Beneficial Effects of Green Tea—A Review - Anabolic Laboratories

21 Pages·2006·0.33 MB·English

Review
Beneficial Effects of Green Tea—A Review
CarmenCabrera,PhD,ReyesArtacho,PhD,RafaelGime´nez,PhD
DepartamentodeNutricio´nyBromatolog´ıa,FacultaddeFarmacia,UniversidaddeGranada,Granada,SPAIN
Keywords:greentea,polyphenols,catechins,antioxidantactivity,humanhealth
Teaisthemostconsumeddrinkintheworldafterwater.Greenteaisa‘non-fermented’tea,andcontains
morecatechins,thanblackteaoroolongtea.Catechinsareinvitroandinvivostrongantioxidants.Inaddition,
itscontentofcertainmineralsandvitaminsincreasestheantioxidantpotentialofthistypeoftea.Sinceancient
times,greenteahasbeenconsideredbythetraditionalChinesemedicineasahealthfulbeverage.Recenthuman
studiessuggestthatgreenteamaycontributetoareductionintheriskofcardiovasculardiseaseandsomeforms
ofcancer,aswellastothepromotionoforalhealthandotherphysiologicalfunctionssuchasanti-hypertensive
effect, body weight control, antibacterial and antivirasic activity, solar ultraviolet protection, bone mineral
densityincrease,anti-fibroticproperties,andneuroprotectivepower.Increasinginterestinitshealthbenefitshas
ledtotheinclusionofgreenteainthegroupofbeverageswithfunctionalproperties.However,althoughallthe
evidence from research on green tea is very promising, future studies are necessary to fully understand its
contributions to human health, and advise its regular consumption in Western diets, in which green tea
consumptionisnowadayslimitedandsporadic.
Keyteachingpoints:
(cid:127) Greenteacontainsnumerouscomponentswithantioxidantactivity:polyphenols(especiallycatechins),minerals,vitamins.
(cid:127) Greenteacontainsmorecatechinsthanblackoroolongteas.
(cid:127) Thestrongantioxidantpotentialofcatechins,andespeciallyEGCG,arewidelydemonstratedinvitroandinanimalstudies.In
addition,catechinspossessantimutagenic,antidiabetic,anti-inflammatory,antibacterialandantiviralproperties.
(cid:127) Recenthumanstudiessuggestthatgreenteamaycontributetoreducetheriskofcardiovasculardiseaseandcancer,andhasanother
beneficialeffectonhealth.
(cid:127) Although research of green tea is very promising, future studies considering dietetic, environmental and life style factors, are
necessarytofullyunderstanditscontributiontohumanhealth.
INTRODUCTION Dependingonthemanufacturingprocess,teasareclassified
intothreemajortypes:‘non-fermented’greentea(producedby
Tea, a product made up from leaf and bud of the plant dryingandsteamingthefreshleavestoinactivatethepolyphe-
Camelliasinensis,isthesecondmostconsumedbeverageinthe noloxidaseandthus,nonoxidationoccurs);‘semi-fermented’
world, well ahead of coffee, beer, wine and carbonated soft oolongtea(producedwhenthefreshleavesaresubjectedtoa
drinks [1–2]. Originating from China, tea has gained the partial fermentation stage before drying); and ‘fermented’
world’stasteinthepast2000years.Theeconomicandsocial black and red (Pu-Erh) teas which undergo a post-harvest
interest of tea is clear and its consumption is part of many fermentation stage before drying and steaming, although the
peopledailyroutine,asaneverydaydrinkandasatherapeutic fermentation of black tea is due to an oxidation catalyzed by
aidinmanyillnesses. polyphenoloxidase,andthatofPu-Erhteaisattainedbyusing
Addressreprintrequeststo:CarmenCabrera,PhD,Dpto.Nutricio´nyBromatolog´ıa,FacultaddeFarmacia,CampusUniversitariodeCartuja,18012-Granada,SPAIN.
E-mail:[email protected].
Abbreviations:CI(cid:1)confidenceinterval,DNA(cid:1)deoxyribonucleicacid,DPPH(cid:1)2,2-diphenyl-l-picrylhydrazylassay,DMPD(cid:1)N,N-dimethyl-p-phenylendiamineassay,
EC(cid:1)((cid:2))-epicatechin,ECG(cid:1)((cid:2))-epicatechin-3-gallate,EGC(cid:1)((cid:2))-epigallocatechin,EGCG(cid:1)((cid:2))-epigallocatechin-3-gallate,FRAP(cid:1)ferricreducingabilityof
plasmaassay,GA(cid:1)gallicacid,GTP(cid:1)greenteapolyphenols,HDL(cid:1)highdensitylipoproteins,HR(cid:1)hazardratio,LDL(cid:1)lowdensitylipoproteins,OR(cid:1)oddratio,
ORAC(cid:1)oxygenradicalabsorbancecapacityassay,PCL(cid:1)photochemiluminescenceassay,RR(cid:1)relativerisk,TEAC(cid:1)Troloxequivalentantioxidantcapacityassay,
TRAP(cid:1)totalradical-trappingantioxidantparameterassay,UV(cid:1)ultraviolet.
JournaloftheAmericanCollegeofNutrition,Vol.25,No.2,79–99(2006)
PublishedbytheAmericanCollegeofNutrition
79
Green Tea: Beneficial Effects
microorganisms [3–4]. McKay and Blumberg [4] reported a rolling stage is very similar to the operation with the same
per capita mean consumption of tea in the world of 120 mL/ nameinblackteaproduction.Greenteaproductionisrestricted
day. Approximately 76–78% of the tea produced and con- mainly to China and Japan [3,6]. Fig. 1 shows the principal
sumed is black tea, 20–22% is green tea and less than 2% is differencesbetweengreenandblackteaprocessing.
