Effects on Sebum Production and Acne Vulgaris

16 Pages·2016·0.94 MB·English

antioxidants
Review
Green Tea and Other Tea Polyphenols: Effects on
Sebum Production and Acne Vulgaris
SuzanaSaric1,ManishaNotay2andRajaK.Sivamani2,*
1 SchoolofMedicine,UniversityofCalifornia—Davis,Sacramento,CA95817,USA;[email protected]
2 DepartmentofDermatology,UniversityofCalifornia—Davis,Sacramento,CA95816,USA;
[email protected]
* Correspondence:[email protected];Tel.:[phone]
AcademicEditors:AlessandraNapolitanoandStanleyOmaye
Received:15August2016;Accepted:26December2016;Published:29December2016
Abstract:Polyphenolsareantioxidantmoleculesfoundinmanyfoodsincludingnuts,fruits,vegetables,
chocolate, wine, and tea. Polyphenols have antimicrobial, anti-inflammatory, and antineoplastic
properties. Recentstudiessuggestthatteapolyphenolsmaybeusedforreducingsebumproduction
intheskinandfortreatmentofacnevulgaris.Thisreviewexaminestheevidenceforuseoftopically
andorallyingestedteapolyphenolsagainstsebumproductionandforacnetreatmentandprevention.
The PubMed database was searched for studies on tea polyphenols, sebum secretion, and acne
vulgaris. Of the 59 studies found, eight met the inclusion criteria. Two studies evaluated tea
polyphenoleffectsonsebumproduction;sixstudiesexaminedteapolyphenoleffectsonacnevulgaris.
Seven studies evaluated topical tea polyphenols; one study examined systemic tea polyphenols.
Noneofthestudiesevaluatedbothtopicalandsystemicteapolyphenols. Teapolyphenolsources
included green tea (six studies) and tea, type not specified (two studies). Overall, there is some
evidencethatteapolyphenolsintopicalformulationmaybebeneficialinreducingsebumsecretion
andintreatmentofacne. Researchstudiesofhighqualityandwithlargesamplesizesareneeded
toassesstheefficacyofteapolyphenolsintopicalandoralpreventionofacnevulgarisandlipid
synthesisbythesebaceousglands.
Keywords: tea;polyphenol;EGCG;catechin;sebum;acnevulgaris
1. Introduction
Polyphenolsarenaturallyoccurringcompoundsfoundinplantsandcommonfoodssuchasnuts,
fruits,vegetables,chocolate,wine,andtea. Afteringestion,polyphenolsareabsorbedintheintestinal
epithelium[1]andhavebeenshowntoreachsystemiccirculation[2–5]. Polyphenolsareantioxidants
and play a role in preventing oxidative damage caused by the reactive oxygen species (ROS) [6].
Theypossessanti-inflammatory[7]andanti-carcinogenicpropertiesandmayaidinthepreventionof
cardiovasculardisease[8],aswellasprotectskinfromultravioletradiation(UVR)[9–11].
Tea is the second most consumed beverage worldwide and an important source of plant
polyphenols in the human diet [12]. Camellia sinensis is the plant that gives rise to a variety of
teas depending on specific processing of the plant [13]. Green tea is produced from fresh leaves
in such a way thatprevents oxidationof polyphenolic components (mainly catechins), oolong tea
polyphenols are partially oxidized, while polyphenols in black tea undergo a high degree of
oxidation[13]. Componentsofgreenteabeveragemeasuredasweightpercentageofextractsolids
include 30%–42% catechins, 5%–10% flavonols, and 2%–4% other flavonoids [13]. Catechins are
dividedintocatechin(C),(−)-epicatechin(EC),(−)-epicatechingallate(ECG),(−)-epigallocatechin
(EGC), and (−)-epigallocatechin-3-gallate (EGCG) (Figures 1 and 2). EGCG is the most abundant
catechinandhasbeenshowntohavebeneficialhealtheffectsonskin[12].
Antioxidants2017,6,2;doi:10.3390/antiox6010002 www.mdpi.com/journal/antioxidants
Antioxidants2017,6,2 2of16
Antioxidants 2017, 6, 2 2 of 16
Antioxidants 2017, 6, 2 2 of 16

Figure 1. Major components of the tea polyphenol family.
Figure1.Majorcomponentsoftheteapolyphenolfamily.
Figure 1. Major components of the tea polyphenol family.

