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

Abstract

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.

Bioavailability and efficiency of rutin as an antioxidant: a human supplementation study

“…This may re¯ect the signi®cantly higher¯avo-noid concentrations used in in vitro studies (10 ± 50 mM; Mower et al, 1984) compared with those achieved following 6 weeks' rutin supplementation (mean plasma quercetin concentration 0.14 + 0.03 mmolal plasma). It therefore appears that the concentrations of¯avonoids necessary for anti-aggregatory activity in vitro have not been attained in vivo by rutin supplementation at the recommended dose or by dietary intake as previously demonstrated by Janssen et al (1998).…”

Mediterranean diet, but not red wine, is associated with beneficial changes in primary haemostasis

“…Previous intervention studies have shown that distinctive components of MD reduce platelet function, and this effect has been proposed as a mechanism contributing to the CV benefit of this diet. In fact, fish oils (Goodnight et al, 1981;Agren et al, 1997;Vognild et al, 1998), a-linolenic acid (Renaud & Nordøy, 1983;Allman et al, 1995;Freese et al, 1994) and various spices (Janssen et al, 1998;Ackerman et al, 2001;Srivastava et al, 1995) induce a decrease of platelet function. The apparent discrepancy of our results with those findings is probably explained by the lower content of each one of these substances in the complete MD, as opposed to the amounts used for single components of MD in selective intervention studies.…”

“…In this context, some of the beneficial effects of MD and wine consumption could be mediated by a reduction in platelet reactivity. Several studies report that diets enriched with fish, a-linolenic acid and spices, abundant in the case of MD, include substances that reduce or could reduce platelet function (Vognild et al, 1998;Allman et al, 1995;Janssen et al, 1998;Ackerman et al, 2001;Srivastava et al, 1995). Similarly, other reports indicate that the intake of moderate amounts of ethanol or nonalcoholic components of wine, for 2 or more weeks, is associated with a decrease in ex vivo platelet function (Pikkar et al, 1987;Pellegrini et al, 1996;Pace-Asciak et al, 1996;Freedman et al, 2001).…”

Consumption of black and green tea has no effect on inflammation, haemostasis and endothelial markers in smoking healthy individuals

“…Janssen and colleagues recently studied the effects of the¯avonoids quercetin and apigenin (from onions and parsley) on haemostasis in healthy volunteers (Jansen et al, 1998). These polyphenols belong to different classes of¯avonoids (¯avonols and¯avones, respectively), but they also did not affect ®brinogen, PAI-1 activity, factor VII coagulant activity, plasminogen, platelet aggregation or thromboxane B2 production.…”