Cited by 610Phytochemicals and Antioxidant ActivitiesFood Chemistry and Fat AnalysisCoffee research and impacts

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Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials

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Hooper, Lee, Kay, Colin, Abdelhamid, Asmaa, Kroon, Paul A, Cohn, Jeffrey S, Rimm, Eric B, Cassidy, Aedín·2012·The American Journal of Clinical Nutrition

DOI 10.3945/ajcn.111.023457

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Abstract

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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Blood pressure-lowering effect of dietary (−)-epicatechin administration in L-NAME-treated rats is associated with restored nitric oxide levels
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Tangeretin Regulates Platelet Function Through Inhibition of Phosphoinositide 3-Kinase and Cyclic Nucleotide Signaling
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Improving the estimation of flavonoid intake for study of health outcomes
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“…30-day intervention trial with 100 mg of purified (−)-epicatechin failed to show any improvement in the same parameter.11 In a previous meta-analysis, Hooper et al. 2012 3 observed improvement in FMD by chocolate/cocoa consumption both acutely and chronically, with no apparent dose-effect…”
Investigation of antioxidant and anti-inflammatory activities as well as the renal protective potential of green coffee extract in high fat-diet/streptozotocin-induced diabetes in male albino rats
Alamri, O., Albeltagy, R. S., Akabawy, A. M. A., Mahgoub, S., Abdel-Mohsen, D. M., Moneim, A. E. A., & Amin, H. K. (2020) · Journal of Functional Foods · doi:10.1016/j.jff.2020.103996 · Cited by 62
A review on phytochemical and pharmacological facets of tropical ethnomedicinal plants as reformed DPP-IV inhibitors to regulate incretin activity
Chhabria, S., Mathur, S., Vadakan, S., Sahoo, D. K., Mishra, P., & Paital, B. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1027237 · Cited by 58
Human O-sulfated metabolites of (−)-epicatechin and methyl-(−)-epicatechin are poor substrates for commercial aryl-sulfatases: Implications for studies concerned with quantifying epicatechin bioavailability
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Self-citation
Flavonoid intake and cardiovascular disease risk
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Pharmacological actions of nobiletin in the modulation of platelet function
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“Epidemiological studies (Middleton et al., 2000; Joshipura et al., 2001; Hubbard et al., 2004; Benavente-Garcia and Castillo, 2008; Hooper et al., 2012) have suggested that regular intake of foods rich in flavonoids can reduce cardiovascular disease risks.”
Background
A metabolomics‐driven approach to predict cocoa product consumption by designing a multimetabolite biomarker model in free‐living subjects from the PREDIMED study
Garcia‐Aloy, M., Llorach, R., Urpí-Sardà, M., Jáuregui, O., Corella, D., Ruiz‐Canela, M., Salas‐Salvadó, J., Fitó, M., Ros, E., Estruch, R., et al. (2014) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201400434 · Cited by 58
“Indeed, this observation could reflect a potential mechanism of action for previously observed associations between chocolate or cocoa intake and improved insulin resistance [23].”
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“Sum 3 (2) 36 (22)(3) 6 (0) 3 (3) 48 (27)”
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Comprehensive Strategies for Metabolic Syndrome: How Nutrition, Dietary Polyphenols, Physical Activity, and Lifestyle Modifications Address Diabesity, Cardiovascular Diseases, and Neurodegenerative Conditions
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“An acute short-term intake (18 weeks) of cocoa, chocolate, and flavan-3-ols also reduced insulin resistance [246].”
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Phytochemicals for Improving Aspects of Cognitive Function and Psychological State Potentially Relevant to Sports Performance
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Dietary Polyphenols and Their Effects on Cell Biochemistry and Pathophysiology 2013
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Flavanone-rich citrus beverages counteract the transient decline in postprandial endothelial function in humans: a randomised, controlled, double-masked, cross-over intervention study
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“Indeed, flavonoid-rich foods and beverages are well reported to improve endothelial 53 function in humans both acutely ((21-24)), short-term (25-27) and long-term ((28-31)).”
