Flavan-3ols intake and cardiovascular outcomes: Systematic Review

Project Summary Title and Description

Flavan-3ols intake and cardiovascular outcomes: Systematic Review
This proposed evidence mapping project will summarize the data related to Flavan-3-ols and its connection to vascular health outcomes and risk factors.
Authors of Report
Methodology description
This study is a systematic review of published literature evaluating the effects of flavan-3-ol intake on CVD outcomes and risk factors. The review was conducted in 2 phases: a first phase of evidence mapping followed by a full systematic review. A comprehensive search of the scientific literature was conducted in MEDLINE, the Cochrane Central databases, and the Commonwealth Agricultural Bureau from inception through March 9, 2019. We included RCTs and prospective cohort studies conducted in adults (≥ 18 years) that quantified the amount of flavan-3-ols consumed per day or per week. Studies that provided sufficient serving size data were also included, provided that estimation of total flavan-3-ol consumption was possible using the USDA or Phenol Explorer databases. Citations were screened in duplicate using predefined eligibility criteria and any disagreements regarding study inclusion or exclusion were resolved in group meetings. The primary outcomes of interest included CVD clinical outcomes [e.g., CVD mortality, chronic heart disease (CHD), stroke, diabetes, and hypertension]; secondary outcomes included risk factors [serum lipids, blood pressures, glucose metabolism, and flow-mediated dilation (FMD)] and biomarkers [high-sensitivity CRP (hsCRP), IL-6, and TNF-α].
Associated publication: Raman G, Avendano EE, Chen S, Wang J, Matson J, Gayer B, Novotny JA, Cassidy A. Dietary intakes of flavan-3-ols and cardiometabolic health: systematic review and meta-analysis of randomized trials and prospective cohort studies. Am J Clin Nutr. 2019 Nov 1;110(5):1067-1078. PMID: 31504087 https://academic.oup.com/ajcn/article/110/5/1067/5554778 - Data was entered into SRDR prospectively.
Funding Source
International Life Sciences Institute (ILSI) North America

Key Questions

1. Is dietary intake of flavan-3ols associated with cardiovascular health outcomes and risk factors among populations relevant to the general North America population?
2. Exclude
3. Exclude

Associated Extraction Forms

Associated Studies (each link opens a new tab)

The acute effect of green tea consumption on endothelial function in healthy individuals.2008
Differential effect of polyphenol-rich dark chocolate on biomarkers of glucose metabolism and cardiovascular risk factors in healthy, overweight and obese subjects: a randomized clinical trial.2012
The regular consumption of a polyphenol-rich apple does not influence endothelial function: a randomised double-blind trial in hypercholesterolemic adults.
The effect of black tea on risk factors of cardiovascular disease in a normal population.2012
Freeze-dried strawberries lower serum cholesterol and lipid peroxidation in adults with abdominal adiposity and elevated serum lipids.2014
Low-energy cranberry juice decreases lipid oxidation and increases plasma antioxidant capacity in women with metabolic syndrome.2011
Blueberries decrease cardiovascular risk factors in obese men and women with metabolic syndrome.2010
Green tea minimally affects biomarkers of inflammation in obese subjects with metabolic syndrome.2011
Strawberries decrease atherosclerotic markers in subjects with metabolic syndrome.2010
Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome.2010
Association between soy and green tea (Camellia sinensis) diminishes hypercholesterolemia and increases total plasma antioxidant potential in dyslipidemic subjects.2008
Green tea extract reduces blood pressure, inflammatory biomarkers, and oxidative stress and improves parameters associated with insulin resistance in obese, hypertensive patients.2012
Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: a randomized controlled trial.2012
Effects of dietary supplementation with the green tea polyphenol epigallocatechin-3-gallate on insulin resistance and associated metabolic risk factors: randomized controlled trial.2009
Health effects of green tea catechins in overweight and obese men: a randomised controlled cross-over trial.
