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• Glutamate,GlutamicAcid,Glutamine,MSG

• Aspartate,Aspartame,Aspar4cAcid

• Nutra‐sweet

• Cysteine(NOTN‐acetyl‐cysteine)

Excitotoxins

So…forthoseofyouwhoarenotfamiliarwiththisprogram…whatdowemeanbyexcitotoxins…

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Glutaminecanbeconvertedtoglutamateplusammonia

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Other“Names”ForExcitotoxins

monosodiumglutamatenutrasweet/aspartame maltedbarelyflourglutamate hydrolyzedprotein maltextractnaturalflavor(s) hydrolyzedvegetableprotein(HVP) maltflavoring(s)naturalflavoring(s) hydrolyzedplantprotein maltedbarley/barleymaltmaltodextrin hydrolyzedoatflour maltedanythingcarrageenan hydrolyzeanything texturedproteingelaFn sodiumcaseinate guargumspice(s) calciumcaseinate soyextractseasoning(s) caseinate soyproteinseasonedsalt disodiumguanylate soyproteinconcentratedoughcondiFoner(s) disodiuminosinate soyproteinisolateyeastextract disodiumcaseinate soysauceautolyzedyeast chicken/pork/beef“flavoring” wheyproteinautolyzedyeastextract chicken/pork/beef“base” wheyproteinisolateautolyzedanything bouillon wheyproteinconcentratebroth vegetablegum kombuextractstock plantproteinextract l‐cysteinesoupbase smokeflavoring(s) ajinomoto

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Proteinsbreakdown

AminoAcids Glutamate

Aspartate

Cysteine

ProteinBreakdown

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Proteinsbreakdown

AminoAcids Glutamate

Aspartate

Cysteine

ProteinBreakdown

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GlutamateReceptorsGlutamateGlutamateisanexci4toryneurotransmiGor

• Peas

• Tomatoes

• Mushrooms

• ParmesanCheese

NaturalFoodsHighinGlutamate

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GlutamateReceptorsGlutamateGlutamateisanexci4toryneurotransmiGor

• Peas

• Tomatoes

• Mushrooms

• ParmesanCheese

NaturalFoodsHighinGlutamate

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• Sulfurcontainingaminoacidsleadtoincreasednorepinephrinerelease.

• Thiseffectappearstobemediatedvias4mula4onofglutamatereceptorsimplyinganexcitotoxinmechanism.

Note:rela4onshipbetweenexcesssulfurviaCBSupregula4onsandglutamate

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Theissueisboththeamountofglutamateaswellasthenumberofglutamatereceptors

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IncreasedNumberofGlutamateReceptors

ExcessiveGlutamate

NeurologicalInflammaFon

GlutamateReceptors

InconjuncFonwith…

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Receptorrecyclingmaygiveinaccuratemeasurementsofthenumberofglutamatereceptorsonau4s4c

braincells.

ReceptorRecycling

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GlutamateReceptors

ActualamountofmRNAforglutamatereceptorsishigherinauFsFcchildren.LevelsofmRNAin10au4sm(A=au4sm)and10control(C=control)postmortemcerebellumsampleswerecomparedusingreversetranscriptasePCR(RT‐PCR).Themeanau4smversusmeancontrolbandintensity(±SEM)issummarizedtotherightofeachRT‐PCR.TheYaxisofeachgraphrepresentsaveragenormalizedintensityofcDNAproductsignals.(A)RT‐PCRconfirma4onofalteredmRNAlevelsinau4sm.Allgenetranscriptsareincreasedinau4smpostmortemcerebellum(*p<0.05).(B)Inves4ga4onofmRNAlevelsofaddi4onalglutamate‐relatedgenes.Excitatoryaminoacidtransporter2(EAAT2)andtheAMPA‐typeglutamatereceptors2and3haveincreasedmRNAlevelsinau4sm(*p<0.05).Glyceraldehyde‐3‐phosphatedehydrogenasebandintensity(right,lowerpanel)wasusedfornormaliza4onofcDNAproductineachsample.

