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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Background
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Background
Short-term supplementation with flavanol-rich cocoa improves lipid profile, antioxidant status and positively influences the AA/EPA ratio in healthy subjects
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“Polyphenols also (1) enhance the production of endothelium-derived hyperpolarizing factor (EDHF) and prostacyclin and (2) inhibit the synthesis of vasoconstrictors such as endothelin-1 and the angiotensinconverting enzyme [14, 17].”
Background
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Background
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Background
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Background
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Background
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Background
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Background
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“incidence of CVD including myocardial infarction, heart failure and stroke (9-11).”
Background
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BackgroundInfluential
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“Furthermore, this flavanol-related increase in vasodilation and improvement in endothelial function can be reversed by L-N-monomethyl arginine, a competitive eNOS inhibitor, resulting in a significant reduction in blood flow.(3,14) It can be argued, therefore, that the reduced BP and cardiovascular risk in individuals…”
BackgroundInfluential
Brachial and Cerebrovascular Functions Are Enhanced in Postmenopausal Women after Ingestion of Chocolate with a High Concentration of Cocoa
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Chocolate Consumption and Risk of Stroke in Women
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CYP1A1 is overexpressed upon incubation of breast cancer cells with a polyphenolic cocoa extract
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“Many examples of the health benefits of cocoa consumption can be found in the literature [18–21].”
Background
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
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“Cocoa is rich in minerals and phytonutrients, namely flavanols, including catechin, epicatechin and proanthocyanidins (PACs), and due to the higher cocoa content, dark chocolate may confer the greatest metabolic benefits when compared to milk or white chocolate [27,28].”
Background
Cocoa Flavanols Protect Human Endothelial Cells from Oxidative Stress
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“functional disorders of vascular endothelia which can lead to endothelial apoptosis and thus alter the function and structure of the vascular tissues [1].”
Background
Fluorescent detection of (−)-epicatechin in microsamples from cacao seeds and cocoa products: Comparison with Folin–Ciocalteu method
Ramírez‐Sánchez, I., Maya-Ramos, L., Ceballos, G. M., & Villarreal, F. J. (2010) · Journal of Food Composition and Analysis · doi:10.1016/j.jfca.2010.03.014 · Cited by 33
(-)-Epicatechin-induced calcium independent eNOS activation: roles of HSP90 and AKT
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“, cocoa) appears to provide beneficial cardiovascular effects [2, 3] The vascular actions of cocoa on the vasculature are related to its ability to activate endothelial nitric oxide synthase (eNOS), and as a consequence nitric oxide (NO) production [3, 4].”
Background
Daily chocolate consumption is inversely associated with insulin resistance and liver enzymes in the Observation of Cardiovascular Risk Factors in Luxembourg study
Alkerwi, A., Sauvageot, N., Crichton, G. E., Elias, M. F., & Stranges, S. (2016) · British Journal Of Nutrition · doi:10.1017/s0007114516000702 · Cited by 32
“Cocoa beans and its derivatives contain different types of physiologically active compounds including, among others, polyphenols and their flavonoids subclasses((6,7)).”
Background
Chemical Characterization, Gastrointestinal Motility and Sensory Evaluation of Dark Chocolate: A Nutraceutical Boosting Consumers’ Health
Caponio, G. R., Lorusso, M. P., Sorrenti, G. T., Marcotrigiano, V., Difonzo, G., Angelis, E. D., Guagnano, R., Ciaula, A. D., Diella, G., Logrieco, A. F., et al. (2020) · Nutrients · doi:10.3390/nu12040939 · Cited by 32
The effect of an apple polyphenol extract rich in epicatechin and flavan-3-ol oligomers on brachial artery flow-mediated vasodilatory function in volunteers with elevated blood pressure
Saarenhovi, M., Salo, P., Scheinin, M., Lehto, J., Lovró, Z., Tiihonen, K., Lehtinen, M. J., Junnila, J. J. T., Hasselwander, O., Tarpila, A., et al. (2017) · Nutrition Journal · doi:10.1186/s12937-017-0291-0 · Cited by 32
Occurrence of heavy metals coupled with elevated levels of essential elements in chocolates: Health risk assessment
Godebo, T. R., Stoner, H. M., Kodsup, P., Bases, B., Marzoni, S., Weil, J., Frey, M., Daley, P., Earnhart, A., Ellias, G., et al. (2024) · Food Research International · doi:10.1016/j.foodres.2024.114360 · Cited by 31
Direct evidence that (−)-epicatechin increases nitric oxide levels in human endothelial cells
Brossette, T., Hundsdörfer, C., Kröncke, K., Sies, H., & Stahl, W. (2011) · European Journal of Nutrition · doi:10.1007/s00394-011-0172-9 · Cited by 31
“Vasodilatory effects of flavanol-rich cocoa have already been demonstrated in humans measuring pulse wave amplitude or flow-mediated dilation of the brachial artery [6, 13 ].”
