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JMED Research

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Cite this Article as: Veronika Husarova and Daniela Ostatnikova (2013), “Monosodium Glutamate o!i"

#$$e"ts and %eir &m'li"ations $or Human &ntake: evie*,+ M#D esear"%, Vol- 2013 (2013), rti"le &D.0/., DO&: 10-112013-.0/.

Research Article

Monosodium Glutamate Toxic Effects and Their

Implications for Human Intake: A Review

Veronika Husarova and Daniela Ostatnikova

Institute of Physiology, Faculty of Medicine, Comenius University, Bratislava, Slovakia

Correspondence should be addressed to !eronika "usarova# nika$husarova%gmail$com

&eceived '( )ctober *+'(# ccepted '- .ovember *+'(# Published */ 0ecember *+'(

cademic 1ditor Umit rslan

Copyright 2 *+'( !eronika "usarova and 0aniela )statnikova$ 0istributed under Creative Commons

CC3B4 ($+

Astract

Monosodium Glutamate (MG) is one o$ t%e *orld4s most *idel5 used $ood additives- &ts to!i"

e$$e"ts %ave 6een s%o*n in numerous animal studies, %o*ever in most o$ t%em, t%e met%od o$administration and t%e doses *ere not similar to %uman MG intake- &n t%is 'a'er *e revie*animal and %uman studies in *%i"% MG e$$e"ts on "entral nervous s5stem, adi'ose tissue and liver,

re'rodu"tive or7ans and ot%er s5stems %ave 6een s%o*n and *e dis"uss t%eir im'li"ations $or

%uman MG intake-

!e"words: 8ood additives, o6esit5, 9%inese restaurant s5ndrome-

Introduction

Monosodium Glutamate (MG) is one o$ t%e*orld4s most e!tensivel5 used $ood additives*%i"% is in7ested as 'art o$ "ommer"iall5

'ro"essed $oods- s a $lavor en%an"er, MGin"reases t%e sa'idit5 o$ $ood- MG 'rodu"es

a $lavor t%at "annot 6e 'rovided 65 ot%er$oods- &t eli"its a taste des"ri6ed in a'anese

as umami, *%i"% is translated to savor544(;irks 200)- &n 1<<1, t%e avera7e intake o$MG in =nited >in7dom *as /0 m7da5 $or

7eneral 'o'ulation individual and ?-./ 7da5$or e!treme users (%odes et al- 1<<1)- %eestimated avera7e dail5 MG intake 'er

'erson in industriali@ed "ountries is 0-3A1-0 7, 6ut it de'ends on t%e MG "ontent in

$oods and an individual4s taste 're$eren"es(Ge%a et al- 2000)- ""ordin7 to a BointinCuir5 65 t%e 7overnments o$ ustralia and

e* Eealand in 2003, a t5'i"al 9%ineserestaurant meal "ontains 6et*een 10 and

100 m7 o$ MG 'er 100 7 (8reeman 200.)-%e oral dose t%at is let%al to 0F o$ su6Be"ts(D0) in rats and mi"e is 1-000A

1/-000 m7k7 6od5 *ei7%t (alker andu'ien 2000)-

tudies 'rovidin7 t%e eviden"e o$ MG to!i"

e$$e"ts %ave raised t%e in"reasin7 interest inMG intake as $lavor en%an"er- euroto!i"e$$e"ts in 6rain, o6esit5 and meta6oli"

de$e"ts, I9%inese restaurant s5ndrome“ anddetrimental e$$e"ts on se! or7ans are t%emost dis"ussed in t%e "onne"tion *it% MG

intake- e 6rie$l5 revie* t%e studies a6outMG e$$e"ts and its 'otential 'at%olo7i"al

in$luen"e on di$$erent s5stems in %umans-

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Veronika Husarova and Daniela Ostatnikova (2013), JMED Research$ DO&: 10-112013-.0/.

Central #ervous $"stem

Glutamate is t%e e!"itator5 neurotransmitterin t%e mammalian "entral nervous s5stem(9) 'la5in7 an im'ortant role in 6ot%

'%5siolo7i"al and 'at%olo7i"al 'ro"esses(Mattson 200/)- Glutamate re"e'tors in"lude

t%ree $amilies o$ ionotro'i" re"e'tors (MD

J Jmet%5lJDJas'artate, MK J LJaminoJ3J%5dro!5JJmet%5lJ?Jiso!a@ole'ro'ioni" a"id

and kainate) and t%ree 7rou's o$meta6otro'i" re"e'tors (mGlu) (Meldrum

2000)- %e5 are dis'ersed t%rou7%out t%e"entral nervous s5stem in"ludin7 am57dala,

%i''o"am'us and %5'ot%alamus *%ere t%e5re7ulate man5 vital meta6oli" and autonomi"$un"tions (9ollison et al- 2012)-

MG is used as an a7ent *%i"% in %i7% doses"auses neuronal ne"rosis in %5'ot%alami"

ar"uate nu"lei in neonatal rats (Kelae@ et al-1<<<)- Ho*ever, MG e$$e"ts are moree!tensive and not limited to %5'ot%alami"

area- MG (? m77, su6"utaneousl5, on 'ostJnatal da5s 1, 3, and ) led to 're$rontal

"ere6ral "orte! "%an7es, in"ludin7 $e*erneurons, s%orter and less rami$ied dendriti"

'ro"esses (Gon@ale@J;ur7os et al- 2001) andloss o$ "orti"al "ell num6er $rom 'ostnatalda5 /J1? "om'ared to "ontrol rats (iveraJ

9ervantes et al- 200?)- %e same dose o$ MGinBe"ted su6"utaneousl5on da5s 2, ?, ., /, and10 o$ 'ostnatal li$e resulted in 30F and ?0F

redu"tion o$ 'ituitar5 *ei7%t in a7es o$ . and12 mont%s res'e"tivel5 (Misko*iak and

Kart5ka 2000)- Kituitar5 *ei7%t a$$e"tionseems to 6e "onne"ted *it% its $un"tionderan7ement- &n"reased

