Cited by 424Food Chemistry and Fat AnalysisPhytochemicals and Antioxidant ActivitiesNitric Oxide and Endothelin Effects

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Cocoa and Cardiovascular Health

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Corti, Roberto, Flammer, Andreas J., Hollenberg, Norman K., Lüscher, Thomas F.·2009·Circulation

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Abstract

Epidemiological data demonstrate that regular dietary intake of plant-derived foods and beverages reduces the risk of coronary heart disease and stroke. Among many ingredients, cocoa might be an important mediator. Indeed, recent research demonstrates a beneficial effect of cocoa on blood pressure, insulin resistance, and vascular and platelet function. Although still debated, a range of potential mechanisms through which cocoa might exert its benefits on cardiovascular health have been proposed, including activation of nitric oxide and antioxidant and antiinflammatory effects. This review summarizes the available data on the cardiovascular effects of cocoa, outlines potential mechanisms involved in the response to cocoa, and highlights the potential clinical implications associated with its consumption.

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“NO from endothelium prevents leukocyte adhesion and migration, smooth muscle cell proliferation, and platelet adhesion and aggregation (Corti et al., 2009).”
BackgroundInfluential
The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: a randomized, controlled trial
Massee, L. A., Ried, K., Pase, M. P., Travica, N., Yoganathan, J., Scholey, A. B., Macpherson, H., Kennedy, G., Sali, A., & Pipingas, A. (2015) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00093 · Cited by 93
“The Kuna are one of few remaining tribes who are protected from vascular ailments, such as arterial hypertension (Corti et al., 2009).”
Background
Survey of Commercially Available Chocolate- and Cocoa-Containing Products in the United States. 2. Comparison of Flavan-3-ol Content with Nonfat Cocoa Solids, Total Polyphenols, and Percent Cacao
Miller, K. B., Hurst, W. J., Flannigan, N., Ou, B., Lee, C. Y., Smith, N. L., & Stuart, D. A. (2009) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf901821x · Cited by 92
Molecular mechanisms underlying the potential antiobesity‐related diseases effect of cocoa polyphenols
Ali, F., Ismail, A., & Kersten, S. (2013) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201300277 · Cited by 95
“The two main molecules that regulate translocation of GLUT4 and adipokines secretion are PI3K and AMPK [138, 139].”
Influential
Flavanols and Methylxanthines in Commercially Available Dark Chocolate: A Study of the Correlation with Nonfat Cocoa Solids
Langer, S., Marshall, L. J., Day, A. J., & Morgan, M. R. A. (2011) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf201398t · Cited by 90
Bioactive compounds in Mexican genotypes of cocoa cotyledon and husk
Hernández‐Hernández, C., Viera, I., Morales‐Sillero, A., Fernández‐Bolaños, J., & Rodríguez‐Gutiérrez, G. (2017) · Food Chemistry · doi:10.1016/j.foodchem.2017.08.018 · Cited by 89
The flavanol (-)-epicatechin and its metabolites protect against oxidative stress in primary endothelial cells via a direct antioxidant effect
Ruijters, E. J. B., Weseler, A. R., Kicken, C. H., Haenen, G. R. M. M., & Bast, A. (2013) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2013.05.029 · Cited by 87
Effects of cocoa extract and a multivitamin on cognitive function: a randomized clinical trial
Baker, L. D., Manson, J. E., Rapp, S. R., Sesso, H. D., Gaussoin, S. A., Shumaker, S. A., & Espeland, M. A. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.12767 · Cited by 88
Nutrition and other lifestyle influences on arterial aging
LaRocca, T. J., Martens, C. R., & Seals, D. R. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.002 · Cited by 83
Habitual chocolate consumption and risk of cardiovascular disease among healthy men and women
Kwok, C. S., Boekholdt, S. M., Lentjes, M. A. H., Loke, Y. K., Luben, R., Yeong, J. K.-Y., Wareham, N. J., Myint, P. K., & Khaw, K. (2015) · Heart · doi:10.1136/heartjnl-2014-307050 · Cited by 87
Cardiovascular risk factors and molecular routes underlying endothelial dysfunction: Novel opportunities for primary prevention
Benincasa, G., Coscioni, E., & Claudio Napoli, A. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115108 · Cited by 84
Dark Chocolate Acutely Improves Walking Autonomy in Patients With Peripheral Artery Disease
Loffredo, L., Perri, L., Catasca, E., Pignatelli, P., Brancorsini, M., Nocella, C., FALCO, E. D., Bartimoccia, S., Frati, G., Carnevale, R., et al. (2014) · Journal of the American Heart Association · doi:10.1161/jaha.114.001072 · Cited by 84
“The vasodilating capacity of dark chocolate could be dependent on the polyphenol antioxidant effect that has been documented in humans by reduction of markers of oxidative stress as well as by an increase of its plasma antioxidant property.(26,27) In accordance with this effect, patients with PAD, when given dark choc…”
Background
Dose-dependent increases in flow-mediated dilation following acute cocoa ingestion in healthy older adults
