Introduction
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Tea is the most widely consumed beverage aside from water, with a per capita worldwide consumption of approximately 0.12 liter per day. Tea is manufactured in four basic forms. Green tea is prepared in such a way as to preclude the oxidation of green leaf polyphenols. During black tea production, oxidation is promoted so that most of these substances are oxidized. Oolong tea is a partially oxidized product. White tea is tea made from new growth buds and young leaves that have been steamed to inactivate polyphenol oxidation, and then dried. The buds may be shielded from sunlight to prevent formation of chlorophyll. Of the approximately 2.5 million metric tons of dried tea manufactured, only 20% is green tea, and less than 2% is oolong tea. Green tea is consumed primarily in China, Japan, and a few countries in North Africa and the Middle East.1
Green tea
The chemical composition of green tea varies with climate, season, horticultural practices, and position of the leaf on the harvested shoot. The major components of interest are the polyphenols. The major polyphenols in green tea are flavonoids. The four major flavonoids in green tea are the catechins epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG) (Figure 1.) Epigallocatechin gallate is viewed as the most significant active
Pharmacokinetics
Pharmacokinetic parameters of EGCG, EGC, and EC were analyzed after administration of a single oral dose of green tea or decaffeinated green tea (20 mg tea solids/kg) or EGCG (2 mg/kg) to eight subjects. The plasma and urine levels of total EGCG, EGC, and EC (free plus conjugated forms) were quantified by high performance liquid chromatography coupled to an electrochemical detector. The plasma concentration time curves of the catechins were fitted in a one-compartment model. The maximum plasma
Antiviral
Epigallocatechin gallate and ECG were found to be potent inhibitors of influenza virus replication in cell culture. This effect was observed in all influenza virus subtypes tested, including A/H1N1, A/H3N2, and B virus. Quantitative analysis revealed that, at high concentration, EGCG and ECG also suppressed viral RNA synthesis in cells, whereas EGC failed to show similar effect. Similarly, EGCG and ECG inhibited the neuraminidase activity more effectively than the EGC. Neuraminidase is an
Atherosclerosis
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Population-based and clinical studies indicate that the antioxidant properties of green tea may help prevent atherosclerosis, particularly coronary artery disease.7
According to Japanese research, green tea reduces the levels of LDL cholesterol, thereby reducing the risk of coronary heart disease. Studies have found that regular consumption of tea protects against heart disease, with one study documenting that the risk was 36% lower for tea drinkers.8
Serum malondialdehyde–modified LDL
Autoimmune diseases
Hsu and Dickinson15 suspected that there may be a link between green tea consumption and autoimmunity after noting that xerostomia, an autoimmune disorder suffered by approximately 30% of elderly Americans, occurs in only one to two percent of Chinese people in the same age group. Sjogren’s syndrome is an autoimmune disorder that affects the salivary glands, leading to xerostomia, and the lacrimal glands, resulting in xerophthalmia. Secondary Sjogren’s syndrome is associated with other
Cardiac arrhythmias
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A study presented at the Heart Rhythm Society’s 25th Annual Scientific Sessions in 200417 found that EGCG could help prevent ventricular arrhythmias, which can follow infarction. Ventricular arrhythmias include ventricular tachycardia and ventricular fibrillation, which are commonly associated with infarction or with the scarring of the heart muscle, which occurrs during the event.
Tea drinkers have been known to have a lower rate of death following a heart attack than those who do not drink
Cancer
The cancer-protective effects of green tea have been reported in several population-based studies. For example, cancer rates tend to be low in countries such as Japan where green tea is regularly consumed. It is not possible to determine from these population-based studies whether green tea actually prevents cancer in people. However, emerging animal and clinical studies are beginning to suggest that EGCG may play an important role in the prevention of cancer.