oolong tea [5]. Black tea is consumed principally in Europe,
NorthAmericaandNorthAfrica(exceptMorocco)whilegreen
Green Tea Composition
tea is widely drunk in China, Japan, Korea and Morocco;
oolongteaispopularinChinaandTaiwan[5–6].InUSA,the Green tea chemical composition is complex: proteins (15–
80%ofteaconsumedisblackicetea[7]. 20%dryweight)whoseenzymesconstituteanimportantfrac-
Although health benefits have been attributed to green tea tion; aminoacids (1–4% dry weight) such as teanine or 5-N-
consumption since the beginning of its history, scientific in- ethylglutamine, glutamic acid, tryptophan, glycine, serine,
vestigations on this beverage and its constituents have been aspartic acid, tyrosine, valine, leucine, threonine, arginine, ly-
underway for less than three decades [4]. In vitro and animal sine;carbohydrates(5–7%dryweight)suchascellulose,pec-
studies, and clinical trials employing putative intermediary tins,glucose,fructose,sucrose;lipidsaslinoleicand(cid:1)-linole-
indicatorsofdisease,particularlybiomarkersofoxidativestress nic acids; sterols as stigmasterol; vitamins (B, C, E); xanthic
status, provide strong evidence that green tea polyphenols bases such as caffeine and theophylline (Fig. 2); pigments as
(GTP)mayplayaroleintheriskandpathogenesisofseveral chlorophyllandcarotenoids;volatilecompoundsasaldehydes,
chronicdiseases,especiallycardiovasculardiseaseandcancer, alcohols, esters, lactones, hydrocarbons, etc.; minerals and
and related pathologies. In addition, several studies suggest a trace elements (5% dry weight) such as Ca, Mg, Cr, Mn, Fe,
beneficialimpactofgreenteaintakeonbonedensity,cognitive Cu,Zn,Mo,Se,Na,P,Co,Sr,Ni,K,FandAl.Duetothegreat
function,dentalcariesandkidneystones,amongothereffects importance of the mineral presence in tea, many studies have
[4–5].Overthelastyears,numerousepidemiologicalandclin- been carried out to determine their levels in green tea leaves
ical studies have revealed several physiological responses to andtheirinfusions.Forexample,Costaetal.[1]observedlarge
greenteawhichmayberelevanttothepromotionofhealthand variationsofthemineralcontent(Al,Ca,MgandMn)ingreen
thepreventionortreatmentofsomechronicdiseases.However, teafromdifferentorigins.Ferna´ndez-Ca´ceresetal.[10]deter-
the results from epidemiological and clinical studies of the minedthecontentofAl,Ba,Ca,Cu,Fe,K,Mg,Mn,Na,Sr,Ti,
relationshipbetweengreenteaconsumptionandhumanhealth andZnin46teasamples,andnocleardifferenceswerefound
are mixed. For example, conflicting results between human betweenmineralcontentofgreenandblackteas.Shuetal.[11]
studies may arise in part, from ignoring socioeconomic and observed the great variations among different tea varieties in
lifestylefactorsaswellasbyinadequatemethodologytodefine accumulatingfluorideandaluminum.Fungetal.[12]indicated
teapreparationandintake[2,4–7]. that black tea had higher Al and F concentrations than green
Foodstuffcanberegardedasfunctionalifitissatisfactorily tea.Xuetal.[13]reportedthatthecontentofSeingreenteas
demonstratedtoaffectbeneficiallyoneormoretargetfunctions wasgreatlyincreasedbyfoliarapplicationofSe-enrichedfer-
inthebody,beyondadequatenutritionaleffectsinawaywhich tilizers; moreover, the selenium-enriched green tea exhibited
is relevant to either the state of well-being and health or the significantlyhigherantioxidantactivitythanregulargreentea.
reductionoftheriskofadisease[5,8–9],sogreenteahasbeen Table 1 summarizes the mean chemical composition of green
proved to have functional properties and at present, its con- tealeavesincomparisonwithblacktealeavesanditsinfusion.
sumptioniswidelyrecommended. Polyphenols constitute the most interesting group of green
Theaimofthisarticleistorevisethemostrecentstudieson tea leaf components, and in consequence, green tea can be
greenteabeneficialeffectsandtoevaluateitspotentialinterest consideredanimportantdietarysourceofpolyphenols,partic-
inWesterndiets. ularly flavonoids. Flavonoids are phenol derivatives synthe-
sizedinsubstantialamounts(0.5–1.5%)andvariety(morethan
4000identified),andwidelydistributedamongplants[14].The
Green Tea Processing
UnitedStatesDepartmentofAgriculture(USDA)hasrecently
Green tea is mainly produced from Camellia sinensis var. published a Database for the Flavonoid Content of Selected
sinensis.TheAssantype(Camelliasinensisvar.assamica)has Foods [15]. The main flavonoids present in green tea include
atoohighcontentofpolyphenols,whichwouldmakegreentea catechins (flavan-3-ols). The four major catechins are ((cid:2))-
taste excessively bitter [3]. The production of green tea is epigallocatechin-3-gallate (EGCG), that represents approxi-
characterized by an initial heating process, which kills the mately 59% of the total of catechins; ((cid:2))-epigallocatechin
enzymepolyphenoloxidase,whichisresponsibleforthecon- (EGC)(19%approximately);((cid:2))-epicatechin-3-gallate(ECG)
version of the flavanols in the leaf into the dark polyphenolic (13.6% approximately); and ((cid:2))-epicatechin (EC) (6.4% ap-
compoundsthatcolourblacktea.Theotherimportantprocess proximately)[4].Greenteaalsocontainsgallicacid(GA)and
isrolling,inwhichleavesarecutandtwisted.Thefinalformof otherphenolicacidssuchaschlorogenicacidandcaffeicacid,
greenteadependsontheparticularvariantbeingproduced.The andflavonolssuchaskaempferol,myricetinandquercetin[15].
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Green Tea: Beneficial Effects
Fig.1.Principaldifferencesbetweengreenandblackteaprocessinganditsinfluenceonthefinalpolyphenolscontent.
Table1.MeanComposition(%)ofGreenTeaandBlack
Tea(andItsInfusion).FromBelitzandGrosh[167]
Compound Greentea* Blacktea* Infusion†
Proteins 15 15 trace
Aminoacids 4 4 3.5
Fibre 26 26 0
Otherscarbohydrates 7 7 4
Fig.2.Chemicalstructureofcaffeineandtheophylline.
Lipids 7 7 trace
Pigments 2 2 trace
Minerals 5 5 4.5
Fig. 3 shows the chemical structure of GA and the four Phenoliccompounds‡ 30 5 4.5
major catechins present in green tea. In black tea the poly- Oxidisedphenoliccompounds§ 0 25 4.5
merized catechins such as theaflavins and thearubigins pre- *Datarefereedtodryweightoftealeaves.
dominate.Blackandgreenteasbothcontainsimilaramount †Blacktea;infusiontime:3min.
