Description
Green tea is derived from the shrub Camellia sinensis, the same plant as used for black tea, but is not fermented (oxidised). A variety of health benefits has been suggested including cancer prevention.
Efficacy
A 2020 Cochrane review on green tea for the prevention of cancer included 142 experimental and observational studies. Overall, the evidence from the studies showed that effects due to consumption of green tea on the risk of cancer were inconsistent.
Prevention of cancer
Green tea supplements versus placebo (based on meta-analysis of RCTs)
Prostate cancer (n=3): a decreased risk was found but the evidence was not conclusive as all participants had a high risk of prostate cancer initially and the results were inconsistent across studies
Gynaecological cancer (n=2): an increased risk was found overall but trial results were contradictory
Non-melanoma skin cancer (n=1): no difference was found but the evidence was based on only one study.
Green tea consumption, high versus low consumption (based on meta-analysis of observational studies)
Overall cancer risk: a lower risk was reported but the evidence was not conclusive with a wide confidence interval
Cancer-related mortality: no difference was found
Specific cancer risk
No difference was found for the following cancers but the evidence is at serious risk of bias and not conclusive: Any gut cancer (n=7); Breast cancer (n=14); Liver cancer; Lung cancer (n=6); Oesophageal cancer (n=17); Pancreatic cancer (n=13); Rectal cancer (n=9); Stomach cancer (n=18); Urinary tract cancer (n=7)
A reduced risk was reported for the following cancers but the evidence was at serious risk of bias: Colorectal cancer (n=16); Colon cancer (n=10); Gynaecological cancer (n=10); Endometrial cancer (n=5); Oral cancer (n=5); Ovarian cancer (n=5); Prostate cancer (n=13)
Supportive care
Quality of life: A slight improvement in quality of life compared with placebo was reported.
Safety
Drinking green tea appears safe at regular, habitual and moderate use (up to 8 cups per day). Adverse effects reported in clinical trials included various gastro-intestinal problems, effects on liver enzymes and allergic reactions. High levels of intake may cause adverse effects due to caffeine and/or epigallocatechin-3-gallate (EGCG) content. Liver-related adverse effects have also been reported, particularly with high intakes or in those with existing liver disease.
Citation
Karen Pilkington and the CAM Cancer Consortium. Green tea (Camellia sinensis) [online document], Dec 8, 2020.
Document history
Latest update: December 2020
Next update due: December 2023
Description, origin, background and characterisation of the medicinal plant
Green tea is derived from Camellia sinensis, an evergreen shrub of the Theaceae family, which grows mainly in parts of Asia, the Middle East and Africa. The leaves are used for tea. It comes from the same plant as black tea but it is produced in a non-fermenting process, thus, is believed to be the strongest tea with the least loss of herbal elements. According to the fermentation degree and plants sources, tea is classified as green tea, white tea, yellow tea, black tea and dark tea. With increasing fermentation, the number of bioactive elements decreases.
Green tea consumption began in China more than 4,000 years ago, when it was reserved for the highest tier of Chinese society. It was not until the 14th century that green tea become widespread throughout China where it has been used for its taste and medicinal qualities in most of Asia. The KissaYojoki (Book of Tea), written by Zen priest Eisai in 1191, describes how drinking green tea can have a positive effect on the five vital organs and discusses tea's medicinal qualities (NARO, 2020). In the 16th century, green tea was introduced to Europe and the USA (WGTA, 2020).
Ingredients and quality requirements
Green tea consists of unfermented Camellia sinensis tea leaves which contain antioxidants. The main active ingredients identified in green tea include flavanol polyphenolic compounds, catechins, such as epicatechin (EC), epicatechin-3-gallate (ECG), epigallocatechin (EGC), and epigallocatechin-3-gallate (EGCG), which are thought to be responsible for the anti-carcinogenic and anti-mutagenic activity (Khan 2013). Other polyphenols in green tea include flavonols and their glycosides and depsides such as cholorogenic acid andquinic acid including one unique to tea (Graham 1992). Minerals such as aluminium and manganese may be present depending on soil conditions. Caffeine and very small amounts of other methylxanthines are also present. Other constituents include pigments (chlorophyll, carotenoids) and volatile compounds (Chacko 2010).
