Dietary non-nutrients and haemostasis in humans : effects of salicylates, flavonoids and ginger

In this thesis we studied the content of acetylsalicylate and total salicylates in foods, and we studied the effects of the dietary non-nutrients salicylates and flavonoids and of certain foods on haemostatic parameters in humans.Acetylsalicylic acid -aspirin- irreversibly inhibits platelet cyclo-oxygenase, leading to decreased platelet thromboxane A _{<font size="-2">2</font>} production and decreased aggregation. Therefore it is effective as an anti-thrombotic drug in doses as low as 30 mg/d. Qualitative analyses by Swain <em>et al</em> suggested the presence of acetylsalicylate in foods. It was estimated that a normal mixed Western diet provides 10-200 mg/d of total salicylate and 3 mg/d of acetylsalicylate. We showed in 10 healthy subjects that 3 mg/d of acetylsalicylic acid decreased mean platelet thromboxane production by 39±8% (±sd). Thus, quantitative data on dietary acetylsalicylate deserved closer investigation. We determined acetylsalicylate and total salicylates in 30 foods using HPLC with fluorescence detection. Acetylsalicylate was lower than the detection limit (0.02 mg/kg for fresh and 0.2 mg/kg for dried products) in all foods. Total salicylates were 0-1 mg/kg in vegetables and fruits, and 3-28 mg/kg in herbs and spices. We showed that urinary excretion was a valid indicator for intake of pure (acetyl)salicylic acid (recovery 77-80%). We then studied urinary salicylate excretion in 17 subjects eating a variety of diets to estimate the content of bio-available salicylates of diets. Median excretion was 1.4 mg/24 h (range 0.8-1.6). Our data suggest that even purely vegetable diets provide less than 6 mg/d of salicylates, and no measurable acetylsalicylate. These amounts are probably too low to affect coronary heart disease risk, and worries about adverse effects of dietary salicylates on the behaviour of children may be unfounded.Others found that dietary flavonoids were associated with a reduced risk of coronary heart disease and stroke. This might be due to effects on haemostasis, because flavonoids have been reported to inhibit platelet aggregation <em>in vitro</em> . We found that concentrations of 2.5 μM of the flavone apigenin inhibited collagen- and ADP-induced platelet aggregation <em>in vitro</em> by about 26%, whereas the flavonols quercetin and quercetin-3-glucoside had no effect. No effects were found on platelet aggregation, thromboxane production, or other haemostatic parameters in 18 healthy subjects after they had consumed large amounts of quercetin- (onions) and apigenin-rich (parsley) foods daily for 7 d each. We conclude that claims for anti-aggregatory effects of flavonoids are based on the <em>in vitro</em> use of concentrations that cannot be attained <em>in vivo</em> . <em></em> Our findings suggest that it is unlikely that reported effects of dietary flavonoids on coronary vascular disease risk are mediated through platelet aggregation or cyclo-oxygenase activity. Possible effects on known risk indicators for coronary heart disease from the coagulation cascade or the fibrinolytic system should be examined in a larger study.It has been claimed that ginger consumption exerts an anti-thrombotic effect by inhibiting platelet thromboxane production. We, however, found no effects on platelet thromboxane production in a placebo-controlled cross-over study in 18 healthy subjects after consumption of raw (-1±9%, mean±sd) or cooked ginger (1±8%).We conclude that contents of (acetyl)salicylate in foods are too low to affect disease risk. We could not confirm the putative anti-thrombotic effect of ginger, onions and parsley on haemostatic parameters in humans.