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Green Tea

Scientific Name(s): Camellia sinensis (L.) Kuntze.
Common Name(s): Green tea, Green Tea Extract, Tea

Clinical Overview

Use

Tea is traditionally consumed as a beverage. Evidence from clinical trials suggests that green tea plays a role in metabolic syndrome because it may have an impact on body weight, glucose homeostasis, and other cardiovascular risk factors. There has been interest in green tea as an agent in cancer prevention. A role in the prevention of stroke and chronic obstructive pulmonary disease (COPD) has also been suggested. Topical as well as oral formulations have been studied for protection from ultraviolet (UV) damage, and a commercial preparation has been approved by the US Food and Drug Administration (FDA) for use in the treatment of anogenital warts.

Dosing

Daily intake of 3 to 5 cups/day (720 to 1,200 mL) of green tea provides at least 180 mg of catechins and at least 60 mg of theanine. Green tea extract should not be taken on an empty stomach due to the potential for hepatotoxicity from excessive levels of epigallocatechin gallate (EGCG).

Anogenital warts: Topical application of sinecatechins (polyphenon E 10% or 15%) was used for up to 16 weeks in a clinical study.

Cardiovascular risks: Green tea catechins or extract (160 to 2,488 mg/day) have been used in trials, often in divided dosages (treatment duration, 2 weeks to 3 months).

Cognitive impairment: Two 430 mg capsules (each capsule containing green tea extract 360 mg and L-theanine 60 mg) administered twice daily, 30 minutes after meals, for 16 weeks (total daily green tea extract dose, 1,440 mg; total daily L-theanine dose, 240 mg).

Depression: 2 to 4 or more cups/day of green tea has been used to lower the prevalence of depressive symptoms.

Diabetes: An EGCG dosage range of 84 to 386 mg/day may be adequate to support glucose homeostasis, based on available literature.

Obesity: ECGC 400 mg twice daily for 8 weeks was used in one clinical trial; green tea extract tablets (containing 125 mg of catechins) and a daily green tea catechin beverage (containing 625 mg of catechins) have also been used in studies of overweight and obese adults.

Contraindications

Contraindications have not been identified; however, use caution in cases of hepatic failure.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Green tea contains caffeine. The FDA advises those who are or may become pregnant to avoid caffeine.

Interactions

See Drug Interactions section.

Adverse Reactions

There are no reports of clinical toxicity from daily tea consumption as a beverage. Adverse events associated with tea extracts (including green tea extract) include headache, dizziness, and GI symptoms. Hepatotoxicity, including 1 fatality, has been associated with high plasma levels of EGCG or its metabolites.

Toxicology

No data.

Botany

Black, oolong, and green tea are produced from the leaves of C. sinensis, which is native to eastern Asia but also grown in other areas. This evergreen shrub or tree grows to over 9 m in height and is pruned at 60 cm to 1.5 m for cultivation. Its dark green, serrated-edged leaves are alternate and oval, while its white and fragrant blossoms appear singly or in clusters.Cooper 2005, USDA 2010 Green tea is the dried leaf component, while black tea is produced by a complex wilting and fermentation process. Oolong tea is produced by a process intermediate to that of green and black tea.

The tea plant can grow at altitudes between 100 and 2,200 m. The native growing area for tea plants, also known as the "tea belt," includes southwestern China, northern Laos, northern Vietnam, Myanmar, Cambodia, and northeastern India.Ahmed 2013

History

The dried, cured leaves of C. sinensis have been used medicinally for more than 5,000 years. In traditional Chinese medicine, drinking green tea was recommended for the prevention of ill health, and in Asia, this is still regarded as a healthy practice.Blumberg 2003, Cooper 2005, McKay 2002, Siddiqui 2004

In 1753, Carl Linnaeus described the tea plant taxonomically in Species Plantarum. Green tea was referred to as "Thea viridis." In the early 1900s, taxonomists documented how green and black teas were from the same species. The Theaceae botanical family includes approximately 600 species. However, 2 plant varieties (small leaf and large leaf) are primarily used for commercial tea. A sweeter taste is associated with the small leaf variety, which is often the source for green tea.Ahmed 2013 In Japan, about 100,000 tons of green tea is consumed every year, with 90% of the product produced domestically.Safdar 2016

Chemistry

The chemistry of tea is complex because of the numerous components formed during the curing and drying process, as well as variations in harvest season, climate, and horticultural and processing practices aimed at producing various drinking teas.Blumberg 2003, Cooper 2005 Quality control and analytical methods are improving, allowing for more confidence in clinical studies.Cooper 2005, Dalluge 1997

Tea leaves contain varying amounts of polyphenols (the majority of which are catechins) as well as smaller quantities of caffeine, theanine, theobromine, theophylline, and phenolic acids.

Other tea constituents include tannins; essential oils; riboflavin; niacin; folic, ascorbic (which is present in fresh leaf but destroyed in making black tea), pantothenic, malic, and oxalic acids; manganese; potassium; magnesium; and fluoride.Boehm 2009, Cooper 2005, Siddiqui 2004

Green tea contains more than 2,000 chemical substances.Coppock 2016 The major polyphenol found in green tea is (-)-epigallocatechin gallate, with lesser amounts of catechin, epicatechin, gallocatechin, gallocatechin gallate, and epicatechin gallate.Boehm 2009, Dalluge 1997 Tea is also a dietary source of the polyphenol quercetin, a flavonoid.Dower 2015

Many green teas are best produced from young, tender leaves. The highest quality green teas are hand plucked versus mechanically harvested. Older leaves are generally not desired and are associated with an astringent flavor. The main steps in processing green tea leaves following harvest include "spreading" (to promote hydrolysis), "fixing" (exposure to heat via pan frying or steaming), "rolling" (to disrupt cell walls and release leaf moisture), "shaping" (into various forms including twists, round, flat, needle, flaky, compressed, and ground powder), and "drying" (by pan drying, basket drying, sun drying, or baking).Ahmed 2013

