Cocoa Phytochemicals: Recent Advances in Molecular Mechanisms on Health

REFERENCES

• Abd El Mohsen , M. M. , Kuhnle , G. , Rechner , A. R. , Schroeter , H. , Rose , S. , Jenner , P. and Rice-Evans , C. A. 2002 . Uptake and metabolism of epicatechin and its access to the brain after oral ingestion . Free Radic. Biol. Med. , 33 : 1693 – 1702 .
   PubMed Web of Science ®Google Scholar
• Andres-Lacueva , C. , Monagas , M. , Khan , N. , Izquierdo-Pulido , M. , Urpi-Sarda , M. , Permanyer , J. and Lamuela-Raventos , R. M. 2008 . Flavanol and flavonol contents of cocoa powder products: Influence of the manufacturing process . J. Agric. Food Chem , 56 : 3111 – 3117 .
   PubMed Web of Science ®Google Scholar
• Arteel , G. E. , Schroeder , P. and Sies , H. 2000 . Reactions of peroxynitrite with cocoa procyanidin oligomers . J. Nutr , 130 : 2100S – 2104S .
   PubMed Web of Science ®Google Scholar
• Baba , S. , Natsume , M. , Yasuda , A. , Nakamura , Y. , Tamura , T. , Osakabe , N. , Kanegae , M. and Kondo , K. 2007a . Plasma LDL and HDL cholesterol and oxidized LDL concentrations are altered in normo- and hypercholesterolemic humans after intake of different levels of cocoa powder . J. Nutr , 137 : 1436 – 1441 .
   PubMed Web of Science ®Google Scholar
• Baba , S. , Osakabe , N. , Kato , Y. , Natsume , M. , Yasuda , A. , Kido , T. , Fukuda , K. , Muto , Y. and Kondo , K. 2007b . Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-cholesterol concentrations in humans . Am. J. Clin. Nutr. , 85 : 709 – 717 .
   PubMed Web of Science ®Google Scholar
• Baba , S. , Osakabe , N. , Yasuda , A. , Natsume , M. , Takizawa , T. , Nakamura , T. and Terao , J. 2000 . Bioavailability of (−)-epicatechin upon intake of chocolate and cocoa in human volunteers . Free Radic. Res. , 33 : 635 – 641 .
   PubMed Web of Science ®Google Scholar
• Barcz , E. , Sommer , E. , Sokolnicka , I. , Gawrychowski , K. , Roszkowska-Purska , K. , Janik , P. and Skopinska-Rozewska , E. 1998 . The influence of theobromine on angiogenic activity and proangiogenic cytokines production of human ovarian cancer cells . Oncol. Rep , 5 : 517 – 520 .
   PubMed Web of Science ®Google Scholar
• Berliner , J. A. and Heinecke , J. W. 1996 . The role of oxidized lipoproteins in atherogenesis . Free Radic. Biol. Med , 20 : 707 – 727 .
   PubMed Web of Science ®Google Scholar
• Biessels , G. J. 2010 . Caffeine, diabetes, cognition, and dementia . J. Alzheimers Dis , 20 ( Suppl. 1 ) : S143 – S150 .
   PubMedGoogle Scholar
• Bisson , J. F. , Nejdi , A. , Rozan , P. , Hidalgo , S. , Lalonde , R. and Messaoudi , M. 2008 . Effects of long-term administration of a cocoa polyphenolic extract (Acticoa powder) on cognitive performances in aged rats . Br. J. Nutr. , 100 : 94 – 101 .
   PubMed Web of Science ®Google Scholar
• Brothers , H. M. , Marchalant , Y. and Wenk , G. L. 2010 . Caffeine attenuates lipopolysaccharide-induced neuroinflammation . Neurosci. Lett. , 480 : 97 – 100 .
   PubMed Web of Science ®Google Scholar
• Buijsse , B. , Feskens , E. J. , Kok , F. J. and Kromhout , D. 2006 . Cocoa intake, blood pressure, and cardiovascular mortality: The Zutphen Elderly Study . Arch. Intern. Med. , 166 : 411 – 417 .
   PubMed Web of Science ®Google Scholar
• Caligiani , A. , Cirlini , M. , Palla , G. , Ravaglia , R. and Arlorio , M. 2007 . GC-MS detection of chiral markers in cocoa beans of different quality and geographic origin . Chirality , 19 : 329 – 334 .
   PubMed Web of Science ®Google Scholar
• Carnesecchi , S. , Schneider , Y. , Lazarus , S. A. , Coehlo , D. , Gosse , F. and Raul , F. 2002 . Flavanols and procyanidins of cocoa and chocolate inhibit growth and polyamine biosynthesis of human colonic cancer cells . Cancer Lett , 175 : 147 – 155 .
   PubMed Web of Science ®Google Scholar
• Chavez-Valdez , R. , Wills-Karp , M. , Ahlawat , R. , Cristofalo , E. A. , Nathan , A. and Gauda , E. B. 2009 . Caffeine modulates TNF-alpha production by cord blood monocytes: The role of adenosine receptors . Pediatr. Res , 65 : 203 – 208 .
   PubMed Web of Science ®Google Scholar
• Chen , X. , Ghribi , O. and Geiger , J. D. 2010 . Caffeine protects against disruptions of the blood-brain barrier in animal models of Alzheimer's and Parkinson's diseases . J. Alzheimers Dis , 20 ( Suppl. 1 ) : S127 – S141 .
   PubMedGoogle Scholar
• Cho , E. S. , Jang , Y. J. , Kang , N. J. , Hwang , M. K. , Kim , Y. T. , Lee , K. W. and Lee , H. J. 2009 . Cocoa procyanidins attenuate 4-hydroxynonenal-induced apoptosis of PC12 cells by directly inhibiting mitogen-activated protein kinase kinase 4 activity . Free Radic. Biol. Med , 46 : 1319 – 1327 .
   PubMed Web of Science ®Google Scholar
• Cho , E. S. , Lee , K. W. and Lee , H. J. 2008 . Cocoa procyanidins protect PC12 cells from hydrogen-peroxide-induced apoptosis by inhibiting activation of p38 MAPK and JNK . Mutat. Res , 640 : 123 – 130 .
