Dietary Antioxidant Flavonoids and Risk of Coronary Heart Disease: the Zutphen Elderly Study
Michael G L Hertog, Edith J M Feskens, Peter C H Hollmark, Martin B Katan, Daan Kromhout

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 atheroscierotic complications in human being are unknown. We measured the content in various foods of the flavonoids quercetin, Kaempferol, myricetin, apigenin and tutcolin. 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% C1.0.20-0 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.

Tea Flavonoids May Protect Against Atherosclerosis: The Rotterdam Study
Johanna M Geleijnse, PhD, Lenore J Lancer, PhD, Albert Hofman, MD: Hubert A P Puls, MD: Jacqueline CM Witteman, PhD.

Background: Epidemiological studies have indicated a protective role of dietary flavonoids in cardiovascular disease but evidence is still conflicting. Tea is the major dietary source for flavonoids in Western populations. We studied the association of tea intake with aortic atherosclerosis in a general population.

Methods: the present analysis formed part of the Rotterdam Study, a prospective study of men and women 55 years and older. Dietary intakes were assessed at baseline by a trained dietician who used a semiquantitative food frequency questionnaire. Calcified plaques in the abdominal aorta were radiographically detected after 2 to 3 years of follow-up. Aortic atherosclerosis was classified as “mild”, “moderate” or “severe”, according to the length of the calcified area (, 1 cm, 1-5 cm and >5cm respectively). The association of tea intake with severity of aortic atherosclerosis was studied in 3454 subjects who were free of cardiovascular disease at baseline. Data were analysed by logistic regression, adjusting for age, sex, body mass index (calculated as weight in kilograms divided by the square of height in meters), smoking, education and intake of alcohol, coffee, vitamin antioxidants total fat and total energy.

Results: Multivariable analyses showed a significant inverse association of tea intake with severe aortic atherosclerosis. Odds ratios decreased from 0.54 (95% confidence interval [CI]. 032-0.92) for drinking 125 to 250 ml (1-2 cups) of tea to 0.31 (CI 0.16-0.59) for drinking more than 500 ml/d (4 cups per day). The associations were stronger in women than in men. The association of tea intake with mild and moderate atherosclerosis was not statistically significant.

Conclusion: This study indicates a protective effect of tea drinking against ischemic heart disease.

The Effects of Japanese Black Tea on Fat Crystal in Arterys
Yokozawa-T, Dong-E, Nakagawa-T, Kim-D-W, Hattori-M, Nakagawa-H.
Biosci-Biotechnol-Biochem 1998 Jan, VOL: 62 (1), P: 44-8, ISSN: 0916-8451.

The atherogenic index was found to be significantly better in rats fed a high-cholesterol diet supplemented with black tea extract than in the ones not given the extract. It was also evident that black tea inhibited the proliferation of smooth muscle cells involved in the development and progression of atherosclerosis, and suppressed the production of oxidized low-density lipoprotein, a cause of lipid accumulation. It thus seems likely that black tea has an antiatherosclerotic action.

Beneficial Effects of Tea on Cardiovascular Disease Risk Associated Factors
Loktionov-A, Bingham-S-A, Vorster-H, Jerling-J-C, Runswick-S-A, BR-J-NUTR, 1998, Vol./Issue/Pg. 79/2 (133-139), ISSN: 0007-1145, Full COPYRIGHT BY Elsevier Science BV, Amsterdam, Netherlands

Apolipoprotein E (ApoE) genotype was determined in sixty-five subjects who had taken part in a 4-week randomised crossover trial to compare the effect of six mugs of black tea per day v. placebo on blood lipids and blood coagulation factors. Four ApoE genotype variants (seven E2/E3, forty-five E3/E3, twelve E3/E4 and one E4/E4) were found. ApoE allele frequency was within the range typical for Caucasian populations (ApoE-E2 5.4%; ApoE-E3 83.8%; ApoE-E4 10.8%). Individuals bearing at least one E4 allele had substantially higher levels of serum total cholesterol, LDL cholesterol and triacylglycerols. Mean plasminogen activator inhibitor (PAI-1) activity was higher in ApoE-E4 allele-bearing individuals (E3/E4 + E4/E4, 11.89 (SE 1.27) U/ml; E3/E3, 9.19 (SE 0.80) U/ml; E2/E3, 7.21 (SE 1.04) U/ml, P values of E4-group v. E3 and E2 being respectively 0.093 and 0.030). These unexpected findings imply that elevated PAI-1 activity may be a hitherto unrecognised additional factor involved in the increased cardiovascular disease risk associated with apoE-E4 allele. The interactions between tea drinking and genotype were also examined. In the E3/E3 homozygotes, HDL-cholesterol was significantly reduced in the tea period (mean placebo 1.54 mumol/l v. mean tea 1.50 mumol/l, P = 0.027). In the E2/E3 group, triacylglycerol concentration was significantly reduced (mean placebo 1.18 mumol/l v. mean tea 1.09 mumol/l, P = 0.039). Tea also caused a significant decrease of PAI-1 activity in the subjects with E2/E3 genotype (mean placebo 7.21 U/ml v. mean tea 5.88 U/ml, P = 0.007). In the other two genotype groups, there was no significant effect of tea.

The results indicate that tea drinking has a beneficial effect on some cardiovascular disease risk-associated factors, especially in E2 allele-bearing individuals. Dietary intervention may be particularly effective in population groups with certain genetic characteristics.

Acute Effects of Ingestion of Black and Green Tea on Lipoprotein oxidation
Jonathan M Hodgson, Ian B Puddey, Kevin D Croft, Valerie Burke, Trevor A Mori, Rima Abu-Amsha Caccetta, American Society for Clinical Nutrition

Background: Tea has been associated with a reduced risk of cardiovascular disease. One proposed mechanism of this risk reduction involves inhibition of lipoprotein oxidation in vivo by antioxidant polyphenolic compounds derived from tea. However, controlled interventions uniformly failed to show that ingestion of tea can inhibit LDL particles from polyphenolic compounds that are present in the aqueous phase of serum.

Objective: The objective of this study was to examine the acute effects of ingestion of black and green tea on ex vivo Cu2+- induced lipoprotein oxidation without prior isolation of lipoproteins from serum.

Design: The acute effects of 4 hot drinks - green tea and black tea (each at a dose equivalent to 4 standard cups), water matched to the teas for caffeine content, and water - were assessed in 20 healthy men by using a Latin-square design. The lag time to lipoprotein diene formation, slope of the propagation phase of the oxidation curve, the area under the oxidation curve were calculated. Urinary concentrations of 4-0-methylgallic acid were used as a marker of uptake and metabolism of polyphenolic compounds from tea.

Results: Significant increases in urinary 4-0-methylgallic acid for black and green tea (P<0.0001) were observed. Caffeine did not significantly influence influence lipoprotein oxidation. Compared with the water control, there was a greater lag time for black tea (5.4+-2.9min;P=0.05) that was of borderline significance and a similar trend for green tea (4.4+-2.8min;P=0.17). Slope and area under the oxidation curve were not altered.

Conclusion: Black tea has a mild acute effect on ex vivo lipoprotein oxidation in human serum.