Cited by 345Phytochemicals and Antioxidant ActivitiesCardiovascular Health and Disease PreventionNitric Oxide and Endothelin Effects

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Sustained Benefits in Vascular Function Through Flavanol-Containing Cocoa in Medicated Diabetic Patients

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Balzer, Jan, Rassaf, Tienush, Heiss, Christian, Kleinbongard, Petra, Lauer, Thomas, Merx, Marc, Heussen, Nicole, Gross, Heidrun B., Keen, Carl L., Schroeter, Hagen, Kelm, Malte·2008·Journal of the American College of Cardiology

DOI 10.1016/j.jacc.2008.01.059

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Abstract

Objectives Our goal was to test feasibility and efficacy of a dietary intervention based on daily intake of flavanol-containing cocoa for improving vascular function of medicated diabetic patients.Background Even in fully medicated diabetic patients, overall prognosis is unfavorable due to deteriorated cardiovascular function. Based on epidemiological data, diets rich in flavanols are associated with a reduced cardiovascular risk.Methods In a feasibility study with 10 diabetic patients, we assessed vascular function as flow-mediated dilation (FMD) of the brachial artery, plasma levels of flavanol metabolites, and tolerability after an acute, single-dose ingestion of cocoa, containing increasing concentrations of flavanols (75, 371, and 963 mg). In a subsequent efficacy study, changes in vascular function in 41 medicated diabetic patients were assessed after a 30-day, thrice-daily dietary intervention with either flavanol-rich cocoa (321 mg flavanols per dose) or a nutrient-matched control (25 mg flavanols per dose). Both studies were undertaken in a randomized, double-masked fashion. Primary and secondary outcome measures included changes in FMD and plasma flavanol metabolites, respectively.Results A single ingestion of flavanol-containing cocoa was dose-dependently associated with significant acute increases in circulating flavanols and FMD (at 2 h: from 3.7 +/- 0.2% to 5.5 +/- 0.4%, p < 0.001). A 30-day, thrice-daily consumption of flavanol-containing cocoa increased baseline FMD by 30% (p < 0.0001), while acute increases of FMD upon ingestion of flavanol-containing cocoa continued to be manifest throughout the study. Treatment was well tolerated without evidence of tachyphylaxia. Endothelium-independent responses, blood pressure, heart rate, and glycemic control were unaffected.Conclusions Diets rich in flavanols reverse vascular dysfunction in diabetes, highlighting therapeutic potentials in cardiovascular disease.

