Cross sectional study of effects of drinking green tea on cardiovascular and liver diseases

Introduction

Tea has recently received a lot of attention as a protective agent against cancer and cardiovascular disease, two important targets of preventive medicine for adults. Green tea has many advantages over chemical preventive agents—tea is non-toxic and thus readily available to the general population.

Several laboratory studies on crude extract or constituents ofblack and green teas have shown inhibitory effects on oxidation and mutagenicity.1 2 3 4 Moreover, one of the catechins, (−)—epigallocatechin gallate, (a main constituent of green tea leaves) significantly inhibited the promotion of tumours and carcinogenesis in animal experiments.5 6 7 8 9 Animal experiments have also studied the protective effects of green tea against cardiovascular disease.10 11 12 Ingestion of extract of green tea in rats has significantly decreased plasma cholesterol and triglyceride concentrations and the ratio oflow and very low density lipoprotein cholesterol concentrations to high density lipoprotein cholesterol concentrations.13 14 15 No clear evidence for protective effects of tea in humans, however, has been reported. Only a few studies have examined the relation between tea intake and the incidence of cancer or cardiovascular disease, and their results were inconsistent.16 17 18

With regard to prevention of cardiovascular disease, the association between tea drinking and serum concentrations of lipids and other markers must be confirmed first. Nevertheless, to our knowledge only one study of green tea has been carried out, and this showed an inverse association between consumption of green tea and serum total cholesterol concentration but not between green tea and triglyceride or lipoprotein concentrations.19 Only a few studies of black tea have been carried out, and they did not find a significant association between consumption of black tea and serum lipid concentration because few “heavy tea drinkers” were included in the study populations.20 21 We investigated the association between consumption of green tea and various serum markers in a Japanese population, with special reference to preventive effects of the tea against cardiovascular disease and disorders of the liver.

Methods

In 1986 we began a prospective cohort study in residents aged over 40 years old in the town of Yoshimi in the prefecture of Saitama. To carry out the epidemiological survey we used a self administered questionnaire covering 90 lifestyle factors—such as present and past eating habits and history of consumption of cigarettes and alcohol—and history of disease, present state of health, and medication. Information on consumption of green tea (categorised as </= 3, 4-9, or >/= 10 cups a day) was extracted from the answers on the questionnaire.

The survey covered 8553 individuals (95% of all residents aged over 40), who were invited to participate in yearly health screening checks. Of those who agreed to participate, 3625 self selected individuals (1371 men, 2254 women) gave peripheral blood samples at each health screening check. Samples taken during 1986-90 were subjected to biochemical and immunological assays. All blood samples were collected between 1 pm and 3 pm after strict fasting of > 12 hours before the health checks in July, August, or September. All assays were started within five hours of the blood samples being taken.

The components of the serum were determined for each blood sample: total protein, albumin, globulin, protein fractionation, total cholesterol, triglyceride, lipoprotein fractions (agarose gel electrophoresis), alanine aminotransferase, aspartate aminotransferase, haemoglobin, packed cell volume, chloride, potassium, sodium, vitamin A, and lipid peroxides (thiobarbituric acid assay). Immunological assays determined the cytotoxic activity of natural killer cells, subsets of T cells, and reactivity of peripheral blood lymphocytes in the presence of phytohaemagglutinin. Blood pressure was measured when the blood samples were taken. Of the 3625 participants, 2255 (780 men, 1475 women) had a yearly health check more than twice during the study period. At these participants' second visit, their blood samples were subjected to assay serum concentrations of selenium, (alpha) fetoprotein, carcinoembryonic antigen, ferritin (radioimmunoassays), and isolation of DNA from lymphocytes. Immunological and genetic characteristics of this cohort population have been reported previously.22 23 24 The present study dealt with only 1371 men as the effects of green tea were not clearly observed among the women, whose serum lipid concentrations and hepatological markers remained low because so few of them were drinkers and smokers.

Multivariate analysis of variance was used to control for the effects of confounding factors with the software package SPSS. Potential covariates considered in this analysis were age, cigarette smoking, alcohol consumption, and relative body weight, which is the ratio of observed weight to the standard one calculated for individual height, sex, and age in the Japanese population. Age was categorised as <40, 40-49, 50-59, 60-69, or >/= 70 years. Cigarette smoking was categorised according to whether subjects had never smoked, were past smokers, or were current smokers and according to the number of cigarettes they smoked daily times the number of years they had been smokers (<500, 500-999, or >/=1000). Alcohol consumption was categorised according to whether subjects had never drunk alcohol, were past drinkers, occasional drinkers, or daily drinkers and according to the amount of alcohol (ml ethanol) they drank daily times the number of years they had been drinking (<500, 500-999, 1000-1499, or >/=1500). Relative body weight was categorised as </=0.79, 0.80-0.89, 0.90-1.09, 1.10-1.19, or >/=1.20.

Results

Discussion

Our cross sectional study showed a close association between high consumption of green tea and normalisation of serum components, which reflects cardiovascular and liver diseases. Increased consumption of green tea, especially more than 10 cups a day, was associated with decreased serum total cholesterol and triglyceride concentrations; increased high density lipoprotein cholesterol concentrations and decreased low density and very low density lipoprotein cholesterol concentrations, resulting in a reduced atherogenic index; decreased serum concentrations of lipid peroxides among smokers; and decreased aspartate aminotransferase and alanine aminotransferase concentrations, and serum ferritin concentration. The associations between green tea and serum total cholesterol and triglyceride concentrations and between green tea and high and low density lipoprotein cholesterol concentrations are well correlated with experimental observations and the prevalence of heart disease in our cohort, implying that green tea may act preventively against cardiovascular disease. Moreover, this is the first time that an inverse association between consumption of green tea and cell damage of the liver, based on serum markers in humans has been reported.

Advancing age was associated with increased consumption of green tea. This could imply that consumption was also associated with being part of a healthier surviving cohort. If this is the case statistical adjustment for age used in this study could be insufficient to eliminate this effect. A follow up study is needed to clarify this problem.

Increased generation of oxygen radicals and subsequent formation of lipid peroxides were suggested to be cytotoxic and sometimes carcinogenic. Various forms of iron participated in radical reaction in vivo.26 27 Thus high stores of body iron were reported to be associated with increased risk of cancers such as lung, liver, and colon but not stomach.28 29 30 With regard to stores of body iron and lipid peroxidation, our cohort data showed a significant association between serum ferritin concentrations, a stable marker for stores of body iron, and serum concentrations of lipid peroxides (correlation coefficient 0.25, P<0.001). The inverse association between the serum concentrations of ferritin and lipid peroxides and consumption of green tea suggests that the tea has protective effects on the development of cancer.

Given the potential implication of our findings, a follow up study of the cohort population is warranted to assess the association between consumption of green tea and various diseases including cancer. A follow up study and intervention study by green tea extract are under way.