Micronutrients and Supplements Info: Bioflavonoids

Bioflavonoids

Description

Bioflavonoids or flavonoids form a large group of thousands of different polyphenolic compounds, most of which having potent antioxidant properties. They are ubiquitous in plants, especially in the leaves, bark, roots, flowers, and seeds.

Bioflavonoids are divided in eight main groups:

Flavan-3-ols (e.g., catechins - in green tea)

Flavonols (e.g., quercetin, myricitin – in onions and elderberry)

Flavones (e.g., luteolin – in parsley)

Flavonones (e.g., hesperetin, in citrus fruit)

Chalcones

Dihydroflavonols

Isoflavones (in soybean)

Proanthocyanidins (in plums) and Anthocyanins (in elderberry)

Function

Most of the effects of bi-flavonoids are the result of their various and potent antioxidant properties. They act as scavengers of free radicals, have anti-tumour development properties, increase the resistance of capillary vessels, decrease thrombotic tendency (anti-platelet aggregation effect), inhibit the release of histamine, just to name a few.

Sources

Flavonoids are ubiquitous in plants. Good sources are apples, onions, tea, white part of citrus fruit and vegetables, chocolate and red wine.

Toxicity

None reported

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Additional Sources of Information:

Flavonoids - Wikipedia

Flavonoids - Linus Pauling Institute

Scientific References

Books

PDR for Nutritional Supplements. Hendler SS, Rorvik DR, eds. Montvale: Medical Economics Company, Inc; 2001.

Scientific articles

A phase II trial of green tea in the treatment of patients with androgen independent metastatic prostate carcinoma. Jatoi A, Ellison N, Burch PA, et al. Cancer. 2003;97(6):1442-1446.

Activation of endothelial nitric-oxide synthase by the p38 MAPK in response to black tea polyphenols. Anter E, Thomas SR, Schulz E, Shapira OM, Vita JA, Keaney JF, Jr. J Biol Chem. 2004;279(45):46637-46643.

Acute effects of ingestion of black tea on postprandial platelet aggregation in human subjects. Hodgson JM, Puddey IB, Burke V, Beilin LJ, Mori TA, Chan SY. Br J Nutr. 2002;87(2):141-145.

Anthocyanin composition of Cabernet Sauvignon and Tempranillo grapes at different stages of ripening. Ryan JM, Revilla E. J Agric Food Chem. 2003;51(11):3372-3378.

Anthocyanins, phenolics, and antioxidant capacity in diverse small fruits: vaccinium, rubus, and ribes. Moyer RA, Hummer KE, Finn CE, Frei B, Wrolstad RE. J Agric Food Chem. 2002;50(3):519-525.

Antioxidant activity of tea polyphenols in vivo: evidence from animal studies. Frei B, Higdon JV. J Nutr. 2003;133(10):3275S-3284S.

Antioxidant flavonols and coronary heart disease risk. Hertog MG, Feskens EJ, Kromhout D. Lancet. 1997;349(9053):699.

Antioxidant flavonols and ischemic heart disease in a Welsh population of men: the Caerphilly Study. Hertog MG, Sweetnam PM, Fehily AM, Elwood PC, Kromhout D. Am J Clin Nutr. 1997;65(5):1489-1494.

Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Manach C, Williamson G, Morand C, Scalbert A, Remesy C. Am J Clin Nutr. 2005;81(1 Suppl):230S-242S.

Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model. Joseph JA, Denisova NA, Arendash G, et al. Nutr Neurosci. 2003;6(3):153-162.

Blueberry supplemented diet: effects on object recognition memory and nuclear factor-kappa B levels in aged rats. Goyarzu P, Malin DH, Lau FC, et al. Nutr Neurosci. 2004;7(2):75-83.

Brain aging and midlife tofu consumption. White LR, Petrovitch H, Ross GW, et al. J Am Coll Nutr. 2000;19(2):242-255.

Catechin content of 18 teas and a green tea extract supplement correlates with the antioxidant capacity. Henning SM, Fajardo-Lira C, Lee HW, Youssefian AA, Go VL, Heber D. Nutr Cancer. 2003;45(2):226-235.