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(2002) · New England Journal of Medicine · doi:10.1056/nejmoa012512 · Cited by 19,011
Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery
Corretti, M. C., Anderson, T. J., Benjamin, E. J., Celermajer, D. S., Charbonneau, F., Creager, M. A., Deanfield, J. E., Drexler, H., Gerhard‐Herman, M. D., Herrington, D. M., et al. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(01)01746-6 · Cited by 4,606
Flavonoids: antioxidants or signalling molecules?
Williams, R. J., Spencer, J. P. E., & Rice-Evans, C. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.01.001 · Cited by 2,016
Flavonoid intake and risk of chronic diseases
Knekt, P., Kumpulainen, J. T., Järvinen, R., Rissanen, H. A., Heliövaara, M., Reunanen, A., Hakulinen, T., & Aromaa, A. (2002) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/76.3.560 · Cited by 1,765
Nitric Oxide Is Responsible for Flow-Dependent Dilatation of Human Peripheral Conduit Arteries In Vivo
Joannidès, R., Haefeli, W. E., Linder, L., Richard, V. J., Bakkali, E. H., Thuillez, C., & Lüscher, T. F. (1995) · Circulation · doi:10.1161/01.cir.91.5.1314 · Cited by 1,622
(–)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans
Schroeter, H., Heiss, C., Balzer, J., Kleinbongard, P., Keen, C. L., Hollenberg, N. K., Sies, H., Kwik-Uribe, C., Schmitz, H. H., & Kelm, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510168103 · Cited by 1,052
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Mink, P. J., Scrafford, C. G., Barraj, L. M., Harnack, L., Hong, C.-P., Nettleton, J. A., & Jacobs, D. R. (2007) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/85.3.895 · Cited by 945
Concentrations of Proanthocyanidins in Common Foods and Estimations of Normal Consumption
Kelm, M. A., Hammerstone, J. F., Beecher, G. R., Holden, J., Haytowitz, D. B., Gebhardt, S. E., Gu, L., & Prior, R. L. (2004) · Journal of Nutrition · doi:10.1093/jn/134.3.613 · Cited by 941
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American Diabetes Association (2006) · Diabetes Care · doi:10.2337/diacare.29.s1.06.s43 · Cited by 924
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Habitual cocoa intake reduces arterial stiffness in postmenopausal women regardless of intake frequency: a randomized parallel-group study
Okamoto, T., Kobayashi, R., Natsume, M., & Nakazato, K. (2016) · Clinical Interventions in Aging · doi:10.2147/cia.s118152 · Cited by 20
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Bapir, M., Untracht, G. R., Cooke, D. D., McVey, J. H., Skene, S. S., Campagnolo, P., Whyte, M., Δικαίος, Ν., Rodriguez‐Mateos, A., Sampson, D. D., et al. (2022) · Food & Function · doi:10.1039/d2fo02017c · Cited by 18
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“In addition to this link between IR and T2DM, the pathologies of endothelial dysfunction and IR appear to co-exist, with both being risk factors in the development of cardiovascular disease [3,4].”
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Functional foods for health promotion: state-of-the-science on dietary flavonoidsï¿½Extended abstracts from the 12thAnnual Conference on Functional Foods for Health Promotion, April 2009
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Gu, L. (2012) · Wiley eBooks · doi:10.1002/9781118229378.ch8 · Cited by 16
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“We based our power calculation on the study of Balzer et al. (2008) [33]; however, this study used a cocoa drink instead of purified CF capsules as the CF source, as well as a different placebo CF composition, which might have caused a Nutrients 2022, 14, 2692 11 of 16 biased calculation.”
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Gröne, M., Duse, D. A., Kramser, N., Ophoff, N., Schweers, H., Voß, F., Quast, C., Sansone, R., Heiß, C., Jung, C., et al. (2023) · Food & Function · doi:10.1039/d3fo01737k · Cited by 6
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Acute Effects of Cocoa Flavanols on Blood Pressure and Peripheral Vascular Reactivity in Type 2 Diabetes Mellitus and Essential Hypertension: A Protocol for an Acute, Randomized, Double-Blinded, Placebo-Controlled Cross-Over Trial
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Donovan, J. L., Holes-Lewis, K., Chavin, K. D., & Egan, B. M. (2011) · doi:10.1002/9781444347098.ch8 · Cited by 5
Prolonged ingestion of dietary cocoa attenuates hemoglobin glycation associated with diabetes mellitus in rats.