'roo'iomelano"ortin m levels andadreno"orti"otro'i" %ormone "on"entration

in t%e adeno'ituitar5 %ave 6een $ound inneonatal MGJtreated rats "om'ared *it%"ontrols (? m77, administrations

intra'eritoneall5) (kultet5ova et al- 1<</)-8urt%ermore, numerous studies %ave s%o*n

t%at neonates treated *it% MG e!%i6itedneuronal "ell deat% *it% redu"tion o$'%otore"e'tor and 7lial "ells (;lanks et al-

1</1, ei$Je%rer et al- 1<, e7an et al-1</1, H5ndman and dler 1</1)-

lt%ou7% t%e to!i" e$$e"ts o$ MG on t%e 9

%ave 6een s%o*n in 'reviousl5 mentionedanimal studies, t%ere are 'ro6lems to a''l5t%ese results to %uman MG intake-u6"utaneous or intra'eritoneal MG

administration in rats "an 6e %ardl5"om'ared *it% 'eroral intake o$ MG-

8OHO #!'ert 9ommittee on 8ood

dditives (#98) in 1<// noted t%at 6loodlevels o$ 7lutamate asso"iated *it% lesions o$

t%e %5'ot%alamus in t%e neonatal mouse*ere not a''roa"%ed in %umans even a$ter

6olus doses o$ 10 7 MG in drinkin7 *ater(Meldrum 2000)- o 'at%olo7i"al "%an7es in

t%e %5'ot%alami" ar"uate nu"lei o$ 're7nantand la"tatin7 $emale rats and t%eir $etuses,su"klin7s, and *eanlin7 mi"e *ere o6served

a$ter MG intake in diet (1?-0, ?2-/ or ?2-0

7k7) (akasaki 1</)- %is "an 6e e!'lained65 t%e results o$ t%e stud5 in 'i7s *%i"% %as

s%o*n t%at less t%an F o$ in7ested7lutamate *as a6sor6ed $rom t%e 7ut intot%e 'ortal 6lood (eeds et al- 1<<.)-

Ho*ever, "ontradi"tor5 results in di$$erent6rain areas %ave 6een $ound in male al6ino

rats $ed 65 a lo*er dose o$ MG (3 7k7da5)mi!ed *it% t%eir $oods $or 1? da5s-

Histolo7i"al e!amination o$ "ere6ellar "orte!s%o*ed de7enerative "%an7es as '5knoti"KurkinBe and 7ranule "ells *it% areas o$

de7eneration surrounded 65 in$lammator5"ells in 7ranular la5er (Has%em et al- 2012)-

&n"onsisten"5 in a6ove mentioned resultsreCuires $urt%er resear"% to elu"idate t%e

me"%anisms o$ MG a"tion in t%e 9 a$tera6sor'tion in %umans- Moreover, t%ein7ested 7lutamate e$$e"ts on 9 must 6e

resear"%ed also in its "onne"tion *it%si7nallin7 $rom t%e 7astrointestinal tra"t- &n

rats, a"tivation o$ 6ot% t%e 7astri" and t%e"elia" 6ran"%es o$ t%e va7us nerve led to t%ea"tivation o$ t%e insular "orte!, lim6i"

s5stem, %5'ot%alamus and nu"leus tra"tussolitaries- 8urt%ermore, as a result o$

'ostin7estive e$$e"ts, MG *as a6le to indu"e$lavorJ're$eren"e learnin7 (;annai and orii2013)-

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%e ne!t im'ortant di$$eren"e 6et*een

rodent and %uman MG intake is a 'eriod o$li$e *it% re7ard to neuronal develo'ment- &t

*as su77ested t%at MG e!"itoto!i"it5 o""ursonl5 *%en t%e 6loodA6rain 6arrier isvulnera6le, $or e!am'le in neonates

(Mat5skova et al- 200/)- #98 in 1<//su77ested t%at in7estion o$ MG *as not

asso"iated *it% elevated levels in maternal

milk and 7lutamate did not readil5 'ass t%e'la"ental 6arrier (alker and u'ien 2000)-

lso t%e 9onsensus meetin7 in 200 noted

t%at 7lutamate did not tres'ass into $etal

"ir"ulation, even in %i7% doses (;e5reut%er et

al- 200)- Ho*ever, t%e o''osite $indin7s%ave 6een s%o*n in animal studies and t%e

7lutamate neuroto!i"it5 in ne*6orns *it%t%e 6e%avioral e$$e"ts rat%er t%an stru"tural

or %istolo7i"al "%an7es remains in Cuestion-

>unmin7 $ilial mi"e *%i"% mot%ers treated*it% MG (2- m77 or ?-0 m77 6od5

*ei7%t) 'er os in 1J21 da5s o$ 're7nan"5

%ad si7ni$i"antl5 im'aired NJma@e

dis"rimination learnin7 in t%e .0-da5,alt%ou7% t%e neuronal dama7e o$ t%e'eriventri"ular or7ans or t%e %5'ot%alamus

*as not o6served (Nu et al- 1<<)- Moreover,

su6neuroto!i" doses o$ MG (2 m77, $or 10da5s) 7iven 'erorall5 to rat neonates led to

si7ni$i"ant de"rease in t%e a"tive avoidan"elearnin7 'er$orman"e at t%e <0t%'ostAdosin7

da5, *%i"% indi"ates t%at earl5Jli$e MG

e!'osure "ould lead to su6tle 6e%avioral

a6errations in adult%ood (li et al- 2000)-

One o$ t%e most im'ortant 'ro6lems in t%e

a''li"ation o$ t%e results o$ animal studies to%uman dietar5 MG e$$e"ts are t%e

di$$eren"es 6et*een doses administered toanimals and t%ose in7ested in $ood o$ a

%uman as a $lavor en%an"er- %e lo*est dosein t%e 'reviousl5 mentioned studies *as 2

7k7 o$ 6od5 *ei7%t t%at "orres'onds to anin7estion o$ 1?0 7 in a 0 k7 man, *%ile t%eavera7e dail5 intake o$ MG is estimated to

6e 0-3A1-0 7 (Ge%a et al- 2000)- %us, $urt%er

animal studies $o"used on MG e$$e"ts on t%e9 in diet s%ould eCuali@e t%e doses to

%uman intake- 8urt%er resear"% s%ould 6edone to elu"idate t%e 6e%avioral e$$e"ts o$'eroral intake o$ MG in various doses and

