EGCG green tea extract health benefit, side effects, effect on metabolism, cancer protection or treatment, does it work for weight loss? by Ray Sahelian, M.D.
July 12 2014

Epigallocatechin Gallate is an anti-oxidant polyphenol found mostly in green tea. it may have health benefits as a nutritional supplement for cancer, atherosclerosis, blood sugar control, HPV virus infection, and neurodegenerative diseases. However, until long term human research is available, it is best to not take too high doses on a daily basis. Many substances are healthy to use in lower amounts but could potentially cause harm if taken in excessive dosages. One option is to take an EGCG supplement 2 or 3 times a week.
   You can obtain this substance through drinking green tea or an extract supplement which lists the amount of EGCG per capsule. On average, a cup of green tea will have roughly 100 mg per 8 ounces. The amount present in green tea varies with different brands of the product, the region it is grown, amount of brewing time, age of the leaves, etc. A cup of green tea may have as much as 20 mg of caffeine.

Green Tea Extract 100 mg ( buy EGCG 35 mg ) 60 Tablets - Source Naturals

Green Tea Extract offers a convenient way to get the benefits of green tea in a highly concentrated pill form. It is standardized for bioflavonoid-like antioxidants known as polyphenols, particularly Epigallocatechin Gallate.  EGCG has been found in scientific studies to be a potent antioxidant. Green tea antioxidants are likely to become more popular with time.

Supplement Facts
Green Tea Extract Yielding 70 mg epigallocatechin gallate per two tablets

Suggested Use, dosage: One EGCG extract tablet a few times a week. Take the tablet in the morning or midday with a meal. Evening use may lead to mild insomnia.

 

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Benefits of EGCG as revealed in studies
EGCG directly interacts with proteins and phospholipids in the plasma membrane and regulates signal transduction pathways, transcription factors, DNA methylation, mitochondrial function, and autophagy to exert many of its beneficial biological actions.

Alzheimer's disease or dementia
Green tea epigallocatechin-3-gallate modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice.
J Neurosci. 2005. Silver Child Development Center, Department of Psychiatry and Behavioral Medicine, University of South Florida, Tampa, Florida

Antioxidant
EGCG's anti-oxidant action protects cells from lipid peroxidation and DNA damage induced by reactive free radicals.

Blood thinning
I read somewhere that EGCG or green tea interferes with platelet formation. Sure enough, when i took 4 pills a day for 4 days at 175mg ea., my platelet count tested half of normal. I stopped the pills, and 4 or 5 days later, my platelet count tested normal.
   We discovered the following studies regarding the influence of platelet aggregation and EGCG, but we did not find studies regarding EGCG influence on platelet count.

Antithrombotic activities of green tea catechins and epigallocatechin gallate.
Thromb Res. 1999.
Green tea catechins and EGCG have the antithrombotic activities and the modes of antithrombotic action may be due to the antiplatelet activities, but not to anticoagulation activities.

Platelet aggregation induced by the C-terminal peptide of thrombospondin-1 (4N1-1) is inhibited by epigallocatechin gallate but not by prostaglandin E1.
Platelets. 2004.
EGCG may inhibit platelet function even under conditions, when 'classical' platelet inhibitors, such as cAMP-elevating agents, are not effective.

Platelet aggregation inhibitors in hot water extract of green tea.
Chem Pharm Bull. 1990.
The effect of hot water extract of green tea on the collagen-induced aggregation of washed rabbit platelets was examined. The extract lowered submaximal aggregation and prolonged the lag time in a dose-dependent manner. It was found that the potency of EGCG is comparable to that of aspirin.

Brain function
EGCG helps with growth of neural cells and is of benefit in memory and cognitive function. It can help release neural progenitor cells which can adapt to different types of brain cells. Molecular Nutrition and Food Research, volume 56, 2012.