   PubMed Web of Science ®Google Scholar
• Cooper , K. A. , Campos-Gimenez , E. , Jimenez Alvarez , D. , Nagy , K. , Donovan , J. L. and Williamson , G. 2007 . Rapid reversed phase ultra-performance liquid chromatography analysis of the major cocoa polyphenols and inter-relationships of their concentrations in chocolate . J. Agric. Food Chem. , 55 : 2841 – 2847 .
   PubMed Web of Science ®Google Scholar
• Cooper , K. A. , Donovan , J. L. , Waterhouse , A. L. and Williamson , G. 2008 . Cocoa and health: A decade of research . Br. J. Nutr , 99 : 1 – 11 .
   PubMed Web of Science ®Google Scholar
• Corti , R. , Flammer , A. J. , Hollenberg , N. K. and Luscher , T. F. 2009 . Cocoa and cardiovascular health . Circulation , 119 : 1433 – 1441 .
   PubMed Web of Science ®Google Scholar
• Counet , C. , Callemien , D. and Collin , S. 2006 . Chocolate and cocoa: New sources of trans-resveratrol and trans-piceid . Food Chem , 98 : 649 – 657 .
   Web of Science ®Google Scholar
• Cuevas , E. , Limon , D. , Perez-Severiano , F. , Diaz , A. , Ortega , L. , Zenteno , E. and Guevara , J. 2009 . Antioxidant effects of epicatechin on the hippocampal toxicity caused by amyloid-beta 25-35 in rats . Eur. J. Pharmacol , 616 : 122 – 127 .
   PubMed Web of Science ®Google Scholar
• de Mendonca , A. and Cunha , R. A. 2010 . Therapeutic opportunities for caffeine in Alzheimer's disease and other neurodegenerative disorders . J. Alzheimers Dis. , 20 ( Suppl. 1) : S1 – S2 .
   PubMedGoogle Scholar
• Deprez , S. , Brezillon , C. , Rabot , S. , Philippe , C. , Mila , I. , Lapierre , C. and Scalbert , A. 2000 . Polymeric proanthocyanidins are catabolized by human colonic microflora into low-molecular-weight phenolic acids . J. Nutr , 130 : 2733 – 2738 .
   PubMed Web of Science ®Google Scholar
• Deprez , S. , Mila , I. , Huneau , J. F. , Tome , D. and Scalbert , A. 2001 . Transport of proanthocyanidin dimer, trimer, and polymer across monolayers of human intestinal epithelial Caco-2 cells . Antioxid. Redox. Signal , 3 : 957 – 967 .
   PubMed Web of Science ®Google Scholar
• Dillinger , T. L. , Barriga , P. , Escarcega , S. , Jimenez , M. , Salazar Lowe , D. and 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 .
   PubMed Web of Science ®Google Scholar
• Donovan , J. L. , Manach , C. , Rios , L. , Morand , C. , Scalbert , A. and Remesy , C. 2002 . Procyanidins are not bioavailable in rats fed a single meal containing a grapeseed extract or the procyanidin dimer B3 . Br. J. Nutr , 87 : 299 – 306 .
   PubMed Web of Science ®Google Scholar
• Dray , C. , Daviaud , D. , Guigne , C. , Valet , P. and Castan-Laurell , I. 2007 . Caffeine reduces TNFalpha up-regulation in human adipose tissue primary culture . J. Physiol. Biochem , 63 : 329 – 336 .
   PubMed Web of Science ®Google Scholar
• Echeverri , D. , Montes , F. R. , Cabrera , M. , Galan , A. and Prieto , A. 2010 . Caffeine's vascular mechanisms of action . Int. J. Vasc. Med. , 2010 : 834060
   PubMedGoogle Scholar
• Engler , M. B. and Engler , M. M. 2006 . The emerging role of flavonoid-rich cocoa and chocolate in cardiovascular health and disease . Nutr. Rev , 64 : 109 – 118 .
   PubMed Web of Science ®Google Scholar
• Engler , M. B. , Engler , M. M. , Chen , C. Y. , Malloy , M. J. , Browne , A. , Chiu , E. Y. , Kwak , H. K. , Milbury , P. , Paul , S. M. , Blumberg , J. and Mietus-Snyder , M. L. 2004 . Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults . J. Am. Coll. Nutr. , 23 : 197 – 204 .
   PubMed Web of Science ®Google Scholar
• Eskelinen , M. H. and Kivipelto , M. 2010 . Caffeine as a protective factor in dementia and Alzheimer's disease . J. Alzheimers Dis , 20 ( Suppl. 1 ) : S167 – S174 .
   PubMedGoogle Scholar
• Fisher , N. D. and Hollenberg , N. K. 2006 . Aging and vascular responses to flavanol-rich cocoa . J. Hypertens , 24 : 1575 – 1580 .
   PubMed Web of Science ®Google Scholar
• Fisher , N. D. , Hughes , M. , Gerhard-Herman , M. and Hollenberg , N. K. 2003 . Flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans . J. Hypertens , 21 : 2281 – 2286 .
   PubMed Web of Science ®Google Scholar
• Forsyth , W. G. 1952 . Cacao polyphenolic substances. I. Fractionation of the fresh bean . Biochem. J , 51 : 511 – 516 .
   PubMed Web of Science ®Google Scholar
• Fraga , C. G. , Actis-Goretta , L. , Ottaviani , J. I. , Carrasquedo , F. , Lotito , S. B. , Lazarus , S. , Schmitz , H. H. and 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 .
   PubMedGoogle Scholar
• Francis , S. T. , Head , K. , Morris , P. G. and Macdonald , I. A. 2006 . The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people . J. Cardiovasc. Pharmacol. , 47 ( Suppl. 2 ) : S215 – S220 .
   PubMed Web of Science ®Google Scholar
• Gasser , P. , Lati , E. , Peno-Mazzarino , L. , Bouzoud , D. , Allegaert , L. and Bernaert , H. 2008 . Cocoa polyphenols and their influence on parameters involved in ex vivo skin restructuring . Int. J. Cosmet Sci , 30 : 339 – 345 .
