Skip to main content Accessibility help

The role of polyphenolic compounds in the diet as inhibitors of platelet function

  • Gary P. Hubbard (a1) (a2), Siegfried Wolffram (a3), Julie A. Lovegrove (a1) and Jonathan M. Gibbins (a2)

Platelets play a substantial role in cardiovascular disease, and for many years there has been a search for dietary components that are able to inhibit platelet function and therefore decrease the risk of cardiovascular disease. Platelets can be inhibited by alcohol, dietary fats and some antioxidants, including a group of compounds, the polyphenols, found in fruits and vegetables. A number of these compounds have been shown to inhibit platelet function both in vitro and in vivo. In the present study the effects of the hydroxycinnamates and the flavonoid quercetin on platelet activation and cell signalling in vitro were investigated. The hydroxycinnamates inhibited platelet function, although not at levels that can be achieved in human plasma by dietary intervention. However, quercetin inhibited platelet aggregation at levels lower than those previously reported. Quercetin was also found to inhibit intracellular Ca mobilisation and whole-cell tyrosine protein phosphorylation in platelets, which are both processes essential for platelet activation. The effect of polyphenols on platelet aggregation in vivo was also investigated. Twenty subjects followed a low-polyphenol diet for 3 d before and also during supplementation. All subjects were supplemented with a polyphenol-rich meal every lunchtime for 5 d. Platelet aggregation and plasma flavonols were measured at baseline and after 5 d of dietary supplementation. Total plasma flavonoids increased significantly after the dietary intervention period (P=0·001). However, no significant changes in ex vivo platelet aggregation were observed. Further investigation of the effects of individual polyphenolic compounds on platelet function, both in vitro and in vivo, is required in order to elucidate their role in the relationship between diet and the risk of cardiovascular disease.

    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      The role of polyphenolic compounds in the diet as inhibitors of platelet function
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      The role of polyphenolic compounds in the diet as inhibitors of platelet function
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      The role of polyphenolic compounds in the diet as inhibitors of platelet function
      Available formats
Corresponding author
*Corresponding author: Mr Gary Hubbard, fax +44 118931 0180,
Hide All
Ader, P, Wessmann, A & Wolffram, S (2000) Bioavailability and metabolism of the flavonol quercetin in the pig. Free Radical Biology and Medicine 28, 10561067.
Aziz, AA, Edwards, CA, Lean, MEJ & Crozier, A (1998) Absorption and excretion of conjugated flavonols, including quercetin-4'-Obeta- glucoside and isorhamnetin-4'-O-beta- glucoside by human volunteers after the consumption of onions. Free Radical Research 29, 257269.
Beretz, A, Cazenave, JP & Anton, R (1982) Inhibition of aggregation and secretion of human-platelets by quercetin and other flavonoids–structure activity relationships. Agents and Actions 12, 382387.
Born, GVR (1962) Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 194, 927929.
Bourne, LC, Rice-Evans, CA (1998) Urinary detection of hydroxycinnamates and flavonoids in humans after high dietary intake of fruit. Free Radical Research 28, 429438.
Bourne, LC, Rice-Evans, CA (1999) Detecting and measuring bioavailability of phenolics and flavonoids in humans: Pharmacokinetics of urinary excretion of dietary ferulic acid. Methods in Enzymology 299, 91106.
Bravo, L (1998) Polyphenols: Chemistry, dietary sources, metabolism, and nutritional significance. Nutrition Reviews 56, 317333.
Calzada, C, Bruckdorfer, KR, Rice-Evans, CA (1997) The influence of antioxidant nutrients on platelet function in healthy volunteers. Atherosclerosis 128, 97105.
Cerbone, AM, Cirillo, F, Coppola, A, Rise, P, Stragliotto, E, Galli, C, Giordano, M, Tremoli, E, Di Minno, G (1999) Persistent impairment of platelet aggregation following cessation of a short-course dietary supplementation of moderate amounts of n -3 fatty acid ethyl esters. Thrombosis and Haemostasis 82, 128133.
Cicmil, M, Thomas, JM, Sage, T, Barry, FA, Leduc, M, Bon, C & Gibbins, JM (2000) Collagen, convulxin, and thrombin stimulate aggregation-independent tyrosine phosphorylation of CD31 in platelets. Evidence for the involvement of Src family kinases. Journal of Biological Chemistry 275, 2733927347.
