American Journal of Clinical Nutrition, Vol 67, 255-262, Copyright © 1998 by The American Society for Clinical Nutrition, Inc

ORIGINAL RESEARCH COMMUNICATIONS

Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: results from an in vitro and a dietary supplement study

K Janssen, RP Mensink, FJ Cox, JL Harryvan, R Hovenier, PC Hollman and MB Katan
Department of Human Nutrition, Agricultural University, Wageningen, The Netherlands.

Intake of dietary flavonols and flavones was inversely associated with risk for cardiovascular disease in several epidemiologic studies. This may have been due to effects on hemostasis because flavonoids have been reported to inhibit platelet aggregation in vitro. We indeed found that 2500 micromol/L of the flavonol quercetin and the flavone apigenin significantly inhibited collagen- and ADP-induced aggregation in platelet-rich plasma and washed platelets by approximately 80-97%. However, lower concentrations, such as might occur in vivo, had no effect. To test this in vivo we fed 18 healthy volunteers 220 g onions/d providing 114 mg quercetin/d, 5 g dried parsley/d providing 84 mg apigenin/d, or a placebo for 7 d each in a randomized crossover experiment with each treatment period lasting 2 wk. Onion consumption raised mean plasma quercetin concentrations to 1.5 micromol/L; plasma apigenin could not be measured. No significant effects of onions or parsley were found on platelet aggregation, thromboxane B2 production, factor VII, or other hemostatic variables. We conclude that the antiaggregatory effects of flavonoids seen in vitro are due to concentrations that cannot be attained in vivo. Effects of dietary flavonols and flavones on cardiovascular risk are possibly not mediated by hemostatic variables.

This article has been cited by other articles:

				S. B. van Waalwijk van Doorn-Khosrovani, J. Janssen, L. M. Maas, R. W.L. Godschalk, J. G. Nijhuis, and F. J. van Schooten Dietary flavonoids induce MLL translocations in primary human CD34+ cells Carcinogenesis, August 1, 2007; 28(8): 1703 - 1709. [Abstract] [Full Text] [PDF]

				J. W. Erdman Jr., D. Balentine, L. Arab, G. Beecher, J. T. Dwyer, J. Folts, J. Harnly, P. Hollman, C. L. Keen, G. Mazza, et al. Flavonoids and Heart Health: Proceedings of the ILSI North America Flavonoids Workshop, May 31-June 1, 2005, Washington, DC J. Nutr., March 1, 2007; 137(3): 718S - 737S. [Abstract] [Full Text] [PDF]

				N. O'Kennedy, L. Crosbie, M. van Lieshout, J. I Broom, D. J Webb, and A. K Duttaroy Effects of antiplatelet components of tomato extract on platelet function in vitro and ex vivo: a time-course cannulation study in healthy humans. Am. J. Clinical Nutrition, September 1, 2006; 84(3): 570 - 579. [Abstract] [Full Text] [PDF]

				P. Pignatelli, S. Di Santo, B. Buchetti, V. Sanguigni, A. Brunelli, and F. Violi Polyphenols enhance platelet nitric oxide by inhibiting protein kinase C-dependent NADPH oxidase activation: effect on platelet recruitment FASEB J, June 1, 2006; 20(8): 1082 - 1089. [Abstract] [Full Text] [PDF]

				G. Williamson and C. Manach Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies Am. J. Clinical Nutrition, January 1, 2005; 81(1): 243S - 255S. [Abstract] [Full Text] [PDF]

				M. Lim, K. McKenzie, A. D. Floyd, E. Kwon, and P. L. Zeitlin Modulation of {Delta}F508 Cystic Fibrosis Transmembrane Regulator Trafficking and Function with 4-Phenylbutyrate and Flavonoids Am. J. Respir. Cell Mol. Biol., September 1, 2004; 31(3): 351 - 357. [Abstract] [Full Text] [PDF]

