As I have learned more about the compounds and mechanisms of green tea, and try to keep up with much of the research in women’s health and natural medicines, it becomes increasingly apparent that green tea has diverse uses in the prevention and treatment of conditions pertinent to women. These conditions include breast cancer, ovarian cancer, cervical dysplasia, polycystic ovarian syndrome, and weight management.
Derived from the tea plant Camellia sinensis, green tea is very high in polyphenols which have potent antioxidant and anti-tumor properties. The major polyphenols in green tea are flavonoids, including catechin, epicatechin, epicatechin gallate, epigallocatechin gallate, and proanthocyanidins. Epigallocatechin gallate (EGCG) is thought to be the most significant active component of green tea. Products with higher EGCG content, are thought to be more potent. Other compounds in green tea include vitamin C, a very small amount of caffeine, theanine, lignins, organic acids, protein and chlorophyll.
The catechins in green tea are thought to have anti-inflammatory activity by COX-1 and COX-2 inhibition, leukotriene inhibition, and nitric oxide synthetase activity. Green tea flavonoids might also reduce lipoprotein oxidation, reduce proliferation of vascular smooth muscle and inhibit the release of arachidonic acid from platelets. However, when used in humans, green tea has not yet shown any consistent effect on cardiovascular risk factors.
A study was recently published in JAMA to investigate the associations between green tea consumption and all-cause and cause-specific mortality. It is called the Ohsaki study, a population-based, prospective cohort study. This study. included Japanese adults aged 40-79 without a history of stroke, coronary heart disease or cancer, at initiation of the study. They were followed for up to 11 years for all cause mortality and for up to 7 years for cause-specific mortality. Green tea consumption was inversely associated with mortality due to all causes and inversely associated with cardiovascular disease. This inverse association for all-cause mortality association and for cardiovascular disease was stronger in women and even a greater association with cardiovascular disease.
Unfortunately, there was no beneficial effect of green tea consumption and reducing the hazard ratio of cancer mortality.
Despite lack of clarity regarding green tea and cancer prevention in humans, there are mechanisms of action of green tea that are compelling: Green tea may protect against some kinds of cancers by preventing blood vessel growth in tumors, inducing apoptosis, reducing oxidative DNA damage, inhibiting tumor promoters, inhibiting hormones and growth factors with the receptor sites, reducing free radical generation and inhibiting important enzyme systems necessary for cancer promotion and proliferation.
Green tea and cancers
Laboratory studies demonstrate that the catechins in green tea, particularly EGCG, inhibit tumor formation and growth through several mechanisms. EGCG has been shown to induce apoptosis in cancer cells lines from prostate, stomach and epidermoid cancers.
Green tea polyphenols have induced apoptosis and inhibited lung cancer cell proliferation in vitro as well. Other examples of in vitro inhibition of EGCG on cancer cells have included colorectal and breast cancer cells.
There have been numerous in vitro and animal studies showing the effects of green tea on reducing as well as preventing breast tumors and inhibiting various enzymes and cell signaling systems. EGCG has demonstrated the ability to inhibit the growth of human breast and prostate tumors transplanted into athymic mice. Green tea extracts given to female rats significantly decreased DMBA-induced mammary tumor burden, invasive tumors, and significantly delayed the onset of a first tumor. Another study fed Sprague-Dawley rats 1% green tea catechins in the diet, was effective in reducing breast tumor promotion, but not the progression of breast cancer. Several in vitro studies have found green tea reduced the rate of proliferation of breast cancer cells.
More recently, green tea extract and EGCG affected angiogenic factor vascular endothelial growth factor (VEGF) expression. The extract or the EGCG significantly decreased the levels of the VEGF peptide secreted into the medium of human breast cancer cells. The green tea was also able to suppress the expression of protein kinase C, a VEGF transcription modulator, and decrease the RNA levels of VEGF. Inhibition of VEGF transcription appears to be involved in the antiangiogenic effects of green tea.
The implication being that green tea could inhibit blood supply to breast cancer tumors or breast cancer cell target sites by inhibiting VEGF and may have potential use for breast cancer treatment and prevention.
