Dietary flavonoids and their potential role in the prevention of cardiovascular disease have gained recent scientific and medical interest due to their antioxidant properties. 1 Oxidative stress due to excess free radicals or reactive oxygen species (ROS) is associated with a number of cardiovascular risk factors, i.e., hypertension, dyslipidemias, diabetes, smoking. Cellular DNA, proteins, and lipids are susceptible to ROS attack which can result in damage to cell membranes and organelles. Tissue damage and pathophysiological processes eventually ensue. The oxidative modification of low density lipoprotein (LDL) due to oxidative stress is believed to be a major contributing factor in atherosclerosis. Thus, dietary flavonoids due to their antioxidant properties may be beneficial in cardiovascular health and disease.
Epidemiological studies suggest flavonoid-rich diets high in fruits and/or vegetables reduce the risk of coronary heart disease. (2-4) A recent meta-analysis of seven prospective cohort studies with 105,000 individuals indicated that high dietary intake of flavonoids from a small number of fruits and vegetables, tea and red wine are inversely associated with coronary heart disease risk. 5 The antioxidant properties of flavonoids are related to their structure, two aromatic rings on the ends bound by an oxygenated heterocycle in the middle which promote free radical scavenging. The flavonoids as a subclass of polyphenols, are ubiquitous micronutrients derived from plants, primarily fruits and vegetables. There are more than 5,000 flavonoids identified and the six major flavonoid categories include: flavanols, flavanones, flavones, isoflavones, flavonols, and anthocyanidins. 6
The various subclasses are listed below and include typical foods or beverages with a substantial content of flavonoids; flavanol (catechin, epicatechin-chocolate, tea, red wine, beans, apricot, cherry, grape, peach, blackberry, apple), flavanones (hesperetin, naringenin, eriodictyol-citrus fruits and juices), flavones (apigenin, luteolin-parsley, celery), isoflavones (daidzein, genisteinsoy products), flavonols (quercetin, kaempferol, myricetin-onions, kale, broccoli, tomato, blueberry, apples, tea, red wine), anthocyanidins (cyanidin, pelargonidin, peonidin, delphinidin, malvidinblueberry, black grape, cherry, blackberry, black currant, rhubarb, strawberry, red wine, plum, red cabbage). 7,8 Interestingly, cocoa and chocolate contain both a high quantity and quality of antioxidant flavonoids, even exceeding black and green tea as well as red wine. 9,10 Dark chocolate ranks the highest of top antioxidant foods as indicated by the oxygen radical absorbance capacity (ORAC) measurement (Figure 1).11,12
Figure 1: Antioxidant Foods rated by
ORAC (Oxygen Radical Absorbance Capacity)
- Middleton E, Kandaswami C and Theoharides T C, ├óÔé¼┼øThe effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer├óÔé¼┼Ñ, Pharmcol. Rev. (2000), 52: pp. 673├óÔé¼ÔÇ£751.
- Liu S, Manson J E, Lee I M, Cole S R, Hennekens C H,Willett W C and Buring J E,├óÔé¼┼øFruit and vegetable intake and risk of cardiovascular disease: the Women™s Health Study├óÔé¼┼Ñ, Am. J. Clin. Nutr. (2000), 72: pp. 922├óÔé¼ÔÇ£928.
- Joshipura K J, Hu F B, Manson J E, Stampfer M J, Rimm E B, Speizer F E, Colditz G,Ascherio A, Rosner B, Spiegelman D, and Willett W C, ├óÔé¼┼øThe effect of fruit and vegetable intake on risk of coronary heart disease├óÔé¼┼Ñ, Ann. Int. Med. (2001), 134: pp. 1,106├óÔé¼ÔÇ£1,114.
- Liu S, Lee I M, Ajani U, Cole S R, Buring J E and Manson J E, ├óÔé¼┼øIntake of vegetables rich in carotenoids and risk of coronary heart disease in men:The Physicians™ Health Study├óÔé¼┼Ñ, Intl. J. Epidermiology (2001), 30: pp. 130├óÔé¼ÔÇ£135.
- Huxley R R and Neil H A W,├óÔé¼┼øThe relation between dietary flavonol intake and coronary heart disease mortality: a meta-analysis of prospective cohort studies├óÔé¼┼Ñ, Europ. J. Clin. Nutr. (2003), 57: pp. 904├óÔé¼ÔÇ£908.