Amoah, S., Osonuga, A., Djankpa, F. T., Osonuga, O. A., Addai, F. K., Affram, K., Dennis, E., & Ayettey, A. S. (2012) · Cited by 4
Gene-based analysis of angiogenesis, mitochondrial and insulin-related pathways in skeletal muscle of older individuals following nutraceutical supplementation
Crossland, H., Pereira, S. L., Smith, K., Phillips, B. E., & Atherton, P. J. (2019) · Journal of Functional Foods · doi:10.1016/j.jff.2019.03.022 · Cited by 4
“, 2015) and closely represents the dose given during chronic intervention studies (Balzer et al., 2008; Engler et al., 2004; Muniyappa et al., 2008).”
Background
Integrated Approach to Hypertension
Lin, C. D., Silvestro, M., Migliorini, R., Tona, F., & Fioranelli, M. (2017) · Springer eBooks · doi:10.1007/978-3-319-40010-5_15 · Cited by 4
Cocoa Consumption and Prevention of Cardiometabolic Diseases and Other Chronic Diseases
Gvozdjáková, A., Singh, R., Singh, R. B., Takahashi, T., Fedačko, J., Hristová, K., Wilczyńska, A., Mojtová, M., & Mojto, V. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813148-0.00019-0 · Cited by 4
Cocoa and chocolate consumption and prevention of cardiovascular diseases and other chronic diseases
Singh, R., Singh, R. B., Mojto, V., Pella, D., Fedačko, J., Vargová, V., Hristová, K., Wilczyńska, A., Mojtová, M., & Gvozdjáková, A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819815-5.00012-4 · Cited by 5
Cocoa, Flavonoids and Cardiovascular Protection
Grassi, D., & Ferri, C. (2013) · Polyphenols in Human Health and Disease · doi:10.1016/b978-0-12-398456-2.00078-5 · Cited by 4
Cocoa Flavanol Supplementation and Risk of Age-Related Macular Degeneration
Christen, W. G., Rist, P. M., Moorthy, M. V., Smith, D. C., Holman, B., Clar, A., Glynn, R. J., Mares, J. A., Sobrin, L., Shadyab, A. H., et al. (2025) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2025.0353 · Cited by 3
Flavonoid-Based Derivatives for Modulating Various Targets of Alzheimer’s Disease
Pandey, J. (2023) · Springer eBooks · doi:10.1007/978-981-99-6038-5_11 · Cited by 3
Dietary Factors and the Risk of Coronary Heart Disease
Kochar, J., Gaziano, J. M., & Djoussé, L. (2011) · Europe PMC (PubMed Central) · Cited by 3
Sociodemographic and Birth Characteristics in Infant Acute Leukemia: A Review
Pérez‐Saldívar, M. L., Mejía‐Aranguré, J. M., Rangel-López, A., & Fajardo, A. (2013) · InTech eBooks · doi:10.5772/54457 · Cited by 3
“Importantly, several biological effects have been observed in in vitro studies of flavonoids, including its antioxidant activity, modulation of enzyme activity, inhibition cell proliferation and use as antibiotics, anti-allergy, antidiarrhea, anti-ulcer and anti-inflammatory agents [103-106].”
Background
Biofactors in food promote health by enhancing mitochondrial function
Shenoy, S. F., Chowanadisai, W., Sharman, E. H., Keen, C. L., Liu, J., & Rucker, R. B. (2011) · California Agriculture · doi:10.3733/ca.v065n03p141 · Cited by 3
Self-citation
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Costello, R. B., Lentino, C. V., Saldanha, L. G., Engler, M. M., Engler, M. B., Srinivas, P. R., & Sempos, C. T. (2014) · British Journal Of Nutrition · doi:10.1017/s0007114514003353 · Cited by 3
Characterization of the Effects of Two Polyphenols-Rich Plant Extracts on Isolated Diabetic Human Mammary Arteries
Badalica, M., Munteanu, M., Sturza, A., Noveanu, L., Streian, C. G., Socaciu, C., Muntean, D. M., Timar, R. Z., & Dragan, S. (2014) · Cited by 3
Exploring Possible Health Effects of Polyphenols in Foods
Yang, J., & Dwyer, J. T. (2017) · Nutrition Today · doi:10.1097/nt.0000000000000206 · Cited by 3
Potentiel des polyphénols à améliorer la protection vasculaire en stimulant la fonction endothéliale
Auger, C., & Schini‐Kerth, V. B. (2014) · Cahiers de Nutrition et de Diététique · doi:10.1016/j.cnd.2014.03.005 · Cited by 3
Authorised EU health claim for cocoa flavanols
Tallon, M. J. (2015) · Elsevier eBooks · doi:10.1016/b978-1-78242-382-9.00004-9 · Cited by 3
Dark Chocolate and (Pre-)Hypertension
Ried, K. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-803-0_23 · Cited by 3
Cocoa Cultivation, Directed Breeding and Polyphenolics
Lieberei, R., Kadow, D., & Seigler, D. S. (2013) · Springer eBooks · doi:10.1007/978-3-642-22144-6_51 · Cited by 3
Preventive Nutrition and the Food Industry: Perspectives on History, Present, and Future Directions
Yach, D., Feldman, Z. A., Bradley, D. G., & Brown, R. (2009) · Humana Press eBooks · doi:10.1007/978-1-60327-542-2_31 · Cited by 3