The composition of green tea, prepared by drying and steaming (to inactivate the oxidase enzyme), is very similar to that of the fresh leaf, except for a few changes that occur extremely rapidly following plucking. The primary difference between green and black teas derives from the fermentation process required to produce black tea. The catechins are converted to the higher-molecular-weight theaflavins (absent in green tea). Less fermentation results in an intermediary, lighter tea known as oolong tea.Cooper 2005

Decaffeination slightly reduces the catechin content of black tea; "herbal teas" are not made from C. sinensis and do not contain caffeine or catechins. The addition of milk to tea does not affect the bioavailability of catechins, but may alter the antioxidant potential, depending on the fat content.Blumberg 2003, Boehm 2009

Uses and Pharmacology

Many of the health benefits of tea drinking are attributed to the antioxidant capacity of the chemical constituentsLuczaj 2005, Siddiqui 2004 and are largely borne out by in vitro experiments and epidemiological studies.Blumberg 2003, Cooper 2005, Cooper 2005, McKay 2002 In vitro experiments show a direct effect of tea on reactive oxygen species and chelation of metal ions, such as iron and copper.Siddiqui 2004 Green tea is considered to be more active than black tea,Mandel 2004 with epicatechin and catechins ranking most potent of 24 tested plant polyphenolic flavonoids.Luczaj 2005, McKay 2002 The various methodologies of antioxidant experiments markedly affects the rankings.Erba 2005, Hakim 2003, Hodgson 2000, Leenen 2000, Rietveld 2003, Young 2002 Most clinical trials demonstrate that tea consumption improves plasma antioxidant capacity and biomarkers of oxidative stress.Luczaj 2005, McKay 2002, Rietveld 2003, Siddiqui 2004

Anogenital warts

Clinical data

In 2006, the FDA approved a green tea–based ointment containing polyphenon E for the treatment of anogenital warts. Randomized, double-blind clinical trials have demonstrated the efficacy of the ointment (Veregen), which is considered to act via antiviral, immunomodulatory, antioxidant, and anti-angiogenesis mechanisms.Meltzer 2009

Anti-inflammatory activity

Clinical data

An author-funded study reported reduction in facial redness in subjects (N=16) treated topically twice daily for up to 12 weeks with a combination product containing resveratrol, green tea polyphenols, and caffeine. A preliminary split-face study in which the topical product (containing green tea polyphenols and caffeine) was applied with and without resveratrol for 8 to 12 weeks demonstrated decreased redness only when resveratrol was added to the green tea-caffeine treatment. These results prompted study of the 16 subjects with the resveratrol-enriched product. Subjective evaluation by trained observers documented improvement in 100% and 81% of subjects' clinical photographs and spectrally enhanced red images, respectively.Ferzil 2013

A double-blind, randomized, placebo­-controlled trial in 80 Iranian women 15 to 55 years of age with systemic lupus erythematosus was conducted to evaluate the effects of green tea extract on disease activity and quality of life. The intervention was comprised of 500 mg of green tea leaf extract (containing 22% polyphenols, and EGCG 121.8 mg per gram of extract) twice daily (total daily dose of 1 g). Adverse effects in the treatment group that led to dropout were GI problems (n=3) and skin rash (n=1). After 12 weeks, women consuming green tea extract reported significantly better scores compared to placebo for disease activity (P=0.004) as well as quality of life, including general health, physical functioning, and vitality. Additionally, auto-antibodies were significantly decreased after 3 months in the green tea extract group (P<0.04).Shamekhi 2017

Antimicrobial activity

In vitro data

Tea has demonstrated in vitro activity against a number of pathogenic bacteria.Bezbaruah 1996, Isogai 1998, Yam 1997 and fungi.Hamilton-Miller 2001 Activity by EGCG against HIV has been demonstrated in vitro, with direct binding to CD4.Cooper 2005

Clinical data

In a double-blind, randomized, placebo-controlled trial conducted in 94 elderly inpatients in 2 Japanese daycare facilities, overall skin symptoms of interdigital tinea pedis (eg, interdigital erythema, desquamation, maceration) improved after 12 weeks of treatment with a foot bath containing green tea polyphenols.Ikeda 2013 Another randomized, controlled trial found no difference in incidence of influenza among Japanese high school students (N=767) who gargled with green tea 3 times a week for 90 days during influenza epidemic season compared with those who gargled with water.Ide 2014

Cancer

Mechanisms for anticancer activity of green tea have been investigated in animal models and laboratory experiments, but not yet demonstrated in vivo in humans. Doses used experimentally may not reflect usual tea consumption, and there may be a combination of effects or a combination of active compounds acting to produce the relationships reported in epidemiological studies.Cooper 2005, Lambert 2003, McKay 2002 The polyphenols in green tea inhibit cell proliferation.Boehm 2009 The polyphenol EGCG increases the activity of antioxidants in specific organs in mice and thereby increases the overall chemoprotective effect of antioxidants in those organs.Boehm 2009, Cooper 2005, Fujiki 2001, McKay 2002 EGCG may also facilitate direct binding to certain carcinogens.Boehm 2009, McKay 2002

Polyphenols, especially catechins, may protect cells from tumor development by enhancing gap junction communication between cells.Boehm 2009, Cooper 2005 Tea blocks tumor growth by sealing the receptors of affected cells.Cooper 2005, Fujiki 2001, Lambert 2003 Polyphenols may assist inhibition of tumorigenesis in a variety of organs including skin, lungs, oral cavity, esophagus, stomach, small intestine, colon, liver, pancreas, ovary, and mammary glands.Cooper 2005, Fujiki 2001, Lambert 2003

Animal and epidemiological data

Continued investigational interest in tea has resulted in epidemiological studies and animal experiments providing evidence of green tea's potential as an anticancer agent. Comprehensive reviews are available but are limited in their findings because studies included are too heterogeneous for meaningful comparisons.Blumberg 2003, Cooper 2005, McKay 2002

Green tea polyphenols induced apoptosis in a variety of cells, including human lymphoid leukemia and human prostate cells,Chung 2003, Cooper 2005, Fujiki 2001, Hou 2004, Lambert 2003 and altered estradiol and sex hormone–binding globulin levels associated with the risk of breast cancer.McKay 2002, Nagata 1998 A risk of esophageal cancer from tea drinking has been suggested in epidemiological studies, but this has also been attributed to the scalding temperatures at which the beverage may be consumed.McKay 2002