(a) (b)
(a) (b)

(c) (d)
(c) (d)
(e)
(e)
Figure 2. Chemical structures of major tea polyphenols. (a) (+)-Catechin (C); (b) (−)-Epicatechin (EC);
FiguFr(eicg) 2u(.r−e)C -2Eh. pCeicmhaetimeccaihclainsl t srgturaucllctaututrere es(sE ooCffG mm);a aj(ojdor) rt e(ta−e )pa-Eopplyoigplahyleplonhcoealsnte. oc(ahls)i .n(+ ()(a-EC)Ga(Ct+e))c;- hC(iena) t (eC(−c))h; -(Eibnp) i((gC−a))l-l;Eop(cbaict)aet(ce−hcih)n-i Eng p(aEilclCaa)tt;e e chin
((cE) G(C−)G-E)p. icatechin gallate (ECG); (d) (−)-Epigallocatechin (EGC); (e) (−)-Epigallocatechin gallate
(EC); (c) (−)-Epicatechin gallate (ECG); (d) (−)-Epigallocatechin (EGC); (e) (−)-Epigallocatechin
(EGCG).
gallate(EGCG).
Antioxidants2017,6,2 3of16
Sebaceous glands are found throughout the human body, especially on the face and scalp,
and they produce sebum—a mixture of lipids [14]. Lipids are produced by other glands in
the body but the two most specific lipids to sebaceous glands are squalene and wax esters [14].
Sebum secretion is associated with hormonal activity in the human body [15] and excess sebum
production is implicated in the development of skin disorders, such as acne vulgaris. Acne is not
alifethreateningconditionbutitcanleavepermanentscaringonthefaceandcausephysicaland
psychologicalmorbidities[16]. Acnemaybecausedbymultiplemechanismsincluding(a)increased
sebumproductionbythesebaceousglands;(b)alteredkeratinizationwithinpilosebaceousfollicles;
(c)proliferationofbacteriaPropionibacteriumacnes(P.acnes);and(d)inflammationaroundpilosebaceous
follicles[16,17].
Recent evidence suggests that there is increased phosphoinositide 3-kinase-Akt-mammalian
target of rapamycin complex 1 (PI3K-Akt-mTORC1) signaling in the skin of patients with acne
vulgaris [18–20] and that increased PI3K-Akt-mTORC1 signaling induces sebum production [21].
Thegreentea-derivedplantsterolshaveshownatherapeuticroleinthetreatmentofacnevulgaris[22].
Im et al., 2012 provided experimental evidence that EGCG treatment of insulin growth factor
(IGF-1)stimulatedSZ95sebocytesdecreasedmTORphosphorylationandthusmTORC1activity[23].
Additionally,VanAlleretal.,2011[24]providedevidencethatEGCGisanATP-competitiveinhibitor
ofbothPI3KandmTOR.MoleculardockingstudiesshowedthatEGCGbindswelltothePI3Kdomain
activesite,agreeingwiththefindingsthatEGCGcompetesforATPbinding. ThemTORkinasealso
belongs to the family of PI3K related kinases. Increased insulin-IGF-1 signaling in acne vulgaris
activates PI3K-Akt-mTORC1 signaling cascade and plays a key role in the Western-diet induced
acne[25]. NaturalmTORC1inhibitors,suchasgreenteapolyphenols,attenuateenhancedmTORC1
signaling[26]. Whencomparedwithothertypesoftea,greenteahasthehighestpolyphenoliccontent,
withEGCGandEGCcomponentsbeingthemostabundant[27].
Therearemultipleacnegradingsystemsbutthereisnogoldstandard[28]thatisconsistently
usedinclinicalpracticeorresearchtrials. Lesioncountinghasbeenvalidatedasareliablemeasure
for acne [29] and requires counting the number of comedones, papules, pustules, and nodules on
the face [30]. The global assessment scale classifies acne into one of five categories based on acne
severity(verymild,mild,moderate,severe,andverysevere)[30]. IntheLeedstechnique,asubject’s
acneiscomparedtoaphotographicmanualandascorefrom1(mild)to10(verysevere)isassigned[30].
TheGlobalAcneGradingSystem(GAGS)wasdevelopedin1997inanefforttoimproveaccuracy,
minimizeinter-andintra-ratervariability,andallowforquickerassessments[30].
Due to the complex nature of acne vulgaris, most treatments have only modest efficacy [31].
Systemictherapiesthatinfluencesebumproductionincludeestrogens,anti-androgens(i.e.,spironolactone),
retinoid (isotretinoin), and oral contraceptives [32]. All these medications predispose individuals
topotentiallyserioussideeffects,thusthereisaneedformorenaturaltherapieswithminimalside
effects. Researchsuggeststhatteapolyphenolsmaybepromisinginthemanagementofacnevulgaris
byreducingsebumproductionintheskinandactingasananti-inflammatory[7]andantimicrobial
agents [33]. In an invitro study, Yoon et al., 2013 [31] showed that EGCG decreases lipogenisis in
sebocytes,inhibitsgrowthofP.acnesandreducesinflammationcausedbyP.acnes. Theaimofthis
reviewistoexaminerecentclinicaltrialsonteapolyphenolsandtheireffectsonsebumproduction
andacnevulgarismanagement.