Background
Dietary Flavanols: A Review of Select Effects on Vascular Function, Blood Pressure, and Exercise Performance
Al-Dashti, Y. A., Holt, R. R., Stebbins, C. L., Keen, C. L., & Hackman, R. M. (2018) · Journal of the American College of Nutrition · doi:10.1080/07315724.2018.1451788 · Cited by 35
“Impaired vascular function is associated with amplified exercise-induced increases in BP (18).”
Background
Stimulatory Effects of the Flavanol (-)-Epicatechin on Cardiac Angiogenesis
Ramírez‐Sánchez, I., Nogueira, L., Moreno‐Ulloa, A., Murphy, A. N., Taub, P. R., Perkins, G. A., Ceballos, G. M., Hogan, M. C., Malek, M. H., & Villarreal, F. J. (2012) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e318269ae0d · Cited by 31
“Cacao seeds contain large amounts of flavonoids, in particular the subtype known as flavanols (up to 7% by weight).(4) Main flavanols in cacao are catechins and epicatechins present in monomeric or multimeric forms.”
Potential of Food and Natural Products to Promote Endothelial and Vascular Health
Auger, C., Amissi, S., Nguyen, P. N., Chabert, P., Idris-Khodja, N., & Schini‐Kerth, V. B. (2016) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000382 · Cited by 33
“Several clinical studies have reported that cocoa-derived products including chocolate, exert a beneficial effect on the cardiovascular system by targeting the endothelial function.(79,80) Consumption of dark chocolate, a product rich in polyphenols (in average 1.”
Background
Theobroma cacao: Review of the Extraction, Isolation, and Bioassay of Its Potential Anti-cancer Compounds.
Baharum, Z., Akim, A. M., Hin, T. Y. Y., Hamid, R. A., & Kasran, R. (2016) · PubMed Central · Cited by 31
Chocolate‐candy consumption and 3‐year weight gain among postmenopausal U.S. women
Greenberg, J. A., Manson, J. E., Buijsse, B., Wang, L., Allison, M., Neuhouser, M. L., Tinker, L. F., Waring, M. E., Isasi, C. R., Martin, L. W., et al. (2015) · Obesity · doi:10.1002/oby.20983 · Cited by 30
“While an emerging body of scientific evidence suggests that dark chocolate may have the ability to decrease cardiovascular disease risk over the short-term (3), much is still unknown about the relationship between long-term chocolate-candy consumption and body weight.”
Background
Cocoa (Theobroma cacao) Seeds and Phytochemicals in Human Health
Kim, J., Lee, K. W., & Lee, H. J. (2011) · Nuts and Seeds in Health and Disease Prevention · doi:10.1016/b978-0-12-375688-6.10042-8 · Cited by 29
Total Phenolic Content and Antioxidant Activity of Different Types of Chocolate, Milk, Semisweet, Dark, and Soy, in Cerebral Cortex, Hippocampus, and Cerebellum of Wistar Rats
Medeiros, N. D. S., Marder, R. K., Wohlenberg, M. F., Funchal, C., & Dani, C. (2015) · Biochemistry Research International · doi:10.1155/2015/294659 · Cited by 28
“Clinical studies have suggested that flavonoids in cocoa may act beneficially in preventing cardiovascular diseases through its effects in reducing blood pressure, improving endothelial function, increasing nitric oxide, reducing platelet aggregation and blood lipids, and decreasing insulin resistance [9, 10].”
Alleviation of Cadmium Chloride–Induced Acute Genotoxicity, Mitochondrial DNA Disruption, and ROS Generation by Chocolate Coadministration in Mice Liver and Kidney Tissues
Mohamed, H. R. H. (2021) · Biological Trace Element Research · doi:10.1007/s12011-021-02981-y · Cited by 28
“Chocolate has also gained great popularity and interest due to its potential physiological and health effects, such as regulating blood pressure, vascular function, insulin levels, prebiotic effects, oxidative processes, glucose homeostasis, and lipid metabolism [14, 16, 17, 43].”
