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Green Tea (5 cups) Daily Reduced Mortality & Cardiovascular Mortality
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Green Tea Consumption and Mortality Due to Cardiovascular Disease, Cancer, and All Causes in Japan
The Ohsaki Study
Shinichi Kuriyama, MD, PhD; Taichi Shimazu, MD; Kaori Ohmori, MD, PhD; Nobutaka Kikuchi, MD; Naoki Nakaya, PhD; Yoshikazu Nishino, MD, PhD; Yoshitaka Tsubono, MD, PhD; Ichiro Tsuji, MD, PhD
JAMA. 2006;296:1255-1265.
Vol. 296 No. 10, September 13, 2006
"....On the basis of a large, population-based, prospective cohort study, we found significant inverse associations of green tea consumption with mortality due to all causes and due to CVD. Compared with participants who consumed less than 1 cup/d of green tea, those who consumed 5 or more cups/d had a risk of all-cause and CVD mortality that was 16% lower (during 11 years of follow-up) and 26% lower (during 7 years of follow-up), respectively. These inverse associations of all-cause and CVD mortality were primarily observed in women, although the inverse association for green tea consumption was observed in both sexes. In contrast, null results were observed in the association between green tea consumption and cancer mortality.... A number of biological mechanisms, including radical scavenging and antioxidant properties, have been proposed for the beneficial effects of green tea in different models of chronic disease.3-6 The present inverse association between green tea consumption and cerebral infarction mortality, but not cerebral hemorrhage, indicates that green tea polyphenols might directly affect atherosclerosis itself, irrespective of traditional CVD risk profiles...."
"....In women, compared with those who consumed less than 1 cup/d of green tea, those who consumed 5 or more cups/d had a 31% lower risk of CVD death..."
"....In men, green tea consumption was significantly associated with reduced mortality due to stroke. In women, green tea consumption also was significantly associated with reduced mortality due to stroke, especially cerebral infarction. Compared with women who consumed less than 1 cup/d of green tea, those who consumed 5 or more cups/d had 42% and 62% lower risk of death due to stroke and cerebral infarction, respectively..."
"...Although the interaction was not significant, the inverse association between green tea consumption and CVD mortality appeared to be more pronounced in participants who had never smoked. Among current smokers (n = 11 614), the multivariate HRs of mortality due to CVD associated with different green tea consumption frequencies were 1.00 (reference) for less than 1 cup/d, 0.79 (95% CI, 0.55-1.14) for 1 to 2 cups/d, 0.81 (95% CI, 0.56-1.17) for 3 to 4 cups/d, and 0.86 (95% CI, 0.62-1.18) for 5 or more cups/d, respectively (P = .43 for trend). The corresponding data among never smokers (n = 18 775) were 1.00, 0.85 (95% CI, 0.62-1.16), 0.69 (95% CI, 0.51-0.95), and 0.75 (95% CI, 0.56-1.00), respectively (P = .03 for trend)...."
Introduction
Tea is the most consumed beverage in the world aside from water. Three billion kilograms of tea are produced each year worldwide.1 Because of the high rates of tea consumption in the global population, even small effects in humans could have large implications for public health.2 Tea is generally consumed in the forms of green, oolong, and black tea, all of which originate from the leaves of the plant Camellia sinensis. Among teas, green tea polyphenols have been extensively studied as cardiovascular disease (CVD) and cancer chemopreventive agents.3-6 Although substantial evidence from in vitro and animal studies indicates that green tea preparations inhibit CVD and carcinogenic processes, the possible protective role of green tea consumption against these diseases in humans remains unclear.
If green tea does protect humans against CVD or cancer, it is expected that consumption of this beverage would substantially contribute to the prolonging of life expectancy, given that CVD and cancer are the 2 leading causes of death worldwide.7 To date, 4 studies8-11 have examined the association between green tea consumption and mortality, but their sample sizes were small and the results were inconsistent.