‡Especiallyflavonoids.
of flavonoids, however they differ in their chemical struc-
§Especiallythearubiginsandtheaflavins.
ture;greenteacontainsmorecatechins(simpleflavonoids),
whiletheoxidationundergonebytheleavesinordertomake
black tea, converts these simple flavonoids into theaflavins changesandthusmodifyingitsproperties.Otherfactorsinflu-
and thearubigins [15]. encing catechin content are the geographical location and
Therelativecatechincontentofgreenteadependsonhow growingconditions(soil,climate,agriculturalpractices,fertil-
the leaves are processed before drying (a certain grade of izers), the type of green tea (e.g., blended, decaffeinated, in-
fermentationandheatingoftealeavesduringthemanufactur- stant,...),andthepreparationoftheinfusion(e.g.,amountof
ingprocesscanresultinpolymerizationofmonopolyphenolic the product used, brew time, temperature) [5,16]. McKay and
compounds such as the catechins, leading to conformational Blumberg [5] reported that decaffeinating reduces slightly the
JOURNALOFTHEAMERICANCOLLEGEOFNUTRITION 81
Green Tea: Beneficial Effects
Fig.3.Chemicalstructureofgallicacidandthefourmajorcatechinsingreentea.GA,gallicacid;EGCG,((cid:2))-epigallocatechin-3-gallate;EGC,
((cid:2))-epigallocatechin;ECG,((cid:2))-epicatechin-3-gallate;EC,((cid:2))-epicatechin.
tea catechin content; also, instant preparations and iced and Bioavailability of Green Tea Catechins
ready-to drink teas present less content of catequins [16–17].
Thepotentialhealtheffectsofcatechinsdependnotonlyon
Theproductionofbottledgreenteabeveragehasencountered
the amount consumed but on their bioavailability which ap-
a browning problem mainly caused by the oxidation of cat-
pears to be very variable. In order to know the catechin bio-
echins[18].
availability and metabolism, it is necessary to evaluate their
WuandWei[5]indicatedthatacupofgreentea(2.5gof
biological activity within target tissues [24]. Following oral
green tea leaves/200 mL of water) may contain 90 mg of
administration of tea catechins to rats, the four principal cat-
EGCG. Lin et al. [19] analyzed 31 commercial teas, and
echins(EC,ECG,EGC,andEGCG)havebeenidentifiedinthe
detectedthatthelevelsofEGCGandtotalcatechinswereinthe
portal vein, indicating that tea catechins are absorbed intesti-
following order: green tea (old leaves) (cid:3) green tea (young
nally[25].Inratsgiven0.6%GTPintheirdrinkingwaterover
leaves)andoolongtea(cid:3)blackteaandPu-Erhtea.Ferna´ndez
a period of 28 days, plasma concentrations of EGCG were
et al. [20] determined the contents of GA, EGCG, EGC, EC
muchlowerthanthoseofEGCorEC,eventhoughtheratioof
andECG,inasetof45teasamples,includingblackandgreen
EGCG to EGC was 5:1 in the GTP solution. When the same
teas from different geographical origins (i.e. China, Japan,
GTP preparation was given to mice, plasma levels of EGCG
Kenya, Sri Lanka, and India); the GA levels were always
weremuchhigherthanthoseofEGCandEC.So,thereappear
higherinblackteabecausetheamountofGAincreasesduring
tobespeciesdifferencesinthebioavailabilityofEGCGcom-
the fermentation process due to its liberation from catechin
pared to the other catechins [26]. In humans, EGCG may be
gallates [21]. The amount of catechins were always higher in lessbioavailablethanothergreenteacatechins.Catechinlevels
green tea; EGCG and EGC were the major catechins present inhumanplasmareachtheirpeak2to4hafteringestion[27].
with average contents of 7.358% and 3.955%, respectively; A recent study in humans compared the pharmacokinetics of
ECGpresentedvaluesrangingbetween0.910and3.556%.For equimolardosesofpureEGC,ECG,andEGCGin10healthy
blacktea,EGCGandECGwerethecatechinspresentinhigher volunteers; average peak plasma concentrations after a single
percentages, with average contents of 1.583 and 0.706%, re- dose of 1.5 mmol were 5.0 (cid:2)mol/L for EGC, 3.1 (cid:2)mol/L for
spectively.Cabreraetal.[22]reportedthemeancontentofthe ECG,and1.3(cid:2)mol/LforEGCG.After24h,plasmaEGCand
four major catechins (EGCG, EGC, ECG and EC) and gallic EGCGreturnedtobaseline,butplasmaECGremainedelevated
acidin45samplesofdifferenttypesofteaincludingblack,red, [28]. In humans, ECG has been found to be more highly
oolongandgreenteas;thehigherlevelsofEGCGappearedin methylatedthanEGCandEGCG,andEGCGhasbeenfoundto
greenteasamples.ResultsaresummarizedinFig.4.However, belessconjugatedthanEGCandEC[29].Unfortunately,little
Henning et al. [23] suggested that the large variation of the publisheddataareavailableontissuedistributionofcatechins
catechincontentinteaisnottakenintoconsiderationinmostof in humans after green tea consumption; however, there are
theepidemiologicalstudies. someinterestingdatafromstudieswithanimals.Kimetal.[26]
82 VOL.25,NO.2
Green Tea: Beneficial Effects
Fig.4.Meancontentofgallicacidandcatechinsindifferenttypesoftea(n(cid:1)45).Datarefereedtodryweightofcommercialsamples(Source:
Cabreraetal.[22]).
observedthatwhenratsweregiven0.6%GTPintheirdrinking polyphenol metabolism [31]. The effect of green tea drinking
wateroveraperiodof28days,substantialamountsofEGCand mayalsodifferbygenotype[32].Tosumup,thereappeartobe
ECwerefoundintheesophagus,largeintestine,kidney,blad- speciesdifferencesinthebioavailabilityofEGCGcomparedto
der, lung, and prostate; EGC and EC concentrations were otherteacatechins.Furtherresearchresultsarelargelyconsis-
relativelylowinliver,spleen,heart,andthyroid;EGCGlevels tentindemonstratingthattheadditionofmilktoteadoesnot
werehigherintheesophagusandlargeintestine,butlowerin interferewithcatechinabsorption[33–35],butmilkmayaffect
otherorgans,likelyduetopoorsystemicabsorptionofEGCG. the antioxidant potential of tea, depending upon milk fat con-
Catechins are rapidly and extensively metabolized; studies in tent, milk volume added, and the method used to assess this
rats indicated that EGCG is mainly excreted through the bile, parameter[33–36].Xuetal.[37]observedthattheepimerisa-
whileEGCandECareexcretedthroughurineandbile.Deter- tionreactionoccurringinmanufacturingcannedandbottledtea
mination of the actual bioavailability of metabolites in tissues drinks would not significantly affect antioxidant activity and
maybemuchmoreimportantthanknowledgeoftheirplasma bioavailabilityoftotalteapolyphenols.
concentration, but data are still very scarce even in animals.