Clinical data

Many epidemiologic studies have shown that green tea may decrease the risk of cancer; however the subject is controversial and requires further study. Long-term and case-control studies suggest an inverse association between tea consumption and the risk of cancer of the colon, rectum, urinary tract, bladder, breast, stomach, esophagus, lung, pancreas, prostate, and squamous skin cells.Cooper 2005, McKay 2002 While some studies have reported no association between green tea and breast cancer risk, several studies from Japan found that increased consumption of green tea correlated with decreased recurrence of stage I and II breast cancer, but not more advanced stages.Cooper 2005 Epidemiologic studies have shown that cancer onset in individuals in Japan who consumed 10 cups/day of green tea was delayed compared to individuals who consumed less than 3 cups/day. However, due to many variables, a definitive link between green tea and cancer effects cannot be made.Cooper 2005, Fujiki 2001 One multicenter case-control study that enrolled newly diagnosed invasive breast cancer patients found no inverse association between consumption of green tea and the risk of breast cancer. In breast cancer cases, a higher proportion were premenopausal, had a family history of breast cancer, were current smokers, and used vitamin supplements; more controls were breastfeeding, were moderately physically active for the past 5 years, and had higher daily vegetable and isoflavone intake.Iwasaki 2014 A double-blind, randomized, placebo-controlled trial in postmenopausal women at risk for breast cancer (N=1,075), known as the Minnesota Green Tea Trial, found no significant difference in incidence of adverse events or serious adverse events in women who consumed green tea extract (EGCG 843 mg) daily for 1 year compared with placebo. However, incidence of nausea and elevated ALT (P<0.001 for each) were significantly higher in the green tea group, while incidence of diarrhea was significantly lower (P=0.02).Dostal 2015

A Cochrane meta-analysis of the effects of green tea in cancer found insufficient and conflicting evidence to support a preventative role.Boehm 2009 The observed anticancer effects are largely attributed to the catechins found in tea, while action on tumors by theanine may be due to enhancement of the immune response.Percival 2008 A Cochrane review found no evidence that green tea prevents progression to malignancy in leukoplakia.Lodi 2004 A meta­-analysis of case-control and cohort studies examining the benefit of green and black teas and coffee on risk of esophageal cancer found green tea and coffee consumption have protective effects, with benefit occurring when case-control studies and studies from China were examined separately. Black tea conferred no benefit. Coffee consumption had a marginally significant inverse relationship, with lower esophageal cancer incidence in those who consumed lower amounts.Zheng 2013 A meta-analysis of 21 cohort and case-control studies (1989-2013) reviewed the effects of tea consumption on prostate cancer risk and found no statistically significant benefit overall, or when stratified by ethnicity (Asian vs non-Asian) or tea type (green vs black). Subanalysis of the 18 case-control studies showed a marginal protective effect.Lin 2014 A meta-analysis of 26 case-control and 12 cohort studies found an overall significant reduction in lung cancer risk (22% reduction) with tea consumption (relative risk [RR], 0.78; 95% CI, 0.7 to 0.83). A total of 33 studies were rated as high quality and 5 were of moderate quality; only meta-analysis of case-control data yielded significant results with significant heterogeneity and without publication bias. A significant protective effect was found for both green tea and black tea (severe heterogeneity; no publication bias) in Western studies as well as studies in China and Japan, and in women but not men (significant heterogeneity and publication bias). No association was found with regard to smoking status. Limitations included ambiguous definition of tea exposure, undefined variation in cup size/dose, and unknown duration of tea consumption.Wang 2014

A phase 2 study assessing the safety and effectiveness of an EGCG-enriched tea drink (double-brewed green tea) in maintaining remission of advanced-stage ovarian cancer in women was discontinued early due to unacceptable high recurrence at 18 months of therapy.Trudel 2013

In a 2014 meta-analysis of 14 articles (19 studies comprising 4,675 oral cancer cases), a significantly lower risk of oral cancer was observed with the highest tea consumption compared to the lowest tea consumption (RR=0.853; I2=23.8%) and with green tea (RR=0.798; I2=0%) but not black tea (RR=0.953; I2=0%); these associations were also demonstrated for Asian (RR=0.866; I2=0%) and white patients (RR=0.822; I2=36.2%).Wang 2014 In 2017, a meta-analysis was conducted to evaluate effects of green tea consumption on the risk of liver cancer. Of the 10 studies included, 6 were cohorts and 4 were case-controls conducted in either China or Japan. Pooled analysis documented a favorable relative risk for the highest consumption category (at least 5 cups/day) compared to non–green tea drinkers (RR=0.62; 95% CI, 0.49 to 0.79) but not compared to the lowest consumption category (0 to 2 cups/day); heterogeneity was high among studies. Similarly, those with a 20- to 30-year history (RR=0.72; 95% CI, 0.53 to 0.99) or more than 30-year history (RR=0.44; 95% CI, 0.19 to 0.96) of green tea consumption had a reduced relative risk of liver cancer, but this effect was not observed in those with a less than 20-year history of green tea consumption. When stratified by gender, women but not men who drank green tea exhibited a reduced risk (RR=0.57; 95% CI, 0.39 to 0.82). No associations were found comparing high or low concentrations of green tea, alcohol consumption, cigarette smoking, or chronic hepatitis B/C infection. A curvilinear dose relationship was observed between green tea intake and risk of liver cancer, with the downward trend in cancer risk most obvious with increased consumption of approximately 4 cups (960 mL) per day or more.Ni 2017

Cardiovascular effects

Epidemiological studies and in vitro experiments show that tea, including green tea, consumption is inversely associated with cardiovascular disease, although a direct cause-effect relationship has not been conclusively demonstrated.Cooper 2005, McKay 2002, Thielecke 2009, Vita 2003 Mechanisms of action under investigation include reduced low-density lipoprotein (LDL) oxidation, enhanced endothelial cell functioning, hypotensive effects, effects on atherosclerosis, platelet aggregation, and improved cholesterol profiles.Babu 2008, Hartley 2013, Thielecke 2009

