GREEN TEA

Green tea has suprisingly few studies, in part due the variations in active compound – EGCG epigallocatechin gallate. This extract which is used in clinical trials (Supplements Library). Results of studies have been quite mixed.

A few post-diagnostic trials show improved outcomes in breast and prostate cancer, and with radiotherapy in lung cancer. Also at least one trial was positive in its results for use with chemotherapy in bladder cancers. A 2014 trial showed short term promise in slowing prostate cancer development when combined with pomegranate, broccoli and turmeric (see References). Another recent study showed supportive actions with to radiotherapy in lung cancer, with reported much improved 5 year progression free survival ( the size of the trial meant this was not statistically verified)

A large scale 2023 meta-analysis across data from multiple countries showed a substantial preventative effect for pre-diagnostic breast cancer survival statistics. And a tendency at least, for lower recurrence in ER+ variants. There are similar pre-diagnostic benefits reported in prostate cancer, where suppression of early stage development phases has been shown ( see References)

Despite this, there is at best mixed evidence from several clinical studies particularly those in prostate cancer, and multiple trials report no measurable impacts. Green tea extract EGCG doses are in the 400 to 800mg range daily, trials in other disease have used 1000mg. Loose leaf japanese green teas such as matcha and sencha have the highest content, and best effects between meals. Adding any kind of milk, even soy, will reduce the availability of EGCG.

Note that some research has shown interactions with oncology treatements like TKIs (tyrosine kinase inhibitors) such as sunitinib. As always, consult with medical professionals.

EXAMPLES OF IMPROVED OUTCOMES

YES

PRE-DIAGNOSIS OR PREVENTION

YES

Highlighted Studies

The objective response rate (ORR) was higher than that of conventionally treated patients (84.6 vs 50% ), while the median PFS and OS were not significantly prolonged. At data cut-off (1 January 2021), 5-year PFS was 33% with EGCG versus 9.3% with conventional treatment, and 5-year OS was 30.3% versus 33.3%, respectively. The mean adjusted esophagitis index and pain index of patients with EGCG application were lower than conventional treatment (5.15 ± 2.75 vs...

We found that increased consumption of [japanese] green tea was correlated with decreased recurrence of stage I and II breast cancer (P<0.05 for crude disease-free survival); the recurrence rate was 16.7 or 24.3% among those consuming ≥5 cups or ≥4 cups per day, respectively, in a seven-year follow-up of stage I and II breast cancer, and the relative risk of recurrence was 0.564

After 1 year, only one tumor was diagnosed among the 30 GTCs-treated men (incidence, ∼3%), whereas nine cancers were found among the 30 placebo-treated men (incidence, 30%). Total prostate-specific antigen did not change significantly between the two arms, but GTCs-treated men showed values constantly lower with respect to placebo-treated ones. International Prostate Symptom Score and quality of life scores of GTCs-treated men with coexistent benign prostate hyperplasia improved, reaching s...

As stated previously, treatment with single-agent erlotinib [a tyrosine kinase inhibitor] did not show any impact on oral CFS [pre-cancer lesions in high risk head and neck cancer groups] compared with the placebo group. Therefore, we believe that our combination of green tea PPE [Green Tea Extract] and erlotinib appears to be much more effective and synergistic in preventing the progression of APLs to invasive cancer in the head and neck, although the finding is based on a small pilot phase ...

