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Inhibition of carcinogenesis by tea: the evidence from experimental studies.

In its various forms, tea is one of the most widely consumed beverages in the world. Elucidation of the chemical components of tea has revealed that the beverage is a rich repository of antioxidants. Among these are the polyphenolics, common to green tea, but also found in black teas together with oxidized polymers that in part account, for the darkened color. Consumption of tea on a regular basis has been associated with reduced risk of several forms of cancer in human populations, with the strongest evidence linking green tea use to reduction in cancer risk in parts of Asia. To understand how tea prevents cancer, studies in animal carcinogenesis models have been done with very encouraging results. This review examines the available data from animal studies on the effects of tea in the prevention of cancer.

Animals↗

Tea drinking and microcytic anemia in infants.

To evaluate the effect of tea drinking on the occurrence of microcytic anemia in infants, we studied 122 healthy infants who underwent routine blood counts at the age of 6-12 months. An overall high frequency of anemia (Hb less than 11 gm/dl-48.4%), microcytosis (MCV less than 70 Mm3-21.3%) and microcytic anemia (19%) was found in the whole group. The percentage of tea drinking infants with microcytic anemia (32.6%) was significantly higher than that of the non-tea drinkers (3.5%). The daily amount of tea drinking was 50-750 ml (median 250 ml). The tea drinkers had significantly lower mean levels of hemoglobin than that of the non-tea drinkers (10.5 +/- 1.2 gm/dl vs 11.2 +/- 0.8 gm/dl, respectively) and significantly lower mean levels of mean corpuscular volume than that of the non-tea drinkers (71.5 +/- 7.1 micron 3 vs 76.1 +/- 4.6 micron 3). There were no significant differences between the two groups in their sex distribution and in the duration of breast feeding. The two groups differed with regard to their ages and social class but a multivariate analysis had excluded the possible confounding effect of these differences on the hematological results. Based on our finding we do not recommend giving tea to infants whose main source of iron is from milk, grains, vegetables or medicinal sources.

Anemia↗

Consumption of green or black tea does not increase resistance of low-density lipoprotein to oxidation in humans.

Epidemiologic studies indicated that tea consumption reduces the risk of cardiovascular disease. We assessed the effect of green or black tea consumption on resistance of low-density lipoprotein (LDL) to oxidation ex vivo and on serum lipid concentrations in healthy volunteers. In a 4-wk parallel comparison trial, 45 volunteers consumed 900 mL (6 cups) mineral water, green tea, or black tea/d. Blood samples drawn while subjects were fasting were obtained before and after the study. The effect on resistance of subsequently isolated LDL to oxidation of adding green or black tea extract to plasma was investigated in an in vitro experiment. Consumption of 900 mL (6 cups) green or black tea/d did not affect serum lipid concentrations, resistance of LDL to oxidation, or markers of oxidative damage to lipids in vivo, although consumption of green tea slightly increased total antioxidant activity of plasma. The in vitro experiment showed that resistance of isolated LDL to oxidation increased only after incubation of plasma with very high amounts of green or black tea. These amounts, when converted to tea catechin concentrations, were much higher than those expected in vivo. We conclude that daily consumption of 900 mL (6 cups) green or black tea/d for 4 wk had no effect on serum lipid concentrations or resistance of LDL to oxidation ex vivo. Future research should focus on mechanisms by which tea flavonoids may reduce the risk of cardiovascular disease other than by increasing the intrinsic antioxidant status of LDL.

Adult↗

Lack of association between tea and cardiovascular disease in college alumni.