Clinical data

Cholesterol-lowering effects of tea have been investigated in numerous clinical trials, including in healthy volunteers, as well as obese children and adults.Babu 2008, Frank 2009, Hooper 2008, Matsuyama 2008, Nantz 2009 Meta-analyses of trials published up to October 2012 evaluated tea flavonoids and/or green tea for reducing the risk of cardiovascular events. A reduction in total cholesterol, LDL cholesterol (LDL-C), and blood pressure was found for green tea, but no effect on high-density lipoprotein cholesterol (HDL-C) was established.Hartley 2013, Hooper 2008 These results are based on a limited number of clinical trials because inclusion criteria for the individual trials and test compounds used were often too heterogeneous for meta-analysis.Hartley 2013, Hooper 2008, Thielecke 2009 Further trials evaluating effects on cholesterol and other cardiovascular markers showed decreases in total and LDL-C for subgroups,Hsu 2008, Nantz 2009 decreases in serum triglycerides,Hsu 2008, Maki 2009 and decreased total cholesterol:HDL-C ratios.Frank 2009

A 2013 Cochrane review evaluated the benefit of green and black teas for primary prevention of cardiovascular disease (CVD). Green tea produced statistically significant reductions in total cholesterol, LDL-C, and blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]). Black tea produced statistically significant reductions in LDL-C and SBP and DBP over 6 months. When both tea types were analyzed together, they showed favorable effects on LDL-C and blood pressure. A small number of trials contributed to the positive results for the individual teas and the pooled data, and the meta-analysis authors noted that studies were at risk of bias.Hartley 2013 A 2014 systematic review and meta-analysis identified 10 randomized controlled trials (N=411) that studied black tea effects on cholesterol levels in healthy patients as well as in those at high cardiovascular risk (ie, prediabetes, hypercholesterolemia, coronary disease); the intervention was given for at least 2 weeks as monotherapy. Black tea consumption produced a reduction in LDL, specifically in those at higher cardiovascular risk (P=0.018 vs healthy subjects). No significant changes were noted in total cholesterol or HDL-C.Zhao 2015 These results were not supported by another 2014 meta­-analysis of 15 parallel or crossover randomized clinical trials that had similar inclusion criteria but found no beneficial effects of black tea on cholesterol parameters (eg, total, HDL, LDL).Wang 2014 Other data for black tea have documented body composition and anthropometry benefit at 3 months in regular tea drinkers compared with placebo (but not at 6 months), with no changes in glucose metabolism, plasma lipids, or endothelial function observed.Bohn 2014 A systematic review and meta-analysis of double-blind, placebo-controlled trials (20 randomized clinical trials; N=1,536) through May 2013 revealed similar results with green tea; statistically significant reductions in SBP, total cholesterol, and LDL-C, with a small effect size on SBP (mean difference [MD], −1.94 mm Hg, P=0.0002) and moderate effects on total cholesterol and LDL-C (MD, −0.13 and −0.19 mmol/L; P<0.0001 and P<0.0004, respectively) were observed. No significant effect was found on DBP, HDL, or triglycerides with green tea. Intervention duration in all trials was at least 2 weeks; however, lifestyle modification was not necessarily consistent across the studies, and only 1 of the randomized clinical trials included all hypertensive participants. Equivocal results were found between manufacturer-funded studies (12 randomized clinical trials; N=1,010) and publicly funded studies (6 randomized clinical trials; N=332) with regard to SBP, with the latter finding no difference.Onakpoya 2014 A trial examining effects on eye strain symptoms for 2 green tea extracts ("Sunrouge" or "Yabukita") with similar catechin content and varying amounts of anthocyanins noted increased SBP and DBP in patients using the anthocyanin-containing tea extract (Sunrouge).Maeda-Yamamoto 2018

Hypotensive effects of tea, including green tea, have been evaluated in other meta-analyses, with some reporting no effect for green teaFrank 2009 and increased blood pressure for black teaHooper 2008; other trials and meta-analyses have reported decreases in systolic pressureGreyling 2014, Matsuyama 2008, Nantz 2009, Peng 2014 and decreases in diastolic pressure.Brown 2009, Fukino 2008, Greyling 2014, Peng 2014 Meta-analyses have documented statistical significance for mean reductions in systolic and/or diastolic blood pressure of 2 mm Hg; however, these effects are small and may not be clinically important.Greyling 2014, Peng 2014, Yarmolinsky 2015 Studies evaluating other markers of cardiovascular stress (inflammation and oxidative stress) include reported decreases in serum amyloid-alpha and malondialdehyde with a decaffeinated green tea product,Nantz 2009 and no effect on endothelial vascular reactivity with an aqueous green tea extract.Frank 2009 No difference over placebo was found in cardiovascular risk markers (ie, waist circumference, total cholesterol, LDL-C, LDL:HDL ratio) in a randomized clinical trial conducted in active older subjects who participated in a pedometer-based walking program and consumed a beverage containing 630 mg/day of green tea catechins.Miyazaki 2013

Endothelial dysfunction and inflammation biomarkers were evaluated after 35 prehypertensive adults ingested pure epicatechin 100 mg/day and quercetin-3-glucoside 160 mg/day for 4 weeks in a double-blind, placebo-controlled, crossover study. Of the 5 endothelial dysfunction biomarkers measured, soluble endothelial selectin was significantly reduced (P=0.03) by epicatechin and quercetin supplementation. No other biomarkers were significantly affected by epicatechin; however, pure quercetin supplementation also reduced inflammatory markers (ie, interleukin 1 [IL-1]beta [P=0.009], z score for inflammation [P=0.02]). As a reference, it's important to note that 4 cups (960 mL) of black tea contain about 19 mg of quercetin.Dower 2015 A systematic review and meta-analysis of randomized controlled trials (published through October 2014) investigating the effects of green tea catechins for at least 2 weeks on the inflammatory biomarker C-reactive protein (CRP), a relatively strong predictor of cardiovascular risk, identified 8 trials (N=377) that ranged in size from 20 to 60 participants. Catechin doses ranged from 160 to 2,488 mg/day for 2 weeks to 3 months. No effect of green tea catechin supplementation on plasma CRP concentrations was identified, regardless of duration, dose, effect size, or healthy versus cardiometabolic history.Serban 2015

CNS effects

A neuroprotective property has been suggested for green tea extracts, especially for EGCG and theanine constituents. The pharmacological impacts are uncertain; however, several researchers have proposed a number of mechanisms by which green tea may act on the CNS that include free radical scavenging, iron-chelation, and anti-inflammatory effects, as well as modulation of enzymes involved in processing amyloid precursor protein.