   PubMedGoogle Scholar
• Gil , M. , Skopinska-Rozewska , E. , Radomska , D. , Demkow , U. , Skurzak , H. , Rochowska , M. , Beuth , J. and Roszkowski , K. 1993 . Effect of purinergic receptor antagonists suramin and theobromine on tumor-induced angiogenesis in BALB/c mice . Folia Biol. (Praha). , 39 : 63 – 68 .
   PubMed Web of Science ®Google Scholar
• Gordon , D. J. , Probstfield , J. L. , Garrison , R. J. , Neaton , J. D. , Castelli , W. P. , Knoke , J. D. , Jacobs , D. R. Jr. , Bangdiwala , S. and Tyroler , H. A. 1989 . High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies . Circulation , 79 : 8 – 15 .
   PubMed Web of Science ®Google Scholar
• Gotti , R. , Furlanetto , S. , Pinzauti , S. and Cavrini , V. 2006 . Analysis of catechins in Theobroma cacao beans by cyclodextrin-modified micellar electrokinetic chromatography . J. Chromatogr. A. , 1112 : 345 – 352 .
   PubMed Web of Science ®Google Scholar
• Grassi , D. , Lippi , C. , Necozione , S. , Desideri , G. and Ferri , C. 2005 . Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons . Am. J. Clin. Nutr. , 81 : 611 – 614 .
   PubMed Web of Science ®Google Scholar
• Gu , L. , House , S. E. , Wu , X. , Ou , B. and Prior , R. L. 2006 . Procyanidin and catechin contents and antioxidant capacity of cocoa and chocolate products . J. Agric. Food Chem. , 54 : 4057 – 4061 .
   PubMed Web of Science ®Google Scholar
• Heinrich , U. , Neukam , K. , Tronnier , H. , Sies , H. and Stahl , W. 2006 . Long-term ingestion of high flavanol cocoa provides photoprotection against UV-induced erythema and improves skin condition in women . J. Nutr. , 136 : 1565 – 1569 .
   PubMed Web of Science ®Google Scholar
• Heiss , C. , Dejam , A. , Kleinbongard , P. , Schewe , T. , Sies , H. and Kelm , M. 2003 . Vascular effects of cocoa rich in flavan-3-ols . JAMA , 290 : 1030 – 1031 .
   PubMed Web of Science ®Google Scholar
• Heiss , C. , Finis , D. , Kleinbongard , P. , Hoffmann , A. , Rassaf , T. , Kelm , M. and Sies , H. 2007 . Sustained increase in flow-mediated dilation after daily intake of high-flavanol cocoa drink over 1 week . J. Cardiovasc. Pharmacol , 49 : 74 – 80 .
   PubMed Web of Science ®Google Scholar
• Heiss , C. , Kleinbongard , P. , Dejam , A. , Perre , S. , Schroeter , H. , Sies , H. and Kelm , M. 2005 . Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers . J. Am. Coll. Cardiol. , 46 : 1276 – 1283 .
   PubMed Web of Science ®Google Scholar
• Heiss , C. , Schroeter , H. , Balzer , J. , Kleinbongard , P. , Matern , S. , Sies , H. and Kelm , M. 2006 . Endothelial function, nitric oxide, and cocoa flavanols . J. Cardiovasc. Pharmacol. , 47 ( Suppl. 2 ) : S128 – S135 . discussion S172– S176
   PubMedGoogle Scholar
• Heo , H. J. and Lee , C. Y. 2005 . Epicatechin and catechin in cocoa inhibit amyloid beta protein induced apoptosis . J. Agric. Food Chem , 53 : 1445 – 1448 .
   PubMed Web of Science ®Google Scholar
• Heptinstall , S. , May , J. , Fox , S. , Kwik-Uribe , C. and Zhao , L. 2006 . Cocoa flavanols and platelet and leukocyte function: Recent in vitro and ex vivo studies in healthy adults . J. Cardiovasc. Pharmacol , 47 ( Suppl. 2 ) : S197 – S205 . discussion S206–S209
   PubMed Web of Science ®Google Scholar
• Hermann , F. , Spieker , L. E. , Ruschitzka , F. , Sudano , I. , Hermann , M. , Binggeli , C. , Luscher , T. F. , Riesen , W. , Noll , G. and Corti , R. 2006 . Dark chocolate improves endothelial and platelet function . Heart , 92 : 119 – 120 .
   PubMed Web of Science ®Google Scholar
• Hollenberg , N. K. , Martinez , G. , McCullough , M. , Meinking , T. , Passan , D. , Preston , M. , Rivera , A. , Taplin , D. and Vicaria-Clement , M. 1997 . Aging, acculturation, salt intake, and hypertension in the Kuna of Panama . Hypertension , 29 : 171 – 176 .
   PubMed Web of Science ®Google Scholar
• Holt , R. R. , Lazarus , S. A. , Sullards , M. C. , Zhu , Q. Y. , Schramm , D. D. , Hammerstone , J. F. , Fraga , C. G. , Schmitz , H. H. and Keen , C. L. 2002 . Procyanidin dimer B2 [epicatechin-(4beta-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa . Am. J. Clin. Nutr. , 76 : 798 – 804 .
   PubMed Web of Science ®Google Scholar
• Innes , A. J. , Kennedy , G. , McLaren , M. , Bancroft , A. J. and Belch , J. J. 2003 . Dark chocolate inhibits platelet aggregation in healthy volunteers . Platelets , 14 : 325 – 327 .
   PubMed Web of Science ®Google Scholar
• Jourdain , C. , Tenca , G. , Deguercy , A. , Troplin , P. and Poelman , D. 2006 . In-vitro effects of polyphenols from cocoa and beta-sitosterol on the growth of human prostate cancer and normal cells . Eur. J. Cancer Prev. , 15 : 353 – 361 .