Reference:Purcell,Neurology2001;57:1618‐1628

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Chronics4mula4onofNMDAleadsto

depressionofAMPA

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Glutamate excitotoxin opioids damageGlutamate glutathione TNFalpha leaky gutGlutamate sleepGlutamate eyecontact

Glutamate acetycholine bladdercontrac4on, strabismus

Glutamate s4ms

ConsequencesofElevatedGlutamate

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Glutamateinrela4ontoGABAlevels

Glutamate

GABA

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• Gabaisnecessaryforspeech.

• Gabacreatesthe“gap”betweenwords

GABA

wordGAPwordGAPwordGAPword

GabaandSpeech

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• Gabaisnecessaryforspeech.

• Gabacreatesthe“gap”betweenwords

GABA

wordGAPwordGAPwordGAPword

GabaandSpeech

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Gaba language/speechGaba anxiety Gaba aggressivebehaviorGaba socialbehaviorGaba eyecontact

Gaba bowelfunc4on

ConsequencesofDecreasedGaba

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Pancreas

Glutamate Gaba

Pancreas

Autoan4bodiestoGAD/rubella

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Pancreas

Glutamate Gaba

Pancreas

GADenzyme

Autoan4bodiestoGAD/rubella

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Glutamateisthegun.

Calciumisthebullet.

GlutamateCalcium

Calcium

Calcium

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http://www.clipart.com/en/close-up?o=754982&memlevel=C&a=c&q=gun&s=1&e=30&show=&c=&cid=&findincat=&g=&cc=&page=
http://www.clipart.com/en/close-up?o=754982&memlevel=C&a=c&q=gun&s=1&e=30&show=&c=&cid=&findincat=&g=&cc=&page=
http://www.clipart.com/en/close-up?o=754982&memlevel=C&a=c&q=gun&s=1&e=30&show=&c=&cid=&findincat=&g=&cc=&page=
http://www.clipart.com/en/close-up?o=754982&memlevel=C&a=c&q=gun&s=1&e=30&show=&c=&cid=&findincat=&g=&cc=&page=
http://www.clipart.com/en/close-up?o=754982&memlevel=C&a=c&q=gun&s=1&e=30&show=&c=&cid=&findincat=&g=&cc=&page=
http://www.clipart.com/en/close-up?o=754982&memlevel=C&a=c&q=gun&s=1&e=30&show=&c=&cid=&findincat=&g=&cc=&page=
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GlutamateandCalcium

Glutamate calciumflowinto neurons

calciumflow nervedamage

nervedamage inflamma4on

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GlutamateandCalcium

Glutamate calciumflowinto neurons

calciumflow nervedamage

nervedamage inflamma4on

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Interac4onbetween

glutamate

and

glycine

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NutriFonIndustryExecuFve,Nov/Dec2002AndriusBaskys,MD,PhD

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polyamines

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• CalciumrequiresvitaminDandvitaminKfor

transport

• VitaminDandvitaminKarefatsolublevitamins

• LowervitaminDandlowervitaminKassociatedwith

gutabsorp4onissues

CalciumTransport

RemembervitaminKismadeinthegutbybacteriaandrequiresSAMe

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• Limi4ngcalciumwillhelplimitinflamma4on

• Magnesiumblocksthedoorforcalciumreversibly

• Zincblocksthedoorpermanently!Toomuchzincwill

s4mulateglutamateatnonNMDAglutamatereceptors.

InflammaFonandCalcium

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Whysimplybalancingglutamateandgabaalongwithotherstep1supportisenoughtotriggermetalexcre4onin

somecases

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“Intheabsenceofglutamate,neuronsareunaffectedbyacuteexposuretomercury,sugges4ngthatneuronaldysfunc4onissecondarytodisturbancesinastrocytes.”

“Coapplica4onofnontoxicconcentra4onsofMeHGandglutamateleadstothetypicalappearanceofneuronallesionsassociatedwithexcitotxins4mula4on”

Brookes,1992/MatyjaandAlbrecht,1993

IMPORTANCEOFGLUTAMATETOMETALTOXICITY

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Aluminuminterfereswith

glutamatedehydrogenase

Mercuryinhibits

glutaminesynthase


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