Beneficial clinical effects of grape seed proanthocyanidin extract on the progression of carotid atherosclerotic plaques.2015
A randomized double-blind placebo-controlled study of Pu'er tea extract on the regulation of metabolic syndrome.2011
A double-blind, placebo-controlled, randomized trial of the effects of dark chocolate and cocoa on variables associated with neuropsychological functioning and cardiovascular health: clinical findings from a sample of healthy, cognitively intact older adults.2008
Dose-related effects of flavanol-rich cocoa on blood pressure.2010
Red wine consumption does not affect oxidizability of low-density lipoproteins in volunteers.1996
Low vs. higher-dose dark chocolate and blood pressure in cardiovascular high-risk patients.2010
Effects of cranberry juice consumption on vascular function in patients with coronary artery disease.2011
Supplementation of the Pure Flavonoids Epicatechin and Quercetin Affects Some Biomarkers of Endothelial Dysfunction and Inflammation in (Pre)Hypertensive Adults: A Randomized Double-Blind, Placebo-Controlled, Crossover Trial.2015
Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: a randomized, double-blind, placebo-controlled, crossover trial.2015
Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease.2001
Favorable effects of berry consumption on platelet function, blood pressure, and HDL cholesterol.2008
Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men.2014
Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial.2008
Polyphenol-rich cranberry juice has a neutral effect on endothelial function but decreases the fraction of osteocalcin-expressing endothelial progenitor cells.2013
Cardiovascular effects of flavanol-rich chocolate in patients with heart failure.2012
Bilberry juice modulates plasma concentration of NF-kappaB related inflammatory markers in subjects at increased risk of CVD.2010
Regular consumption of cocoa powder with milk increases HDL cholesterol and reduces oxidized LDL levels in subjects at high-risk of cardiovascular disease.2012
Bilberries reduce low-grade inflammation in individuals with features of metabolic syndrome.2012
Dark chocolate and reduced snack consumption in mildly hypertensive adults: an intervention study.
Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers.2012
Intake of whole apples or clear apple juice has contrasting effects on plasma lipids in healthy volunteers.2013
Dark chocolate or tomato extract for prehypertension: a randomised controlled trial.2009
Effect of a wild blueberry (Vaccinium angustifolium) drink intervention on markers of oxidative stress, inflammation and endothelial function in humans with cardiovascular risk factors.
Impact of processing on the bioavailability and vascular effects of blueberry (poly)phenols.2014
Intake and time dependence of blueberry flavonoid-induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity.
High-cocoa polyphenol-rich chocolate improves blood pressure in patients with diabetes and hypertension.2015
Evidence that cranberry juice may improve augmentation index in overweight men.2013
Beneficial effects of grape seed extract on malondialdehyde-modified LDL.2007
Tea catechin consumption reduces circulating oxidized low-density lipoprotein.2007
The effect of strawberries in a cholesterol-lowering dietary portfolio.2008
Reduction of body fat and improved lipid profile associated with daily consumption of a Puer tea extract in a hyperlipidemic population: a randomized placebo-controlled trial.
Effects of grape antioxidant dietary fiber in cardiovascular disease risk factors.2008
The efficacy of black tea in ameliorating endothelial function is equivalent to that of green tea.2008
Daily blueberry consumption improves blood pressure and arterial stiffness in postmenopausal women with pre- and stage 1-hypertension: a randomized, double-blind, placebo-controlled clinical trial.2015
The effect of green tea and sour tea on blood pressure of patients with type 2 diabetes: a randomized clinical trial.