Animal data

Animal experiments have shown positive findings for Alzheimer and Parkinson disease models.Cho 2008, Mandel 2004, Mandel 2008, Sun 2008, Weinreb 2004

Clinical data

In one small randomized, double-blind, placebo-controlled study in adults with mild cognitive impairment (N=91), a proprietary combination product (LGNC-07) containing green tea extract and L-theanine was used daily for 16 weeks (total daily green tea extract dose, 1,440 mg; total daily L-theanine dose, 240 mg). Between-group comparisons for improvement in memory at week 16 showed no difference. The green tea/L-theanine group results were better than placebo when stratified according to baseline memory scores. Attention was improved compared with baseline for green tea/L-theanine.Park 2011 In another study in Japanese university students, anxiolytic properties were demonstrated for the theanine component of green tea.L-theanine 2005

A cross-sectional study (N=537) examined the association between green tea, coffee, and caffeine consumption on depressive symptoms in adult Japanese workers. A 41% and 51% lower prevalence of depressive symptoms was associated with higher green tea intake (2 to 3 cups/day and at least 4 cups/day, respectively) compared with those who drank up to 1 cup/day. Workers drinking higher amounts of green tea were also more likely to be female and single; consume n-3 polyunsaturated fatty acids, fruits, and vegetables; and be nonsmokers, and were also less likely to drink alcohol and coffee. Dietary food and drink intake for the preceding month was recorded using a questionnaire, and depressive symptoms were assessed via the Japanese version of the Center for Epidemiologic Studies Depression Scale (comprising 20 questions addressing 6 symptoms of depression in the past week).Pham 2014

Diabetes

Clinical data

Few clinical trials have evaluated green tea extracts or catechins in diabetic populations,Hosoda 2003, Mackenzie 2007, Nagao 2009, Thielecke 2009, Venables 2008 with the majority of findings reported among obese adults or healthy voIunteers.Brown 2009, Dulloo 1999, Fukino 2008 Many studies reported modest positive influence on gIycosyIated hemoglobin (HbA1c); however, a number of studies also reported no effect on insulin sensitivity, fasting blood glucose (FBG), and glucose tolerance.Thielecke 2009, Venables 2008 Two 2013 meta-analyses attempted to summarize the effects of green tea on glycemic control. One of these pooled the available data on green tea catechins with or without caffeine (22 trials, N=1,584) and found a statistically significant (but clinically modest) reduction in FBG (−1.48 mg/dL; 95% CI, −2.57 to −0.4). No significant reductions were observed for other measures, including fasting blood insulin or HbA1c.Zheng 2013 Another group of authors conducted a meta-analysis using slightly different study selection criteria (17 trials, N=1,133) and did not specify caffeine content of the study treatments; this meta-analysis found a statistically significant but clinically modest reduction in HbA1c of −0.3% (95% CI, −0.37% to −0.22%; P<0.01). When data from studies with high Jadad scores were pooled, there was a significant reduction in fasting blood insulin levels (−1.16 microunits/mL; 95% Cl, −1.91 to −0.4; P=0.03).Liu 2013 A 2014 systematic review and meta-analysis of randomized, controlled trials published through December 2011 identified no differences between placebo and green tea (tea or extract) for fasting plasma glucose, serum insulin, oral glucose tolerance test, glycosylated hemoglobin (HbA1c), or homeostasis model of insulin resistance in patients with or at high risk for type 2 diabetes mellitus.Wang 2014 An EGCG dosage range of 84 to 386 mg/day may be adequate to support glucose homeostasis, based on available literature.Thielecke 2009

Pooled data from a meta-analysis of 10 randomized clinical trials (N=608) (published through January 2015) investigating tea or tea extract given for 4 to 16 weeks to patients with type 2 diabetes found a significant effect compared with control for only 2 of 16 anthropomorphic and biochemical indexes: fasting serum insulin (P=0.005) and waist circumference (P=0.009). The latter held true only for interventions given for at least 8 weeks. Data for green tea, when analyzed separately, also showed significantly reduced fasting serum insulin (P=0.04). No significant or meaningful effects of tea or tea extracts on body weight, body mass index, FBG, homeostasis model of insulin resistance, triglycerides, total cholesterol, LDL-C, HDL-C, leptin, creatinine, uric acid, or adiponectin were observed.Li 2016

A cross-sectional, stratified, cluster random sampling of 4,808 Chinese Han residents in the Fujian province evaluated data collected from a standard questionnaire to determine effects of green (nonfermented) versus oolong (partially fermented) tea on the risk of impaired glucose regulation. Participants were excluded if they had conditions affecting diet, lifestyle, and absorption of tea. Subgroup analyses revealed that green tea tended to be consumed by older subjects; oolong tea was generally consumed by younger subjects who also drank milk, exercised less, and had a family history of diabetes. Compared with non-tea drinkers, those who drank tea were more likely to smoke and drink alcohol. A protective effect (defined as an odds ratio [OR] of less than 1) was observed for impaired fasting glucose in green tea drinkers (adjusted OR for green tea consumption of less than 1 cup, 1 to 15 cups, 16 to 30 cups, and more than 30 cups per week were 1 (reference), 0.42 (95% CI, 0.27 to 0.65), 0.23 (95% CI, 0.12 to 0.46), and 0.41 (95% CI, 0.17 to 0.93), respectively, and for impaired glucose tolerance in oolong tea drinkers, especially for those who consumed 16 to 30 cups per week.Huang 2013

