Antioxidants, oxidative stress, and cardiovascular diseases : cross-cultural comparisons and prospective cohort studies

Background: Antioxidants in plant foods have been proposed to reduce the risk of cardiovascular diseases (CVD) by reducing oxidative stress. The objective was to confirm prospective studies on CVD and traditional antioxidants (beta-carotene, alpha-tocopherol), and to investigate emerging antioxidants (alpha-carotene, gamma-tocopherol, cocoa flavanols), and oxidative stress (enzyme activity of glutathione peroxidase-3) with CVD risk. Methods: In cross-cultural studies, the Cretan (Greece) and Zutphen (The Netherlands) cohorts of Seven Countries Study were compared with respect to long-term mortality of coronary heart disease (CHD), diet, and indicators of oxidative stress. In prospective cohort studies, data were used from the Zutphen Elderly Study (~500 men aged 65-84 y), the ‘Survey in Europe on Nutrition and the Elderly: a Concerted Action’ (SENECA, 1168 men and women aged 70-75 y), and the Minnesota Heart Survey (270 men and women aged 26-85 y). Results: The comparison between the Cretan and Zutphen cohorts revealed a 3-fold lower 40-year CHD mortality rate in Crete. This lower mortality in Crete was paralleled by a higher consumption of fruit, tomatoes, and olive oil, amongst others, and by a lower consumption of meat, poultry, and dairy. Consequently, the Cretan men had higher intakes of carotenoids, alpha-tocopherol, vitamin C, and dietary fiber, and lower intakes of trans and saturated fatty acids. This was confirmed at the age of ≥80 years, when the Cretan men had higher plasma concentrations of major dietary antioxidants (major carotenoids and alpha-tocopherol), a lower iron status, and a lower level of oxidative stress. In the Zutphen Elderly Study, the relative risk (RR) of 15-y CVD mortality for 1 standard deviation (SD) increase in dietary intake was 0.81 [95% confidence interval (CI): 0.66-0.99] for alpha-carotene and 0.80 (95% CI: 0.66-0.97) for beta-carotene. The intake of tocopherols was not related to CVD death. In SENECA, plasma concentrations of carotene (sum of alpha- and beta-carotene) were inversely related to CVD mortality (RR for 1 SD increase: 0.83; 95% CI: 0.70-1.00), but plasma concentrations of alpha-tocopherol were not. The daily use of 4 grams of cocoa, a rich source of flavanols, was related to a 3.7 mm Hg lower systolic (95% CI: –7.1 to –0.3) and a 2.1 mm Hg lower (95% CI: –4.0 to –0.2) diastolic blood pressure. The same amount of cocoa was also related to a 50% lower risk of 15-year CVD mortality (RR: 0.50; 95% CI: 0.32-0.78). Finally, in the Minnesota Heart Survey, the odds ratio of CVD mortality for the highest vs. the lowest quartile of glutathione peroxidase-3 activity was 0.42 (95% CI: 0.21-0.86). This inverse relation was confined to those with low concentrations of HDL cholesterol (odds ratio highest vs. lowest quartile: 0.17; 95% CI: 0.06-0.47). Conclusion: The Cretan Mediterranean diet is rich in antioxidants, which may partly contribute to the low observed CHD mortality. The findings on beta-carotene support previous observational studies suggesting that this carotenoid relates to a lower CVD risk. We showed that alpha-carotene is correlated with beta-carotene in the diet, and alpha-carotene was also related to a lower CVD mortality. The results on alpha-tocopherol are in line with the outcomes of clinical trials and do not indicate a role for this vitamin in lowering CVD mortality in elderly populations.