Background
Tolerance for High Flavanol Cocoa Powder in Semisweet Chocolate
Harwood, M. L., Ziegler, G. R., & Hayes, J. E. (2013) · Nutrients · doi:10.3390/nu5062258 · Cited by 29
“However, there is interest in preserving the polyphenol content in foods [7], as these compounds are now being investigated for potential health benefits they may confer to the consumer [8].”
Background
Chocolate consumption and risk of stroke among men and women: A large population-based, prospective cohort study
Dong, J.-Y., Iso, H., Yamagishi, K., Sawada, N., & Tsugane, S. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.03.004 · Cited by 28
Cocoa-induced (Theobroma cacao) effects on cardiovascular system: HDL modulation pathways.
Santos, H. O., & Macedo, R. C. (2018) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2018.06.001 · Cited by 24
Impact of Cocoa Products Intake on Plasma and Urine Metabolites: A Review of Targeted and Non-Targeted Studies in Humans
Mayorga-Gross, A. L., & Esquivel, P. (2019) · Nutrients · doi:10.3390/nu11051163 · Cited by 28
Polyphenols can Potentially Prevent Atherosclerosis and Cardiovascular Disease by Modulating Macrophage Cholesterol Metabolism
Ito, F. (2020) · Current Molecular Pharmacology · doi:10.2174/1874467213666200320153410 · Cited by 30
Improving cocoa beans value chain using a local convection dryer: A case study of Fako division Cameroon.
Tardzenyuy, M. E., Jianguo, Z., Tetteh, A., & Mbuwel, M. P. (2020) · Scientific African · doi:10.1016/j.sciaf.2020.e00343 · Cited by 27
Unraveling the beneficial effects of herbal Lebanese mixture “Za’atar”. History, studies, and properties of a potential healthy food ingredient
Khalil, M., Caponio, G. R., Diab, F., Shanmugam, H., Ciaula, A. D., Khalifeh, H., Vergani, L., Calasso, M. P., Angelis, M. D., & Portincasa, P. (2022) · Journal of Functional Foods · doi:10.1016/j.jff.2022.104993 · Cited by 27
The blood pressure effect and related plasma levels of flavan-3-ols in spontaneously hypertensive rats
Quiñones, M., Margalef, M., Arola‐Arnal, A., Muguerza, B., Miguel, M., & Aleixandre, A. (2015) · Food & Function · doi:10.1039/c5fo00547g · Cited by 27
Theobromine Is Responsible for the Effects of Cocoa on the Antibody Immune Status of Rats
Camps‐Bossacoma, M., Pérez-Cano, F. J., Franch, À., & Castell, M. (2018) · Journal of Nutrition · doi:10.1093/jn/nxx056 · Cited by 26
Gene expression changes by high-polyphenols cocoa powder intake: a randomized crossover clinical study
Barrera‐Reyes, P. K., Hernández-Ramírez, N., Cortés, J., Poquet, L., Redeuil, K. M., Rangel‐Escareño, C., Kussmann, M., Silva‐Zolezzi, I., & Tejero, M. E. (2018) · European Journal of Nutrition · doi:10.1007/s00394-018-1736-8 · Cited by 27
Cocoa, Blood Pressure, and Vascular Function
Sudano, I., Flammer, A. J., Roas, S., Enseleit, F., Ruschitzka, F. T., Corti, R., & Noll, G. (2012) · Current Hypertension Reports · doi:10.1007/s11906-012-0281-8 · Cited by 30
Self-citation
Morphological and genetic diversity of cacao (Theobroma cacao L.) in Uganda
Gopaulchan, D., Motilal, L. A., Bekele, F. L., Clause, S., Ariko, J. O., Ejang, H. P., & Umaharan, P. (2019) · Physiology and Molecular Biology of Plants · doi:10.1007/s12298-018-0632-2 · Cited by 25
Vasorelaxant activity of twenty-one physiologically relevant (poly)phenolic metabolites on isolated mouse arteries
Rymenant, E. V., Grootaert, C., Beerens, K., Needs, P. W., Kroon, P. A., Kerimi, A., Williamson, G., Garcı́a-Villalba, R., González‐Sarrías, A., Tomás-Barberán, F. A., et al. (2017) · Food & Function · doi:10.1039/c7fo01273j · Cited by 24
Cardiovascular Benefits of Dark Chocolate?