Green tea has a high polyphenol content, 40% of which is epigallocatechin gallate (EGCG). A cup of green usually contains 250-350mg tea solids with 30–42% catechins and 3–6% caffeine (Khan 2013). While the EGCG content of tea infusions varies, it has been suggested that 2-3 cups is equivalent to 200mg EGCG (Filippini 2020).
No specific regulations exist for tea products in the European Union as tea and tea products are covered by general food regulations (Heaney 2018). The International Organization for Standardization (ISO) has produced several relevant standards for the basic requirements of green as opposed to black or other forms of tea and methods for determining quantities of various constituents (ISO 2011).
Alleged indications
A variety of health benefits have been suggested including cancer prevention, reduced risk for cardiovascular disease, increased bone density, fat loss promotion and protection against neurodegenerative disease.
Application and dosage
Green tea can be consumed as a brewed beverage or as dietary supplements in form of liquids, capsules, or tablets containing green tea extract. Commercial products, or green tea for medicinal use, are provided by tea manufacturers or different pharmaceutical herbal medicine companies. Water for green tea should be around 80 °C; the higher the quality of the leaves, the lower the temperature; high-quality green teas can have new water several times (Hajiaghaalipour 2016). Currently, there is no established recommended dose for green tea extract. The EGCG content of green tea infusions varies considerably due to plant variety, growing environment, season, age of leaves and manufacturing conditions as well as factors related to infusion such as timing. The European Food Safety Agency (EFSA) suggest that average daily intake of EGCG resulting from the consumption of traditional green tea infusions ranges between 90 and 300 mg, but may be higher in adults who consume large quantities (EFSA 2018). For cancer prevention, studies have examined the effects of habitually drinking between one to ten cups per day, although these findings require confirmation. Doses equivalent to between 200 and 800 mg/day of EGCG have been most frequently used in clinical trials (Filippini 2020).
Mechanism of action
Human studies on the pharmacokinetics of green tea polyphenols have been conducted. Polyphenols from green tea have been shown to be powerful antioxidants with anticarcinogenic properties. EGCG, the most abundant and biologically active polyphenol in green tea, induces apoptosis and suppresses proliferation of cancer cells by modulating multiple signal transduction pathways. EGCG can also covalently bind to cysteine residues in proteins through autoxidation and subsequently modulate protein function (Tanaka 2011). Studies have shown that tea catechins inhibit hepatocyte growth factor receptor (MET kinase) activity in human colon cancer cells (Larsen 2009).
Legal issues
Green tea is sold as beverage or dietary supplement. It therefore does not need to be approved by the Food and Drug Administration (FDA) or European Medicines Agency (EMA) but no medicinal claims associated with green tea can be made.
There have been many population-based prospective/retrospective observational studies conducted in different settings since the 1970s. Randomized controlled trials testing green tea extracts such as EGCG have also been conducted. Considering the large amount of literature, this CAM Cancer summary is based on the findings from a Cochrane review published in March 2020, which assesses, summarises and presents the current evidence on green tea (extract) for cancer prevention.
Prevention
The Cochrane review on green tea for the prevention of cancer included 142 experimental and observational studies (Filippini 2020) Overall, the evidence from the studies showed that effects due to consumption of green tea to reduce the risk of cancer was inconsistent.
Eleven of the studies were randomised controlled trials (RCTs) of green tea extract supplements versus placebo involving 1795 participants in total. Nine of the RCTs reported on cancer risk for cancers including prostate cancer, gynaecological cancer and cancers of the gastrointestinal tract.
All were judged to be high quality based on assessment of the risk of bias. No significant difference was found between the extract and placebo but there was inconsistency in the evidence. Several adverse effects were reported in the clinical trials. The findings for specific cancers are listed under “Description of studies”.
The observational studies, which compared high to low consumption of green tea, consisted of 46 cohort studies and 85 case-control studies involving a total of 1,100,000 participants. The studies were assessed as generally of intermediate to high methodological quality. A lower overall cancer incidence risk was reported but the confidence interval indicated the result was not conclusive (risk ratio 0.83, 95% CI 0.65-1.07). No difference was found for cancer-related mortality (risk ratio 0.99, 95% CI 0.91-1.07).
