Acute Vascular Effects of Chocolate in Healthy Human Volunteers

  • Manuel Rusconi
  • Maria Grazia Rossi
  • Tiziano Moccetti
  • Ario Conti


We have all experienced a sense of impending illness prior to its actual onset. Indeed, a lot of us have felt that either before or during sickness our emotions may have influenced the course of the disease. Such anecdotes have existed since ancient time and in the last decade have been the initial foundation for a new and rapidly developing area of medical research. Central to these sensations, as well as the new field of neuroendocrine-immune interactions, is the realization that our brain and endocrine system can influence our immunity and that the immune system serves as a sensory organ, which ultimately signals the brain. In recent decades, conceptual shifts in biological sciences have provided new evidence to support intuitive beliefs regarding the connection between the mind-body unit, external and/or internal stimuli such as viruses and bacteria, and primordial environmental stimuli such as light-dark cycle, moon cycle, tides, magnetic forces and humidity. Moreover, many new factors such as climate changes, air pollution, the rise in world population, particularly in developing countries, the rise of poverty in developed countries, and their social and environmental effects are becoming increasingly sophisticated. Consequently, the role of human management of the ecosystem, has been reconsidered by each and every one of us, scientists, politicians, and the lay public. On the other hand, methodological communication was not a major problem during the early days of medicine. Treatment modalities were based on a gift from mother nature: plants and extracts thereof. Herbal medicines, which have to be integrated in this vision, have long been an accepted treatment of various diseases throughout the world.


Cocoa Butter Cocoa Bean Healthy Human Volunteer Dark Chocolate Milk Chocolate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank everyone who made the study possible. In particular, in alphabetical order: Andlauer Wilfried, University of Applied Sciences, Sion, Switzerland; Colombo Maria Laura, Faculty of Pharmacy, University of Turin, Turin, Italy; Confiserie Teuscher AG, Zürich, Switzerland; Cosentino Marco and collaborators, Department of Clinical Medicine, University of Insubria, Varese, Italy; Mudry Jean Daniel, Swiss army, Bellinzona, Switzerland; Muggli Franco, Swissarmy, Grenadier School, Isone, Switzerland; Nurses and dieticians of Cardio Centro Ticino, Lugano, Switzerland; Paoletti Rodolfo, Department of Pharmacology, University of Milan, Milan, Italy; Pasotti Marco, Cioccolatieri ticinesi, LuganoTrevano, Switzerland; Rusconi Manuel, co-author of the publication, who has done the work for his PhD title, Locarno, Switzerland; Soldati Gianni, Laboratorio di diagnostica molecolare, Lugano, Switzerland; Technicians of the clinical analysis laboratory of the regional hospital in Lugano, Switzerland; Villettaz Jean Claude, University of Applied Sciences, Sion, Switzerland; Volunteers: all volunteers who participated in the study deserve a special thank; Zanini Giovanni Maria, cantonal pharmacist, Mendrisio, Switzerland.


