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Review Article
Green Tea Catechins: Their Use in Treating and Preventing
Infectious Diseases
Wanda C. Reygaert
Biomedical Sciences Department, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA
Correspondence should be addressed to Wanda C. Reygaert; reygaert@oakland.edu
Received 20 March 2018; Accepted 10 June 2018; Published 17 July 2018
Academic Editor: Chedly Chouchani
Copyright © Wanda C. Reygaert. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Green tea is one of the most popular drinks consumed worldwide. Produced mainly in Asian countries from the leaves of the
Camellia sinensis plant, the potential health benets have been widely studied. Recently, researchers have studied the ability of
green tea to eradicate infectious agents and the ability to actually prevent infections. e important components in green tea that
show antimicrobial properties are the catechins. e four main catechins that occur in green tea are (-)-epicatechin (EC), (-)-
epicatechin--gallate (ECG), (-)-epigallocatechin (EGC), and (-)-epigallocatechin--gallate (EGCG). Of these catechins, EGCG
and EGC are found in the highest amounts in green tea and have been the subject of most of the studies. ese catechins have been
shown to demonstrate a variety of antimicrobial properties, both to organisms aected and in mechanisms used. Consumption of
green tea has been shown to distribute these compounds and/or their metabolites throughout the body, which allows for not only
the possibility of treatment of infections but also the prevention of infections.
1. Introduction
Infectious diseases are a leading cause of morbidity and mor-
tality worldwide. HIV/AIDS and malaria are among the top
teninfectiousdiseasesintheworld;andthemostcommon
types of infections are respiratory tract and diarrheal diseases
[]. With the advent of antimicrobial agents in the mid-s
came the hope that eradication of infectious diseases was
close. Unfortunately, the microorganisms involved were able
to become resistant to the antimicrobial agents, and that
only made it harder to ght these organisms. e CDC has
estimated that each year more than two million people in
the US suer from antibiotic-resistant infections and that as
many as , people die each year from these infections [].
is results in not only increased morbidity and mortality, but
also increased healthcare costs, which can be a huge nancial
burden for many countries. A recent analysis of the medical
costs from healthcare-associated infections (those infections
acquired in a healthcare facility) alone estimated that the
annual costs of these infections in the US are between and
billion dollars []. Antimicrobial resistance issues continue
to impact these costs. One study found that the cost of antimi-
crobial resistance associated illnesses in the US could be as
high as billion dollars ( billion dollars for healthcare
costs and billion dollars for lost productivity) annually [].
To help in the ght against infectious diseases, researchers are
looking at the possibilities of using natural plant products,
which could turn out to provide a tremendous cost savings
in healthcare. One of the plants that is currently being widely
studied is the tea plant, looking especially at green tea.
Tea is one of the most commonly consumed beverages in
the world, and green tea is becoming increasingly popular,
accounting for around % of total global tea production. Tea
is produced from the Camellia sinensis plant and is grown in
over countries. e best areas for growing tea plants are in
specic tropical and subtropical regions. ere are four main
tea types produced: white, green, Oolong, and black tea. e
type of tea is determined by how the tea leaves are processed,
specically by drying and fermentation methods. White tea
is processed the least and uses very young leaves and leaf
buds. Green tea is produced from more mature leaves with no
fermentation. Oolong tea is produced by partially fermenting
the leaves and black tea by fully fermenting the leaves [–].
Green tea is most commonly consumed in China, Japan, and
Korea. Black tea is most commonly consumed in the US and
the UK [].
