Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study.

Lancet, 1993 Oct 23, 342:8878, 1007-11

Flavonoids are polyphenolic antioxidants naturally present in vegetables, fruits, and beverages such as tea and wine. In vitro, flavonoids inhibit oxidation of low-density lipoprotein and reduce thrombotic tendency, but their effects on atherosclerotic complications in human beings are unknown. We measured the content in various foods of the flavonoids quercetin, kaempferol, myricetin, apigenin, and luteolin. We then assessed the flavonoid intake of 805 men aged 65-84 years in 1985 by a cross-check dietary history; the men were then followed up for 5 years. Mean baseline flavonoid intake was 25.9 mg daily. The major sources of intake were tea (61%), onions (13%), and apples (10%). Between 1985 and 1990, 43 men died of coronary heart disease. Fatal or non-fatal myocardial infarction occurred in 38 of 693 men with no history of myocardial infarction at baseline. Flavonoid intake (analysed in tertiles) was significantly inversely associated with mortality from coronary heart disease (p for trend = 0.015) and showed an inverse relation with incidence of myocardial infarction, which was of borderline significance (p for trend = 0.08). The relative risk of coronary heart disease mortality in the highest versus the lowest tertile of flavonoid intake was 0.42 (95% CI 0.20-0.88). After adjustment for age, body-mass index, smoking, serum total and high-density-lipoprotein cholesterol, blood pressure, physical activity, coffee consumption, and intake of energy, vitamin C, vitamin E, beta-carotene, and dietary fibre, the risk was still significant (0.32 [0.15-0.71]). Intakes of tea, onions, and apples were also inversely related to coronary heart disease mortality, but these associations were weaker. Flavonoids in regularly consumed foods may reduce the risk of death from coronary heart disease in elderly men.




(Also see Green Tea, Quercetin, Red Wine, Grape Seed) Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the Zutphen study.

Arch Intern Med, 1996 Mar, 156:6, 637-42

BACKGROUND: Epidemiological studies suggested that consumption of fruit and vegetables may protect against stroke. The hypothesis that dietary antioxidant vitamins and flavonoids account for this observation is investigated in a prospective study. METHODS: A cohort of 552 men aged 50 to 69 years was examined in 1970 and followed up for 15 years. Mean nutrient and food intake was calculated from cross-check dietary histories taken in 1960, 1965, and 1970. The association between antioxidants, selected foods, and stroke incidence was assessed by Cox proportional hazards regression analysis. Adjustment was made for confounding by age, systolic blood pressure, serum cholesterol, cigarette smoking, energy intake, and consumption of fish and alcohol. RESULTS: Forty-two cases of first fatal or nonfatal stroke were documented. Dietary flavonoids (mainly quercetin) were inversely associated with stroke incidence after adjustment for potential confounders, including antioxidant vitamins. The relative risk (RR) of the highest vs the lowest quartile of flavonoid intake ( > or = 28.6 mg/d vs <18.3 mg/d) was 0.27 (95% confidence interval [CI], 0.11 to 0.70). A lower stroke risk was also observed for the highest quartile of beta-carotene intake (RR, 0.54; 95% CI, 0.22 to 1.33). The intake of vitamin C and vitamin E was not associated with stroke risk. Black tea contributed about 70% to flavonoid intake. The RR for a daily consumption of 4.7 cups or more of tea vs less than 2.6 cups of tea was 0.31 (95% CI, 0.12 to 0.84). CONCLUSION: The habitual intake of flavonoids and their major source (tea) may protect against stroke.




