Dark chocolate: consumption for pleasure or therapy?

  • Giuseppe Lippi
  • Massimo FranchiniEmail author
  • Martina Montagnana
  • Emmanuel J. Favaloro
  • Gian Cesare Guidi
  • Giovanni Targher


Traditional chocolate is derived from the cocoa bean, which is one of the most concentrated sources of flavanols, a subgroup of the natural antioxidant plant compounds called flavonoids. Accumulating evidence from the past 10 years demonstrates that moderate consumption of chocolate, especially dark chocolate, may exert protective effects against the development of cardiovascular disease. Several mechanisms have been proposed to explain this positive influence, including metabolic, antihypertensive, anti-inflammatory, and anti-thrombotic effects, as well as effects on insulin sensitivity and vascular endothelial function. Should these results be confirmed in randomised, controlled, cross-over, multi-dose trials, then the pleasure associated with chocolate consumption might also be justified from health and psychological perspectives. However, since dark chocolate has substantially higher levels of flavonoids than milk chocolate, and milk proteins may inhibit absorption of flavonoids, it might be preferable to consume dark chocolate than the white (milk) variety.


Cardiovascular disease Cardiovascular risk Chocolate Cocoa 


  1. 1.
    Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D (1993) Dietary antioxidant flavonoids and risk of coronary heart disease: the zutphen elderly study. Lancet 342:1007–1011. doi: 10.1016/0140-6736(93)92876-U CrossRefPubMedGoogle Scholar
  2. 2.
    Keli SO, Hertog MG, Feskens EJ, Kromhout D (1996) Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the zutphen study. Arch Intern Med 156:637–642. doi: 10.1001/archinte.156.6.637 CrossRefPubMedGoogle Scholar
  3. 3.
    Voutilainen S, Nurmi T, Mursu J, Rissanen TH (2006) Carotenoids and cardiovascular health. Am J Clin Nutr 83:1265–1271PubMedGoogle Scholar
  4. 4.
    Hennig B, Oesterling E, Toborek M (2007) Environmental toxicity, nutrition, and gene interactions in the development of atherosclerosis. Nutr Metab Cardiovasc Dis 17:162–169. doi: 10.1016/j.numecd.2006.01.003 CrossRefPubMedGoogle Scholar
  5. 5.
    Cooper KA, Donovan JL, Waterhouse AL, Williamson G (2008) Cocoa and health: a decade of research. Br J Nutr 99:1–11. doi: 10.1017/S0007114507795296 CrossRefPubMedGoogle Scholar
  6. 6.
    Ross JA, Kasum CM (2002) Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr 22:19–34. doi: 10.1146/annurev.nutr.22.111401.144957 CrossRefPubMedGoogle Scholar
  7. 7.
    Tapiero H, Tew KD, Ba GN, Mathe G (2002) Polyphenols: do they play a role in the prevention of human pathologies? Biomed Pharmacother 56:200–207. doi: 10.1016/S0753-3322(02)00178-6 CrossRefPubMedGoogle Scholar
  8. 8.
    Natsume M, Osakabe N, Yamagishi M et al (2000) Analyses of polyphenols in cacao liquor, cocoa, and chocolate by normal-phase and reversed-phase HPLC. Biosci Biotechnol Biochem 64:2581–2587. doi: 10.1271/bbb.64.2581 CrossRefPubMedGoogle Scholar
  9. 9.
    Vinson JA, 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. doi: 10.1021/jf990312p CrossRefPubMedGoogle Scholar
  10. 10.
    Serafini M, Bugianesi R, Maiani G, Valtuena S, De Santis S, Crozier A (2003) Plasma antioxidants from chocolate. Nature 424:1013. doi: 10.1038/4241013a CrossRefPubMedGoogle Scholar
  11. 11.
    Ding EL, Hutfless SM, Ding X, Girotra S (2006) Chocolate and prevention of cardiovascular disease: a systematic review. Nutr Metab 3:2. doi: 10.1186/1743-7075-3-2 CrossRefGoogle Scholar
  12. 12.
    Dillinger TL, Barriga P, Escarcega S, Jimenez M, Salazar Lowe D, Grivetti LE (2000) Food of the gods: cure for humanity? a cultural history of the medicinal and ritual use of chocolate. J Nutr 130:2057S–2072SPubMedGoogle Scholar
  13. 13.