   PubMed Web of Science ®Google Scholar
• Kang , N. J. , Lee , K. W. , Lee , D. E. , Rogozin , E. A. , Bode , A. M. , Lee , H. J. and Dong , Z. 2008 . Cocoa procyanidins suppress transformation by inhibiting mitogen-activated protein kinase kinase . J. Biol. Chem , 283 : 20664 – 20673 .
   PubMed Web of Science ®Google Scholar
• Kang , S. S. , Han , K. S. , Ku , B. M. , Lee , Y. K. , Hong , J. , Shin , H. Y. , Almonte , A. G. , Woo , D. H. , Brat , D. J. , Hwang , E. M. , Yoo , S. H. , Chung , C. K. , Park , S. H. , Paek , S. H. , Roh , E. J. , Lee , S. J. , Park , J. Y. , Traynelis , S. F. and Lee , C. J. 2010 . Caffeine-mediated inhibition of calcium release channel inositol 1,4,5-trisphosphate receptor subtype 3 blocks glioblastoma invasion and extends survival . Cancer Res. , 70 : 1173 – 1183 .
   PubMed Web of Science ®Google Scholar
• Kenny , D. , Coughlan , M. G. , Pagel , P. S. , Kampine , J. P. and Warltier , D. C. 1994 . Transforming growth factor beta 1 preserves endothelial function after multiple brief coronary artery occlusions and reperfusion . Am. Heart J , 127 : 1456 – 1461 .
   PubMed Web of Science ®Google Scholar
• Kenny , T. P. , Keen , C. L. , Jones , P. , Kung , H. J. , Schmitz , H. H. and Gershwin , M. E. 2004 . Pentameric procyanidins isolated from Theobroma cacao seeds selectively downregulate ErbB2 in human aortic endothelial cells . Exp. Biol. Med. (Maywood). , 229 : 255 – 263 .
   PubMed Web of Science ®Google Scholar
• Kim , J. E. , Son , J. E. , Jung , S. K. , Kang , N. J. , Lee , C. Y. , Lee , K. W. and Lee , H. J. 2010 . Cocoa polyphenols suppress TNF-alpha-induced vascular endothelial growth factor expression by inhibiting phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase kinase-1 (MEK1) activities in mouse epidermal cells . Br. J. Nutr. , 104 : 957 – 964 .
   PubMed Web of Science ®Google Scholar
• Kobayashi-Hattori , K. , Mogi , A. , Matsumoto , Y. and Takita , T. 2005 . Effect of caffeine on the body fat and lipid metabolism of rats fed on a high-fat diet . Biosci. Biotechnol. Biochem. , 69 : 2219 – 2223 .
   PubMed Web of Science ®Google Scholar
• Kostyuk , V. A. , Kraemer , T. , Sies , H. and Schewe , T. 2003 . Myeloperoxidase/ nitrite-mediated lipid peroxidation of low-density lipoprotein as modulated by flavonoids . FEBS Lett , 537 : 146 – 150 .
   PubMed Web of Science ®Google Scholar
• Kraemer , T. , Prakosay , I. , Date , R. A. , Sies , H. and Schewe , T. 2004 . Oxidative modification of low-density lipoprotein: Lipid peroxidation by myeloperoxidase in the presence of nitrite . Biol. Chem , 385 : 809 – 818 .
   PubMed Web of Science ®Google Scholar
• Ku , B. M. , Lee , Y. K. , Jeong , J. Y. , Ryu , J. , Choi , J. , Kim , J. S. , Cho , Y. W. , Roh , G. S. , Kim , H. J. , Cho , G. J. , Choi , W. S. and Kang , S. S. 2010 . Caffeine inhibits cell proliferation and regulates PKA/GSK3beta pathways in U87MG human glioma cells . Mol. Cells , 31 : 275 – 279 .
   PubMed Web of Science ®Google Scholar
• Lee , C. 2000 . Antioxidant ability of caffeine and its metabolites based on the study of oxygen radical absorbing capacity and inhibition of LDL peroxidation . Clin. Chim. Acta , 295 : 141 – 154 .
   PubMed Web of Science ®Google Scholar
• Lee , D. E. , Kang , N. J. , Lee , K. M. , Lee , B. K. , Kim , J. H. , Lee , K. W. and Lee , H. J. 2010 . Cocoa polyphenols attenuate hydrogen peroxide-induced inhibition of gap-junction intercellular communication by blocking phosphorylation of connexin 43 via the MEK/ERK signaling pathway . J. Nutr. Biochem. , 21 : 680 – 686 .
   PubMed Web of Science ®Google Scholar
• Lee , K. W. , Kang , N. J. , Oak , M. H. , Hwang , M. K. , Kim , J. H. , Schini-Kerth , V. B. and Lee , H. J. 2008 . Cocoa procyanidins inhibit expression and activation of MMP-2 in vascular smooth muscle cells by direct inhibition of MEK and MT1-MMP activities . Cardiovasc. Res , 79 : 34 – 41 .
   PubMed Web of Science ®Google Scholar
• Lee , K. W. , Kim , Y. J. , Lee , H. J. and 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 .
   PubMed Web of Science ®Google Scholar
• Lee , K. W. , Kundu , J. K. , Kim , S. O. , Chun , K. S. , Lee , H. J. and 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 .
   PubMed Web of Science ®Google Scholar
• Lijnen , P. J. , Petrov , V. V. and Fagard , R. H. 2000 . Induction of cardiac fibrosis by transforming growth factor-beta(1) . Mol. Genet Metab , 71 : 418 – 435 .
   PubMed Web of Science ®Google Scholar
• Loke , W. M. , Hodgson , J. M. , Proudfoot , J. M. , McKinley , A. J. , Puddey , I. B. and Croft , K. D. 2008 . Pure dietary flavonoids quercetin and (−)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men . Am. J. Clin. Nutr. , 88 : 1018 – 1025 .
   PubMed Web of Science ®Google Scholar
• Lopez-Garcia , E. , van Dam , R. M. , Rajpathak , S. , Willett , W. C. , Manson , J. E. and Hu , F. B. 2006 . Changes in caffeine intake and long-term weight change in men and women . Am. J. Clin. Nutr. , 83 : 674 – 680 .
