Green tea (camellia sinensis) has been studied for both its cancer prevention role and its contribution in cancer reversals. In addition, many other diseases and illness symptoms can benefit from green tea, from cardio-vascular diseases to diabetes, osteoporosis, allergies, inflammation, cholesterol, bad eyesights, infections including periodontal teeth disease. Green tea and its major constituent epigallocatechin gallate (EGCG) (1) have been extensively studied as a potential treatment for a variety of diseases including cancerous tumors (e.g., prostate, lung, colon, pancreatic) and non-malignant tumors. (2).
While the evidence that green tea polyphenols from preclinical and clinical studies in the chemoprevention of prostate and colon cancer is strong, the supporting concomitant evidence for treatment via the reversal pathway remains ongoing, pending more funds for clinical trials (see our future blog on clinical trials). Nevertheless, we can already characterize green tea as a therapeutic anti-cancer agent in that the green tea flavonoids (eg especially Epigallocatechin and EGCG) have been shown to induce apoptosis in human glioblastoma cell (See Exhibit A for the evidence).
Furthermore, when we combine green tea with other polyphenol-rich foods such as pomegranate, broccoli and turmeric, we get a bigger therapeutic bang. In this perspective, different studies have proven beyond any reasonable doubt that synergistic-based polyphonol molecules generate anti-neoplastic effects in laboratory models involving angiogenesis, apoptosis and proliferation. Although some have been investigated in small, phase II studies, this combination has never been fully evaluated within an adequately powered randomised controlled trial until recently a few months ago in last Summer 2014. (See EXHIBIT B for this study)
For those who are aware that nearly 50 percent of all Americans will get at least one cancer diagnosis in his or her life, (see HOM movie-documentary) and are thus motivated to keep cancer at bay, EXHIBIT C reviews a few pieces of cancer prevention proofs, notably for solid cancers like prostate cancer.
To be noted that teas may not be enough, depending of the constellation of circumstances, green tea extracts may be best. In this perspective, when the dosage is right, green tea extract is an effective and safe supplement for the chemoprevention of metachronous colorectal adenomas. (EXHIBIT D).
Lastly, EXHIBIT E shows that green tea affects metabolism, in particular glutamine catabolism via GDH (glutamate dehydrogenase) inhibitors, all of which can be useful in treating various tumors.
THE STATE OF THE EVIDENCE
In 2011 a panel of scientists published a report on green tea’s claimed health effects at the request of the European commission. At the conclusion of this study, the experts found that the claims made for green tea were not supported by enough and good scientific evidence. (3) Some of the reasons for this are flawed studies, not doing a complete job (like invoking some of the studies in this blog), not using organic leafs or tea bags, many of which have chlorine and other insidious synthetic chemicals and not using pristine spring water. There are a little over 6000 green tea studies in the scientific literature, as a conclusion, it may not be wise to dismiss the anti-cancer effects of green tea as tend to do too many conventional oncologists.
On a more favorable note, different meta-analyses in 2014 found evidence that green tea consumption may be associated with a lower risk of esophageal cancer in the Chinese population, a lower risk of lung cancer in women, and a lower risk of oral cancer in Asian Nations. (4). Another analysis of observational data conducted in 2012 suggested that green tea consumption may have a favorable effect on lung cancer risk. The observed effect was strongest in those who consumed more than seven cups of green tea daily. (5) And as we have shown via this blog’s five exhibits, brain, prostate and colon cancers also favorably respond to green tea’s extracts.