- Beecher G R,├óÔé¼┼øOverview of dietary flavonoids: nomenclature, occurrence and intake├óÔé¼┼Ñ, J. Nutr. (2003),133: pp. 3,248S├óÔé¼ÔÇ£3,254S.
- Manach C, Scalbert A, Morand C, R─é┬®m─é┬®sy C and Jim─é┬®nez L,├óÔé¼┼øPolyphenols: food sources and bioavailability├óÔé¼┼Ñ, Am. J. Clin. Nutr. (2004), 79: pp. 727├óÔé¼ÔÇ£747.
- http://www.nal.usda.gov/fnic/foodcomp (accessed September 2003), USDA database for the flavonoid content of selected foods.
- Vinson J A, Proch J and Zubik L,├óÔé¼┼øPhenol antioxidant quantitiy and quality in foods: cocoa, dark chocolate, and milk chocolate├óÔé¼┼Ñ, J.Agric. Food Chem. (1999), 47 (12): pp. 4,821├óÔé¼ÔÇ£4,824.
- Lee K W, Kim Y J, Lee H J and Lee C Y, ├óÔé¼┼øCocoa has more phenolic phytochemicals and a higher antioxidant capacity than teas and red wine├óÔé¼┼Ñ, J.Agric. Food Chem. (2003), 51: pp. 7,292├óÔé¼ÔÇ£7,295.
- U.S. Department of Agriculture, ├óÔé¼┼øCan foods forestall aging?├óÔé¼┼Ñ, Aging Research (1999), 47: pp. 15├óÔé¼ÔÇ£17.
- Adamson G E, Lazarus S A, Mitchell A E, Prior R L, Cao G, Jacobs P H, Kremers B G, Hammerstone J F, Rucker R B, Ritter K A and Schmitz H H,├óÔé¼┼øHPLC method for the quantification of procyanidins in cocoa and chocolate samples and correlation to total antioxidant capacity├óÔé¼┼Ñ, J.Agric. Food Chem. (1999), 47: pp. 4,184├óÔé¼ÔÇ£4,188.
- http://www.fmnh.org/Chocolate/history.html (accessed November 2002), Chocolate Exhibition, The Field Museum, Chicago, IL.
- Lopez R, In: Chocolate The nature of indulgence, Harry N, Abrams, New York, N.Y., 2002.
- Steinberg F M, Holt R R, Schmitz H H and Keen C L,├óÔé¼┼øCocoa procyanidin chain length does not determine ability to protect LDL from oxidation when monomer units are controlled├óÔé¼┼Ñ, J. Nutr. Biochem. (2002), 13: pp. 645├óÔé¼ÔÇ£652.
- Osakabe N, Baba S,Yasuda A, Iwamoto T, Kamiyama M,Takizawa T, Itakura H and Kondo K,├óÔé¼┼øDaily cocoa intake reduces the susceptibility of low-density lipoprotein to oxidation as demonstrated in healthy human volunteers├óÔé¼┼Ñ, Free Rad. Res. (2001), 34: pp. 93├óÔé¼ÔÇ£99.
- Wan Y,Vinson J, Etherton T D, Proch J, Lazarus S A and Kris-Etherton P M, ├óÔé¼┼øEffects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans├óÔé¼┼Ñ, Am. J. Clin. Nutr. (2001), 74: pp. 596├óÔé¼ÔÇ£602.
- Mathur S, Devaraj S, Grundy S M and Jialal I, ├óÔé¼┼øCocoa products decrease low density lipoprotein oxidative susceptibility but do not affect biomarkers of inflammation in humans├óÔé¼┼Ñ, J. Nutr. (2002), 132: pp. 3,663├óÔé¼ÔÇ£3,667.
- Rein D, Lotito S, Holt R R, Keen C L, Schmitz H H and Fraga C G, ├óÔé¼┼øEpicatechin in human plasma: In vivo determination and effect of chocolate consumption on plasma oxidation status├óÔé¼┼Ñ, J. Nutr. (2000), 130: pp. 2,109S├óÔé¼ÔÇ£2,114S.