Monahan, K. D., Feehan, R. P., Kunselman, A. R., Preston, A. G., Miller, D. L., & Lott, M. E. J. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00865.2011 · Cited by 84
Evaluation of the effect of processing on cocoa polyphenols: antiradical activity, anthocyanins and procyanidins profiling from raw beans to chocolate
Bordiga, M., Locatelli, M., Travaglia, F., Coïsson, J. D., Mazza, G., & Arlorio, M. (2015) · International Journal of Food Science & Technology · doi:10.1111/ijfs.12760 · Cited by 84
Dietary cocoa reduces metabolic endotoxemia and adipose tissue inflammation in high-fat fed mice
Gu, Y., Yu, S., Park, J. Y., Harvatine, K. J., & Lambert, J. D. (2014) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2013.12.004 · Cited by 83
“Over the last decade, a growing number of studies have reported the health benefits of cocoa and cocoa flavan-3-ols, particularly reduced risk of cardiometabolic diseases by promoting nitric oxide bioavailability, as well as, through antioxidant, antiinflammatory, and anti-platelet activities [20–25].”
Background
The cardiovascular benefits of dark chocolate
Kerimi, A., & Williamson, G. (2015) · Vascular Pharmacology · doi:10.1016/j.vph.2015.05.011 · Cited by 81
Chocolate consumption and risk of stroke
Larsson, S. C., Virtamo, J. R. K., & Wolk, A. (2012) · Neurology · doi:10.1212/wnl.0b013e31826aacfa · Cited by 80
“6 Stockholm Heart Epidemiology Program, Sweden Nondiabetic men and women hospitalized with a myocardial infarction, 45–70 yr 111 (1,169) Twice or more per week vs never Age, sex, education, smoking, obesity, physical inactivity, alcohol consumption, filtered coffee consumption, and sweet score”
Background
Genome-Wide Analysis of the NAC Domain Transcription Factor Gene Family in Theobroma cacao
Shen, S., Zhang, Q., Shi, Y., Sun, Z., Zhang, Q., Hou, S., Wu, R., Jiang, L., Zhao, X., & Guo, Y. (2019) · Genes · doi:10.3390/genes11010035 · Cited by 77
Cocoa hulls polyphenols stabilized by microencapsulation as functional ingredient for bakery applications.
Papillo, V. A., Locatelli, M., Travaglia, F., Bordiga, M., Garino, C., Coïsson, J., & Arlorio, M. (2019) · Food Research International · doi:10.1016/j.foodres.2018.10.004 · Cited by 65
Polyphenol-rich cranberry juice has a neutral effect on endothelial function but decreases the fraction of osteocalcin-expressing endothelial progenitor cells
Flammer, A. J., Martin, E. A., Gössl, M., Widmer, R. J., Lennon, R. J., Sexton, J. A., Loeffler, D. L., Khosla, S., Lerman, L. O., & Lerman, A. (2012) · European Journal of Nutrition · doi:10.1007/s00394-012-0334-4 · Cited by 78
“Overall, we found 21 [8/42] EPC (CD34/CD133/KDR) counts per 100,000 gated lymphocytes in the cranberry group and 15 [4, 36] in the placebo group.”
BackgroundMethodSelf-citation
Epicatechin limits renal injury by mitochondrial protection in cisplatin nephropathy
Tanabe, K., Tamura, Y., Lanaspa, M. A., Miyazaki, M., Suzuki, N., Sato, W., Maeshima, Y., Schreiner, G. F., Villarreal, F. J., Johnson, R. J., et al. (2012) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00227.2012 · Cited by 77
“Therefore, cocoa powder or dark chocolate is typically rich in epicatechin (8, 13).”
Background
Effect of cocoa on blood pressure
Ried, K., Sullivan, T. R., Fakler, P., Frank, O. R., & Stocks, N. P. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008893.pub2 · Cited by 150
Low vs. Higher-Dose Dark Chocolate and Blood Pressure in Cardiovascular High-Risk Patients
Desch, S., Kobler, D., Schmidt, J., Sonnabend, M., Adams, V., Sareban, M., Eitel, I., Blüher, M., Schuler, G. C., & Thiele, H. (2010) · American Journal of Hypertension · doi:10.1038/ajh.2010.29 · Cited by 75
Balancing virtual land imports by a shift in the diet. Using a land balance approach to assess the sustainability of food consumption. Germany as an example
Meier, T., Christen, O., Semler, E., Jahreis, G., Voget-Kleschin, L., Schrode, A., & Artmann, M. (2013) · Appetite · doi:10.1016/j.appet.2013.11.006 · Cited by 79
“Conversely, an ovo-lacto vegetarian diet is associated with a decreased prevalence of adiposity, hypertonia, stroke and type 2 diabetes (Craig, 2010) as well as a lower all-cause mortality (Orlich et al., 2013).”
Background
Dark chocolate inhibits platelet isoprostanes via NOX2 down‐regulation in smokers
Carnevale, R., Loffredo, L., Pignatelli, P., Nocella, C., Bartimoccia, S., SANTO, S. D., Martino, F., Catasca, E., Perri, L., & Violi, F. (2011) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2011.04558.x · Cited by 74
“Therefore, we aimed to investigate if acute ingestion of polyphenol-rich dark chocolate or milk chocolate, that has lower polyphenol content [20, 21], differently affected platelet-derived oxidative stress and platelet activation.”
BackgroundMethod
Epigenetic associations in relation to cardiovascular prevention and therapeutics
Voelter‐Mahlknecht, S. (2016) · Clinical Epigenetics · doi:10.1186/s13148-016-0170-0 · Cited by 73
“Various studies have indicated a connection between a polyphenol-rich diet and a reduced risk of CVD [13, 22–24].”
Background
Effect of Fermentation and Drying on Procyanidins, Antiradical Activity and Reducing Properties of Cocoa Beans
Mattia, C. D., Martuscelli, M., Sacchetti, G., Scheirlinck, I., Beheydt, B., Mastrocola, D., & Pittia, P. (2012) · Food and Bioprocess Technology · doi:10.1007/s11947-012-1028-x · Cited by 72
