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Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials
Open accessAbstract
Background There is substantial interest in chocolate and flavan-3-ols for the prevention of cardiovascular disease (CVD).Objective The objective was to systematically review the effects of chocolate, cocoa, and flavan-3-ols on major CVD risk factors.Design We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) of chocolate, cocoa, or flavan-3-ols. We contacted authors for additional data and conducted duplicate assessment of study inclusion, data extraction, validity, and random-effects meta-analyses.Results We included 42 acute or short-term chronic (≤18 wk) RCTs that comprised 1297 participants. Insulin resistance (HOMA-IR: -0.67; 95% CI: -0.98, -0.36) was improved by chocolate or cocoa due to significant reductions in serum insulin. Flow-mediated dilatation (FMD) improved after chronic (1.34%; 95% CI: 1.00%, 1.68%) and acute (3.19%; 95% CI: 2.04%, 4.33%) intakes. Effects on HOMA-IR and FMD remained stable to sensitivity analyses. We observed reductions in diastolic blood pressure (BP; -1.60 mm Hg; 95% CI: -2.77, -0.43 mm Hg) and mean arterial pressure (-1.64 mm Hg; 95% CI: -3.27, -0.01 mm Hg) and marginally significant effects on LDL (-0.07 mmol/L; 95% CI: -0.13, 0.00 mmol/L) and HDL (0.03 mmol/L; 95% CI: 0.00, 0.06 mmol/L) cholesterol. Chocolate or cocoa improved FMD regardless of the dose consumed, whereas doses >50 mg epicatechin/d resulted in greater effects on systolic and diastolic BP. GRADE (Grading of Recommendations, Assessment, Development and Evaluation, a tool to assess quality of evidence and strength of recommendations) suggested low- to moderate-quality evidence of beneficial effects, with no suggestion of negative effects. The strength of evidence was lowered due to unclear reporting for allocation concealment, dropouts, missing data on outcomes, and heterogeneity in biomarker results in some studies.Conclusions We found consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR. Larger, longer-duration, and independently funded trials are required to confirm the potential cardiovascular benefits of cocoa flavan-3-ols.
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“In this regard, the level of flavanols used in this current study is comparable to the level of cocoa flavanols fed in previous studies where improvements in brain blood flow, 19 vascular function, and blood pressure were observed.25”
From Benefits in Cognitive Function, Blood Pressure, and Insulin Resistance Through Cocoa Flavanol Consumption in Elderly Subjects With Mild Cognitive Impairment: The Cocoa, Cognition, and Aging (CoCoA) Study (2012) · cites this paper as [25]
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“In this regard, although we did not specifically evaluate the effect of cocoa flavanols on endothelial function, a number of studies, some also from our group, clearly demonstrated the ability of flavonoids to improve NO bioavailability in vasculature, 17,18,25 which, in turn, plays a pivotal role in modulating cerebrovascular tone.28”
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BackgroundTargeting Inflammation by Flavonoids: Novel Therapeutic Strategy for Metabolic Disorders
Farzaei, M. H., Singh, A. K., Kumar, R., Croley, C. R., Pandey, A. K., Coy-Barrera, E. D., Patra, J. K., Das, G., Kerry, R. G., Annunziata, G., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194957 · Cited by 137
“Similarly, Hooper et al. (2012) provided evidence that flavan-3-ols are able to reduce homeostasis model assessment of insulin resistance (HOMA-IR) (−0.67; 95% CI, −0.98, −0.36), in RCTs [236].”
BackgroundInfluentialAguilera, Y., Martin-Cabrejas, M. A., & de Mejía, E. G. (2015) · Phytochemistry Reviews · doi:10.1007/s11101-015-9443-z · Cited by 137
“A recent meta-analysis comprising 42 studies concluded that there were significant effects on HDL (0.03 mM of increase) and LDL cholesterol (0.07 mM of decrease; Hooper et al. 2012).”
MethodInfluentialWest, S. G., McIntyre, M. D., Piotrowski, M. J., Poupin, N., Miller, D. L., Preston, A. G., Wagner, P. R., Groves, L. F., & Skulas‐Ray, A. C. (2013) · British Journal Of Nutrition · doi:10.1017/s0007114513002912 · Cited by 125
“Previous studies((56,59)) have observed improvements in insulin levels or insulin resistance with the consumption of high-flavanol cocoa/chocolate.”