'otentiall5 di$$erent in$luen"e o$ MG on

$etal, neonatal and adult 6rain stru"tures in%umans-

%esit" and Metaolic &isturances

Data $rom animal studies, in *%i"% neonataladministration o$ MG 'rovides a model o$

o6esit5 *it% im'aired 7lu"ose toleran"e and

insulin resistan"e led to "on"erns a6outo6esit5 in %umans usin7 MG in $ood- More

%5'ot%eses %ave 'ro'osed t%e me"%anisms

o$ MG in$luen"e on meta6olism- %e

'otential link 6et*een MG and o6esit5

in"ludes t%e MG e$$e"t on ener75 6alan"e 65in"reasin7 'alata6ilit5 o$ $ood and 65

disru'tin7 t%e %5'ot%alami" si7nalin7"as"ade o$ le'tin a"tion (He et al- 2011,

Hermanussen and res7uerres 2003)- %e

in$lammator5 6asis o$ MGJindu"ed o6esit5*as demonstrated in t%e 1<t% *eeks old rats

*%i"% *ere treated 65 su6"utaneous

inBe"tions o$ 2 m77 o$ MG on 'ostnatal

da5s 2 and ? and 65 su6"utaneous inBe"tionso$ ? m77 on 'ostnatal da5s ., / and 10- MGin"reased m e!'ression o$ interleukinJ.,

tumor ne"rosis $a"torJal'%a, resistin and

le'tin in vis"eral adi'ose tissue, it in"reasedinsulin, resistin and le'tin levels in serum

and it also im'aired 7lu"ose toleran"e(omanJamos et al- 2011)- s liver

transaminases *ere severel5 de'ressed,

aut%ors %5'ot%esi@ed t%at MG "ould indu"e

liver inBur5 likel5 as a "onseCuen"e o$in"i'ient nonal"o%oli" steato%e'atitis,

"ontri6utin7 to in$lammation (omanJamos

et al- 2011)- %e asso"iations o$ liveralterations *it% adi'ose tissue meta6olism in

nonal"o%oli" steato%e'atitis a$ter dietar5MG %ave 6een also s%o*n at 32 *eeks o$

a7e 9;. mi"e *%i"% mot%ers *ere $ed65 lo*Jdose dietar5 monosodium 7lutamate

(0-.? 7l < m7k7) t%rou7%out 7estationand *ere *eaned onto t%e same diet- MGin"reased t%e e!'ression o$ several 7enes

im'li"ated in adi'o"5tes di$$erentiation,

elevated serum $ree $att5 a"ids, tri7l5"erides,insulin and 6ile s5nt%esis (9ollison et al-

20106)- ut%ors %5'ot%esi@ed t%at t%edevelo'ment o$ %e'ati" insulin resistan"e"ould 6e t%e "onseCuen"e o$ dere7ulation

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6et*een liver and adi'ose tissue- &n

a""ordan"e *it% t%ese results are t%e$indin7s o$ elevated as'artateaminotrans$erase and alanineaminotrans$erase in adult male istar rats

treated *it% 0-0? m7k7 and 0-0/ m7k7 o$monosodium 7lutamate mi!ed *it% t%e

7ro*erPs mas% $or ?2 da5s, *it%

de7enerative "%an7es on t%e liver anddilatation o$ t%e "entral vein (#*eka et al-

2011)- O!idative stress a$ter MGadministration 65 a 7ava7e at a dose o$ 0-.

m77 $or 10 da5s %as 6een s%o*n in t%e livero$ rats, in *%i"% MG indu"ed li'id

'ero!idation, de"reased redu"ed 7lutat%ionelevel and in"reased a"tivities o$ 7lutat%ioneJsJtrans$erase, "atalase and su'ero!ide

dismutase (On5ema et al- 200.)-

%e studies indi"ated t%at MG diet

in$luen"ed 6ot% %e'ati" and adi'ose tissue in6ot% adult (On5ema et al- 200., omanJamos et al- 2011) and 'ro7en5 o$ $emale

rodents *it% 7reat im'a"t on o$$s'rin7meta6olism ($i$i and 66as 2011, 9ollison et

al- 20106)- &nterestin7 $indin7 is t%e %i7%era6dominal $at and $at 6od5 *ei7%t in s'ite o$

lo*er dail5 ener75 intake and 6od5 *ei7%t int%e o$$s'rin7s o$ MG $ed rats t%an in t%eo$$s'rin7s o$ %i7% "alori" "%o* $ed rats ($i$i

and 66as 2011)- imilar results "on"ernin7$at "ontent6od5 *ei7%t ratio %ave 6eeno6served in 30 da5s old rats inBe"ted *it% ?

7k7 o$ MG *it%in t%e $irst 10 da5s o$ li$e-Hi7%er adi'o"5te li'id "ontent, "ell diameter,

sur$a"e area and volume in s'ite o$ lo*er6od5 *ei7%t *it% t%e results in arrested7ro*t% and o6esit5 a$ter MG administration

"om'ared to "ontrol rats %ave 6een $ound(Dolniko$$ et al- 2001)-

%e doses and administration o$ MG torodents in ot%er studies desi7ned $or o6esit5,

meta6olism and liver distur6an"es resear"%(9ollison et al- 20106, #*eka et al- 2011) are

more similar to %uman MG intake t%an instudies $o"used on MG e$$e"ts on t%e 9-nimal studies results "ould 6e t%e link to

'otential me"%anisms o$ MG e$$e"ts onmeta6olism in %umans, %o*ever t%e

su6stantial di$$eren"es must 6e noted- %e

$indin7s o$ %i7%er 6od5 $at *ei7%t in s'ite o$

lo*er 6od5 *ei7%t *ere not in a""ordan"e*it% %uman studies in *%i"% MG intake *as'ositivel5 asso"iated *it% ;M& and in"iden"eo$ over*ei7%t in a''arentl5 %ealt%5 9%inese

adults (He et al- 2011)- lt%ou7% t%e'lausi6ilit5 o$ t%e %5'ot%esis o$ MG intake

in "onne"tion *it% o6esit5 %as 6een

dis"ussed (;urse5 et al- 2011) and o''ositeresults %ave 6een 'reviousl5 $ound (%i et al-