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TABLE OF REFERENCES

URL	Rating	Highlight	Highlight 2
https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.686950/full	4	The objective response rate (ORR) was higher than that of conventionally treated patients (84.6 vs 50%, P = 0.045), while the median PFS and OS were not significantly prolonged. At data cut-off (1 January 2021), 5-year PFS was 33% with EGCG versus 9.3% with conventional treatment, and 5-year OS was 30.3% versus 33.3%, respectively. The mean adjusted esophagitis index and pain index of patients with EGCG application were lower than conventional treatment (5.15 ± 2.75 vs 7.17 )	Consistent with previous reports, EGCG could alleviate some esophagitis-related indexes in SCLC patients receiving radiotherapy with an acceptable toxicity. Furthermore, EGCG may increase the ORR without reducing PFS or OS. Further basic and clinical studies should be conducted to testify and clarify the mechanisms of differential effect of EGCG on cancer and normal tissues during radiation.
https://pmc.ncbi.nlm.nih.gov/articles/instance/5921805/pdf/CAS-89-254.pdf	4	We found that increased consumption of green tea was correlated with decreased recurrence of stage I and II breast cancer the recurrence rate was 16.7 or 24.3% among those consuming ≥5 cups or ≥4 cups per day, respectively, in a seven-year follow-up of stage I and II breast cancer, and the relative risk of recurrence was 0.564	In this study, we first examined the association between consumption of green tea prior to clinical cancer onset and various clinical parameters assessed at surgery among 472 patients with stage I, II, and III breast cancer. We found that increased consumption of green tea was closely associated with decreased numbers of axillary lymph node metastases among premenopausal patients with stage I and II breast cancer and with increased expression of progesterone receptor (PgR) and estrogen receptor (ER) among postmenopausal ones
https://aacrjournals.org/cancerres/article/66/2/1234/526429/Chemoprevention-of-Human-Prostate-Cancer-by-Oral	4	After 1 year, only one tumor was diagnosed among the 30 GTCs-treated men (incidence, ∼3%), whereas nine cancers were found among the 30 placebo-treated men (incidence, 30%). Total prostate-specific antigen did not change significantly between the two arms, but GTCs-treated men showed values constantly lower with respect to placebo-treated ones. International Prostate Symptom Score and quality of life scores of GTCs-treated men with coexistent benign prostate hyperplasia improved, reaching statistical significance in the case of International Prostate Symptom Scores	If confirmed, our finding suggests a new scenario in which the incidence of this disease could be greatly reduced by simply making GTCs available to the elderly or men at high-risk, resulting in a tremendous social and clinical impact, especially in the Western countries. The fact that no side or adverse effects have been reported confirm that GTCs, at least at the dosage used here, are safe in humans
https://aacrjournals.org/clincancerres/article/26/22/5860/83115/Phase-Ib-Study-of-Chemoprevention-with-Green-Tea	3.5	After 6 months of intervention, we obtained remarkably high pathologic responses including CR (47%, 8/17) [complete response], PR (18%, 3/17)[partial response], and SD (18%, 3/17) [stable disease], while only 18% (3/17) of patients had PD [progression]. In particular, the most APLs (severe dysplasia or CIS) [advanced pre-cancer lesions]showed also very high pathologic major responses (62%) with excellent median duration of response (33.6 months) in a subset analysis	As shown in the EPOC study and stated previously, treatment with single-agent erlotinib did not show any impact on oral CFS compared with the placebo group (15). Therefore, we believe that our combination of green tea PPE and erlotinib appears to be much more effective and synergistic in preventing the progression of APLs to invasive cancer in the head and neck, although the finding is based on a small pilot phase I study.
https://aacrjournals.org/cancerpreventionresearch/article/10/5/298/46590/A-Phase-II-Randomized-Double-blind-Presurgical	3.5	Taken together, the favorable biomarker changes observed in this study have been associated with anticarcinogenic effects in numerous studies across different tumor types including bladder cancer. While follow-up biologic studies of effect on growth and apoptosis are needed to further corroborate our observations, these EGCG dose-dependent tissue biomarker findings, coupled with similar dose-dependent tissue and plasma pharmacokinetic results, strongly support the potential bladder cancer preventive properties of Polyphenon E.	We demonstrate in a phase II pilot study tissue accumulation of EGCG in nonmalignant bladder urothelium which follows both plasma and urine levels in a dose-dependent fashion. Furthermore, dose-dependent changes in the intermediate endpoint biomarkers, PCNA and clusterin, were observed consistent with potential chemopreventive efficacy. Acknowledging the limitations of this pilot study, we feel these findings indicate Polyphenon E administration results in definable tissue accumulation and more importantly desirable biologic activity which warrant further clinical studies