MECHANISMS OF ACTION
There are many mechanisms of action and their explanation would go beyond the scope of this blog. However, we will briefly detail one of these mechanisms, the ROS pathway. It’s been established that EGCG promotes the formation of reactive oxygen species (ROS) in cancer cells, which damages the mitochondria. Thereafter, the mitochondria responds by producing more reactive oxygen species. The mitochondria then loses its defenses with a breakdown in the expression of antioxidant genes. Penn State Professor and researcher Lambert corroborates:
“EGCG is doing something to damage the mitochondria and that mitochondrial damage sets up a cycle causing more damage and it spirals out, until the cell undergoes programmed cell death,” said Lambert. “It looks like EGCG causes the formation of reactive oxygen species in cancer cells, which damages the mitochondria, and the mitochondria responds by making more reactive oxygen species.” As this mitochondrial demise continues, the cancer cell also reduces the expression of anti-oxidant genes, further lowering its defenses. “So, it’s turning off its mechanism of protection at the same time that EGCG is causing this oxidative stress,” Lambert added. The EGCG did not cause this reaction in normal cells. In fact, it appeared to increase the protective capabilities of the cell, according to the researchers, who report their findings in the online issue of Molecular Nutrition and Food Research.” (Source)
Organic green tea-extract and its two major compounds (epigallocatechin gallate (EGCG) and epicatechin gallate (ECG)) may be a better option than soda pop, coffee, hard alcohol, beer and even fruit juices when it comes to boosting vitality-building metabolic health pathways. As we saw, various pieces of evidences from in vitro, in vivo, epidemiological studies and clinical trials suggest that green tea and its constituents are effective in preventing differet cancers, including, but not limited to prostate and colon cancers. Green tea consumption can also retard emergence of BPH or androgen resistance which are precusors to prostate cancer and address many other illnesses including insulin challenges. (6)
For colon cancer, the recommended dose is 1500 mg/day green tea extract. This amuont reduced the incidence of metachronous adenomas by 50% after one year compared to the non-supplemented group. (http://www.ncbi.nlm.nih.gov/pubmed/18990744). For less aggressive cancers like prostate cancer, 600 mg/day green tea extract may be indicated. This dosage used for one year reduced prostate cancer risk by 80% in men with high-grade prostate intraepithelial neoplasia (HG-PIN) (Cf. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991093/?tool=pubmed
Green tea is one of the three main categories of tea, the other two being black and oolong. Green tea is the least processed of the three and is steamed but, unlike black and oolong, is not fermented. The caffeine content of green tea is about half that of coffee and it’s also available in decaffeinated versions. Given the deleterious impact of chemical agriculture, green tea should be taken in its organic form and straight, as milk, sugar and chemicals like aspartame can negate its therapeutic bllessings. The water used should be a high-alcalin pure spring water without being contained in bpa leeching hormonal disruptors plastic bottles, inter alia. And the tea pot without aluminum, teflon and other causer-cancer agents. Raw organic green tea steeped in the Sun’s rays for a few hours is the best modality.
For those who are in the conventional oncology system, green tea interferes with the chemotherapy drug bortezomib (Velcade) and other boronic acid-based proteasome inhibitors, and should be avoided by people taking this medication. (7). Likewise with patients who are on coumadin or warfarin, given the competitive “blood thinning” effect of green tea. On the other hand, green tea’s theanine can protect against acute hepatic damage induced by the cyto-toxic chemo agent called Doxorubicin (DOX). (cf EXHIBIT F).
Green tea can be combined with supplements like vitamine C and other medicinal herbs, including, but not limited to cannabis cbd and chlorophyl rich herbs, thanks to which the immune system can benefit even more. (See our future blog on the anti-cancer effects of herbs, a few of which are examined in the HOM documentary movie).
But there are preparation exigencies, drug-plant inter-actions and proper administration requirements that need to be examined under medical supervision and holistic guidance in order to minimize risks and maximize efficiency. As Paraclesus concluded over two thousand years ago, any substance can be either a medicine, a food or a poison, depending of the dosage. To which we can also add, depending of the substance’s “purity” and “potency” quality and in relation to what else is taken (drug-plant interaction) and according to each person’s genomic individuality.
Results strongly suggest that flavonoids activate caspases and are therefore potential therapeutic agents for induction of apoptosis in human glioblastoma cells.
Cancer. 2010 Jan 1;116(1):164-76.
Arabinda Das, Naren L Banik, Swapan K Ray
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina.
BACKGROUND:: Human glioblastoma is a deadly brain cancer that continues to defy all current therapeutic strategies. The authors induced apoptosis in human glioblastoma T98G and U87MG cells after treatment with apigenin, (-)-epigallocatechin, (-)-epigallocatechin-3-gallate (EGCG), and genistein, which did not induce apoptosis in human normal astrocytes. METHODS:: Induction of apoptosis was examined using Wright staining and ApopTag assay. Production of reactive oxygen species (ROS) and increase in intracellular free Ca(2+) were measured by fluorescent probes. Analysis of mRNA and Western blotting indicated increases in expression and activities of the stress kinases and cysteine proteases for apoptosis. JC-1 showed changes in mitochondrial membrane potential (DeltaPsi(m)), and use of specific inhibitors confirmed activation of kinases and proteases in apoptosis.