Clifford, MN (1999) Chlorogenic acids and other cinnamates–nature, occurrence and dietary burden. Journal of the Science of Food and Agriculture 79, 362372.
Clifford, MN (2000) Chlorogenic acids and other cinnamates–nature, occurrence, dietary burden, absorption and metabolism. Journal of the Science of Food and Agriculture 80, 10331043.
Conquer, JA, Maiani, G, Azzini, E, Raguzzini, A & Holub, BJ (1998) Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects. Journal of Nutrition 128, 593597.
Freedman, JE, Farhat, JH, Loscalzo, J & Keaney, JF (1996) Platelet inhibition by alpha-tocopherol is independent of its antioxidant activity. Circulation 94 4146Abstr.
Gibbins, JM, Briddon, S, Shutes, A, van, Vugt, MJ de, Winkel, JGJ, Saito, T Watson, SP (1998) The p85 subunit of phosphatidylinositol 3-kinase associates with the Fc receptor gamma-chain and linker for activitor of T cells (LAT) in platelets stimulated by collagen and convulxin. Journal of Biological Chemistry 273, 3443734443.
Gibbins, JM, Okuma, M, Farndale, R, Barnes, M & Watson, SP (1997) Glycoprotein VI is the collagen receptor in platelets which underlies tyrosine phosphorylation of the Fc receptor gamma-chain. FEBS Letters 413, 255259.
Hertog, MGL, Feskens, EJM, Hollman, PCH, Katan, MB & Kromhout, D (1993) Dietary antioxidant flavonoids and risk of coronary heart disease–the Zutphen Elderly Study. Lancet 342, 10071011.
Hertog, MGL, Hollman, PCH & Katan, MB (1992) Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in the Netherlands. Journal of Agricultural and Food Chemistry 40, 23792383.
Hertog, MGL, Kromhout, D, Aravanis, C, Blackburn, H, Buzina, R, Fidanza, F, Giampaoli, S, Jansen, A, Menotti, A, Nedeljkovic, S, Pekkarinen, M, Simic, BS, Toshima, H, Feskens, EJM, Hollman, PCH & Katan, MB (1995) Flavonoid intake and long-term risk of coronary heart-disease and cancer in the Seven Countries Study. Archives of Internal Medicine 155, 381386.
Hertog, MGL, Sweetman, PM, Fehily, AM, Elwood, PC & Kromhout, D (1997) Antioxidant flavonols and ischemic heart disease in a Welsh population of men: The Caerphilly Study. American Journal of Clinical Nutrition 65, 14891494.
Hoffbrand, A & Pettit, J (1995) Essential Haematology London Blackwell Science.
Hollman, PCH & Arts, ICW (2000) Flavonols, flavones and flavanols–nature, occurrence and dietary burden. Journal of the Science of Food and Agriculture 80, 10811093.
Hollman, PCH, Bijsman, M, van, Gameren, Y, Cnossen, EPJ de, Vries, JHM Katan, MB (1999) The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Radical Research 31, 569573.
Hollman, PCH, vanTrijp, JMP & Buysman, M (1996) Fluorescence detection of flavonols in HPLC by postcolumn chelation with aluminum. Analytical Chemistry 68, 35113515.
Hollman, PCH, van, Trijp, JMP, Buysman, M, Van, der, Gaag, MS, Mengelers, MJB, deVries, JHM Katan, MB (1997) Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Letters 418, 152156.
Holvoet, P & Collen, D (1994) Oxidized lipoproteins in atherosclerosis and thrombosis. FASEB Journal 8, 12791284.
Janssen, P, Mensink, RP, Cox, FJJ, Harryvan, JL, Hovenier, R, Hollman, PCH & Katan, MB (1998) Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study. American Journal of Clinical Nutrition 67, 255262.
Keevil, JG, Osman, HE, Reed, JD & Folts, JD (2000) Grape juice, but not orange juice or grapefruit juice, inhibits human platelet aggregation. Journal of Nutrition 130, 5356.
Knekt, P, Reunanen, A, Jarvinen, R, Seppanen, R, Heliovaara, M & Aromaa, A (1994) Antioxidant vitamin intake and coronary mortality in a longitudinal population study. American Journal of Epidemiology 139, 11801189.