2. MaterialsandMethods
2.1. SearchStrategy
On 4 August 2016 the PubMed database was searched for studies that investigated tea
polyphenols,sebumproduction,andacne. Nolimitswereplacedonthepublicationdate. Thesearch
combined keywords “tea”, “green tea”, “EGCG”, “polyphenol”, “catechin”, “sebum” and “acne”.
Nofilterswereselected.
Antioxidants2017,6,2 4of16
2.2. SelectionofStudies
Records were screened by title and/or abstract to exclude studies that did not contribute to
answeringthequestioninthisreview. Inclusioncriteria: (1)publishedinEnglish;(2)intervention
includedateapolyphenol;(3)humanstudy. Exclusioncriteria: (1)invitrostudies;(2)animalstudies;
(3)reviewarticles.
2.3. DataExtraction
Datawasextractedfromselectedstudies(TableA1)asfollows: (1)tea;(2)polyphenolsubtype
andcontent;(3)therapy(topicalorsystemic;dosage);(4)comparison(orcontrol/placebo);(5)subjects
(n,age);(6)studydesign,duration;(7)majoroutcomemeasures;(8)majorresults;(9)adverseevents;
(10)reference.
3. Results
Our search yielded a total of 59 studies. Titles and/or abstracts were screened for inclusion
andexclusioncriteria. Eightarticlesmetthecriteriaandweresubsequentlyanalyzed. Twostudies
examined the effects of tea polyphenols on sebum production, while six studies investigated the
effects of tea polyphenols on acne vulgaris. Seven studies examined the application of topical tea
polyphenolsandonestudyexaminedsystemicteapolyphenols. Noneofthestudiesexaminedboth
topicalandsystemicteapolyphenols.Teapolyphenolsourcesincludedgreenteainsixstudies,whilein
twostudiestheteatypewasnotspecified.
3.1. SebumProductionStudies
Inasingle-blinded,placebocontrolledmonocentricstudybyMahmoodetal.,2013[15]conducted
inPakistan,22non-smoker,healthymenaged22–28years-oldwereenrolledtoinvestigatetheeffects
ofgreenteaandlotusextracttopicalsonfacialsebumproduction. Thiswasasplitbodycomparative
studyinwhichonegroupusedgreentea(GT)topicalononecheekandplacebocontrolontheother
(n=11). Thesecondgroupusedtopicalgreenteaandlotus(GT-L)ononecheekandplacebocontrol
ontheother(n=11). TheGTtopicalconsistedof5%greenteaandtheGT-Lformulationcontained
2.5%greenteaand2.5%lotusextract. Bothgroupswereinstructedtoapplytheirrespectivetopicals
atbedtimefor60days. Sebumeterwasusedtomeasuresebumsecretiononbothcheeksatbaseline
anddays15,30,45,and60. After60days,theGTtopicalgrouphadasignificantreductioninsebum
secretion from baseline, compared to placebo control (27% reduction, p = 0.006). The GT-L group
also had a significant reduction in sebum secretion from baseline to day 60 compared to placebo
control(25%reduction,p=0.002). TherewerenoadverseeventsreportedineitherGTorGT-Lgroup.
ThisstudyshowedthatGTandGT-Ltopicalswerebotheffectiveinsignificantlyreducingsebum
secretion. Additionally,eventhoughtheGT-LcombinationtopicalhadasmallerpercentageofGT
extract(2.5%vs. 5%inGTgroup),GT-LreducedsebumsecretiontoahigherdegreethanGTtopical
alone; this could indicate an additive effect of GT and L extracts. These findings suggest that GT
andGT-Lcombinationtopicalscouldbeusedtotreatskindiseasesthatareassociatedwithincreased
sebumsecretion,suchasacnevulgaris. Limitationsofthisstudyincludeasmallsamplesizeandthatit
onlyincludedhealthymen.Futurestudiesshouldfocusonstudyingtheeffectsofthetwoformulations
inpatientswithacnevulgaris.
InastudybyMahmoodetal., 2010[34], tenhealthymenage24–40years-oldapplied3%GT
topical to their cheeks for eight weeks. A sebumeter was used to measure the amount of sebum
secretionat1,2,3,4,and8weekswhichwasusedtocalculatethepercentchangeinsebumproduction
from week 1 to week 8. The results showed that the 3% GT topical led to a significant reduction
in sebum production during the 8 week study period (p < 0.05). Specifically, sebum production
decreasedbynearly10%inthefirstweekandasmuchas60%byweek8. Nosideeffectswerenoted.