- Wang J F, Schramm D D, Holt R R, Ensunsa J L, Fraga C G, Schmitz H H and Keen C L, ├óÔé¼┼øA dose- response effect from chocolate consumption on plasma epicatechin and oxidative damage├óÔé¼┼Ñ, J. Nutr. (2000), 130: pp. 2,115S├óÔé¼ÔÇ£2,119S.
- Richelle M,Tavazzi I, Enslen M and Offord E A, ├óÔé¼┼øPlasma kinetics in man of epicatechin from black chocolate├óÔé¼┼Ñ, Eur. J. Clin. Nutr. (1999), 53: pp. 22├óÔé¼ÔÇ£26.
- Engler M B, Engler M M, Chen C Y, Malloy MJ , Browne A, Chiu E Y, Kwak H K, Milbury P, Paul S M, Blumberg J and Mietus-Snyder M,├óÔé¼┼øFlavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults├óÔé¼┼Ñ, J.Am. Coll. Nutr. (2004), 23 (3): pp. 197├óÔé¼ÔÇ£204.
- Engler M B and Engler M M,├óÔé¼┼øThe vasculoprotective effects of flavonoid-rich cocoa and chocolate├óÔé¼┼Ñ, Nutrition Research (2004) (In press).
- Serafini M, Bugianesi R, Maiani G,Valtuena S, De Santis S and Crozier A, ├óÔé¼┼øPlasma antioxidants from chocolate├óÔé¼┼Ñ, Nature (2003), 424: p. 1,013.
- Schroeter H, Holt R R, Orozco T J, Schmitz H H and Keen C L,├óÔé¼┼øMilk and absorption of dietary flavanols├óÔé¼┼Ñ, Nature (2003), 426: pp. 787├óÔé¼ÔÇ£788.
- Karim M, McCormick K and Kappagoda C T,├óÔé¼┼øEffects of cocoa extracts an endothelium-dependent relaxation├óÔé¼┼Ñ, J. Nutr. (2000), 130: pp. 2,105S├óÔé¼ÔÇ£2,108S.
- Schramm D D,Wang J F, Holt R R, Ensunsa J L, Gonsalves J L, Lazarus S A, Schmitz H H, German J B and Keen C L, ├óÔé¼┼øChocolate procyanidins decrease the leukotriene-prostacyclin ratio in humans and human aortic endothelial cells├óÔé¼┼Ñ, Am. J. Clin. Nutr. (2001), 73: pp. 36├óÔé¼ÔÇ£40.
- Fisher N D L, Hughes M, Gerhard-Herman M and Hollenberg N K, ├óÔé¼┼øFlavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans├óÔé¼┼Ñ, J. Hypertens (2003), 21: pp. 2,281├óÔé¼ÔÇ£2,286.
- Heiss C, Dejam A, Kleinbongard P, Schewe T, Sies H and Kelm M, ├óÔé¼┼øVascular effects of cocoa rich in flavan-3-ols├óÔé¼┼Ñ, JAMA (2003), 290(8): pp. 1,030├óÔé¼ÔÇ£1,031.
- Corretti M C, Anderson T J, Benjamin E J, Celermajer D, Charbonneau F, Creager M A, Deanfield J, Drexler H, Gerhard- Herman M, Herrington D,Vallance P, Vita J and Vogel R, ├óÔé¼┼øGuidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery-A report of the International Brachial Artery Reactivity Task Force├óÔé¼┼Ñ, J.Am. Coll. Cardiol. (2002), 39 (2): pp. 257├óÔé¼ÔÇ£265.
- Baron A M, Donnerstein R L, Samson R A, Baron J A, Padnick J N and Goldberg S J,├óÔé¼┼øHemodynamic and electrophysiologic effects of acute chocolate ingestion in young adults├óÔé¼┼Ñ, Am. J. Cardiol. (1999), 84: pp. 370├óÔé¼ÔÇ£373.
- Taubert D, Berkels R, Roesen R and Klaus W, ├óÔé¼┼øChocolate and blood pressure in elderly individuals with isolated systolic hypertension├óÔé¼┼Ñ, JAMA (2003), 290 (8): pp. 1,029├óÔé¼ÔÇ£1,030.
- Actis-Goretta L, Ottaviani J I, Keen C L and Fraga C G, ├óÔé¼┼øInhibition of angiotensin converting enzyme (ACE) activity by flavan-3-ols and procyanidins├óÔé¼┼Ñ, FEBS Letters (2003), 555: pp. 597├óÔé¼ÔÇ£600.