Hypouricemic effects

Clinical data

An experimental randomized, open-label study investigated the hypouricemic effects of green tea extract in 30 healthy adults. Capsules containing green tea extract equivalent to 1 g of dried leaves and 62.5 mg of EGCG were taken twice daily after meals. After 2 weeks of 2, 4, or 6 g/day of extract, mean serum uric acid levels decreased in all groups, with no statistical significance among groups. Overall, clearance of uric acid decreased significantly after extract consumption (27.55%; P<0.001); similarly, significant decreases were seen in the groups receiving 2 g/day and 4 g/day (P<0.05 each). Serum antioxidant activity was dose dependent and was increased significantly overall (P=0.001), with the greatest mean increases observed with 6 g/day. Green tea extract was well tolerated; all adverse events were mild, with half occurring in the high-dose group. Abdominal discomfort was the most commonly reported event; others included dry mouth, dizziness, nausea, vomiting, heartburn, constipation, diarrhea, fatigue, palpitation, light-headedness, nocturia, sore throat, insomnia, and increased appetite.Jatuworapruk 2014

Obesity

Clinical data

Placebo-controlled clinical trials suggest that the thermogenic properties of green tea might contribute to weight control,Cooper 2005, Kovacs 2004, McKay 2002, Thielecke 2009 but there is debate regarding the role of caffeine in this effect.Hursel 2009, Kovacs 2004 Catechins may inhibit the enzyme responsible for degradation of norepinephrine.Belza 2009, Thielecke 2009 Most studies report positive findings for increased fat oxidation, changes in abdominal and subcutaneous fat, and decreased waist circumference.Belza 2009, Dulloo 1999, Fukino 2008, Hsu 2008, Maki 2009, Matsuyama 2008, Nagao 2009

Confounders include the quantity and possible adjuvant role of caffeine, as well as the intervention diets used.Thielecke 2009 Dosage ranges used in these trials include EGCG 270 to 800 mg/dayBelza 2009, Brown 2009 and catechins 125 to 625 mg/day.Maki 2009, Shen 2009 A Cochrane systematic review of published data found it difficult to pool study results due to heterogeneity of studies. The reviewers concluded that any weight loss associated with green tea is likely to be statistically and clinically insignificant (mean difference in BMI of −0.2 kg/m2; 95% CI, −0.5 to 0.1; P=0.21 for studies conducted outside Japan).Jurgens 2012

Orodental

Evidence for protection against dental caries comes from kinetic and animal models, with few human trials published. Green tea exhibits antimicrobial actions against oral bacteriaChow 2003, Cooper 2005, Koo 2004, McKay 2002 and provides a natural source of fluoride.Boehm 2009, McKay 2002, Shen 2009 Oolong and green teas appear to inhibit bacterial adherence to tooth surfaces and to inhibit the rate of acid production.Koo 2014, McKay 2002

Clinical data

Black and green tea have been shown to inhibit amylase activity in human saliva.Koo 2014, McKay 2002 In a randomized controlled trial, young adults with acute pericoronitis (N=101) who rinsed with a 5% green tea mouthwash experienced significantly reduced mean pain scores 3 to 5 days postdebridement (P<0.006) and used significantly fewer analgesics (P<0.05) than the control group (chlorhexidine 0.12% rinse).USDA 2010, Vita 2003 Green tea consumption for 3 months as an adjunct to nonsurgical periodontal therapy significantly improved clinical parameters of mild to moderate chronic periodontitis in a double-blind, randomized, placebo-controlled trial (N=120). The mean level of antioxidant measured in gingival crevicular fluid and plasma increased significantly in the green tea group (P<0.001 for each), whereas no significant change in either was seen in controls. Both groups experienced significant improvement from baseline in gingival index, plaque index, incidence of bleeding on probing, and clinical attachment level (P<0.001 for each variable). The overall percentage improvement in gingival index was significantly better with green tea (1.67-fold greater reduction than controls).Chopra 2016

Osteoporosis

Animal data

Animal experiments have demonstrated increased bone density with administration of green tea extract. Bone strength and fracture rates were not reported; therefore, extrapolation of results to humans is difficult.Shen 2009 Mechanisms of action suggested an antioxidant and anti-inflammatory action, as well as direct action on osteoblasts (to increase survival) and osteoclasts (suppression), and an immunological action, including modulation of cytokines. Animal studies also suggest the tannin component of green tea may decrease absorption of calcium to some extentCooper 2005, Shen 2009; the provision of fluoride is recognized as 3 cups (720 mL) of green tea per day, providing approximately 4 mg/day of fluoride.Shen 2009

Clinical data

Epidemiological and case control studies suggest tea consumption helps protect against osteoporosis in older women; however, not all studies find a positive association for increased bone density, and data for bone fractures are conflicting.Cooper 2005, McKay 2002, Shen 2009 Differences in study populations make a meta-analysis difficult. Long-term clinical studies are needed that include outcomes of bone fracture and examination of the bone micro-architecture before conclusive recommendations can be made.

Polycystic ovary disease

Clinical data

A 2017 systematic review and meta-analysis of nutritional supplements and herbal medicines for polycystic ovary syndrome identified 1 randomized controlled trial that investigated the use of C. sinensis for the primary outcome of menstrual regularity. No difference was found between green tea and placebo. Incongruences throughout this paper between reference numbers in the table of studies versus reference numbers in the text led to conflicting data for many interventions; however, no findings of significance were evident for the single study that summarized C. sinensis.Arentz 2017

Respiratory disease

Clinical data

A cross-sectional survey of national data on 13,570 participants found that green tea intake by Koreans at least 40 years of age was correlated with reduced risk of chronic obstructive pulmonary disease (COPD). Incidence of COPD decreased from 14.1% to 5.9% with increased frequency of green tea intake from never to at least twice-a-day consumption (P<0.001). A higher forced expiratory volume in the first second of expiration (FEV1)/forced vital capacity (FVC) (beta=0.008) and slightly reduced risk of COPD (OR, 0.62; 95% CI, 0.4 to 0.97) were noted after adjusting for multiple covariates in those who consumed green tea at least twice a day compared to those who never consumed green tea. Of the 13,570 participants, only 3.7% (n=506) were at least twice-a-day consumers, while the majority (45.9%) were nonconsumers.Oh 2018

Stroke (acute cerebrovascular episode)

