DIET AND NUTRITION
POTENTIAL HEALTH BENEFITS OF GREEN TEA
(CAMELLIA SINENSIS): A NARRATIVE REVIEW
Robert L. Pastore, PhD, and Patrick Fratellone, MD
he plant Camellia sinensis yields a
T variety of white, green, and black
tea. Tea is consumed only second
to water for enjoyment and for
health. Much research is available depict-
ing the health benefits of green tea for a
wide variety of implications, including dif-
ferent types of cancer, heart disease, and
liver disease. Since the 1970s, epidemio-
logical studies of cancer have shown that
in parts of the world where green tea is
consumed, the incidence of solid tumor
cancers such as breast, lung, and gastroin-
testinal cancers is lower. Mouse-model
testing of green tea’s cancer-prevention
properties has shown they protect against
solid tumors. Human research is very
promising using green tea as treatment for
various cancers. In the laboratory, the epi-
gallocatechin gallate component of green
tea has been proven to induce death in
cancer cells from solid tumors. This paper
will review animal and human research on
green tea, focusing on the catechins.
INTRODUCTION
Tea is the most widely consumed beverage
aside from water, with a per capita world-
wide consumption of approximately 0.12
liter per day. Tea is manufactured in four
basic forms. Green tea is prepared in such
a way as to preclude the oxidation of green
leaf polyphenols. During black tea pro-
duction, oxidation is promoted so that
most of these substances are oxidized.
Oolong tea is a partially oxidized product.
White tea is tea made from new growth
buds and young leaves that have been
steamed to inactivate polyphenol oxida-
tion, and then dried. The buds may be
shielded from sunlight to prevent forma-
tion of chlorophyll. Of the approximately
2.5 million metric tons of dried tea manu-
factured, only 20% is green tea, and less
than 2% is oolong tea. Green tea is con-
sumed primarily in China, Japan, and a
Diet and Nutrition
few countries in North Africa and the
Middle East.1
GREEN TEA
The chemical composition of green tea
varies with climate, season, horticultural
practices, and position of the leaf on the
harvested shoot. The major components
of interest are the polyphenols. The ma-
jor polyphenols in green tea are fla-
vonoids. The four major flavonoids in
green tea are the catechins epicatechin
(EC), epigallocatechin (EGC), epicat-
echin gallate (ECG), and epigallocat-
echin gallate (EGCG) (Figure 1). Epigal-
locatechin gallate is viewed as the most
significant active component. The leaf
bud and first leaves are richest in EGCG.
The usual concentration of total poly-
phenols in dried green tea leaves is about
8% to 12%.1,2
Figure 1. Major polyphenols in green tea.
Other compounds of interest in dried
green tea leaves include gallic acid, quer-
cetin, kaempferol, myricetin, caffeic acid,
and chlorogenic acid.3
EXPLORE November/December 2006, Vol. 2, No. 6 531
PHARMACOKINETICS
Pharmacokinetic parameters of EGCG,
EGC, and EC were analyzed after admin-
istration of a single oral dose of green tea
or decaffeinated green tea (20 mg tea sol-
ids/kg) or EGCG (2 mg/kg) to eight sub-
jects. The plasma and urine levels of total
EGCG, EGC, and EC (free plus conju-
gated forms) were quantified by high per-
formance liquid chromatography coupled
to an electrochemical detector. The
plasma concentration time curves of the
catechins were fitted in a one-compart-
ment model. The maximum plasma con-
centrations of EGCG, EGC, and EC in
the three repeated experiments with green
tea were 77.9 ⫾ 22.2, 223.4 ⫾ 35.2, and
124.03 ⫾ 7.86 ng/mL, respectively, and
the corresponding area under the curve
values were 508.2 ⫾ 227, 945.4 ⫾ 438.4,
and 529.5 ⫾ 244.4 ng ⫻ h ⫻ mL(⫺1),
respectively. The time needed to reach the
peak concentrations was in the range of
1.3 to 1.6 hours. The elimination half-lives
were 3.4 ⫾ 0.3, 1.7 ⫾ 0.4, and 2.0 ⫾ 0.4
hours, respectively.4
In the plasma, EGCG was mostly
present in the free form, whereas EGC
and EC were mostly in the conjugated
form. Over 90% of the total urinary
EGC and EC, almost all in the conju-
gated forms, was excreted between zero
and eight hours. Substantial amounts of
4=-O-methyl EGC, at levels higher than
EGC, were detected in the urine and
plasma. The plasma level of 4=-O-methyl
EGC peaked at 1.7 ⫾ 0.5 hours with
a half life of 4.4 ⫾ 1.1 hours. Two
ring-fission metabolites, (⫺)-5-(3=,4=,
5=-trihydroxyphenyl)-gamma-valero-
lactone (M4) and (⫺)-5-(3=,4=-dihy-
droxyphenyl)-valerolactone (M6), ap-
peared in significant amounts after three
hours and peaked at eight to 15 hours in
the urine, as well as in the plasma. These
results may be useful for designing the
dose and dose frequency in intervention
studies with tea and for development of
biomarkers of tea consumption.4
At the Arizona Cancer Center, no sig-
nificant changes were observed in blood
counts and blood chemistry profiles after
repeated administration of green tea poly-
phenol products at the dose of 800 mg of
EGCG daily. There was a greater than 60%
increase in the area under the plasma
EGCG concentration time curve after
four weeks of green tea polyphenol treat-
ment at a dosing schedule of 800 mg once
daily. No significant changes were ob-
served in the pharmacokinetics of EGCG
after repeated green tea polyphenol treat-
ment at a regimen of 400 mg twice daily.