BACKGROUND: Epidemiological studies suggest that tea intake, a major dietary source of flavonoids, may be associated with a decreased risk of cardiovascular disease (CVD). METHODS: We prospectively followed 17 228 subjects (mean age, 59.5 years) initially free of CVD and cancer from the College Alumni Health Study. Participants provided baseline self-reports of tea consumption (cups/day) and coronary risk factors. During a median follow-up of 15 years, there were 3372, 2615, and 757 cases of CVD, coronary heart disease (CHD), and stroke, respectively, ascertained from either self-reports or death certificates. RESULTS: Overall, the median level of tea consumption was 1 cup/day. Compared with participants consuming no tea, the multivariate relative risks (RR) of CVD for those drinking <1, 1, 2, 3, and >/=4 cups/day were 0.99, 0.96, 0.95, 0.91, and 0.95, respectively (P, trend = 0.19). The multivariate RR were 0.97, 0.98, 0.93, 0.85, and 0.98 for CHD (P, trend = 0.25), and 1.05, 0.89, 1.00, 1.09, and 0.83 for stroke (P, trend = 0.53). There was no evidence of effect modification. Changes in tea intake were assessed in a subgroup of 7730 men, with those continuing to drink tea having a non-significant 33% reduction in the risk of stroke. CONCLUSIONS: Tea intake, likely consumed as black tea, was not strongly associated with a reduced risk of CVD in this population of US college alumni.

Cardiovascular Diseases↗

Antifungal effects of Melaleuca alternifolia (tea tree) oil and its components on Candida albicans, Candida glabrata and Saccharomyces cerevisiae.

OBJECTIVES: The aim of this study was to investigate the mechanism of action of tea tree oil and its components against Candida albicans, Candida glabrata and Saccharomyces cerevisiae. METHODS: Yeast cells were treated with tea tree oil or components, at one or more concentrations, for up to 6 h. During this time, alterations in permeability were assessed by measuring the leakage of 260 nm absorbing materials and by the uptake of Methylene Blue dye. Membrane fluidity was measured by 1,6-diphenyl-1,3,5-hexatriene fluorescence. The effects of tea tree oil on glucose-induced medium acidification were quantified by measuring the pH of cell suspensions in the presence of both tea tree oil and glucose. RESULTS: The treatment of C. albicans with tea tree oil and components at concentrations of between 0.25 and 1.0% (v/v) altered both permeability and membrane fluidity. Membrane fluidity was also increased when C. albicans was cultured for 24 h with 0.016%-0.06% (v/v) tea tree oil, as compared with control cells. For all three organisms, glucose-induced acidification of the external medium was inhibited in a dose-dependent manner in the presence of 0.2%, 0.3% and 0.4% tea tree oil. CONCLUSIONS: Data from this study support the hypothesis that tea tree oil and components exert their antifungal actions by altering membrane properties and compromising membrane-associated functions.

Antifungal Agents↗

Green tea polyphenols block endotoxin-induced tumor necrosis factor-production and lethality in a murine model.

Green tea polyphenols are potent antioxidants. They have both anti-cancer and anti-inflammatory effects. However, their mechanisms of actions remain unclear. In inflammation, tumor necrosis factor-alpha(TNFalpha) plays a pivotal role. NF-KB, an oxidative stress -sensitive nuclear transcription factor, controls the expression of many genes including the TNFalpha gene. We postulated that green tea polyphenols regulate TNFalpha gene expression by modulating NF-KB activation through their antioxidant properties. In the macrophage cell line, RAW264.7, (-)epigallocatechin gallate (EGCG), the major green tea polyphenol, decreased lipopolysaccharide (LPS)-induced TNFalpha production in a dose-dependent fashion (50% inhibition at 100 mmol/L). EGCG also inhibited LPS-induced TNFalpha mRNA expression and nuclear NF-KB-binding activity in RAW264.7 cells (30-40% inhibition at 100 mmol/L). Similarly, EGCG inhibited LPS-induced TNFalpha production in elicited mouse peritoneal macrophages. In male BALB/c mice, green tea polyphenols (given by oral gavage 2 h prior to an i.p. injection of 40 mg LPS/kg body wt) decreased LPS-induced TNFalpha production in serum in a dose-responsive fashion. At a dose of 0.5 g green tea polyphenols/kg body wt, serum TNFalpha was reduced by 80% of control. Moreover, 0.5 g green tea polyphenols/kg body wt completely inhibited LPS-induced lethality in male BALB/c mice. We conclude that the anti-inflammatory mechanism of green tea polyphenols is mediated at least in part through down-regulation of TNFalpha gene expression by blocking NF-KB activation. These findings suggest that green tea polyphenols may be effective therapy for a variety of inflammatory processes.

