Principali studi clinici svolti su Cacao e Cioccolato.

1. Orwa C, Mutua A, Kindt R, et al. 2009. Agroforestree Database:a tree reference and selection guide version 4.0. CD-ROM. World Agroforestry Centre ICRAF, Nairobi
Kenya 2009. Available online – version 4.0 Accessed May 2011
2. Grivetti LE. From aphrodisiac to health food: a cultural history of chocolate. In: Karger Gazette, Issue 68 (Chocolate). Basel, Switzerland: S. Karger, 2005
3. Coe SD, Coe MD. The true history of chocolate. 280 p. Rev. ed. New York, Thames and Hudson, 2007
4. Dillinger TL, Barriga P, Escárcega S, et al. Food of the gods: cure for humanity? A cultural history of the medicinal and ritual use of chocolate. J Nutr. 2000;
5. Lippi D. Chocolate and medicine: dangerous liaisons? Nutrition. 2009; 25:1100-1103
6. Lippi D. Chocolate in health and disease. Maturitas. 2010; 67:195-196
7. Beckett ST. The history of chocolate. In: The Science of Chocolate. Beckett ST (Ed.) 2nd Edition, Royal Society of Chemistry: Cambridge, UK, 2008, 1-10
8. Quesnel, VC. Fractionation and properties of the polymeric leucoyanidin of the seeds of Theobroma cacao. Phytochemistry. 1968: 7:1583-1592
9. Singleton VL, Orthofer R, Lamuela-Raventós RM. Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent.
Methods in Enzymology. 1999; 299:152-178
10. Ninfali P, Giorgini S, Biagiotti E, et al. I flavonoidi nel cioccolato fondente e al latte: possibile strategia per la preparazione di cioccolato fortificato. Ingredienti alimentari,
2002: 5:6-10
11. Baba S, Osakabe N, Yasuda A, et al. Bioavailability of (-)-epicatechin upon intake of chocolate and cocoa in human volunteers. Free Radic Res. 2000; 33:635-641
12. Wang JF, Schramm DD, Holt RR, et al. A dose-response effect from chocolate consumption on plasma epicatechin and oxidative damage. J Nutr. 2000;
13. Dreosti IE. Antioxidant polyphenols in tea, cocoa, and wine. Nutrition. 2000; 16:692-694
14. Lotito SB, Fraga CG. Catechins delay lipid oxidation and alphatocopherol and beta-carotene depletion following ascorbate depletion in human plasma. Proc Soc Exp
Biol Med. 2000; 225:32-38
15. Schramm DD, Wang JF, Holt RR, et al. Chocolate procyanidins decrease the leukotriene-prostacyclin ratio in humans and human aortic endothelial cells. Am J Clin
Nutr. 2001; 73:36-40
16. Arteel GE, Schroeder P, Sies H. Reactions of peroxynitrite with cocoa procyanidin oligomers. J Nutr. 2000; 130:2100S-2104S
17. Lüscher TF, Hollenberg NK. Cocoa flavanols and cardiovascular function: introductory. J Cardiovasc Pharmacol.2006; 47:vi-vii
18. Heinrich U, Neukam K, Tronnier H, et al. Long-term ingestion of high flavanol cocoa provides photoprotection against UV-induced erythema and improves skin condition
in women. J Nutr. 2006; 136:1565-1569
19. Williams S, Tamburic S, Lally C. Eating chocolate can significantly protect the skin from UV light. J Cosmet Dermatol. 2009; 8:169-173
20. Cantani A, Ferrara M, Vazzoler C. Case in point: allergy, intolerance or pseudoallergy to chocolate? Riv Eur Sci Med Farmacol. 1989; 11:247-249
21. Ghosh JS. Allergic reactions to chocolate. Am J Clin Nutr. 1977; 30:834-835
22. Patanè S, Marte F, La Rosa FC, et al. Atrial fibrillation associated with chocolate intake abuse and chronic
salbutamol inhalation abuse. Int J Cardiol. 2010; 145:e74-6
23. Kannayiram A, Rezaie A, Hadi S. Chocolate-induced prolonged angiooedema in an elderly patient. Age Ageing. 2008; 37:479-480
24. Natsume M, Osakabe N, Yamagishi M, et al. Analyses of polyphenols in cacao liquor, cocoa, and chocolate by normal-phase and reversedphase HPLC. Biosci
Biotechnol Biochem. 2000; 64:2581-2587
25. Rein D, Paglieroni TG, Pearson DA, et al. Cocoa and wine polyphenols modulate platelet activation and function. J Nutr. 2000; 130:2120S-2126S
26. Arteel GE, Sies H. Protection against peroxynitrite by cocoa polyphenol oligomers. FEBS Lett. 1999; 462:167-170
27. Waterhouse A, Shirley R, Donovan J. Antioxidants in chocolate. Lancet. 1996; 348:834
28. Pearson DA, Schmitz HH, Lazarus SA, et al. Inhibition of in vitro low-density lipoprotein oxidation by oligomeric procyanidins present in chocolate and cocoas.
