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EGCG Health Benefits, Detailed Studies and Discussion

Availability of EGCG
You can obtain EGCG through drinking green or wulong tea or taking a tea extract supplement which
lists the amount of EGCG per capsule. On average, a cup of green or wulong tea will have roughly 100
mg of EGCG per 8 ounces. The amount of EGCG present in tea varies with different brands of the
product, the region the tea is grown, amount of brewing time, age of the tea leaves, etc. A cup of green
tea or wulong tea may have as much as 20 mg of caffeine.

Benefit of EGCG
There have been few human studies directly evaluating the tea extract EGCG. However, laboratory and
animal studies are plentiful. In lab studies, EGCG has been found to be a potent anti-antioxidant and
to have anti-cancer abilities. In animal studies, EGCG has been found to potentially be helpful in
blood sugar control. In human studies, EGCG has been shown to be helpful in reducing infection
from the HPV virus in the cervix and the risk for prostate cancer.


EGCG for Cancer
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, EGCG thwarts the growth of several
cancer cells including breast, prostate, lungs, ovaries, and liver.

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.

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


EGCG and Leukemia
A component of green or wulong tea known as epigallocatechin-3-gallate (EGCG) [epi-gallo-cat-ekin-
3-gal-ate] helps kill leukemia cells by interrupting the communication signals they need to survive.


EGCG and endothelial function in regards to Heart Disease
EGCG Supplementation Reverses Endothelial Dysfunction in Patients with Coronary Artery Disease.

J Am Coll Nutr. 2007 Apr;26(2):95-102. Widlansky ME, Hamburg NM, Anter E, Holbrook M, Kahn DF,
Boston, MA.

We hypothesized that dietary supplementation with epigallocatechin gallate ( EGCG ), a major
catechin in tea, would improve endothelial function in humans. 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 EGCG (150 mg twice daily) or placebo. The order of treatments (EGCG or placebo)
was randomized and there was a one-week washout period between treatments. RESULTS: A total of
42 subjects completed the study, and brachial artery flow-mediated dilation improved from 7 to 8.6
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). CONCLUSION: 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 appearsthat there is improvement initially
but then in the long run no overallmajor change was noted. Unless I am misinterpreting this study.
Anystatisticians out there who can help? My friend Lou Mancano, M.D.,offered this opinion:  "While I
applaud their efforts, I think oneshould be cautious before we can draw conclusions from this EGCG
study.Here are some limitations: One major one is that there were no clinicaloutcomes measured;
second, there was an assumption that a response in abrachial artery would be replicated in a
coronary artery (we know thatdifferent parts of our anatomy respond differently to supplements
andmedications); third, we shouldn't automatically conclude that higherblood flow is necessarily
better (could flow velocity and dilatationinduce plaque rupture, as we indirectly discovered with
sublingualnifedipine 10 or 15 years ago?); fourth, we cannot make any soundrecommendations on
the optimal dose or frequency of EGCG use. I’drecommend waiting for more studies…especially
something with measurableclinical outcomes.  About the flow rate you asked about. Either thatlevel of
change is insignificant, or if it is, the fact that it was notsustained at 2 weeks renders it insignificant
(possibly the body makesan adjustment - we all know our bodies (nature) is always smarter thanthe
substances we place within it)."


EGCG and 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. EGCG 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 Oct;12(5):383-90. Department of Obstetrics and Gynaecology, College of
Medicine, The Catholic University of Korea, Seoul, Korea.

We investigated clinical efficacy of green tea extracts (polyphenon E; poly E and (-)-epigallocatechin-3-
gallate [ EGCG ]) delivered in a form of ointment or capsule in patients with human papilloma virus
(HPV) infected cervical lesions. 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 (74%) under poly E ointment therapy showed a response.
Six out of eight patients under poly E ointment plus poly E capsule therapy (75%) showed a response,
and three out of six patients (50%) under poly E capsule therapy showed a response. Six out of 10
patients (60%) under EGCG capsule therapy showed a response. Overall, a 69% response rate
(35/51) was noted for treatment with green tea extracts, as compared with a 10% response rate (4/39)
in untreated controls (P<0.05). 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.


EGCG and 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.


EGCG and Alzheimer's Disease
In rodent studies, EGCG is able to prevent the deposition of amyloid in brain tissue. Hence, it is
possible that drinking green tea or taking an EGCG supplement could potentially reduce the risk for
AD.

Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and
reduces cerebral amyloidosis in Alzheimer transgenic mice.