Effects of sour tea (Hibiscus sabdariffa) on lipid profile and lipoproteins in patients with type II diabetes.2009
A 6-month randomized pilot study of black tea and cardiovascular risk factors.2007
Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension.2008
A green tea extract high in catechins reduces body fat and cardiovascular risks in humans.2007
A catechin-rich beverage improves obesity and blood glucose control in patients with type 2 diabetes.2009
Effect of cocoa and theobromine consumption on serum HDL-cholesterol concentrations: a randomized controlled trial.2013
Regular daily intake of black tea improves oxidative stress biomarkers and decreases serum C-reactive protein levels in type 2 diabetic patients.2010
Effects of green tea supplementation on elements, total antioxidants, lipids, and glucose values in the serum of obese patients.2012
Acute ingestion of catechin-rich green tea improves postprandial glucose status and increases serum thioredoxin concentrations in postmenopausal women.2014
Effects of grape seed proanthocyanidin extract on menopausal symptoms, body composition, and cardiovascular parameters in middle-aged women: a randomized, double-blind, placebo-controlled pilot study.2014
Effect of Black Tea Consumption on Intracellular Cytokines, Regulatory T Cells and Metabolic Biomarkers in Type 2 Diabetes Patients.2016
The acute and sub-chronic effects of cocoa flavanols on mood, cognitive and cardiovascular health in young healthy adults: a randomized, controlled trial.2015
Cocoa flavanol consumption improves cognitive function, blood pressure control, and metabolic profile in elderly subjects: the Cocoa, Cognition, and Aging (CoCoA) Study--a randomized controlled trial.2015
Six weeks daily ingestion of whole blueberry powder increases natural killer cell counts and reduces arterial stiffness in sedentary males and females.2014
Natural cocoa consumption: Potential to reduce atherogenic factors?2015
Effect of muscadine grape seed supplementation on vascular function in subjects with or at risk for cardiovascular disease: a randomized crossover trial.2010
High-cocoa polyphenol-rich chocolate improves HDL cholesterol in Type 2 diabetes patients.2010
Changes in body weight, blood pressure and selected metabolic biomarkers with an energy-restricted diet including twice daily sweet snacks and once daily sugar-free beverage.2014
Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults.2011
Cranberry juice consumption lowers markers of cardiometabolic risk, including blood pressure and circulating C-reactive protein, triglyceride, and glucose concentrations in adults.2015
Safety and efficacy of cocoa flavanol intake in healthy adults: a randomized, controlled, double-masked trial.2015
Beneficial effects of cocoa on lipid peroxidation and inflammatory markers in type 2 diabetic patients and investigation of probable interactions of cocoa active ingredients with prostaglandin synthase-2 (PTGS-2/COX-2) using virtual analysis.2014
Central arterial hemodynamic effects of dark chocolate ingestion in young healthy people: a randomized and controlled trial.2014
Effects of ellagitannin-rich berries on blood lipids, gut microbiota, and urolithin production in human subjects with symptoms of metabolic syndrome.2013
Purified black tea theaflavins and theaflavins/catechin supplements did not affect serum lipids in healthy individuals with mildly to moderately elevated cholesterol concentrations.2010
Effect of black tea intake on blood cholesterol concentrations in individuals with mild hypercholesterolemia: a diet-controlled randomized trial.2015
Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study.2011
Effects of apple consumption on lipid profile of hyperlipidemic and overweight men.2011
Effects on peripheral and central blood pressure of cocoa with natural or high-dose theobromine: a randomized, double-blind crossover trial.2010
Grape polyphenols reduce blood pressure and increase flow-mediated vasodilation in men with metabolic syndrome.2012
Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial.
Short-term alcohol consumption may have detrimental effect on fibrinolysis and endothelial function: preliminary report of prospective randomised study.2013
Daily consumption of an aqueous green tea extract supplement does not impair liver function or alter cardiovascular disease risk biomarkers in healthy men.2009
Effects of regular ingestion of black tea on haemostasis and cell adhesion molecules in humans.2001
Green tea extract decreases plasma malondialdehyde concentration but does not affect other indicators of oxidative stress, nitric oxide production, or hemostatic factors during a high-linoleic acid diet in healthy females.1999
Randomized controlled trial for an effect of green tea-extract powder supplementation on glucose abnormalities.2008
Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives.2005
Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans.2001
Effects of Initiating Moderate Alcohol Intake on Cardiometabolic Risk in Adults With Type 2 Diabetes: A 2-Year Randomized, Controlled Trial.2015
Wine: does the colour count?1996
Cocoa consumption dose-dependently improves flow-mediated dilation and arterial stiffness decreasing blood pressure in healthy individuals.2015
Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate.2008
Dark chocolate and vascular function in patients with peripheral artery disease: a randomized, controlled cross-over trial.2015
Oxidised LDL levels decreases after the consumption of ready-to-eat meals supplemented with cocoa extract within a hypocaloric diet.2014
Flavanol-rich cocoa ameliorates lipemia-induced endothelial dysfunction.2011
Does supplementation with green tea extract improve insulin resistance in obese type 2 diabetics? A randomized, double-blind, and placebo-controlled clinical trial.2011
Effect of green tea extract on obese women: a randomized, double-blind, placebo-controlled clinical trial.2008
Effects of concord grape juice on appetite, diet, body weight, lipid profile, and antioxidant status of adults.2009
Consumption of a grape extract supplement containing resveratrol decreases oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease: a triple-blind, 6-month follow-up, placebo-controlled, randomized trial.