Methods Enzymol. 2001; 335:350-360
29. Taubert D, Berkels R, Roesen R, et al. Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. JAMA. 2003; 290:1029-1030
30. Allen RR, Carson LA, Kwik-Uribe C, et al. Daily consumption of a dark chocolate containing flavanols and added sterol esters affects cardiovascular risk aactors in a
normotensive population with elevated cholesterol. J. Nutr. 2008; 138:725-731
31. Flammer AJ, Hermann F, Sudano I, et al. Dark chocolate improves coronary vasomotion and reduces platelet reactivity. Circulation. 2007; 116:2376-2382
32. Ross R. Atherosclerosis: an inflammatory disease. New Engl J Med. 1999; 340:115-126
33. Rein D, Paglieroni TG, Wun T, et al. Cocoa Inhibits Platelet Activation and Function. Am J Clin Nutr. 2000; 72:30-35
34. Innes AJ, Kennedy G, McLaren M, et al. Dark chocolate inhibits platelet aggregation in healthy volunteers. Platelets. 2003; 14:325-327
35. Grassi D, Lippi C, Necozione S, et al. Short-term administration of dark chocolate is followed by a significant
increase in insulin sensitivity and a decrease in blood pressure in healthy persons. AmJ Clin Nutr.
2004; 81:611-614
36. Duffy SJ, Vita JA. Effects of phenolics on vascular endothelial function. Curr Opin Lipidol 2003; 14:21-27
37. Sowers JR. Insulin resistance and hypertension. Am J Physiol Heart Circ Physiol. 2004; 286:H1597-602
38. Mackenzie GG, Carrasquedo F, Delfino JM, et al. Epicatechin, catechin, and dimeric procyanidins inhibit PMAinduced NF-kappaB activation at multiple steps in
JurkatTcells. Biochem Pharmacol. 2009; 78:1252- 1262
39. Cai H, Griendling KK, Harrison DG. The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases. Trends Pharmacol Sci. 2003; 24:471-478
40. Prabhakar P, Thatte HS, Goetz RM, et al. Receptor-regulated translocation of endothelial nitric-oxide synthase.J Biol Chem 1998; 273:83-88
41. de Cavanagh EM, Inserra F, Ferder M, et al. From mitochondria to disease: role of the renin-angiotensin system. Am J Nephrol. 2007; 27:545-553
42. Weisburger JH. Prevention of cancer and other chronic diseases worldwide based on sound mechanisms. BioFactors. 2000; 2:73-81
43. Sugimura T. An overview of cancer prevention. Eur J Cancer Prev. 1999; 5:1-8 44. Kovacic P, Somanathan R. Dermal toxicity and environmental contamination:
electron transfer, reactive oxygen species, oxidative stress, cell signaling, and protection by antioxidants. Rev Environ Contam Toxicol.
2010; 203:119-138
45. Valko M, Rhodes CJ, Moncol J, et al. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 2006; 160:1-40
46. Messina M, Hilakivi-Clarke L. Early intake appears to be the key to the proposed protective effects of soy intake against breast cancer. Nutr Cancer. 2009; 61:792-
47. Pellegrini N, Serafini M, Colombi B, et al. Total Antioxidant Capacity of Plant Foods, Beverages and Oils Consumed in Italy Assessed by Three Different In Vitro
Assays. J. Nutr.2003; 133:2812-2819
48. Kris-Etherton PM, Hecker KD, Bonanome A, et al. Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer. Am J Med. 2002;
113Suppl 9B:71S-88S
49. Potter JD. World Cancer Research Fund Panel. Food, Nutrition and the Prevention of Cancer: A Global Perspective Washington, D.C. American Institute for Cancer
Research, 1997
50. Messina MJ. Legumes and soybeans: Overview of their nutritional profiles and health effects. Am J Clin Nutr. 1999; 70:439S-450S
51. Schewe T, Sadik C, Klotz LO, et al. Polyphenols of cocoa: inhibition of mammalian 15-lipoxygenase. Biol Chem. 2001; 382:1687-1696
52. Keen CL. Chocolate: food as medicine/medicine as food. J Am Coll Nutr. 2001; 20:436S-439S
53. Sangboni C, Suzuki N, Sakane T. Polyphenols in chocolate, which have antioxidant activity, modulate immune functions in humans in vitro. Cell Immunol. 1997;
54. Mao TK, Powell J, Van de Water J, et al. The effect of cocoa procyanidins on the transcription and secretion of interleukin 1B in peripheral mononuclear cell. Life Sci.