Cell-cycle dysregulation and anticancer therapy. Stewart ZA, Westfall MD, Pietenpol JA. Trends Pharmacol Sci. 2003;24(3):139-145.

Characterization of major anthocyanins and the color of red-fleshed Budd Blood orange (Citrus sinensis). Lee HS. J Agric Food Chem. 2002;50(5):1243-1246.

Chronic consumption of flavanol-rich cocoa improves endothelial function and decreases vascular cell adhesion molecule in hypercholesterolemic postmenopausal women. Wang-Polagruto JF, Villablanca AC, Polagruto JA, et al. J Cardiovasc Pharmacol. 2006;47 Suppl 2:S177-186; discussion S206-179.

Cocoa and wine polyphenols modulate platelet activation and function. Rein D, Paglieroni TG, Pearson DA, et al. J Nutr. 2000;130(8S Suppl):2120S-2126S.

Cocoa inhibits platelet activation and function. Rein D, Paglieroni TG, Wun T, et al. Am J Clin Nutr. 2000;72(1):30-35.

Common features in the pathways of absorption and metabolism of flavonoids. Williamson G. In: Meskin MS, R. BW, Davies AJ, Lewis DS, Randolph RK, eds. Phytochemicals: Mechanisms of Action. Boca Raton: CRC Press; 2004:21-33.

Concentrations of proanthocyanidins in common foods and estimations of normal consumption. Gu L, Kelm MA, Hammerstone JF, et al. J Nutr. 2004;134(3):613-617.

Consumption of black tea and cancer risk: a prospective cohort study. Goldbohm RA, Hertog MG, Brants HA, van Poppel G, van den Brandt PA. J Natl Cancer Inst. 1996;88(2):93-100.

Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon? Lotito SB, Frei B. Free Radic Biol Med. 2006;41(12):1727-1746.

Contrasting influences of glucuronidation and O-methylation of epicatechin on hydrogen peroxide-induced cell death in neurons and fibroblasts. Spencer JP, Schroeter H, Crossthwaithe AJ, Kuhnle G, Williams RJ, Rice-Evans C. Free Radic Biol Med. 2001;31(9):1139-1146.

C-reactive protein and other inflammatory risk markers in acute coronary syndromes. Blake GJ, Ridker PM. J Am Coll Cardiol. 2003;41(4 Suppl S):37S-42S.

Dark chocolate inhibits platelet aggregation in healthy volunteers. Innes AJ, Kennedy G, McLaren M, Bancroft AJ, Belch JJ. Platelets. 2003;14(5):325-327.

Dietary antioxidants and Parkinson disease. de Rijk MC, Breteler MM, den Breeijen JH, et al. The Rotterdam Study. Arch Neurol. 1997;54(6):762-765.

Dietary catechins and cancer incidence among postmenopausal women: the Iowa Women's Health Study (United States). Arts IC, Jacobs DR, Jr., Gross M, Harnack LJ, Folsom AR. Cancer Causes Control. 2002;13(4):373-382.

Dietary catechins and epithelial cancer incidence: the Zutphen elderly study. Arts IC, Hollman PC, Bueno De Mesquita HB, Feskens EJ, Kromhout D. Int J Cancer. 2001;92(2):298-302.

Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function. Murphy KJ, Chronopoulos AK, Singh I, et al. Am J Clin Nutr. 2003;77(6):1466-1473.

Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women. Yochum L, Kushi LH, Meyer K, Folsom AR. Am J Epidemiol. 1999;149(10):943-949.

Dietary flavonoids and cancer risk in the Zutphen Elderly Study. Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Nutr Cancer. 1994;22(2):175-184.

Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the Zutphen study. Keli SO, Hertog MG, Feskens EJ, Kromhout D. Arch Intern Med. 1996;156(6):637-642.

Dietary flavonoids: bioavailability, metabolic effects, and safety. Ross JA, Kasum CM. Annu Rev Nutr. 2002;22:19-34.

Dietary intake of antioxidants and risk of Alzheimer disease. Engelhart MJ, Geerlings MI, Ruitenberg A, et al. JAMA. 2002;287(24):3223-3229.