Treatment of glioblastoma cells with apigenin, (-)-epigallocatechin, EGCG, or genistein triggered ROS production that induced apoptosis with phosphorylation of p38 mitogen-activated protein kinase (MAPK) and activation of the redox-sensitive c-Jun N-terminal kinase 1 pathway. Pretreatment of cells with ascorbic acid attenuated ROS production and p38 MAPK phosphorylation. Increases in intracellular free Ca(2+) and activation of caspase-4 indicated involvement of endoplasmic reticulum stress in apoptosis. Other events in apoptosis included overexpression of Bax, loss of DeltaPsi(m), mitochondrial release of cytochrome c and Smac into the cytosol, down-regulation of baculoviral inhibitor-of-apoptosis repeat-containing proteins, and activation of calpain, caspase-9, and caspase-3. (-)-Epigallocatechin and EGCG also induced caspase-8 activity. Apigenin, (-)-epigallocatechin, EGCG, and genistein did not induce apoptosis in human normal astrocytes.
Results strongly suggest that flavonoids are potential therapeutic agents for induction of apoptosis in human glioblastoma cells.
Polyphenol-rich foods such as pomegranate, green tea, broccoli and turmeric have demonstrated anti-neoplastic effects in laboratory models involving angiogenesis, apoptosis and proliferation
Prostate Cancer Prostatic Dis. 2014 Jun;17(2):180-6.
A double-blind, placebo-controlled randomised trial evaluating the effect of a polyphenol-rich whole food supplement on PSA progression in men with prostate cancer–the U.K. NCRN Pomi-T study.
Thomas R1, Williams M2, Sharma H2, Chaudry A3, Bellamy P4.
Polyphenol-rich foods such as pomegranate, green tea, broccoli and turmeric have demonstrated anti-neoplastic effects in laboratory models involving angiogenesis, apoptosis and proliferation. Although some have been investigated in small, phase II studies, this combination has never been evaluated within an adequately powered randomised controlled trial.
In total, 199 men, average age 74 years, with localised prostate cancer, 60% managed with primary active surveillance (AS) or 40% with watchful waiting (WW) following previous interventions, were randomised (2:1) to receive an oral capsule containing a blend of pomegranate, green tea, broccoli and turmeric, or an identical placebo for 6 months.
The median rise in PSA in the food supplement group (FSG) was 14.7% (95% confidence intervals (CIs) 3.4-36.7%), as opposed to 78.5% in the placebo group (PG) (95% CI 48.1-115.5%), difference 63.8% (P=0.0008). In all, 8.2% of men in the FSG and 27.7% in the PG opted to leave surveillance at the end of the intervention (χ2 P=0.014). There were no significant differences within the predetermined subgroups of age, Gleason grade, treatment category or body mass index. There were no differences in cholesterol, blood pressure, blood sugar, C-reactive protein or adverse events.
This study found a significant short-term, favourable effect on the percentage rise in PSA in men managed with AS and WW following ingestion of this well-tolerated, specific blend of concentrated foods. Its influence on decision-making suggests that this intervention is clinically meaningful, but further trials will evaluate longer term clinical effects, and other makers of disease progression.
Nutr Cancer. 2009 Nov; 61(6): 836–841.
Green Tea Polyphenols in Chemoprevention of Prostate Cancer: Preclinical and Clinical Studies
Naghma Khan, Vaqar Mustafa Adhami, and Hasan Mukhtar
The prevention of prostate cancer (PCa) is a crucial medical challenge in developed countries. PCa remains surrounded by puzzles in spite of the considerable progress in research, diagnosis and treatment. It is an ideal target for chemoprevention, as clinically significant PCa usually requires more than two decades for development. Green tea and its major constituent epigallocatechin gallate (EGCG) have been extensively studied as a potential treatment for a variety of diseases including cancer. In this review, we highlight the evidences of green tea polyphenols from preclinical and clinical studies in the chemoprevention/chemotherapy of PCa.
Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3020-5.
Green tea extracts for the prevention of metachronous colorectal adenomas: a pilot study.
Shimizu M1, Fukutomi Y, Ninomiya M, Nagura K, Kato T, Araki H, Suganuma M, Fujiki H, Moriwaki H.
Experimental studies indicate the chemopreventive properties of green tea extract (GTE) on colorectal cancer. Epidemiologically, green tea consumption of > 10 cups daily reduced colorectal cancer risk in Japanese. Because colorectal adenomas are the precursors to most sporadic colorectal cancers, we conducted a randomized trial to determine the preventive effect of GTE supplements on metachronous colorectal adenomas by raising green tea consumption in the target population from an average of 6 cups (1.5 g GTE) daily to > or = 10 cups equivalent (2.5 g GTE) by supplemental GTE tablets.
