
Clinical investigations of the potential health benefits of green tea
and its extracts are relatively few; however, epidemiological studies
in various human populations and cohorts provide evidence suggesting
that the regular ingestion of green tea can have important positive
health benefits. In the first part of this section, the results of
some key clinical studies are summarized; in the second part, the
epidemiological evidence is reviewed
Cardiovascular and Circulatory Disorders
Cardiotonics; Cardioprotection
A large investigation of 12,763 middle-aged men from 7 countries
examined the relationship between dietary intake of flavonoids and
heart disease (Hartog et al., 1995). A strong positive correlation
between flavonoid content of the diet and a lower risk of heart
disease was found in these men. Mortality rates from heart disease
varied greatly between different countries and flavonoid intake
resulted in 1/4 of the differences. Following-up on the Netherlands
arm of the study, Hartog and co-workers compared the flavonoid intake
of 805 elderly men with their risk for cardiovascular disease over a
5-yr. period. The primary source of flavonoids in their diet was tea
(61%), onions (13%) and apples (10%). Hartog et al. found that the
volume of flavonoids in the diet inversely correlated to the risk of
death from heart disease, and that the risk of nonfatal heart attack
was similarly inversely correlated. Men with the highest intake of
flavonoids had half the risk of those with the lowest intake.
In a study of black tea in 20,000 middle-aged Norwegian men and
women, those who drank 5 or more cups/day had lower levels of
cholesterol than those who did not drink tea; for men the figure was
9.3 mg/dL lower, and for women 5.8 mg/dL lower. Black tea drinkers
were less likely to die from a heart attack, and systolic blood
pressure in these groups was inversely related to tea consumption
(Stensvold et al., 1992).
Cerebrovascular Dysfunctions
Loss of mental acuity and cognitive functions with age has been
associated with free radical damage to brain tissues and to the
circulatory system which brings oxygen and nutrients to the brain.
Therefore, the antioxidant nature of green tea polyphenols might have
a protective or restorative effect on cerebrovascular impairment. A
Chinese study reported on 46 patients with dementia or other age-
related cerebrovascular deficits who were given green tea polyphenol
supplements for 1 mo. Ninety-one percent of the dementia patients and
60% of those with verbal disorders showed significant improvement.
The treatments appeared to be most effective when initiated in the
early stages of the disease (Mitscher and Dolby, 1998).
Effects on cholesterol and lipid metabolism
Tsubono and Tsugane (1997) randomly selected 207 men (mean age 44.4)
and 164 of their wives (mean age 41.4 years) from 5 regions in Japan
for inclusion in an analysis of cholesterol levels after drawing
their blood 2 wks. earlier. Extensive controls were employed for
dietary and other factors affecting health, including
smoking/nonsmoking, nutrient intake, alcohol intake, education,
physical activity, district of origin, intake of animal fats, fatty
acids, coffee, and oolong tea consumption, and other factors. Among
the women, green tea was consumed at the rate of at least 1 cup/day
by 68% and on the whole they drank 3.1 cups/day. Among the men, 69%
drank at least 1 cup/day, and on average consumed 3.5 cups/day.
Following adjustments for both dietary and nondietary factors, the
researchers found no significant effect of green tea consumption on
lipid profiles, whether of triglycerides, total cholesterol or HDL-
cholesterol.
In contrast, a Japanese study of 1,371 men aged 40 and older, Imai
and Nakachi (1995) found that green tea consumption was strongly
correlated with lower cholesterol levels, even after correcting for
age, smoking, alcohol use, and body weight; men who drank 10 or more
cups/day had significantly lower cholesterol levels, with LDL-
cholesterol decreased and HDL-cholesterol elevated. The tea drinkers
also had a decreased atherogenic index. Consumers of more than 10
cups/day also had decreased levels of hepatological markers in serum,
including aspartate aminotransferase, alanine transferase, and
ferritin. The subjects in the study who smoked had greatly elevated
levels of lipid peroxides in their blood, but of those smokers who
were also among the heaviest consumers of green tea, lipid peroxide
profiles were similar to those of nonsmokers (Imai and Nakachi,
1995). The contrasting results above may be attributable to the
length of green tea use and other dietary differences between the
Japanese study group of Imai and Nakashi (1995) and the relatively
small Dutch group (n=64) in the study by Princen et al. (1998).
Genito-urinary and Renal Disorders Renal disorders
Researchers in China examined the influence of green tea polyphenol
supplements in 25 patients with chronic renal failure due to
diabetes, hypertensive renal disease, or infections. Half received
the standard treatment (low salt, high protein diet) while the other
half received the standard treatment plus green tea polyphenols. The
latter group showed significant improvements in renal function, as
measured by improved blood and urine profiles, edema, lumbago, and
dizziness. Similar results were reported in a study at Long Sai
Hospital in China in 60 patients with chronic renal failure. Kidney
functions in the green tea-supplemented group were significantly
improved after 1-2 mos., versus those receiving standard care alone
(Mitscher and Dolby, 1998). Serum methylguanidine and the
methylguanidine/creatinine ratio were measured in 50 chronic kidney
hemodialysis patients administered a mixture of green tea polyphenols
(Sunphenon©, 200 mg X 2/day) in the form of a jelly for 6 mos. After
this time, the mean serum concentration of methylguanidine showed a
significant decrease of 30% compared to baseline, as did the
methylguanidine/creatinine ratio at the second mo. (from 4.12 X 10-3
to 3.86 X 10-3), which continued throughout the period of green tea
polyphenol administration (Ninomiya et al., 1997).
Immune Disorders; Inflammation and Disease Cancer Cancer prevention
Quantities of tea consumed, when reported in these cohort and case-
control studies, vary widely. At least 10 cups/day was associated
with a decreased risk of gastric cancer in Northern Kyushu, Japan
(Kono et al., 1988); a decreased incidence of all cancers in Saitama
prefecture, Japan was found from at least 3 cups/day (about 100-125
mg EGCg) (Imai et al., 1997); a decrease in cancer incidence in
Shanghai, China, was associated with at least 1 cup of freshly brewed
green tea/wk. for a minimum of 6 mos. during the past 5 yrs. (Yu et
al., 1995); 1 cup/wk. for 6 mos. or longer was associated with lower
risks of developing pancreatic or colorectal cancers in Shanghai (Ji
et al., 1997); and 5 or more cups/day was associated with a decreased
recurrence of breast cancer at stages I and II (p<0.05),>
stage III in Japanese women. In the latter study, no association was
found between tamoxifen use, radiotherapy, or chemotherapy and use of
green tea in the decreased risk of breast cancer recurrence.