Dietary intakes of flavonols and flavones and coronary heart disease in US women. Lin J, Rexrode KM, Hu F, et al. Am J Epidemiol. 2007;165(11):1305-1313.

Dietary soy isoflavones and estrone protect ovariectomized ERalphaKO and wild-type mice from carcinogen-induced colon cancer. Guo JY, Li X, Browning JD, Jr., et al. J Nutr. 2004;134(1):179-182.

Effect of acute and chronic tea consumption on platelet aggregation in patients with coronary artery disease. Duffy SJ, Vita JA, Holbrook M, Swerdloff PL, Keaney JF, Jr. Arterioscler Thromb Vasc Biol. 2001;21(6):1084-1089.

Effect of flavonoids and vitamin E on cyclooxygenase-2 (COX-2) transcription. O'Leary KA, de Pascual-Tereasa S, Needs PW, Bao YP, O'Brien NM, Williamson G. Mutat Res. 2004;551(1-2):245-254.

Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: a randomized controlled trial. Kreijkamp-Kaspers S, Kok L, Grobbee DE, et al. JAMA. 2004;292(1):65-74.

Effect of tea and other dietary factors on iron absorption. Zijp IM, Korver O, Tijburg LB. Crit Rev Food Sci Nutr. 2000;40(5):371-398.

Effects of cacao liquor proanthocyanidins on PhIP-induced mutagenesis in vitro, and in vivo mammary and pancreatic tumorigenesis in female Sprague-Dawley rats. Yamagishi M, Natsume M, Osakabe N, et al. Cancer Lett. 2002;185(2):123-130.

Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. Ramos S. J Nutr Biochem. 2007;18(7):427-442.

Effects of flavonoid-rich beverages on prostacyclin synthesis in humans and human aortic endothelial cells: association with ex vivo platelet function. Polagruto JA, Schramm DD, Wang-Polagruto JF, Lee L, Keen CL. J Med Food. 2003;6(4):301-308.

Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. Taubert D, Roesen R, Lehmann C, Jung N, Schomig E. JAMA. 2007;298(1):49-60.

Effects of phenolics on vascular endothelial function. Curr Opin Lipidol. Duffy SJ, Vita JA. 2003;14(1):21-27.

Effects of tea polyphenols on signal transduction pathways related to cancer chemoprevention. Hou Z, Lambert JD, Chin KV, Yang CS. Mutat Res. 2004;555(1-2):3-19.

Effects of tea, decaffeinated tea, and caffeine on UVB light-induced complete carcinogenesis in SKH-1 mice: demonstration of caffeine as a biologically important constituent of tea. Huang MT, Xie JG, Wang ZY, et al. Cancer Res. 1997;57(13):2623-2629.

Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study. Janssen K, Mensink RP, Cox FJ, et al. Am J Clin Nutr. 1998;67(2):255-262.

Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. Ramassamy C. Eur J Pharmacol. 2006;545(1):51-64.

Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Schroeter H, Heiss C, Balzer J, et al. Proc Natl Acad Sci U S A. 2006;103(4):1024-1029.

Epigallocatechin-3-gallate inhibits epidermal growth factor receptor signaling pathway. Evidence for direct inhibition of ERK1/2 and AKT kinases. Sah JF, Balasubramanian S, Eckert RL, Rorke EA. J Biol Chem. 2004;279(13):12755-12762.

Flavones mitigate tumor necrosis factor-alpha-induced adhesion molecule upregulation in cultured human endothelial cells: role of nuclear factor-kappa B. Choi JS, Choi YJ, Park SH, Kang JS, Kang YH. J Nutr. 2004;134(5):1013-1019.

Flavonoid inhibition of platelet procoagulant activity and phosphoinositide synthesis. Bucki R, Pastore JJ, Giraud F, Sulpice JC, Janmey PA. J Thromb Haemost. 2003;1(8):1820-1828.

Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Mink PJ, Scrafford CG, Barraj LM, et al. Am J Clin Nutr. 2007;85(3):895-909.

Flavonoid intake and cognitive decline over a 10-year period. Letenneur L, Proust-Lima C, Le Gouge A, Dartigues JF, Barberger-Gateau P. Am J Epidemiol. 2007;165(12):1364-1371.