https://www.oncotarget.com/article/16230/text/https://pubmed.ncbi.nlm.nih.gov/28415774/	3.5	Subgroup analysis showed that green tea catechins significantly decreased prostate cancer in HGPIN patients [pre-cancer stage of prostate cancers] (7.60% vs 23.1%, RR = 0.39) The adjusted indirect meta-analysis favored green tea catechins over other chemoprevention agents, and significantly when compared to natural food products combination (RR = 0.355).	The direct and indirect meta-analysis demonstrated that green tea green tea catechins significantly inhibit prostate cancer in HGPIN patients and are better than other chemoprevention agents for prostate cancer. The results of this study have implication for the prostate cancer prevention and support the future clinical study with green tea catechins for HGPIN patients.
https://aacrjournals.org/cancerpreventionresearch/article/2/7/673/48517/Tea-Polyphenols-Decrease-Serum-Levels-of-Prostate	3.5	Our results show a significant reduction in serum levels of PSA, HGF, and VEGF in men with prostate cancer after brief treatment with EGCG (Polyphenon E), with no elevation of liver enzymes. These findings support a potential role for Polyphenon E in the treatment or prevention of prostate cancer.	Lowering biological levels of VEGF in patients with advanced cancer is predicted to increase their overall survival time. Therefore, it is reasonable to propose that reductions in the levels of this cytokine could slow the progression of prostate cancer. Thus, the reduction in serum levels of VEGF in men consuming Polyphenon E seems promising, and additional longer-term studies will be needed to determine if lowering VEGF and HGF serum levels actually translates into a more favorable clinical outcome.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020278/	3.5	..this statistically valid double-blind randomised controlled trial has demonstrated a significant short-term effect on PSA and is food for thought for men living with prostate cancer, 50–70% of whom are reported to have taken ‘over-the-counter' supplements...The favourable effect on PSA progression was significant both in men on primary AS and those experiencing a PSA relapse after radiotherapy. This low cost food supplement was well-tolerated and also influenced clinically relevant decisions, as to whether to switch to interventions with more toxicity. Although these results do not prove a long-term effect, they have provided significant encouragement	The median rise in PSA in the food supplement group (FSG) was 14.7% , as opposed to 78.5% in the placebo group ... In all..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.
https://academic.oup.com/jncics/article/8/1/pkad104/7468128	3.5	Green tea was investigated only in recurrence for prediagnostic intake (2 studies). A nonsignificant association was found for the overall population (HR = 0.74, 95% CI = 0.55 to 1.01; I2 = 0%; P = .98 for heterogeneity). Stratification by stage revealed a significant risk reduction in stage I and II breast cancer (HR = 0.56, 95% CI = 0.38 to 0.83) but not stage III or IV breast cancer	The observed 44% risk reduction in recurrence for stage I and II breast cancer with prediagnostic intake of green tea was based on 2 studies that observed the greatest effect at 3 to 5 cups per day and 5 cups or more per day, respectively. According to WCRF/AICR modified GRADE criteria, these results suggest “probable” grade for soy isoflavones in recurrence and ENL in mortality outcomes but “limited suggestive” for green tea in estrogen receptor–positive disease for recurrence
https://pubmed.ncbi.nlm.nih.gov/28929216/	3	Seven of nine (78%) patients experienced significant improvement based on reduced frequency of bowel movements and bleeding, while five of nine (56%) experienced complete relief. One patient experienced no improvement with EGCG, and one had progression of pouchitis symptoms while taking EGCG. No significant adverse events were noted by patients while taking EGCG.	Pouchitis is the most common complication of ileal pouch-anal anastomosis (IPAA) following total proctocolectomy, affecting up to 50% of patients. Symptoms include increased stool frequency, urgency, cramping, and bleeding. Management of pouchitis is complex in antibiotic refractory cases. Plant-based polyphenolic compounds have shown protective effects against UC.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0091163	3	The HOMA-IR index decreased from 5.4±3.9 to 3.5±2.0 in therapeutic arm only. Adiponectin, apolipoprotein A1, and apolipoprotein B100 increased significantly in both arms, but only glucagon-like peptide 1 increased in the therapeutic arm. However, only decreasing trend in triglyceride was found in between-group comparison. Our study suggested that green tea extract significantly improved insulin resistance and increased glucagon-like peptide 1 only in within-group comparison. The potential effects of green tea extract on insulin resistance and glucagon-like peptide 1 warrant further investigation.	Interestingly, insulin decreased markedly from 15.6±10.4 to 9.3±4.2 (p = 0.000) in the EGCG group and from 17.0±14.8 to 12.3±7.5 (p = 0.039) in the placebo group. But the difference between groups didn’t was not statistically significant. This study evaluates insulin resistance by HOMA-IR index. The HOMA-IR in the EGCG group decreased from 5.4±3.9 to 3.5±2.0 with statistical significance (p = 0.004), while that in the placebo group decreased from 5.9±4.5 to 4.7±3.4 without statistical significance.