Breast tumors which are HER-2 neu positive may also be especially susceptible to green tea. EGCG inhibited mouse mammary tumor HER-2 neu cell growth in vitro, and dose of green tea polyphenols slowed the growth of estrogen receptor-negative breast cancer cell lines.12
In 1998, a study found the more green tea pre-menopausal women with stage I and stage II breast cancer consumed, the fewer metastasized lymph nodes they developed. Additionally, postmenopausal women who consumed green tea experienced an increased progesterone and estrogen status â€“ a finding usually associated with less aggressive forms of breast cancer. No benefit was seen in stage III breast cancer patients. In stage I and II patients, there was a 16.7% recurrence rate for those consuming five cups or more of green tea (with an average of eight cups) per day. For those who consumed four or fewer cups per day (with an average of two), there was a 24.3% recurrence rate. Disease-free survival was also significantly improved in stage I and stage II breast cancer patients who had a greater consumption of green tea, compared to those who consumed less green tea.
Epidemiologic studies, both case-control and cohort in design, have examined the association between tea intake and breast cancer. A meta-analysis of 13 papers provided data on green tea and black tea. For black tea, there were conflicting results in case-control versus cohort studies. Of the eight case-control studies, there was a minor inverse association between black tea and risk of breast cancer. Five cohort studies demonstrated a modest increase in risk associated with black tea intake. However, the results for green tea indicated a lower risk for breast cancer with green tea consumption.
New research has raised the possibility that green and black tea may reduce the risk of ovarian cancer. Investigators evaluated the association between tea consumption (mainly black tea) and the risk of ovarian cancer in women aged 40-76. During an average of 15 years and in 61,057 women, tea consumption was inversely associated with ovarian cancer risk. Compared with women who rarely or never consumed tea, those who drank 2 or more cups daily had a hazard ratio of 0.54 (95% CI, 0.31-0.91) for ovarian cancer. Risk reduction was independent of age of menarche, age at first birth, age at menopause, family history of breast cancer and use of hormone replacement therapy.
Tea consumption may also enhance the survival of women with epithelial ovarian cancer. A cohort of 254 women with confirmed ovarian cancer was followed for a minimum of 3 years. The survival was greater with tea drinkers who consumed at least 1 cup of green tea per day compared to non tea drinkers.
Cervical Dysplasia and HPV
Green tea has recently been shown to influence numerous mechanisms which are favorable towards preventing and/or treating HPV related lesions. Epigallocatechin-3-gallate has been shown to inhibit epidermal growth factor receptor (EGFR) signaling pathway. EGFR activation is required for cervical cell proliferation which suggests agents which inhibit EGFR may be of important therapeutic value in prevention and treatment of cervical dysplasia and genital warts. Two other in vitro studies demonstrated EGCG inhibits the growth of human cervical cancer cell lines, induces apoptosis, inhibits telomerase activity in cervical cell lines and has a role in regulation of gene expression.
Perhaps the most encouraging of the studies was an investigation of the clinical efficacy of green tea extracts delivered vaginally and/or orally in patients with HPV infected cervical lesions. Fifty-one patients with cervical lesions ranging from chronic cervicitis, mild dysplasia, moderate dysplasia and severe dysplasia were divided into four groups as compared with 39 controls. A green tea polyphenol vaginal product was applied locally twice a week to 27 patients. 20 of the 27 patients using the vaginal green tea product showed a response. An oral 200 mg EGCG capsule was taken orally every day for eight to 12 weeks in six patients and three out of the six showed a response. Group three consisted of eight patients using the vaginal product and the oral capsule. Six of eight showed a response. Group 4 consisted of 10 patients using a higher dose EGCG capsule (amount not stated). Six out of the 10 patients with this higher dose EGCG oral capsule only, showed a response. Overall, 35 of 51 (69%) response rate was noted for the green tea products compared with a 10% response rate in the untreated controls. The mechanisms involved appear to be apoptosis, cell cycle arrest, modification of gene expression and anti-tumor effects, specifically, inhibition of cell proliferation. These results demonstrate green tea extracts in the form of a vaginal delivery and an oral capsule are effective strategies for treating cervical lesions.