Polyphenols and Their Interactions With Other Dietary Compounds: Implications for Human Health
Kardum, N., & Glibetić, M. (2018) · Advances in food and nutrition research · doi:10.1016/bs.afnr.2017.12.001 · Cited by 131
Functional Food and Cardiovascular Disease Prevention and Treatment: A Review
Asgary, S., Rastqar, A., & Keshvari, M. (2018) · Journal of the American College of Nutrition · doi:10.1080/07315724.2017.1410867 · Cited by 142
“Also [xxx] consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR More experimental are needed to appear the potential cardiovascular benefits of cocoa flavan-3-ols (217) (Table 3).”
BackgroundVogiatzoglou, A., Mulligan, A. A., Luben, R., Lentjes, M. A. H., Heiß, C., Kelm, M., Merx, M. W., Spencer, J. P. E., Schroeter, H., & Kuhnle, G. (2013) · British Journal Of Nutrition · doi:10.1017/s0007114513003930 · Cited by 122
“Moreover, most Europeans consume less than 50 % of the 200 mg of cocoa flavanols per d considered by the EFSA to be sufficient for improved vascular function and less than 25 % of the 400 mg/d required to observe a reduction of systolic blood pressure((41)).”
BackgroundHigher Dietary Flavonol Intake Is Associated with Lower Incidence of Type 2 Diabetes
Jacques, P. F., Cassidy, A., Rogers, G. T., Peterson, J. J., Meigs, J. B., & Dwyer, J. T. (2013) · Journal of Nutrition · doi:10.3945/jn.113.177212 · Cited by 122
“The available data also suggest that dose of the flavan-3-ol epicatechin may be important for cardiovascular risk, with doses >50 mg being more efficacious; however, too few studies were available to assess the effect of dose on HOMA-IR and insulin (26).”
BackgroundInfluentialSelf-citationIslam, M. A., Alam, F., Solayman, M., Khalil, M. I., Kamal, M. A., & Gan, S. H. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/5137431 · Cited by 127
“Several metaanalyses have also established that the consumption of cocoa could modulate multiple cardiovascular risk factors such as flow-mediated vascular dilatation, activation of platelets [86], insulin resistance [87], and the blood C level [88].”
BackgroundKennedy, D. O. (2014) · Advances in Nutrition · doi:10.3945/an.114.006320 · Cited by 128
“Meta-analyses suggest that these effects are achievable with an optimal dose of 500 mg/d flavanols (14) and within 2 h of consumption (15).”
BackgroundDietary flavonoids and nitrate: effects on nitric oxide and vascular function
Bondonno, C. P., Croft, K. D., Ward, N., Considine, M. J., & Hodgson, J. M. (2015) · Nutrition Reviews · doi:10.1093/nutrit/nuu014 · Cited by 150
Sansone, R., Ottaviani, J. I., Rodriguez‐Mateos, A., Heinen, Y., Noske, D., Spencer, J. P. E., Crozier, A., Merx, M. W., Kelm, M., Schroeter, H., et al. (2016) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.116.140046 · Cited by 118
“An important consequence of this synergism is that it may explain to a certain degree the variability in the magnitude of effects observed in different studies with test materials containing varying amounts of CFs and methylxanthines (23).”
ResultDark chocolate: An overview of its biological activity, processing, and fortification approaches
Samanta, S., Sarkar, T., Chakraborty, R., Ребезов, М. Б., Shariati, M. A., Thiruvengadam, M., & Rengasamy, K. R. R. (2022) · Current Research in Food Science · doi:10.1016/j.crfs.2022.10.017 · Cited by 117
Chocolate, “Food of the Gods”: History, Science, and Human Health
Montagna, M. T., Diella, G., Triggiano, F., Caponio, G. R., Giglio, O. D., Caggiano, G., Ciaula, A. D., & Portincasa, P. (2019) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph16244960 · Cited by 116
“A meta-analysis of randomized trials report that both acute and chronic chocolate and cocoa ingestion effectively increased flow-mediated vasodilatation, reduced systolic and diastolic blood pressure, and reduced serum insulin levels [36].”