   PubMed Web of Science ®Google Scholar
• Lv , X. , Chen , Z. , Li , J. , Zhang , L. , Liu , H. , Huang , C. and Zhu , P. 2010 . Caffeine protects against alcoholic liver injury by attenuating inflammatory response and oxidative stress . Inflamm. Res , 59 : 635 – 645 .
   PubMed Web of Science ®Google Scholar
• Mackenzie , G. G. , Carrasquedo , F. , Delfino , J. M. , Keen , C. L. , Fraga , C. G. and 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 .
   PubMed Web of Science ®Google Scholar
• Mackenzie , G. G. and Oteiza , P. I. 2006 . Modulation of transcription factor NF-kappaB in Hodgkin's lymphoma cell lines: Effect of (−)-epicatechin . Free Radic. Res. , 40 : 1086 – 1094 .
   PubMed Web of Science ®Google Scholar
• Manach , C. , Scalbert , A. , Morand , C. , Remesy , C. and Jimenez , L. 2004 . Polyphenols: Food sources and bioavailability . Am. J. Clin. Nutr , 79 : 727 – 747 .
   PubMed Web of Science ®Google Scholar
• Manach , C. , Williamson , G. , Morand , C. , Scalbert , A. and Remesy , C. 2005 . Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies . Am. J. Clin. Nutr. , 81 : 230S – 242S .
   PubMed Web of Science ®Google Scholar
• Mao , T. , Van De Water , J. , Keen , C. L. , Schmitz , H. H. and Gershwin , M. E. 2000 . Cocoa procyanidins and human cytokine transcription and secretion . J. Nutr. , 130 : 2093S – 2099S .
   PubMed Web of Science ®Google Scholar
• Mao , T. K. , Van De Water , J. , Keen , C. L. , Schmitz , H. H. and Gershwin , M. E. 2002 . Modulation of TNF-alpha secretion in peripheral blood mononuclear cells by cocoa flavanols and procyanidins . Dev. Immunol. , 9 : 135 – 141 .
   PubMedGoogle Scholar
• Mao , T. K. , Van De Water , J. , Keen , C. L. , Schmitz , H. H. and Gershwin , M. E. 2003 . Cocoa flavonols and procyanidins promote transforming growth factor-beta1 homeostasis in peripheral blood mononuclear cells . Exp. Biol. Med. (Maywood). , 228 : 93 – 99 .
   PubMed Web of Science ®Google Scholar
• Merighi , S. , Benini , A. , Mirandola , P. , Gessi , S. , Varani , K. , Simioni , C. , Leung , E. , Maclennan , S. , Baraldi , P. G. and Borea , P. A. 2007 . Caffeine inhibits adenosine-induced accumulation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and interleukin-8 expression in hypoxic human colon cancer cells . Mol. Pharmacol. , 72 : 395 – 406 .
   PubMed Web of Science ®Google Scholar
• Miller , K. B. , Hurst , W. J. , Flannigan , N. , Ou , B. , Lee , C. Y. , Smith , N. and Stuart , D. A. 2009 . Survey of commercially available chocolate- and cocoa-containing products in the United States. 2. Comparison of flavan-3-ol content with nonfat cocoa solids, total polyphenols, and percent cacao . J. Agric. Food Chem , 57 : 9169 – 9180 .
   PubMed Web of Science ®Google Scholar
• Miller , K. B. , Stuart , D. A. , Smith , N. L. , Lee , C. Y. , McHale , N. L. , Flanagan , J. A. , Ou , B. and 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 .
   PubMed Web of Science ®Google Scholar
• Mumford , G. K. , Benowitz , N. L. , Evans , S. M. , Kaminski , B. J. , Preston , K. L. , Sannerud , C. A. and Silverman , K. Griffiths, R. R. 1996 . Absorption rate of methylxanthines following capsules, cola and chocolate . Eur. J. Clin. Pharmacol. , 51 : 319 – 325 .
   PubMed Web of Science ®Google Scholar
• Muniyappa , R. , Hall , G. , Kolodziej , T. L. , Karne , R. J. , Crandon , S. K. and Quon , M. J. 2008 . Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension . Am. J. Clin. Nutr. , 88 : 1685 – 1696 .
   PubMed Web of Science ®Google Scholar
• Murphy , K. J. , Chronopoulos , A. K. , Singh , I. , Francis , M. A. , Moriarty , H. , Pike , M. J. , Turner , A. H. , Mann , N. J. and Sinclair , A. J. 2003 . Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function . Am. J. Clin. Nutr. , 77 : 1466 – 1473 .
   PubMed Web of Science ®Google Scholar
• Mursu , J. , Voutilainen , S. , Nurmi , T. , Rissanen , T. H. , Virtanen , J. K. , Kaikkonen , J. , Nyyssonen , K. and Salonen , J. T. 2004 . Dark chocolate consumption increases HDL cholesterol concentration and chocolate fatty acids may inhibit lipid peroxidation in healthy humans . Free Radic. Biol. Med , 37 : 1351 – 1359 .
   PubMed Web of Science ®Google Scholar
• Nakabayashi , H. , Hashimoto , T. , Ashida , H. , Nishiumi , S. and Kanazawa , K. 2008 . Inhibitory effects of caffeine and its metabolites on intracellular lipid accumulation in murine 3T3-L1 adipocytes . Biofactors. , 34 : 293 – 302 .
   PubMed Web of Science ®Google Scholar
• Natsume , M. , Osakabe , N. , Oyama , M. , Sasaki , M. , Baba , S. , Nakamura , Y. , Osawa , T. and Terao , J. 2003 . Structures of (−)-epicatechin glucuronide identified from plasma and urine after oral ingestion of (−)-epicatechin: Differences between human and rat . Free Radic. Biol. Med. , 34 : 840 – 849 .
   PubMed Web of Science ®Google Scholar
• Nazaruddin , R. , Seng , L. K. , Hassan , O. and Said , M. 2006 . Effect of pulp preconditioning on the content of polyphenols in cocoa beans (Theobroma cacao) during fermentation . Industr. Crops Prod , 24 : 87 – 94 .