Green tea may also play a role in weight management. An increase in fat and calorie metabolism may be caused by the caffeine, catechin and theanine constituents. They appear to stimulate thermogenesis as a means of increasing fat burning and inhibiting fat absorption. In addition, individuals who take green tea extract have been observed to expend more energy and burn more calories than those who do not. In this study demonstrating the thermogenic properties and fat oxidation of green tea, done in Geneva in 1999, the higher dose used contained 50 mg of caffeine and 90 mg of EGCG per 2 capsules. According to this study, dosing is 2 caps with breakfast and 2 caps with lunch.
Polycystic ovarian syndrome
Green tea’s ability to increase the production of sex-hormone-binding globulin and its thermogenic effect also provides a rationale for its use in women with polycystic ovarian syndrome (PCOS). By increasing sex hormone-binding globulin, some free testosterone can be bound up, thereby reducing some of the testosterone-related problems seen in women with PCOS such as hair thinning, acne and facial hair. Obesity is another consideration in approximately 50% of PCOS women. Green tea may be helpful in not only increasing SHBG, but also in the thermogenic effects and weight loss potential.
Dementia, especially Alzheimers Disease, is more common in women than in men. Considerable in vitro and animal evidence shows green tea may possess neuroprotection, help to reduce amyloid precursor protein and scavenge free radicals. These effects may offer enhancement of cognitive function, but no human data has existed until very recently. Higher consumption of green tea, in men and women, was associated with a lower prevalence of cognitive impairment. This study showed an inverse dose response relationship between consumption of green tea and the prevalence of cognitive impairment.
Side effects and dosing
Some individuals are negatively affected by the small amount of caffeine in
green tea and its stimulating effect, leading to nervousness, insomnia, dizziness, agitation, restlessness, confusion and anxiety. These effects are more common when using higher doses of green tea. Some individuals may also have an increase in blood pressure or pulse, especially if consumed in higher amounts and in those who already have even mild hypertension. Allergic reactions can occur and tend to include cough, dyspnea, loss of consciousness and asthma. Rare anaphylaxis reactions can occur to the caffeine in green tea.
Another consideration is withdrawal from the green tea. Although uncommon, withdrawal symptoms have been known to occur, including anxiety, restlessness, muscle tension, nausea and vomiting.
Combining ephedra with caffeine can increase the risk of adverse events including hypertension, seizures, and temporary loss of consciousness. Avoid use during pregnancy and while nursing. Infants whose nursing mothers consume caffeine could suffer from sleep disorders.
The Natural Medicines Comprehensive Database lists the following drugs as have potential adverse interactions with green tea: Adenosine, Alcohol, amphetamines, cimetidine, clozapine, cocaine, contraceptives, disulfiram, ephedrine, estrogens, fluconazole, lithium, monamine oxidase inhibitors, nicotine, quinolone antibiotics, theophylline, verapamil and clopidogrel, ticlopidine, heparin and warfrain.
When dosing green tea capsules, those containing 300 mg of green tea extract with 95% polyphenols, 80% catechins and 55% EGCG, 1 capsule is approximately equal to 3 cups of green tea. The normal amount of green tea consumed traditionally by Japanese adults is about three cups per day, providing about 240 to 320 mg of polyphenols. Green tea suppositories are also now available for use in HPV and cervical dysplasia management.
Summary of Clinical concepts
- Breast Cancer stage I or II= 2-3 green tea extract capsules (containing 95% polyphenols, 80% catechines and 55% EGCG per day) per day or 5-8 cups of tea daily.
- Ovarian cancer prevention= 1 cup per day
- Ovarian cancer treatment adjunct= 2 cups per day
- Cervical atypia= green tea suppositories twice weekly plus one green tea extract capsule per day
- Cervical dysplasias= as part of a comprehensive systemic and local treatment strategy, also include one green tea capsule daily and green tea suppositories twice weekly
- Weight loss= 2 caps of green tea extract with breakfast and 2 with lunch (2 caps = 50 mg caffeine and 90 mg of EGCG)
- PCOS= 250-500 mg of green tea extract per day (95% polyphenols, 80% catechins, 45% EGCG)
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