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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High‐polyphenol chocolate reduces endothelial dysfunction and oxidative stress during acute transient hyperglycaemia in Type 2 diabetes: a pilot randomized controlled trial
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Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol‐rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo‐controlled, crossover trial
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Self-citation
Natural antioxidant ice cream acutely reduces oxidative stress and improves vascular function and physical performance in healthy individuals
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“However, no statistical or marginally significant effects have been reported on HOMA-IR (Zheng et al., 2013), cholesterol (Shrime et al., 2011), LDL (Hooper et al., 2012b), HDL (Hooper et al., 2012b; Jia et al., 2010; Kim et al., 2011; Tokede et al., 2011; Zhang et al., 2013), and triglyceride (Jia…”
BackgroundInfluential
Metabolomic fingerprint in patients at high risk of cardiovascular disease by cocoa intervention
Llorach, R., Urpí-Sardà, M., Tulipani, S., Garcia‐Aloy, M., Monagas, M., & Andrés‐Lacueva, C. (2013) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201200736 · Cited by 51
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“blood vessels improved after chronic and acute intakes of these flavan-3-ol-rich food sources.(23) The flavonoid supplement, Pycnogenol was significantly more effective than compression stockings for”
Polyphenolic extract attenuates fatty acid-induced steatosis and oxidative stress in hepatic and endothelial cells
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Background
Impact of Cocoa Consumption on Inflammation Processes—A Critical Review of Randomized Controlled Trials
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BackgroundMethod
The Impact of Cocoa Flavanols on Cardiovascular Health
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The hypoglycemic effects of guava leaf (Psidium guajava L.) extract are associated with improving endothelial dysfunction in mice with diet-induced obesity
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“Men Women Post-menopausal women n 11252 13633 8176 Age [years] 59 (9) 58 (9) 64 (7) BMI [kg/m 2 ] 27 (3) 26 (4) 27 (4) Cholesterol [mmol/L] 6.”
BackgroundInfluential
Modulation of metabolic syndrome‐related inflammation by cocoa
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Intravenous (−)-epicatechin reduces myocardial ischemic injury by protecting mitochondrial function
Yamazaki, K. G., Andreyev, A. Y., Ortiz-Vilchis, P., Petrosyan, S., Divakaruni, A. S., Wiley, S. E., Fuente, C. D. L., Perkins, G. A., Ceballos, G. M., Villarreal, F. J., et al. (2014) · International Journal of Cardiology · doi:10.1016/j.ijcard.2014.05.009 · Cited by 46
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Background
Coffee and beverages are the major contributors to polyphenol consumption from food and beverages in Japanese middle-aged women
Fukushima, Y., Tashiro, T., Kumagai, A., Ohyanagi, H., Horiuchi, T., Takizawa, K., Sugihara, N., Kishimoto, Y., Taguchi, C., Tani, M., et al. (2014) · Journal of Nutritional Science · doi:10.1017/jns.2014.19 · Cited by 46
Acute effects of brewed cocoa consumption on attention, motivation to perform cognitive work and feelings of anxiety, energy and fatigue: a randomized, placebo-controlled crossover experiment
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Background
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Effects of polyphenols on cardio-metabolic risk factors and risk of type 2 diabetes. A joint position statement of the Diabetes and Nutrition Study Group of the Italian Society of Diabetology (SID), the Italian Association of Dietetics and Clinical Nutrition (ADI) and the Italian Association of Medical Diabetologists (AMD)
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Acute Effects of a Polyphenol-Rich Leaf Extract of Mangifera indica L. (Zynamite) on Cognitive Function in Healthy Adults: A Double-Blind, Placebo-Controlled Crossover Study
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Bilberry-Derived Anthocyanins Prevent IFN-γ-Induced Pro-Inflammatory Signalling and Cytokine Secretion in Human THP-1 Monocytic Cells
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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
ORCID: Hooper, Lee
Kay, Colin
Abdelhamid, Asmaa
Kroon, Paul A
Cohn, Jeffrey S
Rimm, Eric B
Cassidy, Aedín
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)
DOI: 10.3945/ajcn.111.023457
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4010 d)
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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Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials

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