Effectiveness of green tea in a randomized human cohort: relevance to diabetes and its complications.2013
Improvement of endothelial function with dietary flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease.2010
Impact of cocoa flavanol intake on age-dependent vascular stiffness in healthy men: a randomized, controlled, double-masked trial.
Black tea lowers the rate of blood pressure variation: a randomized controlled trial.
Grape polyphenols do not affect vascular function in healthy men.
Effect of green tea (Camellia sinensis) consumption on the components of metabolic syndrome in elderly.2012
Effects of dark chocolate and cocoa consumption on endothelial function and arterial stiffness in overweight adults.
Effect of 2-month controlled green tea intervention on lipoprotein cholesterol, glucose, and hormone levels in healthy postmenopausal women.2012
Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease.2007
Intake and time dependence of blueberry flavonoid-induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity.2013
Effects of dietary supplementation with epigallocatechin-3-gallate on weight loss, energy homeostasis, cardiometabolic risk factors and liver function in obese women: randomised, double-blind, placebo-controlled clinical trial.2014
Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease.
Dose-dependent increases in flow-mediated dilation following acute cocoa ingestion in healthy older adults.2011
Randomized Controlled Intervention of the Effects of Alcohol on Blood Pressure in Premenopausal Women.2015
The effects of green tea consumption on metabolic and anthropometric indices in patients with Type 2 diabetes.2013
Cocoa flavanol intake improves endothelial function and Framingham Risk Score in healthy men and women: a randomised, controlled, double-masked trial: the Flaviola Health Study.2015
Effect of black tea consumption on brachial artery flow-mediated dilation and ischaemia-reperfusion in humans.2014
Randomized controlled trial for an effect of catechin-enriched green tea consumption on adiponectin and cardiovascular disease risk factors.2011
Cerebral blood flow response to flavanol-rich cocoa in healthy elderly humans.2008
Effects of green tea extract on insulin resistance and glucagon-like peptide 1 in patients with type 2 diabetes and lipid abnormalities: a randomized, double-blinded, and placebo-controlled trial.
Dark chocolate acutely improves walking autonomy in patients with peripheral artery disease.2014
Effect of black tea drinking on blood lipids, blood pressure and aspects of bowel habit.1997
Vascular function and atherosclerosis progression after 1 y of flavonoid intake in statin-treated postmenopausal women with type 2 diabetes: a double-blind randomized controlled trial.2013
Chronic ingestion of flavan-3-ols and isoflavones improves insulin sensitivity and lipoprotein status and attenuates estimated 10-year CVD risk in medicated postmenopausal women with type 2 diabetes: a 1-year, double-blind, randomized, controlled trial.2012
A single portion of blueberry (Vaccinium corymbosum L) improves protection against DNA damage but not vascular function in healthy male volunteers.2013
Attenuation of meal-induced inflammatory and thrombotic responses in overweight men and women after 6-week daily strawberry (Fragaria) intake. A randomized placebo-controlled trial.2011
Effect of tea theaflavins and catechins on microvascular function.2014
Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults.2004
Acute and chronic effects of flavanol-rich cocoa on vascular function in subjects with coronary artery disease: a randomized double-blind placebo-controlled study.2006
Different berries and berry fractions have various but slightly positive effects on the associated variables of metabolic diseases on overweight and obese women.2011
Minor effects of green tea catechin supplementation on cardiovascular risk markers in active older people: a randomized controlled trial.2013
Effect of dark chocolate on arterial function in healthy individuals.2005
Greenselect phytosome for borderline metabolic syndrome.2013
Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial.2008
Beneficial effects of a flavanol-enriched cacao beverage on anthropometric and cardiometabolic risk profile in overweight subjects2015
Therapeutic effect of high-dose green tea extract on weight reduction: A randomized, double-blind, placebo-controlled clinical trial.2016
Green Tea Extract and Catechol-O-Methyltransferase Genotype Modify Fasting Serum Insulin and Plasma Adiponectin Concentrations in a Randomized Controlled Trial of Overweight and Obese Postmenopausal Women.2016
Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomized, crossover study.2016
Black Tea Increases Circulating Endothelial Progenitor Cells and Improves Flow Mediated Dilatation Counteracting Deleterious Effects from a Fat Load in Hypertensive Patients: A Randomized Controlled Study.2016
Integration of Traditional and Metabolomics Biomarkers Identifies Prognostic Metabolites for Predicting Responsiveness to Nutritional Intervention against Oxidative Stress and Inflammation.
