Flavonols and flavones in foods and their relation with cancer and coronary heart disease risk

Flavonoids are polyphenolic antioxidants occurring ubiquitously in vegetable foods. Flavonols and flavones inhibit chemically induced tumors in rodents. The flavonol quercetin also inhibits LDL oxidation and platelet aggregation in vitro . We therefore decided to investigate the relation between flavonoid intake and cancer and coronary heart disease risk in humans. The three flavonols quercetin, kaempferol, myricetin, and the two flavones luteolin and apigenin were selected because of their anticarcinogenic and antioxidant activities and because of their ubiquitous occurrence in foods. We first developed and validated a HPLC method for the quantitative determination of these flavonoids in foods. We then determined the flavonol and flavone content of 28 types of vegetables, 12 types of fruits and 9 types of beverages commonly consumed in The Netherlands. Quercetin was the main flavonoid and occurred in most fruits, beverages and in some vegetables. Mean intake of flavonols and flavones combined among Dutch adults was 23 mg/day, and main dietary sources of these flavonoids were tea (48 %), onions (38%), and apples (8 %). Mean flavonol and flavone intake of 805 men aged 65-84 years participating in the Zutphen Elderly Study 1985 was 26 mg/day. During five year followup period 75 men had a first diagnosis of cancer, of which 28 men had lung cancer. Thirty-four men died from all-cause cancer. Intake of flavonols and flavones in 1985 was not related to subsequent (lung) cancer morbidity ( P trend 0.54) and mortality ( P trend 0.51). Between 1985 and 1990 43 men died from coronary heart disease and 38 men had a first myocardial infarction. Intake of flavonols and flavones, expressed as tertiles of intake, was, independently from known risk- and confounding factors, inversely associated with mortality from coronary heart disease ( P trend 0.015) and incidence of a first myocardial infarction ( P trend 0.08). Average intake of flavonols and flavones in 16 cohorts participating in the Seven Countries Study around 1960 was also inversely related to mortality from coronary heart disease after 25 years of follow-up, but it was not related to cancer mortality. In multivariate regression analysis including saturated fat intake, flavonoid intake, and percentage of smokers as independent variables about 90 % of the total variance in coronary heart mortality was explained. Flavonol and flavone intake contributed about 9 % to the explained variance.We conclude that intake of flavonols and flavones may protect against coronary heart disease in humans, but that it does not seem to be an important determinant of cancer risk. However, more experimental, clinical, and epidemiological evidence is needed before firm conclusions on the health effects of these flavonoids can be drawn.