  1. 1.
    McCann SM, Lipton JM et al (eds) (1998) Neuroimmunomodulation: molecular aspects, integrative systems and clinical advances. Ann NY Acad Sci, New YorkGoogle Scholar
  2. 2.
    Savino W, Silva PO, Besedowsky H (eds) (2009) Neuromodulation: from fundamental biology to therapy. Ann NY Acad Sci, New YorkGoogle Scholar
  3. 3.
    Rusconi M, Conti A (2010) Theobroma cacao L., the food of the Goods: a scientific approach beyond myths and claims. Pharmacol Res 61:5–13PubMedCrossRefGoogle Scholar
  4. 4.
    Hooper l, Kroon PA et al (2008) Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr 88:38–50PubMedGoogle Scholar
  5. 5.
    Athyros VG, Kakafika AI et al (2011) Effect of a plant stanol ester-containing spread, placebo spread, or Mediterranean diet on estimated cardiovascular risk and lipid, inflammatory and haemostatic. Nutr Metab Cardiovasc Dis 21(3):213–221PubMedCrossRefGoogle Scholar
  6. 6.
    Kondo K et al (1996) Inhibition of LDL oxidation by cacao. Lancet 348:1514PubMedCrossRefGoogle Scholar
  7. 7.
    Visioli F et al (2009) Chocolate lifestyle and health. Crit Rev Food Sci Nutr 49:299–312PubMedCrossRefGoogle Scholar
  8. 8.
    Di Giuseppe R et al (2008) Regular consumption of dark chocolate is associated with low serum concentration of C-reactive protein in a healthy Italian population. J Nutr 138:1939–1945PubMedGoogle Scholar
  9. 9.
    Faridi Z et al (2008) Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial. Am J Clin Nutr 88:58–63PubMedGoogle Scholar
  10. 10.
    Taubert D et al (2007) Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide. JAMA 298:49–60PubMedCrossRefGoogle Scholar
  11. 11.
    Ramiro-Puig E, Castell M (2009) Cacao: antioxidant and immunomodulator. Br J Nutr 101(7):931–940PubMedCrossRefGoogle Scholar
  12. 12.
    Sanbongi C et al (1997) Polyphenols in chocolate, which have antioxidant activity, modulate immune functions in humans in vitro. Cell Immunol 177:129–136PubMedCrossRefGoogle Scholar
  13. 13.
    Mao TK et al (2002) Modulation of TNF-alpha secretion in peripheral blood mononuclear cells by cacao flavanols and procyanidins. Dev Immunol 9(3):135–141PubMedCrossRefGoogle Scholar
  14. 14.
    Mao TK et al (2003) Cacao flavonols and procyanidins promote transforming growth factor-beta1 homeostasis in peripheral blood mononuclear cells. Exp Biol Med 228(1):93–99Google Scholar
  15. 15.
    Mao TK et al (2002) Effect of cacao flavanols and their related oligomers on the secretion of interleukin-5 in peripheral blood mononuclear cells. J Med Food 5(1):17–22PubMedCrossRefGoogle Scholar
  16. 16.
    Mao TK et al (2000) The effect of cacao procyanidins on the transcription and secretion of interleukin 1 beta in peripheral blood mononuclear cells. Life Sci 66(15):1377–1386PubMedCrossRefGoogle Scholar
  17. 17.
    Jenny M et al (2009) Cacao extracts suppress tryptophan degradation of mitogen-stimulated peripheral blood mononuclear cells. J Ethnopharmacol 122:261–267PubMedCrossRefGoogle Scholar
  18. 18.
    Ramiro-Puig E et al (2007) Cocoa-enriched diet enhances antioxidant enzyme activity and modulates lymphocyte composition in thymus from young rats. J Agric Food Chem 55:6431–6438PubMedCrossRefGoogle Scholar
  19. 19.
    Ramiro-Puig E et al (2007) Spleen lymphocyte function modulated by a cocoa enriched diet. Clin Exp Immunol 149:535–542PubMedCrossRefGoogle Scholar
  20. 20.
    Ramiro-Puig E et al (2008) Intestinal immune system of young rats influenced by cocoa enriched diet. J Nutr Biochem 19:555–565PubMedCrossRefGoogle Scholar
  21. 21.
    Schramm DD 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
  22. 22.
    Ramiro E et al (2005) Effect of Theobroma cacao flavonoids on immune activation of a lymphoid cell line. Br J Nutr 93:859–866PubMedCrossRefGoogle Scholar
  23. 23.
    Mao T et al (2000) Cacao procyanidins and human cytokine transcription and secretion. J Nutr 130:2093S–2099SPubMedGoogle Scholar
  24. 24.
    Mowen KA, Glimcher LH (2004) Signaling pathways in Th2 development. Immunol Rev 202:203–222PubMedCrossRefGoogle Scholar
  25. 25.
    Ramiro-Puig E, Casadeus G et al (2009) Neuroprotective effect of cacao flavonoids on in vitro oxidative stress. Eur J Nutr 48:54–61PubMedCrossRefGoogle Scholar
  26. 26.
    Selmi C, Cocchi CA et al (2008) Review Chocolate at heart: The anti-inflammatory impact of cacao flavanols. Mol Nutr Food Res 52:1340–1348PubMedCrossRefGoogle Scholar
  27. 27.
    Tomas-Barberan F et al (2007) A new process to develop a cacao powder with higher flavonoid monomer content and enhanced bioavailability in healthy humans. J Agric Food Chem 55:3926–3935PubMedCrossRefGoogle Scholar
  28. 28.
    Hollenberg NK et al (2004) Cacao, flavanols and cardiovascular risk. Br J Cardiol 11(5):379–386Google Scholar