Acute effect of cocoa on vascular function in chronic kidney disease patients: a pilot study
Ferreira, C. (2025) · Library, Museums and Press - UDSpace (University of Delaware) · doi:10.58088/1pqm-ge12 · Cited by 3
Mediating role of inflammatory markers in the association between dietary isorhamnetin consumption and CKD risk
Liu, C., Kong, H., Li, G., Peng, W., & Liu, P. (2025) · Medicine · doi:10.1097/md.0000000000044703 · Cited by 2
“42–44] Considering the contribution of endothelial dysfunction to renal impairment, flavonoid-mediated vascular improvements may confer indirect nephroprotective benefits.”
Food and Health Forum meeting – nutritional approaches to cardiovascular health: workshop report
Mitchell, H. L., Gibbins, J. M., Griffin, B. A., Lovegrove, J. A., Stowell, J. D., & FOOT, E. A. (2012) · Nutrition Bulletin · doi:10.1111/j.1467-3010.2012.01984.x · Cited by 2
Theobroma cacao
Lim, T. K. (2011) · Springer eBooks · doi:10.1007/978-94-007-2534-8_30 · Cited by 3
The effect of chocolate consumption (Theobroma cacao L.) on level of blood cholesterol and triglyceride in hypertension patients at Jatiroto Health Center, Indonesia
Ulkhasanah, M. E., Hadisaputro, S., & Pujiastuti, R. S. E. (2019) · GHMJ (Global Health Management Journal) · doi:10.35898/ghmj-31272 · Cited by 2
“Dark chocolate with flavonoid-rich also improved endothelial function after regular consumption for 30 days [17].”
Background
A comparison of the effects of green tea and cocoa on glycaemic control and insulin sensitivity in patients with type 2 diabetes mellitus: a systematic review and meta-analysis
Alkhudaydi, H. M. S., & Spencer, J. P. E. (2024) · Nutrition and Healthy Aging · doi:10.3233/nha-230204 · Cited by 2
The impact of a superfood chocolate beverage on indices of peripheral vascular function
Kolade, J. O., & Brothers, R. M. (2025) · Physiological Reports · doi:10.14814/phy2.70448 · Cited by 2
“…Banpouri, et al., 2023; Ghavami, Ziaei, et al., 2023; Reynolds et al., 2022; Tejani et al., 2023; Theuwissen & Mensink, 2008), natural cocoa (Balzer et al., 2008; Heiss et al., 2005, 2010; Hurr et al., 2015; Jia et al., 2010; Sansone et al., 2015; Schroeter et al., 2006; Sun et al., 2019),…”
Influential
Polyphenol-Rich Dark Chocolate in Treatment of Diabetes Mellitus Risk Factors
Al‐Dujaili, E. A. S., Tsang, C., & Almoosawi, S. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-803-0_25 · Cited by 2
Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover
Tzounis, X., Rodriguez‐Mateos, A., Vulevic, J., Gibson, G. R., Kwik-Uribe, C. L., & Spencer, J. P. E. (2011) · Cited by 2
A single intake of a resveratrol-arginine conjugate improves microvascular function compared to trans-resveratrol in postmenopausal women
Djurica, D., Ren, J., Holt, R. R., Feng, X., Carlson, C. R., Shindel, A. W., Keen, C. L., & Hackman, R. M. (2016) · PharmaNutrition · doi:10.1016/j.phanu.2016.05.002 · Cited by 3
Self-citation
The Relationship between Snacking and Risk of Individual Components of Metabolic Syndrome in Normal-weight Adults: A Cross-sectional Study
Javid, A. Z., Niknejad, N., Shahbazian, H. B., Latifi, S. M., Niknejad, B., & Hormoznejad, R. (2017) · Journal of Nutrition and Food Security · Cited by 2
Other common and exotic foods with growing importance as antidiabetic agents
Habtemariam, S. (2019) · Elsevier eBooks · doi:10.1016/b978-0-08-102922-0.00025-0 · Cited by 2
Potential use of plant-based therapeutics for the management of SARS-COV2 infection in diabetes mellitus – a review
Deora, N., & Venkatraman, K. (2024) · Journal of Herbal Medicine · doi:10.1016/j.hermed.2024.100923 · Cited by 1
Serum lipids changes following cocoa intake in type 2 diabetes patients: a graded dose-response systematic review and meta-analysis of clinical trials
Anari, R., Mohseni, H., Motamed, S., Anari, E., & Amani, R. (2025) · Acta Diabetologica · doi:10.1007/s00592-025-02554-8 · Cited by 1
Cocoa flavanols alleviate early diastolic dysfunction by decreasing left atrial volume in a randomized double blinded trial in healthy older individuals
Duse, D. A., Gröne, M., Ophoff, N., Kramser, N., Schweers, H., Ottaviani, J. I., Schroeter, H., Quast, C., Bönner, F., Heiß, C., et al. (2025) · Food & Function · doi:10.1039/d5fo02589c · Cited by 1
Self-citation
Plant derived natural products as antidiabetic agents
Swati, K., Bhatt, P., Singh, S., & Bhandari, P. (2026) · Studies in natural products chemistry · doi:10.1016/b978-0-443-49146-7.00003-0 · Cited by 1