- Murphy K J, Chronopoulos A K, Singh I, Francis M A, Moriarty H, Pike M J,Turner A H, Mann N J and Sinclair A J,├óÔé¼┼øDietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function├óÔé¼┼Ñ, Am. J. Clin. Nutr. (2003), 77: pp.
- Pearson D A, Paglieroni T G, Rein D,Wun T, Schramm D D,Wang J F, Holt R R, Gosselin R, Schmitz H H and Keen C L,├óÔé¼┼øThe effects of flavonol-rich cocoa and aspirin on ex vivo platelet function├óÔé¼┼Ñ, Thromb. Res. (2002), 106: pp. 191├óÔé¼ÔÇ£197.
- Holt R R, Schramm D D, Keen C L, Lazarus S A and Schmitz H H,├óÔé¼┼øChocolate consumption and platelet function├óÔé¼┼Ñ, JAMA (2002), 287: pp. 2,212├óÔé¼ÔÇ£2,213.
- Rein D, Paglieroni T G, Pearson D A,Wun T, Schmitz H H, Gosselin R and Keen C L,├óÔé¼┼øCocoa and wine polyphenols modulate platelet activation and function├óÔé¼┼Ñ, J. Nutr. (2000), 130: pp. 2,120S├óÔé¼ÔÇ£2,126S.
- Rein D, Paglieroni T G,Wun T, Pearson D A, Schmitz H H, Gosselin R and Keen C L,├óÔé¼┼øCocoa inhibits platelet activation and function├óÔé¼┼Ñ, Am. J. Clin. Nutr. (2000), 72: pp. 30├óÔé¼ÔÇ£35.
- Kris-Etherton P M and Keen C L, ├óÔé¼┼øEvidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health├óÔé¼┼Ñ, Curr. Opin. Lipidol. (2002), 13: pp. 41├óÔé¼ÔÇ£49.
- Ikeda U, ├óÔé¼┼øInflammation and coronary artery disease├óÔé¼┼Ñ, Current Vascular Pharmacology (2003), 1 (1); pp. 65├óÔé¼ÔÇ£70.
- Mao T K, Powell J,Van de Water J, Keen C L, Schmitz H H, Hammerstone J F and Gershwin M E, ├óÔé¼┼øThe effect of cocoa procyanidins on the transcription and secretion of interleukin 1 in peripheral blood mononuclear cells├óÔé¼┼Ñ, Life Sci. (2000), 66 (15): pp. 1,377├óÔé¼ÔÇ£1,386.
- Sanbongi C, Suzuki N and Sakane T,├óÔé¼┼øPolyphenols in chocolate, which have antioxidant activity, modulate immune functions in humans in vitro├óÔé¼┼Ñ, Cell Immunol. (1997), 177: pp. 129├óÔé¼ÔÇ£136.
- Mackenzie G G, Carrasquedo F, Delfino J M, Keen C L, Fraga C G and Oteiza P I, ├óÔé¼┼øEpicatechin, catechin, and dimeric procyanidins inhibit PMA-induced NF-B activation at multiple steps in Jurkat T cells├óÔé¼┼Ñ, The FASEB J. (2004), 18: pp. 167├óÔé¼ÔÇ£169.
- Connor W E,├óÔé¼┼øHarbingers of coronary heart disease: dietary saturated fatty acids and cholesterol. Is chocolate benign because of its stearic acid content?├óÔé¼┼Ñ, Am. J. Clin. Nutr. (1999), 70: pp. 951├óÔé¼ÔÇ£952.
- Kris-Etherton P M and Mustad V A,├óÔé¼┼øChocolate feeding studies: a novel approach for evaluating the plasma lipid effects of stearic acid├óÔé¼┼Ñ, Am. J. Clin. Nutr. (1994), 60 (suppl): pp. 1,029S├óÔé¼ÔÇ£1,036S.
- Kris-Etherton P M, Derr J A, Mustad V A, Seligson F H and Pearson T A,├óÔé¼┼øEffects of a milk chocolate bar per day substituted for a high-carbohydrate snack in young men on an NCEP/AHA Step 1 diet├óÔé¼┼Ñ, Am. J. Clin. Nutr. (1994), 60 (suppl): pp. 1,037S├óÔé¼ÔÇ£1,042S.