Description of studies
The findings for specific cancers are briefly presented below but further details can be found in the Cochrane review (Filippini 2020):
Green tea supplements (based on meta-analysis of RCTs)
- Prostate cancer: a decreased risk was found with green tea compared with placebo (based on 3 RCTs with 201 participants) but the evidence was not conclusive as all participants had a high risk of prostate cancer initially and the results were inconsistent across studies (95% CI 0.18 to 1.36)
- Gynaecological cancer: an increased risk was found with green tea compared with placebo was found based on 2 RCTs with 1157 participants but findings of the trials were contradictory (95% CI 0.41 to 5.48)
- Non-melanoma skin cancer: no difference was found between green tea and placebo but this finding was based on only one RCT with 1075 participants
- Adverse effects: included mild to moderate nausea, diarrhoea, constipation, indigestion and reflux; raised liver enzymes and increased blood pressure; insomnia and dizziness; rash or allergic skin reactions
Green tea consumption, high versus low consumption (based on meta-analysis of observational studies)
No difference was found between high and low levels of green tea consumption for the prevention of the following cancers (number of studies in brackets) but the evidence was affected by a serious risk of bias as it was based mainly on case-control studies and was not conclusive. Details of the risk ratios and further information on the evidence can be found in the Cochrane review, specifically in the Summary of Findings tables (Filippini 2020):
- Any gut cancer (7 studies)
- Breast cancer (14 studies)
- Liver cancer (6 studies)
- Lung cancer (17 studies)
- Oesophageal cancer (13 studies)
- Pancreatic cancer (9 studies)
- Rectal cancer (9 studies)
- Stomach cancer (18 studies)
- Urinary tract cancer (7 studies)
A reduced risk was reported for the following cancers but the evidence was affected by a serious risk of bias as it was based mainly on case-control studies. Details of the risk ratios and further information on the evidence can be found in the Cochrane review, specifically in the Summary of Findings tables (Filippini 2020):
- Colorectal cancer (16 studies)
- Colon cancer (10 studies)
- Gynaecological cancer (10 studies)
- Endometrial cancer (5 studies)
- Oral cancer (5 studies)
- Ovarian cancer (5 studies)
- Prostate cancer (13 studies)
Supportive care
The Cochrane review also assessed the effects of consumption of supplemental green tea extracts on quality of life based on four RCTs.
- A slight improvement in quality of life, compared with placebo was reported in three trials while a fourth RCT found no difference.
Description of studies
Two RCTs assessed quality of life linked to urinary tract symptoms in men at risk of prostate cancer and one trial assessed quality of life linked to uterine fibroids in women at risk of uterine cancer. While beneficial effects were reported, the different outcome measures used prevented meta-analysis being carried out to confirm an effect. In addition, a fourth RCT also in prostate cancer prevention found no difference in quality of life. Further details of the studies and measures can be found in the Cochrane review (Filippini 2020)
According to the current systematic reviews/meta-analysis, drinking green tea appears to be safe at moderate, regular and habitual use. A range of adverse effects has been reported in clinical trials with green tea extract supplements. There are some safety concerns linked to higher intake of green tea and related specifically to EGCG and caffeine content.
Adverse events
The most recent and comprehensive systematic review (Cochrane review of green tea in prevention on cancer) found that a range of adverse effects were reported with green tea extract supplements used in clinical trials (Filippini 2020). These include mild to moderate nausea, diarrhoea, constipation, indigestion and reflux; raised liver enzymes and increased blood pressure; insomnia and dizziness; rash or allergic skin reactions. All were reported to be more frequent in the green tea groups compared with those on placebo treatment. Clinical pharmacokinetic and animal toxicological information indicated that consumption of green tea concentrated extracts on an empty stomach was more likely to lead to gastrointestinal disorders than consumption after food (Bedrood 2018).