    Buijsse B, Feskens EJM, Kok FJ, Kromhout D (2006) Cocoa intake, blood pressure, and cardiovascular mortality: the zutphen elderly study. Arch Intern Med 166:411–417. doi: 10.1001/.411 CrossRefPubMedGoogle Scholar
  14. 14.
    McCullough ML, Chevaux K, Jackson L et al (2006) Hypertension, the Kuna, and the epidemiology of flavanols. J Cardiovasc Pharmacol 47:S103–S109. doi: 10.1097/00005344-200606001-00003 CrossRefPubMedGoogle Scholar
  15. 15.
    Chevaux K, Jackson L, Villar ME et al (2001) Proximate, mineral and procyanidin content of certain food and beverages consumed by the Kuna Amerinds of Panama. J Food Compost Anal 14:553–563. doi: 10.1006/jfca.2001.1027 CrossRefGoogle Scholar
  16. 16.
    Bayard V, Chamorro F, Motta J, Hollenberg NK (2007) Does flavanol intake influence mortality from nitric oxide-dependent processes? Ischemic heart disease, stroke, diabetes mellitus, and cancer in Panama. Int J Med Sci 4:53–58PubMedGoogle Scholar
  17. 17.
    Kris-Etherton PM, Keen CL (2002) Evidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health. Curr Opin Lipidol 13:41–49. doi: 10.1097/00041433-200202000-00007 CrossRefPubMedGoogle Scholar
  18. 18.
    Richelle M, Tavazzi I, Enslen M, Offord EA (1999) Plasma kinetics in man of epicatechin from black chocolate. Eur J Clin Nutr 53:22–26. doi: 10.1038/sj.ejcn.1600673 CrossRefPubMedGoogle Scholar
  19. 19.
    Wang JF, Schramm DD, Holt RR et al (2000) A dose-response effect from chocolate consumption on plasma epicatechin and oxidative damage. J Nutr 130(8S Suppl):2115S–2119SPubMedGoogle Scholar
  20. 20.
    Rice-Evans CA, Miller NJ, Paganga G (1996) Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 20:933–956. doi: 10.1016/0891-5849(95)02227-9 CrossRefPubMedGoogle Scholar
  21. 21.
    Lee KW, Kim YJ, Lee HJ, Lee CY (2003) Cocoa has more phenolic phytochemicals and a higher antioxidant capacity than teas and red wine. J Agric Food Chem 51:7292–7295. doi: 10.1021/jf0344385 CrossRefPubMedGoogle Scholar
  22. 22.
    Osakabe N, Natsume M, Adachi T et al (2000) Effects of cacao liquor polyphenols on the susceptibility of low-density lipoprotein to oxidation in hypercholesterolemic rabbits. J Atheroscler Thromb 7:164–168PubMedGoogle Scholar
  23. 23.
    Osakabe N, Yasuda A, Natsume M, Takizawa T, Terao J, Kondo K (2002) Catechins and their oligomers linked by C4–C8 bonds are major cacao polyphenols and protect low-density lipoprotein from oxidation in vitro. Exp Biol Med 227:51–56Google Scholar
  24. 24.
    Kondo K, Hirano R, Matsumoto A, Igarashi O, Itakura H (1996) Inhibition of LDL oxidation by cocoa. Lancet 348:1514. doi: 10.1016/S0140-6736(05)65927-2 CrossRefPubMedGoogle Scholar
  25. 25.
    Waterhouse AL, Shirley JR, Donovan JL (1996) Antioxidants in chocolate. Lancet 348:834. doi: 10.1016/S0140-6736(05)65262-2 CrossRefPubMedGoogle Scholar
  26. 26.
    Wan Y, Vinson JA, Etherton TD, Proch J, Lazarus SA, Kris-Etherton PM (2001) Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans. Am J Clin Nutr 74:596–602PubMedGoogle Scholar
  27. 27.
    Mathur S, Devaraj S, Grundy SM, Jialal I (2002) Cocoa products decrease low density lipoprotein oxidative susceptibility but do not affect biomarkers of inflammation in humans. J Nutr 132:3663–3667PubMedGoogle Scholar
  28. 28.
    Rein D, Lotito S, Holt RR, Keen CL, Schmitz HH, Fraga CG (2000) Epicatechin in human plasma: in vivo determination and effect of chocolate consumption on plasma oxidation status. J Nutr 130(8S Suppl):2109S–2114SPubMedGoogle Scholar
  29. 29.