Flavonoid intake and risk of cancer: a prospective cohort study. Goldbohm RA, Van den Brandt PA, Hertog MG, Brants HA, Van Poppel G. Am J Epidemiol. 1995;41:s61.

Flavonoid intake and risk of chronic diseases. Knekt P, Kumpulainen J, Jarvinen R, et al. Am J Clin Nutr. 2002;76(3):560-568.

Flavonoid intake and the risk of cardiovascular disease in women. Sesso HD, Gaziano JM, Liu S, Buring JE. Am J Clin Nutr. 2003;77(6):1400-1408.

Flavonoid permeability across an in situ model of the blood-brain barrier. Youdim KA, Qaiser MZ, Begley DJ, Rice-Evans CA, Abbott NJ. Free Radic Biol Med. 2004;36(5):592-604.

Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults. Engler MB, Engler MM, Chen CY, et al. J Am Coll Nutr. 2004;23(3):197-204.

Flavonoids and the aging brain. Schmitt-Schillig S, Schaffer S, Weber CC, Eckert GP, Muller WE. J Physiol Pharmacol. 2005;56 Suppl 1:23-36.

Flavonoids as peroxynitrite scavengers: the role of the hydroxyl groups. Heijnen CG, Haenen GR, van Acker FA, van der Vijgh WJ, Bast A. Toxicol In Vitro. 2001;15(1):3-6.

Flavonoids inhibit VEGF/bFGF-induced angiogenesis in vitro by inhibiting the matrix-degrading proteases. Kim MH. J Cell Biochem. 2003;89(3):529-538.

Flavonoids: antioxidants or signalling molecules? Williams RJ, Spencer JP, Rice-Evans C. Free Radic Biol Med. 2004;36(7):838-849.

Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation. Keevil JG, Osman HE, Reed JD, Folts JD. J Nutr. 2000;130(1):53-56.

Green tea epigallocatechin-3-gallate inhibits platelet signalling pathways triggered by both proteolytic and non-proteolytic agonists. Deana R, Turetta L, Donella-Deana A, et al. Thromb Haemost. 2003;89(5):866-874.

Green tea extracts decrease carcinogen-induced mammary tumor burden in rats and rate of breast cancer cell proliferation in culture. Kavanagh KT, Hafer LJ, Kim DW, et al. J Cell Biochem. 2001;82(3):387-398.

Growth inhibition and cell cycle arrest effects of epigallocatechin gallate in the NBT-II bladder tumour cell line. Chen JJ, Ye ZQ, Koo MW. BJU Int. 2004;93(7):1082-1086.

Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Liu RH. Am J Clin Nutr. 2003;78(3 Suppl):517S-520S.

Individual and interactive effects of apigenin analogs on G2/M cell-cycle arrest in human colon carcinoma cell lines. Wang W, VanAlstyne PC, Irons KA, Chen S, Stewart JW, Birt DF. Nutr Cancer. 2004;48(1):106-114.

Induction of human UDP-glucuronosyltransferase UGT1A1 by flavonoids-structural requirements. Walle UK, Walle T. Drug Metab Dispos. 2002;30(5):564-569.

Induction of xenobiotic enzymes by the MAP kinase pathway and the antioxidant or electrophile response element (ARE/EpRE). Kong AN, Owuor E, Yu R, et al. Drug Metab Rev. 2001;33(3-4):255-271.

Inhibition of inducible isoforms of cyclooxygenase and nitric oxide synthase by flavonoid hesperidin in mouse macrophage cell line. Sakata K, Hirose Y, Qiao Z, Tanaka T, Mori H. Cancer Lett. 2003;199(2):139-145.

Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. Gupta S, Hastak K, Ahmad N, Lewin JS, Mukhtar H. Proc Natl Acad Sci U S A. 2001;98(18):10350-10355.

Inhibitory effect of dietary flavonol quercetin on 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Balasubramanian S, Govindasamy S. Carcinogenesis. 1996;17(4):877-879.