The pharmacokinetics of the conjugated
metabolites of EGC and EC were not af-
fected by repeated green tea polyphenol
treatment.5
ANTIVIRAL
Epigallocatechin gallate and ECG were
found to be potent inhibitors of influenza
virus replication in cell culture. This effect
was observed in all influenza virus sub-
types tested, including A/H1N1,
A/H3N2, and B virus. Quantitative anal-
ysis revealed that, at high concentration,
EGCG and ECG also suppressed viral
RNA synthesis in cells, whereas EGC
failed to show similar effect. Similarly,
EGCG and ECG inhibited the neuramin-
idase activity more effectively than the
EGC. Neuraminidase is an antigenic gly-
coprotein enzyme found on the surface of
the influenza virus. Neuraminidase has
functions that aid in the efficiency of virus
release from cells.6
ATHEROSCLEROSIS
Population-based and clinical studies indi-
cate that the antioxidant properties of
green tea may help prevent atherosclero-
sis, particularly coronary artery disease.7
According to Japanese research, green
tea reduces the levels of LDL cholesterol,
thereby reducing the risk of coronary heart
disease. Studies have found that regular
consumption of tea protects against heart
disease, with one study documenting that
the risk was 36% lower for tea drinkers.8
Serum malondialdehyde–modified LDL
concentrations and urine 8-epi-prostaglan-
din (PG) F(2alpha) were measured in 22
healthy male nonsmokers to determine in-
532 EXPLORE November/December 2006, Vol. 2, No. 6
hibition of LDL oxidation by green tea. Sub-
jects drank seven cups/day of water for two
weeks and drank seven cups/day of green tea
for the next two weeks. Of the 22 subjects,
20 had been in the habit of drinking green
tea before the study. Plasma catechin con-
centrations significantly decreased at the
end of the water period and then increased
at the end of the green tea period. Although
no change in plasma LDL-cholesterol con-
centrations (110 ⫾ 33 vs. 113 ⫾ 28 mg/dL;
P⫽ NS) was found, malondialdehyde-mod-
ified LDL concentrations (84 ⫾ 45 vs. 76 ⫾
40 IU/L; P⬍ .05) and the ratio of malondi-
aldehyde-modified LDL/LDL-cholesterol
(0.74 ⫾ 0.21 vs. 0.65 ⫾ 0.20; P⬍ .02) signif-
icantly decreased at the end of the green tea
period. However, no significant changes
were observed in urine 8-epi-PGF(2alpha)
concentrations, in platelet aggregation, or in
plasma TXB(2), 6-keto-PGF(1alpha) or ma-
trix metalloproteinase concentrations.9
Preliminary research also indicates that
tea polyphenols may reduce the activity of
platelets. Preincubation with EGCG con-
centration– dependently inhibited throm-
bin-induced aggregation and phosphory-
lation of p38 mitogen–activated protein
kinase and extracellular signal–regulated
kinases-1/2. In contrast, EGCG stimu-
lated tyrosine phosphorylation of platelet
proteins, including Syk and SLP-76 but in-
hibited phosphorylation of focal adhesion
kinase. Other catechins did not inhibit
platelet aggregation.10
One population-based study found that
men who drink green tea are more likely to
have lower total cholesterol than those
who do not drink green tea. The subjects
were 13,916 workers (8,476 men and 5,440
women) aged 40 to 69 years at over 1,000
workplaces in Nagano prefecture, central
Japan. They did not have morbid condi-
tions affecting serum cholesterol levels.
Serum concentrations of total cholesterol,
high-density lipoprotein cholesterol, and
triglycerides were measured at the screen-
ing. Green tea consumption was statisti-
cally significantly associated with lower
levels of serum total cholesterol in both
men and women, whereas its associations
with serum triglycerides and high-density
lipoprotein cholesterol were not statisti-
cally significant. The inverse association
of serum total cholesterol with green tea
consumption appeared to level off at the
consumption of more than 10 cups/day.
Excluding the outlying subjects drinking
more than 10 cups/day (0.4%), the regres-
sion analysis adjusting for age, body mass
index, ethanol intake, smoking habit, cof-
fee intake, and type of work showed that
daily consumption of one cup of green tea
was associated with a reduction in serum
total cholesterol by 0.015 mmol/L (95%
confidence interval, 0.006-0.024; P⬍ .001)
in men and 0.015 mmol/L (95% confi-
dence interval, 0.004-0.025; P⬍ .01) in
women. After additional adjustment for
selected dietary factors, the inverse associ-
ation remained statistically significant;
one cup of green tea per day was associated
with a reduction in serum total cholesterol
by 0.010 mmol/L (95% confidence inter-
val, 0.001-0.019; P ⫽ .03) in men and
0.012 mmol/L (95% confidence interval,
0.001 to 0.022; P⫽ .03) in women.11
Bursill and Roach12 attempted to find the
mechanism in green tea that may reduce
cholesterol. HepG2 cells were incubated
with the main green tea catechins. Epigallo-
catechin gallate was the only catechin to in-
crease LDL receptor binding activity (three-
fold) and protein (2.5-fold) above controls.