2010), t%e de"reased 6od5 *ei7%t in mi"e"ould 6e asso"iated *it% t%e $a"t t%at mi"e

neonatall5 inBe"ted *it% MG did not 6e"omeo6ese until 'u6ert5 (Dolniko$$ et al- 2001)-

%us, it is 'ossi6le t%at MG %as di$$erente$$e"ts on t%e $un"tion o$ adi'ose tissue inimmature individuals and adults-

%e ot%er im'ortant di$$eren"e 6et*een t%eout"omes o$ animal and %uman studies are

t%e 'at%ome"%anisms 'otentiall5 leadin7 too6esit5- %ile o6esit5 a$ter MG diet in rats"ould 6e t%e result o$ le'tin resistan"e

(Dolniko$$ et al- 2001), in %umans MG "ouldlead to o6esit5 due to t%e in"rease in t%e

intake o$ %i7% "alori" savor5 $oods, in *%i"%MG en%an"es likin7 resultin7 in learnin7

rein$or"ement (;annai and orii 2013,Neomans et al- 200/)- &n a""ordan"e *it% t%is%5'ot%esis is t%e $indin7 o$ a si7ni$i"ant

in"rease o$ %un7er and savor5 $lavor sou'intake, even in t%e a6sen"e o$ MG, *%i"% %as6een o6served in a 7rou' o$ volunteers

'reviousl5 trained in $our sessions *%ere t%esou' *as "onsumed *it% added MG

(Neomans et al- 200/)- Ho*ever, t%e o''ositeresults in"ludin7 su6Be"tive assessments o$%un7er %ave 6een s%o*n in adults

su''lemented $or . da5s *it% a nutritionaldose o$ MG (2 7da5)- MG did not a$$e"t

%un7er and $ullness o$ sensations, %o*ever itsi7ni$i"antl5 in"reased 7astri" distension $or2 %ours $ollo*in7 t%e meal- MG intake *as

also asso"iated *it% in"reased levels o$ some"ir"ulatin7 amino a"ids (leu"ine, isoleu"ine,

valine, l5sine, "5steine, alanine, t5rosine, andtr5'to'%an) "om'ared *it% "ontrols- o"%an7es in t%e 'ost'randial 7lu"ose and

insulin *ere noted 6et*een MG and a9lJsu''lemented meals used in "ontrols (;outr5

et al- 2011), *%i"% is a si7ni$i"ant di$$eren"e

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$rom 'reviousl5 mentioned animal studies-

Ho*ever t%e insulin res'onse in min'ost'randiall5 'ositivel5 "orrelated *it% t%e

'lasma 7lutamate "on"entration durin7 t%eoral 7lu"ose toleran"e test, *%i"% indi"atest%at 7lutamate "an 'arti"i'ate in t%e insulin

res'onse to nutrients durin7 $ood intake(9%evassus et al- 2002)- %e MG in$luen"e

on insulin release in %umans s%ould 6e also

evaluated immediatel5 a$ter MG intake, ast%e e$$erent 'an"reati" 6ran"% o$ va7us nerve

"ould stimulate insulin se"retion durin7 t%e

"e'%ali" '%ase a$ter tastin7 MG, *%i"% *as

s%o*n in rats (iiBima et al- 1<<0)-

8urt%ermore, animal studies results are

a''li"a6le *it% di$$i"ult5 to %umans as%uman $ood is mu"% more diverse, ri"% and

"om6ined *it% anot%er su6stan"es

'otentiall5 leadin7 to 'otentiation orin%i6ition o$ 'arti"ular "om'ounds e$$e"ts- &t

%as 6een s%o*n, t%at MG (120 m7k7da5)

in "om6ination *it% as'artame elevated

6od5 *ei7%t and "aused 2-3J$old in"rease in$astin7 6lood 7lu"ose "om'ared to standard"%o* and also "aused in"reased insulin

resistan"e durin7 t%e &nsulin oleran"e est

"om'ared to as'artame alone (0m7k7da5), *%i"% "aused 1-.J$old in"rease

in $astin7 6lood 7lu"ose *it% redu"tion o$insulin sensitivit5 durin7 an &nsulin

oleran"e est in mi"e (9ollison et al- 2012)-

MG "om6ined *it% dietar5 transJ$at

in"reased "entral adi'osit5 and d5sli'idemia"om'ared to mi"e $ed *it% eit%er transJ$att5

a"idsJenri"%ed diet or dietar5 MG alone

(9ollison et al- 2010a)-

&n"on"lusion t%e animal studies %ave s%o*nt%at MG 'eroral administration in doses

similar to avera7e %uman intake (#*eka etal- 2011) and t%e intake in e!treme users

(9ollison et al- 20106) led to distur6an"es inmeta6olism *it% t%e in"rease in more'arameters in"ludin7 insulin, $att5 a"ids and

tri7l5"erides in serum,it in"reased t%e

e!'ression o$ several 7enes im'li"ated inadi'o"5tes di$$erentiation and it also a$$e"ted

t%e liver $un"tion resultin7 in elevation o$transaminase levels and 6ile s5nt%esis-Ho*ever, t%e a''li"ation o$ t%ese results to

%uman MG intake is di$$i"ult due to

di$$eren"es in me"%anisms *%i"% "ould'otentiall5 lead to o6esit5 and 'ossi6ile

"om6ination *it% anot%er su6stan"es leadin7to 'otentiation or in%i6ition o$ 'arti"ular"om'ounds e$$e"ts- %e "ontradi"tions in t%e

results o$ %uman studies reCuire $urt%erresear"% to evaluate t%e in$luen"e o$ t%e

dietar5 MG intake on o6esit5, meta6oli" and

7astrointestinal $un"tions-

Chinese Restaurant $"ndrome

%e I9%inese restaurant s5ndrome “(9)

*as $or t%e $irst time des"ri6ed more t%an ?05ears a7o- %e ori7inal des"ri'tion o$

s5m'toms %avin7 t%eir onset a6out 20minutes a$ter startin7 t%e meal in"luded

num6ness or 6urnin7 at t%e 6a"k o$ t%e ne"k,

radiatin7 into 6ot% arms and sometimes intot%e anterior t%ora!, *%i"% *as asso"iated