Cancer
Toxicol Appl Pharmacol. 2013 Dec 1. Green tea polyphenol, (-)-epigallocatechin-3-gallate, induces toxicity in human skin cancer cells by targeting β-catenin signaling. These data suggest that induction of cytotoxicity in skin cancer cells by EGCG is mediated by targeting of β-catenin signaling and that the β-catenin signaling is upregulated by inflammatory mediators.

EGCG induces apoptosis in human cancer cell lines. Apoptosis means the death of a cell, and in the case of a cancer cell, apoptosis is a good thing. In test tubes, it thwarts the growth of several cancer cells including breast, prostate, lungs, ovaries, and liver. This substance inhibits telomerase and DNA methyltransferase, two enzymes involved in cancer gene expression and cellular immortality.

Regarding EGCG supplementation in conjunction with chemo drugs such as cyclophosphamide is there any research data supporting it? If so, for what kind of cancer & at what stage would it be beneficial (or detrimental)?
    Human research with EGCG and cancer is lacking, therefore is little information to base a meaningful answer regarding its role in cancer, either by itself or in combination with other chemotherapy drugs.

Cervical Dysplasia with the HPV Virus
EGCG, when given to women with cervical dysplasia at a dose of 200 mg for a period of 12 weeks, showed a positive response. It may be a potential therapy regimen for patients with HPV infected cervical lesions.

Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions.
Eur J Cancer Prev. 2003.
Fifty-one patients with cervical lesions (chronic cervicitis, mild dysplasia, moderate dysplasia and severe dysplasia) were divided into four groups, as compared with 39 untreated patients as a control. Poly E ointment was applied locally to 27 patients twice a week. For oral delivery, a 200 mg of poly E or EGCG capsule was taken orally every day for eight to 12 weeks. In the study, 20 out of 27 patients under poly E ointment therapy showed a response. Six out of eight patients under poly E ointment plus poly E capsule therapy showed a response, and three out of six patients under poly E capsule therapy showed a response. Six out of 10 patients under EGCG capsule therapy showed a response. Overall, a 69% response rate was noted for treatment with green tea extracts, as compared with a 10% response rate in untreated controls. Thus, the data collected here demonstrated that green tea extracts in a form of ointment and capsule are effective for treating cervical lesions, suggesting that green tea extracts can be a potential therapy regimen for patients with HPV infected cervical lesions.

Leukemia
A component of green tea known as epigallocatechin-3-gallate helps kill leukemia cells by interrupting the communication signals they need to survive.

Prostate cancer
Dr. Saverio Bettuzzi from the University of Parma in Italy gave men 600 mg a day of concentrated green tea catechins, containing 300 mg EGCG, or a placebo for a year. All the men had premalignant prostate cancer, putting them at risk of progression to full cancer. After a year, only one man (3%) in the group on green tea capsules developed prostate cancer compared with 9 men (28%) on placebo.

Diabetes
Epigallocatechin gallate supplementation alleviates diabetes in rodents.
J Nutr. 2006.

