Theobroma cacao and Theobroma grandiflorum: Bioactive Compounds and Associated Health Benefits

  • Maria Inés GenoveseEmail author
  • Helena Rudge de Moraes Barros
Living reference work entry
Part of the Reference Series in Phytochemistry book series (RSP)


The genus Theobroma comprises about 20 species, among them cocoa (Theobroma cacao L.), with the highest economic importance, and cupuassu (T. grandiflorum), of growing interest. Chemical compositions of cocoa and cupuassu unprocessed fresh seeds, pulps, and products (chocolate and cupulate) are presented, and the effects of processing in profile and quantity of the bioactive compounds, namely polyphenols and methylxanthines, are discussed. Dietary consumption of cocoa and dark chocolate has been associated to beneficial effects on health, mainly related to polyphenols and their antioxidant and anti-inflammatory activities affecting important signaling pathways and also modulating intestinal microbiota. Vasodilation and cardioprotective effects of cocoa polyphenols are related to release of nitric oxide (NO) through activation of endothelial NO synthase. Significant improvement of insulin resistance and flow-mediated dilatation (FMD) and reductions in diastolic blood pressure and mean arterial pressure were reported. In particular, the effects of cocoa and cupuassu polyphenols on obesity and glucose metabolism are reviewed.


Cocoa Cupuassu Polyphenols Obesity Glucose metabolism 



Arachidonic acid


Alanine aminotransferase


AMP-activated protein kinase


Aspartate aminotransferase


Body mass index


Dry weight


Fatty acid


Free fatty acids


Flow-mediated dilatation


Fresh weight




Glucagon-like peptide


Glucose transporter


Glutathione peroxidase


Glutathione reductase


Glycogen synthase


Glycogen synthase kinase 3


High-density lipoprotein


High fat


Heme oxygenase-1


Homeostatic model assessment of cell function


Insulin receptor substrate


Jun N-terminal kinase


Low-density lipoprotein




Mesenteric white adipose tissue


Nuclear factor kappa B


Nitric oxide


Nuclear factor erythroid 2-related factor


Phosphoenolpyruvate carboxykinase


Reactive oxygen species


Superoxide dismutase


Type 2 diabetes

Tb/Cf ratio

Theobromine/caffeine ratio


Thiobarbituric acid reactive substances


Total cholesterol




Toll-like receptor 4


Uncoupling protein


Very low-density lipoprotein


  1. 1.
    Rusconi M, Conti A (2010) Theobroma cacao L., the food of the gods: a scientific approach beyond myths and claims. Pharmacol Res 61:5–13CrossRefGoogle Scholar
  2. 2.
    Nazaré RFR, Barbosa WC, Viégas RMF (1990) Processamento das sementes de cupuaçu para obtenção de cupulate, 1st edition; Boletim de Pesquisa EMBRAPA, n.108, EMBRAPA – CPATU (Empresa Brasileira de Pesquisa Agropecuária – Centro de Pesquisa Agropecuária do Trópico Úmido), Belém, 38pGoogle Scholar
  3. 3.
    Wollgast J, 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(6):423–447CrossRefGoogle Scholar
  4. 4.
    Caprioli G, Fiorini D, Maggi F, Nicoletti M, Ricciutelli M, Toniolo C, Prosper B, Vittori S, Sagratini G (2016) Nutritional composition, bioactive compounds and volatile profile of cocoa beans from different regions of Cameroon. Int J Food Sci Nutr 67(4):422–430CrossRefGoogle Scholar
  5. 5.