Hindawi
BioMed Research International
Volume 2018, Article ID 9105261, 9 pages
https://doi.org/10.1155/2018/9105261
BioMed Research International
Green tea has been shown to have anticarcinogenic, anti-
inammatory, antimicrobial, and antioxidant properties and
is benecial in cardiovascular disease (CVD), diabetes and
obesity, and neurologic and oral health. e anticarcinogenic
properties include controlling cell proliferation, apoptosis
and angiogenesis in tumor cells [–]. Inammation is a
component of many conditions and diseases including aging,
arthritis, cancer, CVD, diabetes, and obesity. e general
anti-inammatory properties of green tea include the ability
to decrease the denaturation of proteins and increase the
production of anti-inammatory cytokines [, ]. Oxidative
stress results from the damaging eects of reactive oxy-
gen species (ROS). e antioxidant properties of green tea
include the ability to limit the amount of free radicals by
binding to ROS, upregulating basal levels of antioxidant
enzymes, and increasing the activity of these antioxidant
enzymes[,,].eeectsofgreenteaonCVDinclude
the anti-inammatory and antioxidant eects. In addition,
the consumption of green tea has been shown to inhibit
atherosclerosis, reduce total lipid levels, and improve the ratio
ofLDLtoHDL[,].Diabetesandobesityareclosely
associated with a spectrum of disorders known as metabolic
syndrome (MetS) which includes increased waist diameter,
elevated plasma triglycerides, decreased HDL, increased
fasting blood glucose, and elevated blood pressure [, ].
Type diabetes is also associated with insulin resistance and
sometimes decreased insulin production. Green tea has been
shown to increase insulin receptor sensitivity and stimulate
glucose-induced insulin secretion [, ]. Obesity is a result
of an increase in fat mass which is caused by increase in the
size of fat cells. Green tea has been shown to inhibit digestive
enzymes and absorption of fat, which leads to decreased
body waist circumference, intra-abdominal fat, plasma total
and LDL cholesterol, triglycerides, and blood pressure [–
]. e challenges of inammation and oxidative stress
can lead to DNA damage, protein misfolding, and loss of
ATP production in mitochondria. is can result in cell
death and loss of cognitive functions in the brain. e anti-
inammatory and antioxidant properties of green tea also
protect neurons, and green tea metabolites have been shown
to cross the blood brain barrier [–]. Green tea has
been shown to be antimicrobial against most oral bacteria.
In addition, it has been shown to improve oral health by
increasing the activity of oral peroxidases, preventing the
development and progression of periodontitis, and reducing
dentin erosion and tooth loss, and it has a role in improving
bad breath [–].
2. Green Tea Composition
e components in green tea that are the most medically
relevant are the polyphenols. e most pertinent polyphenols
are the avonoids; and the most pertinent avonoids are the
catechins. e catechins comprise -% of the avonoids
and around % of the water-soluble solids in green tea.
Green tea contains more catechins than the other teas, mainly
becauseofthewayitisprocessedaerharvesting.e
amount of catechins in green tea can also be aected by where
the tea is grown, the growth conditions, when it is harvested,
how the leaves are processed, and the brewing temperature
and length of time of brewing. ese factors lead to a huge
variation in catechin content among the varieties and brands
of green tea consumed [–].
e four main catechins found in green tea are
(-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-
epicatechin--gallate (ECG), and (-)-epigallocatechin--
gallate (EGCG). e most abundant catechin is EGCG
(∼%), and the next most abundant is EGC (∼%), then
ECG (∼%), and EC (∼%). EGCG is the most studied
in association with health, but EGC and ECG have been
studiedaswell.Asmentionedabove,therecanbeawide
variation in the amount of catechins in any particular green
tea beverage, although standardized extracts are available for
use as supplements [, , ].
In order to be eective in the body these catechins need
to be bioavailable aer consumption. Once in the body, the
catechins undergo metabolic processing in the liver and small
intestine and colon. is processing produces glucuronide
and sulfate conjugates or methyl epicatechins. Native forms
of ECG and EGCG and metabolites of EC and EGC can be
detected and measured in blood plasma. No forms of ECG
and EGCG can be detected in urine, only metabolites of EC
and EGC [, ]. Catechins are generally most stable in
solutionatapHrangeof-.Itisnowknownthathuman
serum albumin acts as a stabilizer, binding to the catechins
and then transporting them []. Various studies in humans
have found that the peak concentrations of catechins and
their metabolites occur in blood plasma between . and
hours aer ingestion and in urine between and hours aer
ingestion. e levels of these peak concentrations are aected
by an individual’s metabolism and of course by the amount
of catechins in the ingested type of green tea. Commonly,
the levels found in the body are directly proportional to the
amount of catechins consumed [–]. Tables and show
examples of blood plasma and urine concentration studies in
humans.
3. Antimicrobial Properties
e antimicrobial eects of green tea catechins (GTCs) on
microorganisms have been studied for many years. Green
tea has been shown to combat these organisms in various
ways, directly and indirectly, and has been shown to work
synergistically with some antibiotic agents. Other known
health benets of green tea such as the anti-inammatory and
antioxidant eects may also contribute to the antimicrobial
eects. Studies conducted on Escherichia coli found that
exposure to green tea polyphenols (GTPs) resulted in major
gene expression changes for genes, with upregulation
occurring in nine genes and downregulation in eight genes
[–]. Table shows a summar y of the antimicrobial eects
of green tea on bacteria.
4. Effects on the Bacteria Cell Membrane
OneofthemajorpropertiesofGTCsistheabilitytobindto
bacterial cell membranes. is binding can lead to interfer-
ence in various bacterial processes and can damage the cell
BioMed Research International
T : Amount of EGCG in blood plasma aer a single dose.
EGCG dose (mg) Cmax (ng/ml) Reference
. []
.
.
.
. []
.
[]
. []
[]
. []
.
.
.
.
.
. []
.
.
[]
T : Amount of EGC in -hour urine collection.
EGC dose (mg) Amount in hour urine (mg) Reference
. []
.
.
.
∼. []
. []
. []
∼. []
∼.
∼.
membrane resulting in increased permeability and leading to
cell lysis. Because EGCG is negatively charged it can combine
with the positively charged bacterial cell membrane, espe-
cially in gram positive bacteria. e lipopolysaccharide (LPS)
on the outer membrane of gram negative bacteria makes
them more resistant to binding by GTCs [, , , ].
Studies with E. coli and Pseudomonas aeruginosa have shown
that EGCG binding to the bacterial cell membrane can result
in generation of H2O2whichisinvolvedindamagetothe
cell membrane [, ]. Studies with Staphylococcus aureus
have shown that this assault on the cell membrane causes
a major cell wall stress response, resulting in upregulation
of peptidoglycan biosynthesis genes and an alteration in cell
wall structure. In methicillin-resistant Staphylococcus aureus
(MRSA) strains, this change in peptidoglycan biosynthesis
genes results in the production of PBP (penicillin-binding
protein ), which is what confers resistance to 𝛽-lactam
drugs. Production of PBP is also inhibited by EGCG [,
, ]. An important result of green tea binding is the loss of
bacterial ability to bind to host cells. Studies using human and
mammalian cells lines have shown that various bacteria such
as Fusobacterium nucleatum,Staphylococcus epidermidis,and
Helicobacter pylori have signicantly decreased adherence to
these cells [, , ]. Other important results are the loss
of the ability for quorum sensing and biolm formation of
P. a e r u g i n o s a ,F. n u cleat u m ,andStreptococcus mutans [,
,].Damagetothecellmembranealsoresultsinlossof
function to transmembrane transporter proteins which are
responsible for secretion of toxins and eux of substances
such as antimicrobial agents [, , , ].
5. Effects on Other Bacterial Cell Functions
ere are a wide variety of other eects that GTCs have on
bacterial functions. An important one which can aect most
bacteria is the ability of GTCs to inhibit bacterial fatty acid
biosynthesis by inhibiting enzymes involved in the biosyn-
thetic pathway. Because this is an essential pathway for most
bacteria, researchers are looking at targeting this pathway in
antimicrobial drug development. Fatty acids are important
forbuildingcellmembranes,asanenergysource,andare
involved in the production of toxic bacterial metabolites
[, ]. Another target is the folate biosynthesis pathway.
e enzyme dihydrofolate reductase (DHFR) is essential in
this pathway, and is known to be a target for certain sulfa
drugs. EGCG has also been shown to inhibit DHFR activity
[, ]. Other important eects against enzymes include
inhibition of bacterial DNA gyrase, inhibition of bacterial
ATP synthase activity, and inhibition of bacterial protein
tyrosine phosphatase and cysteine proteases [, , ].