   Web of Science ®Google Scholar
• Nehlig , A. , Daval , J. L. and Debry , G. 1992 . Caffeine and the central nervous system: Mechanisms of action, biochemical, metabolic and psychostimulant effects . Brain Res. Brain Res. Rev. , 17 : 139 – 170 .
   PubMed Web of Science ®Google Scholar
• Okano , J. , Nagahara , T. , Matsumoto , K. and Murawaki , Y. 2008 . Caffeine inhibits the proliferation of liver cancer cells and activates the MEK/ERK/EGFR signalling pathway . Basic Clin. Pharmacol. Toxicol , 102 : 543 – 551 .
   PubMed Web of Science ®Google Scholar
• Osakabe , N. , Baba , S. , Yasuda , A. , Iwamoto , T. , Kamiyama , M. , Takizawa , T. , Itakura , H. and 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 .
   PubMed Web of Science ®Google Scholar
• Osakabe , N. , Yamagishi , M. , Sanbongi , C. , Natsume , M. , Takizawa , T. and Osawa , T. 1998 . The antioxidative substances in cacao liquor . J. Nutr. Sci. Vitaminol. (Tokyo). , 44 : 313 – 321 .
   PubMed Web of Science ®Google Scholar
• Ottaviani , J. I. , Carrasquedo , F. , Keen , C. L. , Lazarus , S. A. , Schmitz , H. H. and Fraga , C. G. 2002 . Influence of flavan-3-ols and procyanidins on UVC-mediated formation of 8-oxo-7,8-dihydro-2′-deoxyguanosine in isolated DNA . Arch. Biochem. Biophys , 406 : 203 – 208 .
   PubMed Web of Science ®Google Scholar
• Pan , T. , Jankovic , J. and Le , W. 2003 . Potential therapeutic properties of green tea polyphenols in Parkinson's disease . Drugs Aging , 20 : 711 – 721 .
   PubMed Web of Science ®Google Scholar
• Pearson , D. A. , Paglieroni , T. G. , Rein , D. , Wun , T. , Schramm , D. D. , Wang , J. F. , Holt , R. R. , Gosselin , R. , Schmitz , H. H. and Keen , C. L. 2002 . The effects of flavanol-rich cocoa and aspirin on ex vivo platelet function . Thromb. Res , 106 : 191 – 197 .
   PubMed Web of Science ®Google Scholar
• Peng , L. , Khan , N. , Afaq , F. , Ye , C. and Mukhtar , H. 2010 . In vitro and in vivo effects of water extract of white cocoa tea (Camellia ptilophylla) against human prostate cancer . Pharm. Res , 27 : 1128 – 1137 .
   PubMed Web of Science ®Google Scholar
• Pettipher , G. L. 1986 . An improved method for the extraction and quantitation of anthocyanins in cocoa beans and its use as an index of the degree of fermentation . J. Sci. Food Agric , 37 : 289 – 296 .
   Web of Science ®Google Scholar
• Podrez , E. A. , Abu-Soud , H. M. and Hazen , S. L. 2000 . Myeloperoxidase-generated oxidants and atherosclerosis . Free Radic. Biol. Med , 28 : 1717 – 1725 .
   PubMed Web of Science ®Google Scholar
• Prediger , R. D. 2010 . Effects of caffeine in Parkinson's disease: From neuroprotection to the management of motor and non-motor symptoms . J. Alzheimers Dis , 20 ( Suppl. 1 ) : S205 – S220 .
   PubMed Web of Science ®Google Scholar
• Ptolemy , A. S. , Tzioumis , E. , Thomke , A. , Rifai , S. and Kellogg , M. 2010 . Quantification of theobromine and caffeine in saliva, plasma and urine via liquid chromatography-tandem mass spectrometry: A single analytical protocol applicable to cocoa intervention studies . J. Chromatogr. B Analyt. Technol. Biomed. Life Sci , 878 : 409 – 416 .
   PubMed Web of Science ®Google Scholar
• 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 . Pura
   PubMed Web of Science ®Google Scholar
• Ramiro , E. , Franch , A. , Castellote , C. , Perez-Cano , F. , Permanyer , J. , Izquierdo-Pulido , M. and Castell , M. 2005 . Flavonoids from Theobroma cacao down-regulate inflammatory mediators . J. Agric. Food Chem. , 53 : 8506 – 8511 .
   PubMed Web of Science ®Google Scholar
• Ramiro-Puig , E. and Castell , M. 2009 . Cocoa: Antioxidant and immunomodulator . Br. J. Nutr , 101 : 931 – 940 .
   PubMed Web of Science ®Google Scholar
• Rein , D. , Lotito , S. , Holt , R. R. , Keen , C. L. , Schmitz , H. H. and Fraga , C. G. 2000 . Epicatechin in human plasma: In vivo determination and effect of chocolate consumption on plasma oxidation status . J. Nutr , 130 : 2109S – 2114S .
   PubMed Web of Science ®Google Scholar
• Richelle , M. , Tavazzi , I. , Enslen , M. and Offord , E. A. 1999 . Plasma kinetics in man of epicatechin from black chocolate . Eur. J. Clin. Nutr , 53 : 22 – 26 .
   PubMed Web of Science ®Google Scholar
• Rios , L. Y. , Gonthier , M. P. , Remesy , C. , Mila , I. , Lapierre , C. , Lazarus , S. A. , Williamson , G. and Scalbert , A. 2003 . Chocolate intake increases urinary excretion of polyphenol-derived phenolic acids in healthy human subjects . Am. J. Clin. Nutr , 77 : 912 – 918 .
   PubMed Web of Science ®Google Scholar
• Ritchie , K. , Carriere , I. , de Mendonca , A. , Portet , F. , Dartigues , J. F. , Rouaud , O. , Barberger-Gateau , P. and Ancelin , M. L. 2007 . The neuroprotective effects of caffeine: A prospective population study (the Three City Study) . Neurology , 69 : 536 – 545 .