Administration, Oral↗

Antimutagenicity and catechin content of soluble instant teas.

The antimutagenic properties of soluble instant teas were examined using the bacterial Ames assay. Inhibition of the numbers of revertants induced from a number of known mutagens indicates that aqueous extracts of instant teas have antimutagenic activity and antioxidative properties, and can inhibit nitrosation reactions. Despite a significant reduction in the amounts of major green tea catechins, quantified using reversed-phase HPLC with electro-chemical detection, no differences in antimutagenicity were observed between the instant teas, a black fermented tea and a green tea. Oxidation of polyphenolic compounds which occurs during the production of instant tea does not therefore decrease the antioxidant, free radical scavenging and antimutagenic properties. This suggests that catechins are not the only compounds responsible for the protective effects of teas.

Antimutagenic Agents↗

Green tea in chemoprevention of cancer.

The concept of prevention of cancer using naturally occurring substances that could be included in the diet consumed by the human population is gaining increasing attention. Tea, next to water, is the most popularly consumed beverage in the world and it is grown in about 30 countries. Abundant data, amassed from several laboratories around the world in the last ten years, provided convincing evidence that polyphenolic antioxidants present in tea afford protection against cancer risk in many animal-tumor bioassay systems. The epidemiological studies, though inconclusive, have also suggested that the consumption of tea is associated with a lowered risk of cancer. Much of this work has been done on green tea; less is known about black tea. Green tea contains many polyphenolic antioxidants, and (-)-epigallocatechin-3-gallate (EGCG) is the key polyphenolic antioxidant believed to be responsible for most of the cancer chemopreventive properties of green tea. This review will discuss these effects and the molecular mechanisms associated with the biological response to green-tea polyphenols.

Humans↗

Tea consumption and lung cancer risk: a case-control study in Okinawa, Japan.

To disclose the relationship between tea consumption and lung cancer risk, we analyzed the data from a case-control study conducted in Okinawa, Japan from 1988 to 1991. The analysis, based on 333 cases and 666 age-, sex- and residence-matched controls, provided the following major findings. (a) The greater the intake of Okinawa tea (a partially fermented tea), the smaller the risk, particularly in women. For females, the odds ratios (and 95% confidence intervals) for those who consumed 1-4, 5-9, and 10 cups or more of Okinawan tea every day, relative to non-daily tea drinkers, were 0.77 (0.28-2.13), 0.77 (0.26-2.25) and 0.38 (0.12-1.18), respectively (trend: P = 0.032). The corresponding odds ratios for males were 0.85 (0.45-1.55), 0.85 (0.45-1.56) and 0.57 (0.31-1.06) (trend: P = 0.053). (b) The risk reduction by Okinawan tea consumption was detected mainly in squamous cell carcinoma. Daily tea consumption significantly decreased the risk of squamous cell carcinoma in males and females, the odds ratios being 0.50 (95% confidence interval 0.27-0.93) and 0.08 (0.01-0.68), respectively. These findings suggest a protective effect of tea consumption against lung cancer in humans.

Adenocarcinoma↗

Influence of drinking green tea on breast cancer malignancy among Japanese patients.