Suggesting further studies, the authors noted that the significance
of consuming green tea before breast cancer was clinically diagnosed
or when taken after surgical intervention could not be determined
with their data (Nakachi et al., 1998). Conversely, a recent
prospective study of gastric cancer incidence among Japanese people
(5,610 men and 6,297 women) residing in Hawaii found green tea
consumption positively associated with gastric cancer (Galanis et
al., 1998), a finding also reported in a hospital-based case-control
study of 210 Taiwanese men and women recently diagnosed with stomach
cancer. However, the positive association was only of slight
statistical significance (p<0.10)>
Kohlmeier et al. (1997) reviewed the epidemiologic literature
suggesting an association (either positive or negative) between tea
consumption and cancer prevention in stomach, colon, and lung
cancers, and concluded that unequivocal evidence of protective
effects of tea-drinking on cancers could not be derived from the
existing data. With respect to stomach cancer, Kohlmeier et al.
asserted that no convincing claims could be made for a protective
effect of tea because of the shortcomings of the studies. They
concluded that if there is a beneficial association between tea
drinking and stomach cancer, the effect is likely to be significant
only in high-risk populations having a high intake of tea. In the
case of colon cancer, the evidence seemed to suggest a protective
effect of green tea consumption on the development of colon cancer;
however, many of these studies suffered from the same kinds of
methodological weaknesses that influenced the stomach cancer studies.
They suggested that a meta-analysis of the data might considerably
strengthen the conclusions. Only 4 epidemiologic studies on the
influence of tea drinking on lung cancer were reviewed, emphasing
again the problems of a small number of studies and serious
methodological flaws, in particular the failure to account for the
confounding effects of smoking. In 2 of the lung cancer studies, the
incidence of cancer was actually higher in the tea consuming
populations, but the researchers state that no conclusions can be
justified due to the inadequate study design and failure to control
for confounding variables.
Yang and Wang (1993) reviewed the epidemiological studies on
associations between tea and various types of cancers. They cited 10
studies which found no correlation between pancreatic cancer and tea
consumption, while one case-control study had found a positive
correlation and 2 studies showed a negative correlation. In addition,
the authors recounted that 2 studies indicated a negative association
between tea consumption and uterine cancer.
A positive correlation has been postulated between tea consumption
and the development of esophageal cancer, based on findings that
higher incidences occur in geographical regions where tea consumption
is high relative to water consumption. Yang and Wang (1993) point out
that other studies did not support this, although there did seem to
be evidence that consumption of very hot tea, rather than tea per se,
was a significant risk factor for esophageal cancer. With respect to
stomach cancer, significant negative correlations have been reported
between the incidence and green tea consumption, and case-control
studies in Japan indicated that individuals consuming green tea
frequently or in larger quantities had a lower risk of developing
gastric cancer. The authors note that in other case control studies,
however, including Buffalo, Kansas City, Nagoya, Japan, Piraeus,
Greece, Milan, Italy, Spain, and Turkey, no statistical association
between tea consumption and stomach cancer was found; nor were
statistical associations found between tea consumption and bladder,
urinary tract, or breast cancer. Contradictory findings were found
for colon and rectal cancer; 3 studies indicated a positive
association with tea-drinking, and 3 indicated a negative
association. Similarly, with respect to liver, kidney, and lung
cancers, studies have found both positive and negative correlations.
No correlations have been found between tea consumption and
nasopharyngeal cancers.
Yang and Wang (1993) pointed to the difficulties inherent in
interpreting the data derived from cohort and case-control studies of
this kind, emphasizing that there was often a lack of information on
the type, quantity, and temperature of the tea consumed, and problems
in adjusting for confounding factors, such as smoking and alcohol.
The fact that black tea is predominantly consumed in the West while
green tea is the usual beverage of choice in Japan, and that both
green and black tea are consumed in China, were given as further
variables adding to the complexity of such studies and contributing
to their lack of consistency and often contradictory conclusions.
More recently, Chow et al. (1999) of the National Cancer Institute,
Division of Cancer Epidemiology and Genetics, cited these and other
inconsistencies in the epidemiological data available and called for
further research on the influence of tea on cancer risk in humans.
They advise that until that time, the influence of tea on cancer
incidence remains inconclusive (Chow et al., 1999).
Hamajima et al. (1999) conducted a phase II study of the effect of
green tea extract (Polyphenon Capsules, Mitsui Norin Co., Ltd.,
Tokyo) on serum pepsinogen levels in outpatients of both sexes (ages
40-69) who previously underwent gastroscopy at a cancer hospital and
were found without stomach disease. Pepsinogen levels were measured
as an indictor of gastric atrophy, since atrophic gastritis is
recognized as a risk factor for developing stomach cancer. The
patients measured for pepsinogen levels were divided into 2 groups:
77 (mean age 57.8) who would take 2 capsules of the non-decaffeinated
green tea extract (100 mg/capsule, standardized to contain 50%
epigallocatechin gallate) after each of 3 daily mealtimes for 1 yr.,
and 86 patients (mean age 58.9) who would take 1 capsule/day after
breakfast for 1 yr. The majority of these subjects drank at least 3
cups of tea/day and the 6 capsules/day was equivalent to 10 cups/day.
Measured by radioimmunoassay, pepsinogen levels in the 1 capsule/day
group increased by an average of 3.5 ng/mL, which was not
significantly different from levels of the 6 capsule/day group at 3.1
ng/mL. Alcohol, tea, and smoking were found to have no affect on
pepsinogen levels. Hamajima et al. concluded that average pepsinogen
levels are not affected by green tea polyphenol capsules.
Shim et al. (1995) compared the chemopreventive effect of coffee and
green tea among 52 male smokers (ages 20-52) judged clinically
healthy. The subjects were selected from 357 males who completed a
questionnaire designed to eliminate confounding subjects, such as
those who had been exposed to alcohol, radiation, or toxic chemicals,
or who had a pre-existing disease. The subjects selected were male
smokers who were regular coffee drinkers or regular green tea
drinkers (2-3 cups/day for 6 mos.), and male smokers and nonsmokers
who drank neither beverage. All the smokers smoked over 10
cigarettes/day. Noting that frequencies of sister chromatid exchange
(FSCE) in the peripheral lymphocytes (mitogen-stimulated) affords a
far more sensitive marker of mutagenic activity than measuring
chromosomal aberrations, Shim et al. compared the FSCE of the 3
groups of smokers to a group of nonsmokers. At the outset, the FSCE
of smokers was significantly higher (35%) compared to nonsmokers.
Measured after 6 mos., the FSCE of coffee-drinking smokers showed no
statistically significant difference compared to smokers. The FSCE
was significantly higher among the smokers who did not drink coffee
or green tea regularly compared to smokers who were regular green tea-
drinkers, and, most notably, the FSCE of the green tea-drinking
smokers was not significantly different from that of the nonsmokers.
Immune modulation Immunoprotection
Researchers in China conducted a study of green tea polyphenols in 60
patients undergoing radiation or chemotherapy for various types of
cancers. Patients receiving supplementation with green tea
polyphenols for 1 mo., starting on the first day of the therapy,
maintained stable white blood cell counts throughout their treatment.
Those receiving a standard medication for maintaining blood quality
experienced decreasing numbers of white blood cells over the
treatment period, and those given no supplemental medications showed
very dramatic drops in white blood cell counts, suggesting that the
tea polyphenolics were beneficial in maintaining the blood profile in
patients undergoing radiation or chemotherapy (Mitscher and Dolby,
1998).
Another unpublished study from China reported of 60 patients who had
low white blood cell counts from a variety of diseases, 31 of whom
had various cancers and were undergoing radiation and chemotherapy.
After taking green tea supplements for 30 days, 60% of the patients
showed an increase in white blood cell counts of more than 50%, and
31% showed their counts had increased by 30% to 50%. Importantly,
patients with low white cell counts resulting from radiation therapy
showed a 100% response to green tea polyphenols; patients receiving
chemotherapy had a good response, but a less dramatic one. Blood
counts in most patients remained normal for at least 2 mos. after
supplementation was suspended, and no serious side effects were noted
(Mitscher and Dolby, 1998).
Infectious diseases Microbial infections
In a clinical study, Ooshima et al. (1994) administered thorough
dental examinations and assessed the levels of bacteria in the mouths
of 35 volunteers (ages 18 -29). The volunteers followed different
regimens for 2 periods, each 4-days long. In the first, they ate a
normal diet but refrained from brushing or other oral hygiene
procedures, except for rinsing their mouths with a solution of tea
polyphenols after each meal and before bedtime. In the second
regimen, the same procedure was followed except the rinse did not
contain any active ingredients. Bacterial counts and follow-up dental
exams were performed at the end of each period. In 34 volunteers,
bacterial counts were reduced and plaque deposition was significantly
decreased by the polyphenol treatment, even though none of the
patients had been brushing or flossing. The results suggested that
the tea polyphenols inhibit plaque deposition.
Metabolic and Nutritional Disorders Aging and senescence; longevity enhancement
One study examined the effects of regular green tea ingestion on
longevity in 3,380 Japanese women over a 9-yr. period. All of the
women were teachers of the Japanese tea ceremony and were at least 50
yrs. old at the start of the study. As green tea is a major component
of the tea ceremony, it was assumed that these women ingested more
than an average amount. The researchers recorded all deaths that
occurred in this group over 9 yrs. and compared the incidence of
mortality to that of other Japanese women throughout Japan during the
same period. They found a smaller percentage of the green tea
drinkers died (280 verusus 512 in the general population) and
concluded that green tea was indicated as a possible protective
factor against several diseases of high mortality, such as heart
diseases, cancer, and cerebrovascular diseases (Sadakata et al.,
1992).
Epidemiological studies of green tea have focused mainly on two
areas: cancer, and fewer in number, cardiovascular diseases. In the
absence of well-designed, multi-center clinical trials involving
large numbers of subjects, epidemiological studies on the influence
of green tea consumption on disease incidences in large population
samples can provide evidence for or against the potential preventive
and therapeutic benefits of regular green tea ingestion. Such studies
are often complicated, however, by the existence of confounding
behavioral or dietary factors (e.g., smoking, alcohol consumption),
and the lack of quantitative information on the amount, frequency,
and consistency of tea ingestion by subjects in the study cohort or
case-control population. Therefore, these studies are usually
indicative rather than definitive of probable effects. For those
reasons, epidemiological studies on the long-term use of green tea
have turned up both positive and negative correlations with disease
incidences.
Antioxidant activity
Katiyar et al. (1999) studied the effect of topical EGCg on human
skin irradiated with ultraviolet B (UVB) in an effort to determine
protective effects against immunological functions besides protection
against erythema. Studies in mice had shown sunscreen provided no
protection against UVB-induced local cutaneous or systemic
immunological functions, despite protecting against sunburn. UVB was
applied at an equivalent dose of 4 MED (4 minimal erythema dose) to
the buttocks of healthy adults who volunteered for the study. Prior
to the irradiation, skin areas (2.5 cm2) received topically applied
EGCg (3 mg/100 mL acetone), no treatment, and a third area vehicle
only (acetone). The area of skin treated with EGCg 30 min. prior
showed significantly less erythema at 48 hrs. post-irradiation
compared to the other treatments. As for immunological effects of UVB
exposure, the skin left untreated showed increased infiltration of
monocytes/macrophages and of neutrophils, which are primarily
responsible for generating radical oxygen species which can lead to
skin damage. By comparison, the skin pretreated with EGCg showed less
dead cells and an inhibition of macrophage/neutrophil infiltration,
as measured by tissue levels of myeloperoxidase. The researchers note
that cyclooxygenase activity is induced in mouse skin by the
application of tumor promoter and in human skin following UVB
irradiation. Topical pretreatment with EGCg also significantly
inhibited UVB-induced cyclooxygenase activity in the skin of the
volunteers, as shown by significantly less prostaglandin (PG)
metabolite formation. EGCg pretreatment inhibited PGE2 formation by
64% (p<0.0005),>
and 47%, respectively.
In 12 healthy volunteers (ages 20-25), Pietta et al. (1998) examined
the total antioxidant activity of green tea extract (600 mg,
equivalent to 400 mg total green tea catechins) compared to a Ginkgo
extract (1.6 g, equivalent to 100 mg ginkgolides and 400 mg ginkgo
flavonoids) and placebo (maltodextrin). None of the volunteers were
taking antioxidant supplements and all had a habitually low intake of
flavonoids. Following a fast overnight and subsequent ingestion of
the test substances, venous blood was tested for total radical-
trapping antioxidant potential (TRAP) once each hr. after they
ingested the test substances for 6 hrs., and compared to TRAP from
blood taken before ingestion. Using the Trolox equivalent antioxidant
capacity method of Miller et al. (1996), Pietta and co-workers found
a longer lasting and more rapid TAA from the Ginkgo extract compared
to the green tea extract, despite the fact that in vitro tests using
the same methods showed the green tea extract to have a higher TAA
(5.2 mM Trolox) than the Ginkgo extract (2.4 mM Trolox) (Pietta et
al., 1998). This result only serves to emphasize the need for in vivo
tests to confirm more immediate in vitro data.
A randomized, single-blind, placebo-controlled parallel study of 64
healthy smokers (males and females, ages 22-46, 10 or more
cigarettes/day) in the Netherlands examined the effect of black tea,
green tea, green tea polyphenols (GTP), or water on plasma
antioxidants and plasma LDL oxidation ex vivo (Princen et al., 1998).
Subjects were forbidden to add milk to their tea, told to adhere to
their regular diet, and had to refrain from consuming red wine or tea
(apart from the prescribed tea), and to either drink more than 100 mL
of fruit juice or eat more than 2 oranges/day. The treatment period
lasted 4 wks. and there were no adverse effects. No changes were
found in plasma levels or LDL levels of vitamin E in either the black
tea (150 mL or 6 cups/day) or green tea group (150 mL or 6 cups/day)
compared to the control group (mineral water 150 mL/day). However,
the GTP group (6 capsules X 4/day = 900 mg GTP 4 X/day) showed a
significant drop in their plasma levels of vitamin E and LDL vitamin
E content, compared to the control group (p=0.102). Yet neither the
black tea, green tea, or GTP group showed any significant difference
in ex vivo LDL oxidation, despite an estimated 3.5-fold greater
amount of catechins in green tea compared to black tea. The plasma
from 1 subject in each treatment group showed significantly increased
lag times in vitro from the addition of GTP directly into the copper
ion and AAPH oxidation assays, as expected from earlier research
results. Thus, Princen et al. concluded that GTP remain unproven as
in vivo antioxidants of LDL, and that neither GTP, green tea, or
black tea have any ex vivo antioxidant effect on LDL (Princen et al.,
1998). A similar study by Hof et al. (1997) in nonsmokers (n=45) also
found no significant change in LDL resistance to oxidation ex vivo
after 4 wks. of either green or black tea or mineral water (6
cups/day).
In a study on tea in 10 adults, 5 drank about 2 cups of green tea,
while a second group of 5 adults drank an equivalent amount of black
tea. Blood samples were collected prior to drinking and at 30, 50,
and 80 min. and assessed for antioxidant capacity. Both green and
black tea improved the antioxidant capacity of the blood; however,
the blood from those who received green tea was about 6 times more
efficient. The antioxidant effects peaked at 30 min. in the green tea
drinkers, and at 50 min. in the blood from those the black tea group.
The rapidity of the change in antioxidant capacity suggested that the
polyphenols were absorbed in the upper part of the gastrointestinal
tract (Serafini et al., 1996).
Laboratory studies indicate that the flavonoids of green tea
(polyphenols or catechins) are responsible for the antioxidant
properties of tea, and, by extension, most of the health benefits may
be traceable to this antioxidant activity. In a study at the
University of Nebraska, 10 volunteers were fed a controlled diet over
a 2-wk. period, including beverages at each meal: green tea, black
tea, decaffeinated black tea, or a non-tea beverage. Urine, blood,
and feces were collected and analyzed for polyphenolics; those given
green tea had the highest levels, followed by black tea,
decaffeinated black tea, and no tea. These results established that
green tea polyphenolics are bioavailable (He and Kies, 1994).
Obesity & Weight Loss
Green tea polyphenolics have been shown to inhibit the activity of
amylase, a carbohydrate-digesting enzyme present in saliva. By
inhibiting this enzyme, researchers theorized that green tea
polyphenolics may favor the slow digestion of carbohydrates, which
prevents sharp spikes of insulin in the blood and favors fat-burning
over fat storage. In a small, double-blind, placebo-controlled study
in 60 middle-aged obese women (30-45 yrs. old), subjects were placed
on a diet of 1,800 calories/day and randomly assigned to either a
green tea supplement group or a placebo supplement group. Capsules
were taken at each meal for 30 days (250 mg X 8/day in 3 divided
doses starting with 2 X 250 mg at breakfast). After 2 wks., the green
tea group had lost twice as much weight as those given placebo on the
same diet. After a full 4 wks. of treatment, the women in the green
tea group had lost 3 X (2.9 kg) as much weight as the placebo group
(0.935 kg). Compared to the placebo group, the green tea group also
showed a significantly greater reduction in waist size (-2.1±1.37 cm
versus -0.48±0.97 cm), and their blood triglyceride levels compared
to the placebo group showed a significant decrease (-0.207±0.195 g/L
versus -0.033±0.14 g/L on placebo). No side effects, including sleep
loss, were reported (Lecomte, 1985).
Pharmacokinetics; Pharmacodynamics
The most abundant polyphenol in green tea, EGCg is widely distributed
in the organs of male and female mice 24 hrs. after oral
administration. Highest amounts of radiolabeled EGCg were found in
the order of stomach > colon > small intestine in females, and colon
> stomach > small intestine in males. In other organs the levels of
radiolabeled EGCg incorporated were highest in the order of liver >
brain > kidney > lung in female mice, and in the order of liver >
kidney > brain > lung in males. Blood levels were practically equal
in both sexes after 24 hrs. A second single dose administered orally
to female mice 6 hrs. later resulted in as high as 5.9 X the amount
of EGCg already distributed following the first dose. Levels were
enhanced 4-fold in the bone, bladder, brain, liver, lung and
pancreas, and 1.3- to 2.0-fold in the digestive tract. At 24 hrs.,
levels of EGCg were enhanced in the same organs greater than 3-fold
compared to the single administration. As the authors note, their
data suggest that the Japanese tradition of drinking green tea
throughout the day may result in a higher concentration of the green
tea polyphenols being maintained than from infrequent dosing
(Suganuma et al., 1998).
A recent bioavailability study of decaffeinated (>0.1%) green tea
(Lipton Company, Englewood Cliffs, NJ) was conducted in 18 healthy
human adult volunteers at Memorial Sloan-Kettering Cancer Center in
New York, NY (Yang et al., 1998a). Using green tea solids dissolved
in 500 mL hot water, they found no significant increase in maximum
plasma concentrations of green tea catechins from an oral dose of 4.5
g, suggesting a saturation level is achieved at a dose of 3 to4.5 g.
Following ingestion of the green tea (4.5 g), plasma levels of (–)-
epigallocatechin, (–)-epicatechin, and EGCg peaked at from 1.5 to 2.5
hrs. and were undetectable after 24 hrs. The time to reach maximum
plasma concentrations of EC and EGC (1.3-1.8 hrs.) was shorter than
that of EGCg (1.6-2.7 hrs.). Although dosage increases of these
polyphenols had no affect on these times, the urinary elimination
half-life of EGCg (5.0-5.5 hrs.) was longer than EC and or EGC (2.5-
3.4 hrs.). Total urinary (–)-epicatechin (EC) and (–)-
epigallocatechin (EGC) showed greater than 90% excretion within 8
hrs., but EGCg was not excreted and a dose-response relationship
between increased dosages of green tea and urinary excretion of
urinary EC and EGC was not found (Yang et al., 1998a).
By the topical route, EGCg (10% w/w) in the form of a hydrophilic
ointment (USP) at a dose of 17 mg EGCg showed an uptake of 1-20% on
mouse or human skin. Systemic levels of EGCg were negligible,
however, and EGCg showed transdermal penetration only in mouse skin
(Dvorakova et al., 1999).
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and its extracts are relatively few; however, epidemiological studies
in various human populations and cohorts provide evidence suggesting
that the regular ingestion of green tea can have important positive
health benefits. In the first part of this section, the results of
some key clinical studies are summarized; in the second part, the
epidemiological evidence is reviewed
Cardiovascular and Circulatory Disorders
Cardiotonics; Cardioprotection
A large investigation of 12,763 middle-aged men from 7 countries
examined the relationship between dietary intake of flavonoids and
heart disease (Hartog et al., 1995). A strong positive correlation
between flavonoid content of the diet and a lower risk of heart
disease was found in these men. Mortality rates from heart disease
varied greatly between different countries and flavonoid intake
resulted in 1/4 of the differences. Following-up on the Netherlands
arm of the study, Hartog and co-workers compared the flavonoid intake
of 805 elderly men with their risk for cardiovascular disease over a
5-yr. period. The primary source of flavonoids in their diet was tea
(61%), onions (13%) and apples (10%). Hartog et al. found that the
volume of flavonoids in the diet inversely correlated to the risk of
death from heart disease, and that the risk of nonfatal heart attack
was similarly inversely correlated. Men with the highest intake of
flavonoids had half the risk of those with the lowest intake.
In a study of black tea in 20,000 middle-aged Norwegian men and
women, those who drank 5 or more cups/day had lower levels of
cholesterol than those who did not drink tea; for men the figure was
9.3 mg/dL lower, and for women 5.8 mg/dL lower. Black tea drinkers
were less likely to die from a heart attack, and systolic blood
pressure in these groups was inversely related to tea consumption
(Stensvold et al., 1992).
Cerebrovascular Dysfunctions
Loss of mental acuity and cognitive functions with age has been
associated with free radical damage to brain tissues and to the
circulatory system which brings oxygen and nutrients to the brain.
Therefore, the antioxidant nature of green tea polyphenols might have
a protective or restorative effect on cerebrovascular impairment. A
Chinese study reported on 46 patients with dementia or other age-
related cerebrovascular deficits who were given green tea polyphenol
supplements for 1 mo. Ninety-one percent of the dementia patients and
60% of those with verbal disorders showed significant improvement.
The treatments appeared to be most effective when initiated in the
early stages of the disease (Mitscher and Dolby, 1998).
Effects on cholesterol and lipid metabolism
Tsubono and Tsugane (1997) randomly selected 207 men (mean age 44.4)
and 164 of their wives (mean age 41.4 years) from 5 regions in Japan
for inclusion in an analysis of cholesterol levels after drawing
their blood 2 wks. earlier. Extensive controls were employed for
dietary and other factors affecting health, including
smoking/nonsmoking, nutrient intake, alcohol intake, education,
physical activity, district of origin, intake of animal fats, fatty
acids, coffee, and oolong tea consumption, and other factors. Among
the women, green tea was consumed at the rate of at least 1 cup/day
by 68% and on the whole they drank 3.1 cups/day. Among the men, 69%
drank at least 1 cup/day, and on average consumed 3.5 cups/day.
Following adjustments for both dietary and nondietary factors, the
researchers found no significant effect of green tea consumption on
lipid profiles, whether of triglycerides, total cholesterol or HDL-
cholesterol.
In contrast, a Japanese study of 1,371 men aged 40 and older, Imai
and Nakachi (1995) found that green tea consumption was strongly
correlated with lower cholesterol levels, even after correcting for
age, smoking, alcohol use, and body weight; men who drank 10 or more
cups/day had significantly lower cholesterol levels, with LDL-
cholesterol decreased and HDL-cholesterol elevated. The tea drinkers
also had a decreased atherogenic index. Consumers of more than 10
cups/day also had decreased levels of hepatological markers in serum,
including aspartate aminotransferase, alanine transferase, and
ferritin. The subjects in the study who smoked had greatly elevated
levels of lipid peroxides in their blood, but of those smokers who
were also among the heaviest consumers of green tea, lipid peroxide
profiles were similar to those of nonsmokers (Imai and Nakachi,
1995). The contrasting results above may be attributable to the
length of green tea use and other dietary differences between the
Japanese study group of Imai and Nakashi (1995) and the relatively
small Dutch group (n=64) in the study by Princen et al. (1998).
Genito-urinary and Renal Disorders Renal disorders
Researchers in China examined the influence of green tea polyphenol
supplements in 25 patients with chronic renal failure due to
diabetes, hypertensive renal disease, or infections. Half received
the standard treatment (low salt, high protein diet) while the other
half received the standard treatment plus green tea polyphenols. The
latter group showed significant improvements in renal function, as
measured by improved blood and urine profiles, edema, lumbago, and
dizziness. Similar results were reported in a study at Long Sai
Hospital in China in 60 patients with chronic renal failure. Kidney
functions in the green tea-supplemented group were significantly
improved after 1-2 mos., versus those receiving standard care alone
(Mitscher and Dolby, 1998). Serum methylguanidine and the
methylguanidine/creatinine ratio were measured in 50 chronic kidney
hemodialysis patients administered a mixture of green tea polyphenols
(Sunphenon©, 200 mg X 2/day) in the form of a jelly for 6 mos. After
this time, the mean serum concentration of methylguanidine showed a
significant decrease of 30% compared to baseline, as did the
methylguanidine/creatinine ratio at the second mo. (from 4.12 X 10-3
to 3.86 X 10-3), which continued throughout the period of green tea
polyphenol administration (Ninomiya et al., 1997).
Immune Disorders; Inflammation and Disease Cancer Cancer prevention
Quantities of tea consumed, when reported in these cohort and case-
control studies, vary widely. At least 10 cups/day was associated
with a decreased risk of gastric cancer in Northern Kyushu, Japan
(Kono et al., 1988); a decreased incidence of all cancers in Saitama
prefecture, Japan was found from at least 3 cups/day (about 100-125
mg EGCg) (Imai et al., 1997); a decrease in cancer incidence in
Shanghai, China, was associated with at least 1 cup of freshly brewed
green tea/wk. for a minimum of 6 mos. during the past 5 yrs. (Yu et
al., 1995); 1 cup/wk. for 6 mos. or longer was associated with lower
risks of developing pancreatic or colorectal cancers in Shanghai (Ji
et al., 1997); and 5 or more cups/day was associated with a decreased
recurrence of breast cancer at stages I and II (p<0.05),>
stage III in Japanese women. In the latter study, no association was
found between tamoxifen use, radiotherapy, or chemotherapy and use of
green tea in the decreased risk of breast cancer recurrence.
Suggesting further studies, the authors noted that the significance
of consuming green tea before breast cancer was clinically diagnosed
or when taken after surgical intervention could not be determined
with their data (Nakachi et al., 1998). Conversely, a recent
prospective study of gastric cancer incidence among Japanese people
(5,610 men and 6,297 women) residing in Hawaii found green tea
consumption positively associated with gastric cancer (Galanis et
al., 1998), a finding also reported in a hospital-based case-control
study of 210 Taiwanese men and women recently diagnosed with stomach
cancer. However, the positive association was only of slight
statistical significance (p<0.10)>
Kohlmeier et al. (1997) reviewed the epidemiologic literature
suggesting an association (either positive or negative) between tea
consumption and cancer prevention in stomach, colon, and lung
cancers, and concluded that unequivocal evidence of protective
effects of tea-drinking on cancers could not be derived from the
existing data. With respect to stomach cancer, Kohlmeier et al.
asserted that no convincing claims could be made for a protective
effect of tea because of the shortcomings of the studies. They
concluded that if there is a beneficial association between tea
drinking and stomach cancer, the effect is likely to be significant
only in high-risk populations having a high intake of tea. In the
case of colon cancer, the evidence seemed to suggest a protective
effect of green tea consumption on the development of colon cancer;
however, many of these studies suffered from the same kinds of
methodological weaknesses that influenced the stomach cancer studies.
They suggested that a meta-analysis of the data might considerably
strengthen the conclusions. Only 4 epidemiologic studies on the
influence of tea drinking on lung cancer were reviewed, emphasing
again the problems of a small number of studies and serious
methodological flaws, in particular the failure to account for the
confounding effects of smoking. In 2 of the lung cancer studies, the
incidence of cancer was actually higher in the tea consuming
populations, but the researchers state that no conclusions can be
justified due to the inadequate study design and failure to control
for confounding variables.
Yang and Wang (1993) reviewed the epidemiological studies on
associations between tea and various types of cancers. They cited 10
studies which found no correlation between pancreatic cancer and tea
consumption, while one case-control study had found a positive
correlation and 2 studies showed a negative correlation. In addition,
the authors recounted that 2 studies indicated a negative association
between tea consumption and uterine cancer.
A positive correlation has been postulated between tea consumption
and the development of esophageal cancer, based on findings that
higher incidences occur in geographical regions where tea consumption
is high relative to water consumption. Yang and Wang (1993) point out
that other studies did not support this, although there did seem to
be evidence that consumption of very hot tea, rather than tea per se,
was a significant risk factor for esophageal cancer. With respect to
stomach cancer, significant negative correlations have been reported
between the incidence and green tea consumption, and case-control
studies in Japan indicated that individuals consuming green tea
frequently or in larger quantities had a lower risk of developing
gastric cancer. The authors note that in other case control studies,
however, including Buffalo, Kansas City, Nagoya, Japan, Piraeus,
Greece, Milan, Italy, Spain, and Turkey, no statistical association
between tea consumption and stomach cancer was found; nor were
statistical associations found between tea consumption and bladder,
urinary tract, or breast cancer. Contradictory findings were found
for colon and rectal cancer; 3 studies indicated a positive
association with tea-drinking, and 3 indicated a negative
association. Similarly, with respect to liver, kidney, and lung
cancers, studies have found both positive and negative correlations.
No correlations have been found between tea consumption and
nasopharyngeal cancers.
Yang and Wang (1993) pointed to the difficulties inherent in
interpreting the data derived from cohort and case-control studies of
this kind, emphasizing that there was often a lack of information on
the type, quantity, and temperature of the tea consumed, and problems
in adjusting for confounding factors, such as smoking and alcohol.
The fact that black tea is predominantly consumed in the West while
green tea is the usual beverage of choice in Japan, and that both
green and black tea are consumed in China, were given as further
variables adding to the complexity of such studies and contributing
to their lack of consistency and often contradictory conclusions.
More recently, Chow et al. (1999) of the National Cancer Institute,
Division of Cancer Epidemiology and Genetics, cited these and other
inconsistencies in the epidemiological data available and called for
further research on the influence of tea on cancer risk in humans.
They advise that until that time, the influence of tea on cancer
incidence remains inconclusive (Chow et al., 1999).
Hamajima et al. (1999) conducted a phase II study of the effect of
green tea extract (Polyphenon Capsules, Mitsui Norin Co., Ltd.,
Tokyo) on serum pepsinogen levels in outpatients of both sexes (ages
40-69) who previously underwent gastroscopy at a cancer hospital and
were found without stomach disease. Pepsinogen levels were measured
as an indictor of gastric atrophy, since atrophic gastritis is
recognized as a risk factor for developing stomach cancer. The
patients measured for pepsinogen levels were divided into 2 groups:
77 (mean age 57.8) who would take 2 capsules of the non-decaffeinated
green tea extract (100 mg/capsule, standardized to contain 50%
epigallocatechin gallate) after each of 3 daily mealtimes for 1 yr.,
and 86 patients (mean age 58.9) who would take 1 capsule/day after
breakfast for 1 yr. The majority of these subjects drank at least 3
cups of tea/day and the 6 capsules/day was equivalent to 10 cups/day.
Measured by radioimmunoassay, pepsinogen levels in the 1 capsule/day
group increased by an average of 3.5 ng/mL, which was not
significantly different from levels of the 6 capsule/day group at 3.1
ng/mL. Alcohol, tea, and smoking were found to have no affect on
pepsinogen levels. Hamajima et al. concluded that average pepsinogen
levels are not affected by green tea polyphenol capsules.
Shim et al. (1995) compared the chemopreventive effect of coffee and
green tea among 52 male smokers (ages 20-52) judged clinically
healthy. The subjects were selected from 357 males who completed a
questionnaire designed to eliminate confounding subjects, such as
those who had been exposed to alcohol, radiation, or toxic chemicals,
or who had a pre-existing disease. The subjects selected were male
smokers who were regular coffee drinkers or regular green tea
drinkers (2-3 cups/day for 6 mos.), and male smokers and nonsmokers
who drank neither beverage. All the smokers smoked over 10
cigarettes/day. Noting that frequencies of sister chromatid exchange
(FSCE) in the peripheral lymphocytes (mitogen-stimulated) affords a
far more sensitive marker of mutagenic activity than measuring
chromosomal aberrations, Shim et al. compared the FSCE of the 3
groups of smokers to a group of nonsmokers. At the outset, the FSCE
of smokers was significantly higher (35%) compared to nonsmokers.
Measured after 6 mos., the FSCE of coffee-drinking smokers showed no
statistically significant difference compared to smokers. The FSCE
was significantly higher among the smokers who did not drink coffee
or green tea regularly compared to smokers who were regular green tea-
drinkers, and, most notably, the FSCE of the green tea-drinking
smokers was not significantly different from that of the nonsmokers.
Immune modulation Immunoprotection
Researchers in China conducted a study of green tea polyphenols in 60
patients undergoing radiation or chemotherapy for various types of
cancers. Patients receiving supplementation with green tea
polyphenols for 1 mo., starting on the first day of the therapy,
maintained stable white blood cell counts throughout their treatment.
Those receiving a standard medication for maintaining blood quality
experienced decreasing numbers of white blood cells over the
treatment period, and those given no supplemental medications showed
very dramatic drops in white blood cell counts, suggesting that the
tea polyphenolics were beneficial in maintaining the blood profile in
patients undergoing radiation or chemotherapy (Mitscher and Dolby,
1998).
Another unpublished study from China reported of 60 patients who had
low white blood cell counts from a variety of diseases, 31 of whom
had various cancers and were undergoing radiation and chemotherapy.
After taking green tea supplements for 30 days, 60% of the patients
showed an increase in white blood cell counts of more than 50%, and
31% showed their counts had increased by 30% to 50%. Importantly,
patients with low white cell counts resulting from radiation therapy
showed a 100% response to green tea polyphenols; patients receiving
chemotherapy had a good response, but a less dramatic one. Blood
counts in most patients remained normal for at least 2 mos. after
supplementation was suspended, and no serious side effects were noted
(Mitscher and Dolby, 1998).
Infectious diseases Microbial infections
In a clinical study, Ooshima et al. (1994) administered thorough
dental examinations and assessed the levels of bacteria in the mouths
of 35 volunteers (ages 18 -29). The volunteers followed different
regimens for 2 periods, each 4-days long. In the first, they ate a
normal diet but refrained from brushing or other oral hygiene
procedures, except for rinsing their mouths with a solution of tea
polyphenols after each meal and before bedtime. In the second
regimen, the same procedure was followed except the rinse did not
contain any active ingredients. Bacterial counts and follow-up dental
exams were performed at the end of each period. In 34 volunteers,
bacterial counts were reduced and plaque deposition was significantly
decreased by the polyphenol treatment, even though none of the
patients had been brushing or flossing. The results suggested that
the tea polyphenols inhibit plaque deposition.
Metabolic and Nutritional Disorders Aging and senescence; longevity enhancement
One study examined the effects of regular green tea ingestion on
longevity in 3,380 Japanese women over a 9-yr. period. All of the
women were teachers of the Japanese tea ceremony and were at least 50
yrs. old at the start of the study. As green tea is a major component
of the tea ceremony, it was assumed that these women ingested more
than an average amount. The researchers recorded all deaths that
occurred in this group over 9 yrs. and compared the incidence of
mortality to that of other Japanese women throughout Japan during the
same period. They found a smaller percentage of the green tea
drinkers died (280 verusus 512 in the general population) and
concluded that green tea was indicated as a possible protective
factor against several diseases of high mortality, such as heart
diseases, cancer, and cerebrovascular diseases (Sadakata et al.,
1992).
Epidemiological studies of green tea have focused mainly on two
areas: cancer, and fewer in number, cardiovascular diseases. In the
absence of well-designed, multi-center clinical trials involving
large numbers of subjects, epidemiological studies on the influence
of green tea consumption on disease incidences in large population
samples can provide evidence for or against the potential preventive
and therapeutic benefits of regular green tea ingestion. Such studies
are often complicated, however, by the existence of confounding
behavioral or dietary factors (e.g., smoking, alcohol consumption),
and the lack of quantitative information on the amount, frequency,
and consistency of tea ingestion by subjects in the study cohort or
case-control population. Therefore, these studies are usually
indicative rather than definitive of probable effects. For those
reasons, epidemiological studies on the long-term use of green tea
have turned up both positive and negative correlations with disease
incidences.
Antioxidant activity
Katiyar et al. (1999) studied the effect of topical EGCg on human
skin irradiated with ultraviolet B (UVB) in an effort to determine
protective effects against immunological functions besides protection
against erythema. Studies in mice had shown sunscreen provided no
protection against UVB-induced local cutaneous or systemic
immunological functions, despite protecting against sunburn. UVB was
applied at an equivalent dose of 4 MED (4 minimal erythema dose) to
the buttocks of healthy adults who volunteered for the study. Prior
to the irradiation, skin areas (2.5 cm2) received topically applied
EGCg (3 mg/100 mL acetone), no treatment, and a third area vehicle
only (acetone). The area of skin treated with EGCg 30 min. prior
showed significantly less erythema at 48 hrs. post-irradiation
compared to the other treatments. As for immunological effects of UVB
exposure, the skin left untreated showed increased infiltration of
monocytes/macrophages and of neutrophils, which are primarily
responsible for generating radical oxygen species which can lead to
skin damage. By comparison, the skin pretreated with EGCg showed less
dead cells and an inhibition of macrophage/neutrophil infiltration,
as measured by tissue levels of myeloperoxidase. The researchers note
that cyclooxygenase activity is induced in mouse skin by the
application of tumor promoter and in human skin following UVB
irradiation. Topical pretreatment with EGCg also significantly
inhibited UVB-induced cyclooxygenase activity in the skin of the
volunteers, as shown by significantly less prostaglandin (PG)
metabolite formation. EGCg pretreatment inhibited PGE2 formation by
64% (p<0.0005),>
and 47%, respectively.
In 12 healthy volunteers (ages 20-25), Pietta et al. (1998) examined
the total antioxidant activity of green tea extract (600 mg,
equivalent to 400 mg total green tea catechins) compared to a Ginkgo
extract (1.6 g, equivalent to 100 mg ginkgolides and 400 mg ginkgo
flavonoids) and placebo (maltodextrin). None of the volunteers were
taking antioxidant supplements and all had a habitually low intake of
flavonoids. Following a fast overnight and subsequent ingestion of
the test substances, venous blood was tested for total radical-
trapping antioxidant potential (TRAP) once each hr. after they
ingested the test substances for 6 hrs., and compared to TRAP from
blood taken before ingestion. Using the Trolox equivalent antioxidant
capacity method of Miller et al. (1996), Pietta and co-workers found
a longer lasting and more rapid TAA from the Ginkgo extract compared
to the green tea extract, despite the fact that in vitro tests using
the same methods showed the green tea extract to have a higher TAA
(5.2 mM Trolox) than the Ginkgo extract (2.4 mM Trolox) (Pietta et
al., 1998). This result only serves to emphasize the need for in vivo
tests to confirm more immediate in vitro data.
A randomized, single-blind, placebo-controlled parallel study of 64
healthy smokers (males and females, ages 22-46, 10 or more
cigarettes/day) in the Netherlands examined the effect of black tea,
green tea, green tea polyphenols (GTP), or water on plasma
antioxidants and plasma LDL oxidation ex vivo (Princen et al., 1998).
Subjects were forbidden to add milk to their tea, told to adhere to
their regular diet, and had to refrain from consuming red wine or tea
(apart from the prescribed tea), and to either drink more than 100 mL
of fruit juice or eat more than 2 oranges/day. The treatment period
lasted 4 wks. and there were no adverse effects. No changes were
found in plasma levels or LDL levels of vitamin E in either the black
tea (150 mL or 6 cups/day) or green tea group (150 mL or 6 cups/day)
compared to the control group (mineral water 150 mL/day). However,
the GTP group (6 capsules X 4/day = 900 mg GTP 4 X/day) showed a
significant drop in their plasma levels of vitamin E and LDL vitamin
E content, compared to the control group (p=0.102). Yet neither the
black tea, green tea, or GTP group showed any significant difference
in ex vivo LDL oxidation, despite an estimated 3.5-fold greater
amount of catechins in green tea compared to black tea. The plasma
from 1 subject in each treatment group showed significantly increased
lag times in vitro from the addition of GTP directly into the copper
ion and AAPH oxidation assays, as expected from earlier research
results. Thus, Princen et al. concluded that GTP remain unproven as
in vivo antioxidants of LDL, and that neither GTP, green tea, or
black tea have any ex vivo antioxidant effect on LDL (Princen et al.,
1998). A similar study by Hof et al. (1997) in nonsmokers (n=45) also
found no significant change in LDL resistance to oxidation ex vivo
after 4 wks. of either green or black tea or mineral water (6
cups/day).
In a study on tea in 10 adults, 5 drank about 2 cups of green tea,
while a second group of 5 adults drank an equivalent amount of black
tea. Blood samples were collected prior to drinking and at 30, 50,
and 80 min. and assessed for antioxidant capacity. Both green and
black tea improved the antioxidant capacity of the blood; however,
the blood from those who received green tea was about 6 times more
efficient. The antioxidant effects peaked at 30 min. in the green tea
drinkers, and at 50 min. in the blood from those the black tea group.
The rapidity of the change in antioxidant capacity suggested that the
polyphenols were absorbed in the upper part of the gastrointestinal
tract (Serafini et al., 1996).
Laboratory studies indicate that the flavonoids of green tea
(polyphenols or catechins) are responsible for the antioxidant
properties of tea, and, by extension, most of the health benefits may
be traceable to this antioxidant activity. In a study at the
University of Nebraska, 10 volunteers were fed a controlled diet over
a 2-wk. period, including beverages at each meal: green tea, black
tea, decaffeinated black tea, or a non-tea beverage. Urine, blood,
and feces were collected and analyzed for polyphenolics; those given
green tea had the highest levels, followed by black tea,
decaffeinated black tea, and no tea. These results established that
green tea polyphenolics are bioavailable (He and Kies, 1994).
Obesity & Weight Loss
Green tea polyphenolics have been shown to inhibit the activity of
amylase, a carbohydrate-digesting enzyme present in saliva. By
inhibiting this enzyme, researchers theorized that green tea
polyphenolics may favor the slow digestion of carbohydrates, which
prevents sharp spikes of insulin in the blood and favors fat-burning
over fat storage. In a small, double-blind, placebo-controlled study
in 60 middle-aged obese women (30-45 yrs. old), subjects were placed
on a diet of 1,800 calories/day and randomly assigned to either a
green tea supplement group or a placebo supplement group. Capsules
were taken at each meal for 30 days (250 mg X 8/day in 3 divided
doses starting with 2 X 250 mg at breakfast). After 2 wks., the green
tea group had lost twice as much weight as those given placebo on the
same diet. After a full 4 wks. of treatment, the women in the green
tea group had lost 3 X (2.9 kg) as much weight as the placebo group
(0.935 kg). Compared to the placebo group, the green tea group also
showed a significantly greater reduction in waist size (-2.1±1.37 cm
versus -0.48±0.97 cm), and their blood triglyceride levels compared
to the placebo group showed a significant decrease (-0.207±0.195 g/L
versus -0.033±0.14 g/L on placebo). No side effects, including sleep
loss, were reported (Lecomte, 1985).
Pharmacokinetics; Pharmacodynamics
The most abundant polyphenol in green tea, EGCg is widely distributed
in the organs of male and female mice 24 hrs. after oral
administration. Highest amounts of radiolabeled EGCg were found in
the order of stomach > colon > small intestine in females, and colon
> stomach > small intestine in males. In other organs the levels of
radiolabeled EGCg incorporated were highest in the order of liver >
brain > kidney > lung in female mice, and in the order of liver >
kidney > brain > lung in males. Blood levels were practically equal
in both sexes after 24 hrs. A second single dose administered orally
to female mice 6 hrs. later resulted in as high as 5.9 X the amount
of EGCg already distributed following the first dose. Levels were
enhanced 4-fold in the bone, bladder, brain, liver, lung and
pancreas, and 1.3- to 2.0-fold in the digestive tract. At 24 hrs.,
levels of EGCg were enhanced in the same organs greater than 3-fold
compared to the single administration. As the authors note, their
data suggest that the Japanese tradition of drinking green tea
throughout the day may result in a higher concentration of the green
tea polyphenols being maintained than from infrequent dosing
(Suganuma et al., 1998).
A recent bioavailability study of decaffeinated (>0.1%) green tea
(Lipton Company, Englewood Cliffs, NJ) was conducted in 18 healthy
human adult volunteers at Memorial Sloan-Kettering Cancer Center in
New York, NY (Yang et al., 1998a). Using green tea solids dissolved
in 500 mL hot water, they found no significant increase in maximum
plasma concentrations of green tea catechins from an oral dose of 4.5
g, suggesting a saturation level is achieved at a dose of 3 to4.5 g.
Following ingestion of the green tea (4.5 g), plasma levels of (–)-
epigallocatechin, (–)-epicatechin, and EGCg peaked at from 1.5 to 2.5
hrs. and were undetectable after 24 hrs. The time to reach maximum
plasma concentrations of EC and EGC (1.3-1.8 hrs.) was shorter than
that of EGCg (1.6-2.7 hrs.). Although dosage increases of these
polyphenols had no affect on these times, the urinary elimination
half-life of EGCg (5.0-5.5 hrs.) was longer than EC and or EGC (2.5-
3.4 hrs.). Total urinary (–)-epicatechin (EC) and (–)-
epigallocatechin (EGC) showed greater than 90% excretion within 8
hrs., but EGCg was not excreted and a dose-response relationship
between increased dosages of green tea and urinary excretion of
urinary EC and EGC was not found (Yang et al., 1998a).
By the topical route, EGCg (10% w/w) in the form of a hydrophilic
ointment (USP) at a dose of 17 mg EGCg showed an uptake of 1-20% on
mouse or human skin. Systemic levels of EGCg were negligible,
however, and EGCg showed transdermal penetration only in mouse skin
(Dvorakova et al., 1999).
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useful information, thanks and best regards: Benefits of Green Tea
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