BackgroundPanickar, K. S. (2012) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201200431 · Cited by 115
Evidence of Lifestyle Modification in the Management of Hypercholesterolemia
Mannu, G., Zaman, M., Gupta, A., Rehman, H. U., & Myint, P. K. (2013) · Current Cardiology Reviews · doi:10.2174/157340313805076313 · Cited by 121
The role of nutraceuticals in the prevention of cardiovascular disease
Sosnowska, B., Penson, P. E., & Banach, M. (2017) · Cardiovascular Diagnosis and Therapy · doi:10.21037/cdt.2017.03.20 · Cited by 117
“However, no effect upon fasting glucose or HbA1c was observed (51).”
BackgroundIglesias‐Aguirre, C. E., Cortés‐Martín, A., Ávila‐Gálvez, M. Á., Giménez‐Bastida, J. A., Selma, M. V., González‐Sarrías, A., & Espín, J. C. (2021) · Food & Function · doi:10.1039/d1fo02033a · Cited by 123
Grassi, D., Desideri, G., Necozione, S., Giosia, P. D., Barnabei, R., Allegaert, L., Bernaert, H., & Ferri, C. (2014) · Journal of Hypertension · doi:10.1097/hjh.0000000000000412 · Cited by 112
“As suggested in the above metaanalysis [48], our study also provided evidence on dosedependent effects with respect to the epicatechin content.”
ResultInfluentialPolyphenols and atherosclerosis: A critical review of clinical effects on LDL oxidation
Ahmadi, A., Jamialahmadi, T., & Sahebkar, A. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106414 · Cited by 119
Cocoa, Blood Pressure, and Vascular Function
Ludovici, V., Barthelmes, J., Nägele, M. P., Enseleit, F., Ferri, C., Flammer, A. J., Ruschitzka, F. T., & Sudano, I. (2017) · Frontiers in Nutrition · doi:10.3389/fnut.2017.00036 · Cited by 114
Raman, G., Avendano, E. E., Chen, S., Wang, J., Matson, J., Gayer, B., Novotny, J. A., & Cassidy, A. (2019) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz178 · Cited by 110
“Our RCT results concur with 2 previous meta-analyses that only evaluated a limited number of foods and reported beneficial effects on outcomes including HDL cholesterol, blood pressure, HOMAIR, and FMD (7, 50).”
ResultSelf-citationMilenković, D., Morand, C., Cassidy, A., Konić‐Ristić, A., Tomás-Barberán, F. A., Ordovás, J. M., Kroon, P. A., Caterina, R. D., & Rodriguez‐Mateos, A. (2017) · Advances in Nutrition · doi:10.3945/an.116.013623 · Cited by 113
“The most convincing clinical evidence for the cardioprotective benefits of the consumption of dietary polyphenols relates to their observed beneficial effect on endothelial function (13, 14).”
BackgroundSelf-citationNatural Bioactive Compounds Useful in Clinical Management of Metabolic Syndrome
Noce, A., Lauro, M. D., Daniele, F. D., Zaitseva, A. P., Marrone, G., Borboni, P., & Daniele, N. D. (2021) · Nutrients · doi:10.3390/nu13020630 · Cited by 120
“contain a particular flavanols called flavan-3-ols, which appear to have a beneficial effect on CV disease, protecting against endothelial damage and improving insulin sensitivity [94,112,155].”
BackgroundYuan, S., Li, X., Jin, Y., & Lu, J. (2017) · Nutrients · doi:10.3390/nu9070688 · Cited by 108
Koutsos, A., Riccadonna, S., Ulaszewska, M., Franceschi, P., Trôst, K., Galvin, A., Braune, T., Fava, F., Perenzoni, D., Mattivi, F., et al. (2019) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz282 · Cited by 117
“Longer-term studies with PA-rich foods/beverages such as chocolate (43) and tea (44) have also reported beneficial effects on vascular function.”
BackgroundIn vitro fermentation of juçara pulp ( Euterpe edulis ) by human colonic microbiota
Guergoletto, K. B., Costabile, A., Flores, G., García, S., & Gibson, G. R. (2015) · Food Chemistry · doi:10.1016/j.foodchem.2015.09.048 · Cited by 116
“…including their anti-inflammatory, antioxidant, anticarcinogenic, antiadipogenic, antidiabetic and neuroprotective potentials, suggesting an association between the consumption of polyphenol-rich foods and a reduced risk of several chronic diseases (Jennings, et al., 2012; Hooper et al., 2012).”