    Torres-Moreno M, Torrescasana E, Salas-Salvadò J, Blanch C (2015) Nutritional composition and fatty acids profile in cocoa beans and chocolates with different geographical origin and processing conditions. Food Chem 166:125–132CrossRefGoogle Scholar
  6. 6.
    Pugliese AG, Tomas-Barberan FA, Truchado P, Genovese MI (2013) Flavonoids, proanthocyanidins, vitamin C, and antioxidant activity of Theobroma grandiflorum (Cupuassu) pulp and seeds. J Agric Food Chem 61(11):2720–2728CrossRefGoogle Scholar
  7. 7.
    Pugliese AG (2010). Compostos fenólicos do cupuaçu (Theobroma grandiflorum) e do cupulate: composição e possíveis benefícios. Dissertation, University of São PauloGoogle Scholar
  8. 8.
    Lannes SCS, Medeiros ML, Gioielli LA (2004) Rheological properties of cupuassu and cocoa fats. Grasas Aceites 55(2):115–121CrossRefGoogle Scholar
  9. 9.
    Lannes SCS, Medeiros ML, Amaral RL (2002) Formulação de “chocolate” de cupuaçu e reologia do produto líquido. Braz J Pharm Sci 38:463–467Google Scholar
  10. 10.
    Lucas V (2001) Fracionamento térmico e obtenção de gorduras de cupuaçu alternativas à manteiga de cacau para uso na fabricação de chocolate. 195 p. Phd thesis – Faculdade de Engenharia Química, UNICAMP, Campinas. Accessed 3 July 2017
  11. 11.
    Bezerra CV, Rodrigues AMD, de Oliveira PD, da Silva DA, da Silva LHM (2017) Technological properties of amazonian oils and fats and their applications in the food industry. Food Chem 221:1466–1473. CrossRefGoogle Scholar
  12. 12.
    Salgado JM, Rodrigues BS, Donado-Pestana CM, Dias CTD, Morzelle MC (2011) Cupuassu (Theobroma grandiflorum) peel as potential source of dietary Fiber and phytochemicals in whole-bread preparations. Plant Foods Hum Nutr 66(4):384–390CrossRefGoogle Scholar
  13. 13.
    Belscak A, Komes D, Horzic D, Ganic KK, Karlovic D (2009) Comparative study of commercially available cocoa products in terms of their bioactive composition. Food Res Int 42(5–6):707–716CrossRefGoogle Scholar
  14. 14.
    Petyaev IM, Bashmakov YK (2016) Cocobiota: implications for human health. J Nutr Metab:7906927. 3 pagesGoogle Scholar
  15. 15.
    Franco R, Oñatibia-Astibia A, Martínez-Pinilla E (2013) Health benefits of Methylxanthines in cacao and chocolate. Forum Nutr 5(10):4159–4173Google Scholar
  16. 16.
    Carrillo LC, Londoño-Londoño J, Gil A (2014) Comparison of polyphenol, methylxanthines and antioxidant activity in Theobroma cacao beans from different cocoa-growing areas in Colombia. Food Res Int 60:273–280CrossRefGoogle Scholar
  17. 17.
    Peláez PP, Bardón I, Camasca P (2016) Methylxanthine and catechin content of fresh and fermented cocoa beans, dried cocoa beans, and cocoa liquor. Sci Agropecu 7(4):355–365CrossRefGoogle Scholar
  18. 18.
    Trognitz B, Cros E, Assemat S, Davrieux F, Forestier-Chiron N, Ayestas E, Kuant A, Scheldeman X, Hermann M (2013) Diversity of cacao trees in Waslala, Nicaragua: associations between genotype spectra, product quality and yield potential. PLoS One 8(1):e54079CrossRefGoogle Scholar
  19. 19.
    Camu N, De Winter T, Addo SK, Takrama JS, Bernaert H, De Vuyst L (2008) Fermentation of cocoa beans: influence of microbial activities and polyphenol concentrations on the flavour of chocolate. J Sci Food Agr 88(13):2288–2297CrossRefGoogle Scholar
  20. 20.