Some specic bacterial eects include reducing bacterial H2S
production and inhibiting hemolytic activity of F. nucl e a t u m,
inhibiting the ability of Listeria monocytogenes to escape
from the macrophage phagosome by inhibiting activity of
listeriolysin O, and inhibiting the ability of E. coli to transfer
plasmid content via conjugation [, , ].
6. Synergism
SinceGTCsareknowntohaveantimicrobialaction,
researchers have begun assessing the potential synergism
of these catechins with other known antimicrobial agents.
Green tea catechins have now been shown to act in
synergy with imipenem against MRSA; with metronida-
zole against Porphyromonas gingivalis;withazithromycin,
cefepime, ciprooxacin, chloramphenicol, doxycycline, ery-
thromycin, nalidixic acid, piperacillin, or tobramycin against
E. coli; with ampicillin, Cefalotin, doxycycline, erythromycin,
penicillin, or tetracycline against Enterobacter aerogenes;
with chloramphenicol or tetracycline against Pseudomonas
aeruginosa; and with aztreonam, ceazidime, ciprooxacin,
gentamicin, meropenem, or tetracycline against Acinetobac-
ter baumannii. e ability of GTCs to inhibit the function of
BioMed Research International
T : Antimicrobial eects of green tea catechins.
Organism Eects References
Cell Membrane Binding to bacterial cell membrane [–]
Associated Eects Damaging bacterial cell membrane []
Inhibits ability of bacteria to bind to host cells [, ]
Inhibits ability of bacteria to form biolms [, , ]
Disrupts bacterial quorum sensing []
Interferes with bacterial membrane transporters [, , ]
Bacterial Cell Functions Inhibits bacterial DNA gyrase []
Eects Reduces bacterial H2S production []
Inhibits bacterial hemolytic action [, ]
Inhibition of bacterial DHFR enzyme []
Inhibits bacterial fatty acid synthesis enzymes []
Increases bacterial internal ROS levels []
T : Synergism of green tea with antimicrobial agents.
Antimicrobial Action Drug Synergism
Inhibit Cell Wall Synthesis ampicillin
ampicillin/sulbactam
amoxicillin
aztreonam
cefalotin
cefepime
cefotaxime
ceazidime
imipenem
meropenem
oxacillin
penicillin
piperacillin
Inhibit Protein Synthesis amikacin
azithromycin
chloramphenicol
doxycycline
erythromycin
gentamicin
tetracycline
tobramycin
Inhibit Nucleic Acid Synthesis ciprooxacin
levooxacin
metronidazole
nalidixic acid
bacterial eux pumps (as mentioned previously) also plays
a role in at least an additive antimicrobial eect for GTCs
and many antimicrobial drugs, especially in gram negative
bacteria that possess RND-type eux pumps [, , ,
–]. Table lists antimicrobial agents that have shown
synergy with GTCs and the targets of these drugs.
7. Effects on Other Microorganisms
Green tea catechins have also been shown to be eective
against a number of viruses, parasites, fungi, and even prions.
e main antiviral eects include inhibiting the virus from
binding to and entering host cells (adenovirus, enterovirus,
H B V, H C V, H I V, H S V, i n u e n z a , a n d r o t a v i r u s ) ; i n h i b i t i n g
viral RNA and DNA synthesis and viral gene transcription
(enterovirus, EBV, HBV, HCV, and HIV); and destroying
and functionally altering various viral molecules (adenovirus,
HSV, and inuenza) [, –]. Studies performed with
adult healthcare workers to determine if green tea supple-
mentscouldpreventinfectionwithvirusescausinginuenza
showed signicantly fewer instances of inuenza symptoms
and a reduced incidence of laboratory-conrmed inuenza
cases versus the control group [].
e main eect of GTCs on various parasite infections
isadecreaseinparasitenumbersandgrowth.Othereects
noted were fragmentation of parasite DNA and reduced fatty
acid synthesis in the parasites. Studies with parasites include
Plasmodium falciparum,Babesia spp., Try p anosom a b r u cei,
Trypano s o ma cruzi,andLeishmania braziliensis [–].