https://www.frontiersin.org/articles/10.3389/fnut.2022.1084455/full	2	However, our findings revealed that green tea supplementation has favorable effects on the glycemic profile by decreasing both FBS and HbA1c. Although the antioxidant content and anti-obesity of green tea (which is discussed above) are involved in the favorable effects of GTE on glycemic profile, (99, 106–108) in our study, some other possible mechanisms can contribute. It has been shown that green tea can increase circulating adiponectin (91). It is well-documented that adiponectin is the most abundant peptide secreted by adipocytes, whose increases are considered a therapeutic target in obesity-related diseases, including insulin resistance and T2DM (109, 110). Therefore, the adiponectin-increasing effects of green tea can be a possible mechanism for its hypoglycemic effects.	However, our findings underlined that green tea also can have positive effects on lipid profile by increasing HDL which was not seen in the previous meta-analyses. Moreover, we showed that green tea supplementation can decrease TG if intervention lasts more than 12 weeks. The possible mechanisms underlying the positive effects of green tea on lipid profile. The hypolipidemic effects of GTE can be attributed to the high content of flavonoids, especially catechins, which are potent antioxidants (91). One of these catechins high in green tea is epigallocatechin (57). It is well-known that dietary supplements with antioxidant properties may have hypolipidemic effects
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350188/	2	Twenty-seven trials involving 2194 subjects were included in the meta-analysis. The pooled results showed that green tea significantly lowered fasting blood glucose by − 1.44 mg/dL... However, green tea consumption did not significantly affect fasting insulin	Recent mechanistic studies have examined the effects of green tea consumption on glucose control and provided further evidence for the biological plausibility of these findings. Green tea may affect glucose control through different mechanisms. First, tea catechins have been reported to reduce carbohydrate absorption from the intestine via inhibition of intestinal sucrose, alpha-amylase, and alpha-glucosidase [10]. Second, Tea catechins might also inhibit the hepatic gluconeogenesis through regulation of the expression of gluconeogenic genes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777853/	2	Glucose and insulin levels decreased nonsignificantly in the PPE groups but increased in the placebo group; statistically significant differences in changes in glucose (P=0.008) and insulin (P=0.01) were found. In summary, green tea (400 and 800 mg EGCG as PPE; ~5–10 cups) supplementation for 2 months had suggestive beneficial effects on LDL cholesterol concentrations and glucose-related markers.	The increases in EGC and EC were significantly larger in the 800 mg than in the 400 PPE group but the changes in metabolites (Me-EGC, M4 and M6) did not differ significantly between the two PPE groups. The differences in changes in all five catechins differed significantly between the placebo and the two PPE groups
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240975/	2	The results suggest that green tea supplementation significantly lowered both serum TC and LDL cholesterol concentrations. In addition, we demonstrated a trend toward decrease in triglyceride concentrations, although it did not attain significance, presumably because of the limited participants or duration for which the triglyceride concentrations were reported; however, green tea did not significantly affect the levels of HDL cholesterol. These findings are generally in accordance with the results from previous meta-analyses, which also identified a significant correlation between green tea supplementation and improvements in TC and LDL cholesterol concentration	The weighted mean reductions in TC and LDL cholesterol appearing due to green tea supplementation as observed in the present study (TC: 4.66 mg/dL; LDL cholesterol: 4.55 mg/dL), corresponding to reductions of 2–5%, might be important for primary prevention of cardiovascular health. Studies have reported that a 1% reduction in TC or LDL cholesterol was clinically associated with a 2–3% or 1% decreased risk of CVD, respectively [60]. Importantly, green tea intake did not negatively affect the serum HDL cholesterol levels. Thus, green tea supplementation mainly reduces the serum TC and LDL cholesterol concentrations but has limited effect on HDL cholesterol.
https://cancerci.biomedcentral.com/articles/10.1186/s12935-019-0762-9#	1	EGCG inhibited the proliferation, viability, and cell cycle progression in human thyroid carcinoma cells. EGCG decreased the migration and invasion, but increased the apoptosis of human thyroid carcinoma cells. EGCG reduced the protein levels of phospho (p)-epidermal growth factor receptor (EGFR), H-RAS, p-RAF, p-MEK1/2, and p-extracellular signal-regulated protein kinase 1/2 (ERK1/2) in human thyroid carcinoma cells. EGCG inhibited the growth of human thyroid carcinoma xenografts by inducing apoptosis and down-regulating angiogenesis.	Administration of EGCG decreased the expression level of CD31 in human thyroid carcinoma xenograft tumors. In addition, EGCG increased the expression level of cleaved PARP but decreased the expression level of p-ERK1/2. Taken together, these results suggest that EGCG could reduce the growth and angiogenesis, as well as induce apoptosis of human thyroid carcinoma xenograft tumors.