Consequently,themetabolismandbioavailabilityofindividual
Green Tea and Human Health
tea catechins and the pharmacokinetics of their metabolites
requirefurtherclarification. Green tea has been considered a medicine and a healthful
Lu et al. [30] reported that GTP have biological activities beveragesinceancienttimes.ThetraditionalChinesemedicine
including modulation of key signal transduction pathways; has recommended this plant for headaches, body aches and
however,thepossiblesignificanceoftheseactivitiesininhibi- pains,digestion,depression,detoxification,asanenergizerand,
tion of carcinogenesis in vivo depends on the polyphenol bio- ingeneral,toprolonglife.Greentealeavescontainthreemain
availability.Theseauthorsobservedthatafteroraladministra- componentswhichactuponhumanhealth:xanthicbases(caf-
tionofgreenteatorats,about14%ofEGC,31%ofEC,and feineandtheophylline),essentialoilsandespecially,polyphe-
(cid:4)1% of EGCG appeared in the blood; in mice, the bioavail- nolic compounds. Caffeine acts mainly upon the central ner-
abilityofEGCGwashigher,butthebiologicalactivitiesofthe vous system, stimulating wakefulness, facilitating ideas
catechinmetabolitesstillneedtobeinvestigated.Inter-individ- associationanddecreasingthesensationoffatigue[38].Some
ual variations in the bioavailability of GTP can be substantial oftheeffectscausedbycaffeineareinfluencedbytheophylline
and may be due, in part, to differences in colonic microflora teacontent.Theophyllineinducespsychoactiveactivity,italso
and genetic polymorphisms among the enzymes involved in has a slightly inotrope and vasodilator effect, and a much
JOURNALOFTHEAMERICANCOLLEGEOFNUTRITION 83
Green Tea: Beneficial Effects
higherdiureticeffectthancaffeine.However,itsmostinterest- proxylradicalsandinhibitinglipidperoxidation[49–50].How-
ingeffectscanbeseenatthebronchopulmonarandrespiratory ever,theantioxidantcapacityofcatechinsdeterminedinvitro
level. Theophylline causes a non-specific relaxation on the isdependentuponthetypeofassayemployedanditdoesnot
bronchial smooth muscle, and respiratory stimulation is also reflectfactorssuchasbioavailabilityandmetabolism.Thefact
observed. Essential oils are in a great extent volatile and they thatcatechinsarerapidlyandextensivelymetabolizedempha-
evaporatefromthebeverageaftersometime,thusitisnotvery sizestheimportanceofdemonstratingtheirantioxidantactivity
convenienttooverextendthebrewingtime.Amongtheirprop- invivotobetterrepresentthephysiologicalimpactofgreentea
erties, the one of facilitating digestion must be highlighted consumption. Frei and Higdon [51] reported that in order to
[5,39].Greenteaisthetypeofteawiththehigherpercentage determinewhetherornotGTPactaseffectiveantioxidantsin
of essential oils [38–39]. However, green tea has received a vivo, future studies in animals and humans should employ
greatdealofattentionespeciallyduetoitscontentofpolyphe- sensitiveandspecificbiomarkersofoxidativedamageoflipids,
nols,whicharestrongantioxidantsandpresentimportantbio- proteinsandDNA.
logical properties. Numerous studies have also demonstrated Nevertheless, a substantial number of human intervention
studies with green tea demonstrate a significant increase in
that the aqueous extract of GTP possesses antimutagenic, an-
plasma antioxidant capacity in humans after consumption of
tidiabetic,antibacterial,anti-inflammatory,andhypocholester-
moderateamounts(1–6cups/day);therearealsoinitialindica-
olemic properties [21,40–44]. Beneficial effects in oral dis-
tionswhichshowthattheenhancedbloodantioxidantpotential
eases such as protection against dental caries, periodontal
leadstoareducedoxidativedamageinmacromoleculessuchas
disease, and tooth loss (which may significantly affect a per-
DNA and lipids [2,4,23,28,37]. However, these authors indi-
son’s overall health) have been also described [5]. Among all
cated that the measurement of oxidative damage through bi-
GTP,catechinsandgallicacidhavebeenespeciallyconsidered
omarkersneedstobefurtherestablished.McKayandBlumberg
tobethemainplayersinthebeneficialeffectsonhumanhealth
[4] reported that the repeated consumption of green tea and
nextdetailed.
encapsulatedgreenteaextractsforonetofourweekshasbeen
Antioxidant Activity. Green tea is considered a dietary
demonstrated to decrease biomarkers of oxidative status. Fur-
sourceofantioxidantnutrients:greenteaisrichinpolyphenols
thermore,Klaunigetal.[52]observedinastudywith40male
(catechins and gallic acid, particularly), but it also contains
smokers in China and 27 men and women (smokers and non-
carotenoids, tocopherols, ascorbic acid (vitamin C), minerals
smokers) in the United States, that oxidative DNA damage,
such as Cr, Mn, Se or Zn, and certain phytochemical com-
lipid peroxidation, and free radical generation were reduced
pounds.ThesecompoundscouldincreasetheGTPantioxidant
after consuming (cid:5)6 cups/day of green tea for seven days.
potential.GTPpresentantioxidantactivityinvitrobyscaveng-
Therefore, GTP may contribute to defenses against oxidative
ingreactiveoxygenandnitrogenspeciesandchelatingredox-
damages [5]. Erba et al. [53] suggest the ability of green tea,
active transition metal ions; GTP can chelate metal ions like
consumedwithinabalancedcontrolleddiet,toimproveoverall
iron and copper to prevent their participation in Fenton and
theantioxidativestatusandtoprotectagainstoxidativedamage
Haber-Weiss reactions [4,45–46]. They may also function in-
inhumans.