    Lo Coco F, Lanuzza F, Micali G, Cappellano G (2007) Determination of theobromine, theophylline, and caffeine in by-products of Cupuacu and cacao seeds by high-performance liquid chromatography. J Chromatogr Sci 45:273–275CrossRefGoogle Scholar
  21. 21.
    Bruna C, Eichholz I, Rohn S, Kroh LW, Huyskens-Keil S (2009) Bioactive compounds and antioxidant activity of cocoa hulls (Theobroma cacao L.) from different origins. J App Bot Food Qual 83(1):9–13Google Scholar
  22. 22.
    Yang H, Protiva P, Cui B, Ma C, Baggett S, Hequet V, Mori S, Weinstein IB, Kennelly EJ (2003) New bioactive polyphenols from Theobroma grandiflorum (“cupuaçu”). J Nat Prod 66:1501–1504CrossRefGoogle Scholar
  23. 23.
    Kuskoski EM, Asuero AG, Troncoso AM, Mancini-Filho J, Fett R (2005) Aplicación de diversos métodos químicos para determinar actividad antioxidante em pulpa de frutos. Ciênc Tecnol Aliment 25:726–732CrossRefGoogle Scholar
  24. 24.
    McShea A, Ramiro-Puig E, Munro SB, Casadesus G, Castell M, Smith MA (2008) Clinical benefit and preservation of flavonols in dark chocolate manufacturing. Nutr Rev 66(11):630–641CrossRefGoogle Scholar
  25. 25.
    Oracz J, Zyzelewicz D, Nebesny E (2015) The content of polyphenolic compounds in cocoa beans (Theobroma cacao L.), depending on variety, growing region, and processing operations: a review. Crit Rev Food Sci Nutr 55(9):1176–1192CrossRefGoogle Scholar
  26. 26.
    Andres-Lacueva C, Monagas M, Khan N, Izquierdo-Pulido M, Urpi-Sarda M, Permanyer J, Lamuela-Raventos RM (2008) Flavanol and flavonol contents of cocoa powder products: influence of the manufacturing process. J Agric Food Chem 56(9):3111–3117CrossRefGoogle Scholar
  27. 27.
    Todorovic V, Milenkovic M, Vidovic B, Todorovic Z, Sobajic S (2017) Correlation between antimicrobial, antioxidant activity, and polyphenols of alkalized/nonalkalized cocoa powders. J Food Sci 82(4):1020–1027CrossRefGoogle Scholar
  28. 28.
    Tomas-Barberan FA, Cienfuegos-Jovellanos E, Marin A, Muguerza B, Gil-Izquierdo A, Cerda B, Zafrilla P, Morillas J, Mulero J, Ibarra A, Pasamar MA, Ramon D, Espin JC (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(10):3926–3935CrossRefGoogle Scholar
  29. 29.
    Hooper L, Kay C, Abdelhamid A (2012) Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. Am J Clin Nutr 95(3):740–775CrossRefGoogle Scholar
  30. 30.
    Magrone T, Russo MA, Jirillo E (2017) Cocoa and dark chocolate polyphenols: from biology to clinical applications. Front Immunol 8:677CrossRefGoogle Scholar
  31. 31.
    Bohannon J, Koch D, Homm P, Driehaus A (2015) Chocolate with high cocoa content as a weight-loss accelerator. Int Arch Med 8(55):1–8Google Scholar
  32. 32.
    Farhat G, Drummond S, Fyfe L, Al-Dujaili EAS (2014) Dark chocolate: an obesity paradox or a culprit for weight gain? Phytother Res 28(6):791–797CrossRefGoogle Scholar
  33. 33.
    Rabadan-Chávez G, Quevedo-Corona L, Garcia AM, Reyes-Maldonado E, Jaramillo-Flores ME (2016) Cocoa powder, cocoa extract and epicatechin attenuate hypercaloric diet-induced obesity through enhanced β-oxidation and energy expenditure in white adipose tissue. J Funct Foods 20:54–67CrossRefGoogle Scholar
  34. 34.
    Cuenca-García M, Ruiz JR, Ortega FB, Castillo MJ (2014) HELENA study group association between chocolate consumption and fatness in European adolescents. Nutr 30:236–239CrossRefGoogle Scholar
