Green Tea and Women’s Health, Part 1

Green Tea and Women’s Health, Part 1

by | Dec 1, 2023

Editor Note: This article, the first of a three-part series, was originally written in 2007.

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 proanthocyanins. 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 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.1 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 reduced the hazard ratio of cancer mortality.

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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,2 stomach,3 and epidermoid cancers.4

Green tea polyphenols have induced apoptosis and inhibited lung cancer cell proliferation in vitro as well.5 Other examples of in vitro inhibition of EGCG on cancer cells have included colorectal and breast cancer cells.6

Breast Cancer

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.7 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.8 Another study  fed Sprague-Dawley rats1% green tea catechins in the diet, was effective in reducing breast tumor promotion, but not the progression of breast cancer.9  Several in vitro studies have found  green tea reduced the rate of proliferation of breast cancer cells.10,11

More recently, green tea extract and EGCG affected angiogenic factor vascular endothelial growth factor (VEGF) expression.12 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 that 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,13 and dose of green tea polyphenols slowed the growth of estrogen receptor-negative breast cancer cell lines.14

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.15 Additionally, postmenopausal women who consumed green tea experienced an increased progesterone and estrogen status – 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.16 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.

Ovarian Cancer. 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.17 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.18

Cervical Dysplasia and HPV. Green tea has recently been shown to influence numerous mechanisms that are favorable towards preventing and/or treating HPV-related lesions. Epigallocatechin3-gallate has been shown to inhibit epidermal growth factor receptor (EGFR) signaling pathway.19  EGFR activation is required for cervical cell proliferation, which suggests  agents that 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.20,21

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.22  A green tea polyphenol vaginal product was applied locally twice a week to 27 patients. Twenty 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 3 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.

Weight loss. 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.23 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).24    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.

Cognitive Impairment. Dementia, especially Alzheimer’s 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.25 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 having potential adverse interactions with green tea:  Adenosine, alcohol, amphetamines, cimetidine, clozapine, cocaine, contraceptives, disulfiram, ephedrine, estrogens, fluconazole, lithium, monoamine oxidase inhibitors, nicotine, quinolone antibiotics, theophylline, verapamil and clopidogrel, ticlopidine, heparin and warfarin.

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

  1. 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.
  2. Ovarian cancer prevention: 1 cup per day
  3. Ovarian cancer treatment adjunct: 2 cups per day
  4. Cervical atypia: green tea suppositories twice weekly plus one green tea extract capsule per day
  5. 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
  6. 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)

