The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Sustained Benefits in Vascular Function Through Flavanol-Containing Cocoa in Medicated Diabetic Patients
Open accessAbstract
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Dietary interventions have indicated improved vascular function linked to the consumption of polyphenols from different sources, including cocoa and dealcoholized red wine (60, 168, 225, 417, 834).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [60]
In the citing paper
“Differing in part from Balzer et al. (11), we observed small but significant increases in FMD and CD34 ϩ / KDR ϩ -CAC after the LoFI regimen.”
Citations
Cites
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
(2002) · New England Journal of Medicine · doi:10.1056/nejmoa012512 · Cited by 19,011
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
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
Self-citationFlavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women
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
Self-citationDiagnosis and Classification of Diabetes Mellitus
American Diabetes Association (2006) · Diabetes Care · doi:10.2337/diacare.29.s1.06.s43 · Cited by 924
Brachial Flow-Mediated Dilation Predicts Incident Cardiovascular Events in Older Adults
Yeboah, J., Crouse, J. R., Hsu, F., Burke, G. L., & Herrington, D. M. (2007) · Circulation · doi:10.1161/circulationaha.106.678276 · Cited by 902
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–345 of 345
Cocoa and Chocolate in Humans: The Rationale for Clinical Studies on Healthy Volunteers
Conti, A., Pinorini-Godly, M. T., & Colombo, M. L. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-803-0_40 · Cited by 1
Polyphenol-Rich Cocoa and Chocolate: Potential Role in the Prevention of Diabetes
Almoosawi, S., & Al‐Dujaili, E. A. S. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-803-0_24 · Cited by 1
Highlights of the Year in JACC 2008
DeMaria, A. N., Ben‐Yehuda, O., Bax, J. J., Feld, G. K., Greenberg, B., Lew, W. Y. W., Lima, J. A. C., Maisel, A. S., Narayan, S. M., Sahn, D. J., et al. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.12.005 · Cited by 1
Biregani, A. N., Hassan, M. K., Poursoleiman, F., Reza, J. Z., Rahmanian, M., & Dehghani, A. (2014) · Iranian journal of diabetes and obesity · Cited by 1
López, C. D. (2025) · Open Journal of Pharmacology and Pharmacotherapeutics · doi:10.17352/ojpp.000026 · Cited by 1
Walters, J. (2011) · Elsevier eBooks · doi:10.1016/b978-0-7295-3908-1.10010-7 · Cited by 1
Zoccali, C., & Mallamaci, F. (2015) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.12141115 · Cited by 1
“Findings in the study by Rassaf and coworkers (18) have a high internal coherence, because cocoa flavanols increased the FMD response to forearm ischemia in both the acute and chronic settings and because the same intervention mitigated the negative effect of hemodialysis on endothelium-dependent vasodilation.”
BackgroundAl Sharif, S. (2018) · CentAUR (University of Reading) · doi:10.48683/1926.00084848 · Cited by 1
Dietary Flavanols: Biochemical Basis of Short‐Term and Longer‐Term Vascular Responses
SCHEWE, T., Steffen, Y., Kravets, E., & Sies, H. (2009) · doi:10.1002/9780470531792.ch6 · Cited by 1
Farhat, G. (2014) · Queen Margaret University Publications Repository (Queen Margaret University) · Cited by 1
Endothelial function in peripheral artery disease – diagnosis and risk stratification
Petrikhovich, O., Rassaf, T., & Rammos, C. (2024) · VASA · doi:10.1024/0301-1526/a001132 · Cited by 1
Self-citationEndothelial Progenitor Cells and Nitric Oxide: Matching Partners in Biomedicine
Keymel, S., Özüyaman, B., Grau, M., Kelm, M., & Kleinbongard, P. (2010) · Springer eBooks · doi:10.1007/978-3-642-11865-4_10
Self-citationHarrison, M. (2014) · Texas ScholarWorks (Texas Digital Library)
Vogl, J. T. (2011) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-10523
Food of the Gods: the Role of Chocolate in Cardiovascular Health
Milbers, K. (2012) · UBC Faculty of Medicine medical journal
Dietary Flavonoids as Modulators of NO Bioavailability in Acute and Chronic Cardiovascular Diseases
Totzeck, M., Kelm, M., & Rassaf, T. (2011) · Humana Press eBooks · doi:10.1007/978-1-60761-616-0_8
Self-citationConsumption of cocoa flavanols results in acute improvements in mood and cognitive
Scholey, A. B., French, S., Morris, P., Kennedy, D. O., Milne, A., & Haskell, C. F. (2009)
Mogollon, J. A. (2012) · Corpus Université Laval (Université Laval)
Endothelial Control of Vascular Tone by Chocolate and Other Polyphenols
Auger, C., Idris-Khodja, N., & Schini‐Kerth, V. B. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-803-0_20
Nitric oxide mediated cardiovascular benefits of dietary nitrate and polyphenols
Bondonno, C. P. (2012) · UWA Profiles and Research Repository (University of Western Australia)
Cardiovascular Disease Biomarkers in Clinical Use and Their Modulation by Functional Foods
Basu, A., Morris, S., Basu, P., & Lyons, T. J. (2016) · Springer eBooks · doi:10.1007/978-94-007-7678-4_37
A Promising New Dietary Intervention to Reduce Cardiovascular Risk in Type 2 Diabetes
Campia, U., & Panza, J. A. (2008)
Esser, D. (2013) · doi:10.18174/266223
“This timeframe was chosen, because effects of flavanol consumption on vascular function are most pronounced two hours after consumption [17].”