    Osakabe N, Baba S, Yasuda A et al (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. doi: 10.1080/10715760100300091 CrossRefPubMedGoogle Scholar
  30. 30.
    Adamson GE, Lazarus SA, Mitchell AE et al (1999) HPLC method for the quantification of procyanidins in cocoa and chocolate samples and correlation to total antioxidant capacity. J Agric Food Chem 47:4184–4188. doi: 10.1021/jf990317m CrossRefPubMedGoogle Scholar
  31. 31.
    Vinson JA, Proch J, Bose P (2001) Determination of quantity and quality of polyphenol antioxidants in foods and beverages. Methods Enzymol 335:103–114. doi: 10.1016/S0076-6879(01)35235-7 CrossRefPubMedGoogle Scholar
  32. 32.
    Kurosawa T, Itoh F, Nozaki A et al (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. doi: 10.1016/j.atherosclerosis.2004.12.003 CrossRefPubMedGoogle Scholar
  33. 33.
    Fraga CG, Actis-Goretta L, Ottaviani JI et al (2005) Regular consumption of a flavanol-rich chocolate can improve oxidant stress in young soccer players. Clin Dev Immunol 12:11–17. doi: 10.1080/10446670410001722159 CrossRefPubMedGoogle Scholar
  34. 34.
    Grassi D, Lippi C, Necozione S, Desideri G, 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 81:611–614PubMedGoogle Scholar
  35. 35.
    Grassi D, Necozione S, Lippi C et al (2005) Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension 46:398–405. doi: 10.1161/01.HYP.0000174990.46027.70 CrossRefPubMedGoogle Scholar
  36. 36.
    Allen RR, Carson L, Kwik-Uribe C, Evans EM, Erdman JW Jr (2008) Daily consumption of a dark chocolate containing flavanols and added sterol esters affects cardiovascular risk factors in a normotensive population with elevated cholesterol. J Nutr 138:725–731PubMedGoogle Scholar
  37. 37.
    Wiswedel I, Hirsch D, Kropf S et al (2004) Flavanol-rich cocoa drink lowers plasma F(2)-isoprostane concentrations in humans. Free Radic Biol Med 37:411–421. doi: 10.1016/j.freeradbiomed.2004.05.013 CrossRefPubMedGoogle Scholar
  38. 38.
    Lean ME, Noroozi M, Kelly I et al (1999) Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA. Diabetes 48:176–181. doi: 10.2337/diabetes.48.1.176 CrossRefPubMedGoogle Scholar
  39. 39.
    Baba S, Natsume M, Yasuda A et al (2007) 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 137:1436–1441PubMedGoogle Scholar
  40. 40.
    Baba S, Osakabe N, Kato Y et al (2007) 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 85:709–717PubMedGoogle Scholar
  41. 41.
    Mursu J, Voutilainen S, Nurmi T et al (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. doi: 10.1016/j.freeradbiomed.2004.06.002 CrossRefPubMedGoogle Scholar
  42. 42.
    Taubert D, Berkels R, Roesen R, Klaus W (2003) Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. JAMA 290:1029–1030. doi: 10.1001/jama.290.8.1029 CrossRefPubMedGoogle Scholar
  43. 43.
    Taubert D, Roesen R, Lehmann C, Jung N, Schomig E (2007) Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. JAMA 298:49–60. doi: 10.1001/jama.298.1.49 CrossRefPubMedGoogle Scholar
  44. 44.
    Taubert D, Roesen R, Schomig E (2007) Effect of cocoa and tea intake on blood pressure: a meta-analysis. Arch Intern Med 67:626–634. doi: 10.1001/archinte.167.7.626 CrossRefGoogle Scholar
  45. 45.
    Franco OH, Bonneux L, de Laet C, Peeters A, Steyerberg EW, Mackenbach JP (2004) The Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to reduce cardiovascular disease by more than 75%. BMJ 329:1447–1450. doi: 10.1136/bmj.329.7480.1447 CrossRefPubMedGoogle Scholar
  46. 46.
    Hollenberg NK, Schmitz H, Macdonald I, Poulter N (2004) Cocoa, flavanols and cardiovascular risk. Br J Cardiol 11:379–386Google Scholar
  47. 47.
    Stamler JS (2004) S-nitrosothiols in the blood: roles, amounts, and methods of analysis. Circ Res 94:414–417. doi: 10.1161/01.RES.0000122071.55721.BC CrossRefPubMedGoogle Scholar
  48. 48.