Heart disease and endothelial function
Acute EGCG Supplementation Reverses Endothelial Dysfunction in Patients with Coronary Artery Disease.
J Am Coll Nutr. 2007. Section of Cardiology, Boston Medical Center, Boston, MA.
We examined the effects of EGCG on endothelial function in a double blind, placebo-controlled, crossover design study. We measured brachial artery flow-mediated dilation by vascular ultrasound at six time points: prior to treatment with EGCG or placebo, two hours after an initial dose of EGCG (300 mg) or placebo, and after two weeks of treatment with (150 mg twice daily) or placebo. A total of 42 subjects completed the study, and brachial artery flow-mediated dilation improved from 7 to 8.6 two hours after the first dose of 300 mg, but was similar to baseline after two weeks of treatment with the final measurements made approximately 14 hours after the last dose. Placebo treatment had no significant effect, and there were no changes in reactive hyperemia or the response to sublingual nitroglycerin. The changes in vascular function paralleled plasma EGCG concentrations, which increased from 2.6 to 92 ng/ml after acute EGCG, but were unchanged from baseline after two weeks of treatment (3.4). EGCG acutely improves endothelial function in humans with coronary artery disease, and may account for a portion of the beneficial effects of flavonoid-rich food on endothelial function.
   My comments: I am not sure how to interpret this study. It appears that there is improvement initially but then in the long run no overall major change was noted. Unless I am misinterpreting this study. Any statisticians out there who can help? My friend Lou Mancano, M.D., offered this opinion:  "While I applaud their efforts, I think one should be cautious before we can draw conclusions from this study. Here are some limitations: One major one is that there were no clinical outcomes measured; second, there was an assumption that a response in a brachial artery would be replicated in a coronary artery (we know that different parts of our anatomy respond differently to supplements and medications); third, we shouldn't automatically conclude that higher blood flow is necessarily better (could flow velocity and dilatation induce plaque rupture, as we indirectly discovered with sublingual nifedipine 10 or 15 years ago?); fourth, we cannot make any sound recommendations on the optimal dose or frequency of EGCG use. I’d recommend waiting for more studies…especially something with measurable clinical outcomes.  About the flow rate you asked about. Either that level of change is insignificant, or if it is, the fact that it was not sustained at 2 weeks renders it insignificant (possibly the body makes an adjustment - we all know our bodies (nature) is always smarter than the substances we place within it)."

Weight Loss
Research with EGCG and weigh loss in humans is still quite early, and at this time it appears that green tea and EGCG may help slightly with weight loss when used in high amounts, but long term benefit versus potential risk of high EGCG consumption has yet to be determined.

Enviga, a sparkling green tea containing green tea extracts, calcium, and caffeine was conceived by Beverage Partners Worldwide -- a joint venture of Nestle S.A. and The Coca-Cola Company. "Enviga increases calorie burning. It represents the perfect partnership of science and nature," said Dr. Rhona Applebaum, chief scientist, The Coca- Cola Company. "Enviga contains the optimum blend of green tea extracts, caffeine and naturally active plant micronutrients designed to work with your body to increase calorie burning, thus creating a negative calorie effect." The Nestle Research Center in Lausanne, Switzerland, has studied the properties and benefits of green tea for decades as part of its extensive global tea business. A recent study conducted by the Center in collaboration with the University of Lausanne revealed that consuming the equivalent of three Enviga beverages over the course of the day resulted in a noticeable increase in calorie burning. "The accumulated body of scientific research shows the ability of green tea's powerful antioxidant EGCG to speed up metabolism and increase energy use, especially when combined with caffeine," said Nestle researcher Dr. Hilary Green. Studies have shown that when EGCG and caffeine are present at the levels comparable to that in three cans of Enviga, healthy subjects in the lean to normal weight range can experience an average increase in calorie burning by 60 - 100 calories. Enviga provides 90 mg of EGCG in each serving.
     Dr. Sahelian says: I think it is premature to make the claim that ingesting Enviga leads to long term weight loss. I am concerned about the overstimulation of heart muscle when so much green tea and caffeine are ingested. It is possible that many people will continue drinking their coffee throughout the day while ingesting one or more cans of Enviga, hence potentially increasing their blood pressure and causing heart problems. Now that one of the largest companies in the US is heavily promoting green tea and EGCG, it is time to seriously evaluate the potential benefit and harm of overconsumption. I am concerned about the overstimulation of heart muscle when so much green tea and caffeine are ingested, and the potential for irritability, anxiety, and insomnia.