For caffeinated and decaffeinated green tea and supplements, several incidents of liver toxicity have been observed, although prevention of liver disease has also been observed in epidemiological studies. Clinical studies have reported grade 1 transaminitis; low grade gastrointestinal toxicity has also been reported. Liver enzymes (ALT and AST) should be monitored in patients taking high dose green tea supplements. One systematic review identified a total of 34 cases of hepatitis following the consumption of preparations containing green tea between 1999 and 2008, however the review concluded that the toxicity related to concomitant medications could also be involved (Mazzanti 2009). A more recent systematic review found evidence of liver enzymes elevations in a small number of cases (Isomura 2016).Due to concerns about possible harmful effects on the liver, however, the European Food Safety Agency (EFSA) carried out an assessment of the safety of green tea catechins from dietary sources. The EFSA concluded that catechins from green tea infusions and similar drinks are generally safe but catechin doses of 800 mg/day or more when taken as food supplements may be linked to initial signs of liver damage (EFSA, 2018). A full systematic review by the United States Pharmacopiea identified adverse event case reports indicating hepatotoxicity with EGCG intake between 140 mg to ∼1000 mg/day (Oketch-Rabah et al, 2020). Susceptibility was very varied possibly due to genetic factors. Based on these findings, the USP requires cautionary labelling recommending avoiding taking on an empty stomach or by those with liver disease. Discontinuing use and consulting a healthcare practitioner if liver-related symptoms such as abdominal pain, dark urine, or jaundice develop are also recommended.
For preparations that contain caffeine, caffeine-related side effects are observed, including increased gastric acidity, effects on blood glucose and elevated catecholamine levels. Reviews of the evidence by North America healthcare organisations indicate that drinking up to 8 cups of green tea daily, or approximately 400 mg of caffeine, is not associated with significant adverse effects or increased risk of major chronic diseases (Natural Medicines, 2020). Doses of caffeine above 600 mg per day, or approximately 12 cups of green tea, have been associated with significant adverse events.
Interactions
Green tea can act as an antioxidant and induce superoxide dismutase enzyme, which could scavenge the free oxygen radicals generated by radiotherapy (Thomas 2011).Green tea consumption was shown to increase the plasma concentration of 5-FU (5-fluorouracil) in a pharmacokinetic study in rats and in vitro (Qiao 2011).Conclusions from existing pre-clinical studies regarding potential antagonism between bortezomib and green tea components are inconsistent (Bannerman et al 2011; Golden et al 2009) but it has been recommended that patients on bortezomib do not take green tea (Natural Medicines 2020)
Anticoagulants: theoretical concerns and a case report suggest that large quantities (about 1 gallon/day) of green tea may antagonize warfarin, perhaps due to vitamin K content. Green tea also has antiplatelet activity.
Bortezomib: in vitro and in vivo testing suggest that EGCG could inhibit activity of bortezomib in multiple myeloma (for which bortezomib is approved) or glioblastoma. However, in vivo testing found this effect only at unrealistically high concentrations in an experimental prostate cancer model.
Cytochrome P450 3A4: high dose green tea may inhibit CYP450 3A4, and one case of clinically significant interaction with tacrolimus has been reported. Beverage use and low dose supplements (<800 mg/d) are unlikely to affect this enzyme, based on human trials.
5-fluoruracil: high doses of green tea might, in theory, increase the effects and side effects
Hepatotoxic drugs: monitor liver enzymes more closely due to potential hepatotoxicity.
P-glycoprotein: EGCG inhibits P-glycoprotein and may cause interaction with irinotecan or verapamil; it prolongs the half-life of irinotecan, potentially enhancing both activity and adverse potential.
Sunitinib: a case and laboratory study suggest a possible interaction between green tea and sunitinib.
Tamoxifen: green tea may increase tamoxifen bioavailability.
UGT (uridine 5’ diphospho-glucuronosyltranferase) substrates: green tea may increase side effects of drugs metabolized by this enzyme due to increased exposure (Frenkel 2013).
Contraindications
Pregnant women, nursing mothers and patients with cardiac problems are usually advised to avoid or limit their intake to two cups daily (Sarma et al 2008).People with known allergy or hypersensitivity to caffeine or tannin should avoid green tea (Brown 1999). Most healthy women can safely consume up to 300mg caffeine daily although over 200mg has been associated with an increased risk of miscarriage in some women with slow caffeine metabolism (Health Canada 2020; Natural Medicines 2020).
Warnings
Consumption of high doses of green tea or green tea extract may cause nausea, vomiting, abdominal bloating and pain, dyspepsia, flatulence, and diarrhoea. Excess consumption of caffeine from green tea may also cause central nervous system stimulation such as dizziness, insomnia, tremors, restlessness and confusion, and diuresis, irregularities in heart rate, and psychomotor agitation. Doses of caffeine greater than 600 mg per day, or approximately 12 cups of green tea, have been associated with cardiac arrhythmias (Natural Medicines 2020).
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