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• Glutamate,GlutamicAcid,Glutamine,MSG

• Aspartate,Aspartame,Aspar4cAcid

• Nutra‐sweet

• Cysteine(NOTN‐acetyl‐cysteine)

Excitotoxins

So…forthoseofyouwhoarenotfamiliarwiththisprogram…whatdowemeanbyexcitotoxins…

Glutaminecanbeconvertedtoglutamateplusammonia

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

Proteinsbreakdown

AminoAcids Glutamate

Aspartate

Cysteine

ProteinBreakdown

Proteinsbreakdown

AminoAcids Glutamate

Aspartate

Cysteine

ProteinBreakdown

GlutamateReceptorsGlutamateGlutamateisanexci4toryneurotransmiGor

• Peas

• Tomatoes

• Mushrooms

• ParmesanCheese

NaturalFoodsHighinGlutamate

GlutamateReceptorsGlutamateGlutamateisanexci4toryneurotransmiGor

• Peas

• Tomatoes

• Mushrooms

• ParmesanCheese

NaturalFoodsHighinGlutamate

• Sulfurcontainingaminoacidsleadtoincreasednorepinephrinerelease.

• Thiseffectappearstobemediatedvias4mula4onofglutamatereceptorsimplyinganexcitotoxinmechanism.

Note:rela4onshipbetweenexcesssulfurviaCBSupregula4onsandglutamate

Theissueisboththeamountofglutamateaswellasthenumberofglutamatereceptors

IncreasedNumberofGlutamateReceptors

ExcessiveGlutamate

NeurologicalInflammaFon

GlutamateReceptors

InconjuncFonwith…

Receptorrecyclingmaygiveinaccuratemeasurementsofthenumberofglutamatereceptorsonau4s4c

braincells.

ReceptorRecycling

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

Chronics4mula4onofNMDAleadsto

depressionofAMPA

Glutamate excitotoxin opioids damageGlutamate glutathione TNFalpha leaky gutGlutamate sleepGlutamate eyecontact

Glutamate acetycholine bladdercontrac4on, strabismus

Glutamate s4ms

ConsequencesofElevatedGlutamate

Glutamateinrela4ontoGABAlevels

Glutamate

GABA

• Gabaisnecessaryforspeech.

• Gabacreatesthe“gap”betweenwords

GABA

wordGAPwordGAPwordGAPword

GabaandSpeech

• Gabaisnecessaryforspeech.

• Gabacreatesthe“gap”betweenwords

GABA

wordGAPwordGAPwordGAPword

GabaandSpeech

Gaba language/speechGaba anxiety Gaba aggressivebehaviorGaba socialbehaviorGaba eyecontact

Gaba bowelfunc4on

ConsequencesofDecreasedGaba

Pancreas

Glutamate Gaba

Pancreas

Autoan4bodiestoGAD/rubella

Pancreas

Glutamate Gaba

Pancreas

GADenzyme

Autoan4bodiestoGAD/rubella

Glutamateisthegun.

Calciumisthebullet.

GlutamateCalcium

Calcium

Calcium

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GlutamateandCalcium

Glutamate calciumflowinto neurons

calciumflow nervedamage

nervedamage inflamma4on

GlutamateandCalcium

Glutamate calciumflowinto neurons

calciumflow nervedamage

nervedamage inflamma4on

Interac4onbetween

glutamate

and

glycine

NutriFonIndustryExecuFve,Nov/Dec2002AndriusBaskys,MD,PhD

polyamines

• CalciumrequiresvitaminDandvitaminKfor

transport

• VitaminDandvitaminKarefatsolublevitamins

• LowervitaminDandlowervitaminKassociatedwith

gutabsorp4onissues

CalciumTransport

RemembervitaminKismadeinthegutbybacteriaandrequiresSAMe

• Limi4ngcalciumwillhelplimitinflamma4on

• Magnesiumblocksthedoorforcalciumreversibly

• Zincblocksthedoorpermanently!Toomuchzincwill

s4mulateglutamateatnonNMDAglutamatereceptors.

InflammaFonandCalcium

Whysimplybalancingglutamateandgabaalongwithotherstep1supportisenoughtotriggermetalexcre4onin

somecases

“Intheabsenceofglutamate,neuronsareunaffectedbyacuteexposuretomercury,sugges4ngthatneuronaldysfunc4onissecondarytodisturbancesinastrocytes.”

“Coapplica4onofnontoxicconcentra4onsofMeHGandglutamateleadstothetypicalappearanceofneuronallesionsassociatedwithexcitotxins4mula4on”

Brookes,1992/MatyjaandAlbrecht,1993

IMPORTANCEOFGLUTAMATETOMETALTOXICITY

Aluminuminterfereswith

glutamatedehydrogenase

Mercuryinhibits

glutaminesynthase

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