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Thromb Haemost 2014; 112(06): 1151-1158
DOI: 10.1160/th14-05-0450
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Effects of dark chocolate consumption on the prothrombotic response to acute psychosocial stress in healthy men

Roland von Känel
1   Department of Neurology, Inselspital, Bern University Hospital, and University of Bern, Switzerland
2   Department of Clinical Research, University of Bern, Switzerland
3   Department of Psychosomatic Medicine, Clinic Barmelweid, Barmelweid, Switzerland
,
Rebecca E. Meister
1   Department of Neurology, Inselspital, Bern University Hospital, and University of Bern, Switzerland
2   Department of Clinical Research, University of Bern, Switzerland
4   Clinical Psychology and Psychotherapy, Psychological Institute, University of Zurich, Switzerland
,
Monika Stutz
5   Thrombosis Research Laboratory, Inselspital, Bern University Hospital, Switzerland
,
Petra Kummer
4   Clinical Psychology and Psychotherapy, Psychological Institute, University of Zurich, Switzerland
,
Angela Arpagaus
4   Clinical Psychology and Psychotherapy, Psychological Institute, University of Zurich, Switzerland
,
Susanne Huber
4   Clinical Psychology and Psychotherapy, Psychological Institute, University of Zurich, Switzerland
,
Ulrike Ehlert
4   Clinical Psychology and Psychotherapy, Psychological Institute, University of Zurich, Switzerland
,
Petra H. Wirtz
6   Biological and Health Psychology, Department of Psychology, University of Bern, Switzerland
7   Work and Health Psychology, University of Konstanz, Konstanz, Germany
› Author Affiliations Financial support: This work was funded by research grants from the Swiss Cocoa and Chocolate Foundation (Grant 2009) and the Swiss National Science Foundation (Grant PP00P1_128565/1) (both to PHW). The funding bodies had no influence on the study design, data collection and analyses, the writing of the manuscript, or the decision to submit the manuscript for publication.
Further Information

Publication History

Received: 21 May 2014

Accepted after major revision: 22 July 2014

Publication Date:
18 November 2017 (online)

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Summary

Flavanoid-rich dark chocolate consumption benefits cardiovascular health, but underlying mechanisms are elusive. We investigated the acute effect of dark chocolate on the reactivity of prothrombotic measures to psychosocial stress. Healthy men aged 20–50 years (mean ± SD: 35.7 ± 8.8) were assigned to a single serving of either 50 g of flavonoid-rich dark chocolate (n=31) or 50 g of optically identical flavonoid-free placebo chocolate (n=34). Two hours after chocolate consumption, both groups underwent an acute standardised psychosocial stress task combining public speaking and mental arithmetic. We determined plasma levels of four stress-responsive prothrombotic measures (i. e., fibrinogen, clotting factor VIII activity, von Willebrand Factor antigen, fibrin D-dimer) prior to chocolate consumption, immediately before and after stress, and at 10 minutes and 20 minutes after stress cessation. We also measured the flavonoid epicatechin, and the catecholamines epinephrine and norepinephrine in plasma. The dark chocolate group showed a significantly attenuated stress reactivity of the hypercoagulability marker D-dimer (F=3.87, p=0.017) relative to the placebo chocolate group. Moreover, the blunted D-dimer stress reactivity related to higher plasma levels of the flavonoid epicatechin assessed before stress (F=3.32, p = 0.031) but not to stress-induced changes in catecholamines (p’s=0.35). There were no significant group differences in the other coagulation measures (p’s≥0.87). Adjustments for covariates did not alter these findings. In conclusion, our findings indicate that a single consumption of flavonoid- rich dark chocolate blunted the acute prothrombotic response to psychosocial stress, thereby perhaps mitigating the risk of acute coronary syndromes triggered by emotional stress.