Effects of encapsulated green tea and Guarana extracts containing a mixture of epigallocatechin-3-gallate and caffeine on 24 h energy expenditure and fat oxidation in men.
Br J Nutr. 2005.  Laval University, Ste-Foy, Quebec, Canada.
Fourteen subjects took part to this randomized, placebo-controlled, double-blind, cross-over study. Each subject was tested five times in a metabolic chamber to measure 24 h energy expenditure, substrate oxidation and blood pressure. During each stay, the subjects ingested a capsule of placebo or capsules containing 200 mg caffeine and a variable dose of EGCG (90, 200, 300 or 400 mg) three times daily, 30 min before standardized meals. Twenty-four hour energy expenditure increased significantly by about 750 kJ with all EGCG caffeine mixtures compared with placebo. No effect of the EGCG caffeine mixture was observed for lipid oxidation. Systolic and diastolic blood pressure increased by about 7 and 5 mmHg, respectively, with the EGCG caffeine mixtures compared with placebo. This increase was significant only for 24 h diastolic blood pressure. The main finding of the study was the increase in 24 h energy expenditure with the mixtures. However, this increase was similar with all doses of EGCG in the mixtures.

EGCG side effects, is it safe?
Alertness, stimulation, insomnia, are potential side effects on high dosages.

On your website, you say that it can cause anxiety / insomnia. Is that only the caffeinated EGCG supplements, or is that true of it by itself, even without caffeine?
   My experience thus far is that these symptoms can be caused without caffeine.

Toxicity of green tea extracts and their constituents in rat hepatocytes in primary culture.
Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin-Schroedinger-Strasse, Kaiserslautern, Germany.
Recent reports on sporadic cases of liver disorders (acute hepatitis, icterus, hepatocellular necrosis) after ingestion of dietary supplements based on hydro-alcoholic extracts from green tea leaves led to restrictions of the marketing of such products in certain countries of the EU. Since green tea is considered to exert a number of beneficial health effects, and, therefore, green tea products are widely used as dietary supplements, we were interested in the possible mechanism of liver toxicity of green tea extracts and in the components involved in such effects. Seven hours after seeding on collagen, rat hepatocytes in primary culture were treated with various hydro-alcoholic green tea extracts. In a separate series of experiments, the green tea constituents epicatechin, epigallocatechin-3-gallate, caffeine and theanine were tested at concentrations reflecting their levels in a typical green tea extract. Cytotoxicity was found with EGCG only. Our results suggest that high concentrations of green tea extract can exert acute toxicity in rat liver cells. EGCG seems to be a key constituent responsible for this effect. The relatively low bioavailability of catechins reported after oral exposure to green tea argues, however, against a causal role of these constituents in the reported liver disorders.
   A. Dr. Sahelian responds: It is very difficult to interpret lab studies done in a test tube versus what would occur if the same supplement were taken orally, particularly with a meal. I am not a big fan of taking large doses of isolated substances from herbs, such as a high amount of EGCG, preferring to take the whole powder or a weakly concentrated extract. Many people think the higher the dose of a substance they supplement, the healthier they will be, but that may not always be the case, and often is not the case. So, for the time being, I don't see the need to take a high dose of EGCG unless perhaps under medically supervised treatment for a health condition.

I am wondering is green tea and EGCG supplement have effects on the thyroid? Is it safe to take with Tapazole medication?
    A. I have not seen any studies in humans regarding influence on thyroid gland or interaction with Tapazole drug.

EGCG content in cup of green tea
I am estimating, based on the study listed below, that the amount of EGCG or catechins found in a cup of green tea averages to about 100 mg. This is a rough estimate.

Total phenol, catechin, and caffeine contents of teas commonly consumed in the United kingdom.
J Agric Food Chem. 2002.
Levels of total phenol, catechins, and caffeine in teas commonly consumed in the United Kingdom have been determined using reversed phase high-performance liquid chromatography. Tea bags or tea leaves were purchased from local supermarkets and extracted in boiling water for 5 min. The resulting data showed considerable variability in both total phenols [80-134 mg/g of dry matter (DM) in black teas and 87-106 mg/g of DM in green teas] and catechins (5-47, 51-84, and 8-13 mg/g of DM in black, green, and fruit teas, respectively); this was most probably a result of differing agronomic conditions, leaf age, and storage during and after transport, as well as the degree of fermentation. Caffeine contents of black teas (22-28 mg/g of DM) were significantly higher than in less fermented green teas (11-20 mg/g of DM). The relative concentration of the five major tea catechins ranked EGCG > ECG > EC > EGC > C. The estimated U.K. dietary intakes of total tea catechins, calculated on the basis of an average tea consumption of three cups of tea (200 mL cup, 1% tea leaves w/v), were 61, 92, and 405 mg/day from fruit teas, black teas, and green teas, respectively. The calculated caffeine intake ranged between 92 and 146 mg/day. In addition, many individuals will consume much larger quantities of tea, of various strengths (as determined by the brewing conditions employed).