Antioxidants2017,6,2 5of16
Limitationsofthisstudyincludesmallsamplesize,nocomparisontreatmentorplacebocontrol,andit
didnottestindividualswithskindiseasesknowntohavehighsebumproduction.
3.2. AcneStudies
3.2.1. TopicalTeaPolyphenols
Sharquieetal.,2008[35]conductedasingle-blindrandomizedclinicaltrialexamining2%tea
lotionand5%zincsulphatesolutionintreatmentofacnevulgaris. Theteatypewasnotspecified.
Forty-sevensubjects(33women,14men)aged13–27years-oldwereenrolledbetweenJune2006and
December2007inIraq. Subjectswererandomlyassignedoneoftwogroups: 2%tealotion(n=24)
or 5% zinc sulphate solution (n = 23); both groups applied their respective topical twice daily for
2months. Inflammatorylesioncountingwasperformedevery2weeksandgradedasfollows: mild
acne(<20pustulesand<10papules)andmoderateacne(20–40pustulesand>30papules). Itwas
consideredthatsubjectshada“goodresponse”totreatmentiftheinflammatorylesioncountdecreased
by>50%;“moderateresponse”whendecreasewas10%–50%;and“noresponse”whenlesioncount
decreased by <10%. The 2% tea lotion group experienced a significant reduction in inflammatory
lesioncount(papulecountdecreasewithtreatment,p=0.0001;pustulecountdecreasewithtreatment,
p=0.003). Eighty-fivepercentofsubjectshadagoodormoderateresponseand15%hadnoresponse
totreatment. Therewasnosignificantdifferenceininflammatorylesioncount(papuleorpustule)in
thegrouptreatedwith5%zincsulphatecomparedtobaseline. Adverseeventreportedbythe2%tea
lotion group was mild itching (5 subjects) at the beginning of the treatment period. The 5% zinc
sulphategroupalsoreporteditching(2subjects),aswellasburningsensation(5subjects). Noserious
side effects were reported in either group. One limitation of this study is the small sample size
(n=20ineachgroupthatcompletedthestudy). Nevertheless,2%tealotionispromisingforitseffect
ofdecreasinginflammatorylesioncount. Futurestudiescouldbedonetocompareittootherknown
topicaltreatmentsforacnetofurtherassessitsefficacyandsafetyprofile.
Arandomly-assignedsplitbody(face)trialwasconductedbyYoonetal.,2013[31]toexamine
theeffectivenessof1%EGCGand5%EGCGtopicalscomparedtovehiclecontaining3%ethanolin
decreasingacnelesioncount.Eachgroupappliedtheassignedtopicaltoonesideoftheface(1%EGCG
or5%EGCG);bothgroupsappliedthevehicletopicaltotheothersideofface. Non-inflammatory
and inflammatory lesions were counted. A revised Leeds score, which represents inflammatory
and non-inflammatory acne counts, was used as a global assessment of acne severity. The mean
Leeds score at baseline was 5.1 ± 0.4. At eight weeks, the mean Leeds score for the 1% EGCG
groupwas1.2±0.4andforthe5%EGCGgroupitwas1.7±0.6. ThereductioninLeedsscorewas
significantinboth1%EGCGand5%EGCGgroups(p<0.05). Specifically,non-inflammatorylesions
reducedby79%andinflammatorylesionsby89%aftereightweeksof1%EGCGusecomparedto
baseline(p<0.05). Thenon-inflammatoryandinflammatorylesionreductionwassimilarin5%EGCG
group(p<0.05),however,thespecificlesioncountsandpercentageimprovementwerenotprovided.
Overall,thisstudyshowedthat1%and5%EGCGwerebotheffectiveinimprovingacnevulgaris
withoutmajorsideeffects.
Asingle-blindrandomizedcontrolledstudybySharquieetal.,2006[36]investigatedtheeffects
of2%tealotioncomparedtoplacebolotioninitsabilitytodecreaseacnelesioncount. Sixtysubjects,
aged14–22years-old(35women,25men)participatedinthestudyforadurationof2monthsbetween
October 2002 and October 2004 in Iraq. The treatment group applied 2% tea lotion twice a day
for 2 months and inflammatory lesion count (papules and pustules) was done at weeks 4 and 8.
Thecontrolgroupunderwentthesameprocedurebutusedacontrollotion,whichconsistedofdistilled
water. The2%tealotiongrouphadasignificantdecreaseininflammatorylesioncountat8weeks
post-treatment (baseline papules 12 ± 3.3, week 8 papules 8.1 ± 19, p < 0.001; baseline pustules
20.7±5.8,week8pustules8.9±2.3,p<0.001). Eighty-eightpercentofsubjectsinthetreatmentgroup
reported being fully or partially satisfied with the treatment outcome and 12% were not satisfied.
Antioxidants2017,6,2 6of16
Thecontrolgroupdidnothaveasignificantreductioninlesioncountat8weekscomparedtobaseline.
Inthisgroup,83.3%ofsubjectswerenotsatisfiedwiththeoutcomeand16.7%werepartiallyorfully
satisfied. Therewerenoadverseeventsreported. Thisstudysuggeststhat2%tealotionisaneffective
topicalalternativeinacnemanagement.
Elsaieetal.,2009[37]studiedtheeffectivenessof2%greentealotioninreducingacneseverity.
The study had 20 subjects, aged 15–36 years-old (14 women, 6 men) and was conducted in Egypt
betweenMay2007andFebruary2008. Acneseveritywasassessedatbaselineviatotallesioncount
(TLC)forpustulesandpapulesandseverityindex(SI).TheTLCatbaselinewasconsidered100%
and any decrease during treatment was considered an improvement. Baseline images were taken
and subjects were instructed to apply the 2% green tea lotion twice daily for 6 weeks with follow
upevery2weeks. TheresultsshowedameanTLCdecreasefrom24(baseline)to10after6weeks
oftreatment(58.33%reduction,p<0.0001,95%confidenceinterval(CI)=8.58–19.42). ThemeanSI
alsodecreasedfrom2.05(baseline)to1.25after6weeksoftreatment(39.02%reduction,p<0.0001,
95%CI=0.54–1.26). Fivesubjectsreportedstingingsensationoritching,buttheseresolvedwithin
2–3daysoftreatment. Smallsamplesizeandlackofcomparison,orcontrolgroup,werelimitations
inthisstudy. Thetrueeffectofthetopicalgreentealotionwasnotclearwiththelackofacontrol
treatment. Nevertheless,itshowedthat2%greentealotioncouldbebeneficialinacnetreatmentby
reducingacnelesioncountandwarrantsfuturecontrolledstudies.
In a study by Jung et al., 2012 [38] conducted in Korea, a green tea extract compound called
polyphenon-60wasusedtoexamineitspotentialtherapeuticeffectsonacnevulgaris. Sixtysubjects
withmildtomoderateacneapplied20mg/mLpolyphenon-60twicedailyfor8weeks; theiracne
lesioncountwasassessedatbaselineandweek8. Eightweekspost-treatmentwithpolyphenon-60,
therewasa61%decreaseinopencomedones(p<0.05)and28%decreaseinthenumberofpustules
(p<0.05)comparedtobaseline. Therewasnosignificantdecreaseinthenumberofclosedcomedones
atweek8comparedtobaseline.Nomajoradverseeventswerenoted.Thisstudydidnothaveacontrol
grouporcontroltreatment.
3.2.2. SystemicTeaPolyphenols
Luetal.,2016[39]conductedarandomized,double-blind,placebocontrolledtrialtoinvestigate
whether systemic green tea supplementation could improve acne in post-adolescent women.
The study enrolled 80 women aged 25–45 years-old with moderate to severe acne, as determined
by the Investigators Global Assessment score of 3 or 4 (scale 0–5). The study was conducted in
Taiwan between May 2012 and October 2013. One group (n = 40) received 1500 mg decaffeinated
greenteadaily(1capsule500mgGT30minaftermeal,3timesdaily)forfourweeks. Thesecond
group received cellulose capsules (placebo), which looked identical to GT capsules for blinding
purposes. Ablindeddermatologistrecordedinflammatoryandnon-inflammatorylesioncountsonthe
forehead,cheeks,nose,perioralarea,chin,andentirefaceatbaselineandatfourweekspost-treatment.
Therewasasignificantdecreaseintheinflammatorylesioncountsonthenose(p=0.03),perioralarea
(p=0.04), and chin (p=0.03) in the green tea group compared to placebo group. There was no
significant difference in lesion counts on forehead, cheek, or in the total lesion count between GT
and placebo groups. Within the GT group, subjects had significantly lower inflammatory lesion
countsontheforehead(p=0.04)andcheeks(p=0.04),aswellaslowertotallesioncount(p=0.03)at
theendoftreatmentcomparedtobaseline. Withintheplacebogroup,therewassignificantdecreasein
inflammatorylesioncountoncheeks(p=0.01)andchin(p=0.01),aswellastotallesioncount(p=0.02).