2000; 66: 1377-1386
55. Sato M, Miyazaki T, Kambe F, et al. Quercetin, a bioflavonoid, inhibits the induction of interleukin 8 and monocyte chemoattractant protein-1 expression by tumor
necrosis factor-alpha in cultured human synovial cells. J Rheumatol. 1997; 24:1680-1684
56. Rotondo S, Rajtar G, Manarini S, et al. Effect of trans-reservatrol, a natural polyphenolic compound, on human polymorphonuclear leukocyte function. Br J Pharmocol.
1998; 123:1691-1699
57. Osakabe N, Sanbongi C, Yamagishi M, et al. Effects of polyphenol substances derived from Theobroma cacao on gastric mucosal lesion induced by ethanol. Biosci
Biotechnol Biochem. 1998; 62:1535-1538
58. Mozaffarieh M, Grieshaber MC, Orgül S, et al. The potential value of natural antioxidative treatment in glaucoma. Surv Ophthalmol. 2008; 53:479-505
59. Bartlett H, Eperjesi F. An ideal ocular nutritional supplement? Ophthalmic Physiol Opt 2004; 24:339-349
60. Zoric L, Miric D, Milenkovic S, et al: Pseudo-exfoliation syndrome and its antioxidative protection deficiency as risk factors for age-related cataract. Eur J Ophthalmol.
2006; 16:268-273
61. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006; 90:262-267
62. Tuck MW, Crick RP. The projected increase in glaucoma due to an ageing population. Ophthalmic Physiol Opt. 2003; 23:175-179
63. Ortega N, Reguant J, Romero MP, et al. Effect of fat content on the digestibility and bioaccessibility of cocoa polyphenol by an in vitro digestion model. J Agric Food
Chem. 2009; 57:5743-5749
64. Cooper K, Donovan J, Waterhouse A, et al. Cocoa and health: A decade of research. Br. J. Nutr. 2008; 99:1-11
65. Spencer J, Chaudry F, Pannala A, et al. Decomposition of cocoa procyanidins in the gastric milieu. Biochem. Biophys. Res. Commun. 2000; 47:4184-4188
66. Schramm D, Karim M, Schrader H, et al. Food effects on the absorption and pharmacokinetics of cocoa flavanols.Life Sci. 2003; 73:857-869
67. Fogliano V, Corollaro ML, Vitaglione P, et al. In vitro bioaccessibility and gut biotransformation of polyphenols present in the water-insoluble cocoa fraction. Mol Nutr
Food Res. 2011 Feb 3. doi: 10.1002/mnfr.201000360
68. Tzounis X, Rodriguez-Mateos A, Vulevic J, et al. Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind,
crossover intervention study. American Journal of Clinical Nutrition. 2011; 93:62-72
69. Lahtinen SJ, Ouwehand AC, Salminen SJ, et al Effect of starch- and lipid-based encapsulation on the culturability of two Bifidobacterium longum strains. Letters in
Applied Microbiology. 2007; 44:500-505
70. Possemiers S, Marzorati M, Verstraete W, et al. Bacteria and chocolate: a successful combination for probiotic delivery. Int J Food Microbiol. 2010; 141:97-103
71. Picard C, Fioramonti J, Francois A, et al. Review article: bifidobacteria as probiotic agents — physiological effects and clinical benefits. Aliment Pharmacol Ther. 2005;
72. Saikali J, Picard C, Freitas M, et al. Fermented milks, probiotic cultures, and colon cancer. Nutr Cancer 2004; 49:14-24
73. Januszewska R, Viaene J. Sensory segments in preference for plain chocolate across Belgium and Poland. Food Quality and Preference. 2001; 12:97-107
74. Thamke I, Dürrschmid K, Rohm H. Sensory description of dark chocolates by consumers LWT – Food science and Technology, 2009; 42:534-539
75. Parker G, Parker I, Brotchie H. Mood effects of chocolate. Journal of Affective Disorders. 2006; 92:149-159
76. Macht M, Dettmer D. Everyday mood and emotions after eating a chocolate bar or an apple. Appetite. 2006; 46:332-336
77. Macht M, Mueller J. Immediate effects of chocolate on experimentally induced mood states. Appetite. 2007; 49:667-674
78. Macht M, Haupt C, Ellgring H. The perceived function of eating is changed during examination stress: a field study. Eating Behaviors. 2005; 6:109-112
79. Pollard TM, Steptoe A, Canaan L, et al. Effects of academic examination stress on eating behavior and blood lipid levels. International Journal of Behavioral Medicine.