*it% a $eelin7 o$ 7eneral *eakness and

'al'itation (P9%inese restaurant s5ndromeP

1<./)- %e s5m'toms o$ $lus%in7, di@@iness,s5n"o'e, and $a"ial 'ressure *ere des"ri6edlater (Ge%a et al- 2000)- Monosodium

7lutamate *as *idel5 6elieved to 6e

asso"iated *it% 9, %o*ever revie*s o$relevant studies %ave 'ro'osed t%at t%e

studies *%i"% asso"iated MG *it% 9 didnot %ave t%e ro6ust e!'erimental desi7n,

results *ere in"onsistent and t%e $reCuen"5

o$ res'onses to MG intake *as not %i7%

enou7% to 6rin7 eviden"e t%at MG is t%etri77er o$ 9 (Eaut"ke et al- 1</., 8reeman

200.)- %us t%ere a''ears to 6e little reason

to em6ark on an e!tensive *orku' andtreatment re7imen *it% a 'resum'tive

dia7nosis o$ MG into!i"ation (Eaut"ke et al-1</.)- Heada"%es or ot%er s5m'toms a$ter

9%inese $ood intake "ould 6e rat%erasso"iated *it% e!"e'tionall5 %i7%

"on"entrations o$ $at and sodium t5'i"al $or9%inese restaurant meals (8reeman 200.)-

$ter ?0 5ears o$ resear"% *e "an "on"lude

t%at t%e s5m'toms o$ 9 %ave not 6een'roved to 6e asso"iated *it% MG "om'ound

in 9%inese $ood and t%e 'revalen"e o$ t%et5'i"al s5m'toms is ver5 lo*- &na Cuestionnaire surve5 in 1<< in"ludin7

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3222 res'ondents onl5 1J2F re'orted

s5m'toms "%ara"teristi" $or 9 and onl50-1<F asso"iated t%e "%ara"teristi"s5m'toms *it% "onsum'tion o$ 9%inese $ood(>err et al- 1<<)- Moreover, t%e s5m'toms

e!'erien"ed 65 'eo'le *%o re'orted t%esensitivit5 to MG, are in"onsistent- s >err

(1<<) 'ro'osed: I&$ t%e *ord Qs5ndromeQ is

to 6e used to des"ri6e s5m'toms attri6utedto s'e"i$i" $ood in7redients, t%e limits o$ t%e

Qs5ndromeQ must 6e s'e"i$ied-“ (>err et al-1<<)- %us, t%e 'arti"ular s5m'toms o$ 9

s%ould 6e studied in dou6leJ6lind and'la"e6oJ"ontrolled "onditions to identi$5

MG 'ossi6le ne7ative dietar5 e$$e"ts- u"%stud5 *as "ondu"ted to investi7ate %eada"%e,'ain and me"%ani"al sensitivit5 in 'eri"ranial

mus"les a$ter oral administration o$ MG (

or 10 m7k7) or a9l (2? m7k7, 'la"e6o)-o mus"le 'ain or "%an7es in me"%ani"al

sensitivit5 %ave 6een dete"ted- Ho*ever,re'orts o$ %eada"%e and tenderness o$'eri"ranial mus"le in"reased a$ter MG,

$urt%ermore elevation o$ s5stoli" 6lood'ressure %as 6een o6served in t%e MG

session *it% 10 m7k7 "om'ared *it% MG m7k7 and 'la"e6o (;aadJHansen et al-

2010)- %us, alt%ou7% it is not 'ro6a6le t%atintake o$ MG is s'e"i$i"all5 "onne"ted to t%e"om'le! 9, MG "ould 'rodu"e 'arti"ular

s5m'toms *%i"% are or are not a 'art o$ t%eori7inal des"ri'tion o$ 9-

Reproductive %r'ans

%e e$$e"ts o$ MG on t%e re'rodu"tives5stem are do"umented in a smaller num6ert%an t%e e$$e"ts 'reviousl5 mentioned and to

our 6est kno*led7e t%e5 are limited onl5 toanimal studies- &n male *iss l6ino mi"e

su6"utaneous administration o$ MG ata dose o$ 2 m77 durin7 t%e 'erinatal 'eriodat t%e 2nd, ?t%, .t%, /t% and 10t% da5s o$ li$e

lead to t%e in"rease in t%e num6er o$ t%e'a"%5tene sta7e o$ 'rimar5 s'ermato"5te at

t%e t% da5 o$ li$e "om'ared to "ontrols(Das and G%os% 2010)- %e dou6le dose (?m77) o$ MG administered at t%e same time

to ne*6orn rats resulted in t%e de"reased*ei7%t o$ 'ituitar5 7lands and testes and

lo*ered testosterone level in ? mont%s old

se!uall5 mature male rats (Misko*iak et al-

1<<3)- &n $emale *iss l6ino mi"e,su6"utaneous inBe"tion o$ MG (2 m77) att%e same 'erinatal 'eriod (2nd, ?t%, .t%, /t%and 10t% da5 o$ li$e) led to in"reased

num6er o$ t%e 'rimar5 $olli"les *it%out an5in"rease in num6er o$ Gra$$ian $olli"les in

ovarian tissue at t%e t% da5 o$ li$e (Das and

G%os% 2011)-

Great limitation o$ t%ese studies is t%esu6"utaneous a''li"ation and 'eriod o$ MG

administration *%i"% makes t%e results%ardl5 a''li"a6le to %uman medi"ine- 8rom

t%is 'oint o$ vie*, more im'ortant are t%estudies in *%i"% MG *as mi!ed *it% t%e7ro*erPs mas% in adults- &n adult $emale

istar rats $ed 65 MG at t%e doses o$ 0-0?

m7k7 or 0-0/ m7k7 on a dail5 6asis t%e'at%olo7i"al "%an7es %ave 6een o6served in

ovaries (#*eka and OmPinia6o%s 2011) and$allo'ian tu6e (#*eka et al- 2010)- MG"aused "ellular %5'ertro'%5 o$ t%e t%e"a