Epigallocatechin gallate increased the con-
version of sterol regulatory element binding
protein-1 (SREBP-1) to its active form
(⫹56%) and lowered the cellular cholesterol
concentration (⫺28%). At 50 microM,
EGCG significantly lowered cellular choles-
terol synthesis, explaining the reduction in
cellular cholesterol.
In a cross-cultural correlation study of
16 cohorts, known as the Seven Countries
Study, the higher polyphenol intake of
green tea was inversely correlated with
mortality rates of coronary heart disease
after 25 years of follow-up.13,14
AUTOIMMUNE DISEASES
Hsu and Dickinson15 suspected that there
may be a link between green tea consump-
tion and autoimmunity after noting that
xerostomia, an autoimmune disorder suf-
fered by approximately 30% of elderly
Americans, occurs in only one to two per-
cent of Chinese people in the same age
group. Sjogren’s syndrome is an autoim-
mune disorder that affects the salivary
glands, leading to xerostomia, and the lac-
rimal glands, resulting in xerophthalmia.
Secondary Sjogren’s syndrome is associ-
ated with other autoimmune disorders
such as systemic rheumatic diseases and
systemic lupus erythematosis, which can
Diet and Nutrition
affect multiple organs, including the epi-
dermis. By studying cells in salivary glands
and skin tissue, Hsu and Dickinson found
that cells exposed to EGCG showed RNA
and protein levels, indicating autoantigen
levels were suppressed in these normal
cells.
Green tea needs more research for auto-
immune diseases. As a model of autoim-
munity, researchers discovered that green
tea polyphenol extract attenuates inflam-
mation in interleukin-2-deficient mice.16
CARDIAC ARRHYTHMIAS
A study presented at the Heart Rhythm
Society’s 25th Annual Scientific Sessions
in 200417 found that EGCG could help
prevent ventricular arrhythmias, which
can follow infarction. Ventricular arrhyth-
mias include ventricular tachycardia and
ventricular fibrillation, which are com-
monly associated with infarction or with
the scarring of the heart muscle, which
occurrs during the event.
Tea drinkers have been known to have a
lower rate of death following a heart attack
than those who do not drink tea. A team
from the University of Heidelberg sought
to find out why. By studying frog egg cells,
Kelemen et al17 found that EGCG inhib-
ited human-ether-a-gogo related gene po-
tassium channels, which are involved in
cardiac repolarization. The human-ether-
a-gogo related gene potassium channel is
present in long QT syndrome, a cardiac
electrical disorder that can be inherited or
caused by taking certain medications. In-
dividuals with the disorder are susceptible
to ventricular fibrillation. Human-ether-a-
gogo related gene potassium channels are
also over expressed in extracardiac tumors.
CANCER
The cancer-protective effects of green tea
have been reported in several population-
based studies. For example, cancer rates
tend to be low in countries such as Japan
where green tea is regularly consumed. It is
not possible to determine from these pop-
ulation-based studies whether green tea ac-
tually prevents cancer in people. How-
ever, emerging animal and clinical studies
are beginning to suggest that EGCG may
play an important role in the prevention
of cancer.
It has been suggested that EGCG and
other tea catechins suppress tumor pro-
Diet and Nutrition
motion by inhibiting the release of tumor
necrosis factor-alpha, which is believed to
stimulate tumor promotion and progres-
sion of initiated cells as well as premalig-
nant cells.18
Furthermore, EGCG was shown to re-
duce specific binding of both the 12-Otet-
radecanoylphorbol-13-acetate (TPA)-type
and the okadaic acid-type tumor promot-
ers (the two major classes of tumor-pro-
moting agents) to their receptors. This
“sealing” effect of EGCG is achieved by its
interaction with the phospholipid bilayer
of the cell membrane.19,20
When non-Hodgkin’s lymphoma cells
were transplanted into mice, green tea pre-
vented 50% of the tumors from taking
hold and significantly inhibited growth of
the tumors.21
BLADDER CANCER
A few studies have examined the relation-
ship between bladder cancer and green tea
consumption. In one study that compared
people with and without bladder cancer,
researchers found that women who drank
black tea and powdered green tea were less
likely to develop bladder cancer.22
Epigallocatechin gallate inhibited
growth of the NBT-II bladder tumor cells
in a dose- and time-dependent manner.
Flow cytometry showed a G0/G1 arrest in
cells when cultured with EGCG at doses
of 10, 20, or 40 ␮mol/L for 48 or 72 hours.