In vitro data

An in vitro analysis documented the protective effect of EGCG, in combination with heparin, on apolipoprotein A-1 amyloid associated with atherosclerosis.Townsend 2018

Clinical data

Large epidemiological studies have shown an inverse association between green tea consumption and the incidence of stroke.Fraser 2007 However, smaller case control studies provide equivocal results.Arab 2009, Li 2009 A meta-analysis of 10 trials meeting inclusion criteria for analysis showed consumption of 3 cups (720 mL) or more per day of green tea reduced the incidence of stroke and reduced mortality from stroke.Li 2009 The meta-analysis included 3 trials from Japan and Finland that provided stronger support for this finding than the 3 trials included from US-based populations, which had wider confidence intervals.Li 2009 Suggested mechanisms of action involve impacts on hypertension, atherosclerosis, and thrombogenesis.Arab 2009, Fraser 2007

UV protection

Clinical data

Green tea extract (2% to 3%) has been evaluated for use as a topical photoprotective agent. Clinical studies have demonstrated a dose-independent protective effect via mechanisms other than a screening effect (the sun protection factor for the test materials was minimal). Erythema and inflammation consequent to solar-simulated UV exposure was reduced and was suggested to be related to protection against cutaneous immunosuppression and an antioxidant effect.Camouse 2009, Janjua 2009 However, a 2-year clinical study found no superiority of green tea polyphenols taken orally over placebo on photoaging, based on clinical and histological assessments.Toda 1989 Similar results were found in a 3-month double-blind, randomized, placebo-controlled trial in 50 healthy adults who received 2,700 mg/day of green tea extract orally (1,080 mg/day of green tea catechins) plus 100 mg/day of vitamin C. No difference was found between the treatment and placebo groups in median sunburn threshold, skin erythema, leukocyte infiltration, or eicosanoid response to UV radiation inflammatory challenge.Farrar 2015

Dosing

Pharmacokinetic studies of tea have been conducted in humans, with measurable levels of various chemical compounds found in the plasma, feces, and urine. Chemical constituents cross the blood-brain barrier.Chow 2003, Chow 2005, He 1994, Henning 2004, Mulder 2005, Spencer 2003, van het Hof 1998 Bioavailability of active compounds appears to be unaffected by the addition of milk to tea, and can be enhanced in a fasted state.Blumberg 2003, Leenen 2000, McKay 2002, Sarma 2008, van het Hof 1998 Plasma levels of EGCG are increased 5-fold when green tea extracts are consumed in the fasted state and may lead to potentially toxic doses. Therefore, extracts must be taken with meals.Briggs 1990 Sitting in a hot spring bath after drinking green tea may increase absorption of green tea catechins.Hayasaka 2013

Daily intake of 3 to 5 cups/day (720 to 1,200 mL) of green tea provides at least 180 mg/day of catechins and at least 60 mg of theanine.Boehm 2009, Cooper 2005

Anogenital warts

Topical application of sinecatechins (polyphenon E 10% or 15%) for up to 16 weeks.Meltzer 2009

Cardiovascular effect

Green tea catechins or extract (160 to 2,488 mg/day) have been used in trials, often in divided dosages (treatment duration, 2 weeks to 3 months).Frank 2009, Nantz 2009, Serban 2015

Cognitive impairment

In one small study using a combination nutraceutical (LGNC-07) containing green tea extract and L-theanine, two 430 mg capsules (each capsule containing green tea extract 360 mg and L-theanine 60 mg) were administered twice daily, 30 minutes after meals, for 16 weeks (total daily green tea extract dose, 1,440 mg; total daily L-theanine dose, 240 mg).Park 2011

Depression

2 to 4 or more cups/day of green tea has been used to lower the prevalence of depressive symptoms.Pham 2014

Diabetes

An EGCG dosage range of 84 to 386 mg/day may be adequate to support glucose homeostasis, based on available literature.Thielecke 2009

Obesity

ECGC 400 mg twice daily for 8 weeks was used in one clinical trialBrown 2009; green tea extract tablets (containing 125 mg of catechins) and a daily green tea catechin beverage (containing 625 mg of catechins) have also been used in studies of overweight and obese adults.Belza 2009, Maki 2009

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Due to the caffeine content of tea, use during pregnancy should be limited because caffeine crosses the placenta and reaches fetal blood and tissue in levels similar to those of maternal concentrations. Excessive caffeine intake (greater than 600 mg/day) has been weakly associated with increased fetal loss, low birth weight, premature delivery, increased incidence of fetal breathing activity, and decreased baseline fetal heart rate.Taylor 1999 Caffeine is present in the milk of breast-feeding mothers. Folic acid levels may be decreased in pregnant women who consume green tea. Animal data are inconclusive.Moussally 2012, Shiraishi 2010, Zielinsky 2012

Interactions

Acenocoumarol: Green tea may enhance the adverse/toxic effect of acenocoumarol. Particularly, the risk of bleeding may be increased due to possible antiplatelet effects of green tea. Green tea may diminish the anticoagulant effect of acenocoumarol. Monitor therapy.Booth 1995, Booth 1995, Booth 1993, Kang 1999, Sato 1989, Tanabe 2008, Taylor 1999

Agents with antiplatelet properties: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of agents with antiplatelet properties. Bleeding may occur. Consider therapy modification.Mousa 2010, Spolarich 2007, Stanger 2012, Ulbricht 2008

Anticoagulants: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of anticoagulants. Bleeding may occur. Consider therapy modification.Mousa 2010, Spolarich 2007, Stanger 2012, Ulbricht 2008

Bortezomib: Green tea may diminish the antineoplastic effect of bortezomib. Avoid combination.Golden 2009, Liu 2008

Clozapine: Animal studies document how green tea decreases the bioavailability or concentration of clozapine. Avoid combination.Albassam 2017

Diltiazem and verapamil: Animal studies document how green tea increases the bioavailability or concentrations of both of these calcium channel blockers. Avoid combination.Albassam 2017

Folic acid: Green tea may decrease the serum concentration of folic acid. Monitor therapy.Alemdaroglu 2008, Alemdaroglu 2007