Authors: Balzer, J., Rassaf, T., Heiss, C., Kleinbongard, P., Lauer, T., Merx, M., Heussen, N., Gross, H. B., Keen, C. L., Schroeter, H., & Kelm, M.
Affiliations: Universitätsklinikum Aachen (DE)
University of California, Davis (US)
Corresponding author: Kelm, Malte
ORCID: Rassaf, Tienush
Heiss, Christian
Kleinbongard, Petra
Heussen, Nicole
Keen, Carl L.
Schroeter, Hagen
Kelm, Malte
Venue: Journal of the American College of Cardiology
Publisher: Elsevier BV
Published: 2008-06
Volume: 51
Issue: 22
Pages: 2141-2149
ISSN: 0735-1097 (ISSN-L)
DOI: 10.1016/j.jacc.2008.01.059
OpenAlex: W2143536568
Cited by: 345
References: 34
Citations by year: 2026: 2 · 2025: 11 · 2024: 12 · 2023: 9 · 2022: 8 · 2021: 11 · 2020: 15 · 2019: 13 · 2018: 25 · 2017: 23 · 2016: 20 · 2015: 27 · 2014: 19 · 2013: 27 · 2012: 42
FWCI: 16.42
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1871 d)
Locations: Journal of the American College of Cardiology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Keywords: flavan-3-ols, Theobroma cacao, vascular function, flow-mediated dilation, diabetes mellitus, endothelial function, dietary intervention, brachial artery, cardiovascular risk, tachyphylaxis, glycemic control
MeSH terms: Aged, Aged, 80 and over, Brachial Artery, Cacao, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Double-Blind Method, Endothelium, Vascular, Feasibility Studies, Female, Humans, Male, Middle Aged, Prognosis, Risk Factors, Time Factors, Cross-Over Studies, Flavonols

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Sustained Benefits in Vascular Function Through Flavanol-Containing Cocoa in Medicated Diabetic Patients

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