BackgroundResultGrassi, D., Desideri, G., Necozione, S., Ruggieri, F., Blumberg, J. B., Stornello, M., & Ferri, C. (2012) · Hypertension · doi:10.1161/hypertensionaha.112.193995 · Cited by 113
“Indeed, concordantly with all our findings, a very recent meta-analysis reported that, although FMD was improved after chronic and acute flavonoid-rich DC intakes, significant reductions in DBP and mean arterial pressure were observed after chronic but not after acute intake of DC.36 Inherent limitations of our study…”
InfluentialThe role of nutrition and nutraceutical supplements in the treatment of hypertension
Houston, M. C. (2014) · World Journal of Cardiology · doi:10.4330/wjc.v6.i2.38 · Cited by 108
Sutulic, S., & Williamson, G. (2013) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071811-150642 · Cited by 112
“sion (100) and both chocolate and cocoa with improvements in flow-mediated dilation (57).”
BackgroundKonar, N., Toker, Ö. S., Oba, Ş., & Sağdıç, O. (2016) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2016.01.002 · Cited by 106
Pleiotropic preventive effects of dietary polyphenols in cardiovascular diseases
Kishimoto, Y., Tani, M., & Kondo, K. (2013) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2013.29 · Cited by 104
van den Driessche, J. J., Plat, J., & Mensink, R. P. (2018) · Food & Function · doi:10.1039/c7fo01792h · Cited by 114
Clinical Advances in Immunonutrition and Atherosclerosis: A Review
Ruiz-León, A. M., Lapuente, M., Estruch, R., & Casas, R. M. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00837 · Cited by 104
Dietary flavonoid intake and cardiovascular risk: a population-based cohort study
Ponzo, V., Goitre, I., Fadda, M., Gambino, R., Francesco, A. D., Soldati, L., Gentile, L., Magistroni, P., Cassader, M., & Bo, S. (2015) · Journal of Translational Medicine · doi:10.1186/s12967-015-0573-2 · Cited by 116
Hu, Y., Pan, Z. J., Liao, W., Li, J., Gruget, P., Kitts, D. D., & Lu, X. (2016) · Food Chemistry · doi:10.1016/j.foodchem.2016.01.130 · Cited by 102
“Chocolate and cocoa-containing products are a source of non-nutrient bioactive polyphenols with potential health benefits including reduced risk of cardiovascular disease (Hooper et al., 2012) and prebiotic activity (Tzounis et al.”
BackgroundAntidiabetic actions of cocoa flavanols
Martín, M. Á., Goya, L., & Ramos, S. (2016) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500961 · Cited by 106
Munir, K. M., Chandrasekaran, S., Gao, F., & Quon, M. J. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00377.2013 · Cited by 103
Metadata
- Authors
- Hooper, L., Kay, C., Abdelhamid, A., Kroon, P. A., Cohn, J. S., Rimm, E. B., & Cassidy, A.
- Affiliations
- University of East Anglia (GB)
- Corresponding author
- Hooper, Lee
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 95
- Issue
- 3
- Pages
- 740-751
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2129761592
- Cited by
- 610
- References
- 90
- Citations by year
- 2026: 15 · 2025: 19 · 2024: 32 · 2023: 24 · 2022: 29 · 2021: 35 · 2020: 37 · 2019: 43 · 2018: 63 · 2017: 56 · 2016: 64 · 2015: 54 · 2014: 50 · 2013: 66 · 2012: 22
- FWCI
- 6.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Research Portal (Queen's University Belfast) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- GlaxoSmithKline
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council (BBS/E/F/00044434)
- Topics
- Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
- Life Sciences › Agricultural and Biological Sciences › Food Science › Food Chemistry and Fat Analysis
- Health Sciences › Medicine › Pharmacology (medical) › Coffee research and impacts
- Keywords
- chocolate, Theobroma cacao, flavan-3-ols, epicatechin, cardiovascular disease prevention, insulin resistance, flow-mediated dilation, endothelial function, blood pressure, LDL cholesterol, HDL cholesterol, cardiovascular risk factors, dose-response relationship, quality of evidence, GRADE, adverse effects
- MeSH terms
- Blood Glucose, Blood Pressure, Cacao, Candy, Cardiovascular Diseases, Cardiovascular System, Flavonoids, Humans, Insulin, Risk Factors, Reproducibility of Results, Biomarkers, Randomized Controlled Trials as Topic
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