We therefore designed this prospective analysis to examine the association between green tea consumption and mortality due to all causes, CVD, and cancer within a large population-based cohort study of 40 530 persons in Miyagi Prefecture in northeastern Japan, where green tea is widely consumed. Within this region, 80% of the population drinks green tea and more than half of them consume 3 or more cups/d.12
Author Comments
On the basis of a large, population-based, prospective cohort study, we found significant inverse associations of green tea consumption with mortality due to all causes and due to CVD. Compared with participants who consumed less than 1 cup/d of green tea, those who consumed 5 or more cups/d had a risk of all-cause and CVD mortality that was 16% lower (during 11 years of follow-up) and 26% lower (during 7 years of follow-up), respectively. These inverse associations of all-cause and CVD mortality were primarily observed in women, although the inverse association for green tea consumption was observed in both sexes. In contrast, null results were observed in the association between green tea consumption and cancer mortality.
Sato et al8 found a significant inverse association between green tea consumption and stroke mortality in 5910 participants over a 4-year period. Nakachi et al9, 11 reported an observed association between increased consumption of green tea and significantly lower risk of CVD death among 8552 individuals with a follow-up period of 11 to 13 years. Our findings were consistent with these results. In contrast, Iwai et al10 did not observe significant association between green tea consumption and all-cause mortality, but the results were consistent with an inverse association between green tea consumption and all-cause mortality. The study had a much smaller sample size (2855 participants with 9.9 years of follow-up), and nonsignificant results might be due to low statistical power. Nakachi et al9, 11 also demonstrated that green tea consumption was associated with reduced mortality due to cancer, in contrast with our findings.
The reason for the discrepancy between men and women for the associations of green tea consumption and risk of all-cause and CVD mortality is uncertain. One possibility is the residual confounding by cigarette smoking. Men were more likely to smoke (Table 1 and Table 2), and the inverse associations between green tea consumption and CVD mortality appeared to be more pronounced in participants who had never smoked, although tests for interaction between green tea consumption categories and smoking in the analyses of CVD mortality yielded nonsignificant results. These results suggest that higher rates of smoking may mask the association of green tea consumption with CVD mortality among men.
Our finding of an inverse association between green tea consumption and CVD mortality appeared to be a threshold effect rather than a dose-response relationship, such that persons who consume at least 1 cup/d may receive some benefit. There may be differences in dietary intake and health characteristics besides green tea consumption between the lowest fourth and the highest three fourths of the distribution, suggesting that the observed association may be somehow explained by selection bias. However, in our models we adjusted for various potential confounders, and the estimates did not change substantially from the age- and sex-adjusted estimates.
Our results for CVD mortality may be partly explained by the effect of green tea on CVD risk profile. Previous studies have suggested that green tea may have beneficial effects on CVD risk profile, such as hypertension and obesity.21-22 However, the present results of stratified analysis show that inverse associations were also evident among lean participants and among those who had no history of hypertension. Therefore, mechanisms other than the effects on traditional CVD risk factors might play a role. Green tea polyphenols, especially (-)-epigallocatechin-3-gallate, might explain the observed association with reduced all-cause and CVD mortality, irrespective of CVD risk profiles.23-24 A number of biological mechanisms, including radical scavenging and antioxidant properties, have been proposed for the beneficial effects of green tea in different models of chronic disease.3-6 The present inverse association between green tea consumption and cerebral infarction mortality, but not cerebral hemorrhage, indicates that green tea polyphenols might directly affect atherosclerosis itself, irrespective of traditional CVD risk profiles.
We observed weak or null relationships between black tea or oolong tea and mortality. The discrepancy between green tea and other teas might indicate the specific role of substances rich in green tea. However, the smaller variations in the consumption of black tea or oolong tea may have contributed in part to the noted lack of association with mortality.
Our study has limitations. First, the number of cases of individual CVD and cancer was only modest at best. Therefore, our study may not have had sufficient statistical power for detecting significant results in coronary heart disease or for detecting small increases or decreases in the risk of cancer at individual sites, as associated with green tea consumption. Second, 10.4% (during 7 years of follow-up) and 13.9% (during 11 years of follow-up) of total participants were lost to follow-up. However, this proportion did not vary across the green tea consumption categories (10.6%, 9.7%, 10.2%, and 10.8% of participants from the lowest to highest green tea consumption categories, respectively, were lost to follow-up during 7 years of follow-up, and 15.2%, 14.8%, 13.4%, and 12.4% of participants, respectively, were lost to follow-up during 11 years of follow-up). Therefore, we consider it unlikely that the association between green tea consumption and mortality was substantially distorted by the effect of loss to follow-up. Third, since green tea consumption was assessed on the basis on self-administered questionnaires, some misclassification of consumption status could arise in estimating the effect of the beverage. However, this misclassification may be nondifferential and would tend to result in underestimation of the impact of green tea consumption.