Herbs (anticoagulant/antiplatelet properties): Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of other herbs (anticoagulant/antiplatelet properties). Bleeding may occur. Consider therapy modification.Mousa 2010, Spolarich 2007, Stanger 2012, Ulbricht 2008

Nadolol: Green tea may decreases the serum concentration of nadolol. Avoid combination or consider therapy modification.Misaka 2014, Roth 2011

Nonsteroidal anti-inflammatory agents: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of nonsteroidal anti-inflammatory agents. Bleeding may occur. Consider therapy modification.Mousa 2010, Spolarich 2007, Stanger 2012, Ulbricht 2008

Quetiapine: Animal studies document how green tea decreases the bioavailability or concentrations of quetiapine. Avoid combination.Albassam 2017

Salicylates: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of salicylates. Bleeding may occur. Consider therapy modification.Spolarich 2007, Ulbricht 2008

Simvastatin: Green tea may increase the serum concentration of simvastatin. Specifically, simvastatin lactone concentrations may be increased. Monitor therapy.Chow 2006, Donovan 2004, Werba 2008

Tamoxifen: Animal studies document how green tea increases the bioavailability or concentrations of tamoxifen. Avoid combination.Albassam 2017

Thrombolytic agents: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of thrombolytic agents. Bleeding may occur. Consider therapy modification.Mousa 2010, Spolarich 2007, Stanger 2012, Ulbricht 2008

Vitamin K antagonists: Green tea may enhance the adverse/toxic effect of vitamin K antagonists. Particularly, the risk of bleeding may be increased due to possible antiplatelet effects of green tea. Green tea may diminish the anticoagulant effect of vitamin K antagonists. Monitor therapy.Booth 1995, Booth 1995, Booth 1993, Kang 1999, Rietveld 2003, Sato 1989, Tanabe 2008, USDA 2010

Warfarin: Green tea interacts significantly with warfarin; avoid use.Page 2016 Green tea may enhance the adverse/toxic effect of warfarin. Particularly, the risk of bleeding may be increased due to possible antiplatelet effects of green tea. Green tea may diminish the anticoagulant effect of warfarin. Monitor therapy.Booth 1995, Booth 1995, Booth 1993, Kang 1999, Sato 1989, Tanabe 2008, Taylor 1999

Adverse Reactions

There are no reports of clinical toxicity from daily tea consumption (ie, green tea, black tea, decaffeinated black tea). Adverse events recorded in pharmacokinetic studies in humans using tea extracts (including green tea extract) include headache, dizziness, and GI symptoms.He 1994 Mild reactions reported in a small randomized, open-label study included dry mouth, dizziness, nausea, vomiting, heartburn, constipation, diarrhea, fatigue, palpitation, light-headedness, nocturia, sore throat, insomnia, and increased appetite; abdominal discomfort was the most commonly reported event.Jatuworapruk 2014

Hepatotoxicity has been reported, leading to withdrawal of a green tea extract weight-loss product (Exolise) from the market in France and Spain. Additionally, acute impending liver failure was attributed to a green tea extract weight loss supplement (Green Tea Fat Burner) in a 16-year-old obese male; jaundice symptoms were noticed within 2 months of initiating the supplement.Patel 2013 Severe acute reversible hepatitis was described in a 63-year-old woman after approximately 2 months of daily consumption of highly concentrated decaffeinated green tea capsules (725 mg of extract daily). All other etiologies were ruled out, and analysis of capsules revealed no contaminants.Pillukat 2014 A review of 34 case studies of hepatotoxicity, including 1 fatality, found possible causality due to EGCG or its metabolites. Onset of toxicity occurred within 3 months in 70% of cases, with increased transaminases and bilirubin levels evident.Mousa 2010 A systematic review of hepatic adverse reactions with green tea–based herbal supplements published between 2008 and March 2015 identified 8 probable cases and 11 possible cases. The analysis documented a longer latency period before hepatic reactions (mean, 179 days) with preparations containing only green tea compared with multicomponent formulations (mean, 44 days). Additionally, resolution of liver injury was achieved in 100% of green tea product users within a mean recovery time of 64 days, in contrast to multicomponent green tea products that resulted in more serious hepatotoxicity (including liver transplantation) and mean recovery time of 118 days when resolution did occur.Mazzanti 2015, Whitsett 2014

Data collected between 2004 and 2013 among 8 US centers in the Drug-induced Liver Injury Network revealed 15.5% (130) of hepatotoxicity cases were caused by herbals and dietary supplements, whereas 85% (709) were related to medications. Of the 130 related cases of liver injury related to supplements, 65% were from nonbodybuilding supplements and occurred most often in Hispanic/Latinos compared to non-Hispanic whites and non-Hispanic blacks. Liver transplant was also more frequent with toxicity from nonbodybuilding supplements (13%) than with conventional medications (3%) (P<0.001). Overall, the number of severe liver injury cases was significantly higher from supplements than conventional medications (P=0.02). Of the 217 supplemental products implicated in liver injury, green tea was among the 22% (116) of the single-­ingredient products.Navarro 2014

Plasma levels of EGCG are increased 5-fold when green tea extracts are taken in the fasted state and may lead to potentially toxic doses. Green tea extract should not be taken on an empty stomach.Briggs 1990

Toxicology

Literature reviews document no major teratogenic, mutagenic, or carcinogenic substances in green tea. Furthermore, green tea and its main catechins are associated with weak developmental toxicity effects. In rats, EGCG oral median lethal dose (LD50) values are estimated to be between 200 and 2,000 mg/kg, with the lowest dose being safe and the higher dose inducing mortality.Bedrood 2017 For adults with normal liver function, human safety data documents a safe daily consumption level of 300 mg of EGCG.Hu 2018

Multidose pharmacokinetic studies of EGCG capsules suggest a daily dosage of 800 mg/day (approximately equivalent to 16 Japanese-style cups of green tea) for up to 4 weeks is safe and well tolerated.Briggs 1990, Chow 2005

Oral administration of high-dose green tea extract and catechins was hepatotoxic in rats. Similarly, low-dose intraperitoneal administration led to severe hepatic necrosis and mortality.Mousa 2010

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