J Neurosci. 2005 Sep 21;25(38):8807-14. Silver Child Development Center, Department of Psychiatry
and Behavioral Medicine, University of South Florida, Tampa, Florida

Alzheimer's disease (AD) is a progressive neurodegenerative disorder pathologically characterized by
deposition of beta-amyloid (Abeta) peptides as senile plaques in the brain. Recent studies suggest
that green tea flavonoids may be used for the prevention and treatment of a variety of
neurodegenerative diseases. Here, we report that EGCG, the main polyphenolic constituent of green
tea, reduces Abeta generation in both murine neuron-like cells (N2a) transfected with the human
"Swedish" mutant amyloid precursor protein (APP) and in primary neurons derived from Swedish
mutant APP-overexpressing mice (Tg APPsw line 2576). In concert with these observations, we find
that EGCG markedly promotes cleavage of the alpha-C-terminal fragment of APP and elevates the N-
terminal APP cleavage product, soluble APP-alpha. These cleavage events are associated with
elevated alpha-secretase activity and enhanced hydrolysis of tumor necrosis factor alpha-converting
enzyme, a primary candidate alpha-secretase. As a validation of these findings in vivo, we treated Tg
APPsw transgenic mice overproducing Abeta with EGCG and found decreased Abeta levels and
plaques associated with promotion of the nonamyloidogenic alpha-secretase proteolytic pathway.
These data raise the possibility that EGCG dietary supplementation may provide effective prophylaxis
for AD.


EGCG and Diabetes
A rodent study shows EGCG to have promise as a remedy for diabetes.Epigallocatechin gallate
(EGCG) supplementation alleviates diabetes in rodents.

J Nutr. 2006 Oct;136(10):2512-8. DSM Nutritional Products Ltd, Department of Human Nutrition and
Health, CH-4002 Basel, Switzerland.

This study investigated the antidiabetic effects of the most abundant green tea catechin,
epigallocatechin gallate ( EGCG, TEAVIGO ), in rodent models of type 2 diabetes mellitus and H4IIE
rat hepatoma cells. We assessed glucose and insulin tolerance in db/db mice and ZDF rats after they
ingested EGCG. Using gene microarray and real-time quantitative RT-PCR we investigated the effect
of EGCG on gene expression in H4IIE rat hepatoma cells as well as in liver and adipose tissue of
db/db mice. EGCG improved oral glucose tolerance and blood glucose in food-deprived rats in a
dose-dependent manner. Plasma concentrations of triacylglycerol were reduced and glucose-
stimulated insulin secretion was enhanced. In H4IIE cells, EGCG downregulated genes involved in
gluconeogenesis and the synthesis of fatty acids, triacylgycerol, and cholesterol. EGCG decreased
the mRNA expression of phosphoenolpyruvate carboxykinase in H4IIE cells as well as in liver and
adipose tissue of db/db mice. Glucokinase mRNA expression was upregulated in the liver of db/db
mice in a dose-dependent manner. This study shows that EGCG beneficially modifies glucose and
lipid metabolism in H4IIE cells and markedly enhances glucose tolerance in diabetic rodents. Dietary
supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and
treatment of type 2 diabetes mellitus.

EGCG Summary
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.

EGCG questions
Dear Dr. Sahelian,First of all, I would like to thank you for providing outstanding information about
herbs and supplements. I rely on your research every day. I root around in Pubmed a lot, but in doing
so I am very aware of the disadvantages of lacking a medical education. In digging up material on
theanine, I came across the abstract appended below. Since I take 350mg of EGCG each day, my
interest was aroused, to put it mildly. What is your take on this study?

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 52, D-67663 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 hepatotoxicity 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 (two different native 80% ethanolic dry extracts and an 80% ethanolic dry extract cleared from
lipophilic compounds). Cells were washed, and reduction of resazurin, used as a viability parameter
monitoring intact mitochondrial function, was determined. It was found that all seven green tea
extracts examined enhanced resazurin reduction significantly at a concentration range of 100-500
microg/ml medium, while a significant decrease was observed at 1-3mg/ml medium. Decreased
levels were concomitant with abundant necrosis as observed by microscopic inspection of the
cultures and with increased leakage of lactate dehydrogenase activity from the cells. 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.
Synthetic (+)-epigallocatechin (200 microM) was used for comparison. Cytotoxicity was found with
EGCG only. The concomitant addition of 0.25 mM ascorbate/0.05 mM alpha-tocopherol had no
influence on cytotoxicity. In conclusion, 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.
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