Healthy or unhealthy behavior, in association with high green tea consumption, could have confounded the correlation between green tea consumption and mortality. Almost all Japanese persons consume green tea as one of their favorite beverages and it is unlikely that green tea consumption was driven by health concerns. Therefore, the possibility that the observed inverse associations between green tea and mortality were confounded by habits related to health consciousness is small. However, although we statistically controlled for a variety of potential confounding factors and conducted analysis after excluding death during the first 3 years of follow-up, and the findings were robust, we could not eliminate residual confounding. Clinical trials are ultimately necessary to confirm the protective effect of green tea on mortality.
ABSTRACT
Context: Green tea polyphenols have been extensively studied as cardiovascular disease and cancer chemopreventive agents in vitro and in animal studies. However, the effects of green tea consumption in humans remain unclear.
Objective: To investigate the associations between green tea consumption and all-cause and cause-specific mortality.
Design, Setting, and Participants: The Ohsaki National Health Insurance Cohort Study, a population-based, prospective cohort study initiated in 1994 among 40 530 Japanese adults aged 40 to 79 years without history of stroke, coronary heart disease, or cancer at baseline. Participants were followed up for up to 11 years (1995-2005) for all-cause mortality and for up to 7 years (1995-2001) for cause-specific mortality.
Main Outcome Measures: Mortality due to cardiovascular disease, cancer, and all causes.
Results:
Over 11 years of follow-up (follow-up rate, 86.1%), 4209 participants died, and over 7 years of follow-up (follow-up rate, 89.6%), 892 participants died of cardiovascular disease and 1134 participants died of cancer.
Green tea consumption was inversely associated with mortality due to all causes and due to cardiovascular disease. The inverse association with all-cause mortality was stronger in women (P = .03 for interaction with sex).
In men, the multivariate hazard ratios of mortality due to all causes associated with different green tea consumption frequencies were 1.00 (reference) for less than 1 cup/d, 0.93 (95% confidence interval [CI], 0.83-1.05) for 1 to 2 cups/d, 0.95 (95% CI, 0.85-1.06) for 3 to 4 cups/d, and 0.88 (95% CI, 0.79-0.98) for 5 or more cups/d, respectively (P = .03 for trend).
The corresponding data for women were 1.00, 0.98 (95% CI, 0.84-1.15), 0.82 (95% CI, 0.70-0.95), and 0.77 (95% CI, 0.67-0.89), respectively (P<.001 for trend).
The inverse association with cardiovascular disease mortality was stronger than that with all-cause mortality. This inverse association was also stronger in women (P = .08 for interaction with sex). In women, the multivariate hazard ratios of cardiovascular disease mortality across increasing green tea consumption categories were 1.00, 0.84 (95% CI, 0.63-1.12), 0.69 (95% CI, 0.52-0.93), and 0.69 (95% CI, 0.53-0.90), respectively (P = .004 for trend).
Among the types of cardiovascular disease mortality, the strongest inverse association was observed for stroke mortality.
In contrast, the hazard ratios of cancer mortality were not significantly different from 1.00 in all green tea categories compared with the lowest-consumption category.
Conclusion: Green tea consumption is associated with reduced mortality due to all causes and due to cardiovascular disease but not with reduced mortality due to cancer.
Author Affiliations: Division of Epidemiology, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine (Drs Kuriyama, Shimazu, Ohmori, Kikuchi, Nakaya, and Tsuji), and Division of Health Policy, Tohoku University School of Public Policy (Dr Tsubono), Sendai, Japan; Division of Epidemiology, Miyagi Cancer Center Research Institute, Natori, Japan (Dr Nishino).
RESULTS
Baseline characteristics of the participants by green tea consumption category are shown in Table 1 and Table 2. Participants who consumed green tea more often tended to be older and were more likely to be unemployed, to engage in sports or exercise, and to have a history of hypertension and diabetes mellitus and were less likely to walk, for both men and women. Men were also more likely to have a history of gastric ulcer and women to be obese. Men and women were both also more likely to consume individual foods or beverages such as miso (soybean paste) soup, soybean products, total fish, dairy products, total fruits, total vegetables, oolong tea, and black tea, but less likely to consume coffee. There were no apparent associations between smoking status or alcohol drinking and green tea consumption categories.