  35. 35.
    Golomb BA, Koperski S, White HL (2012) Association between more frequent chocolate consumption and lower body mass index. Arch Int Med 172(6):519–521CrossRefGoogle Scholar
  36. 36.
    Strandberg TE, Strandberg AY, Pitkälä K, Salomaa VV, Tilvis RS et al (2008) Chocolate, well-being and health among elderly men. Eur J Clin Nutr 62:247–253CrossRefGoogle Scholar
  37. 37.
    Davison K, Coates AM, Buckley JD, Howe PRC (2008) Effect of cocoa flavanols and exercise on cardiometabolic risk factors in overweight and obese subjects. Int J Obes 32(8):1289–1296CrossRefGoogle Scholar
  38. 38.
    Grassi D, Necozione S, Lippi C, Croce G, Valeri L, Pasqualetti P, Ferri C (2005) Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension 46(2):398–405CrossRefGoogle Scholar
  39. 39.
    Shrime MG, Bauer SR, McDonald AC, Chowdhury NH, Coltart CEM, Ding EL (2011) Flavonoid-rich cocoa consumption affects multiple cardiovascular risk factors in a meta-analysis of short-term studies. J Nutr 141(11):1982–1988CrossRefGoogle Scholar
  40. 40.
    Yeh M, Platkin C, Estrella P, Allinger D, Elbaum R, Brumaru B, Wyka K (2016) Chocolate consumption and health beliefs and its relation to BMI in college students. J Obes Weight Loss 2:1–7Google Scholar
  41. 41.
    Taubert D, Roesen R. Lehmann C, Jung N, Schomig E (2007) Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide. JAMA. 298:49–60Google Scholar
  42. 42.
    Nickols-Richardson SM, Piehowski KE, Metzgar CJ, Miller, DL, Preston AG (2014) Changes in body weight, blood pressure and selected metabolic biomarkers with an energy-restricted diet including twice daily sweet snacks and once daily sugar-free beverage. Nutrition Research and Practice 8(6):695–704Google Scholar
  43. 43.
    Desch S, Kobler D, Schmidt J, Sonnabend M, Adams V, Sareban M, Thiele H (2010) Low vs. Higher-Dose Dark Chocolate and Blood Pressure in Cardiovascular High-Risk Patients. Am J Hypertens 23(6):694–700Google Scholar
  44. 44.
    Greenberg JA, Buijsse B (2013) Habitual Chocolate Consumption May Increase Body Weight in a Dose-Response Manner. PLoS ONE 8(8)Google Scholar
  45. 45.
    Ali F, Ismail A, Esa NM, Pei CP, Kersten S (2015) Hepatic genome-wide expression of lipid metabolism in diet-induced obesity rats treated with cocoa polyphenols. J Funct Foods 17: 969–978Google Scholar
  46. 46.
    Dorenkott MR, Griffin LE, Goodrich KM, Thompson-Witrick KA, Fundaro G, Ye L, Neilson AP (2014) Oligomeric cocoa procyanidins possess enhanced bioactivity compared to monomeric and polymeric cocoa procyanidins for preventing the development of obesity, insulin resistance, and impaired glucose tolerance during high-fat feeding. J Agric Food Chem 62(10):2216–2227Google Scholar
  47. 47.
    Gu Y, Yu S, Park JY, Harvatine K, Lambert JD (2014) Dietary cocoa reduces metabolic endotoxemia and adipose tissue inflammation in high-fat fed mice. J Nutr Biochem 25(4): 439–445Google Scholar
  48. 48.
    Matsui N, Ito R, Nishimura E, Yoshikawa M, Kato M, Kamei M, Hashizume S (2005) Ingested cocoa can prevent high-fat diet-induced obesity by regulating the expression of genes for fatty acid metabolism. Nutr 21(5):594–601Google Scholar
  49. 49.
