EGCG by Ray Sahelian, M.D. Health Benefits of EGCG, a green tea extract
EGCG - In the future you're going to see these initials quite often. Epigallocatechin Gallate ( EGCG ) is an anti-oxidant polyphenol found mostly in green tea. EGCG may have health benefit 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 of EGCG 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.
Green Tea Extract, 100 mg ( Yielding 35 mg EGCG ), 60 Tablets - Source Naturals
Suggested Use: 1
green tea EGCG extract tablet a few times a week. Take EGCG green tea extract in the morning or midday
with a meal. Evening use may lead to mild insomnia.
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EGCG and Cancer
EGCG induces apoptosis in human cancer cell lines. EGCG inhibits
telomerase and DNA methyltransferase, two enzymes involved in cancer gene
expression and cellular immortality.
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 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
Acute 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, Elliott JG, Keaney JF, Vita JA. Section of Cardiology,
Boston Medical Center, 88 East Newton Street, 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 two hours after the first dose of 300 mg of EGCG, but was similar to
baseline (7.8) 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). 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 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 EGCG 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)."
EGCG and Alzheimer's Disease
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 Weight Loss
The big boys are on it now.
Enviga, a sparkling green tea
containing green tea extracts, calcium, and caffeine was conceived by Beverage Partners Worldwide (BPW) -- 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 ( EGCG ), caffeine and naturally active plant micronutrients
designed to work with your body to increase calorie burning, thus creating
a negative calorie effect. It makes this product stand out as unique.
Enviga brings the benefits of green tea to the forefront in a convenient
and accessible, great tasting beverage."
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 EGCGto 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.
EGCG is a naturally occurring antioxidant in tea, including green tea.
Enviga provides 90 mg of EGCG in each serving.
"We've seen a shift in consumers' attitudes toward diet and health and
wellness, with more consumers seeking product choices that support active
lifestyles, rather than dieting," said John Hackett, senior vice
president, Coca-Cola North America Marketing. "Enviga is a great tasting
beverage that invigorates your metabolism to gently burn calories, and
it's a positive step people can take as part of a balanced lifestyle --
like taking the stairs."
Enviga will be available in three delicious flavors -- green tea, berry
and peach -- in the ready-to-drink tea section at supermarkets, mass
merchandisers, convenience and drug stores, and club stores.
Enviga will be sold in individual 12-ounce sleek cans as well as six-can
and 12-can multi-packs. Suggested retail price for Enviga will be $1.29 -
$1.49 (single can).
"Enviga brings together Nestle's expertise in nutritional science and
extensive knowledge in the benefits of green tea with Coca-Cola's
consumer, marketing and distribution resources to create a new global
beverage category with unique consumer benefits -- a beverage with
negative calories," said Leslie Novos, CEO of Beverage Partners Worldwide.
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 in Enviga. 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.
Effect of long-term oral administration of green tea
extract on weight gain and glucose tolerance in Zucker diabetic (ZDF) rats.
J Herb Pharmacother. 2005;5(3):55-65.Botanical Center in Vivo Care, 700 West
State St, West Lafayette, IN, 47907, USA.
There have been some claims that green tea reduces weight and lowers blood
glucose in diabetes. Intraperitoneal injections of green tea catechins in
diabetic rats have shown beneficial effects. To determine if oral administration
of green tea would prevent development of diabetes, young Zucker diabetic rats
were dosed with green tea extract containing 50-125 mg/kg of EGCG starting at 7
weeks of age, before the appearance of excessive weight gain and glucose
elevation. While there was a trend toward lower weight gain and average daily
glucose, there was no statistically significant difference.
EGCG and Caffeine Combination
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 Sep;94(3):432-6. Division of Kinesiology, Laval University,
Ste-Foy, Quebec, Canada, G1K 7P4.