It has been suggested that EGCG and
Bladder cancer
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A few studies have examined the relationship between bladder cancer and green tea consumption. In one study that compared people with and without bladder cancer, researchers found that women who drank black tea and powdered green tea were less likely to develop bladder cancer.22
Epigallocatechin gallate inhibited growth of the NBT-II bladder tumor cells in a dose- and time-dependent manner. Flow cytometry showed a G0/G1 arrest in cells when cultured with EGCG at doses of 10, 20, or 40 μmol/L for
Breast cancer
Epigallocatechin gallate, EGC, and ECG reduce the proliferation of human breast cancer cells in vitro and decrease breast tumor growth in rodents. Furthermore, in vitro studies have demonstrated that the combination of EGCG and tamoxifen is synergistically cytotoxic to ERalpha- breast cancer cells. These results suggest that the catechins have significant potential in the treatment of breast cancer.25
A Japanese study comparing 472 women with breast cancer who drank differing amounts of green
Cervical cancer
Ahn et al27 investigated the anticancer effects of EGCG in human papillomavirus (HPV)-16 associated cervical cancer cell line, CaSki cells. The growth inhibitory mechanisms and regulation of gene expression by EGCG were also evaluated. Epigallocatechin gallate showed growth inhibitory effects in CaSki cells in a dose-dependent fashion, with an inhibitory dose (ID)50 of approximately 35 μmol/L. When CaSki cells were further tested for EGCG-induced apoptosis, apoptotic cells were significantly
Colorectal cancer
A study at the Linus Pauling Institute at Oregon State University on mice that were genetically predisposed to develop tumors in their intestines, revealed after 12 weeks of treatment that mice that were given green tea had significantly fewer tumors than mice that received no treatment.28
Phenol sulfotransferases are involved in cancer growth, and EGCG was shown to inhibit this activity in a human colon cancer cell line.29
Esophageal cancer
Studies in laboratory animals have found that green tea polyphenols inhibit the growth of esophageal cancer cells.30 However, results of studies in people have been conflicting. In fact, some evidence suggests the hotter the tea (or any other hot beverage), the greater the risk of developing esophageal cancer. However, researchers reporting on a case-control study found that Chinese men and women who drink green tea have a reduced risk of up to 60% of developing esophageal cancer.31 Taking
Lung cancer
Consumption of green tea was found to be associated with a reduced risk of lung cancer among nonsmokers.32 Treatment of human lung cancer cell line A549 cells with EGCG significantly inhibited the expression levels of hnRNP B1 mRNA and the elevated levels of hnRNP B1 protein, both of which are elevated in cancer cells. Furthermore, EGCG inhibited the promoter activity of hnRNP A2/B1 gene expression, preventing lung cancer.33
Osteosarcoma
Current treatment of osteosarcoma is associated with poor prognosis, especially due to the increased risk of developing other cancers with chemotherapy. Roomi et al34 investigated the effect of a unique mixture of nutrients containing lysine, proline, arginine, ascorbic acid, and EGCG on human osteosarcoma cell lines U-2OS, MNNG-HOS, and Ewing’s sarcoma SK-ES-1 by measuring cell proliferation, expression of matrix metalloproteinase-2 (MMP-2), MMP-9, and invasive and angiogenesis potential. The
Pancreatic cancer
Takada et al35 tested whether EGCG affects proliferative and invasive activity of human pancreatic carcinoma cells. The results indicate that the growth of all three pancreatic carcinoma cells (PANC-1, MIA PaCa-2 and BxPC-3) was significantly suppressed by EGCG treatment in a dose-dependent manner. Epigallocatechin gallate may be a potent biologic inhibitor of pancreatic carcinoma, reducing their proliferative and invasive activity.
Prostate cancer
The first strong evidence of green tea and its potential towards prostate cancer appeared when Paschka et al36 tested EGCG on the prostate cancer cell lines LNCaP, PC-3, and DU145. Epigallocatechin gallate proved to be the most potent catechin at inhibiting cell growth. The inhibition induced by EGCG was found to occur via apoptotic cell death as shown by changes in nuclear morphology and DNA fragmentation.