directly as antioxidants through 1) inhibition of the redox-
Antimutagenic and Anticarcinogenic Potential. Life-
sensitive transcription factors; 2) inhibition of ‘pro-oxidant’
style-related diseases, including cancer, are also characterized
enzymes, such as inducible nitric oxide synthase, lipoxygen-
asaging-relateddiseases,whereagingmaybethemostpotent
ases, cyclooxygenases and xanthine oxidase; and 3) induction
causalfactor.Therefore,preventionoflifestyle-relateddiseases
ofantioxidantenzymes,suchasglutathione-S-transferasesand
will depend on slowing the aging process and avoiding the
superoxidedismutases.
clinical appearance the disease. Dietary components that are
The antioxidant capacity of GTP has been assessed by capableofretardingcellularagingandinhibitingthegrowthof
severalmethods.Forexample,Caoetal.[47]usingtheoxygen cancer cells without affecting the growth of normal cells are
radicalabsorbancecapacity(ORAC)assayfoundthatgreentea receiving considerable attention for the development of novel
hasamuchhigherantioxidantactivityagainstperoxylradicals cancer-preventiveapproaches[54–56].Theroleofgreenteain
than vegetables such as garlic, kale, spinach and Brussels protection against cancer has been supported by ample evi-
sprouts. Using the ferric reducing ability of plasma (FRAP) dence from studies in cell culture and animal models [54].
assay. Langley-Evans [48] found that the total antioxidant Animal studies have shown that green tea inhibit carcinogen-
capacity of green tea is more potent than that of black tea. esis of the skin, lung, oral cavity, esophagus, stomach, liver,
SaffariandSadrzadeh[49]investigatedtheantioxidantcapac- kidney,prostateandotherorgans[55,57–60].Insomestudies,
ityofEGCGusingerythrocytemembrane-bound.ATPasesas theinhibitioncorrelatedwithanincreaseintumorcellapopto-
a model, and the results indicated that EGCG is a powerful sisandadecreaseincellproliferation[56].Today,greenteais
antioxidantthatiscapableofprotectingerythrocytemembrane- accepted as a cancer preventive on the basis of numerous in
bound ATPases against oxidative stress. Several studies have vitro, in vivo and epidemiological studies. The Chemopreven-
shownthatEGCGcanactinvitroasanantioxidantbytrapping tionBranchoftheNationalCancerInstitutehasinitiatedaplan
84 VOL.25,NO.2
Green Tea: Beneficial Effects
for developing tea compounds as cancer-chemopreventive These authors suggested that dietary soy phytochemical con-
agents in human trials [61]. The chemopreventive effects of centrate plus green tea may be used as a potential effective
greenteadependon:(1)itsantioxidantaction;(2)thespecific dietary regimen for inhibiting progression of estrogen-depen-
inductionofdetoxifyingenzymes;(3)itsmolecularregulatory dentbreastcancer.
functions on cellular growth, development and apoptosis; and Zhangetal.[72]reportedthatovariancancerriskdeclined
(4) a selective improvement in the function of the intestinal withincreasingfrequencyanddurationofgreenteaconsump-
bacteria flora. D’Alessandro et al. [62] also indicated that an tion. Green tea is also an effective chemopreventive agent to
important aspect of cancer risk is related to inflammatory humanprostatecancer.Inthesamelineofresearch,Yuetal.
response;currently,anti-inflammatoryagentsareusedinche- [73] reported that EGCG inhibited the growth of prostate
mopreventive strategies. The inflammatory response involves cancer adenoma cells and induced apoptosis. Jian et al. [74]
theproductionofcytokinesandproinflammatoryoxidantssuch conductedacase-controlstudyinChinainordertoinvestigate
ashypochlorousacidandperoxynitriteproducedbyneutrophils whether green tea consumption has an etiological association
andmacrophages,respectively.Theseoxidantsreactwithphe- withprostatecancer.Prostatecancerriskdeclinedwithincreas-
nolic tyrosine residues on proteins to form chloro- and nitro- ingfrequency,durationandquantityofgreenteaconsumption.
tyrosine. Green tea catechins and soy isoflavones have also Thedose-responserelationshipswerealsosignificant,suggest-
been shown to be chemopreventive; the aromatic nature of ing that green tea is protective against prostate cancer.
polyphenolsmakesthempotentialtargetsofhypochlorousacid Yamamoto et al. [59] reported that GTP could be applied to
and peroxynitrite, and these reactions may create novel phar- enhance the effectiveness of chemo/radiation therapy to pro-
macophores at the site of inflammation. In addition, a major motecancercelldeathwhileprotectingnormalcells.