Inhibitory effects of green tea on carcinogenesis have been investigated in numerous laboratory studies using (-)-epigallocatechin gallate (EGCG) or crude green tea extract, and there is also some epidemiologic evidence. Further, EGCG has been reported to inhibit the growth of cancer cells, lung metastasis in an animal model, and urokinase activity. In this study, we first examined the association between consumption of green tea prior to clinical cancer onset and various clinical parameters assessed at surgery among 472 patients with stage I, II, and III breast cancer. We found that increased consumption of green tea was closely associated with decreased numbers of axillary lymph node metastases among premenopausal patients with stage I and II breast cancer and with increased expression of progesterone receptor (PgR) and estrogen receptor (ER) among postmenopausal ones. Since these are potential prognostic factors, we then investigated the prognosis of breast cancer with special reference to consumption of green tea, in a follow-up study of these patients. We found that increased consumption of green tea was correlated with decreased recurrence of stage I and II breast cancer (P < 0.05 for crude disease-free survival); the recurrence rate was 16.7 or 24.3% among those consuming > or = 5 cups or < or = 4 cups per day, respectively, in a seven-year follow-up of stage I and II breast cancer, and the relative risk of recurrence was 0.564 (95% confidence interval, 0.350-0.911) after adjustment for other lifestyle factors. However, no improvement in prognosis was observed in stage III breast cancer. Our results indicate that increased consumption of green tea prior to clinical cancer onset is significantly associated with improved prognosis of stage I and II breast cancer, and this association may be related to a modifying effect of green tea on the clinical characteristics of the cancer.

Adult↗

HTLV-1 provirus load in peripheral blood lymphocytes of HTLV-1 carriers is diminished by green tea drinking.

Human T-cell lymphotropic virus type 1 (HTLV-1) is causatively associated with adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since a high level of HTLV-1 provirus load in circulating lymphocytes is thought to be a risk for ATL and HAM/TSP, diminution of HTLV-1 provirus load in the circulation may prevent these intractable diseases. Our previous study (Jpn J Cancer Res 2000; 91: 34-40) demonstrated that green tea polyphenols inhibit in vitro growth of ATL cells, as well as HTLV-1-infected T-cells. The present study aimed to investigate the in vivo effect of green tea polyphenols on HTLV-1 provirus load in peripheral blood lymphocytes on HTLV-1 carriers. We recruited 83 asymptomatic HTLV-1 carriers to examine HTLV-1 provirus DNA with or without administration of capsulated green tea extract powder. Thirty-seven subjects were followed up for 5 months by measuring HTLV-1 provirus load after daily intake of 9 capsules of green tea extract powder per day (equivalent to 10 cups of regular green tea), and 46 subjects lived ad libitum without intake of any green tea capsule. The real-time PCR quantification of HTLV-1 DNA revealed a wide range of variation of HTLV-1 provirus load among asymptomatic HTLV-1 carriers (0.2-200.2 copies of HTLV-1 provirus load per 1000 peripheral blood lymphocytes). Daily intake of the capsulated green tea for 5 months significantly diminished the HTLV-1 provirus load as compared with the controls (P = 0.031). These results suggest that green tea drinking suppresses proliferation of HTLV-1-infected lymphocytes in vivo.

Administration, Oral↗

The genetics of tea and coffee drinking and preference for source of caffeine in a large community sample of Australian twins.