Keywords

Blood coagulation - cardiovascular disease - catecholamines - epicatechin - psychological stress
 

  • References

  • 1 Buitrago-Lopez A, Sanderson J, Johnson L. et al. Chocolate consumption and cardiometabolic disorders: systematic review and meta-analysis. Br Med J 2011; 343: d4488.
    CrossrefPubMedGoogle Scholar
  • 2 Arranz S, Valderas-Martinez P, Chiva-Blanch G. et al. Cardioprotective effects of cocoa: clinical evidence from randomized clinical intervention trials in humans. Mol Nutr Food Res 2013; 57: 936-947.
    CrossrefPubMedGoogle Scholar
  • 3 Hooper L, Kroon PA, Rimm EB. et al. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2008; 88: 38-50.
    CrossrefPubMedGoogle Scholar
  • 4 Wollgast J, Anklam E. Review in polyphenols in Theobroma cacao: changes in composition during the manufacture of chocolate and methodology for identification and quantification. Food Res Int 2000; 33: 423-447.
    CrossrefPubMedGoogle Scholar
  • 5 Cooper KA, Campos-Giménez E, Jimé nez Alvarez D. et al. 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 2007; 55: 2841-2847.
    CrossrefPubMedGoogle Scholar
  • 6 Schroeter H, Heiss C, Balzer J. et al. (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci USA 2006; 103: 1024-1029.
    CrossrefPubMedGoogle Scholar
  • 7 von Känel R. Psychosocial stress and cardiovascular risk : current opinion. Swiss Med Wkly 2012; 142: w13502.
    CrossrefPubMedGoogle Scholar
  • 8 Leor J, Poole WK, Kloner RA. Sudden cardiac death triggered by an earthquake. N Engl J Med 1996; 334: 413-419.
    CrossrefPubMedGoogle Scholar
  • 9 Mostofsky E, Maclure M, Tofler GH. et al. Relation of outbursts of anger and risk of acute myocardial infarction. Am J Cardiol 2013; 112: 343-348.
    CrossrefPubMedGoogle Scholar
  • 10 Bhattacharyya MR, Steptoe A. Emotional triggers of acute coronary syndromes: strength of evidence, biological processes, and clinical implications. Prog Cardiovasc Dis 2007; 49: 353-365.
    CrossrefPubMedGoogle Scholar
  • 11 Strike PC, Magid K, Whitehead DL. et al. Pathophysiological processes underlying emotional triggering of acute cardiac events. Proc Natl Acad Sci USA 2006; 103: 4322-4327.
    CrossrefPubMedGoogle Scholar
  • 12 Servoss SJ, Januzzi JL, Muller JE. Triggers of acute coronary syndromes. Prog Cardiovasc Dis 2002; 44: 369-380.
    CrossrefPubMedGoogle Scholar
  • 13 Hassellund SS, Flaa A, Sandvik L. et al. Effects of anthocyanins on blood pressure and stress reactivity: a double-blind randomized placebo-controlled crossover study. J Hum Hypertens 2012; 26: 396-404.
    CrossrefPubMedGoogle Scholar
  • 14 Steptoe A, Gibson EL, Vuononvirta R. et al. The effects of tea on psychophysiological stress responsivity and post-stress recovery: a randomised double-blind trial. Psychopharmacology 2007; 190: 81-89.
    CrossrefPubMedGoogle Scholar
  • 15 Wirtz PH, von Känel R, Meister R. et al. Dark chocolate intake buffers stress reactivity in humans. J Am Coll Cardiol 2014; 63: 2297-2299.
    CrossrefPubMedGoogle Scholar
  • 16 von Känel R, Dimsdale JE. Effects of sympathetic activation by adrenergic infusions on hemostasis in vivo. Eur J Haematol 2000; 65: 357-369.
    CrossrefPubMedGoogle Scholar
  • 17 Rein D, Paglieroni TG, Wun T. et al. Cocoa inhibits platelet activation and function. Am J Clin Nutr 2000; 72: 30-35.
    CrossrefPubMedGoogle Scholar
  • 18 Stote 1 KS, Clevidence BA, Novotny JA. et al. Effect of cocoa and green tea on biomarkers of glucose regulation, oxidative stress, inflammation and hemostasis in obese adults at risk for insulin resistance. Eur J Clin Nutr 2012; 66: 1153-1159.
    CrossrefPubMedGoogle Scholar