				K. W. Lee and G. Y. H. Lip Effects of Lifestyle on Hemostasis, Fibrinolysis, and Platelet Reactivity: A Systematic Review Arch Intern Med, October 27, 2003; 163(19): 2368 - 2392. [Abstract] [Full Text] [PDF]

				S. Rajaram The effect of vegetarian diet, plant foods, and phytochemicals on hemostasis and thrombosis Am. J. Clinical Nutrition, September 1, 2003; 78(3): 552S - 558. [Abstract] [Full Text] [PDF]

				G. I. Togna, A. R. Togna, M. Franconi, C. Marra, and M. Guiso Olive Oil Isochromans Inhibit Human Platelet Reactivity J. Nutr., August 1, 2003; 133(8): 2532 - 2536. [Abstract] [Full Text] [PDF]

				D. Shanmuganayagam, M. R. Beahm, H. E. Osman, C. G. Krueger, J. D. Reed, and J. D. Folts Grape Seed and Grape Skin Extracts Elicit a Greater Antiplatelet Effect When Used in Combination than When Used Individually in Dogs and Humans J. Nutr., December 1, 2002; 132(12): 3592 - 3598. [Abstract] [Full Text] [PDF]

				A. Bovy, R. de Vos, M. Kemper, E. Schijlen, M. Almenar Pertejo, S. Muir, G. Collins, S. Robinson, M. Verhoeyen, S. Hughes, et al. High-Flavonol Tomatoes Resulting from the Heterologous Expression of the Maize Transcription Factor Genes LC and C1 PLANT CELL, October 1, 2002; 14(10): 2509 - 2526. [Abstract] [Full Text] [PDF]

				F. Violi, P. Pignatelli, F.M. Pulcinelli, J. E. Freedman, C. Parker III, L. Li, J. A. Perlman, B. Frei, V. Ivanov, L. R. Deak, et al. Synergism Among Flavonoids in Inhibiting Platelet Aggregation and H2O2 Production Response Circulation, February 26, 2002; 105 (8): e53 - e53. [Full Text] [PDF]

				K. J. Anderson, S. S. Teuber, A. Gobeille, P. Cremin, A. L. Waterhouse, and F. M. Steinberg Walnut Polyphenolics Inhibit In Vitro Human Plasma and LDL Oxidation J. Nutr., November 1, 2001; 131(11): 2837 - 2842. [Abstract] [Full Text] [PDF]

				W. H. Briggs, J. D. Folts, H. E. Osman, and I. L. Goldman Administration of Raw Onion Inhibits Platelet-Mediated Thrombosis in Dogs J. Nutr., October 1, 2001; 131(10): 2619 - 2622. [Abstract] [Full Text] [PDF]

				M. P.M. DE MAAT Effects of Diet, Drugs, and Genes on Plasma Fibrinogen Levels Ann. N.Y. Acad. Sci., June 1, 2001; 936(1): 509 - 521. [Abstract] [Full Text] [PDF]

				S. J. Duffy, J. A. Vita, M. Holbrook, P. L. Swerdloff, and J. F. Keaney Jr Effect of Acute and Chronic Tea Consumption on Platelet Aggregation in Patients With Coronary Artery Disease Arterioscler. Thromb. Vasc. Biol., June 1, 2001; 21(6): 1084 - 1089. [Abstract] [Full Text] [PDF]

				P. Pignatelli, F. M Pulcinelli, A. Celestini, L. Lenti, A. Ghiselli, P. P. Gazzaniga, and F. Violi The flavonoids quercetin and catechin synergistically inhibit platelet function by antagonizing the intracellular production of hydrogen peroxide Am. J. Clinical Nutrition, November 1, 2000; 72(5): 1150 - 1155. [Abstract] [Full Text] [PDF]

				B. Illek and H. Fischer Flavonoids stimulate Cl conductance of human airway epithelium in vitro and in vivo Am J Physiol Lung Cell Mol Physiol, November 1, 1998; 275(5): L902 - L910. [Abstract] [Full Text] [PDF]