The apoptotic DNA ladder test showed
that EGCG at 10 ␮mol/L induced early
apoptosis after 48 hours of incubation. A
down-regulation of cyclin D1 was de-
tected by reverse transcription polymerase
chain reaction when the cells were incu-
bated with EGCG (20 ␮mol/L for 48
hours. Epigallocatechin gallate also down-
regulated protein expression of cyclin D1,
cyclin-dependent kinase 4/6 and phos-
phorylated retinoblastoma protein, in
both a time- and dose-dependent manner,
when detected by Western blot.23
In the February 15, 2005 issue of Clini-
cal Cancer Research, Lu et al24 demon-
strated that green tea extract interrupts a
process that is crucial in allowing bladder
cancer to become invasive. According to
this study on human bladder cancer cell
lines, green tea extract affects actin remod-
eling, an event associated with cell move-
ment. For cancer to grow and spread, the
malignant cells must be able to move in
EXPLORE November/December 2006, Vol. 2, No. 6 533
order to invade other healthy cells and
eventually other organs. The cells rely on
actin remodeling, which is carefully regu-
lated by complex signaling pathways, in-
cluding the rho pathway. By inducing rho
signaling, green tea extract made the can-
cer cells more mature and made them
bind together more closely—a process
called cell adhesion. Both the maturity of
the cells and the adhesion inhibited the
mobility of the cancer cells.
BREAST CANCER
Epigallocatechin gallate, EGC, and ECG
reduce the proliferation of human breast
cancer cells in vitro and decrease breast
tumor growth in rodents. Furthermore, in
vitro studies have demonstrated that the
combination of EGCG and tamoxifen is
synergistically cytotoxic to ERalpha-
breast cancer cells. These results suggest
that the catechins have significant poten-
tial in the treatment of breast cancer.25
A Japanese study comparing 472
women with breast cancer who drank dif-
fering amounts of green tea indicates that
EGCG may decrease both the severity of
the initial diagnosis and the likelihood of
recurrence.26 Fujiki26 found that women
with Stage I, II, and III breast cancers who
drank five or more cups of green tea per
day were less likely to have cancer that
spread to the lymph nodes. In addition,
the greater consumption of green tea by
women with Stage I or II breast cancer was
associated with lower incidence of recur-
rence. No correlation was shown with
women who had Stage III cancers. An-
other Japanese study showed less overall
incidence of cancer among 8,000 people
who drank 10 or more cups of green tea a
day.
CERVICAL CANCER
Ahn et al27 investigated the anticancer ef-
fects of EGCG in human papillomavirus
(HPV)-16 associated cervical cancer cell
line, CaSki cells. The growth inhibitory
mechanisms and regulation of gene ex-
pression by EGCG were also evaluated.
Epigallocatechin gallate showed growth
inhibitory effects in CaSki cells in a dose-
dependent fashion, with an inhibitory
dose (ID)50 of approximately 35 ␮mol/L.
When CaSki cells were further tested for
EGCG-induced apoptosis, apoptotic cells
were significantly observed after 24 hours
at 100 ␮mol/L EGCG. In contrast, an in-
significant induction of apoptotic cells
was observed at 35 ␮mol/L EGCG. How-
ever, cell cycles at the G1 phase were ar-
rested at 35 ␮mol/L EGCG, suggesting
that cell cycle arrests might precede apo-
ptosis. When CaSki cells were tested for
their gene expression using 384 cDNA mi-
croarray, an alteration in the gene expres-
sion was observed by EGCG treatment.
Epigallocatechin gallate downregulated
the expression of 16 genes over time more
than twofold. In contrast, EGCG upregu-
lated the expression of four genes more
than twofold, suggesting a possible gene
regulatory role of EGCG. This data sup-
ports that EGCG can inhibit cervical can-
cer cell growth through induction of apo-
ptosis and cell cycle arrest as well as
regulation of gene expression in vitro. Fur-
thermore, in vivo antitumor effects of
EGCG were also observed. Thus, EGCG
likely provides an additional option for a
new and potential drug approach for cer-
vical cancer patients.
COLORECTAL CANCER
A study at the Linus Pauling Institute at
Oregon State University on mice that were
genetically predisposed to develop tumors
in their intestines, revealed after 12 weeks
of treatment that mice that were given
green tea had significantly fewer tumors
than mice that received no treatment.28
Phenol sulfotransferases are involved in
cancer growth, and EGCG was shown to
inhibit this activity in a human colon can-
cer cell line.29
ESOPHAGEAL CANCER
Studies in laboratory animals have found
that green tea polyphenols inhibit the
growth of esophageal cancer cells.30 How-
ever, results of studies in people have been
conflicting. In fact, some evidence sug-
gests the hotter the tea (or any other hot
beverage), the greater the risk of develop-
ing esophageal cancer. However, research-
ers reporting on a case-control study
found that Chinese men and women who
drink green tea have a reduced risk of up to
60% of developing esophageal cancer.31
Taking green tea extract removes any risk
associated with elevated temperature.
534 EXPLORE November/December 2006, Vol. 2, No. 6
LUNG CANCER
Consumption of green tea was found to
be associated with a reduced risk of lung
cancer among nonsmokers.32 Treatment
of human lung cancer cell line A549 cells
with EGCG significantly inhibited the ex-
pression levels of hnRNP B1 mRNA and
the elevated levels of hnRNP B1 protein,
both of which are elevated in cancer cells.