BackgroundMethodInfluentialDietary Proanthocyanidin Modulation of Pancreatic β Cells
Pinent, M., González‐Abuín, N., Blay, M., & Ardèvol, A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801585-8.00016-6 · Cited by 1
The psychopharmacological effects of blackcurrant phytochemicals in humans
Watson, A. (2014) · Northumbria Research Link (Northumbria University)
Dark chocolate as a antioxidant food: Product development and sensory evaluation
Agrahari, K., & Baranwal, R. (2018) · FOOD SCIENCE RESEARCH JOURNAL · doi:10.15740/has/fsrj/9.2/318-321
Potential of Polyphenols as Therapeutic Options in Type 2 Diabetes
Nasrabadi, E. N. (2018) · Griffith Research Online · doi:10.25904/1912/3203
Plotnikoff, G. A., & Dusek, J. A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-35868-2.00024-4
Nitric oxide and phosphodiesterase-5 inhibitors: possible treatments for COVID-19 in diabetes
Whyte, M., VAS, P. R., Kelly, P. A., Heiß, C., & Feher, M. D. (2020) · British Journal of Diabetes · doi:10.15277/bjd.2020.257
Obtención de un extracto de cacao y café con alto contenido de compuestos bioactivos
ACOSTA-OTÁLVARO, E. V. (2021) · doi:10.31428/10317/10317
(2011) · Elsevier eBooks · doi:10.1016/b978-0-7295-3908-1.10013-2
(2011) · Journal of Nutrition · doi:10.3945/jn.111.152470
Dietary Flavonoids as Modulators of NO Bioavailability in Acute and Chronic Cardiovascular Diseases
Totzeck, M., & Rassaf, T. (2017) · Springer eBooks · doi:10.1007/978-3-319-46189-2_10
Self-citationCardiovascular Disease Biomarkers in Clinical Use and Their Modulation by Functional Foods
Basu, A., Morris, S., Basu, P., & Lyons, T. J. (2015) · Springer eBooks · doi:10.1007/978-94-007-7741-5_37-1
Plotnikoff, G. A., & Dusek, J. A. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4377-1793-8.00023-6
Mayorga-Gross, A. L., & Montoya‐Arroyo, A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-823811-0.00009-2
Gołdys, R., Bernacka, K., Urbanowicz, I., & Fecka, I. (2023) · Farmacja Polska · doi:10.32383/farmpol/163450
Popescu, L., Crăciunescu, E. L., Novac, A. C., Negruțiu, M. L., Duma, V.-F., Tudor, A., Mostovei, A., Jumanca, D. E., & Sinescu, C. G. (2024) · Romanian Journal of Oral Rehabilitation · doi:10.62610/rjor.2024.2.16.19
“Chocolate is perceived as fattening food because of energy density but studies show that small amounts of cocoa [4, 5] or dark chocolate [6] in daily dose of 25g (125kcal) slightly increase body weight after 3 months but 6 g (30kcal) consummate daily is not associated with any weight gain [7].”
International consumption and stocks of cocoa
Dand, R. (2011) · Elsevier eBooks · doi:10.1016/b978-0-85709-125-3.50007-0
Шушпанова, Т. В., Смирнова, И. Н., Gameeva, E. V., Степанова, А. М., Зайцев, А. А., Тицкая, Е. В., Zaripova, T. N., Новожеева, Т. П., Safronov, S. M., Боев, Р. Г., et al. (2026) · Успехи геронтологии · doi:10.34922/ae.2025.38.5.004
Cocoa flavanols, exercise and the brain
Decroix, L. (2018) · theses.fr (ABES) · doi:10.70675/a6a02e44z61a4z4d24zadbdz0879e1c3e607
Lee, H.-H. (2018) · theses.fr (ABES) · doi:10.70675/01af62dfzd4a2z462fz9af0z66d5873040e9
Acute Vascular Effects of Chocolate in Healthy Human Volunteers
Rusconi, M., Rossi, M. G., Moccetti, T., & Conti, A. (2012) · Springer eBooks · doi:10.1007/978-88-470-2038-2_7
The effect of oligomeric procyanidins on endothelial function and cholesterol homeostasis
Rull, G. (2012) · OpenGrey (Institut de l'Information Scientifique et Technique)
Metadata
- 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
- 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)
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review