It has been reported that green tea has a thermogenic effect, due to its
caffeine content and probably also to the catechin, EGCG. The main aim of the
present study was to compare the effect of a mixture of green tea and Guarana
extracts containing a fixed dose of caffeine and variable doses of EGCG on 24 h
energy expenditure and fat oxidation. 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 EGCG caffeine mixtures. However, this increase was
similar with all doses of EGCG in the mixtures.
EGCG and Diabetes
A rodent study shows EGCG to have promise as a remedy for diabetes.
Epigallocatechin gallate 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 for Human Papilloma Virus
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 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 Jan 30;50(3):565-70. Khokhar S, Magnusdottir SG.
Procter Department of Food Science, University of Leeds, Leeds LS2 9JT, United
Kingdom.
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).
EGCG oral dosage study
A single ascending dose study of epigallocatechin gallate in healthy
volunteers.
J Int Med Res. 2003 Mar-Apr;31(2):88-101. Roche Vitamins Ltd, Human
Nutrition and Health, Research and Development, Basel, Switzerland.
This randomized, double-blind, placebo-controlled study assessed the safety,
tolerability and plasma kinetic behaviour of single oral doses of 94% pure
crystalline bulk EGCG under fasting conditions in 60 healthy male volunteers. In
each group of 10 subjects, eight received oral EGCG in single doses of 50 mg,
100 mg, 200 mg, 400 mg, 800 mg or 1600 mg, and two received placebo. In each
dosage group, the kinetic profile revealed rapid absorption with a one-peak
plasma concentration versus time course, followed by a multiphasic decrease
consisting of a distribution phase and an elimination phase. The mean
AUC(0-infinity) of total EGCG varied between 442 and 10,368 ng.h/ml. The
according mean Cmax values ranged from 130 to 3392 ng/ml and were observed after
1.3-2.2 h. The mean t1/2z values were seen between 1.9 and 4.6 h. Single oral
doses of EGCG up to 1600 mg were safe and very well tolerated.
EGCG discussed in October, 2006
newsletter
"Enviga increases calorie burning. It represents the perfect partnership of
science and nature," says Dr. Rhona Applebaum, chief scientist, The Coca- Cola
Company. "Enviga contains the optimum blend of green tea extracts (EGCG),
caffeine and naturally active plant micronutrients designed to work with your
body to increase calorie burning, thus creating a negative calorie effect." The
press release continues: "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," adds Nestle
researcher Dr. Hilary Green. Nestle is cooperating with Coca-Cola Company to
promote this product.
Enviga will be available to the consumer in a few weeks. However, in many
newspaper articles that followed the press release, health experts dismissed
claims that Enviga would burn calories by speeding up the drinker's metabolic
rate, and cast doubt on the chances it would help people lose weight.
My thoughts: 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 of green tea. I think it is premature to
make the claim that ingesting Enviga leads to weight loss. The Coca Cola Company
has not provided any direct research that indicates drinking several cans of
this green tea and caffeine product is safe and effective in the long run, yet
their press release makes quite promising statements. 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. 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.
EGCG, one of the beneficial substances in green tea, shows a lot of promise. 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 EGCG 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.
EGCG Article written October 2006
for Today's Health and Wellness magazine
EGCG - In the future you're going to see these initials quite often. EGCG is
short for epigallocatechin gallate, a substance found in certain herbs,
particularly in green tea. You undoubtedly have heard of the many benefits of
green tea. Does EGCG measure up to the claims you have heard or read?
Availability of EGCG
You can obtain EGCG through drinking green tea or taking a green tea extract
supplement which lists the amount of EGCG per capsule. On average, a cup of
green tea will have roughly 100 mg of EGCG per 8 ounces. The amount of EGCG
present in green tea varies with different brands of the product, the region the
green tea is grown, amount of brewing time, age of the green tea leaves, etc. A
cup of green tea may have as much as 20 mg of caffeine.
Benefit of EGCG
There have been few human studies directly evaluating the green 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 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.
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.