Antiproliferative effects of citrus flavonoids on a human squamous cell carcinoma in vitro

Cancer Lett, 1991 Feb, 56(2): 147-52

We examined the effects of four plant flavonoids (quercetin, taxifolin, nobiletin and tangeretin) on the in vitro growth of a human squamous cell carcinoma cell line (HTB43). Cell cultures were treated with each flavonoid (2-8 micrograms/ml) for 3-7 days. Cell viability, as determined by counting cells, correlated well with that obtained from a colorimetric assay for cellular growth utilizing 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide. The polymethoxylated flavonoids, nobiletin and tangeretin, markedly inhibited cell growth at all concentrations tested on days 5 and 7. On day 3, the inhibition observed was 70-72% at 8 micrograms/ml, while on day 5, it ranged from 61-88% at 2-4 micrograms/ml. Quercetin and taxifolin exhibited no significant inhibition at any of the concentrations tested. This difference in activity may be due to the relatively greater membrane uptake of the polymethoxylated flavonoids since methoxylation of the phenolic groups decreases hydrophilicity of the flavonoid.




Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study [published erratum appears in Arch Intern Med 1995 Jun 12;155(11):1184]

Arch Intern Med, 1995 Feb, 155:4, 381-6

OBJECTIVE: To determine whether flavonoid intake explains differences in mortality rates from chronic diseases between populations. DESIGN: Cross-cultural correlation study. SETTING/PARTICIPANTS: Sixteen cohorts of the Seven Countries Study in whom flavonoid intake at baseline around 1960 was estimated by flavonoid analysis of equivalent food composites that represented the average diet in the cohorts. MAIN OUTCOME MEASURES: Mortality from coronary heart disease, cancer (various sites), and all causes in the 16 cohorts after 25 years of follow-up. RESULTS: Average intake of antioxidant flavonoids was inversely associated with mortality from coronary heart disease and explained about 25% of the variance in coronary heart disease rates in the 16 cohorts. In multivariate analysis, intake of saturated fat (73%; P = 0.0001), flavonoid intake (8%, P = .01), and percentage of smokers per cohort (9%; P = .03) explained together, independent of intake of alcohol and antioxidant vitamins, 90% of the variance in coronary heart disease rates. Flavonoid intake was not independently associated with mortality from other causes. CONCLUSIONS: Average flavonoid intake may partly contribute to differences in coronary heart disease mortality across populations, but it does not seem to be an important determinant of cancer mortality.




Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study.

Lancet, 1993 Oct 23, 342:8878, 1007-11

Flavonoids are polyphenolic antioxidants naturally present in vegetables, fruits, and beverages such as tea and wine. In vitro, flavonoids inhibit oxidation of low-density lipoprotein and reduce thrombotic tendency, but their effects on atherosclerotic complications in human beings are unknown. We measured the content in various foods of the flavonoids quercetin, kaempferol, myricetin, apigenin, and luteolin. We then assessed the flavonoid intake of 805 men aged 65-84 years in 1985 by a cross-check dietary history; the men were then followed up for 5 years. Mean baseline flavonoid intake was 25.9 mg daily. The major sources of intake were tea (61%), onions (13%), and apples (10%). Between 1985 and 1990, 43 men died of coronary heart disease. Fatal or non-fatal myocardial infarction occurred in 38 of 693 men with no history of myocardial infarction at baseline. Flavonoid intake (analysed in tertiles) was significantly inversely associated with mortality from coronary heart disease (p for trend = 0.015) and showed an inverse relation with incidence of myocardial infarction, which was of borderline significance (p for trend = 0.08). The relative risk of coronary heart disease mortality in the highest versus the lowest tertile of flavonoid intake was 0.42 (95% CI 0.20-0.88). After adjustment for age, body-mass index, smoking, serum total and high-density-lipoprotein cholesterol, blood pressure, physical activity, coffee consumption, and intake of energy, vitamin C, vitamin E, beta-carotene, and dietary fibre, the risk was still significant (0.32 [0.15-0.71]). Intakes of tea, onions, and apples were also inversely related to coronary heart disease mortality, but these associations were weaker. Flavonoids in regularly consumed foods may reduce the risk of death from coronary heart disease in elderly men.




(Also see Green Tea, Quercetin, Red Wine, Grape Seed) Dietary flavonoids, antioxidant vitamins, and incidence of stroke: the Zutphen study.

