Polyphenols, Inflammation, and Cardiovascular Disease Authors
Vascular Biology (RS Rosenson, Section Editor)
First Online: 20 March 2013 DOI:
Cite this article as: Tangney, C.C. & Rasmussen, H.E. Curr Atheroscler Rep (2013) 15: 324. doi:10.1007/s11883-013-0324-x Part of the following topical collections: Topical Collection on Vascular Biology
Polyphenols are compounds found in foods such as tea, coffee, cocoa, olive oil, and red wine and have been studied to determine if their intake may modify cardiovascular disease (CVD) risk. Historically, biologic actions of polyphenols have been attributed to antioxidant activities, but recent evidence suggests that immunomodulatory and vasodilatory properties of polyphenols may also contribute to CVD risk reduction. These properties will be discussed, and recent epidemiological evidence and intervention trials will be reviewed. Further identification of polyphenols in foods and accurate assessment of exposures through measurement of biomarkers (i.e., polyphenol metabolites) could provide the needed impetus to examine the impact of polyphenol-rich foods on CVD intermediate outcomes (especially those signifying chronic inflammation) and hard endpoints among high risk patients. Although we have mechanistic insight into how polyphenols may function in CVD risk reduction, further research is needed before definitive recommendations for consumption can be made.
This article is part of the Topical Collection on
References Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
García-Villalba R, Carrasco-Pancorbo A, Nevedomskaya E, et al. Exploratory analysis of human urine by LC-ESI-TOF MS after high intake of olive oil: understanding the metabolism of polyphenols. Anal Bioanal Chem. 2010;398:463–75.
Marzocchella L, Fantini M, Benvenuto M, et al. Dietary flavonoids: molecular mechanisms of action as anti-inflammatory agents. Recent Pat Inflamm Allergy Drug Discov. 2011;5:200–20.
Gimeno E, Fito M, Lamuela-Raventos RM, et al. Effect of ingestion of virgin olive oil on human low-density lipoprotein composition. Eur J Clin Nutr. 2002;56:114–20.
USDA Nutrient Data Laboratory: USDA database for flavonoids content of selected foods. Release 3.0. 2011. Available from:
Neveu V, Perez-Jimenez J, Vos F, et al. Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database (Oxford) 2010; 2010:ba024.
Rothwell JA, Urpi-Sarda M, Boto-Ordoñez M, et al. Phenol-Explorer 2.0: a major update of the Phenol-Explorer database integrating data on polyphenol metabolism and pharmacokinetics in humans and experimental animals. Database (Oxford) 2012, 2012.
Ovaskainen ML, Torronen R, Koponen JM, et al. Dietary intake and major food sources of polyphenols in Finnish adults. J Nutr. 2008;138:562–6.
Perez-Jimenez J, Fezeu L, Touvier M, et al. Dietary intake of 337 polyphenols in French adults. Am J Clin Nutr. 2011;93:1220–8.
• Tresserra-Rimbau A, Medina-Remón A, Pérez-Jiménez J, et al. Dietary intake and major food sources of polyphenols in a Spanish population at high cardiovascular risk: The PREDIMED study. Nutr Metab Cardiovasc Dis 2013, in press.
This group examines the total polyphenols and its classes including flavonoids and phenolic acids in diets of Spanish subjects in the PREDIMED trial. The distribution of polyphenols (from olives, and olive oils) is contrasted with those from the Su.VI.MAX (French) population sample. Both reports rely on composition data from the Phenol Explorer database.
Spencer JP, Abd El Mohsen MM, Minihane AM, Mathers JC. Biomarkers of the intake of dietary polyphenols: strengths, limitations and application in nutrition research. Br J Nutr. 2008;99:12–22.
Caruso D, Visioli F, Patelli R, et al. Urinary excretion of olive oil phenols and their metabolites in humans. Metabolism. 2001;50:1426–8.
Orozco-Solano MI, Ferreiro-Vera C, Priego-Capote F, Luque de Castro MD. Automated method for determination of olive oil phenols and metabolites in human plasma and application in intervention studies. J Chromatogr. 2012;1258:108–16.
de la Torre-Carbot K, Chavez-Servin JL, Jauregui O, et al. Elevated circulating LDL phenol levels in men who consumed virgin rather than refined olive oil are associated with less oxidation of plasma LDL. J Nutr. 2010;140:501–8.
Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868–74.
Ross R. Atherosclerosis–an inflammatory disease. N Engl J Med. 1999;340:115–26.
Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med. 1996;20:933–56.
Steffen Y, Gruber C, Schewe T, Sies H. Mono-O-methylated flavanols and other flavonoids as inhibitors of endothelial NADPH oxidase. Arch Biochem Biophys. 2008;469:209–19.
Borriello A, Cucciolla V, Della Ragione F, Galletti P. Dietary polyphenols: focus on resveratrol, a promising agent in the prevention of cardiovascular diseases and control of glucose homeostasis. Nutr Metab Cardiovasc Dis. 2010;20:618–25.
