflammation and factors that may regulate inflammatory response. J. Periodontol., 79, 1503-1507.
106. Vauzour, D., Vafeiadou, K., Rodríguez-Mateos, A., Rendeiro, C. & Spencer, J. P. (2008). The neuroprotective potential of flavonoids: a multiplicity of effects. Genes Nutr., 3, 115-126.
107. Verstraeten, S. V., Mackenzie, G. G., Oteiza, P. I. & Fraga, C. G. (2008). (-)-Epicatechin and related procyanidins modulate intracellular calcium and prevent oxidation in Jurkat T cells. Free Radic. Res., 42, 864-872.
108. Vinson, J. A., Proch, J. & Zubik, L. (1999). Phenol antioxidant quantity and quality in foods: cocoa, dark chocolate, and milk chocolate. J. Agric. Food Chem., 47, 4821-4824.
109. Vinson, J. A., Proch, J., Bose, P., Muchler, S., Taffera, P., Shuta, D., Samman, N. & Agbor, G. A. (2006). Chocolate is a powerful ex vivo and in vivo antioxidant, an antiatherosclerotic agent in an animal model, and a significant contributor to antioxidants in the European and American Diets. J. Agric. Food Chem., 54, 8071-8076.
110. Visioli, F., Bernaert, H., Corti, R., Ferri, C., Heptinstall, S., Molinari, E., Poli, A., Serafini, M., Smit, H. J., Vinson, J. A., Violi, F., Paoletti, R. (2009). Chocolate, lifestyle, and health. Crit. Rev. Food Sci. Nutr., 49, 299-312.
111. Wang, J. F., Schramm, D. D, Holt, R. R., Ensunsa, J. L., Fraga, C. G., Schmitz, H. H. & Keen, C. L. (2000). A dose-response effect from chocolate consumption on plasma epicatechin and oxidative damage. J. Nutr., 130, 2115S-2119S.
112. Williams, R. J., Spencer, J. P. & Rice-Evans, C. (2004). Flavonoids: antioxidants or signalling Free Radic. Biol. Med., 36, 838-849.
113. Wisman, K. N., Perkins, A. A., Jeffers, M. D. & Hagerman, A. E. (2008). Accurate assessment of the bioactivities of redox-active polyphenolics in cell culture. J. Agric. Food Chem., 56, 7831-7837.
114. Yilmaz, Y. & Toledo, R. T. (2004). Major flavonoids in grape seeds and skins: antioxidant capacity of catechin, epicatechin, and gallic acid. J. Agric. Food Chem., 52, 255-260.
115. Youn, H. S., Lee, J. Y., Saitoh, S. I., Miyake, K., Kang, K. W., Choi, Y. J. & Hwang, D. H. (2006). Suppression of MyD88- and TRIF-dependent signaling pathways of toll-like receptor by (-)-epigallocatechin-3-gallate, a polyphenol component of green tea. Biochem. Pharmacol., 72, 850-859.
116. Zhu, Q. Y., Holt, R. R., Lazarus, S. A., Orozco, T. J. & Keen, C. L. (2002). Inhibitory effects of cocoa flavanols and procyanidin oligomers on free radical-induced erythrocyte hemolysis. Exp. Biol. Med., 227, 321-329.
117. Zhu, Q. Y., Schramm, D. D., Gross, H. B., Holt, R. R., Kim, S. H., Yamaguchi, T., Kwik-Uribe, C. L. & Keen, C. L. (2005). Influence of cocoa flavonols and procyanidins on free radical induced human erythrocyte hemolysis. Clin. Dev. Immunol., 12, 27-34.