    Foster MW, Pawloski JR, Singel DJ, Stamler JS (2005) Role of circulating S-nitrosothiols in control of blood pressure. Hypertension 45:15–17. doi: 10.1161/01.HYP.0000165021.91304.f5 CrossRefPubMedGoogle Scholar
  49. 49.
    Sowers JR (2004) Insulin resistance and hypertension. Am J Physiol Heart Circ Physiol 286:H1597–H1602. doi: 10.1152/ajpheart.00026.2004 CrossRefPubMedGoogle Scholar
  50. 50.
    Mackenzie GG, Carrasquedo F, Delfino JM, Keen CL, Fraga CG, Oteiza PI (2004) Epicatechin, catechin, and dimeric procyanidins inhibit PMA induced NF-kappaB activation at multiple steps in JurkatTcells. FASEB J 18:167–169PubMedGoogle Scholar
  51. 51.
    de Cavanagh EM, Piotrkowski B, Basso N et al (2003) Enalapril and losartan attenuate mitochondrial dysfunction in aged rats. FASEB J 17:1096–1098PubMedGoogle Scholar
  52. 52.
    Actis-Goretta L, Ottaviani JI, Keen CL, Fraga CG (2003) Inhibition of angiotensin converting enzyme (ACE) activity by flavan-3-ols and procyanidins. FEBS Lett 555:597–600. doi: 10.1016/S0014-5793(03)01355-3 CrossRefPubMedGoogle Scholar
  53. 53.
    Engler MB, Engler MM, Chen CY et al (2004) Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults. J Am Coll Nutr 23:197–204PubMedGoogle Scholar
  54. 54.
    Heiss C, Dejam A, Kleinbongard P, Schewe T, Sies H, Kelm M (2003) Vascular effects of cocoa rich in flavan-3-ols. JAMA 290:1030–1031. doi: 10.1001/jama.290.8.1030 CrossRefPubMedGoogle Scholar
  55. 55.
    Karim M, McCormick K, Kappagoda CT (2000) Effects of cocoa extracts on endothelium-dependent relaxation. J Nutr 130(8S Suppl):2105S–2108SPubMedGoogle Scholar
  56. 56.
    Fisher ND, Hughes M, Gerhard-Herman M, Hollenberg NK (2003) Flavonol rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans. J Hypertens 21:2281–2286. doi: 10.1097/00004872-200312000-00016 CrossRefPubMedGoogle Scholar
  57. 57.
    Vlachopoulos C, Aznaouridis K, Alexopoulos N, Economou E, Andreadou I, Stefanadis C (2005) Effect of dark chocolate on arterial function in healthy individuals. Am J Hypertens 18:785–791. doi: 10.1016/j.amjhyper.2004.12.008 CrossRefPubMedGoogle Scholar
  58. 58.
    Shiina Y, Funabashi N, Lee K, et al (2007) Acute effect of oral flavonoid-rich dark chocolate intake on coronary circulation, as compared with non-flavonoid white chocolate, by transthoracic Doppler echocardiography in healthy adults. Int J Cardiol [Epub ahead of print]Google Scholar
  59. 59.
    Mann GE, Rowlands DJ, Li FY, de Winter P, Siow RC (2007) Activation of endothelial nitric oxide synthase by dietary isoflavones: role of NO in Nrf2-mediated antioxidant gene expression. Cardiovasc Res 75:261–274. doi: 10.1016/j.cardiores.2007.04.004 CrossRefPubMedGoogle Scholar
  60. 60.
    Schramm DD, Wang JF, Holt RR et al (2001) Chocolate procyanidins decrease the leukotriene-prostacyclin ratio in humans and human aortic endothelial cells. Am J Clin Nutr 73:36–40PubMedGoogle Scholar
  61. 61.
    Schewe T, Sadik C, Klotz LO, Yoshimoto T, Kuhn H, Sies H (2001) Polyphenols of cocoa: inhibition of mammalian 15-lipoxygenase. Biol Chem 382:1687–1696. doi: 10.1515/BC.2001.204 CrossRefPubMedGoogle Scholar
  62. 62.
    Schewe T, Kuhn H, Sies H (2002) Flavonoids of cocoa inhibit recombinant human 5-lipoxygenase. J Nutr 132:1825–1829PubMedGoogle Scholar
  63. 63.