Furthermore, EGCG inhibited the pro-
moter activity of hnRNP A2/B1 gene ex-
pression, preventing lung cancer.33
OSTEOSARCOMA
Current treatment of osteosarcoma is as-
sociated with poor prognosis, especially
due to the increased risk of developing
other cancers with chemotherapy.
Roomi et al34 investigated the effect of a
unique mixture of nutrients containing
lysine, proline, arginine, ascorbic acid,
and EGCG on human osteosarcoma cell
lines U-2OS, MNNG-HOS, and Ewing’s
sarcoma SK-ES-1 by measuring cell pro-
liferation, expression of matrix metallo-
proteinase-2 (MMP-2), MMP-9, and in-
vasive and angiogenesis potential. The
invasion of osteosarcoma U-2OS and
MNNG-HOS cells through Matrigel was
significantly reduced in a dose-depen-
dent fashion, with 100% inhibition of
invasion of U-2OS cells at 100 ␮g/mL,
and MNNG cells at 50 ␮g/mL concen-
tration of the synergistically acting nu-
trient mixture. Ewing’s sarcoma SK-ES-1
cells were not invasive. The nutrient syn-
ergy exhibited a dose response antipro-
liferative effect on osteosarcoma U-2OS
cells, reaching 67% at 1000 ␮g/mL of
nutrient synergy; no significant suppres-
sion of cell proliferation was seen with
MNNG or Ewing’s sarcoma cells. Zy-
mography showed dose-dependent inhi-
bition of MMP secretion by all three cell
lines in the presence of nutrient synergy.
Vascular endothelial growth factor se-
cretion by U-2OS cells was completely
blocked at 500 microg/mL of nutrient
synergy. Nutrient synergy is an interest-
ing candidate for therapeutic use in the
treatment of osteosarcoma, by inhibit-
ing cancer cell invasion, and secretion of
MMPs and vascular endothelial growth
factor, all critical parameters for cancer
control and prevention.
PANCREATIC CANCER
Takada et al35 tested whether EGCG af-
fects proliferative and invasive activity of
human pancreatic carcinoma cells. The re-
sults indicate that the growth of all three
pancreatic carcinoma cells (PANC-1, MIA
PaCa-2 and BxPC-3) was significantly sup-
pressed by EGCG treatment in a dose-de-
pendent manner. Epigallocatechin gallate
may be a potent biologic inhibitor of pan-
creatic carcinoma, reducing their prolifer-
ative and invasive activity.
PROSTATE CANCER
The first strong evidence of green tea and
its potential towards prostate cancer ap-
peared when Paschka et al36 tested EGCG
on the prostate cancer cell lines LNCaP,
PC-3, and DU145. Epigallocatechin gal-
late proved to be the most potent catechin
at inhibiting cell growth. The inhibition
induced by EGCG was found to occur via
apoptotic cell death as shown by changes
in nuclear morphology and DNA frag-
mentation.
Epigallocatechin gallate acts against
urokinase (an enzyme often found in large
amounts in human cancers), inhibits orni-
thine decarboxylase (a rate-limiting en-
zyme closely associated with tumor pro-
motion), and blocks type 1 5-alpha
reductase (5AR).37 Inhibitors of 5AR may
be effective in the treatment of 5 alpha-
dihydrotestosterone– dependent abnor-
malities such as benign prostate hyperpla-
sia, prostate cancer, and certain skin
diseases.37
Urokinase breaks down the basement
membrane of cell junctions that may be a
key step in the process of tumor cell me-
tastasis as well as tumor growth. Epigallo-
catechin gallate attaches to urokinase and
prevents these actions.38
Epigallocatechin gallate was shown to
inhibit growth and induce regression of
human prostate and breast cancers in
athymic mice.39
SKIN CANCER
Studies suggest that EGCG and green tea
polyphenols have anti-inflammatory and
anticancer properties that may help pre-
vent the onset and growth of skin tumors.
Topical application of EGCG may pre-
vent UV-B–induced immunosuppression
and precancerous cell changes after UV-B
exposure.40
Diet and Nutrition
STOMACH CANCER
Laboratory studies have found that green
tea polyphenols inhibit the growth of
stomach cancer cells in test tubes. The ex-
posure of human stomach cancer KATO
III cells to EGCG led to both growth in-
hibition and the induction of apoptosis.41
LEUKEMIA
A study at the Mayo Clinic in 2003 by Lee et
al42 looked at the effects of EGCG on
chronic lymphocytic B cells isolated from
leukemia patients. In the study, Lee et al
showed that the addition of EGCG to these
cells reduced the vascular endothelial
growth factor-receptor phosphorylation.
This led to the disruption of the vascular
endothelial growth factor– dependent auto-
crine pathway that protects the cells from
apoptosis.
This provides strong evidence that this
inhibitory effect may have profound ef-
fects on tumors that depend on this cyto-
kine for progression. This data suggests
that green tea could be used in combina-
tion with other agents in addressing leuke-
mia.