   PubMed Web of Science ®Google Scholar
• Ross , R. 1999 . Atherosclerosis—an inflammatory disease . N. Engl. J. Med , 340 : 115 – 126 .
   PubMed Web of Science ®Google Scholar
• Ruzaidi , A. , Amin , I. , Nawalyah , A. G. , Hamid , M. and Faizul , H. A. 2005 . The effect of Malaysian cocoa extract on glucose levels and lipid profiles in diabetic rats . J. Ethnopharmacol , 98 : 55 – 60 .
   PubMed Web of Science ®Google Scholar
• Schewe , T. , Steffen , Y. and Sies , H. 2008 . How do dietary flavanols improve vascular function? A position paper . Arch. Biochem. Biophys , 476 : 102 – 106 .
   PubMed Web of Science ®Google Scholar
• Scholey , A. B. , French , S. J. , Morris , P. J. , Kennedy , D. O. , Milne , A. L. and Haskell , C. F. 2010 . Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort . J. Psychopharmacol , 24 : 1505 – 1514 .
   PubMed Web of Science ®Google Scholar
• Schramm , D. D. , Karim , M. , Schrader , H. R. , Holt , R. R. , Kirkpatrick , N. J. , Polagruto , J. A. , Ensunsa , J. L. , Schmitz , H. H. and Keen , C. L. 2003 . Food effects on the absorption and pharmacokinetics of cocoa flavanols . Life Sci , 73 : 857 – 869 .
   PubMed Web of Science ®Google Scholar
• Schroeter , H. , Heiss , C. , Balzer , J. , Kleinbongard , P. , Keen , C. L. , Hollenberg , N. K. , Sies , H. , Kwik-Uribe , C. , Schmitz , H. H. and Kelm , M. 2006 . (−)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans . Proc. Natl. Acad. Sci. USA , 103 : 1024 – 1029 .
   PubMed Web of Science ®Google Scholar
• Schroeter , H. , Williams , R. J. , Matin , R. , Iversen , L. and Rice-Evans , C. A. 2000 . Phenolic antioxidants attenuate neuronal cell death following uptake of oxidized low-density lipoprotein . Free Radic. Biol. Med , 29 : 1222 – 1233 .
   PubMed Web of Science ®Google Scholar
• Selmi , C. , Cocchi , C. A. , Lanfredini , M. , Keen , C. L. and Gershwin , M. E. 2008 . Chocolate at heart: The anti-inflammatory impact of cocoa flavanols . Mol. Nutr. Food Res , 52 : 1340 – 1348 .
   PubMed Web of Science ®Google Scholar
• Selmi , C. , Mao , T. K. , Keen , C. L. , Schmitz , H. H. and Eric Gershwin , M. 2006 . The anti-inflammatory properties of cocoa flavanols . J. Cardiovasc. Pharmacol , 47 ( Suppl. 2 ) : S163 – S171 . discussion S172– S176
   PubMedGoogle Scholar
• Shah , Z. A. , Li , R. C. , Ahmad , A. S. , Kensler , T. W. , Yamamoto , M. , Biswal , S. and Dore , S. 2010 . The flavanol (−)-epicatechin prevents stroke damage through the Nrf2/HO1 pathway . J. Cereb. Blood Flow Metab , 30 : 1951 – 1961 .
   PubMed Web of Science ®Google Scholar
• Shepherd , J. , Cobbe , S. M. , Ford , I. , Isles , C. G. , Lorimer , A. R. , MacFarlane , P. W. , McKillop , J. H. and Packard , C. J. 1995 . Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group . N. Engl. J. Med. , 333 : 1301 – 1307 .
   PubMed Web of Science ®Google Scholar
• Sies , H. , Schewe , T. , Heiss , C. and Kelm , M. 2005 . Cocoa polyphenols and inflammatory mediators . Am. J. Clin. Nutr , 81 : 304S – 312S .
   PubMed Web of Science ®Google Scholar
• Skopinska-Rozewska , E. , Janik , P. , Przybyszewska , M. , Sommer , E. and Bialas-Chromiec , B. 1998 . Inhibitory effect of theobromine on induction of angiogenesis and VEGF mRNA expression in v-raf transfectants of human urothelial cells HCV-29 . Int. J. Mol. Med , 2 : 649 – 652 .
   PubMed Web of Science ®Google Scholar
• Smit , H. J. and Blackburn , R. J. 2005 . Reinforcing effects of caffeine and theobromine as found in chocolate . Psychopharmacology (Berl). , 181 : 101 – 106 .
   PubMed Web of Science ®Google Scholar
• Smit , H. J. , Gaffan , E. A. and Rogers , P. J. 2004 . Methylxanthines are the psycho-pharmacologically active constituents of chocolate . Psychopharmacology (Berl). , 176 : 412 – 419 .
   PubMed Web of Science ®Google Scholar
• Smit , H. J. and Rogers , P. J. 2000 . Effects of low doses of caffeine on cognitive performance, mood and thirst in low and higher caffeine consumers . Psychopharmacology (Berl). , 152 : 167 – 173 .
   PubMed Web of Science ®Google Scholar
• Spencer , J. P. 2009 . Flavonoids and brain health: Multiple effects underpinned by common mechanisms . Genes Nutr , 4 : 243 – 250 .
   PubMed Web of Science ®Google Scholar
• Stamler , J. , Wentworth , D. and Neaton , J. D. 1986 . Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT) . JAMA , 256 : 2823 – 2828 .
   PubMed Web of Science ®Google Scholar
• Steinberg , F. M. , Bearden , M. M. and Keen , C. L. 2003 . Cocoa and chocolate flavonoids: Implications for cardiovascular health . J. Am. Diet Assoc , 103 : 215 – 223 .
   PubMed Web of Science ®Google Scholar
• Tarka , S. M. Jr. 1982 . The toxicology of cocoa and methylxanthines: A review of the literature . Crit. Rev. Toxicol. , 9 : 275 – 312 .
   PubMed Web of Science ®Google Scholar
• Taubert , D. , Roesen , R. and Schomig , E. 2007 . Effect of cocoa and tea intake on blood pressure: A meta-analysis . Arch. Intern. Med , 167 : 626 – 634 .