Kroon, PA & Williamson, G (1999) Hydroxycinnamates in plants and food: current and future perspectives. Journal of the Science of Food and Agriculture 79, 355361.
Landolfi, R, Mower, RL & Steiner, M (1984) Modification of platelet-function and arachidonic-acid metabolism by bioflavonoids–structure activity relations. Biochemical Pharmacology 33, 15251530.
Liu, W & Liang, NC (2000) Inhibitory effect of disodium qurecetin-7, 4'-disulfate on aggregation of pig platelets induced by thrombin and its mechanism. Acta Pharmacologica Sinica 21, 737741.
McAnlis, GT, McEneny, J, Pearce, J & Young, IS (1999) Absorption and antioxidant effects of quercetin from onions, in man. European Journal of Clinical Nutrition 53, 9296.
O'Reilly, JD, Sanders, TAB & Wiseman, H (2000) Flavonoids protect against oxidative damage to LDL in vitro: Use in selection of a flavonoid rich diet and relevance to LDL oxidation resistance ex vivo?. Free Radical Research 33, 419426.
Poole, A, Gibbins, JM, Turner, M, van, Vugt, MJ, de Winkel, JGJ, Saito, T, Tybulewicz, VLJ, Watson SP (1997) The Fc receptor gamma-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen. EMBO Journal 16, 23332341.
Radtke, J, Linseisen, J & Wolfram, G (1998) Phenolic acid intake of adults in a Bavarian subgroup of the national food consumption survey. Zeitschrift fur Ernahrungswissenschaft 37, 190197.
Rimm, EB, Katan, MB, Ascherio, A, Stampfer, MJ & Willett, WC (1996) Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Annals of Internal Medicine 125, 384389.
Russo, P, Tedesco, I, Russo, M, Russo, GL, Venezia, A & Cicala, C (2001) Effects of de-alcoholated red wine and its phenolic fractions on platelet aggregation. Nutrition Metabolism and Cardiovascular Diseases 11, 2529.
Salonen, JT, Salonen, R, Seppanen, K, Rintakiikka, S, Kuukka, M, Korpela, H, Alfthan, G, Kantola, M & Schalch, W (1991) Effects of antioxidant supplementation on platelet-function–a randomized pair-matched, placebo-controlled, double-blind trial in men with low antioxidant status. American Journal of Clinical Nutrition 53, 12221229.
Serebruany, VL, Lowry, DR, Fuzailov, SY, Levine, DJ, O'Connor, CM & Gurbel, PA (2000) Moderate alcohol consumption is associated with decreased platelet activity in patients presenting with acute myocardial infarction. Journal of Thrombosis and Thrombolysis 9, 229234.
Smith, JB, Selak, MA, Dangelmaier, C & Daniel, JL (1992) Cytosolic calcium as a second messenger for collagen-induced platelet responses. Biochemical Journal 288, 925929.
Thorogood, M (1997) Do vegetables and fruit protect against coronary heart disease? Studies among vegetarians. In Preventing Coronary Heart Disease: The Role of Antioxidants, Vegetables and Fruit: Report of an Expert Meeting 2937 [Rogers, L, Sharp, I, editor]. London: The Stationery Office.
Tzeng, SH, Ko, WC, Ko, FN & Teng, CM (1991) Inhibition of platelet-aggregation by some flavonoids. Thrombosis Research 64, 91100.
US Department of Agriculture (1992) The Food Pyramid Guide: A Guide to Food Choice. Home and Garden Bulletinno 252 Washington, DC: US Department of Agriculture.
Vinson, J (1998) Flavonoids in foods as in vitro and in vivo anti-oxidants. Flavonoids in the Living System New York: Plenum Press.
You, KM, Jong, HG & Kim, HP (1999) Inhibition of cyclooxy-genase/lipoxygenase from human platelets by polyhydroxylated/methoxylated flavonoids isolated from medicinal plants. Archives of Pharmacal Research 22, 1824.
Zhao, XY, Gu, ZL, Attele, AS & Yuan, CS (1999) Effects of quercetin on the release of endothelin, prostacyclin and tissue plasminogen activator from human endothelial cells in culture. Journal of Ethnopharmacology 67, 279285.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Proceedings of the Nutrition Society
  • ISSN: 0029-6651
  • EISSN: 1475-2719
  • URL: /core/journals/proceedings-of-the-nutrition-society
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed