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[SANET-MG] green tea
ISIS Press Release 18/01/07
Green Tea, The Elixir of Life?
Two cups or more of green tea a day for reducing risks of heart disease,
cancers, Alzheimer's, obesity, arthritis, diabetes, infections, malaria,
AIDS … Dr. Mae-Wan Ho
A fully referenced version of this article is posted on ISIS members’
website.
Green tea miracle brewing
Green tea, the everyday beverage for hundreds of millions in Japan and
China (see Box 1), has emerged as the latest ‘miracle drug' for
preventing just about any ailment humans can suffer from. Unlike
patented medicines, green tea has no toxic or harmful side effects, not
surprisingly, as its use goes back thousands, if not hundreds of
thousands of years. It is cheap and widely available, and if the
avalanche of scientific evidence proves right, it could do more than
anything else to deliver health to the nation. So why aren't governments
in the industrialised nations encouraging people to drink green tea for
health? It would cut down on sicknesses and death, avoid drugs and drug
side effects that have come to be accepted as almost inevitable, improve
national productivity, and save billions from the national health budget.
It would also put the pharmaceutical industry out of a lot of business
selling numerous expensive patented drugs targeted at the individual
diseases.
Box 1
Tea consumption through the ages
Tea has been brewed from the leaves of Camellia sinensis in China as far
back as 2737 BC, while archaeological evidence reveals that infusions of
leaves from various wild plants including tea might have been consumed
for more than 500 000 years [1]. Tea was traditionally used to reduce
inflammation, improve blood flow, treat infectious diseases, purify the
body and maintain mental equilibrium.
Today, it is the most popular beverage worldwide, second only to water,
and per capita worldwide consumption is approximately 40L/y. About 3
billion kilograms of tea are produced and consumed annually and growing
at a rate of 2.1 percent a year.
Commercial teas come in three major categories: unfermented green, fully
fermented black, and semi-fermented oolong. Most of the tea consumed in
the world is black tea, with green tea accounting for 20 percent. Tea
contains more than 4 000 chemical compounds that may affect the human
body, but most attention has been focussed on the polyphenolic compounds
(see Box 2)
The Food and Drug Administration (FDA) in the United States, widely
criticised for ‘fast-tracking' pharmaceutical drugs over the past decade
[2], issued a rejection of health claims that drinking green tea
contributes to preventing cardiovascular diseases in May 2006 [3], and
less than a year before, issued a rejection of health claims of green
tea preventing cancers [4] ( Green Tea Against Cancers , this series).
But the medical and scientific community apparently disagree.
The “Asian paradox”
“We do not yet have a full explanation for the ‘Asian paradox,' which
refers to the very low incidence of both heart disease and cancer in
Asia, even though consumption of cigarettes is greater than in most
other countries,” said Bauer Sumpio, M.D., professor and Chief of
Vascular Surgery in the Department of Surgery at Yale University, New
Haven, Connecticut, USA [5].
Sumpio is lead author of an article in the Journal of the American
College of Surgeons published also in May 2006 [1] reviewing nearly 150
scientific publications on green tea including reports on numerous
epidemiological, clinical and experimental studies. The evidence
suggests that the average 1.2 litres of green tea consumed daily by many
people in Asia may hold the key to the Asian paradox. The active
chemicals are generally thought to be the green tea polyphenols, the
most abundant (and effective) of which is (-)-epigallocatechin-3-gallate
(EGCG) (see Fig 1, Box 2).
Box 2
Green tea polyphenols
Green tea is rich in the polyphenolic compounds – bonded benzene rings
with multiple hydroxyl groups. Polyphenols are classified by structure
into flavonoids and non-flavonoids, and those in tea are mainly
flavonoids. Catechins make up 80 percent of the flavonoids in green tea.
The levels of catechins are generally 30 to 50 percent lower in black
teas [6], as some catechins are converted into theaflavins.
Tea catechins exist as two stereochemical isomers (forms), catechins and
epicatechins, depending on the configuration of the
3',4'-dihydroxyphenyl and hydroxyl groups at the 2- and 3- positions of
the C-ring (see Fig. 1). Each stereochemical isomer, in turn, exists as
two optical isomers:(+) and (-), which are mirror images of each other;
(-)-catechin can be modified by esterification with gallic acid.
Theaflavins are formed by enzyme-catalysed dimerization (two molecules
joining) of catechins.
Tea polyphenols are strong antioxidants, but they seem to have a wide
variety of biological effects not directly related to antioxidation (see
main text). Evidence also suggests that the biological effects of green
tea are over and above those that can be ascribed to individual
catechins such as EGCG, or even a mixture of green tea polyphenols.
EGCG has been shown to play a key role in preventing hardening of the
arteries. It reduces the amount of blood platelet aggregation, regulates
lipids, and inhibits the proliferation and migration of smooth muscle
cells, all of which are important factors in reducing cardiovascular
disease. EGCG also prevents the growth of certain tumours.
Tea, according to studies reviewed, improves gastrointestinal function
and alcohol metabolism; it improves kidney, liver and pancreatic
function, protects skin and eyes and alleviates arthritis.
Tea has been used in managing and preventing allergies, diabetes,
bacterial and viral infections, tooth cavities, to reduce or cure
disease with an inflammatory component and to improve neurological and
psychological health.
Green tea reduces risks from cardiovascular disease and cancer
Sumpio and colleagues [1] cited numerous studies to support the idea
that green tea reduces the risks of cardiovascular disease as well as
cancer, and additional reports documenting this have appeared since
their review.
A meta-analysis on 17 studies published in 2001 reported 11 percent
decrease in myocardial infarction when three cups of tea were consumed
daily.
A prospective cohort study published in 2002 involving 1 935 patients
with a history of myocardial infarction found that age- and
gender-adjusted mortality was reduced with tea drinking. Moderate tea
drinkers (less than 14 cups of tea/week) presented a relative risk of
0.69, while heavy tea drinkers (14 cups or more /week) presented a
relative risk of 0.61 compared with non-drinkers.
Another prospective study involving 8 552 Japanese men and women
published in 1997 found a relative risk for cardiovascular disease of
0.52 for men and 0.82 for women who consumed more than 10 cups of green
tea a day compared with those consuming less than 3 cups. This study
also found a decreased relative risk for cancer of 0.54 for men and 0.57
for women who drank more than 10 cups of green tea per day compared with
those who drank less than 3 cups. Furthermore, there was delayed cancer
onset for those who drank the larger quantities of green tea: up to 7
years for women, and 3 years for men.
In a case-control study published in 1988, epidemiologists in Japan
reported a decrease of gastric cancer in subjects consuming more than 10
cups of green tea per day.
A review of cohort studies in 1998 suggest green tea protects against
many cancers including esophageal, stomach, pancreatic, colon, and
urinary bladder cancers.
A population-based, case-control study of breast cancer among Chinese,
Japanese and Philippine women conducted in Los Angeles County involved
501 breast cancer patients and 594 matched controls. It found no
decreased breast cancer risk from drinking black tea, only from drinking
green tea. The relative risks adjusted for ethnicity, geographic
location and food consumption were 1.00, 0.71 and 0.53 for people
drinking no green tea, 0-85.7 mL/day, and more than 85.7 mL/day
respectively.
A clinical trial published in 2004 involving 1 507 men and women in
Taiwan ages 20 years and older found that habitual consumption of 120
mL/d of green tea or oolong tea for at least one year considerably
reduced the risk of hypertension (high blood pressure). After adjusting
for different confounding factors such as age, gender, personal and
family medical history, dietary and lifestyle factors the risk of
hypertension compared to non-drinkers was reduced by 46 percent for
those who drank 120 to 599 mL/d, and by 65 percent for those who drank
600mL/d or more [7].
The Ohsaki National Health Insurance Cohort Study was initiated in 1994,
and involved 40 530 Japanese adults aged 40 to 79 years with no history
of stroke, coronary heart disease or cancer at baseline. Participants
were followed up for up to 11 years for all cause mortality. Green tea
consumption was inversely associated with mortality due to all causes
and due to cardiovascular disease, but not cancer [8].
In another study, 203 patients who underwent coronary angiography were
enrolled, and green tea consumption was significantly higher in patients
without coronary artery disease than in those with the disease [9].
How green tea delivers its health benefits
As green tea is rich in polyphenols, also known as flavonoids,
investigations on how green tea delivers its health benefits have
focussed on green tea flavonoids, and a plethora of cellular and
molecular effects have been documented [1].
Heart disease and cancers
The association between flavonoid intake and heart disease was assessed.
Three prospective epidemiologic studies: the Seven Countries Study, the
Zutphen Elderly Study and a Finnish cohort study, all published in the
1990s, revealed a clear inverse correlation between mortality rates from
coronary heart disease and flavonoid intake.
Cell and cell culture studies indicate that EGCG, and to a lesser extent
other catechins in green tea, decrease oxidation of low density
lipoprotein (LDL) and inhibit the proliferation of smooth muscle cell
and endothelial cells, thereby potentially reducing the risk of
arteriosclerosis. EGCG also prevents blood vessel and tube formation,
causing cessation of cancer growth and preventing certain types of
tumours from spreading.
EGCG can act on platelets and other cells to prevent platelet
aggregation as shown in many experiments on isolated cells or cell
cultures, suggesting that green tea polyphenols have antithrombotic
action in preventing blood clots.
Green tea can produce weight loss through the activation of
thermogenesis (producing heat by burning fat), thereby reducing obesity,
one of the risk factors of heart disease.
Green tea inhibits smooth muscle cell invasion through the basement
membrane barrier of the blood vessels, a key event involved in the
development and progression of arteriosclerosis (hardening of the
arteries) and injury-induced vascular remodelling. EGCG reduces the
expression of a matrix metalloproteinase that is important in the
migration and growth of endothelial cells and smooth muscle cells.
EGCG induces the transcription factor nuclear factor- k B that promotes
smooth muscle cell death. Several catechins especially EGCG inhibit the
endothelial growth factor, a key protein involved in blood vessel
formation. The sum of these activities results in the cessation and
potentially the reversal of various vascular diseases and cancer growth.
New data from 1 031 healthy Caucasian men 35-59 years old, part of a
large cross-sectional community based study in Ghent University,
Belgium, focusing on job stress and health, show that tea drinkers were
less obese, smoked less and drank less alcohol and coffee. The
inflammation markers, C-reactive protein, serum amyloid A and
haptoglobin, were significantly inversely associated with tea
consumption [10]. The authors conclude that tea drinking might be of
interest in reducing the inflammatory process underlying cardiovascular
disease.
Tea catechins are potent inhibitors of carcinogenesis at the three
stages of cancer development: initiation, promotion and progression [1].
Polyphenols from green tea can prevent the formation of nitrosamines in
cancer initiation. Nitrosamines are carcinogens also found in tobacco.
Tea polyphenolics inhibit the formation of heterocyclic amines,
genotoxic carcinogens found in cooked meat and fish, and associated with
pancreatic, colon, and breast cancers. EGCG shows the strongest effects
against mutations, DNA scissions, and nonenzymic interception of
superoxide anions that damage DNA. Another tea polyphenol, ECG is one of
the most efficient enzymatic scavengers of free radicals, directly
neutralising procarcinogens.
A new study from several universities in Tainan, Taiwan showed that
pu-erh tea (a black tea fermented for a long time), green tea, oolong
tea, and black tea all have strong antimutagenic action against a number
of mutagens including aflatoxin B1 [11]
With respect to cancer promotion, EGCG inhibits the protein kinase
activator, an enzyme involved in the cell activation process leading to
promotion of tumours [1]. EGCG induces cellular senescence by strongly
inhibiting telomerase activity, limiting the cancer cells' lifespan in
leukaemia and in solid tumours. EGCG blocks activator protein-1, a
signal transducer associated with the development of skin cancer and
other tumours
With regard to cancer progression, numerous reports indicate that tea
polyphenols inhibit the growth of malignant cells and induce cell death.
EGCG inhibits urokinase, a proteolytic enzyme necessary for cancer
growth, tissue invasion and metastasis (cancer spreading).
Neurodegenerative diseases
A significant number of reports indicate that naturally occurring green
tea polyphenols/flavonoids can protect neurons in many ways, through
antioxidant/radical scavenging, anti-inflammation and iron-chelation. A
cross-sectional analysis published in 2006 found that higher consumption
of green tea among the elderly in Japan is associated with lower
prevalence of cognitive impairment [12]. The subjects were 1 003
Japanese aged 70 years and older. The relative risks for cognitive
impairment associated with different frequencies of green tea
consumption were 1.00 for 3 cups and less a week, 0.62 for 4-6 cups/week
or 1 cup/day, and 0.46 for 2 cups or more a day. This may explain the
relatively lower prevalence of dementia, especially Alzheimer's disease
in Japan than in Europe and North America.
In line with the in vivo findings, many cell culture studies have
demonstrated that EGCG protected neurons against neurotoxins, and via
numerous molecular mechanisms. Researchers at the Eve Topf Center for
Neurodegenerative Diseases and Technion, Haifa, Israel, have recently
demonstrated that very low levels of EGCG (1 m M) promoted the survival
of neurons by enhancing short-term degradation of the cell-death Bad
protein [13]. This low concentration is less than one-hundredth of those
that destroy cancer cells [4, 5].
Other chronic diseases
Green tea has been associated with the prevention and treatment of many
other systemic disorders. In diabetes, green tea can reduce blood
glucose levels and suppress the activity of glucose transporters in the
intestinal epithelium reducing dietary glucose intake [1].
Green tea has anti-inflammatory properties and EGCG was reported to
inhibit histamine release by 90 percent in rat cell culture. This
anti-inflammatory effect may also benefit people suffering from arthritis.
In terms of kidney disease, catechins increase sodium and prostaglandin
E 2 excrection and improves renal circulation.
Green tea modulates the activity of the intestinal microflora and
improves bowel function.
Antimicrobial and antiviral action
Green tea protects against infections through its antibacterial and
antiviral activity [1]. Extracts of green tea inhibit the effects of
Campylobacter jejuni, E. coli , Helicobacter pylori , Vibrio cholerae ,
Salmonella , Shigella , Clostridium , Mycoplasma , Pseudomonas and
Cryptococcus .
A recent investigation found that Pu-erh tea, green tea, oolong tea and
black tea all have antimicrobial action against Staphylococcus and
Bacillus , but not E. coli [11].
Crude extracts of green tea as well as two of its main constituents,
EGCG and ECG strongly inhibit the growth of the malarial parasite,
Plasmodium falciparum in vitro, with IC50 (concentrations giving 50
percent inhibition) in the tens of micromoles/L range [14]. EGCG and ECG
also potentiate the effect of artemisin, lowering the IC50 of artemisin
from 14 nM to 8.4 nM and 9.5 nM respectively.
Tea strongly inhibit viruses including rotavirus and influenza A virus
in animal cell cultures.
The green tea flavonoid, EGCG, was found to inhibit the replication of
HIV-1 [15], the human immunedeficieny virus generally supposed to cause
AIDS disease (but see Unraveling AIDS [16]). In a new report,
researchers at Sheffield University UK, and Baylor College of Medicine
and Texas Children's Hospital in the US, demonstrated that EGCG binds to
CD4 - the cell surface receptor for HIV-1 entry into cells – with
extraordinary high affinity, with a binding constant approximately 10
nanomoles/L, thereby preventing the HIV-1 surface glycoprotein gp120
from binding to human CD4+ T cells, the first stage in gaining entry to
the cells.
In another report published in 2005, researchers at the Lindsley F.
Kimball Research Institute, New York Blood Center, in the US, and
Southern Medical University Guangzhoug, Guangdong, in China,
demonstrated that green tea as well as black tea polyphenols can inhibit
HIV-replication by blocking the formation of a ‘fusion bundle' by the
HIV-1 surface glycoprotein gp41, at micromolar concentrations, a
hundredth of those that kill cancer cells. Virus-cell fusion is
necessary for the virus to enter the cell. The most effective was the
green tea polyphenol, 2',2”-bisepigallocatechin digallate (BGCDG) with a
CC50 (concentration giving 50 percent inhibition of viral cell fusion)
of 0.64 m M, while that of the major green tea polyphenol EGCG was 3.44
m M. The CC50 of black tea TF2B (epitheaflavin-3'-gallate) was 1.28 m M,
and that of TF3 (theaflavin digallate), 1.96 m M.
Numerous animal studies corroborated the main findings
Numerous animal studies corroborated the results of human studies and
studies on cells and cell cultures, and many potential mechanisms of
action have been identified. Some of the animal experiments involve
drastic interventions and creation of disease models, and it is
questionable whether they are justifiable on ethical grounds, as they
add so little to what we already know from human and other non-animal
studies.
The evidence is strong
Sumpio and colleagues' comprehensive review covers papers published 2005
and earlier [1].
They concluded that more studies are needed to better understand green
tea's mode of action, particularly at the cellular level. But they also
state that, “The evidence is strong that green tea consumption is a
useful dietary habit to lower the risk and treat a number of chronic
diseases.”
“Prevention is the best cure.” They continue, “The consumption of 6 to
10 cups of tea per day might constitute an aid to increased health,
longevity and quality of life.”
They also suggest tea as a potential solution to some of the major
health problems of the elderly and society.
New studies have added further weight to the evidence on the health
benefits of green tea and its importance in addressing current major
health problems [4] ( Green Tea Against Cancers , this series).
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