Epigallocatechin gallate acts against urokinase (an enzyme often found in large amounts
Skin cancer
Studies suggest that EGCG and green tea polyphenols have anti-inflammatory and anticancer properties that may help prevent the onset and growth of skin tumors. Topical application of EGCG may prevent UV-B–induced immunosuppression and precancerous cell changes after UV-B exposure.40
Stomach cancer
Laboratory studies have found that green tea polyphenols inhibit the growth of stomach cancer cells in test tubes. The exposure of human stomach cancer KATO III cells to EGCG led to both growth inhibition and the induction of apoptosis.41
Leukemia
A study at the Mayo Clinic in 2003 by Lee et al42 looked at the effects of EGCG on chronic lymphocytic B cells isolated from leukemia patients. In the study, Lee et al showed that the addition of EGCG to these cells reduced the vascular endothelial growth factor-receptor phosphorylation. This led to the disruption of the vascular endothelial growth factor–dependent autocrine pathway that protects the cells from apoptosis.
This provides strong evidence that this inhibitory effect may have
Human immunodeficiency virus
Epigallocatechin gallate prevents the binding of HIV to human T cells, the first step in HIV infection. Nance and Shearer43 demonstrated that EGCG inhibited the binding of human immunodeficiency virus (HIV) to human CD4(+) lymphocytes, which is a crucial step in HIV infection. For infection to develop, the viruses need entry into CD4(+) lymphocytes through a step dependent on adhesion to the CD4 molecule and subsequent intracellular viral proliferation. Epigallocatechin gallate showed a strong
Hope for hair loss?
An animal study by Esfandiari and Kelley44 found that 33% of randomly assigned female BALB/black mice (60 in total), which had developed spontaneous hair loss on the head, neck, and dorsal areas, and who received green tea extract in their drinking water, developed hair regrowth within a period of six months. The researchers did not observe any spontaneous remission or hair regrowth among the controls. Moreover, 8% of the control rodents showed progressive hair loss during the study, whereas
Skin health
Research using pooled human keratinocytes (skin cells) to study the normal growth of the skin cells alone and comparing it to the growth of the cells when exposed to EGCG revealed that EGCG reactivated dying skin cells. Cells that migrate toward the surface of the skin normally live about 28 days, and by day 20, they sit on the epidermis getting ready to die and slough off. Current research seems to show that EGCG reactivates epidermis cells.45
Athletic enhancement
A study published in the American Journal of Physiology. Regulatory, Integrative and Comparative Physiology tested the effect of green tea extract on exercise endurance of lab rats. Over 10 weeks, endurance exercise performance was boosted up to 24% with green tea extract supplementation. It is important to note that EGCG alone did not have the same effect. A combination extract containing EGCG plus naturally occurring polyphenols improved endurance. Additionally, evidence indicates that the
Joint health
Stimulation of human chondrocytes with IL-1 beta (5 ng/mL) for 24 hours resulted in significantly enhanced production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) when compared to untreated controls (P< .001). Pretreament of human chondrocytes with EGCG showed a dose-dependent inhibition in the production of NO and PGE(2) by 48% and 24%, respectively, and correlated with the inhibition of iNOS and COX-2 activities (P< .005). In addition, IL-1 beta–induced expression of iNOS and COX-2
Inflammatory bowel disease (IBD)
Green tea may help reduce inflammation associated with Crohn’s disease and ulcerative colitis.49 It was determined that EGCG can inhibit proinflammatory interleukin 8 (IL-8) in a study of human lung alveolar epithelial cells (A549 line),50 doing the same in the gastrointestinal tract seemed possible.