We recruited 136 patients, removed their colorectal adenomas by endoscopic polypectomy, and 1 year later confirmed the clean colon (i.e., no polyp) at the second colonoscopy. The patients were then randomized into two groups while maintaining their lifestyle on green tea drinking: 71 patients supplemented with 1.5 g GTE per day for 12 months and 65 control patients without supplementation. Follow-up colonoscopy was conducted 12 months later in 125 patients (65 in the control group and 60 in the GTE group).
The incidence of metachronous adenomas at the end-point colonoscopy was 31% (20 of 65) in the control group and 15% (9 of 60) in the GTE group (relative risk, 0.49; 95% confidence interval, 0.24-0.99; P < 0.05). The size of relapsed adenomas was also smaller in the GTE group than in the control group (P < 0.001). No serious adverse events occurred in the GTE group.
GTE is an effective supplement for the chemoprevention of metachronous colorectal adenomas.
Green Tea Polyphenols Control Dysregulated Glutamate Dehydrogenase in Transgenic Mice by Hijacking the ADP Activation Site
Changhong Li‡,1, Ming Li§,1, Pan Chen‡, Srinivas Narayan¶, Franz M. Matschinsky‖, Michael J. Bennett¶, Charles A. Stanley‡ and Thomas J. Smith§,2From the ‡Division of Endocrinology and
¶Department of Pathology and Laboratory Medicine, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
Glutamate dehydrogenase (GDH) catalyzes the oxidative deamination of L-glutamate and, in animals, is extensively regulated by a number of metabolites. Gain of function mutations in GDH that abrogate GTP inhibition cause the hyperinsulinism/hyperammonemia syndrome (HHS), resulting in increased pancreatic β-cell responsiveness to leucine and susceptibility to hypoglycemia following high protein meals. We have previously shown that two of the polyphenols from green tea (epigallocatechin gallate (EGCG) and epicatechin gallate (ECG)) inhibit GDH in vitro and that EGCG blocks GDH-mediated insulin secretion in wild type rat islets. Using structural and site-directed mutagenesis studies, we demonstrate that ECG binds to the same site as the allosteric regulator, ADP. Perifusion assays using pancreatic islets from transgenic mice expressing a human HHS form of GDH demonstrate that the hyperresponse to glutamine caused by dysregulated GDH is blocked by the addition of EGCG. As observed in HHS patients, these transgenic mice are hypersensitive to amino acid feeding, and this is abrogated by oral administration of EGCG prior to challenge. Finally, the low basal blood glucose level in the HHS mouse model is improved upon chronic administration of EGCG. These results suggest that this common natural product or some derivative thereof may prove useful in controlling this genetic disorder. Of broader clinical implication is that other groups have shown that restriction of glutamine catabolism via these GDH inhibitors can be useful in treating various tumors. This HHS transgenic mouse model offers a highly useful means to test these agents in vivo.
Food Chem Toxicol. 2015 Feb 10.
Theanine prevents doxorubicin-induced acute hepatotoxicity by reducing intrinsic apoptotic response.
Nagai K1, Oda A2, Konishi H2.
Doxorubicin (DOX) is widely used as an antitumor agent with topoisomerase II inhibiting activity; however, its dosage and duration of administration have been strictly limited due to dose-related organ damage. The present study investigated whether theanine, an amino acid found in green tea leaves, could reduce DOX-induced acute hepatotoxicity and the apoptotic response in mice. Activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, biomarkers of hepatic impairment, were markedly increased after the administration of 20 mg/kg DOX, whereas the degree of these elevations was significantly attenuated by 10 mg/kg theanine, which was consistent with histological hepatic images assessed by microscopic examination. The hepatic expression of Bax and Fas, representative intrinsic and extrinsic apoptotic molecules, respectively, was significantly increased by dosing with DOX. However, the elevation in the hepatic expression of Bax, but not Fas, was suppressed to control levels by theanine. The formation of cleaved caspase-3 protein in the group given DOX with theanine was significantly lower than that in the group treated with DOX alone.
These results suggest that theanine can protect against acute hepatic damage induced by DOX, which is attributed to the suppression of intrinsic caspase-3-dependent apoptotic signaling.