HUMAN IMMUNODEFICIENCY
VIRUS
Epigallocatechin gallate prevents the
binding of HIV to human T cells, the first
step in HIV infection. Nance and
Shearer43 demonstrated that EGCG in-
hibited the binding of human immunode-
ficiency virus (HIV) to human CD4(⫹)
lymphocytes, which is a crucial step in
HIV infection. For infection to develop,
the viruses need entry into CD4(⫹) lym-
phocytes through a step dependent on ad-
hesion to the CD4 molecule and subse-
quent intracellular viral proliferation.
Epigallocatechin gallate showed a strong
affinity for CD4, and by binding them,
could effectively inhibit the binding of the
HIV envelope (gp120). This data opens
new perspectives for the treatment of this
life-threatening disease. Additional re-
search is necessary for the clinical applica-
tion of EGCG as an anti-HIV drug.
HOPE FOR HAIR LOSS?
An animal study by Esfandiari and
Kelley44 found that 33% of randomly as-
signed female BALB/black mice (60 in to-
Diet and Nutrition
tal), which had developed spontaneous
hair loss on the head, neck, and dorsal
areas, and who received green tea extract
in their drinking water, developed hair re-
growth within a period of six months. The
researchers did not observe any spontane-
ous remission or hair regrowth among the
controls. Moreover, 8% of the control ro-
dents showed progressive hair loss during
the study, whereas none of the mice who
received green tea extract showed any pro-
gressive hair loss.
The control rodents developed second-
ary infections resultant of their extensive,
progressive hair loss. Kelley concluded
that anti-inflammatory and stress inhibi-
tory effects of green tea polyphenols may
influence hair regrowth among mice. Fur-
ther studies are in progress to explore the
mechanisms and factors involved in hair
regrowth in association with the polyphe-
nols in green tea.
SKIN HEALTH
Research using pooled human keratino-
cytes (skin cells) to study the normal
growth of the skin cells alone and compar-
ing it to the growth of the cells when ex-
posed to EGCG revealed that EGCG reac-
tivated dying skin cells. Cells that migrate
toward the surface of the skin normally
live about 28 days, and by day 20, they sit
on the epidermis getting ready to die and
slough off. Current research seems to
show that EGCG reactivates epidermis
cells.45
ATHLETIC ENHANCEMENT
A study published in the American Journal
of Physiology. Regulatory, Integrative and
Comparative Physiology tested the effect of
green tea extract on exercise endurance of
lab rats. Over 10 weeks, endurance exer-
cise performance was boosted up to 24%
with green tea extract supplementation. It
is important to note that EGCG alone did
not have the same effect. A combination
extract containing EGCG plus naturally
occurring polyphenols improved endur-
ance. Additionally, evidence indicates
that the performance enhancement comes
from green tea polyphenols and not caf-
feine.46
JOINT HEALTH
Stimulation of human chondrocytes with
IL-1 beta (5 ng/mL) for 24 hours resulted
EXPLORE November/December 2006, Vol. 2, No. 6 535
in significantly enhanced production of
nitric oxide (NO) and prostaglandin E(2)
(PGE(2)) when compared to untreated
controls (P⬍ .001). Pretreament of human
chondrocytes with EGCG showed a dose-
dependent inhibition in the production of
NO and PGE(2) by 48% and 24%, respec-
tively, and correlated with the inhibition
of iNOS and COX-2 activities (P⬍ .005).
In addition, IL-1 beta–induced expression
of iNOS and COX-2 was also markedly
inhibited in human chondrocytes pre-
treated with EGCG (P⬍ .001). Parallel to
these findings, EGCG also inhibited the
IL-1 beta-induced LDH release in chon-
drocytes cultures. Overall, the study sug-
gests that EGCG affords protection
against IL-1 beta-induced production of
catabolic mediators NO and PGE(2) in
human chondrocytes by regulating the ex-
pression and catalytic activity of their re-
spective enzymes. The data indicates that
ECGC may be of potential therapeutic
value for inhibiting cartilage resorption in
arthritic joints.47
Some interesting research from Ad-
cocks et al48 shows that EGCG protects
cartilage destruction in test-tube models
of cartilage loss that mimic what happens
in the arthritic joint.
INFLAMMATORY BOWEL DISEASE
(IBD)
Green tea may help reduce inflammation
associated with Crohn’s disease and ulcer-
ative colitis.49 It was determined that
EGCG can inhibit proinflammatory inter-
leukin 8 (IL-8) in a study of human lung
alveolar epithelial cells (A549 line),50 do-
ing the same in the gastrointestinal tract
seemed possible.