  • 19 Abou-Agag LH, Aikens ML, Tabengwa EM. et al. Polyphyenolics increase t-PA and u-PA gene transcription in cultured human endothelial cells. Alcohol Clin Exp Res 2001; 25: 155-162.
    CrossrefPubMedGoogle Scholar
  • 20 Austin AW, Wissmann T, von Känel R. Stress and hemostasis: an update. Semin Thromb Hemost 2013; 39: 902-912.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Holt RR, Actis-Goretta L, Momma TY. et al. Dietary flavanols and platelet reactivity. J Cardiovasc Pharmacol 2006; 47 (Suppl. 02) S187-196.
    CrossrefPubMedGoogle Scholar
  • 22 Wirtz PH, Ehlert U, Emini L. et al. Anticipatory cognitive stress appraisal and the procoagulant stress response in men. Psychosom Med 2006; 68: 851-858.
    CrossrefPubMedGoogle Scholar
  • 23 Rein D, Lotito S, Holt RR. et al. Epicatechin in human plasma: In vivo determination and effect of chocolate consumption on plasma oxidation status. J Nutr 2000; 130: 2109-2114S.
    CrossrefPubMedGoogle Scholar
  • 24 Kirschbaum C, Pirke KM, Hellhammer DH. The ’trier social stress test’--a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 1993; 28: 76-81.
    CrossrefPubMedGoogle Scholar
  • 25 von Känel R, Preckel D, Zgraggen L. et al. The effect of natural habituation on coagulation responses to acute mental stress and recovery in men. Thromb Hae-most 2004; 92: 1327-1335.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Ehrenreich H, Schuck J, Stender N. et al. Endocrine and hemodynamic effects of stress versus systemic CRF in alcoholics during early and medium term abstinence. Alcohol Clin Exp Res 1997; 21: 1285-1293.
    CrossrefPubMedGoogle Scholar
  • 27 Kotani A, Miyashita N, Kusu F. Determination of catechins in human plasma after commercial canned green tea ingestion by high-performance liquid chromatography with electrochemical detection using a microbore column. J Chromatogr B Analyt Technol Biomed Life Sci 2003; 788: 269-275.
    CrossrefPubMedGoogle Scholar
  • 28 Hornung R, Reed L. Estimation of average concentration in the presence of nondectable values. Appl Occup Environ Hyg 1990; 05: 46-51.
    CrossrefPubMedGoogle Scholar
  • 29 Faul F, Erdfelder E, Buchner A. et al. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 2009; 41: 1149-1160.
    CrossrefPubMedGoogle Scholar
  • 30 Adam SS, Key NS, Greenberg CS. D-dimer antigen: current concepts and future prospects. Blood 2009; 113: 2878-2887.
    CrossrefPubMedGoogle Scholar
  • 31 Kleinegris MC, ten Cate H, ten Cate-Hoek AJ. D-dimer as a marker for cardiovascular and arterial thrombotic events in patients with peripheral arterial disease. A systematic review. Thromb Haemost 2013; 110: 233-243.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Danesh J, Whincup P, Walker M. et al. Fibrin D-dimer and coronary heart disease: prospective study and meta-analysis. Circulation 2001; 103: 2323-2327.
    CrossrefPubMedGoogle Scholar
  • 33 Akgul O, Uyarel H. D-dimer: a novel predictive marker for cardiovascular disease. Int J Cardiol 2013; 168: 4930-4931.
    CrossrefPubMedGoogle Scholar
  • 34 Akgul O, Uyarel H, Pusuroglu H. et al. Predictive value of elevated D-dimer in patients undergoing primary angioplasty for ST elevation myocardial infarction. Blood Coagul Fibrinolysis 2013; 24: 704-710.
    CrossrefPubMedGoogle Scholar
  • 35 von Känel R, Dimsdale JE, Ziegler MG. et al. Effect of acute psychological stress on the hypercoagulable state in subjects (spousal caregivers of patients with Alzheimer‘s disease) with coronary or cerebrovascular disease and/or systemic hypertension. Am J Cardiol 2001; 87: 1405-1408.
    CrossrefPubMedGoogle Scholar
  • 36 Strike PC, Magid K, Brydon L. et al. Exaggerated platelet and hemodynamic reactivity to mental stress in men with coronary artery disease. Psychosom Med 2004; 66: 492-500.