“…which possess antioxidant activity and have been reported to exert a protective effect against cardiovascular diseases, cancer and inflammatory processes in the human body (Engler et al. 2004; Heiss et al. 2005; Serafini et al. 2003; Jourdain et al. 2006; Corti et al. 2009; Cooper et al. 2008).”
Effects of (−)-Epicatechin on Myocardial Infarct Size and Left Ventricular Remodeling After Permanent Coronary Occlusion
Yamazaki, K. G., Taub, P. R., Barraza-Hidalgo, M., Rivas, M. M., Zambon, A. C., Ceballos, G. M., & Villarreal, F. J. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.01.055 · Cited by 71
Beneficial effects of dark chocolate on exercise capacity in sedentary subjects: underlying mechanisms. A double blind, randomized, placebo controlled trial
Taub, P. R., Ramírez‐Sánchez, I., Patel, M., Higginbotham, E., Moreno‐Ulloa, A., Román-Pintos, L. M., Phillips, P., Perkins, G. A., Ceballos, G. M., & Villarreal, F. J. (2016) · Food & Function · doi:10.1039/c6fo00611f · Cited by 71
Cocoa consumption reduces NF-κB activation in peripheral blood mononuclear cells in humans
Vázquez-Agell, M., Urpí-Sardà, M., Sacanella, E., Camino-López, S., Chiva‐Blanch, G., Llorente‐Cortés, V., Tobías, E., Roura, E., Andrés‐Lacueva, C., Lamuela-Raventós, R. M., et al. (2011) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2011.03.015 · Cited by 70
“Cardiovascular protection by flavonoid-rich diets has mainly been attributed to noninflammatory mechanisms [4], such as vasodilatation [5], reduction in plasma cholesterol concentrations [6], insulin resistance [7] and blood pressure [8], as well as modulation of platelet function [9].”
Background
Antioxidant properties of cold and hot water extracts of cocoa, Hibiscus flower extract, and ginger beverage blends
Awe, F. B., Fagbemi, T. N., Ifesan, B. O., & Badejo, A. A. (2013) · Food Research International · doi:10.1016/j.foodres.2013.01.021 · Cited by 70
Fish Consumption in Healthy Adults Is Associated with Decreased Circulating Biomarkers of Endothelial Dysfunction and Inflammation during a 6-Year Follow-Up
van Bussel, B. C. T., Henry, R. M. A., Schalkwijk, C. G., Ferreira, I., Feskens, E. J. M., Streppel, M. T., Smulders, Y. M., Twisk, J. W. R., & Stehouwer, C. D. A. (2011) · Journal of Nutrition · doi:10.3945/jn.111.139733 · Cited by 67
Theobromine, caffeine, and theophylline metabolites in human plasma and urine after consumption of soluble cocoa products with different methylxanthine contents
Martínez‐López, S., Sarriá, B., Gómez‐Juaristi, M., Goya, L., Mateos, R., & Bravo, L. (2014) · Food Research International · doi:10.1016/j.foodres.2014.03.009 · Cited by 72
Integrative Medicine for Cardiovascular Disease and Prevention
Aggarwal, M., Aggarwal, B., & Rao, J. (2017) · Medical Clinics of North America · doi:10.1016/j.mcna.2017.04.007 · Cited by 71
Platelet NOX, a novel target for anti-thrombotic treatment
Pignatelli, P., & Violi, F. (2014) · Thrombosis and Haemostasis · doi:10.1160/th13-10-0818 · Cited by 71
“The study showed that 2 h after administration of dark chocolate, which is, differently from milk chocolate, rich in polyphenols (64), platelet activation was significantly inhibited coincidentally with impaired NOX2-derived ROS (63).”
Background
Is chocolate consumption associated with health outcomes? An umbrella review of systematic reviews and meta-analyses
Veronese, N., Demurtas, J., Celotto, S., Caruso, M. G., Maggi, S., Bolzetta, F., Firth, J., Smith, L., Schofield, P., Koyanagi, A., et al. (2018) · Clinical Nutrition · doi:10.1016/j.clnu.2018.05.019 · Cited by 66
“quintiles, quartiles, continuous); ( 5 number of included studies and participants in each meta-analysis; (6) the inclusion criteria for studied population; (7) effect size used in each me ta-analysis; (8) study design (case-control, prospective, RCTs); (9) number of cases and control s in each study.”
Method
Cocoa and cocoa bean shells role in human health: An updated review
Cinar, Z. Ö., Atanassova, M., Tumer, T. B., Caruso, G., Antika, G., Sharma, S., Sharifi‐Rad, J., & Pezzani, R. (2021) · Journal of Food Composition and Analysis · doi:10.1016/j.jfca.2021.104115 · Cited by 66
Chemical composition of cupuassu (Theobroma grandiflorum) and cocoa (Theobroma cacao) liquors and their effects on streptozotocin-induced diabetic rats
de Oliveira, T. B., & Genovese, M. I. (2013) · Food Research International · doi:10.1016/j.foodres.2013.02.019 · Cited by 66
Antioxidant and antiplatelet activity by polyphenol‐rich nutrients: focus on extra virgin olive oil and cocoa
Loffredo, L., Perri, L., Nocella, C., & Violi, F. (2016) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12923 · Cited by 65
Effect of Cocoa Polyphenolic Extract on Macrophage Polarization from Proinflammatory M1 to Anti‐Inflammatory M2 State
Dugo, L., Belluomo, M. G., Fanali, C., Russo, M., Cacciola, F., Maccarrone, M., & Sardanelli, A. M. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/6293740 · Cited by 67
Effects of Cocoa Extract and Dark Chocolate on Angiotensin-converting Enzyme and Nitric Oxide in Human Endothelial Cells and Healthy Volunteers–A Nutrigenomics Perspective
Persson, I. A. ‐., Persson, K., Hägg, S., & Andersson, R. G. G. (2010) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3181fe62e3 · Cited by 64