    Yamashita Y, Okabe M, Natsume M, Ashida H (2012) Prevention mechanisms of glucose intolerance and obesity by cacao liquor procyanidin extract in high-fat diet-fed C57BL/6 mice. Arch Biochem Bioph 527(2):1–10Google Scholar
  50. 50.
    Barros, HRM. (2016) Effects of camu camu and cupuassu phenolic compounds on obesity and type 2 diabetes mellitus development. Tesis. Acessed 20 july 2017
  51. 51.
    Oliveira TB, Rogero MM, Genovese MI (2015) Poliphenolic-rich extracts from cocoa (Theobroma cacao L.) and cupuassu (Theobroma grandiflorum Willd. Ex Spreng. K. Shum) liquors: A comparison of metabolic effects in high-fat fed rats. PharmaNutrition 3(2):20–28Google Scholar
  52. 52.
    Yun JW (2010) Possible anti-obesity therapeutics from nature–a review. Phytochemistry 71(14–15):1625–41Google Scholar
  53. 53.
    Garcia-Conesa MT (2015)  Dietary Polyphenols against Metabolic Disorders: How Far Have We Progressed in the Understanding of the Molecular Mechanisms of Action of These Compounds? Crit Rev Food Sci NutrGoogle Scholar
  54. 54.
    Gu Y, Hurst WJ, Stuart D, Lambert JD (2011) Inhibition of key digestive enzymes by cocoa extracts and procyanidins. J Agric Food Chem 59(10):5305–5311Google Scholar
  55. 55.
    Min SY, Yang H, Seo SG, Shin SH, Chung M-Y, Kim J, Lee KW (2013) Cocoa polyphenols suppress adipogenesis in vitro and obesity in vivo by targeting insulin receptor. Internat J Obes 37(4):584–92Google Scholar
  56. 56.
    Ali F, Ismail A, Esa NM, Pei C (2016) Cocoa polyphenols treatment ameliorates visceral obesity by reduction lipogenesis and promoting fatty acid oxidation genes in obese rats through interfering with AMPK pathway. Eur J Lipid Sci Technol 118(4):564–575Google Scholar
  57. 57.
    Fidaleo M, Fracassi A, Zuorro A, Lavecchia R, Moreno S, Sartori C (2014) Cocoa protective effects against abnormal fat storage and oxidative stress induced by a high-fat diet involve PPAR alpha signalling activation. Food Funct 5(11):2931–2939Google Scholar
  58. 58.
    Ali F, Ismail A, Esa NM, Pei CP, Kersten S (2015) Hepatic genome-wide expression of lipid metabolism in diet-induced obesity rats treated with cocoa polyphenols. J Funct Foods 17:969–978Google Scholar
  59. 59.
    Gu Y, Yu S, Lambert JD (2014) Dietary cocoa ameliorates obesity-related inflammation in high fat-fed mice. Eur J Nutr 53(1):149–158Google Scholar
  60. 60.
    Cordero-Herrera I, Martin MA, Escriva F, Alvarez C et al (2015) Cocoa-rich diet ameliorates hepatic insulin resistance by modulating insulin signaling and glucose homeostasis in Zucker diabetic fatty rats. J. Nutr. Biochem 26:704–712Google Scholar
  61. 61.
    Cordero-Herrera I, Martin MA, Goya L, Ramos S (2015) Cocoa intake ameliorates hepatic oxidative stress in young Zucker diabetic fatty rats. Food Res Int 69:194–201Google Scholar
  62. 62.
    Grassi D, Desideri G, Necozione S, Lippi C, Casale R, Properzi G, Blumberg JB, Ferri C (2008) Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate. J Nutr 138:1671–1676Google Scholar
  63. 63.
    Martin MA, Goya L, Ramos S (2016) Antidiabetic actions of cocoa flavanols. Mol Nutr Food Res 60(8):1756–1769Google Scholar
  64. 64.
    Tomaru M, Takano H, Osakabe N, Yasuda A, Inoue K-I, Yanagisawa R, et al (2007) Dietary supplementation with cacao liquor proanthocyanidins prevents elevation of blood glucose levels in diabetic obese mice. Nutr 23:351–5Google Scholar
  65. 65.