    CrossrefPubMedGoogle Scholar
  • 37 Mittleman MA, Maclure M, Sherwood JB. et al. Triggering of acute myocardial infarction onset by episodes of anger. Determinants of Myocardial Infarction Onset Study Investigators. Circulation 1995; 92: 1720-1725.
    CrossrefPubMedGoogle Scholar
  • 38 Aschbacher K, von Känel R, Mills PJ. et al. Longitudinal platelet reactivity to acute psychological stress among older men and women. Stress 2009; 12: 426-433.
    CrossrefPubMedGoogle Scholar
  • 39 Kloner RA. Natural and unnatural triggers of myocardial infarction. Prog Cardiovasc Dis 2006; 48: 285-300.
    CrossrefPubMedGoogle Scholar
  • 40 Bravo L. Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev 1998; 56: 317-333.
    PubMedGoogle Scholar
  • 41 Richelle M, Tavazzi I, Enslen M. et al. Plasma kinetics in man of epicatechin from black chocolate. Eur J Clin Nutr 1999; 53: 22.
    CrossrefPubMedGoogle Scholar
  • 42 Roura E, Andrés-Lacueva C, Jáuregui O. et al. Rapid liquid chromatography tandem mass spectrometry assay to quantify plasma (-)-epicatechin metabolites after ingestion of a standard portion of cocoa beverage in humans. J Agric Food Chem 2005; 53: 6190-6194.
    CrossrefPubMedGoogle Scholar
  • 43 Serafini M, Bugianesi R, Maiani G. et al. Plasma antioxidants from chocolate. Nature 2003; 424: 1013.
    CrossrefPubMedGoogle Scholar
  • 44 Carnevale R, Loffredo L, Pignatelli P. et al. Dark chocolate inhibits platelet isoprostanes via NOX2 down-regulation in smokers. J Thromb Haemost 2012; 10: 125-132.
    CrossrefPubMedGoogle Scholar
  • 45 Cuenca-García M, Ruiz JR, Ortega FB. et al. Association between chocolate consumption and fatness in European adolescents. Nutrition 2014; 30: 236-239.
    CrossrefPubMedGoogle Scholar
  • 46 Hughes LA, Arts IC, Ambergen T. et al. Higher dietary flavone, flavonol, and catechin intakes are associated with less of an increase in BMI over time in women: a longitudinal analysis from the Netherlands Cohort Study. Am J Clin Nutr 2008; 88: 1341-1352.
    PubMedGoogle Scholar
  • 47 Tousoulis D, Kampoli AM, Tentolouris C. et al. The role of nitric oxide on endothelial function. Curr Vasc Pharmacol 2012; 10: 4-18.
    CrossrefPubMedGoogle Scholar
  • 48 Asakura H, Okudaira M, Ontachi Y. et al. Antithrombotic role of nitric oxide in rats under physiological conditions. Thromb Haemost 2004; 91: 71-75.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 49 Brossette T, Hundsdörfer C, Kröncke KD. et al. Direct evidence that (-)-epicatechin increases nitric oxide levels in human endothelial cells. Eur J Nutr 2011; 50: 595-599.
    CrossrefPubMedGoogle Scholar
  • 50 Holt RR, Schramm DD, Keen CL. et al. Chocolate consumption and platelet function. J Am Med Assoc 2002; 287: 2212-2213.
    CrossrefPubMedGoogle Scholar
  • 51 Innes AJ, Kennedy G, McLaren M. et al. Dark chocolate inhibits platelet aggregation in healthy volunteers. Platelets 2003; 14: 325-327.
    CrossrefPubMedGoogle Scholar
  • 52 Brummel-Ziedins KE, Everse SJ, Mann KG. et al. J Thromb Thrombolysis 2014; 37: 32-44.
    CrossrefPubMed
  • 53 von Känel R, Mills PJ, Ziegler MG. et al. Effect of beta2-adrenergic receptor functioning and increased norepinephrine on the hypercoagulable state with mental stress. Am Heart J 2002; 144: 68-72.
    CrossrefPubMedGoogle Scholar
  • 54 Bijak M, Saluk J, Ponczek MB. et al. Antithrombin effect of polyphenol-rich extracts from black chokeberry and grape seeds. Phytother Res 2013; 27: 71-76.
    CrossrefPubMedGoogle Scholar
  • 55 Ostertag LM, O‘Kennedy N, Kroon PA. et al. Impact of dietary polyphenols on human platelet function--a critical review of controlled dietary intervention studies. Mol Nutr Food Res 2010; 54: 60-81.
    CrossrefPubMedGoogle Scholar