mechanism of the anticarcinogenic activity of green tea in On the one hand, epidemiological studies have suggested
animalsistheimpairmentoftheinteractionofcarcinogenswith thathighconsumptionofgreenteaprotectsagainstthedevel-
DNA leading to mutations. Nevertheless, the antimutagenic opment of chronic active gastritis and decreases the risk of
activityofgreenteaaswellasitsunderlyingmechanismsmust stomach cancer; in addition, the ingestion of green tea before
be reviewed, and the role of GTP, the postulated bioactive fastingprotectstheintestinalmucosaagainstatrophy[75].On
components, and caffeine must be critically evaluated. EGCG the other hand, Borrelli et al. [76] concluded in a systematic
fromgreenteaespeciallyimpartsagrowthinhibitoryeffecton review, that an inverse association does not seem to exist
cancercells[56,63–64].EGCGpossessespromisinganticancer between green tea consumption and the risk of gastric and
potential due to its antioxidant, antimutagenic and chemopre- intestinal cancer, although green tea did show a protective
ventiveproperties[65–66]. effectonadenomatouspolypsandchronicgastritis[76].Inthe
Rosengren[67]indicatedthatthegreenteacatechinsreduce sameway,Hoshiyamaetal.[66]andKoizumietal.[77]found
the proliferation of breast cancer cells in vitro and decrease no association between green tea consumption and the risk of
breast tumor growth in rodents. Furthermore, in vitro studies stomach cancer; these authors indicated that green tea con-
havedemonstratedthatthecombinationofEGCGandtamox- sumptionhadnoprotectiveeffectagainststomachcancer,and
ifen is synergistically cytotoxic to breast cancer cells; these suggestedtheimplicationofotherfactorssuchasage,smoking,
results suggest that the catechins have significant potential in socioeconomicstatus,Helicobacterpyloriinfection,historyof
the treatment of breast cancer. Mittal et al. [56] reported that pectic ulcer, and family history of stomach cancer along with
the treatment with EGCG decreased cell viability at different certain dietary components. Sasazuki et al. [78] reported an
stagesstudied(approx.80%inhibition)inhumanbreastcarci- inverse association between green tea consumption and distal
nomaMCF-7cells,buthadnoadverseeffectonthegrowthof gastriccanceramongwomen;however,theseauthorsindicated
normalmammarycells.Theseauthorsfoundthatthistreatment that more prospective studies with detailed information are
inhibitedtelomeraseactivity(40–55%);telomeraseiselevated needed to confirm the role of green tea in the occurrence of
in(cid:3)90%ofbreastcarcinomasandthereforehasreceivedmuch gastric cancer. Il’yasova et al. [7] examined the association
attention as a target for breast cancer therapy and cancer betweenblackteaconsumptionandcoloncancerinapopula-
diagnostic research. According to Wu et al. [68], green tea tion-based study in North Carolina, and concluded that, con-
drinkers showed a significantly reduced risk of breast cancer; trarytoexpectation,blackteadrinkingdidnotdecreasetherisk
comparedtowomenwhodidnotdrinkgreentearegularly(i.e., ofcoloncancer.However,itisimportanttoremarkthatmajor
less than once a month). Furthermore, there was a significant riskfactorsforcolorectalcancerarefamilyhistoryofcolorectal
trend of decreasing risk with increasing amount of green tea cancer, exposure to non-steroid anti-inflammatory drugs, cer-
intake.TwostudiesinJapanesewomendiagnosedwithbreast tainmeatcookingpractices,smoking,lowphysicalactivityand
cancerindicatethatgreenteaconsumptionisinverselyassoci- anelevatedbodymassindex,andelevatedintakeofredmeat
atedwiththerateofrecurrence,especiallyintheearlystagesof andalcoholicbeverages.Dataontheeffectsofgreenteainthe
breastcancer[69–70].Zhouetal.[71]alsoreportedthatbreast preventionofthistypeofcancerarenotavailable.
cancer is significantly less prevalent among Asian women, Severalauthorshavenotedthatsomeepidemiologicalstud-
whosedietscontainhighintakeofsoyproductsandgreentea. ies have generated inconsistent results [54,79]. Some of these
JOURNALOFTHEAMERICANCOLLEGEOFNUTRITION 85
Green Tea: Beneficial Effects
Table2.EpidemiologicalStudiesontheAssociationbetweenGreenTeaConsumptionandCancerRisk
Greentea
Country Typeofstudy/subjects Healtheffects Reference
consumption
Breastcancer
Japan Prospectivestudy (cid:3)6cups/day Adecreaseoftheriskofcancerrecurrenceis Inoueetal.[70]
1160femaleinvasive 3–5cups/day observedwithaconsumptionof(cid:3)3cups/
breastcancer(mean 0–2cups/day dayoftea(HR(cid:1)0.69,95%CI(cid:1)0.22–
age(cid:1)51.5y) 0.84).Thisdecreaseismainlyinearlystage
cases.
USA Case-controlstudy (cid:3)85.7mL/day Thereisasignificanttrendofdecreasingrisk Wuetal.[68]
Asian-american 0–85.7mL/day ofbreastcancerwithincreasingamountof
women nodrinkers teaintake,(OR(cid:1)1,95%CI(cid:1)0.51–0.99;
501breastcancer OR(cid:1)0.71,95%CI(cid:1)0.51–0.99;OR(cid:1)
patientsand594 0.53,95%CI(cid:1)0.35–0.78)respectively,in
controls associationwithno,0–85mL/dayand
(cid:3)85.7mL/day.
Japan Pooledoftwo 5cups/day Teaintakeisnotassociatedwithalowerrisk Suzukietal.
prospectivestudies (cid:4)1cups/day ofbreastcancer(RRforwomendrinking [168]
with35004women (cid:3)5cups/daycomparedwith(cid:4)1cup/day(cid:1)
0.84,95%CI(cid:1)0.57–1.24).
Ovariancancer
China Case-controlstudy Validated Increasingfrequencyanddurationoftea Zhangetal.[72]
254ovariancancer questionnaire drinkingcanreducetheriskofovariancancer
patientsand652 (OR(cid:1)0.39forthosedrinkingteadaily,OR
controls (cid:1)0.23forthosedrinkingteafor(cid:3)30years,
comparedwithnonteadrinkers).
Prostatecancer
China Case-controlstudy Face-to-faceinterview Theprostatecancerriskdeclinedwithincreasing: Jianetal.[74]
130prostate usingastructured frequency(non-drinkersforteadrinkingOR(cid:1)
adenocarcinoma questionnaire 0.28,95%CI(cid:1)0.17–0.47),duration(OR(cid:1)
patientsand274 (Almostallthetea 0.12,95%CI(cid:1)0.06–0.26fordrinkingteaover
controls consumedisgreen 40years)andquantityofteaconsumption(OR
tea) (cid:1)0.09,95%CI(cid:1)0.04–0.21)forthose
consumingmorethan1.5kgoftealeavesyearly
andOR(cid:1)0.27,95%CI(cid:1)0.15–0.48forthose
drinkingmorethan1L/day).
Gastro-intestinalcancer
Japan Case-controlstudy 6cups/day Consumptionofmorethan6cups/dayvs Huangetal.
887gastriccancerand 3–5cups/day neverdrinkingdecreasedtheriskofgastric [169]
28619controlage: 1–2cups/day cancer.
20–79y never
Japan Cross-sectionalstudy (cid:3)10cups/day Consumptionofmorethan10cups/day Shibataetal.
636menandwomen 0–9cups/day reducestheriskofchronicatrophicgastritis [170]
meanage:men:59.2 (OR(cid:1)0.59,95%CI(cid:1)0.42–0.86).
y,women:60.4y
Japan Cross-sectionalstudy (cid:3)5cups/day Norelationshipbetweenteaconsumptionand Kuwaharaetal.