Review and benefit
EGCG may have health benefit as a nutritional supplement for cancer, heart disease, certain viral infections, and neurodegenerative conditions, and perhaps weight loss. However, at this time we don't know the long term safety of taking a high dose EGCG supplement by itself. It is clear from epidemiological studies that long term drinking of green tea is safe and healthy as demonstrated in studies with Japanese green tea drinkers.
   In lab studies the potential health benefits ascribed to green tea and EGCG include antioxidant effects, cancer chemoprevention, improving cardiovascular health, preventing fat formation, protecting the skin from the damage caused by ionizing radiation, and others. The compound has been shown to regulate dozens of disease-specific molecular targets. However, at this time, it is too early to say whether consuming large amounts of EGCG will provide more benefit than harm. There are countless beneficial substances in herbs and plant products that have been shown to have similar benefits. For instance, lycopene from tomatoes, curcumin from turmeric, resveratrol from grapes, genistein from soy, etc. How do we know whether taking a very high dose of a single substance is safe in the long run? Logic tells us that ingesting smaller amounts of many substances is healthier than taking a large dose of just one. Oranges are a healthy fruit. But, does it make sense to only eat several oranges a day and no other fruits? One would think that eating a variety of fruits would be a healthier option. Same with green tea and EGCG. I would recommend you avoid the temptation of taking too much of this beneficial substance until we have long term studies to indicate its safety. You may be better off just drinking an old fashioned cup of regular green tea or taking a green tea extract capsule.

Questions
Q. I subscribe to a newsletter and recently had this emailed to me: "Looking for a simple, safe pill to fight fat and control weight? Try EGCG, the main antioxidant in green tea. It burns calories by boosting metabolism and can actually kill fat cells and stop the creation of new fat cells. When fat cells were exposed to EGCG for 3 or 4 days, more than 50% of the cells died. The newsletter also says that the best dose is 300 mg.
   A. It is premature at this time, until actual human studies are done, to take a large amount since we don't know the long term side effects. A substance can be beneficial in small amounts, such as when ingested in green tea, but we don't know whether taking a high dose can be helpful or harmful. Not enough research has been done to know the ideal dosage.

Please, could you help me find how to purchase the loose EGCG powder? The amount I need to take for my CLL chronic lymphocytic leukemia is too great for the # of capsules I would need to ingest. I have a recipe from a reliable scientific source for a candy and I can't find the loose substance. I would be happy to purchase it from you.
    I am not aware of such powder products being sold. One has to be careful taking too high a dosage of this substance since it may cause restlessness, insomnia, and rapid heart beat.

Products
Natrol Inc., a manufacturer and distributor of branded nutritional products, has launched Slenderite, a supplement combining five ingredients. The ingredients in Slenderite -- Phase 2 Starch Neutralizer; EGCG (Green Tea); Caffeine; Chromium Picolinate and 5-HTP are promoted for healthy weight control. According to Eric Schick, Vice President of Marketing, “Slenderite contains five key ingredients that are well-known and trusted by consumers. Slenderite provides consumers with the convenience of one product containing all five ingredients to support their weight loss goals.”  Phase 2 is from Pharmachem Laboratories, Inc. being promoted to delay the digestion and absorption of carbohydrates. Phase 2 is claimed to work by inhibiting the digestive enzyme responsible for converting starch into simple sugars the body can absorb.