https://www.oncotarget.com/article/7567/text/	1	EGCG enhanced 5FU-induced cytotoxicity and inhibited proliferation in 5FUR cell lines through enhancement of apoptosis and cell cycle arrest. The 5FUR cells showed higher spheroid forming capacity compared to parental cells, indicating higher CSC population. EGCG treatment in these cells resulted in suppression of SDCSC formation and enhanced 5FU sensitivity to SDCSCs. Furthermore, EGCG suppressed Notch1, Bmi1, Suz12, and Ezh2, and upregulated self-renewal suppressive-miRNAs, miR-34a, miR-145, and miR-200c, which are some of the key pathways targeted in 5FUR CRC cells. These findings were validated in vivo,	In summary, we demonstrated for the first time that EGCG enhances 5FU sensitivity in chemoresistant CRC by targeting CSCs. Herein, we provide novel insights into the molecular mechanisms underpinning the biology behind chemoresistance in CRC, and demonstrate that EGCG inhibits multiple self-renewal driving pathways including Notch and Bmi1, Ezh2, and Suz12, through upregulation of the expression of key tumor suppressive miRNAs. In view of the limitations of the current generation of chemotherapeutic drugs that are inefficient at targeting CSCs, the use of natural products like EGCG in CRC may provide a safe and effective adjunctive approach in overcoming therapeutic resistance in CRC.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104695/	1	More importantly, with the bone metastases studies, we found that treatment of mice i.p. with the combination therapy reduced bone metastases and increased mouse survival rates by more than 70% to 80%. In conclusion, based on the preclinical mouse tumor modeling studies presented here, we believe that EGCG might be effectively used at high dosages delivered locally to increase the efficacy of taxanes in eradicating highly aggressive and metastatic tumors in patients	The combined drug treatment also increased apoptosis rates significantly from less than 3% in untreated cells to more than 25% in treated cells. More importantly, we found that the combination therapy had a synergistic additive effect in blocking growth and eradicating established tumors in mouse tumor modeling studies. A significant increase in overall, disease-free mouse survival rates was observed after treatment of mice harboring primary tumors (i.e., >90%) and metastatic lesions (>70%). The implication is that EGCG combined with taxane might be used to treat patients with advanced prostate cancer and metastatic disease.
https://link.springer.com/article/10.1134/S160767292360029X	1	This study proposes a dichotomous use of low-concentration EGCG in chemotherapy. During the first cycle of combined treatment with oxaliplatin (OXA), low-concentration EGCG antagonized the cytotoxic effect of OXA on colorectal cancer (CRC) cells. However, when OXA was subsequently administered, the sensitivity of CRC cells markedly increased. Although low-concentration EGCG counteracted OXA, it reduced the OXA-induced secretion of vascular endothelial growth factor by tumor cells, thereby contributing to the increase in the sensitivity of tumor cells to the second round of OXA treatment. Therefore, low-concentration EGCG showed potential as a viable adjunct to modulate chemosensitivity in CRC.	Although neutralizing antibodies or inhibitors of VEGF are commercially available, these drugs pose the risk of oversuppressing VEGF, which may limit the execution of its normal physiological functions and subsequently cause a series of side effects such as bleeding and gastric perforation [22]. In this regard, low-concentration EGCG may moderately suppress VEGF. These observations not only highlighted the dual role of EGCG in modulating chemosensitivity but also revealed a novel interface between dietary polyphenols and VEGF regulation in the context of chemotherapy.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0073464	1	Here, we demonstrate for the first time that the green tea polyphenol EGCG has multiple inhibitory effects on highly malignant IBC [inflammatory breast cancer] cells. EGCG treatment in culture reduces IBC cell proliferation, invasive phenotype and ability to promote lymphangiogenesis at low doses and survival at higher doses. Notably, EGCG decreases growth and lymphangiogenic potential of pre-existing tumors derived from ALDH-positive stem-like cells, which have been associated with poor prognosis of IBC patients.	The ability of EGCG to repress a wider array of factors and have more profound phenotypic effects on SUM-149 cells compared to SUM-190 cells may be a result of differences in molecular subtypes, cellular heterogeneity or intrinsic signaling pathways between the two IBC tumors from which they were derived. SUM-149 cells have a triple negative hormone receptor status and are more highly proliferative compared to SUM-190 cells, which are ER-, PR- and Her-2 amplified. Importantly, the triple-negative subtype of IBC has been associated with decreased overall survival and increased rate of locoregional relapse [50]. Thus, our results showing more profound effects on the SUM-149 cell line, suggest the use of EGCG in combination with standard treatments for the triple-negative subtype of IBC may be particularly effective.