Over 11 years of follow-up, among 374 174 accrued person-years, the total number of deaths was 4209. The follow-up rate was 86.1%. Table 3 shows the association between green tea consumption and the HRs and associated 95% CIs of mortality due to all causes. We found that green tea consumption was inversely associated with mortality due to all causes and that the inverse association was more pronounced in women (P = .03 for interaction with sex). In men, the multivariate HRs of mortality due to all causes associated with different green tea consumption frequencies were 1.00 (reference) for less than 1 cup/d, 0.93 (95% CI, 0.83-1.05) for 1 to 2 cups/d, 0.95 (95% CI, 0.85-1.06) for 3 to 4 cups/d, and 0.88 (95% CI, 0.79-0.98) for 5 or more cups/d, respectively (P = .03 for trend). The corresponding data in women were 1.00, 0.98 (95% CI, 0.84-1.15), 0.82 (95% CI, 0.70-0.95), and 0.77 (95% CI, 0.67-0.89), respectively (P<.001 for trend). We included a variety of potential confounders in our multivariate models; however, the results did not change substantially even after adjustment for these variables. Comparison between the age- and sex-adjusted model and multivariate model suggested that the estimates were not biased by multicollinearity. When we excluded the 1018 participants who died in the first 3 years of follow-up, the results also did not change substantially.
Over 7 years of follow-up, among 252 101 total accrued person-years, the total number of deaths was 2931 (892 from CVD and 1134 from cancer). The follow-up rate was 89.6%. Table 4 shows the association between green tea consumption and the HRs and associated 95% CIs of mortality due to CVD and cancer. We found that green tea consumption was inversely associated with mortality due to CVD but not with that due to cancer. The inverse association with CVD mortality was stronger than that with all-cause mortality and the inverse association was also more pronounced in women (P = .08 for interaction with sex). In women, compared with those who consumed less than 1 cup/d of green tea, those who consumed 5 or more cups/d had a 31% lower risk of CVD death. In contrast, the association between green tea consumption and cancer mortality was substantially different. The HRs of cancer mortality were not significantly different from 1.00 in all green tea consumption categories compared with the lowest-consumption (referent) category.
We further investigated the association between green tea consumption and specific CVD and cancer mortality (Table 5, Table 6, and Table 7). In men, green tea consumption was significantly associated with reduced mortality due to stroke. In women, green tea consumption also was significantly associated with reduced mortality due to stroke, especially cerebral infarction. Compared with women who consumed less than 1 cup/d of green tea, those who consumed 5 or more cups/d had 42% and 62% lower risk of death due to stroke and cerebral infarction, respectively. In both men and women, the multivariate HRs of gastric, lung, and colorectal cancer mortality were mostly above unity but not statistically significant.
We conducted further stratified analyses of CVD mortality examining subgroups defined by traditional CVD risk factors and dietary factors. The results in all subgroups showed the same inverse relationship between green tea consumption and CVD mortality, with no interactions noted. Although the interaction was not significant, the inverse association between green tea consumption and CVD mortality appeared to be more pronounced in participants who had never smoked. Among current smokers (n = 11 614), the multivariate HRs of mortality due to CVD associated with different green tea consumption frequencies were 1.00 (reference) for less than 1 cup/d, 0.79 (95% CI, 0.55-1.14) for 1 to 2 cups/d, 0.81 (95% CI, 0.56-1.17) for 3 to 4 cups/d, and 0.86 (95% CI, 0.62-1.18) for 5 or more cups/d, respectively (P = .43 for trend). The corresponding data among never smokers (n = 18 775) were 1.00, 0.85 (95% CI, 0.62-1.16), 0.69 (95% CI, 0.51-0.95), and 0.75 (95% CI, 0.56-1.00), respectively (P = .03 for trend).
The multivariate HRs of all-cause mortality according to green tea, oolong tea, and black tea consumption frequencies are compared in Table 8. Green tea consumption was associated with reduced mortality. In contrast, a weak or null association was observed between consumption of black tea or oolong tea and the HRs of all-cause mortality. We were unable to examine the associations between oolong tea or black tea and CVD or cancer mortality because of insufficient numbers of cases of disease among the higher-consumption categories of those beverages.
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