Ahsan MK, Lekli I, Ray D, et al. Redox regulation of cell survival by the thioredoxin superfamily: an implication of redox gene therapy in the heart. Antioxid Redox Signal. 2009;11:2741–58.
Xia N, Daiber A, Habermeier A, et al. Resveratrol reverses endothelial nitric-oxide synthase uncoupling in apolipoprotein E knockout mice. J Pharmacol Exp Ther. 2010;335:149–54.
Spanier G, Xu H, Xia N, et al. Resveratrol reduces endothelial oxidative stress by modulating the gene expression of superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1) and NADPH oxidase subunit (Nox4). J Physiol Pharmacol. 2009;60:111–6.
Ungvari Z, Bagi Z, Feher A, et al. Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2. Am J Physiol Heart Circ Physiol. 2010;299:H18–24.
• Kostyuk VA, Potapovich AI, Suhan TO, et al. Antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation. Eur J Pharmacol 2011; 658:248-56.
These researchers present endothelial cell culture studies that support the role of plant polyphenols in vascular inflammation as not only antioxidants but also as modulators of inflammatory redox signaling pathways.
Al-Awwadi NA, Araiz C, Bornet A, et al. Extracts enriched in different polyphenolic families normalize increased cardiac NADPH oxidase expression while having differential effects on insulin resistance, hypertension, and cardiac hypertrophy in high-fructose-fed rats. J Agric Food Chem. 2005;53:151–7.
Covas MI, Nyyssonen K, Poulsen HE, et al. The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial. Ann Intern Med. 2006;145:333–41.
•• Hollman PC, Cassidy A, Comte B, et al. The biological relevance of direct antioxidant effects of polyphenols for cardiovascular health in humans is not established. J Nutr 2011; 141:989S-1009S.
This report reflects the consensus among international experts regarding the biological relevance of antioxidant effects of polyphenols in cardiovascular health and suggests a broader view of these bioactive compounds in modulation of inflammation balance.
Deng YH, Alex D, Huang HQ, et al. Inhibition of TNF–mediated endothelial cell-monocyte cell adhesion and adhesion molecules expression by the resveratrol derivative, trans-3,5,4′-trimethoxystilbene. Phytother Res. 2011;25:451–7.
Rius C, Abu-Taha M, Hermenegildo C, et al. Trans- but not cis-resveratrol impairs angiotensin-II-mediated vascular inflammation through inhibition of NF-kB activation and peroxisome proliferator-activated receptor-gamma upregulation. J Immunol. 2010;185:3718–27.
Olholm J, Paulsen SK, Cullberg KB, et al. Anti-inflammatory effect of resveratrol on adipokine expression and secretion in human adipose tissue explants. Int J Obes (Lond). 2010;34:1546–53.
Boesch-Saadatmandi C, Loboda A, Wagner AE, et al. Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucuronide on inflammatory gene expression: role of miR-155. J Nutr Biochem. 2011;22:293–9.
Andriantsitohaina R, Auger C, Chataigneau T, et al. Molecular mechanisms of the cardiovascular protective effects of polyphenols. Br J Nutr. 2012;108:1532–49.
Romero M, Jimenez R, Sanchez M, et al. Quercetin inhibits vascular superoxide production induced by endothelin-1: role of NADPH oxidase, uncoupled eNOS and PKC. Atherosclerosis. 2009;202:58–67.
Chalopin M, Tesse A, Martinez MC, et al. Estrogen receptor alpha as a key target of red wine polyphenols action on the endothelium. PLoS One. 2010;5:e8554.
Duarte J, Andriambeloson E, Diebolt M, Andriantsitohaina R. Wine polyphenols stimulate superoxide anion production to promote calcium signaling and endothelial-dependent vasodilatation. Physiol Res. 2004;53:595–602.
Ndiaye M, Chataigneau M, Lobysheva I, et al. Red wine polyphenol-induced, endothelium-dependent NO-mediated relaxation is due to the redox-sensitive PI3-kinase/Akt-dependent phosphorylation of endothelial NO-synthase in the isolated porcine coronary artery. FASEB J. 2005;19:455–7.
Anselm E, Chataigneau M, Ndiaye M, et al. Grape juice causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of eNOS. Cardiovasc Res. 2007;73:404–13.
• Chiva-Blanch G, Urpi-Sarda M, Llorach R, et al. Differential effects of polyphenols and alcohol of red wine on the expression of adhesion molecules and inflammatory cytokines related to atherosclerosis: A randomized clinical trial (American Journal of Clinical Nutrition (2012) 95; (326-34)). Am J Clin Nutr 2012, 95:1506.
The report describes the findings from a randomized trial in which subjects of high cardiovascular risk were presented in crossover design: 30 g daily of red wine for 30 day, 30 g gin daily for the same period and 30 g daily of dealcoholized red wine to ascertain what constituents are responsible for observed changes in adhesion molecules and cytokines.
Estruch R, Martinez-Gonzalez MA, Corella D, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med. 2006;145:1–11.