   PubMed Web of Science ®Google Scholar
• Tomaru , M. , Takano , H. , Osakabe , N. , Yasuda , A. , Inoue , K. , Yanagisawa , R. , Ohwatari , T. and Uematsu , H. 2007 . Dietary supplementation with cacao liquor proanthocyanidins prevents elevation of blood glucose levels in diabetic obese mice . Nutrition , 23 : 351 – 355 .
   PubMed Web of Science ®Google Scholar
• Umemura , T. , Ueda , K. , Nishioka , K. , Hidaka , T. , Takemoto , H. , Nakamura , S. , Jitsuiki , D. , Soga , J. , Goto , C. , Chayama , K. , Yoshizumi , M. and Higashi , Y. 2006 . Effects of acute administration of caffeine on vascular function . Am. J. Cardiol , 98 : 1538 – 1541 .
   PubMed Web of Science ®Google Scholar
• Van Praag , H. , Lucero , M. J. , Yeo , G. W. , Stecker , K. , Heivand , N. , Zhao , C. , Yip , E. , Afanador , M. , Schroeter , H. , Hammerstone , J. and Gage , F. H. 2007 . Plant-derived flavanol (−)epicatechin enhances angiogenesis and retention of spatial memory in mice . J. Neurosci. , 27 : 5869 – 5878 .
   PubMed Web of Science ®Google Scholar
• Vlachopoulos , C. , Aznaouridis , K. , Alexopoulos , N. , Economou , E. , Andreadou , I. and Stefanadis , C. 2005 . Effect of dark chocolate on arterial function in healthy individuals . Am. J. Hypertens , 18 : 785 – 791 .
   PubMed Web of Science ®Google Scholar
• Wan , Y. , Vinson , J. A. , Etherton , T. D. , Proch , J. , Lazarus , S. A. and Kris-Etherton , P. M. 2001 . Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans . Am. J. Clin. Nutr , 74 : 596 – 602 .
   PubMed Web of Science ®Google Scholar
• Wang , J. F. , Schramm , D. D. , Holt , R. R. , Ensunsa , J. L. , Fraga , C. G. , Schmitz , H. H. and Keen , C. L. 2000 . A dose-response effect from chocolate consumption on plasma epicatechin and oxidative damage . J. Nutr , 130 : 2115S – 2119S .
   PubMed Web of Science ®Google Scholar
• Wang-Polagruto , J. F. , Villablanca , A. C. , Polagruto , J. A. , Lee , L. , Holt , R. R. , Schrader , H. R. , Ensunsa , J. L. , Steinberg , F. M. , Schmitz , H. H. and Keen , C. L. 2006 . Chronic consumption of flavanol-rich cocoa improves endothelial function and decreases vascular cell adhesion molecule in hypercholesterolemic postmenopausal women . J. Cardiovasc. Pharmacol , 47 ( Suppl. 2 ) : S177 – S186 . discussion S206– S209
   PubMed Web of Science ®Google Scholar
• Waterhouse , A. L. , Shirley , J. R. and Donovan , J. L. 1996 . Antioxidants in chocolate . Lancet. , 348 : 834
   PubMed Web of Science ®Google Scholar
• Weisburger , J. H. 2001 . Chemopreventive effects of cocoa polyphenols on chronic diseases . Exp. Biol. Med. (Maywood). , 226 : 891 – 897 .
   PubMed Web of Science ®Google Scholar
• Wollgast , J. and Anklam , E. 2000 . Review on polyphenols in Theobroma cacao: Changes in composition during the manufacture of chocolate and methodology for identification and quantification . Food Res. Int. , 33 : 423 – 447 .
   Web of Science ®Google Scholar
• Yamada , T. , Yamada , Y. , Okano , Y. , Terashima , T. and Yokogoshi , H. 2009 . Anxiolytic effects of short- and long-term administration of cacao mass on rat elevated T-maze test . J. Nutr. Biochem. , 20 : 948 – 955 .
   PubMed Web of Science ®Google Scholar
• Yamagishi , M. , Natsume , M. , Osakabe , N. , Nakamura , H. , Furukawa , F. , Imazawa , T. , Nishikawa , A. and Hirose , M. 2002 . Effects of cacao liquor proanthocyanidins on PhIP-induced mutagenesis in vitro, and in vivo mammary and pancreatic tumorigenesis in female Sprague-Dawley rats . Cancer Lett. , 185 : 123 – 130 .
   PubMed Web of Science ®Google Scholar
• Yamagishi , M. , Natsume , M. , Osakabe , N. , Okazaki , K. , Furukawa , F. , Imazawa , T. , Nishikawa , A. and Hirose , M. 2003 . Chemoprevention of lung carcinogenesis by cacao liquor proanthocyanidins in a male rat multi-organ carcinogenesis model . Cancer Lett , 191 : 49 – 57 .
   PubMed Web of Science ®Google Scholar
• Yamagishi , M. , Osakab , N. , Takizawa , T. and Osawa , T. 2001 . Cacao liquor polyphenols reduce oxidative stress without maintaining alpha-tocopherol levels in rats fed a vitamin E-deficient diet . Lipids , 36 : 67 – 71 .
   PubMed Web of Science ®Google Scholar
• Yang , H. , Rouse , J. , Lukes , L. , Lancaster , M. , Veenstra , T. , Zhou , M. , Shi , Y. , Park , Y. G. and Hunter , K. 2004 . Caffeine suppresses metastasis in a transgenic mouse model: A prototype molecule for prophylaxis of metastasis . Clin. Exp. Metastasis. , 21 : 719 – 735 .
   PubMed Web of Science ®Google Scholar
• Yasuda , A. , Natsume , M. , Sasaki , K. , Baba , S. , Nakamura , Y. , Kanegae , M. and Nagaoka , S. 2008 . Cacao procyanidins reduce plasma cholesterol and increase fecal steroid excretion in rats fed a high-cholesterol diet . Biofactors. , 33 : 211 – 223 .
   PubMed Web of Science ®Google Scholar