566men 3–4cups/day riskofchronicatrophicgastritis(OR(cid:1)0.7, [171]
age:50–55y (cid:4)3cups/day 95%CI(cid:1)0.5–1.2).
Japan Prospectivecohort (cid:3)10cups/day Consumptionofmorethan10cups/day Nakachietal.
study 4–9cups/day decreasetheriskofstomachcancer(OR(cid:1) [88]
8552adults (cid:4)3cups/day 0.69,95%CI(cid:1)0.23–1.88)andcolorectal
cancer(OR(cid:1)0.56,95%CI(cid:1)0.22–1.4).
Japan Prospectivecohortstudy (cid:3)5cups/day Norelationbetweenteaconsumptionand Naganoetal.
14873menand23667 2–4cups/day reducedriskofstomachcancer(OR(cid:1) [79]
women 0–1cups/day 0.95,95%CI(cid:1)0.76–1.2),coloncancer
Hiroshimaatomicbomb (OR(cid:1)1.0,95%CI(cid:1)0.76–1.4)orrectum
survivors cancer(OR(cid:1)1.3,95%CI(cid:1)0.77–2.1).
China Case-controlstudy 21cups/week Significantinverseassociationbetweentea Setiawanetal.
166chronicatrophic 1–21cups/week drinkingandgastriccancer(OR(cid:1)0.39, [172]
gastritis,133gastric never 95%CI(cid:1)0.15–1.01)orchronicatrophic
cancerand433 gastritis(OR(cid:1)0.52,95%CI(cid:1)
controls 0.28–0.99).
(Tablecontinues)
86 VOL.25,NO.2
Green Tea: Beneficial Effects
Table2.Continued
Typeof Greentea
Country Healtheffects Reference
study/subjects consumption
Japan Prospectivecohort (cid:3)5cups/day Noassociationwithriskofgastriccancer Tsubonoetal.
study 3–4cups/day men:(OR(cid:1)1.16,95%CI(cid:1)0.9–2.6), [173]
11902menand 1–2cups/day women:(OR(cid:1)0.8,95%CI(cid:1)0.5–1.3).
14409women (cid:4)1cup/day
(meanage:46.4y)
Japan Prospectivecohort (cid:3)10cups/day Noassociationbetweenteaconsumptionand Hoshiyamaetal.
study 5–9cups/day stomachcancerdeath;men:(OR(cid:1)1.00, [174]
30370menand 3–4cups/day 95%CI(cid:1)0.5–2),women:(OR(cid:1)0.7,95%
42481women 1–2cups/day CI(cid:1)0.3–2).
(cid:4)1cup/day
Japan Prospectivecohort Everyday Noassociationbetweenteaconsumptionand Fujinoetal.
study 3times/week stomachcancerdeath;men:(OR(cid:1)1.11, [175]
18746menand (cid:4)3times/week 95%CI(cid:1)0.75–1.63),women:(OR(cid:1)
26184women 1.43,95%CI(cid:1)0.78–2.62).
Japan Case-controlstudy (cid:3)10cups/day Noinverseassociationbetweentea Hoshiyamaetal.
157incidentstomach 5–9cups/day consumptionandtheriskofstomach [66]
cancerand285 3–4cups/day cancer.
controls 1–2cups/day
(cid:4)1cup/day
Esophagealcancer
China Prospective Interventiongroup:5 DGTtrialdidnotshowapparentdifference Wangetal.
interventional mg/dayof betweenthetreatmentandplacebogroupin [176]
study decaffeinategreen alleviatingtheesophagealprecancerous
778esophageal tea(DGT)for12 lesionsandabnormalcellproliferation.
precancerous months.
lesion
Bladdercancer
Japan Prospectivecohort Amailsurvey Teaconsumptionisnotrelatedtoriskof Naganoetal.
study bladdercancer [177]
14873menand
23667women
Hiroshimaatomic
bombsurvivors
Lungcancer
China Case-controlstudy Face-to-face Amongnon-smokingwomen,consumptionof Zhongetal.
649lungcancer interviews greenteawasassociatedwithareducedrisk [178]
womenand675 oflungcancer(OR(cid:1)0.65,95%CI(cid:1)
controlswomen 0.45–0.93),andtherisksdecreasedwith
increasingconsumption.
Cancerincidence
Japan Prospectivestudy (cid:3)5times/day Teaconsumptionisunrelatedtoincidenceof Naganoetal.
38540people 2–4times/day cancersunderstudy.(RR(cid:1)1,95%CI(cid:1) [79]
(14.873men, 1time/day 0.91–1.1,andRR(cid:1)0.98,95%CI(cid:1)0.88–
meanage52.8y never 1.1forallcancerconsumingteatwiceto
and23667women, fourtimesperdayandfiveormoretimes
meanage58.8y) perday,ascomparedwiththoseconsuming
teaonceperdayorless).
HR(cid:1)hazardratio;OR(cid:1)oddratio;RR(cid:1)relativerisk;CI(cid:1)confidenceinterval.