Adverseeventsincludedmildconstipationandabdominaldiscomfort(threesubjects). Placebogroup
adverseeventsincludedthirstanddifficultyfallingasleep(twosubjects). However,nomajorside
effectswerereported. EventhoughdecaffeinatedGTtreatmentresultedindecreasedlesioncounts
onnose,perioralarea,andchincomparedtoplacebo,theplacebogroupitselfhadsignificantwithin
groupdifferenceinlesioncountsbeforeandaftertreatment. Additionalstudieswithmoresubjects
andlongerdurationareneededtoassesstheeffectivenessofsystemicgreenteaintreatmentofacne.
Antioxidants2017,6,2 7of16
4. Discussion
Polyphenols are naturally occurring compounds found in many common foods and plants,
including Camellia sinensis [13], the plant that gives rise to a variety of teas. Their natural-based
ingredients,costeffectivenessandnon-invasiveattributeshavemadethemincreasinglyattractive
to patients, compared to prescription drugs [40], and this has led to an increase in polyphenol
studies examining their effects on the skin. In this review, we include eight studies focusing on
teapolyphenolsandtheireffectsonsebumproductionandacne. Alleightstudiesreportedthattea
polyphenolswereeffectiveateitherreducingsebumproductionorimprovingacneseverityinatleast
oneoutcomemeasure.
4.1. TeaPolyphenolBioavailability
Bioavailability of polyphenols varies depending on the polyphenol forms within the dietary
source[41].EGCG,themostabundantcatechinfoundintea,isprimarilyabsorbedinthesmallintestine
andmetabolizedbycolonicflorainthelargeintestine[42]. Studiesshowthatbioavailabilityvaries
amongcatechinswhereEGCGisreadilypresentinplasmaafterintake,indicatinghighbioavailability,
whereas galloylated catechins have never been recovered in urine samples [41]. Fasting, fish oils,
albumin, soft water, piperine, Vitamin C and storage in cool and dry conditions can increase
the oral bioavailability of EGCG [42]. Oral bioavailability is reduced by oxidation with air, metal
ions,catechol-O-methyltransferase(COMT)polymorphisms,andgastrointestinalinactivation[43].
Yangetal.,1998[44]showedthatmaximalEGCG,EGC,andECplasmaconcentrationwasreached
between1.5and2.5hafterconsumptionofgreentea,andtheybecameundetectableinplasmaafter24h.
Studieshavefoundextensivevarianceinbioavailabilityacrosspolyphenols,includingteapolyphenols,
whichmaybedrivenbythenatureofstudysubjectdietsandtheirlevelsofmetabolizingenzymes[41].
Therefore,futurestudiesareneededtofurtherinvestigatebioavailabilityofteapolyphenols.
4.2. SkinPenetration
ThepartitioncoefficientsofteapolyphenolsareshowninTable1[45].EGCisthemosthydrophilic
molecule,whileECGistheleastpolar[45].AstudybydalBeloetal.,2009[46]investigatedapplication
of6%greenteaextractonthehumanskinobtainedfromabdominalsurgery. Theresultsshowedthat
EGCGwasretainedwithintheskin,withhigherlevelsofEGCGdetectedinthestratumcorneum,
followed by the epidermis and dermis. This suggests that EGCG is more non-polar as non-polar
compounds tend to stay in the stratum corneum rather than get into the epidermis and dermis.
Additionally,astudybyZillichetal.,2013[47]usedexvivopigskinandshowedthatbothsizeof
themoleculeandhydrophobicityofthemoleculeimpactskinpermeationofgreenteacompounds.
However,studiesonhumanskinpenetrationbyteapolyphenolsarelimitedinnumberandfurther
researchinthisareaiswarranted.
Table1.Partitioncoefficientsofgreenteapolyphenols.
Polyphenol K(non-polar/polar)
Epicatechingallate(ECG) 6.25
Epigallocatechingallate(EGCG) 2.94
Epicatechin(EC) 2.38
Catechin(C) 2.33
Epigallocatechin(EGC) 0.93
4.3. Tolerability
Overall,studiesshowthattopicalandsystemicteapolyphenolstendtobewelltolerated. Astudy
by Elsaie et al. [37] showed minimal side effects to 2% green tea topical. Ten percent of subjects
experienced stinging, which resolved within 48 h, and 15% of subjects experienced local pruritus,
whichresolvedbydaythree. InastudybyLuetal.,2016[39],systemicgreenteawasgiventosubjects
Antioxidants2017,6,2 8of16
threetimesdailyforfourweeksandthisregimenwaswelltolerated.Onesubjectexperiencedmild
constipationandtwoothersexperiencedmildabdominalpain.Oftheeightstudiesincludedinthisreview,
nonereportedmajoradverseeventsandtheteapolyphenolsweregenerallywelltoleratedintopicaland
systemicformulations.Furtherstudiesinvestigatingtheimpactofvariousdosagesshouldbeconsidered.
