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 2 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 et al 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 in vitro . We found that concentrations of 2.5 μM of the flavone apigenin inhibited collagen- and ADP-induced platelet aggregation in vitro 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 in vitro use of concentrations that cannot be attained in vivo . 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

Acetylsalicylate and salicylates in foods

Acetylsalicylic acid is effective in the prevention of cardiovascular disease. It was suggested that fruits and vegetables provide unknown amounts of acetylsalicylic acid. We could not find any acetylsalicylic acid in 30 foods using HPLC with fluorescence detection (detection limits: 0.02 mg/kg for fresh, and 0.2 mg/kg for dried products). We showed that urinary excretion of salicylates is a valid indicator for intake, and found a median salicylate excretion of 10 mol (1.4 mg) in 24 h urine of 17 volunteers eating a variety of diets. Our data suggest that the content of (acetyl)salicylic acid of diets may be too low to affect disease risk

Determination of acetylsalicylic acid and salicylic acid in foods, using HPLC with fluorescence detection.

We developed a specific and sensitive HPLC method with fluorescence detection for the determination of free acetylsalicylic acid, free salicylic acid, and free salicylic acid plus salicylic acid after alkaline hydrolysis (free-plus-bound) in foods. Acetylsalicylic acid was detected after postcolumn hydrolysis to salicylic acid. With the method for free acetylsalicylic acid and salicylic acid, recovery was 95-98␏or acetylsalicylic acid added to foods and 92-102␏or salicylic acid. Recovery of added salicylic acid was 79-94␏or the free-plus-bound salicylic acid method. The limit of detection was 0.02 mg/kg for fresh and 0.2 mg/kg for dried foods for all substances. We did not find acetylsalicylic acid in any of 30 foods previously thought to be high in salicylates. The contents of free-plus-bound salicylic acid and of free salicylic acid ranged from 0 to 1 mg/kg in vegetables and fruits and from 3 to 28 mg/kg in herbs and spices. Thus the tested foods did not contain acetylsalicylic acid and only small amounts of salicylic acid. Our data suggest that the average daily intake of acetylsalicylic acid from foods is nil and that of salicylic acid is 0-5 mg/day