After oral administration, EGCG is re-
tained in the gastrointestinal tract, where it
is thought to exert preventive functions
against inflammatory bowel disease and
colon cancer.51 Porath et al51 tested the
human colon adenocarcinoma cell lines
HT29 and T84 to investigate the effect of
EGCG on intestinal inflammation. HT29
and T84 cells were stimulated with tumor
necrosis factor (TNF)-␣ to induce the in-
flammatory condition and to trigger the
inflammatory cascade in vitro and treated
with EGCG to study its effect on inflam-
matory processes. Treatment of TNF-␣-
stimulated HT29 cells with EGCG dose
dependently inhibited the synthesis of
IL-8, MIP-3␣, and PGE2. Treatment with
EGCG also inhibited the production of
IL-8 and MIP-3␣ in TNF-␣–stimulated
T84 cells. Gene expression analysis in
both HT29 and T84 cells revealed that
EGCG downregulates genes involved in
inflammatory pathways. This study shows
that EGCG acts broadly on the produc-
tion of chemokines and PGE2 in the che-
mokine and eicosanoid pathways of colon
epithelial cells. Therefore, EGCG might
prove useful for the prevention and/or at-
tenuation of colonic disorders.
Green tea constituents have biological
activity in inhibiting PGE2 synthesis. Au-
gust et al52 measured the dose-related bio-
logical effects of administration of a single
dose of green tea on the rectal mucosa of
normal subjects. Baseline blood and rectal
biopsy samples were obtained before the
volunteers drank green tea solids dissolved
in warm water. Blood samples were taken
two, four, eight, and 24 hours after the tea
administration. Rectal biopsies were ob-
tained at four, eight, and 24 hours. Prosta-
glandin E2 (PGE2) levels were analyzed by
enzyme-linked immunosorbent assay. De-
creased levels of PGE2 in rectal mucosa
were observed at four and eight hours after
consumption of green tea. Ten of 14 sub-
jects demonstrated at least a 50% inhibi-
tion of PGE2 levels at four hours.
DIABETES
Green tea has been used traditionally to
control blood sugar in the body. Animal
studies suggest that green tea may help
prevent the development of type 1 diabe-
tes and slow the progression once it has
developed.53
EGCG has been found to increase insu-
lin sensitivity and may repair damaged
beta cells.54-56
High-performance liquid chromatogra-
phy fractionation of tea extracts utilizing a
Waters SymmetryPrep C18 column
showed that the majority of the insulin-
potentiating activity for green tea was due
to EGCG. Several known compounds
found in tea were shown to enhance insu-
lin with the greatest activity due to EGCG
followed by ECG, tannins, and theafla-
vins. Caffeine, catechin, and EC displayed
insignificant insulin-enhancing activities.
Addition of lemon to the tea did not affect
the insulin-potentiating activity. Addition
of five grams of two percent milk per cup
536 EXPLORE November/December 2006, Vol. 2, No. 6
decreased the insulin-potentiating activity
one third, and addition of 50 grams of
milk per cup decreased the insulin-poten-
tiating activity approximately 90%. Non-
dairy creamers and soy milk also decreased
the insulin-enhancing activity.56
LIVER DISEASE
Population-based studies have shown that
men who drink more than 10 cups of
green tea per day are less likely to develop
disorders of the liver. Green tea also ap-
pears to protect the liver from the damag-
ing effects of toxic substances such as al-
cohol. Animal studies have shown that
green tea helps protect against the devel-
opment of liver tumors in mice. Kuo and
Lin57 examined EGCG for its effect on
proliferation and cell cycle progression in
a human liver cancer cell line, Hep G2.
The results showed that EGCG inhibited
the proliferation of Hep G2 by inducing
apoptosis and blocking cell cycle progres-
sion in the G1 phase. Enzyme-linked im-
munosorbent assay showed that EGCG
significantly increased the expression of
p53 and p21/WAF1 protein, and this con-
tributed to cell cycle arrest.
NEUROPROTECTIVE PROPERTY
In the Journal of Neurochemistry, EGCG
protected lab mice from a neurotoxin (N-
methyl-4-phenyl-1,2,3,6-tetrahydropyri-
dine) in the mouse model of Parkinson’s
disease.
N-methyl-4-phenyl-1,2,3,6-tetrahydro-
pyridine neurotoxin caused dopamine
neuron loss in substantia nigra concomi-
tant with a depletion in striatal dopamine
and tyrosine hydroxylase protein levels.
Pretreatment of mice with EGCG pre-
vented these effects. In addition, EGCG
increased the activities of antioxidant en-
zymes in the brain. The researchers be-
lieve the neuroprotective effects are due to
EGCG’s ability to pass the blood brain
barrier and promote antioxidant manufac-
ture.58
Levites et al58 concluded that the brain
penetrating property of green tea polyphe-
nols, as well as their antioxidant and iron-
chelating properties may make green tea
compounds an important class of drugs to
be developed for treatment of neurode-
generative diseases where oxidative stress
has been implicated.