References

  1. Kuriyama S, Shimazu T, Ohmori K, et al.  Green tea consumption, and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study. JAMA 2006 Sept 13; 296 (10): 1255-1265.
  2. Paschka A, et al.  Induction of apoptosis in prostate cancer cell lines by the green tea components, epigallocatechine-3-gallate.  Cancer Lett 1998;130(1-2):1-7
  3. Hibasami H, et al.  Induction of apoptosis in human stomach cancer cells by green tea catechins.  Oncol Rep 1998;5:527-529.
  4. Ahmad N, et al.  Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells.  J Natl Cancer Inst 1997;89:1881-1886.
  5. Yang G, et al.  Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols.  Carcinogenesis 1998;19:611-616.
  6. Chen Z, et al.  Green tea epigallocatechin gallate shows a pronounced growth inhibitory effect on cancerous cells but not on their normal counterparts.  Cancer Lett 1998;129:173-179.
  7. Liao S, Umekita Y, Guo J, et al.  A growth inhibition and regression of human prostate and breast tumors in athymic mice by tea epigallocatechin gallate.  Cancer Letters, 1995; 96:297-301.
  8. Kavanagh, K, Hafer L, Kim D, et al.  Green tea extracts decrease carcinogen-induced mammary tumor burden in rats and rate of breast cancer cell proliferation in culture.  J Cell Biochem 2001; 82: 387-398.
  9. Hirose M, Hoshiya T, Akegi K, et al.  Inhibition of mammary gland carcinogenesis by green tea catechins and other naturally occurring antioxidants in female Sprague-Dawley rats pretreated with 7,12dimethylbenz(a)anthraacene.  Cancer Lett 1994;83:149-156.
  10. Kavanagh, K, Hafer L, Kim D, et al.  Green tea extracts decrease carcinogen-induced mammary tumor burden in rats and rate of breast cancer cell proliferation in culture.  J Cell Biochem, 2001; 82:387-398.
  11. Araki R, Inoue S, Osborne M, Telang, N.  Chemoprevention of mammary preneoplasia.  In vitro effects of a green tea polyphenol.  Ann N.Y. Acad Sci, 1995;768;215-222.
  12. Sartippour M, Zhi-Ming S, Heber D, et al.  Green tea inhibits vascular endothelial growth factor induction inhuman breast cancer cells.  N Nutr 2002;132:2307-2311.
  13. Pianetti S, Guo S, Kavanagh K, Sonenshein G.  Green tea polyphenol epigallocatechin-3 gallate inhibits Her-2/Neu signaling, proliferation, and transformed phenotype of breast cancer cells. Cancer Res 2002;62:652-655
  14. Fujiki H, et al. Cancer Prevention with Green Tea and Its Principal Constituent, EGCG: from Early Investigations to Current Focus on Human Cancer Stem Cells. Mol Cells. 2018 Feb 28; 41(2): 73–82.
  15. Nakachi K, Suemasu K, Suga K, et al.  Influence of drinking green tea on breast cancer malignancy among Japanese patients.  Japan J Cancer Res 1998;89:254-261
  16. Sun C, Yuan J, Koh W, Yu M.  Green tea, black tea and breast cancer risk: a meta-analysis of epidemiological studies.  Carcinogenesis 2006;27(7): 1310-1215.
  17. Larsson S, Wolk A.  Tea consumption and ovarian cancer risk in a population-based cohort. Arch Intern Med 2005;165(22): 2683-2686
  18. Zhang M, Lee A, Binns C, Xie X.  Green tea consumption enhances survival of epithelial ovarian cancer. Int J Cancer 2004;112(3): 465-469.
  19. Sah J, Balasubramanian S, Eckert R, Rorke E.  Epigallocatechin-3-gallate inhibits epidermal growth factor receptor signaling pathway.  Evidence for direct inhibit of ERK ½ and AKT kinases.  J Biol Chem 2004;79(13): 12755-12762.
  20. Ahn W, Huh S, Bae S, et al.  A major constituent of green tea, EGCG, inhibits the growth of a human cervical cancer cell line, CaSki cells, through apoptosis G(1) arrest, and regulation of gene expression.  DNA Cell Biol 2003;22(3): 217-224.
  21. Yokoyama M, Noguchi M, Nakao Y, et al.  The tea polyphenol, (-) – epigallocatechin gallate effects on growth, apoptosis, and telomerase activity in cervical cell lines.  Gynecol Oncol 2004;92(1): 197-204.
  22. Ahn W, Yoo J, Huh S, et al.  Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions.  Eur J Cancer Preve 2003;12(5): 383-390.
  23. Dulloo, A, et al.  Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-hour energy expenditure and fat oxidation in humans.  Am J Clin Nutr 1990;70:1040-1045
  24. Nigata C, Kabuto M, Shimizu H.  Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenstrual Japanese women.  Nutrition and Cancer 1998;30(1): 21-24.
  25. Kuriyama S, Hozawa A, Ohmori K, et al.  Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project. Am J Clin Nutr 2006;83:355-361

Published December 2, 2023

Author

  • Dr. Tori Hudson, Naturopathic Physician, graduated from the National University of Natural Medicine (NUNM) in 1984 and has served the college in several capacities, including: Medical Director, Associate Academic Dean, and Academic Dean. She is currently a clinical adjunct professor at NUNM), Southwest College of Naturopathic Medicine, Bastyr University and the Canadian College of Naturopathic Medicine. Dr Hudson has been in practice for 40 years, is the medical director of her clinic, “A Woman’s Time” in Portland, Oregon, co-owner and director of product research and education for VITANICA and the program director for the Institute of Women’s Health and Integrative Medicine. She is also the founder and co-director of NERC (Naturopathic Education and Research Consortium), a non-profit organization for accredited naturopathic residencies.

    Dr. Hudson has been appointed as a faculty member of the Fellowship in Integrative Health and Medicine, Academy of Integrative Health & Medicine.

    Dr. Hudson was awarded the 1990 President’s award from the American Association of Naturopathic Physicians for her research in women’s health, the 1999 prestigious Naturopathic Physician of the Year award, the 2003 NUNM Alumni Pioneer Award., the 2009 Natural Products Association Pioneer Award and in 2012 was inducted into the NUNM Hall of Fame. In 2016, she was the recipient of the annual Oregon Association of Naturopathic Physician’s “Living Legends” award.

    In 2021 she received the 2020 American Botanical Council’s prestigious Fredi Kronenberg Excellence in Research and Education in Botanicals in Women’s Health Award for 2020.

    She is a nationally recognized author (book: Women’s Encyclopedia of Natural Medicine second edition, McGraw Hill 2008) and the Menopause Companion (2023), speaker, educator, researcher, and clinician. Dr. Hudson serves on several editorial boards, advisory panels and as a consultant to the natural products industry. She also writes monthly columns and freelance articles for several publications.

    www.drtorihudson.com
    www.instituteofwomenshealth.com
    www.awomanstime.com
    www.vitanica.com

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