AIMS: To investigate the genetic and environmental influences on tea consumption and their commonalities with coffee consumption; and to further examine the genetic and environmental aetiology of preference for tea/coffee. DESIGN: A classical twin design was used in which the similarity of identical and non-identical twins is compared, enabling estimates of genetic, common environmental and unique environmental influence on the trait. SETTING AND PARTICIPANTS: An Australian population-based sample of 1796 identical (i.e. monozygotic) and 2013 non-identical (i.e. dizygotic) twin pairs aged 16-87 years was studied, roughly three-fifths of whom were female. The sample represented approximately 70% of those approached for study participation. MEASUREMENTS: As part of a Health and Lifestyle Questionnaire, respondents were asked how many cups of each tea and coffee they consumed per day. Additional measures of 'total tea and coffee consumption' and 'preference for coffee' were calculated. FINDINGS: Age was positively associated with tea consumption but negatively associated with coffee preference; women consumed more beverages than men, but showed a lower preference for coffee. An inverse relation between tea and coffee consumption--larger in females (-0.41) than males (-0.34)--was supported. This association was mediated entirely by the unique environment in males, and by both the unique environment (68.3%) and genes (31.7%) in females. Tea and coffee drinking were shown to have similar heritabilities (0.46) in males, but tea consumption was influenced by common environmental factors whereas coffee consumption was not. Coffee preference was shown to be influenced by genes (0.42) and the unique environment (0.58). CONCLUSIONS: As the patterns of genetic and environmental variation were shown to differ for tea and coffee consumption it may be more informative to retain them as separate measures of caffeine intake in future studies of stimulant use and taste perception.

Adolescent↗

Candidate foods in the Asia-Pacific region for cardiovascular protection: Oriental tea.

Chinese tea and the major health effects include: antimicrobial, anti-ultraviolet radiation, anticancer, lowering blood lipid and glucose, and protecting against coronary heart diseases. In contrast to the extensive studies on the protective effects of tea on cancer, fewer studies on the health effects of tea on cardiovascular diseases (CVD) have been published. This paper summarises the research results on the possible protective effects of tea on CVD available in China. The results from animal studies clearly demonstrated that tea pigments are effective in lowering blood lipid levels and preventing plaque formation in the aorta. However, the evidence of tea pigments in protecting ischemia heart disease (IHD) in humans is less convincing. One large well-designed ecological study reported an inverse correlation between tea drinking and IHD mortality; but the inverse correlation disappeared after controlling possible confounding factors. However, the effects in improving blood lipid levels and rheology biomarkers in hyperlipidemia subjects or CVD patients by tea pigments seem promising. However, these studies were not well-designed, controlled randomized clinical trials. This made the assessment difficult and inconclusive.

Animals↗

The propensity of different brands of tea and coffee to cause staining associated with chlorhexidine.

Dental staining is a well known and probably the most problematic side effect of using chlorhexidine oral products. Whatever mechanisms are involved, there is no doubt that cationic antiseptics, such as chlorhexidine, can precipitate or bind to surfaces anionic chromogens contained in foods and beverages. The aim of this study in vitro was to determine whether, under controlled conditions, different brands of tea or coffee varied in their propensity to cause staining associated with chlorhexidine. Optically clear acrylic specimens were cycled through saliva, chlorhexidine and different tea and coffee solutions. Staining was measured using a spectrophotometer. After 15 cycles, it was apparent that staining varied at the extreme, both within and between the tea and coffee groups. All coffee brands produced less staining than the tea brands. The least staining coffee and least staining tea brands were approximately 3x less chromogenic than the most staining equivalent beverage. Previous randomised controlled clinical trials have indicated that tea and coffee contribute to dental and tongue staining associated with chlorhexidine mouthrinses. Additionally, abstinence from tea and coffee significantly reduces staining. The results of this study in vitro suggest that when abstinence is difficult, tea and coffee brands of low chromogenicity may be recommended. Clearly these data in vitro require validation in vivo.

Analysis of Variance↗

Contribution of presystemic hepatic extraction to the low oral bioavailability of green tea catechins in rats.