    Fernández-Millán E, Ramos S, Alvarez C, Bravo L, Goya L, Martín MÁ (2014) Microbial phenolic metabolites improve glucose-stimulated insulin secretion and protect pancreatic beta cells against tert-butyl hydroperoxide-induced toxicity via ERKs and PKC pathways. Food Chem Toxicol 66:245–253Google Scholar
  66. 66.
    Fernandez-Millan E, Cordero-Herrera I, Ramos S, Escriva F, Alvarez C, Goya L Martin MA (2015) Cocoa-rich diet attenuates beta cell mass loss and function in young Zucker diabetic fatty rats by preventing oxidative stress and beta cell apoptosis. Molecular Nutrition & Food Research 59(4):820–824Google Scholar
  67. 67.
    Andújar I, Recio M C, Giner RM, Ríos JL (2012) Cocoa polyphenols and their potential benefits for human health. Oxidative Medicine and Cellular LongevityGoogle Scholar
  68. 68.
    Hanhineva K, Törrönen R, Bondia-Pons I, Pekkinen J, Kolehmainen M, Mykkänen H, et al (2010) Impact of dietary polyphenols on carbohydratemetabolism. Int J Mol Sci 11:1365–402Google Scholar
  69. 69.
    Anhê FF, Desjardins Y, Pilon G, Dudonné S, Genovese M I, Lajolo FM, Marette A (2013) Polyphenols and type 2 diabetes: A prospective review. PharmaNutrition 1(4):105–114Google Scholar
  70. 70.
    Barret A, Ndou T, Hughey CA, Straut C, Howel A, Dai Z, Kaletunc G (2013) Inhibition of α-amylase and glucoamylase by tannins extracted from cocoa, pomegranates, cranberries, and grapes. J Agric Food Chem 61(7):1477–86Google Scholar
  71. 71.
    Johnston K, Sharp P, Clifford M, Morgan L (2005) Dietary polyphenols decrease glucose uptake by human intestinal Caco-2 cells. FEBS Lett 579(7):1653–7Google Scholar
  72. 72.
    Katz DL, Doughty K, Ali A (2011) Cocoa and Chocolate in Human Health and Disease. Antioxid Redox Signal 15(10):2779–2811Google Scholar
  73. 73.
    Gonçalves AESS, Lajolo FM, Genovese MI (2010) Chemical composition and antioxidant/antidiabetic potential of brazilian native fruits and commercial frozen pulps. J Agric Food Chem 58(8):4666–4674Google Scholar
  74. 74.
    Kim Y, Keogh JB, Clifton PM (2016) Polyphenols and Glycemic Control. Nutrients 8(1):17Google Scholar
  75. 75.
    Strat KM, Rowley TJ, Smithson AT, Tessem JS, Hulver MW, Liu D, Davy BM, Davy KP, Neilson AP (2016) Mechanisms by which cocoa flavanols improve metabolic syndrome and related disorders. J Nutr Biochem 35:1–21Google Scholar
  76. 76.
    Jalil A-M-M, Ismail A, Pei C-P, Hamid M, Kamaruddin S-H-S (2008) Effects of cocoa extract on glucometabolism, oxidative stress, and antioxidant enzymes in obese- diabetic (Ob-db) rats. J Agric Food Chem 56:7877–84Google Scholar
  77. 77.
    Yamashita Y, Okabe M, Natsume M, Ashida H (2012a) Cacao liquor procyanidin extract improves glucose tolerance by enhancing GLUT4 translocation and glucose uptake in skeletal muscle. J Nutr Sci, 1, e 2Google Scholar
  78. 78.
    Oliveira TB, Genovese MI (2013) Chemical composition of cupuassu (Theobroma grandiflorum) and cocoa (Theobroma cacao) liquors and their effects on streptozotocin-induced diabetic rats. Food Res Internatl 51(2):929–935Google Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Maria Inés Genovese
    • 1
    Email author
  • Helena Rudge de Moraes Barros
    • 1
  1. 1.Department of Food Science and Experimental NutritionUniversity of São PauloSão PauloBrazil

Personalised recommendations