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Preclinical evaluation of the diuretic and saluretic effects of (-)-epicatechin and the result of its combination with standard diuretics
Mariano, L. N. B., Boeing, T., da Silva, R. D. C. V., Filho, V. C., Niero, R., da Silva, L. M., de Souza, P., & de Andrade, S. F. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.08.045 · Cited by 23
Chronic and acute effects of cocoa products intake on arterial stiffness and platelet count and function: A systematic review and dose-response Meta-analysis of randomized clinical trials
Azad, B. J., Daneshzad, E., Meysamie, A. P., & Koohdani, F. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2020.1733484 · Cited by 23
Exploring the Therapeutic Potential of Theobroma cacao L.: Insights from In Vitro, In Vivo, and Nanoparticle Studies on Anti-Inflammatory and Anticancer Effects
Sitarek, P., Merecz-Sadowska, A., Sikora, J., Osicka, W., Śpiewak, I., Picot, L., & Kowalczyk, T. (2024) · Antioxidants · doi:10.3390/antiox13111376 · Cited by 25
“Theobroma cacao appears to have anticancer and anti-inflammatory properties thanks to its flavonoid, polyphenol, and alkaloid content [13–15].”
Co-administration of the flavanol (-)-epicatechin with doxycycline synergistically reduces infarct size in a model of ischemia reperfusion injury by inhibition of mitochondrial swelling
Ortiz-Vilchis, P., Yamazaki, K. G., Rubio‐Gayosso, I., Ramírez‐Sánchez, I., Calzada, C., Romero‐Perez, D., Ortiz, A., Meaney, E., Taub, P. R., Villarreal, F. J., et al. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.09.042 · Cited by 22
“Published evidenced indicates that the beneficial effects of cacao is most likely mediated by EPI (Corti et al., 2009).”
Background
Relationship between chocolate consumption and overall and cause-specific mortality, systematic review and updated meta-analysis
Zhao, B., Gan, L., Yu, K. F., Männistö, S., Huang, J., & Albanes, D. (2022) · European Journal of Epidemiology · doi:10.1007/s10654-022-00858-5 · Cited by 22
Potential mechanisms of multimodal prehabilitation effects on surgical complications: a narrative review
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Blooming reduces the antioxidant capacity of dark chocolate in rats without lowering its capacity to improve lipid profiles
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“Since flavanols can also influence other vascular effects, such as inflammation, platelet aggregation, and nitric oxide-mediated endothelial changes [39–41], effects of bloomed chocolates on the other risk factors of CVD also remain to be determined.”
Background
A single dose of dark chocolate increases parasympathetic modulation and heart rate variability in healthy subjects
Duarte, A. A. M., Mostarda, C. T., Irigoyen, M. C., & Rigatto, K. (2016) · Revista de Nutrição · doi:10.1590/1678-98652016000600002 · Cited by 21
Compositional Variation among Black Tea Across Geographies and Their Potential Influence on Endothelial Nitric Oxide and Antioxidant Activity
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Targeting the AKT‐P53 / CREB pathway with epicatechin for improved prognosis of traumatic brain injury
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Cocoa Consumption, Cocoa Flavonoids, and Effects on Cardiovascular Risk Factors: An Evidence-Based Review
Bauer, S. R., Ding, E. L., & Smit, L. A. (2011) · Current Cardiovascular Risk Reports · doi:10.1007/s12170-011-0157-5 · Cited by 20
Anticancer Agents from Non-Edible Parts of Theobroma cacao
Zainal, B. (2014) · Natural Products Chemistry & Research · doi:10.4172/2329-6836.1000134 · Cited by 20
“Recent investigation on Panama’s Kuna Indian population revealed that Kuna Indians living on the islands, and heavy consumers of cocoa, had significantly lower rates of heart disease, cancer, and diabetes mellitus compared to those on the mainland, who do not consume cocoa [5].”
Background
Preclinical Studies and Translational Applications of Intracerebral Hemorrhage
Siaw-Debrah, F., Nyanzu, M. K., Ni, H., Lin, X., Xu, Z., Ruan, L., Zhuge, Q., & Huang, L. (2017) · BioMed Research International · doi:10.1155/2017/5135429 · Cited by 21
“Consumption of EC rich products has been identified to reduce blood pressure and the incidence of cardiopulmonary diseases [60].”
Background
Dietary Cocoa Powder Improves Hyperlipidemia and Reduces Atherosclerosis in apoE Deficient Mice through the Inhibition of Hepatic Endoplasmic Reticulum Stress
Guan, H., Lin, Y., Bai, L., An, Y., Shang, J., Wang, Z., Zhao, S., Fan, J., & Liu, E. (2016) · Mediators of Inflammation · doi:10.1155/2016/1937572 · Cited by 20
“It has been demonstrated that cocoa powder has a number of physiological effects, such as antioxidant effects, anti-inflammatory effects, and improvement of endothelial cell functions, which improve cardiovascular functions [4, 5].”

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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