not - dr amy yasko - recovering autistic children and...
TRANSCRIPT
• 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
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