Fungi that have been aected by GTCs include Aspergillus
niger,Candida spp., Penicillium sp., Microsporum canis,
Trichophyton mentagrophytes,andTrichophyton rubrum.
Research testing for synergistic eects found that EGCG
showed synergism with amphotericin B, uconazole, and
miconazole in Candida spp.; and in Candida tropicalis strains
that were resistant to uconazole, EGCG, and uconazole
together induced apoptosis in the yeast cells [, –].
Prions are proteins that are considered to be infective
agents because the abnormally structured (𝛽-sheet) forms are
able to induce normally structured (𝛼-helix) forms to change
shape. In the abnormal shape, protein function is lost and
protein aggregation occurs in cells. Unlike other infectious
agents, prions cannot be destroyed using autoclaving; the
proteins have to be degraded to be noninfectious. Research
using yeast cells found that EGCG could inhibit the 𝛽-sheet
prions from changing the 𝛼-helical forms and could induce
reversal of the 𝛽-sheet forms back to 𝛼-helical forms [].
BioMed Research International
8. Antimicrobial Scope
ere is a large amount of research that has assessed the
antimicrobial eects of green tea catechins on a wide variety
of microorganisms, including many gram negative and gram
positive bacteria, some viruses, fungi, and prions. One of the
most clinically important bacteria that has been researched is
S. aureus, especially MRSA strains. e most studied gram
negative bacteria is E. coli which is known for causing the
majority of urinary tract infections. ere are several recently
published manuscripts that contain extensive information on
which organisms are aected by green tea catechins [, ,
, ].
9. Prevention of Infection
SinceithasbeenshownthatGTCshavemultipletypesof
antimicrobial abilities against so many organisms, it would
be expected that green tea catechins could also prevent
infections. One study was mentioned previously describing
how green tea reduced the number of colds and inuenza
incidents. Another study involving adults showed that con-
suming green tea supplements twice daily for months
resulted in % fewer instances of cold or inuenza symptoms
andnearly%fewerillnessesoformoredaysduration
[]. A study involving children found that, in school-
aged children who consumed green tea on a regular basis,
the number of incidents of inuenza A or B was inversely
associatedwiththenumberofcupsofgreenteaconsumed
per day or per week []. Another study with Japanese nursey
school children who gargled with green tea (or placebos) at
least once each day found that there were up to times fewer
instances of illnesses with fevers in the green tea gargling
group []. Two other studies with adults found that gargling
with a green tea extract (GTE) solution resulted in at least
half as many cases of inuenza in the GTE gargling groups
compared with the control groups [, ].
10. Conclusions
e research into the eects of green tea on human health
hasshownthatitcanbeanimportantdietaryfactorin
the prevention and treatment of various diseases such as
arthritis,cancer,CVD,diabetesandobesity,infections,andin
neurologic and oral health. Studies that were originally per-
formedinanimalsandcelllineshavebecomemorefrequently
performed using humans. is type of research is vital if we
are to fully discover what benets GTCs can have in health
issues. e more researchers that become involved in this,
the clearer the answers. e studies on antimicrobial eects
are providing very promising data, especially if GTCs prove
to have synergistic abilities with many of the currently used
antimicrobial agents and perhaps with drugs used to treat
other diseases. e emergence of various multidrug-resistant
bacteria, along with a dearth of eective antimicrobial drugs,
makes the potential of green tea an extremely timely issue.
erearealsomanyareasacrosstheglobewherethecostof
drugs is currently beyond the earning power of most of the
population. Green tea is relatively inexpensive and fairly easy
to obtain for most people. It could prove to be an answer for
improving health on a global scale.
Conflicts of Interest
e author declares that there are no conicts of interest
regarding the publication of this paper.
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