4.4. MechanismsofAction
Acne is thought to be due to the activity of bacteria called Propionibacterium acnes
(P. acnes), sebum production by the sebaceous gland, keratinization of the follicular keratinocytes,
and inflammation [17]. Various mechanisms of action for the clinical efficacy of tea polyphenols
in reducing acne severity have been suggested. P. acnes [48], Propionibacterium granulosum [49],
Staphylococcusaureus[49]andStaphylococcusepidermidis[49]arebacteriapresentontheskinofacne
patients. ArecentstudybyLietal.,2015[50]suggeststhattheclinicalefficacyofgreenteapolyphenols
may be due to their anti-microbial properties against these bacteria. The study compared topical
greenteaextract(EGCGcontentof0.081%),pomegranatejuice,andpomegranateextractinterms
oftheiranti-microbialproperties. Theresultsshowedthat98%ofP.acnes,P.granulosum,S.aureus,
and S. epidermidis was inhibited at concentrations of 400 µg gallic acid equivalents (GAE)/mL GT
orless.
In addition to the anti-microbial properties of tea polyphenols, other mechanisms have been
proposed to explain the improvement in acne from topical green tea administration. Yoon et al.,
2013 [31] postulated that this improvement was due to the modulation of the M locus protein
kinase-Sterolregulatoryelement-bindingprotein1(MLPK-SREBP-1)signalingpathway,whichleads
toreductioninlipogenesis. Additionally,EGCGincreasedapoptosisoftheSEB-1celllineofsebocytes
and led to a reduction in the mean colony forming units of P. acnes. Altogether, these findings
further support the notion that EGCG has anti-microbial activity against P. acnes. EGCG was also
foundtoreducetranscriptionofthenuclearfactor-κB(NF-kB)pathwayandreduceinflammation.
Overall, studies suggest that tea polyphenols exert their effect on sebum production and acne via
severalmechanisms,includingactingasanti-microbial,anti-lipogenic,anti-inflammatorymolecules.
4.5. Limitations
Interpretationofthisreviewshouldbeconsideredinlightofthelimitednumberofstudiesthat
wereavailable. Manyofthestudieshadsmallsamplesizesandsomestudieshadpoorresearchdesign,
includingalackofcontrolgroup. Morestudiesofhighqualityareneededtoestablishtheefficacyof
teapolyphenolsforcontrollingsebumproduction,aswellaspreventingormanagingacnevulgaris.
5. Conclusions
Our search produced a limited number of results for how tea polyphenols may be used in
reducingsebumsecretionandacnepathology.Whileallthestudiesusedsomeformofteapolyphenols,
theexposureswerenotuniform. Somestudiesincludedunknowntypesofteaandwithunspecified
amountsofteapolyphenolsasexposure. However,basedonthisreviewthereissomeevidencethat
tea polyphenols used orally and topically may be beneficial for skin health and more specifically,
forreducingsebumproductionbythesebaceousglandsandforthepreventionandtreatmentofacne
vulgaris. Physiciansandotherhealthcareprofessionalsshouldbeawareofthestudiesexamining
thebeneficialeffectsofteapolyphenolsastheycouldpotentiallybeusedasalternativesinskincare.
Researchstudiesofhighqualityandwithlargesamplesizesareneededtoassesstheefficacyoftea
polyphenolsintopicalandoralpreventionofacnevulgarisandlipidsynthesisbythesebaceousglands.
AuthorContributions: SuzanaSaricandRajaK.Sivamaniconceivedanddesignedthereview;SuzanaSaric,
ManishaNotay,andRajaK.Sivamanicriticallyevaluatedthearticlesforinclusioninthisreview;SuzanaSaricand
ManishaNotaywrotethefirstdraftofthismanuscript;RajaK.Sivamaniperformedcriticaleditingandprovided
overalloversightforthereview.
ConflictsofInterest:Theauthorsdeclarenoconflictofinterest.
Antioxidants2017,6,2 9of16
AppendixA
TableA1.Teapolyphenolstudies—summary.