1995; 2:299-320
80. Striegel-Moore RH, Morrison JA, Schreiber G, et al. Emotion-induced eating and sucrose intake in children: the NHLBI growth and health study. International Journal
of Eating Disorders. 1999; 25:389-398
81. Kandiah J, Yake M, Jones M, et al. Stress influences appetite and comfort food preferences in college women. Nutrition Research. 2006; 26:118-123
82. Drewnowski A, Kurth C, Ho J, et al. Food preferences in human obesity: carbohydrates versus fats. Appetite. 1992; 18:207-221
83. Weingarten HP, Elston D. Food cravings in a college population. Appetite. 1991; 17:167-175
84. Rozin P, Michener W. Towards a psychology of food choice. Danone Chair Publication, Institut Danone. Brussels, Belgium. 1998
85. Benton D, Donohoe RT. The effects of nutrients on mood. Public Health Nutr. 1999; 2:403-409
86. Bruinsma K, Taren DL. Chocolate: food or drug? J Am Diet Assoc. 1999; 99:1249-1256
87. Nakamura H, Takishima T, Kometani T, et al. Psychological stress-reducing effect of chocolate enriched with gamma-aminobutyric acid (GABA) in humans: assessment
of stress using heart rate variability and salivary chromogranin A. Int J Food Sci Nutr. 2009; 22:1-8
88. Watanabe M, Maemura K, Kanbara K, et al. GABA and GABA receptors in the central nervous system andother organs. Int Rev Cytol. 2002; 213:1-47
89. Fisher ND, Sorond FA, Hollenberg NK. Cocoa flavanols and brain perfusion. J Cardiovasc Pharmacol. 2006; 47:S210-214
90. Francis ST, Head K, Morris PG, et al. The effect of flavanol-rich cocoa on the fMRI response to a cognitive task in healthy young people. J Cardiovasc Pharmacol.
2006; 47:S215-220
91. Crews WD Jr, Harrison DW, Wright JW. A double-blind, placebo-controlled, randomized trial of the effects of dark chocolate and cocoa on variables associated with
neuropsychological functioning and cardiovascular health: clinical findings from a sample of healthy, cognitively intact older adults. Am J
Clin Nutr. 2008; 87:872-880
92. Scholey AB, French SJ, Morris PJ, et al. Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental
effort. J Psychopharmacol. 2010; 24:1505-1514
93. Field DT, Williams CM, Butler LT. Consumption of cocoa flavanols results in an acute improvement in visual and cognitive functions. Physiol Behav. 2011; 103:255-
94. Spencer JP. Flavonoids and brain health: multiple effects underpinned by common mechanisms. Genes Nutr. 2009; 4:243-250
95. Spencer JP. Beyond antioxidants: the cellular and molecular interactions of flavonoids and how these underpin their actions on the brain. Proc Nutr Soc. 2010;
96. Farag MA, Huhman DV, Lei Z, et al. Metabolic profiling and systematic identification of flavonoids and isoflavonoids in roots and cell suspension cultures of Medicago
truncatula using HPLC-UV-ESI-MS and GC-MS. Phytochemistry. 2007; 68:342-354
97. Guo S, Bezard E, Zhao B. Protective effect of green tea polyphenols on the SH-SY5Y cells against 6-OHDA induced apoptosis through ROS-NO pathway. Free
Radic Biol Med. 2005; 39:682-695
98. Reznichenko L, Amit T, Youdim MB, et al. Green tea polyphenol (-)-epigallocatechin-3-gallate induces neurorescue of long-term serum-deprived PC12 cells and
promotes neurite outgrowth. J Neurochem. 2005; 93:1157-1167
99. Tsuji E, Uchida T, Fukui A, et al. Evaluation of bitterness suppression of macrolide dry syrups by jellies. Chem Pharm Bull. 2006; 54:310-314
100.Ishizaka T, Okada S, Takemoto E, et al. The suppression of enhanced bitterness intensity of macrolide dry syrup mixed with an acidic powder. Chem Pharm Bull
(Tokyo). 2007; 55:1452-1457
101.Lee KW, Kim YJ, Lee HJ, et al. Cocoa has more phenolic phytochemicals and a higher antioxidant capacity than teas and red wine. J Agric Food Chem. 2003;
102.Selmi C, Cocchi CA, Lanfredini M, et al. Chocolate at heart: the anti-inflammatory impact of cocoa flavanols. Mol Nutr Food Res. 2008; 52:1340-1348
103.Monagas M, Khan N, Andres-Lacueva C, et al. Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease.
Am J Clin Nutr. 2009; 90:1144-1150
104.Morris K, Taren D. Eating Your Way to Happiness: Chocolate, Brain Metabolism, and Mood. In: Karger Gazette, Issue 68 (Chocolate). Basel, Switzerland: S. Karger,
105.Katz D, Doughty K, Ali A. Cocoa and Chocolate in Human Health and Disease. Antioxid Redox Signal. 2011 Apr 7. [Epub ahead of print]