Green tea extract is able to induce spe-
cifically the neutral endopeptidase (NEP)
activity and to inhibit the proliferation of
SK-N-SH cells; the angiotensin-convert-
ing enzyme activity is not influenced un-
der the same conditions. The treatment of
the cells with arabinosylcytosine and
green tea extract results in a strong en-
hancement of cellular NEP activity,
whereas cellular angiotensin– converting
enzyme activity was not changed signifi-
cantly, indicating a green tea extract–spe-
cific regulation of NEP expression. Be-
cause of its role in the degradation of
amyloid beta peptides, this enzyme induc-
tion of NEP by long-term treatment with
green tea extract may have a beneficial ef-
fect regarding the prevention of forming
amyloid plaques.59
ANTIOXIDANT PROPERTIES
The early evidence of antioxidant proper-
ties of EGCG came from the experimental
data that showed EGCG induced inhibi-
tion of soybean lipoxygenase (IC50 ⫽
10-20 ␮mol/L).60 Later, it was reported
that EGCG inhibited TPA-induced oxida-
tive DNA base modification in HeLa cells,
inhibited Cu2⫹ mediated oxidation of
low-density lipoprotein (LDL), reduced
tert-butyl hydroperoxide-induced lipid
peroxidation, and blocked the production
of reactive oxygen species derived from
NADPH-cytochrome P450-mediated oxi-
dation of the cooked meat carcinogen,
2-amino-3methylimidazo[4,5-f]quino-
line.61 When using the oxygen radical ab-
sorbance capacity, green tea was found to
have a greater antioxidant activity than
Brussel sprouts, garlic, kale and spinach.62
CANDIDA ALBICANS
Martinez et al63 studied the effect of
EGCG on Candida albicans dihydrofolate
reductase. EGCG is an efficient inhibitor
of C albicans dihydrofolate reductase (K(i)
⫽ 0.7 ␮mol/L). Epigallocatechin gallate
showed synergy with inhibitors of the er-
gosterol biosynthesis pathway in C albi-
cans such as azole antifungals and terbin-
afine. Epigallocatechin gallate acts as an
antifolate compound on C albicans, dis-
turbing its folic acid metabolism. This ef-
fect could explain the molecular mecha-
nism for the synergy between EGCG and
azole antifungals and could represent a
Diet and Nutrition
starting point for therapies involving anti-
folates and azoles used as an alternative for
the treatment of C albicans infections.
WEIGHT LOSS
Studies suggest that EGCG may boost me-
tabolism and help burn fat. Dulloo et al64
showed that resting metabolic rate in-
creased by four percent after 90 mg of
EGCG was consumed three times per day
in human test subjects.
Westerterp-Plantenga et al65 concluded
that in habitual low-caffeine consumers, a
green tea-caffeine mixture improved
weight loss, partly through thermogenesis
and fat oxidation.
An animal study involving EGCG
caused rats to lose up to 21% of their body
weight. Rats injected with EGCG lost their
appetites and consumed up to 60% less
food after seven days of daily injections.
Epigallocatechin gallate seems to desensi-
tize leptin receptors (leptin may play a role
in appetite) in the study animals.66
IRON-OVERLOAD
Secondary iron overload is found in beta-
thalassemia patients because of increased
dietary iron absorption and multiple
blood transfusions. Excessive iron cata-
lyzes free-radical generation, leading to ox-
idative damage and vital organ dysfunc-
tion. Nontransferrin-bound iron detected
in thalassemic plasma is highly toxic and
chelatable. Though used to treat iron over-
load, desferrioxamine and deferiprone
also have adverse effects. The Fe(3⫹) was
found to bind to green tea crude extract
and form a complex. Green tea crude ex-
tract time- and dose-dependently de-
creased plasma nontransferrin-bound iron
concentration and counteracted the in-
crease of oxidative stress in both Fe(2⫹)-
EDTA-treated human plasma and eryth-
rocytes. Green tea could be relevant for
management of iron overload and oxida-
tive stress.67
CONTRAINDICATIONS
Green tea contains vitamin K and may in-
terfere with warfarin.68 However, that was
based on one individual consuming a gal-
lon of green tea daily while on the medi-
cation. Based on current literature, there
does not appear to be any significant side-
Diet and Nutrition
effects or toxicity associated with regular
green tea consumption.
Patients sensitive to caffeine should use
caffeine-free green tea or a caffeine-free ex-
tract.
CONCLUSION
Green tea, from capsules to tea bags, is
consumed throughout the world. The
years of safe consumption of this bever-
age, backed up by the numerous studies
showing health benefits, warrant a gen-
eral recommendation to consume it reg-
ularly. This abstract demonstrates by
documented studies the benefits of
green tea for its anti-inflammatory and
antioxidant potential. It has been used
to treat cardiovascular diseases, oral cav-
ity diseases, cardiovascular uses, and Par-
kinson’s disease. There is also a wide
range of uses for green tea in diabetes,
exercise enhancement, inflammatory
bowel disease, and skin disorders. Most
impressive are the well-controlled epide-
miologic studies, aimed at altering the
brain aging process, which can serve as
neuroprotective agents.
Although the human clinical data is still
limited, this abstract shows that green tea
has its place in both the conventional and
alternative medical communities.
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Robert L. Pastore, PhD, is Director of Clin-
ical Nutrition, Fratellone Medical Associates,
and a Certified Nutrition Specialist.
Patrick Fratellone, MD, is an attending phy-
sician at Beth Israel Medical Center, St Luke’s-
Roosevelt Hospital, New York City, NY and is
a graduate of the University of Arizona’s Pro-
gram in Integrative Medicine, Associate Fel-
lowship in Tucson, AZ.