Arch Intern Med, 1996 Mar, 156:6, 637-42

BACKGROUND: Epidemiological studies suggested that consumption of fruit and vegetables may protect against stroke. The hypothesis that dietary antioxidant vitamins and flavonoids account for this observation is investigated in a prospective study. METHODS: A cohort of 552 men aged 50 to 69 years was examined in 1970 and followed up for 15 years. Mean nutrient and food intake was calculated from cross-check dietary histories taken in 1960, 1965, and 1970. The association between antioxidants, selected foods, and stroke incidence was assessed by Cox proportional hazards regression analysis. Adjustment was made for confounding by age, systolic blood pressure, serum cholesterol, cigarette smoking, energy intake, and consumption of fish and alcohol. RESULTS: Forty-two cases of first fatal or nonfatal stroke were documented. Dietary flavonoids (mainly quercetin) were inversely associated with stroke incidence after adjustment for potential confounders, including antioxidant vitamins. The relative risk (RR) of the highest vs the lowest quartile of flavonoid intake ( > or = 28.6 mg/d vs <18.3 mg/d) was 0.27 (95% confidence interval [CI], 0.11 to 0.70). A lower stroke risk was also observed for the highest quartile of beta-carotene intake (RR, 0.54; 95% CI, 0.22 to 1.33). The intake of vitamin C and vitamin E was not associated with stroke risk. Black tea contributed about 70% to flavonoid intake. The RR for a daily consumption of 4.7 cups or more of tea vs less than 2.6 cups of tea was 0.31 (95% CI, 0.12 to 0.84). CONCLUSION: The habitual intake of flavonoids and their major source (tea) may protect against stroke.




Antiproliferative effects of citrus flavonoids on a human squamous cell carcinoma in vitro

Cancer Lett, 1991 Feb, 56(2): 147-52

We examined the effects of four plant flavonoids (quercetin, taxifolin, nobiletin and tangeretin) on the in vitro growth of a human squamous cell carcinoma cell line (HTB43). Cell cultures were treated with each flavonoid (2-8 micrograms/ml) for 3-7 days. Cell viability, as determined by counting cells, correlated well with that obtained from a colorimetric assay for cellular growth utilizing 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide. The polymethoxylated flavonoids, nobiletin and tangeretin, markedly inhibited cell growth at all concentrations tested on days 5 and 7. On day 3, the inhibition observed was 70-72% at 8 micrograms/ml, while on day 5, it ranged from 61-88% at 2-4 micrograms/ml. Quercetin and taxifolin exhibited no significant inhibition at any of the concentrations tested. This difference in activity may be due to the relatively greater membrane uptake of the polymethoxylated flavonoids since methoxylation of the phenolic groups decreases hydrophilicity of the flavonoid.




Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study [published erratum appears in Arch Intern Med 1995 Jun 12;155(11):1184]

Arch Intern Med, 1995 Feb, 155:4, 381-6

OBJECTIVE: To determine whether flavonoid intake explains differences in mortality rates from chronic diseases between populations. DESIGN: Cross-cultural correlation study. SETTING/PARTICIPANTS: Sixteen cohorts of the Seven Countries Study in whom flavonoid intake at baseline around 1960 was estimated by flavonoid analysis of equivalent food composites that represented the average diet in the cohorts. MAIN OUTCOME MEASURES: Mortality from coronary heart disease, cancer (various sites), and all causes in the 16 cohorts after 25 years of follow-up. RESULTS: Average intake of antioxidant flavonoids was inversely associated with mortality from coronary heart disease and explained about 25% of the variance in coronary heart disease rates in the 16 cohorts. In multivariate analysis, intake of saturated fat (73%; P = 0.0001), flavonoid intake (8%, P = .01), and percentage of smokers per cohort (9%; P = .03) explained together, independent of intake of alcohol and antioxidant vitamins, 90% of the variance in coronary heart disease rates. Flavonoid intake was not independently associated with mortality from other causes. CONCLUSIONS: Average flavonoid intake may partly contribute to differences in coronary heart disease mortality across populations, but it does not seem to be an important determinant of cancer mortality.