Mena MP, Sacanella E, Vazquez-Agell M, et al. Inhibition of circulating immune cell activation: a molecular antiinflammatory effect of the Mediterranean diet. Am J Clin Nutr. 2009;89:248–56.
Dell’Agli M, Fagnani R, Mitro N, et al. Minor components of olive oil modulate proatherogenic adhesion molecules involved in endothelial activation. J Agric Food Chem. 2006;54:3259–64.
Dell’Agli M, Fagnani R, Galli GV, et al. Olive oil phenols modulate the expression of metalloproteinase 9 in THP-1 cells by acting on nuclear factor-kappaB signaling. J Agric Food Chem. 2010;58:2246–52.
Fitzpatrick DF, Hirschfield SL, Coffey RG. Endothelium-dependent vasorelaxing activity of wine and other grape products. Am J Physiol. 1993;265:H774–8.
Schini-Kerth VB, Auger C, Kim JH, et al. Nutritional improvement of the endothelial control of vascular tone by polyphenols: role of NO and EDHF. Pflugers Arch. 2010;459:853–62.
Duthie GG, Pedersen MW, Gardner PT, et al. The effect of whisky and wine consumption on total phenol content and antioxidant capacity of plasma from healthy volunteers. Eur J Clin Nutr. 1998;52:733–6.
Iwamoto Y, Maruhashi T, Fujii Y, et al. Intima-media thickness of brachial artery, vascular function, and cardiovascular risk factors. Arterioscler Thromb Vasc Biol. 2012;32:2295–303.
Agewall S, Wright S, Doughty RN, et al. Does a glass of red wine improve endothelial function? Eur Heart J. 2000;21:74–8.
Engler MB, Engler MM, Chen CY, et al. Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults. J Am Coll Nutr. 2004;23:197–204.
• Hooper L, Kay C, Abdelhamid A, et al. Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. Am J Clin Nutr 2012; 95:740-51.
This paper is a thorough review of recent studies examining these polyphenol-rich foods on cardiovascular outcomes
Duffy SJ, Keaney Jr JF, Holbrook M, et al. Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. Circulation. 2001;104:151–6.
Lekakis J, Rallidis LS, Andreadou I, et al. Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. Eur J Cardiovasc Prev Rehabil. 2005;12:596–600.
Inaba Y, Chen JA, Bergmann SR. Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis. Int J Cardiovasc Imaging. 2010;26:631–40.
Peterson JJ, Dwyer JT, Jacques PF, McCullough ML. Associations between flavonoids and cardiovascular disease incidence or mortality in European and US populations. Nutr Rev. 2012;70:491–508.
Cassidy A, Rimm EB, O’Reilly EJ, et al. Dietary flavonoids and risk of stroke in women. Stroke. 2012;43:946–51.
McCullough ML, Peterson JJ, Patel R, et al. Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults. Am J Clin Nutr. 2012;95:454–64.
Hollman PC, Geelen A, Kromhout D. Dietary flavonol intake may lower stroke risk in men and women. J Nutr. 2010;140:600–4.
Cassidy A, O’Reilly EJ, Kay C, et al. Habitual intake of flavonoid subclasses and incident hypertension in adults. Am J Clin Nutr. 2011;93:338–47.
Samieri C, Feart C, Proust-Lima C, et al. Olive oil consumption, plasma oleic acid, and stroke incidence: the Three-City Study. Neurology. 2011;77:418–25.
Erdman Jr JW, Balentine D, Arab L, et al. Flavonoids and heart health: proceedings of the ILSI North America Flavonoids Workshop, May 31-June 1, 2005, Washington, DC. J Nutr. 2007;137:718S–37.
Peterson J, Dwyer J, Adlercreutz H, et al. Dietary lignans: physiology and potential for cardiovascular disease risk reduction. Nutr Rev. 2010;68:571–603.
USDA Nutrient Data Laboratory:USDA database for the isoflavone content of selected foods. Release 2.0. 2008. Available from:
USDA. Nutrient Data Laboratory:USDA database for proanthocyanidin content of selected foods. 2004, Available from:
Pérez-Jiménez J, Fezeu L, Touvier M, et al. Dietary intake of 337 polyphenols in French adults. Am J Clin Nutr. 2011;93:1220–8.
Salas-Salvado J, Bullo M, Babio N, et al. Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial. Diabetes Care. 2011;34:14–9.
Salas-Salvado J, Fernandez-Ballart J, Ros E, et al. Effect of a Mediterranean diet supplemented with nuts on metabolic syndrome status: one-year results of the PREDIMED randomized trial. Arch Intern Med. 2008;168:2449–58.
Medina-Remon A, Zamora-Ros R, Rotches-Ribalta M, et al. Total polyphenol excretion and blood pressure in subjects at high cardiovascular risk. Nutr Metab Cardiovasc Dis. 2011;21:323–31.
Estruch R, Ros E, Salas-Salvado J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. New Engl J Med. 2013 doi:
© Springer Science+Business Media New York 2013