    Vlachopoulos CV, Alexopoulos NA, Aznaouridis KA et al (2007) Relation of habitual cocoa consumption to aortic stiffness and wave reflections, and to central hemodynamics in healthy individuals. Am J Cardiol 99:1473–1475. doi: 10.1016/j.amjcard.2006.12.081 CrossRefPubMedGoogle Scholar
  64. 64.
    Kurlandsky SB, Stote KS (2006) Cardioprotective effects ofchocolate and almond consumption in healthy women. Nutr Res 26:509–516. doi: 10.1016/j.nutres.2006.08.007 CrossRefGoogle Scholar
  65. 65.
    Ridker PM, Hennekens CH, Buring JE, Rifai N (2000) C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 342:836–843. doi: 10.1056/NEJM200003233421202 CrossRefPubMedGoogle Scholar
  66. 66.
    Pai JK, Pischon T, Ma J et al (2004) Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med 351:2599–2610. doi: 10.1056/NEJMoa040967 CrossRefPubMedGoogle Scholar
  67. 67.
    Ridker PM, Cannon CP, Morrow D et al (2005) C-reactive protein levels and outcomes after statin therapy. N Engl J Med 352:20–28. doi: 10.1056/NEJMoa042378 CrossRefPubMedGoogle Scholar
  68. 68.
    Margolis KL, Manson JE, Greenland P et al (2005) Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: the women’s health initiative observational study. Arch Intern Med 165:500–508. doi: 10.1001/archinte.165.5.500 CrossRefPubMedGoogle Scholar
  69. 69.
    Ridker PM, Rifai N, Rose L, Buring JE, Cook NR (2002) Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 347:1557–1565. doi: 10.1056/NEJMoa021993 CrossRefPubMedGoogle Scholar
  70. 70.
    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. doi: 10.1006/cimm.1997.1109 CrossRefPubMedGoogle Scholar
  71. 71.
    Mao TK, Powell J, Van de Water J et al (2000) The effect of cocoa procyanidins on the transcription and secretion of interleukin 1 beta in peripheral blood mononuclear cells. Life Sci 66:1377–1386. doi: 10.1016/S0024-3205(00)00449-5 CrossRefPubMedGoogle Scholar
  72. 72.
    Mao T, Van De Water J, Keen CL, Schmitz HH, Gershwin ME (2000) Cocoa procyanidins and human cytokine transcription and secretion. J Nutr 130(8S Suppl):2093S–2099SPubMedGoogle Scholar
  73. 73.
    Mao TK, Van de Water J, Keen CL, Schmitz HH, Gershwin ME (2002) Effect of cocoa flavanols and their related oligomers on the secretion of interleukin-5 in peripheral blood mononuclear cells. J Med Food 5:17–22. doi: 10.1089/109662002753723188 CrossRefPubMedGoogle Scholar
  74. 74.
    Mao TK, van de Water J, Keen CL, Schmitz HH, Gershwin ME (2002) Modulation of TNF-alpha secretion in peripheral blood mononuclear cells by cocoa flavanols and procyanidins. Dev Immunol 9:135–141. doi: 10.1080/1044667031000137601 CrossRefPubMedGoogle Scholar
  75. 75.
    Mao TK, Van De Water J, Keen CL, Schmitz HH, Gershwin ME (2003) Cocoa flavonols and procyanidins promote transforming growth factor-beta1 homeostasis in peripheral blood mononuclear cells. Exp Biol Med 228:93–99Google Scholar
  76. 76.
    Selmi C, Mao TK, Keen CL, Schmitz HH, Eric Gershwin M (2006) The anti-inflammatory properties of cocoa flavanols. J Cardiovasc Pharmacol 47(Suppl 2):S163–S171. doi: 10.1097/00005344-200606001-00010 CrossRefPubMedGoogle Scholar
  77. 77.
    Pearson DA, Holt RR, Rein D, Paglieroni T, Schmitz HH, Keen CL (2005) Flavanols and platelet reactivity. Clin Dev Immunol 12:1–9. doi: 10.1080/10446670410001722140 CrossRefPubMedGoogle Scholar
  78. 78.
    Lamuela-Raventos RM, Romero-Perez AI, Andres-Lacueva C, Tornero A (2005) Review: health effects of cocoa flavonoids. Food Sci Tech Int 11:159–176. doi: 10.1177/1082013205054498 CrossRefGoogle Scholar
  79. 79.