studiesrelatedteaconsumptionwithreducedriskofcancer.In greentea.Thesestudiesdonotprovideconsistentevidenceto
a similar way, other authors found that tea lacks protective supportthetheoryfromanimalstudiesandbasicresearchoftea
activityagainstcertainhumancancers;theseresultsraiseques- beingapotentchemopreventiveagent.Anegativeassociation
tions about the actual role of green tea components in human is stronger in observational epidemiologic studies of rectal
cancer that need to be addressed. For example, Arab and cancerthanincoloncancer.Thereisnoconsistentadjustment
Il’yasova[80]providedabriefsynopsisof30studiesaimedat for important potential confounders of any tea relationship,
examiningteaconsumptionasafactorintheincidenceofcolon such as coffee and alcohol consumption and physical activity
and rectal cancers; the 30 papers examined populations in 12 levels. Finally, these authors indicated that the assessment of
countriesandprovideddataonconsumptionofbothblackand teainmostofthesestudieswasbasedonasinglequestionand
JOURNALOFTHEAMERICANCOLLEGEOFNUTRITION 87
Green Tea: Beneficial Effects
therefore may have significant measurement error compared cardiovascular function through mechanisms of action related
withmorerecentstudiesspecificallyaimedatassessinggreen to LDL-cholesterol oxidation [4,89]. The oxidation of LDL-
tea consumption. Table 2 summarizes some recent epidemio- cholesterol,associatedwithariskforatherosclerosisandheart
logicalstudiesontheassociationofgreenteaconsumptionand disease, is inhibited by green tea due to EC and EGCG anti-
cancerrisk. oxidantactivity.TheinvitroantioxidantactivityofEGCGon
Anti-Hypertensive Effect And Cardiovascular Disease LDLoxidationwasstrongerthanthatofEC[90].Inaccordance
Risk.Greenteahaslongbeenbelievedtopossesshypotensive with these observations, Trevisanato and Kim [91] indicated
effects in popular Chinese medicine. However, conflicting re- that GTP may slow atherogenesis by reducing the oxidative
sultshavebeenshownamongtrialsandanimalstudiesonthe modificationofLDL-cholesterolandassociatedeventssuchas
relation between tea consumption and blood pressure. Epide- foam cell formation, endothelial cytotoxicity and induction of
miologicalevidenceaboutthelong-termeffectofgreenteaon proinflammatorycytokines.GomikawaandIshikawa[90]sug-
hypertensive risk is also inconsistent. Negishi et al. [81] ob- gested that catechins suppressed the susceptibilities of human
served that both black and green tea polyphenols attenuate LDL to oxidation by CuSO in vitro and plasma oxidation in
4
blood pressure increases, through their antioxidant properties, vivo after ground green tea ingestion. Recent bioavailability
in stroke-prone spontaneously hypertensive rats, but the
studies indicate that GTP can accumulate in the body at con-
amounts of polyphenols used in this experiment correspond
centrations comparable to those employed in vitro by several
approx. to those 1L of tea. Recently, some epidemiological
investigators [31]. Other data report that catechins have been
studies indicated that green tea consumption slightly reduces
shown to reduce plasma cholesterol levels and the rate of
bloodpressure.Yangetal.[82]concludedthathabitualmod-
cholesterolabsorption.Raederstorffetal.[92]investigatedthe
eratestrengthgreenteaoroolongteaconsumption,120mL/day
dose-responseandthemechanismofactionofEGCGonthese
ormorefor1yearsignificantlyreducestheriskofdeveloping
parametersinratswhichwerefedadiethighincholesteroland
hypertension in the Chinese population. Hodgson et al. [83]
fat; after 4 weeks of treatment, total cholesterol and LDL-
reportedthatlong-termregularingestionofgreenteamayhave
cholesterol plasma levels were significantly reduced in the
afavorableeffectonbloodpressureinolderwomen.However,
group fed 1% EGCG when compared to the non-treatment
other studies do not support a hypotensive effect of green tea
group. Plasma triglycerides and HDL-cholesterol did not
[4].Singhetal.[84],andMurakamiandOhsato[85]reported
change significantly. These authors suggested that one of the
that dietary green tea intake preserves and improves arterial
underlyingmechanismsbywhichEGCGaffectslipidmetabo-
compliance and endothelial function. Green tea consumption
lism is by interfering with the micellar solubilization of cho-
has also been inversely associated with the development and
lesterol in the digestive tract, which then in turn decreases
progression of atherosclerosis, which is consistent with the
cholesterol absorption. Yokozawa et al. [93] reported that the
former observations. Geleijnse et al. [86] in their prospective
administration of GTP effectively inhibited LDL-cholesterol
Rotterdamstudywith3454adults,55yearsofageorolder,and
oxidation and elevated serum antioxidative activity. Further-
with a follow-up duration ranging from two to three years,
more,GTPincreasedthelevelsofHDL-cholesterol,leadingto
examinedaorticatherosclerosisviaX-raymeasurementofcal-
dose-dependent improvement of the atherogenic index. Thus,
cifieddepositsintheabdominalaorta;theoddsratio(OR)for
GTP may exert an antiatherosclerotic action by virtue of its
drinking 125–250 mL (1–2 cups) of black tea daily was 0.54
(95% CI (cid:1) 0.32–0.92) and decreased to 0.31 (95% CI (cid:1) antioxidantpropertiesandbyincreasingHDL-cholesterollev-
0.16–0.59) when (cid:3)500 mL/day (more than four cups) were els. Consistent with these results are the data reported by
Hertog et al. [94] that demonstrated an inverse correlation
consumed. Data on green tea are reported by Sasazuki et al.
between catechin intake and coronary heart disease mortality
[87] who in a cross sectional study of 512 coronary patients
(302 men and 210 women) established that green tea may be after a 25-year follow-up of 12763 men from seven different
protectiveagainstcoronaryatherosclerosisinmen(OR(cid:1)0.5, countries. Similarly, another research showed that men and
95%CI(cid:1)0.2–1.2forconsumptionof2–3cups,andOR(cid:1)0.4, womenfromtheBostonAreaHealthstudywhoconsumedone
95% CI (cid:1) 0.2–0.9 for (cid:3)4 cups per day as compared with a or more cups per day of green tea in the previous year had a
consumption of one cup per day or less), but not in women. 44%lowerriskofmyocardialinfarctionthanthosewhodrank
Nakachietal.[88]inaprospectivecohortstudyof8522men notea[95].Recently,Petersetal.[96]haveprovidedameta-
andwomenconcludedthatconsuming(cid:3)10cups/dayislinked analysisthatsuggestedadecreaseintherateofcardiovascular
withadecreasedrelativerisk(RR)ofdeathfromcardiovascu- disease outcomes with increasing green tea consumption.
lar disease in men (RR (cid:1) 0.58, 95% CI (cid:1) 0.34–0.99) and in Throughsevenstudiestheincidencerateofmyocardialinfarc-
women(RR(cid:1)0.82,95%CI(cid:1)0.49–1.38). tion was estimated to decrease by 11% with an increase in
Epidemiologicalstudiessuggestthatgreenteaconsumption greenteaconsumptionofthreecupsperday(RR(cid:1)0.89;95%
isassociatedwithareducedcardiovasculardiseaserisk,butthe CI(cid:1)0.79–1.019).Inaddition,aninverseassociationofgreen
mechanisms for these observations have remained uncertain. tea intake and myocardial infarction and its genetic variation
Severalstudieshavedemonstratedthatgreenteamayaffectthe hasbeenfoundbyHiranoetal.[97]andOhmorietal.[98].
88 VOL.25,NO.2