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 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. In fact, retail surveys show that
consumers often have the same ingredients in their shopping carts, but in
separate supplements. 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. EGCG is a powerful antioxidant contained in green
tea. Slenderite pairs EGCG with caffeine. Slenderite is available nationally at
food, drug and mass market stores. Founded in 1980, Natrol, Inc. (NASDAQ: NTOL)
is a diversified nutrition company that manufactures and markets nutritional
products, herbal teas and sports nutrition products under the Natrol, Laci Le
Beau and Prolab brands, respectively. Natrol markets more than 50 categories of
products, with more than 500 stock-keeping units (SKU’s) designed to meet a wide
range of consumer needs. The products are available in thousands of food, drug,
mass market and independent health food stores, catalogs and Internet sites,
gyms and specialty stores nationally and in select foreign countries.
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.
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. That's what many experts now
advise. Unlike the many phony weight-loss pills on the market, EGCG really is
effective. EGCG (epigallo-cathechin-gallate) burns more 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 of EGCG is 300 mg.
A. It is premature at this time, until actual human studies are
done, to take a large amount of EGCG since we don't know the long term side
effects. A substance such as EGCG 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 with EGCG to know the
ideal dosage.
Q. I read somewhere that EGCG or green tea interferes
with platelet formation. Sure enough, when i took 4 pills a day for 3 or 4 days
of EGCG 175mg ea., my platelet count tested half of normal. I stopped the pills,
and 4 or 5 days later, my platelet count tested normal.
A. 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.
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 Nov;15(7):455-7. Medizinische Universitatspoliklinik Bonn,
Bonn, Germany.
The C-terminal peptide of thrombospondin (4N1-1) stimulates distinct
signalling pathways but induces an activation-independent platelet aggregation.
This study demonstrates inhibitory effects of epigallocatechin gallate ( EGCG ,
a major flavonoid component of green tea, on 4N1-1-induced aggregation of washed
human platelets. Thrombin (0.1 U/ml)-induced platelet aggregation was completely
inhibited by prostaglandin E1 (PGE1, 300 nM). In contrast, platelet aggregation
induced by 4N1-1 (100 microM) was not affected by PGE1. However,
epigallocatechin gallate (EGCG), but not other catechins from green tea,
concentration-dependently inhibited 4N1-1-induced platelet aggregation. Thus,
dietary components, such as EGCG, may inhibit platelet function even under
conditions, when 'classical' platelet inhibitors, such as cAMP-elevating agents,
are not effective.
Antithrombotic activities of green tea catechins and
(-)-epigallocatechin gallate.
Thromb Res. 1999 Nov 1;96(3):229-37. College of Pharmacy, Chungbuk National
University, Cheongju, Korea.
The antithrombotic activities and mode of action of green tea catechins (GTC)
and (-)-epigallocatechin gallate ( EGCG ), a major compound of GTC, were
investigated. Effects of green tea catechins and EGCG on the murine pulmonary
thrombosis in vivo, human platelet aggregation in vitro, and ex vivo, and
coagulation parameters were examined. These results suggest that 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 inhibitors in hot water extract of
green tea.
Chem Pharm Bull (Tokyo). 1990 Mar;38(3):790-3. Ito-en Central Research
Institute, Shizuoka, Japan.
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. After
fractionation of the extract, it was revealed that the tea catechins (tannins)
are active principles for inhibition and that ester-type catechins are more
effective than free-type catechins. One of the ester type catechins,
epigallocatechin gallate ( EGCG ), suppressed the collagen-induced platelet
aggregation completely at the concentration of 0.2 mg/ml (= 0.45 mM). Comparing
IC50 values of EGCG and aspirin it was found that the potency of EGCG is
comparable to that of aspirin. Thrombin- and platelet activating factor (PAF)-induced
aggregation was also inhibited by EGCG. The elevation of cyclic adenosine
3',5'-monophosphate (cAMP) level was not observed in EGCG treated platelets.
EGCG emails
Q. Dear Dr Sahelian, 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)?
A. Human research with EGCG and cancer is lacking, therefore is
little information to base a meaningful answer regarding the role of EGCG
supplement use in cancer, either by itself or in combination with other
chemotherapy drugs.