Inhibitory effects and toxicity of green tea polyphenols for gastrointestinal carcinogenesis. Yamane T, Nakatani H, Kikuoka N, et al. Cancer. 1996;77(8 Suppl):1662-1667.

Inhibitory effects of epigallocatechin-3-gallate on N-nitrosomethylbenzylamine-induced esophageal tumorigenesis in F344 rats. Li ZG, Shimada Y, Sato F, et al. Int J Oncol. 2002;21(6):1275-1283.

Intake of flavonoids and risk of dementia. Commenges D, Scotet V, Renaud S, Jacqmin-Gadda H, Barberger-Gateau P, Dartigues JF. Eur J Epidemiol. 2000;16(4):357-363.

Intake of flavonoids, carotenoids, vitamins C and E, and risk of stroke in male smokers. Hirvonen T, Virtamo J, Korhonen P, Albanes D, Pietinen P. Stroke. 2000;31(10):2301-2306.

Intake of flavonols and flavones and risk of coronary heart disease in male smokers. Hirvonen T, Pietinen P, Virtanen M, et al. Epidemiology. 2001;12(1):62-67.

Intake of specific carotenoids and flavonoids and the risk of lung cancer in women in Barcelona, Spain. Garcia-Closas R, Agudo A, Gonzalez CA, Riboli E. Nutr Cancer. 1998;32(3):154-158.

Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant activity. Mira L, Fernandez MT, Santos M, Rocha R, Florencio MH, Jennings KR. Free Radic Res. 2002;36(11):1199-1208.

Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam Study. Geleijnse JM, Launer LJ, Van der Kuip DA, Hofman A, Witteman JC. Am J Clin Nutr. 2002;75(5):880-886.

Luteolin inhibits vascular endothelial growth factor-induced angiogenesis; inhibition of endothelial cell survival and proliferation by targeting phosphatidylinositol 3'-kinase activity. Bagli E, Stefaniotou M, Morbidelli L, et al. Cancer Res. 2004;64(21):7936-7946.

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Mechanisms and applications of non-steroidal anti-inflammatory drugs in the chemoprevention of cancer. Steele VE, Hawk ET, Viner JL, Lubet RA. Mutat Res. 2003;523-524:137-144.

Mechanisms of cancer prevention by tea constituents. Lambert JD, Yang CS. J Nutr. 2003;133(10):3262S-3267S.

Metabolism of dietary soy isoflavones to equol by human intestinal microflora--implications for health. Yuan JP, Wang JH, Liu X. Mol Nutr Food Res. 2007;51(7):765-781.

Midlife dietary intake of antioxidants and risk of late-life incident dementia: the Honolulu-Asia Aging Study. Laurin D, Masaki KH, Foley DJ, White LR, Launer LJ. Am J Epidemiol. 2004;159(10):959-967.

Modulation of pro-survival Akt/protein kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability. Spencer JP, Rice-Evans C, Williams RJ. J Biol Chem. 2003;278(37):34783-34793.

No difference in platelet activation or inflammation markers after diets rich or poor in vegetables, berries and apple in healthy subjects. Freese R, Vaarala O, Turpeinen AM, Mutanen M. Eur J Nutr. 2004;43(3):175-182.

Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines. Haddad AQ, Venkateswaran V, Viswanathan L, Teahan SJ, Fleshner NE, Klotz LH. Prostate Cancer Prostatic Dis. 2006;9(1):68-76.

On the ability of four flavonoids, baicilein, luteolin, naringenin, and quercetin, to suppress the Fenton reaction of the iron-ATP complex. Cheng IF, Breen K. Biometals. 2000;13(1):77-83.

Overview of dietary flavonoids: nomenclature, occurrence and intake. Beecher GR. J Nutr. 2003;133(10):3248S-3254S.

Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Chow HH, Cai Y, Hakim IA, et al. Clin Cancer Res. 2003;9(9):3312-3319.

Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Ferry DR, Smith A, Malkhandi J, et al. Clin Cancer Res. 1996;2(4):659-668.

Phase I trial of oral green tea extract in adult patients with solid tumors. Pisters KM, Newman RA, Coldman B, et al. J Clin Oncol. 2001;19(6):1830-1838.