Polyphenol
Therapy(Topicalor Comparison(or
Tea Subtypesand Subjects(n,Age) StudyDesign,Duration MajorOutcomeMeasures MajorResults AdverseEvents Reference
Systemic;Dosage) Control/Placebo)
Content
SebumProductionStudies
Single-blinded,
placebo-controlled, G1(GTgroup):
monocentricstudy; significantreduction
Pakistan(months insebumsecretion
December-February); frombaselineto
2groups(G): 60daysoftreatment
G1:usedGTtopicalonone comparedtoplacebo
cheek,placeboontheother; control(p=0.0060)
n=11; (27%decrease
GTformulation: G2:GT-Ltopicalonone Percentchangeinsebumsecretion frombaseline);
5%greentea; Greentea+Lotus n=22; cheek,placeboontheother; every15days(calculatedbyformula G2(GT-Lgroup):
Greentea Mahmoodetal.,
Greentea GT-Lformulation: (GT)Topical (GT-L)Topical; allhealthymen; n=11. %change=((Dx−D0)/D0)×100; significantreduction Nonereported 2013[15]
2.5%greentea+ PlaceboTopical Age22–28years-old. Interventionlength: Dx=sebumvalueonday15,3045,60; insebumsecretion
2.5%lotusextract. 60days; D0=baselinesebumvalue) frombaselineto
Amountofteapolyphenol: 60daysoftreatment
informationnotprovided; comparedtoplacebo
Frequencyofapplication: control(p=0.0002)
oncedailyatbedtime; (25%decrease
Followuptime:baseline, frombaseline);
day15,30,45,60; Placebo:nosignificant
Sebumexcretiononboth effectonreducing
cheeksmeasuredwith sebumsecretion.
Sebumeterateachvisit.
Therapeuticstudy
Interventionlength:
60days;
Percentchangeinskinsebum 3%GTEformulation
Frequencyoftopicaluse:
production(calculatedviaformula decreasedsebum
n=10; notstated;
%change=((A−B)/B)×100 productionbynearly Mahmoodetal.,
Greentea 3%GTextract Topical Nocontrolgroup Age24to40years-old; Amountoftopical:
A=individualvalueofanyparameter 10%atweek1, 2010[34]
allhealthymen notstated;
(from1stto8thweek); and60%atweek8)
Followup:skinsebum
B=zerovalueforthatparameter. (p<0.05)
productionmeasuredat
week1,2,3,4,6,and8
viasebumeter.
Antioxidants2017,6,2 10of16
TableA1.Cont.
Polyphenol
Therapy(Topicalor Comparison(or
Tea Subtypesand Subjects(n,Age) StudyDesign,Duration MajorOutcomeMeasures MajorResults AdverseEvents Reference
Systemic;Dosage) Control/Placebo)
Content
AcneStudies
Betweengroup
comparison:G1vs.
G2:significant
reductionin
inflammatorylesion
countsonnose
(p=0.03),perioralarea
(p=0.04)andchin
(p=0.03);no
Randomized,doubleblind,
differenceintotal
placebocontrolledtrial;
lesioncount;
May2012to
n=80; G1didnothave
October2013,Taiwan;
Amountof Allwomen; significantreduction G1:1subject
Interventionlength:
teapolyphenols: Age25–45years-old onforehead,cheek developedmild
4weeks;
EachGTE withmoderateto andtotallesioncount constipation,
Followup:baselineandat
capsulecontained: severeacne comparedtoplacebo; 2subjects
Systemic 4weeks;
285.6mgEGCG, (determinedby Acnelesioncounts(inflammatoryand Withingroup abdominal
DecaffeinatedGTE; G1:receiveddecaffeinated
78.7mgECG, Placebo Investigator’sGlobal non-inflammatory)recordedforentire comparison: discomfortafter Luetal.,
Greentea eachcapsule500mg GTEfor4weeksn=40;
38.5mgEGC, (cellulose) Assessment(scoreof3 facebyblindeddermatologistat G1:Comparedwith GTEtreatment; 2016[39]
decaffeinatedGTE G2:placebo(purecellulose)
24mgEC, or4onascale0to5)); baselineandat4weeks baseline,G1 G2:1subject
orcellulose for4weeksn=40;
21.25mgGCG, Noneofthewomen (decaffeinatedGTE) thirsty,1difficulty
Productspackagedinto
<0.3mgGC, receivedsystemic hadsignificantlylower fallingasleep;
identicalcapsulesfor
<0.3mgcaffeine, retinoidorhormone numberof Nomajoradverse
blindingpurposes;
51.65mgcellulose treatmentduring inflammatorylesions effectsnoted.
Frequency:Subjectstook
previous3months. onforehead(p=0.04),
1capsule30minafter
cheeks(p=0.04)and
meals3timesdailyfor
entireface(totallesion
4weeks.
count)(p=0.003);
G2:inplacebogroup,
therewassignificant
reductionin
inflammatorylesion
countoncheeks
(p=0.01),chin
(p=0.01)andentire
face(p=0.02).