Paul Knekt

Abstract Objective : To study the association between dietary intake of flavonoids and subsequent coronary mortality. Design : A cohort study based on data collected at the Finnish mobile clinic health examination survey from 1967-72 and followed up until 1992. Settings : 30 communities from different parts of Finland. Subjects : 5133 Finnish men and women aged 30-69 years and free from heart disease at baseline. Main outcome measure : Dietary intake of flavonoids, total mortality, and coronary mortality. Results : In women a significant inverse gradient was observed between dietary intake of flavonoids and total and coronary mortality. The relative risks between highest and lowest quarters of flavonoid intake adjusted for age, smoking, serum cholesterol concentration, blood pressure, and body mass index were 0.69 (95% confidence interval 0.53 to 0.90) and 0.54 (0.33 to 0.87) for total and coronary mortality, respectively. The corresponding values for men were 0.76 (0.63 to 0.93) and 0.78 (0.56 to 1.08), respectively. Adjustment for intake of antioxidant vitamins and fatty acids weakened the associations for women; the relative risks for coronary heart disease were 0.73 (0.41 to 1.32) and 0.67 (0.44 to 1.00) in women and men, respectively. Intakes of onions and apples, the main dietary sources of flavonoids, presented similar associations. The relative risks for coronary mortality between highest and lowest quarters of apple intake were 0.57 (0.36 to 0.91) and 0.81 (0.61 to 1.09) for women and men, respectively. The corresponding values for onions were 0.50 (0.30 to 0.82) and 0.74 (0.53 to 1.02), respectively. Conclusion : The results suggest that people with very low intakes of flavonoids have higher risks of coronary disease. Key messages Key messages The protective effect of flavonoids was associated with a diet high in intake of apples and onions The effect may be mediated through prevention of oxidation of low density lipoproteins but other mechanisms could be involved Flavonoids offer an explanation for the suggested beneficial effect of fruits and vegetables in coronary heart disease Further studies should concentrate on the effects of various flavonoid compounds and on populations with different intakes

Flavonoids are effective antioxidants and, in theory, may provide protection against cancer, although direct human evidence of this is scarce. The relation between the intake of antioxidant flavonoids and subsequent risk of cancer was studied among 9,959 Finnish men and women aged 15-99 years and initially cancer free. Food consumption was estimated by the dietary history method, covering the total habitual diet during the previous year. During a follow-up in 1967-1991, 997 cancer cases and 151 lung cancer cases were diagnosed. An inverse association was observed between the intake of flavonoids and incidence of all sites of cancer combined. The sex- and age-adjusted relative risk of all sites of cancer combined between the highest and lowest quartiles of flavonoid intake was 0.80 (95% confidence interval 0.67-0.96). This association was mainly a result of lung cancer, which presented a corresponding relative risk of 0.54 (95% confidence interval 0.34-0.87). The association between flavonoid intake and lung cancer incidence was not due to the intake of antioxidant vitamins or other potential confounding factors, as adjustment for factors such as smoking and intakes of energy, vitamin E, vitamin C, and beta-carotene did not materially alter the results. The association was strongest in persons under 50 years of age and in nonsmokers with relative risks of 0.33 (95% confidence interval 0.15-0.77) and 0.13 (95% confidence interval 0.03-0.58), respectively. Of the major dietary flavonoid sources, the consumption of apples showed an inverse association with lung cancer incidence, with a relative risk of 0.42 (95% confidence interval 0.23-0.76) after adjustment for the intake of other fruits and vegetables. The results are in line with the hypothesis that flavonoid intake in some circumstances may be involved in the cancer process, resulting in lowered risks.

Oxidation of lipoproteins is hypothesized to promote atherosclerosis and, thus, a high intake of antioxidant nutrients may protect against coronary heart disease. The relation between the intakes of dietary carotene, vitamin C, and vitamin E and the subsequent coronary mortality was studied in a cohort of 5,133 Finnish men and women aged 30-69 years and initially free from heart disease. Food consumption was estimated by the dietary history method covering the total habitual diet during the previous year. Altogether, 244 new fatal coronary heart disease cases occurred during a mean follow-up of 14 years beginning in 1966-1972. An inverse association was observed between dietary vitamin E intake and coronary mortality in both men and women with relative risks of 0.68 (p for trend = 0.01) and 0.35 (p for trend < 0.01), respectively, between the highest and lowest tertiles of the intake. Similar associations were observed for the dietary intake of vitamin C and carotenoids among women and for the intake of important food sources of these micronutrients, i.e., of vegetables and fruits, among both men and women. The associations were not attributable to confounding by major nondietary risk factors of coronary heart disease, i.e., age, smoking, serum cholesterol, hypertension, or relative weight. The results support the hypothesis that antioxidant vitamins protect against coronary heart disease, but it cannot be excluded that foods rich in these micronutrients also contain other constituents that provide the protection.