Polyphenols: food sources and bioavailability. Manach C, Scalbert A, Morand C, Remesy C, Jimenez L. Am J Clin Nutr. 2004;79(5):727-747.

Protective effect of flavonoids against aging- and lipopolysaccharide-induced cognitive impairment in mice. Patil CS, Singh VP, Satyanarayan PS, Jain NK, Singh A, Kulkarni SK. Pharmacology. 2003;69(2):59-67.

Psychological assessment of the effects of treatment with phytoestrogens on postmenopausal women: a randomized, double-blind, crossover, placebo-controlled study. Casini ML, Marelli G, Papaleo E, Ferrari A, D'Ambrosio F, Unfer V. Fertil Steril. 2006;85(4):972-978.

Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease. Stein JH, Keevil JG, Wiebe DA, Aeschlimann S, Folts JD. Circulation. 1999;100(10):1050-1055.

Quantitation of polyphenols in different apple varieties. Vrhovsek U, Rigo A,

Tonon D, Mattivi F. J Agric Food Chem. 2004;52(21):6532-6538.

Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial. Shoskes DA, Zeitlin SI, Shahed A, Rajfer J. Urology. 1999;54(6):960-963.

Quercetin intake and the incidence of cerebrovascular disease. Knekt P, Isotupa S, Rissanen H, et al. Eur J Clin Nutr. 2000;54(5):415-417.

Quercetin suppresses proinflammatory cytokines production through MAP kinases andNF-kappaB pathway in lipopolysaccharide-stimulated macrophage. Cho SY, Park SJ, Kwon MJ, et al. Mol Cell Biochem. 2003;243(1-2):153-160.

Regular ingestion of black tea improves brachial artery vasodilator function. Hodgson JM, Puddey IB, Burke V, Watts GF, Beilin LJ. Clin Sci (Lond). 2002;102(2):195-201.

Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Rimm EB, Katan MB, Ascherio A, Stampfer MJ, Willett WC.

Ann Intern Med. 1996;125(5):384-389.

Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. Joseph JA, Shukitt-Hale B, Denisova NA, et al. J Neurosci. 1999;19(18):8114-8121.

Role of oxidative modifications in atherosclerosis. Stocker R, Keaney JF, Jr. Physiol Rev. 2004;84(4):1381-1478.

Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Freedman JE, Parker C, 3rd, Li L, et al. Circulation. 2001;103(23):2792-2798.

Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. Duffy SJ, Keaney JF, Jr., Holbrook M, et al. Circulation. 2001;104(2):151-156.

Superoxide radical scavenging activity of the major polyphenols in fresh plums. Chun OK, Kim DO, Lee CY. J Agric Food Chem. 2003;51(27):8067-8072.

Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial. Balzer J, Rassaf T, Heiss C, et al. J Am Coll Cardiol. 2008;51(22):2141-2149.

Tea and tea polyphenols inhibit cell hyperproliferation, lung tumorigenesis, and tumor progression. Yang CS, Yang GY, Landau JM, Kim S, Liao J. Exp Lung Res. 1998;24(4):629-639.

Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions. Higdon JV, Frei B. Crit Rev Food Sci Nutr. 2003;43(1):89-143.

Tea consumption and cardiovascular disease: effects on endothelial function. Vita JA. J Nutr. 2003;133(10):3293S-3297S.

The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones. Setchell KD, Brown NM, Lydeking-Olsen E. J Nutr. 2002;132(12):3577-3584.

The role of polyphenolic compounds in the diet as inhibitors of platelet function. Hubbard GP, Wolffram S, Lovegrove JA, Gibbins JM. Proc Nutr Soc. 2003;62(2):469-478.

The tea flavonoid epigallocatechin-3-gallate reduces cytokine-induced VCAM-1 expression and monocyte adhesion to endothelial cells. Ludwig A, Lorenz M, Grimbo N, et al. Biochem Biophys Res Commun. 2004;316(3):659-665.

USDA database for the flavonoid content of selected foods. U.S. Department of Agriculture. foods. March 2003.

USDA database for the proanthocyanidin content of selected foods. U.S. Department of Agriculture. August, 2004. .