After oral administration, EGCG is retained in the gastrointestinal tract, where it is thought to exert preventive functions against inflammatory bowel disease and colon cancer.51 Porath et al51
Diabetes
Green tea has been used traditionally to control blood sugar in the body. Animal studies suggest that green tea may help prevent the development of type 1 diabetes and slow the progression once it has developed.53
EGCG has been found to increase insulin sensitivity and may repair damaged beta cells.54, 55, 56
High-performance liquid chromatography fractionation of tea extracts utilizing a Waters SymmetryPrep C18 column showed that the majority of the insulin-potentiating activity for green tea
Liver disease
Population-based studies have shown that men who drink more than 10 cups of green tea per day are less likely to develop disorders of the liver. Green tea also appears to protect the liver from the damaging effects of toxic substances such as alcohol. Animal studies have shown that green tea helps protect against the development of liver tumors in mice. Kuo and Lin57 examined EGCG for its effect on proliferation and cell cycle progression in a human liver cancer cell line, Hep G2. The results
Neuroprotective property
In the Journal of Neurochemistry, EGCG protected lab mice from a neurotoxin (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in the mouse model of Parkinson’s disease.
N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxin caused dopamine neuron loss in substantia nigra concomitant with a depletion in striatal dopamine and tyrosine hydroxylase protein levels. Pretreatment of mice with EGCG prevented these effects. In addition, EGCG increased the activities of antioxidant enzymes in the brain. The
Antioxidant properties
The early evidence of antioxidant properties of EGCG came from the experimental data that showed EGCG induced inhibition of soybean lipoxygenase (IC50 = 10-20 μmol/L).60 Later, it was reported that EGCG inhibited TPA-induced oxidative DNA base modification in HeLa cells, inhibited Cu2+ mediated oxidation of low-density lipoprotein (LDL), reduced tert-butyl hydroperoxide-induced lipid peroxidation, and blocked the production of reactive oxygen species derived from NADPH-cytochrome P450-mediated
Candida albicans
Martinez et al63 studied the effect of EGCG on Candida albicans dihydrofolate reductase. EGCG is an efficient inhibitor of C albicans dihydrofolate reductase (K(i) = 0.7 μmol/L). Epigallocatechin gallate showed synergy with inhibitors of the ergosterol biosynthesis pathway in C albicans such as azole antifungals and terbinafine. Epigallocatechin gallate acts as an antifolate compound on C albicans, disturbing its folic acid metabolism. This effect could explain the molecular mechanism for the
Weight loss
Studies suggest that EGCG may boost metabolism and help burn fat. Dulloo et al64 showed that resting metabolic rate increased by four percent after 90 mg of EGCG was consumed three times per day in human test subjects.
Westerterp-Plantenga et al65 concluded that in habitual low-caffeine consumers, a green tea-caffeine mixture improved weight loss, partly through thermogenesis and fat oxidation.
An animal study involving EGCG caused rats to lose up to 21% of their body weight. Rats injected with
Iron-Overload
Secondary iron overload is found in beta-thalassemia patients because of increased dietary iron absorption and multiple blood transfusions. Excessive iron catalyzes free-radical generation, leading to oxidative damage and vital organ dysfunction. Nontransferrin-bound iron detected in thalassemic plasma is highly toxic and chelatable. Though used to treat iron overload, desferrioxamine and deferiprone also have adverse effects. The Fe(3+) was found to bind to green tea crude extract and form a
Contraindications
Green tea contains vitamin K and may interfere with warfarin.68 However, that was based on one individual consuming a gallon of green tea daily while on the medication. Based on current literature, there does not appear to be any significant side-effects or toxicity associated with regular green tea consumption.
Patients sensitive to caffeine should use caffeine-free green tea or a caffeine-free extract.
Conclusion
Green tea, from capsules to tea bags, is consumed throughout the world. The years of safe consumption of this beverage, backed up by the numerous studies showing health benefits, warrant a general recommendation to consume it regularly. This abstract demonstrates by documented studies the benefits of green tea for its anti-inflammatory and antioxidant potential. It has been used to treat cardiovascular diseases, oral cavity diseases, cardiovascular uses, and Parkinson’s disease. There is also a
Robert L. Pastore, PhD, is Director of Clinical Nutrition, Fratellone Medical Associates, and a Certified Nutrition Specialist.