Authors: Corti, R., Flammer, A. J., Hollenberg, N. K., & Lüscher, T. F.
Affiliations: Brigham and Women's Hospital (US)
From the Cardiovascular Center, Cardiology University Hospital, Zurich, Switzerland (R.C., A.J.F., T.F.L.), and Department of Medicine and Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (N.K.H.).
ORCID: Corti, Roberto
Flammer, Andreas J.
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2009-03-17
Volume: 119
Issue: 10
Pages: 1433-1441
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/circulationaha.108.827022
OpenAlex: W2105296434
Cited by: 424
References: 105
Citations by year: 2026: 6 · 2025: 9 · 2024: 14 · 2023: 12 · 2022: 23 · 2021: 17 · 2020: 15 · 2019: 19 · 2018: 35 · 2017: 29 · 2016: 30 · 2015: 27 · 2014: 31 · 2013: 38 · 2012: 46
FWCI: 5.34
Type: journal article
Language: en
Open access: green
www.zora.uzh.ch
Licence: other-oa
Locations: Circulation (publishedVersion)
PubMed (publishedVersion)
Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
Zurich Open Repository and Archive (University of Zurich)
Topics: Life Sciences › Agricultural and Biological Sciences › Food Science › Food Chemistry and Fat Analysis
Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Keywords: Theobroma cacao, cardiovascular health, coronary artery disease, stroke, blood pressure, insulin resistance, vascular function, platelet function, nitric oxide, antioxidant activity, anti-inflammatory activity, plant-based foods
MeSH terms: Adult, Aged, Antioxidants, Beverages, Cacao, Catechin, Endothelium, Vascular, Female, Flavonoids, Food Handling, Heart Diseases, Humans, Hyperlipidemias, Hypertension, Indians, Central American, Insulin Resistance, Iowa, Male, Phytotherapy, Medicine, Traditional, Middle Aged, Nitric Oxide, Platelet Aggregation, Switzerland, Overweight

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