$olli"uli, destru"tion o$ t%e 6asementmem6rane and stroma "ells va"uolations in

t%e ovaries- De7enerative and atro'%i"'ro"esses *ere o6served at 6ot% doses *it%

more 'ronoun"ed "%an7es in t%e 7rou'treated *it% %i7%er dose (0-0/ m7k7) o$MG (#*eka and OmPinia6o%s 2011)-

imilarl5 in $allo'ian tu6e, 6ot% MG doses"aused distortion o$ t%e 6asement mem6rane*it% t%e se'aration o$ t%e endosal'in! $rom

t%e m5osal'in!, %o*ever in rats takin7 0-0/m7k7, va"uolations and l5sed red 6lood "ells

a''eared in some 'arts o$ t%e stroma "ells(#*eka et al- 2010)- lt%ou7% t%ese studies%ave s%o*n t%e e$$e"ts o$ MG on $emale

re'rodu"tive or7ans in relevant doses a$ter'eroral intake, $urt%er studies must 6e done

to "orro6orate t%ese results and to e!'loret%e in7ested MG e$$e"ts also on male se!or7ans-

%ther M$G Effects

MG intake and its deleterious e$$e"ts %ave6een 'ro'osed also in t%e "onne"tion *it%

several ot%er s5stems- One o$ t%e moste!tensive dis"ussions %as 6een dire"ted to

MG as a tri77er o$ ast%ma- lt%ou7% t%ere

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are a $e* ane"dotal re'orts o$ MG

sensitivit5 linked to ast%ma, revie*s %aves%o*n t%at t%ese studies did not %ave t%e

ro6ust e!'erimental desi7n and *ere notre'rodu"i6le to 6rin7 t%e eviden"e t%at MGis related to ast%ma res'onse (8reeman

200., ;eausoleil et al- 200)- lso t%e ne*erstud5 a6out t%e dietar5 'atterns and MG

intake %as $ailed to 'rove t%e "onne"tion

6et*een MG and ast%ma in 9%inese adults(%i et al- 20126)- Moreover, t%ere is no

eviden"e to su''ort t%e avoidan"e o$ MG in

adults *it% "%roni" ast%ma (E%ou et al-

2012), *%i"% is su''orted 65 an animal

stud5 o$ an oval6uminJindu"ed ast%mamouse model $ed *it% a diet "ontainin7 0-F

or F MG t%e *eek 6e$ore t%e $irstoval6umin inBe"tion and $or t%e su6seCuent

3J*eek 'eriod, in *%i"% MG did not %ave

t%e in$luen"e on eosino'%il in$iltration,'rodu"tion o$ %2 "5tokines and "ir"ulatin7

&7# "on"entrations in t%e lun7s and did not

a$$e"t t%e indu"ed air*a5

%5'erres'onsiveness (Noneda et al- 2011)-

everal studies %ave 6rou7%t eviden"e a6out

t%e asso"iations 6et*een MGJindu"ed

o6esit5 and ot%er s5stems- %e inBe"tions o$MG in t%e $irst da5s o$ li$e leadin7 to MGJ

indu"ed o6esit5 resulted in t%e in"rease o$mean arterial 6lood 'ressure and redu"tion

o$ %eart rate varia6ilit5, 6rad5"ardi"

res'onses, va7al and s5m'at%eti" e$$e"ts at

33 *eeks "om'ared to "ontrol rats (>onradet al- 2012)-

Mi"e o6esit5 model indu"ed 65 MG %ass%o*n a si7ni$i"antl5 7reater $all in "ore

tem'erature a$ter a"ute "old e!'osure (?de7rees 9 $or t*o %ours) and did not

mo6ili@e 6ro*n adi'ose tissue li'ids a$tere!'osure to ? de7rees 9elsius $or si! %ours

*%ereas "ontrol animals did- %e aut%ors'ro'osed t%at MGJtreated mi"e %adde$e"tive "old indu"ed t%ermo7enesis, *%i"%

"ould result $rom im'aired a"tivation o$

t%ermo7eni" me"%anisms in 6ro*n adi'osetissue (Moss et al- 1</)-

%uman stud5 evaluatin7 t%e relations%i'6et*een MG and %emo7lo6in in 11<

9%inese men and *omen %as $ound a 'ositive

asso"iation 6et*een MG intake and%emo7lo6in in"rease onl5 in men- %e

aut%ors %5'ot%esi@ed t%at MG e$$e"t "ould6e mediated via le'tin due to t%e 'otentialrole o$ le'tin in %emato'oiesis (%i et al-

2012a)-

tudies indi"ate t%at MG in$luen"es are

"om'le! and its e$$e"ts on 'arti"ular s5stemlead to t%e "%an7es in t%e ot%er s5stem-

8urt%er resear"% s%ould 6e $o"used on

"%an7es in various s5stems and t%eir

"ommuni"ation evoked 65 MG intake in

nutritional doses in men and *omen-

(revention of M$G Toxic Effects

%e studies *%i"% 6rou7%t t%e eviden"e

a6out t%e deleterious e$$e"ts o$ MGadministration led to $urt%er resear"% o$

'otential 'rote"tive e$$e"ts o$ di$$erent

mole"ules, es'e"iall5 antio!idants-

Vitamin 9 in a dose 100 m7k7da5 7iven viaa metal oro7astri" tu6e simultaneousl5 *it%

MG at a dose o$ 3 7k7da5 mi!ed *it%

$oods $or 1? da5s %as 6een s%o*n to %avea 'rote"tive role a7ainst to!i" nerve "ell and

astro"5te 7lial $i6rillar5 a"idi" 'roteindama7e in "ere6ellar "orte! in male al6ino

rats (Has%em et al- 2012)- ll vitamin 9

(200m7k7), vitamin # (200 m7k7) and

Cuer"etin (10 m7k7) 7iven 'erorall5 *eree$$e"tive in redu"tion o$ t%e MGJindu"ed

in"rease in malondialde%5de, modulated

7lut%atione levels and 7lutat%ioneJJtrans$erase a"tivit5 and *ere e$$e"tive in

amelioratin7 t%e e$$e"ts o$ MG on t%esu'ero!ide dismutase and "atalase a"tivit5 in

t%e liver, kidne5 and 6rain in MGJtreatedrats (? m77, intra'eritoneall5 $or 10 da5s)-

ll antio!idants redu"ed MGJin"rease inserum alanine aminotrans$erase, as'artateaminotrans$erase and SJ7lutam5l trans$erase