  29. 29.
    Taubert D et al (2003) Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. JAMA 290(8):1029–1030PubMedCrossRefGoogle Scholar
  30. 30.
    Grassi D et al (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(3):611–614PubMedGoogle Scholar
  31. 31.
    Moore KW et al (1993) Interleukin 10. Ann Rev Immunol 11:165–190CrossRefGoogle Scholar
  32. 32.
    Beutler B et al (1998) Tumor necrosis factor: a macrophage hormone governing cellular metabolism and inflammatory response. Endocr Rev 9:57CrossRefGoogle Scholar
  33. 33.
    Janssen O, Kaebelitz D (1998) Tumor necrosis factor selectively inhibits activation of human B cells by Epstein-Barr virus. J Immunol 140:125Google Scholar
  34. 34.
    Beutler B et al (1988) Catechin (Tumor Necrosis Factor): a macrophage hormone governing cellular metabolism and inflammatory response. Endocr Rev 9:57PubMedCrossRefGoogle Scholar
  35. 35.
    Maury P (1986) Acta Scan 220:387CrossRefGoogle Scholar
  36. 36.
    Janssen O, Kabelitz D (1988) Tumor necrosis factor selectively inhibits activation of human B cells by Eppstein Barr Virus. J Immunol 140:125PubMedGoogle Scholar
  37. 37.
    Waage A et al (1987) Association between tumor necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet 14:355CrossRefGoogle Scholar
  38. 38.
    Scuderi P et al (1986) Raised serum levels of tumor necrosis factor in parasitic infections. Lancet 13:1364–1365CrossRefGoogle Scholar
  39. 39.
    Gaumond B et al (1988) Proceedings of the 88th Annual Meeting of the American Society for MicrobiologyGoogle Scholar
  40. 40.
    Israël-Biet D et al (1991) Tumor necrosis factor production in HIV seropositive subjects. Relationship with lung opportunistics infections and HIV expression in alveolar macrophages. J Immunol 147:490PubMedGoogle Scholar
  41. 41.
    Krishnan VL et al (1990) Alveolar macrophages in AIDS patients: increased spontaneous tumor necrosis factor alpha production in Pneumocystis carinii pneumonia. Clin Exp Immunol 80:156–160PubMedCrossRefGoogle Scholar
  42. 42.
    Reddy MM et al (1988) Tumor necrosis factor and HIV p24 antigen in the serum of HIVinfected population. J AIDS 1:436Google Scholar
  43. 43.
    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
  44. 44.
    Fisher ND, Hughes M et al (2003) Flavanol-rich cacao induces nitric-oxide-dependent vasodilation in healthy humans. J Hypertens 21:2281–2286PubMedCrossRefGoogle Scholar
  45. 45.
    Taubert D et al (2007) Effect of low habitual cacao intake on blood pressure and bioactive nitric oxide. A randomized controlled trial. JAMA 298:49–60PubMedCrossRefGoogle Scholar
  46. 46.
    Hooper l, Kroon PA et al (2008) Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr 88:38–50PubMedGoogle Scholar
  47. 47.
    Hollenberg NK (2006) Vascular action of cacao flavanols in humans: the roots of the story. J Cardiovasc Pharmacol 47:S99–S102CrossRefGoogle Scholar
  48. 48.
    Wurtman RJ, Wurtman JJ (1989) Carbohydrates and depression. Sci Am 260:68–75PubMedCrossRefGoogle Scholar
  49. 49.
    Parker G et al (2006) Mood state effects of chocolate. J Affect Disord 92:149–159PubMedCrossRefGoogle Scholar
  50. 50.
    Balzer J, Rassaf T et al (2008) Sustained benefits in vascular function through flavanol-containing cacao in medicated diabetic patients: a double-masked, randomized, controlled trial. J Am Coll Cardio 51:2141CrossRefGoogle Scholar
  51. 51.
    Weingarten HP, Elston D (1991) Food cravings in a college population. Appetite 17:167–175PubMedCrossRefGoogle Scholar
  52. 52.
    Rozin P, Levine E, Stoess C (1991) Chocolate craving and liking. Appetite 17:199–212PubMedCrossRefGoogle Scholar
  53. 53.
    Drewnowski A (1992) Food preferences and the opioid peptide system. Trends Food Sci Technol 3:97–99CrossRefGoogle Scholar
  54. 54.
    Michener W, Rozin P (1994) Pharmacological versus sensory factors in the satiation of chocolate craving. Physiol Behav 56:419–422PubMedCrossRefGoogle Scholar
  55. 55.
    DiTomaso E et al (1996) Brain cannabinoids in chocolate. Nature 382:677–678CrossRefGoogle Scholar
  56. 56.
    Facchini F, Hollenbeck CB et al (1992) Demonstration of a relationship between white blood cell count, insulin resistance, and several risk factors for coronary heart disease in women. J Intern Med 232:267–272PubMedCrossRefGoogle Scholar
  57. 57.
    Thompson GR, Grundy SM (2005) History and development of plant sterol and stanol esters for cholesterol-lowering purposes. Am J Cardiol 96:3–9CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Manuel Rusconi
  • Maria Grazia Rossi
  • Tiziano Moccetti
  • Ario Conti
    • 1
  1. 1.Alpine Foundation for Life SciencesOlivone, TicinoSwitzerland

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