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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.
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“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]
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“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.”
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Dietary Epicatechin Promotes Survival of Obese Diabetic Mice and Drosophila melanogaster
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Cocoa and Human Health: From Head to Foot—A Review
de Araújo, Q. R., Gattward, J. N., Almoosawi, S., Silva, M. D. G. C. P. C., Dantas, P. A. D. S., & Júnior, Q. R. D. A. (2013) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2012.657921 · Cited by 98
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Impact of cocoa flavanols on human health
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Goya, L., Kongor, J. E., & de Pascual‐Teresa, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214365 · Cited by 97
The impact of chocolate on cardiovascular health
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Analysis of Antioxidant-Rich Phytochemicals: Xu/Analysis of Antioxidant-Rich Phytochemicals
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AGING OF THE SUBVENTRICULAR ZONE NEURAL STEM CELL NICHE.
Conover, J. C., & Shook, B. A. (2011) · Europe PMC (PubMed Central) · Cited by 92
Arranz, S., Valderas-Martínez, P., Chiva‐Blanch, G., Casas, R. M., Urpí-Sardà, M., Lamuela-Raventós, R. M., & Estruch, R. (2013) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201200595 · Cited by 91
Ali, F., Ismail, A., & Kersten, S. (2013) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201300277 · Cited by 95
“Recent study investigated the effect of flavonol-rich cocoa on vascular function in mediated diabetic patients in a double-masked, randomized, controlled trial [74].”
Mechanisms by which cocoa flavanols improve metabolic syndrome and related disorders
Strat, K. M., Rowley, T. J., Smithson, A. T., Tessem, J. S., Hulver, M. W., Liu, D., Davy, B. M., Davy, K. P., & Neilson, A. P. (2016) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2015.12.008 · Cited by 93
“Many studies have examined the effects of chronic cocoa treatments on LDL cholesterol, HDL cholesterol, and triglycerides [78, 79, 84, 156, 170-173].”
BackgroundGhaffari, S., & Roshanravan, N. (2019) · Food Research International · doi:10.1016/j.foodres.2019.108749 · Cited by 95
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
Rodriguez-Mateos, A., Hezel, M., Aydin, H., Kelm, M., Lundberg, J. O., Weitzberg, E., Spencer, J. P. E., & Heiss, C. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.12.009 · Cited by 88
“Smokers seem to have the highest improvements [6,26], and diabetics the lowest [7].”
BackgroundResultSelf-citationCardiovascular Effects of Flavonoids
Sánchez, M., Romero, M., Gómez‐Guzmán, M., Tamargo, J. L., Pérez‐Vizcaíno, F., & Duarte, J. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867326666181220094721 · Cited by 87
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
Camfield, D., Scholey, A. B., Pipingas, A., Silberstein, R. B., Kras, M., Nolidin, K., Wesnes, K. A., Pase, M. P., & Stough, C. K. K. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.11.013 · Cited by 84
“remain to be elucidated, they may be related to changes in the pool of bioavailable nitric oxide [1,12,20] as well as sub-chronic and acute increases in blood flow following cocoa ingestion [1,7,11].”
BackgroundRacial disparities in cardiovascular disease risk: mechanisms of vascular dysfunction
Brothers, R. M., Fadel, P. J., & Keller, D. M. (2019) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00126.2019 · Cited by 82
Vascular Protection by Natural Product-Derived Polyphenols:In VitroandIn VivoEvidence
Schini‐Kerth, V. B., Étienne-Selloum, N., Chataigneau, T., & Auger, C. (2011) · Planta Medica · doi:10.1055/s-0030-1250737 · Cited by 81
Lee, Y., Berryman, C. E., West, S. G., Chen, C. ‐. O., Blumberg, J. B., Lapsley, K. G., Preston, A. G., Fleming, J. A., & Kris‐Etherton, P. M. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.116.005162 · Cited by 87
“Numerous randomized controlled trials have shown that the consumption of dark chocolate or cocoa has favorable effects on blood pressure(24,38) and endothelial function measured by FMD.(35,39) These reports are inconsistent with our findings that there were no treatment effects on blood pressure and measures of vascul…”
ResultDose-related effects of flavanol-rich cocoa on blood pressure
Davison, K., Berry, N., Misan, G., Coates, A. M., Buckley, J. D., & Howe, P. R. C. (2010) · Journal of Human Hypertension · doi:10.1038/jhh.2009.105 · Cited by 80
Curtis, P. J., Potter, J. F., Kroon, P. A., Wilson, P., Dhatariya, K., Sampson, M., & Cassidy, A. (2013) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.112.043745 · Cited by 80
“Medicated with insulin [n (%)] 9 (19) 9 (20)”
BackgroundResultInfluentialBasu, A., Betts, N. M., Leyva, M. J., Fu, D., Aston, C. E., & Lyons, T. J. (2015) · Journal of Nutrition · doi:10.3945/jn.115.215772 · Cited by 80
“Vascular benefits of acute cocoa supplementation were also reported in postprandial studies of healthy volunteers (23, 53, 54) and in volunteers with T2D (37).”
BackgroundImpact of cocoa flavanol consumption on blood pressure responsiveness to exercise
Berry, N., Davison, K., Coates, A. M., Buckley, J. D., & Howe, P. R. C. (2010) · British Journal Of Nutrition · doi:10.1017/s0007114509993382 · Cited by 78
“Previous research has demonstrated a peak effect of cocoa flavanols on FMD at 2 h after consumption((16)), which returns to baseline 6 h after consumption((20,21)).”
Protective effects of tea, red wine and cocoa in diabetes. Evidences from human studies
Martín, M. Á., Goya, L., & Ramos, S. (2017) · Food and Chemical Toxicology · doi:10.1016/j.fct.2017.09.015 · Cited by 81
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
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