(8arom6i and On5ema 200.)- imilar results

%ave 6een $ound in t%e stud5 o$ vitamin #e$$e"ts in rats $ed 65 MG at a dose 0-. m77

65 7ava7e- Vitamin # (0-2 m77) si7ni$i"antl5redu"ed t%e li'id 'ero!idation, it in"reasedt%e 7lutat%ione level and de"reased t%e

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%e'ati" a"tivities o$ 7lutat%ioneJsJ

trans$erase, "atalase and su'ero!idedismutase in liver- %e a"tivities o$ alanineaminotrans$erase, as'artateaminotrans$erase and SJ7lutam5l trans$erase

in serum *ere also si7ni$i"antl5 redu"ed(On5ema et al- 200.)-

Tuer"etin ( m7k7, administered in30 da5Jold male istar rats over ?2 da5s)

%as 6een s%o*n to normali@e HDJ"%olesterol, redu"e insulin, le'tin, 7lu"ose

and "reatinine levels and in"reased7lutat%ione 'ero!idase and su'ero!ide

dismutase a"tivities a$ter MG su6"utaneousa''li"ation (? m77 administered in neonatalrats $rom 2- to 12-da5) (eiva et al- 2012)-

Krote"tive e$$e"ts o$ 'retreatment *it%diltia@em $rom t%e develo'ment o$

mor'%olo7i"al and $un"tional disorders inovaries %ave 6een s%o*n in $emale rat 'u'streated *it% MG (;oBani" et al- 200<)-

Conclusions

Monosodium 7lutamate (MG) is one o$ t%e

*orld4s most *idel5 used $ood additives*%i"% en%an"es t%e $lavor o$ $ood- MG to!i"e$$e"ts on "entral nervous s5stem, adi'ose

tissue, %e'ati" tissue and re'rodu"tiveor7ans *ere s%o*n in numerous animalstudies, %o*ever t%e met%od o$

administration and t%e used doses in most o$t%em *ere not "om'ara6le *it% %uman MG

intake- nimal studies in *%i"% MG *asadministered 'erorall5 in doses similar toavera7e %uman intake or intake o$ e!treme

users s%o*ed t%at MG led to distur6an"es inmeta6olism *it% t%e in"rease in more

'arameters in"ludin7 insulin, $att5 a"ids andtri7l5"erides in serum, MG in"reased t%ee!'ression o$ several 7enes im'li"ated in

adi'o"5tes di$$erentiation, it a$$e"ted t%eliver $un"tion resultin7 in elevation o$

transaminases levels and 6ile s5nt%esis, italso led to o!idative stress in liver and to t%e'at%olo7i"al "%an7es in ovaries and $allo'ian

tu6e- MG intake in %uman studies *asasso"iated *it% in"reased levels o$ several

"ir"ulatin7 amino a"ids, %o*ever no "%an7es

in t%e 'ost'randial 7lu"ose and insulin *ere

$ound, *%i"% *as in "ontradi"tion to animalstudies results-%e relations%i' 6et*eenMG and in"reased %emo7lo6in *as s%o*n inmen and MG intake *as asso"iated *it%

%eada"%e and su6Be"tivel5 re'orted'eri"ranial mus"le tenderness- 9%inese

restaurant s5ndrome and ast%ma *ere not

'roved to 6e asso"iated *it% MG intake-Vitamin 9, vitamin #, Cuer"etin and diltia@em

%ad 'rote"tive e$$e"ts on MGJindu"ed to!i""%an7es-

Acknowled'ement

%e *ork *as su''orted 65 7rant KVVJ02?J11-

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>onrad, - K-, 8ara%, V-, odri7ues, ;-, i"%i,

- ;-, Ma"%ado, =- 8-, o'es, H- 8-, DP7ord"%aan, ;-, De n7elis, >- U &ri7o5en, M- 9-(2012)- “Monosodium Glutamate eonatal

reatment &ndu"es 9ardiovas"ularutonomi" 8un"tion 9%an7es in odents,+

1linics (ao Kaulo), .(10), 120<J1?-

Mattson, M- K- (200/)- “Glutamate andeurotro'%i" 8a"tors in euronal Klasti"it5and Disease,+ %nnals o the ew ;or<

%cadem- o 3ciences, 11??, <J112-

Mat5skova, -, Maletinska, -, Mai!nerova, -,

Kirnik, E-, >iss, - U Eele@na, ;- (200/)-“9om'arison o$ t%e O6esit5 K%enot5'es

elated to Monosodium Glutamate #$$e"t onr"uate u"leus andor t%e Hi7% 8at Diet8eedin7 in 9;. and M& Mi"e,+

,h-siological Research, (), 2J3?-

Meldrum, ;- - (2000)- “Glutamate as aeurotransmitter in t%e ;rain: evie* o$K%5siolo75 and Kat%olo75,+ Journal o

utrition, 130(? u''l), 100J1-

Misko*iak, ;-, imano*ski, - U Kart5ka, M-(1<<3)- “X#$$e"t o$ Kerinatal dministrationo$ Monosodium Glutamate (MG) on t%e

e'rodu"tive 5stem o$ t%e Male atY,+Endo<r-nologia ,ols<a, ??(?), ?<J0-

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Misko*iak, ;- U Kart5ka, M- (2000)-

“eonatal reatment *it% MonosodiumGlutamate (MG): tru"ture o$ t%e HJ

&mmunorea"tive Kituitar5 9ells,+ istolog-

and istopatholog- , 1(2), ?1J<-

Moss, D-, Ma, - U 9ameron, D- K- (1</)-“De$e"tive %ermore7ulator5 %ermo7enesis

in Monosodium GlutamateJ&ndu"ed O6esit5

in Mi"e,+ Metabolism, 3?(), .2.J30-

iiBima, -, o7i5ama, - U da"%i, - (1<<0)-

“9e'%ali"JK%ase &nsulin elease &ndu"ed 65

aste timulus o$ Monosodium Glutamate

(=mami aste),+ ,h-siolog- 6eha8ior ,?/(.), <0J/-

On5ema, O- O-, 8arom6i, #- O-, #merole, G- O-,

=ko%a, - &- U On5e@e, G- O- (200.)- “#$$e"t o$

Vitamin # on Monosodium Glutamate&ndu"ed He'atoto!i"it5 and O!idative tress

in ats,+ &ndian Journal o 6iochemestr-

6ioph-sics, ?3(1), 20J?-

Kelae@, ;-, ;la@Cue@, - -, Kastor, 8- #-,an"%e@, - U mat, K- (1<<<)-

“e"tin%isto"%emistr5 and =ltrastru"ture o$

Mi"ro7lial es'onse to MonosodiumGlutamateJMediated euroto!i"it5 in t%e

r"uate u"leus,+ istolog- and

histopatholog- , 1?(1), 1.J?-

eeds, K- -, ;urrin, D- G-, a%oor, 8-, 5kes, -,

Henr5, - U 8ra@er, #- M- (1<<.)- “#nteralGlutamate is almost 9om'letel5 Meta6oli@ed