Green tea and green tea catechins have been shown to possess potent cancer-preventive activities in rodent cancer models. At present, epidemiological evidence of the protective effect of green tea consumption against the development of human cancers is not conclusive. Oral bioavailability of green tea catechins has been shown to be low in animals and possibly in humans. This study is designed to determine the contribution of first-pass hepatic elimination to the low oral bioavailability of green tea catechins. Green tea catechin mixture was dosed to rats by intravenous or intraportal infusion. Blood samples were collected after dosing and analyzed using high-performance liquid chromatography with the coulometric electrode array detection system. The systemic clearance of epigallocatechin gallate (EGCG), epigallocatechin (EGC), and epicatechin (EC) was 8.9, 6.3, and 9.4 ml/min, respectively. The steady state volume of distribution (V(ss)) of EGCG, EGC, and EC was 432, 220, and 187 ml, respectively. We found that high percentage of green tea catechins escaped first-pass hepatic elimination, with 87.0, 108.3, and 94.9% of EGCG, EGC, and EC, respectively, available in the systemic blood following intraportal infusion. Our results suggest that factors within the gastrointestinal tract such as limited membrane permeability, transporter mediated intestinal secretion, or gut wall metabolism may contribute more significantly to the low oral bioavailability of green tea catechins.

Animals↗

[Effect of tea extracts, catechin and caffeine against type-I allergic reaction].

The antiallergic effects of green tea, oolong tea, and black tea extracts by hot water were examined. These extracts inhibited the passive cutaneous anaphylaxis (PCA) reaction of rat after oral administration. Three tea catechins, (--)-epigallocatechin (EGC), (--)-epicatechin gallate (ECg), and (--)-epigallocatechin gallate (EGCg) isolated from green tea showed stronger inhibitory effects than that of a green tea extract on the PCA reaction. The inhibitory effects of EGC and EGCg on the PCA reaction were greater than that of ECg. Caffeine also showed a inhibitory effect on the PCA reaction. These results indicate that tea could provide a significant protection against the type-I allergic reaction. These findings also suggest that tea catechins and caffeine play an important role in having an inhibitory effect on the type-I allergic reaction.

Administration, Oral↗

Effects of green tea intake on the development of coronary artery disease.

BACKGROUND: Green tea, a popular beverage in Japan, contains many polyphenolic antioxidants, which might prevent atherosclerosis. This study was designed to determine whether the consumption of green tea is proportionately associated with a decreased incidence of coronary artery disease (CAD) and the cardiovascular and cerebrovascular prognosis. METHODS AND RESULTS: The study group comprised 203 patients who underwent coronary angiography (109 patients with significant coronary stenosis and 94 patients without). Predictors for CAD were analyzed and the patients' cardiovascular and cerebrovascular events were followed. Green tea consumption was significantly higher in patients without CAD than in those with CAD (5.9+/-0.5 vs 3.5+/-0.3 cups/day; p<0.001). An inverse relationship between the intake of green tea and the incidence of CAD was observed (p<0.001). The green tea intake per day was an independent predictor for CAD based on a multivariate logistic regression analysis (odds ratio: 0.84 and 95% confidence interval: 0.76-0.91). In contrast, the green tea intake was not a predictor of cardiovascular and cerebrovascular events based on the Cox proportional hazard model. CONCLUSIONS: Green tea consumption was associated with a lower incidence of CAD in the present study population in Japan. Therefore, the more green tea patients consume, the less likely they are to have CAD.

Beverages↗

Autonomic nervous responses according to preference for the odor of jasmine tea.

The effect of jasmine tea odor on the autonomic nervous system was investigated by a power spectral analysis of the heart rate variability. We assigned eight volunteers to two groups with either a predilection for or antipathy toward the jasmine tea odor. We tested both high- and low-intensity jasmine tea odors. The low-intensity odor was produced by diluting 20-fold the jasmine tea used for the high-intensity odor test. The low-intensity odor produced an increase in parasympathetic nervous activity in both the predilection and antipathy groups. The high-intensity odor produced an increase in parasympathetic nervous activity in the predilection group, but an increase in sympathetic nervous activity in the antipathy group. The odor of Chinese green tea, a basic ingredient of jasmine tea, produced no effects similar to those of the jasmine tea odor. These results suggest that the jasmine tea odor activated the parasympathetic nerve, whereas the higher-intensity odor activated the sympathetic nerve in those subjects who disliked the odor.

Administration, Inhalation↗