Concord grape juice, cognitive function, and driving performance: a 12-wk, placebo-controlled, randomized crossover trial in mothers of preteen children.2016
Effects of a mixed berry beverage on cognitive functions and cardiometabolic risk markers; A randomized cross-over study in healthy older adults.
Beneficial effect of a polyphenol-rich diet on cardiovascular risk: a randomised control trial.2016
Short-term Effects of Green Tea on Blood Pressure, Endothelial Function, and Metabolic Profile in Obese Prehypertensive Women: A Crossover Randomized Clinical Trial.2017
Habitual cocoa intake reduces arterial stiffness in postmenopausal women regardless of intake frequency: a randomized parallel-group study.
Strawberry and cranberry polyphenols improve insulin sensitivity in insulin-resistant, non-diabetic adults: a parallel, double-blind, controlled and randomised clinical trial.2017
Cranberry (poly)phenol metabolites correlate with improvements in vascular function: A double-blind, randomized, controlled, dose-response, crossover study.2016
Effects of high flavanol dark chocolate on cardiovascular function and platelet aggregation.2015
Red or white wine consumption effect on atherosclerosis in healthy individuals (In Vino Veritas study).2017
Impact of cocoa flavanol intake on age-dependent vascular stiffness in healthy men: a randomized, controlled, double-masked trial.2015
Effects of dietary strawberry powder on blood lipids and inflammatory markers in obese human subjects.2012
Blueberries improve endothelial function, but not blood pressure, in adults with metabolic syndrome: a randomized, double-blind, placebo-controlled clinical trial.
Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function.2003
Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women.2010
Effect of modest alcohol consumption over 1-2 weeks on the coronary microcirculation of normal subjects.2010
The Effects of Dark Chocolate Consumption on Lipid Profile, Fasting Blood Sugar, Liver Enzymes, Inflammation, and Antioxidant Status in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized, Placebo-Controlled, Pilot study2015
A Randomized, Placebo-Controlled Study on the Safety and Efficacy of Daily Ingestion of Green Tea (2018
Effects of green tea extract on overweight and obese women with high levels of low density-lipoprotein-cholesterol (LDL-C): a randomised, double-blind, and cross-over placebo-controlled clinical trial.2018
Gender difference in the effects of cacao polyphenols on blood pressure and glucose/lipid metabolism in prediabetic subjects: a double-blinded, randomized, placebo-controlled crossover trial.2019
Lack of acute or chronic effects of epicatechin-rich and procyanidin-rich apple extracts on blood pressure and cardiometabolic biomarkers in adults with moderately elevated blood pressure: a randomized, placebo-controlled crossover trial.2018
Regular Intake of a Usual Serving Size of Flavanol-Rich Cocoa Powder Does Not Affect Cardiometabolic Parameters in Stably Treated Patients with Type 2 Diabetes and Hypertension-A Double-Blinded, Randomized, Placebo-Controlled Trial.2018

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