in 8irst Kass 65 t%e Gastrointestinal ra"t o$

&n$ant Ki7s,+ %merican Journal o ,h-siolog- ,20(3 Kt 1), #?13J/-

e7an, - -, oeske, - -, ut%, - H-,

Des%muk%, K- U Namamura, H- &- (1</1)-“edu"tions in etinal GammaJmino6ut5ri"

"id (G;) 9ontent and inX3HY8lunitra@e'am ;indin7 a$ter KostnatalMonosodium Glutamate &nBe"tions in ats,+

Journal o ,harmacolog- and E4perimental

9herapeutics, 21/(3), <1J.-

ei$Je%rer, -, ;er7ent%al, - U Hanninen, -(1<)- “#$$e"ts o$ Monosodium Glutamateon 9%i"k #m6r5o etina in 9ulture,+

&n8estigati8e +phthalmolog-b Visual 3cience,

1?(2), 11?J2?-

%odes, -, it%erle5, - 9-, orman, - -,ood, - U ord, D- - (1<<1)- “ urve5 o$t%e Monosodium Glutamate 9ontent o$ 8oods

and an #stimation o$ t%e Dietar5 &ntake o$Monosodium Glutamate,+ =ood %dditi8es

1ontaminants, /(), ..3J2-

iveraJ9ervantes, M- 9-, orres, - -, 8eriaJ

Velas"o, -, rmendari@J;orunda, - U ;easJ

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e"e'tor #!'ression and 9orti"al euronal

Deat% are sso"iated *it% '3/ in GlutamateJ&ndu"ed #!"itoto!i"it5 in Vivo,+ Journal o

euroscience Research, .(), ./J/-

omanJamos, -, lman@aJKere@, - 9-,

Gar"iaJMa"edo, -, ;lan"asJ8lores, G-, 8ortisJ;arrera, -, asso, #- &-, Gar"iaJoren@ana, M-,

9am'osJe'ulveda, - #-, 9ru@, M- U lar"onJ

7uilar, 8- - (2011)- “Monosodium Glutamate

eonatal &nto!i"ation sso"iated *it%O6esit5 in dult ta7e is 9%ara"teri@ed 659%roni" &n$lammation and &n"reased m

#!'ression o$ Kero!isome Kroli$eratorJ

"tivated e"e'tors in Mi"e,+ 6asic 1linical,harmacolog- 9o4icolog- , 10/(.), ?0.J13-

eiva, 8- - 8-, 9%u$$a, - G- -, ;ra7a, 9- K-,

morim, - K- - U 8ernandes, - - H- (2012)-

“Tuer"etin meliorates Glu"ose and i'id

Meta6olism and &m'roves ntio!idant tatusin Kostnatall5 Monosodium GlutamateJ

&ndu"ed Meta6oli" lterations,+ =ood and

1hemical 9o4icolog- , 0(10), 3.J.1-

%i, E-, us"om6eJMars%, - D-, ittert, G- -,Nuan, ;-, Dai, N-, Kan, W- U a5lor, - -

(2010)- “Monosodium Glutamate is notsso"iated *it% O6esit5 or a Greater

Krevalen"e o$ ei7%t Gain over Nears:8indin7s $rom t%e ian7su utrition tud5 o$9%inese dults,+ 6ritish Journal o utrition,

10?(3), ?J.3-

%i, E-, Nuan, ;-, a5lor, - -, Dal Grande, #-

U ittert, G- - (2012a)- “MonosodiumGlutamate &ntake &n"reases Hemo7lo6in

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evel over Nears amon7 9%inese dults,+

%mino %cids, ?3(3), 13/<J<-

%i, E-, Nuan, ;-, ittert, G- -, Kan, W-, Dai, N-,dams, - U a5lor, - - (20126)-

“Monosodium Glutamate &ntake, Dietar5Katterns and st%ma in 9%inese dults,+ ,o3

+ne, (12), e1.-

kultet5ova, &-, >iss, - U e@ova, D- (1<</)-

“euroto!i" esions &ndu"ed 65 MonosodiumGlutamate esult in &n"reased

deno'ituitar5 Kroo'iomelano"ortin Gene#!'ression and De"reased 9orti"osterone

9learan"e in ats,+ euroendocrinolog- ,.(.), ?12J20-

akasaki, N- (1</)- “tudies on ;rain

esions a$ter dministration o$ MonosodiumJGlutamate to Mi"e- &&- 6sen"e o$ ;rain

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alker, - U u'ien, - - (2000)- “%e a$et5

#valuation o$ Monosodium Glutamate,+ Journal o utrition, 130(? u''l), 10?<J

2-

Neomans, M- -, Gould, - -, Mo6ini, - U

Kres"ott, - (200/)- “"Cuired 8lavor""e'tan"e and &ntake 8a"ilitated 65Monosodium Glutamate in Humans,+

,h-siolog- 6eha8ior , <3(?J), </J..-

Noneda, -, 9%in, >-, orii, >- U akai, -(2011)- “#$$e"ts o$ Oral MonosodiumGlutamate in Mouse Models o$ st%ma,+ =ood

and 1hemical 9o4icolog- , ?<(1), 2<<J30?-

Nu, -, E%ao, N-, %i, -, Ma, - U Nu, - (1<<)-“#$$e"ts o$ Maternal Oral dministration o$Monosodium Glutamate at a ate ta7e o$

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Eaut"ke, - -, "%*art@, - - U Mueller, #- -(1</.)- “9%inese estaurant 5ndrome:

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608765

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