    Rein D, Paglieroni TG, Wun T et al (2000) Cocoa inhibits platelet activation and function. Am J Clin Nutr 72:30–35PubMedGoogle Scholar
  80. 80.
    Holt RR, Schramm DD, Keen CL, Lazarus SA, Schmitz HH (2002) Chocolate consumption and platelet function. JAMA 287:2212–2213. doi: 10.1001/jama.287.17.2212 CrossRefPubMedGoogle Scholar
  81. 81.
    Pearson DA, Paglieroni TG, Rein D et al (2002) The effects of flavanol-rich cocoa and aspirin on ex vivo platelet function. Thromb Res 106:191–197. doi: 10.1016/S0049-3848(02)00128-7 CrossRefPubMedGoogle Scholar
  82. 82.
    Heptinstall S, May J, Fox S, Kwik-Uribe C, Zhao L (2006) Cocoa flavanols and platelet and leukocyte function: recent in vitro and ex vivo studies in healthy adults. J Cardiovasc Pharmacol 47:S197–S205. doi: 10.1097/00005344-200606001-00015 CrossRefPubMedGoogle Scholar
  83. 83.
    Holt RR, Actis-Goretta L, Momma TY, Keen CL (2006) Dietary flavanols and platelet reactivity. J Cardiovasc Pharmacol 47:S187–S196. doi: 10.1097/00005344-200606001-00014 CrossRefPubMedGoogle Scholar
  84. 84.
    Guerrero J, Lozano ML, Castillo J, Benavente-García O, Vicente V, Rivera J (2005) Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor. J Thromb Haemost 3:369–376. doi: 10.1111/j.1538-7836.2004.01099.x CrossRefPubMedGoogle Scholar
  85. 85.
    Sies H, Schewe T, Heiss C, Kelm M (2005) Cocoa polyphenols and inflammatory mediators. Am J Clin Nutr 81:304S–312SPubMedGoogle Scholar
  86. 86.
    Blache D, Durand P, Prost M, Loreau N (2002) (+)-Catechin inhibits platelet hyperactivity induced by an acute iron load in vivo. Free Radic Biol Med 33:1670–1680. doi: 10.1016/S0891-5849(02)01139-5 CrossRefPubMedGoogle Scholar
  87. 87.
    Oteiza PI, Erlejman AG, Verstraeten SV, Keen CL, Fraga CG (2005) Flavonoid-membrane interactions: a protective role of flavonoids at the membrane surface? Clin Dev Immunol 12:19–25. doi: 10.1080/10446670410001722168 CrossRefPubMedGoogle Scholar
  88. 88.
    Abou-Agag LH, Aikens ML, Tabengwa EM et al (2001) Polyphyenolics increase t-PA and u-PA gene transcription in cultured human endothelial cells. Alcohol Clin Exp Res 25:155–162. doi: 10.1111/j.1530-0277.2001.tb02193.x CrossRefPubMedGoogle Scholar
  89. 89.
    Aron PM, Kennedy JA (2008) Flavan-3-ols: nature, occurrence and biological activity. Mol Nutr Food Res 52:79–104. doi: 10.1002/mnfr.200700137 CrossRefPubMedGoogle Scholar
  90. 90.
    Rolls ET, McCabe C (2007) Enhanced affective brain representations of chocolate in cravers vs. non-cravers. Eur J Neurosci 26:1067–1076. doi: 10.1111/j.1460-9568.2007.05724.x CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Giuseppe Lippi
    • 1
  • Massimo Franchini
    • 1
    • 2
    Email author
  • Martina Montagnana
    • 1
  • Emmanuel J. Favaloro
    • 3
  • Gian Cesare Guidi
    • 1
  • Giovanni Targher
    • 4
  1. 1.Sezione di Chimica Clinica, Dipartimento di Scienze Biomediche e MorfologicheUniversità di VeronaVeronaItaly
  2. 2.Servizio di Immunoematologia e Trasfusione, Dipartimento di Patologia e Medicina di LaboratorioAzienda Ospedaliero-Universitaria di ParmaParmaItaly
  3. 3.Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR)Westmead HospitalWestmeadAustralia
  4. 4.Sezione di Endocrinologia, Dipartimento di Scienze Biomediche e ChirurgicheUniversità di VeronaVeronaItaly

Personalised recommendations