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Sulfateisthemostcommonnutri5onaldeficiencythatyouneverheardof

StephanieSeneffMITCSAIL

March27,2018

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InMemoryOfJohnBala5necz

January19,1937– August6,2017

ZenHoneycu)JackWilson

RachelParent

TonyMitra

ShivChopra SomeJohnBala5necz“Groupies”

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JohnBala5neczEmailmessagetoJackWilson:

“SinceyouareasuperDIN(i.e.doitnow)person,andareeveneducaWngdoctorsoneataWme,whydon’tyoucontactDavidMathews,thea)orneyinTexas,whoisbuildingacaseagainstMonsanto(dmlawfirm.com).Hemightevenpostyourlatestpamphletinhiswebsite...Yourinfomightevenspeeduphisdecisiontostartthelawsuitofthecentury.”

Outline•  IntroducWon•  CholesterolSulfate•  Glycocalyx&HeparanSulfate•  BileAcids•  Glyphosate•  DiseasesLinkedtoSulfateDeficiency•  CurcuminandOtherFlavonoids•  PrevenWonofDiseasethroughDietandLifestyle

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TheBigIdeas•  Cardiovasculardiseaseisacholesterolsulfatedeficiencyproblem

•  HeparansulfatedeficiencyisakeyfactorinauWsm•  Mostmoderndiseasesthatareontherisearemechanismstorenewsulfatesupplytotheblood

•  Glyphosate(theacWveingredientinthepervasiveherbicideRoundup)disruptsthebody’sabilitytoproperlysynthesizeanduWlizesulfate

•  Taurineisastorageformofsulfate

Taurine:BriefChemistryRefresherCourse

Sulfate=SO4-2=

Taurine=C2H7NO3S= =

=

•  Taurineistheonlysulfonatedaminoacid-  Itdoesnotincorporateintoproteins-  Itisthemostcommonfreeaminoacidinthebody-  ItisstoredinlargequanWWesintheheart,brainandliver

•  Humancellscannotmetabolizetaurine,butmicrobescanextractitssulfuratomtosynthesizesulfateormethionineforthehost

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PerinatalTaurineisEssen5al*•  TaurineaccumulatesinmaternalWssuesduringpregnancy,andisreleasedtothefetusduringtheperinatalperiod

•  Mother'smilkisrichintaurine,anditaccumulatesintheneonatalbrain

•  Taurinedeficiencyinthemomleadsto:–  GrowthretardaWonintheoffspring(insufficientmethionine?)–  Impaireddevelopmentofcentralnervoussystemandpancreas–  ImpairedglucosetoleranceandvasculardysfuncWon

•  GestaWonaldiabetesinoffspringtransmitstheeffectstothenextgeneraWon

*LAertsandFAVanAssche.JPerinatMed.2002;30(4):281-6.

RoundupandGMOCrops

GMORoundup-Readycorn,soy,canola,sugarbeetsco)on,tobaccoandalfalfa

Whatisglyphosate?

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Glyphosatevs.OtherPes5cides:UsageintheUnitedStates*

*h)p://sustainablepulse.com/wp-content/uploads/GMO-health.pdf

Glyphosate

*Figure15,Seneffetal.,AgriculturalSciences,2015,6,42-70

Au5smPrevalence:6yearolds*

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TheyKnewaLongTimeAgo*•  ArWclepublishedin1960•  Fedcholesteroltomonkeys–  inducedatherosclerosis

•  Ifsulfur-containingnutrientsareadded,atherosclerosisisprevented

•  Thesenutrientsprovidesourceofsulfatetoenablecholesteroltransport

*G.V.Mannetal.,Am.J.Clin.Nutr.8,491-497,1960.

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TheyKnewaLongTimeAgo*•  ArWclepublishedin1960•  Fedcholesteroltomonkeys–  inducedatherosclerosis

•  Ifsulfur-containingnutrientsareadded,atherosclerosisisprevented

•  Thesenutrientsprovidesourceofsulfatetoenablecholesteroltransport

*G.V.Mannetal.,Am.J.Clin.Nutr.8,491-497,1960.

"AformofvasculardiseaseresemblinghumanatherosclerosishasbeenproducedintheNewWorldprimateCebusfatuella....Inordertoproducethesephenomena,thedietshadtoberichincholesterol,cholineandneutralfatbutrelaWvelylowinorganicsulfurcompounds.WithoutthisdeprivaWonoforganicsulfurtheresponseoftheserumlipidstocholesterolfeedingwassmall."

HeartDiseaseMortalityandSunlight*

*Grimesetal.,Q.J.Med.1996;89:579-589

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•  Cholesterolsulfatesuppliesoxygen,sulfur,cholesterol,energyandnegaWvechargetoalltheWssues– AlsoprotectsskinfromUVdamageandkeepsmicrobesout

•  SulfateissynthesizedfromsulfideintheskinandbloodstreamuWlizingenergyinsunlight

•  EndothelialNitricOxideSynthase(eNOS)performsthemagic

Theskinisasolarpoweredba)ery!

AProvoca5veProposal*

*SSeneffetal.,Entropy2012,14,2492-2530.







MelaninconvertsUVlighttovisiblelight,andtheflavinsineNOSrespondtobluelightby

emiungelectrons

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Theseelectronsproducesuperoxidefromoxygenthatcombineswith

sulfurtoformsulfate

CholesterolandCholesterolSulfate

SULFATE

SulfaWonmakescholesterolwater-solubleandthereforemucheasiertotransport

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Cholesterolsulfateprovidesnega5vecharge*

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Redbloodcellsexportcholesterolsulfatetothecapillarywall,supplyingitwithcholesterol,sulfate,andnegaWvecharge

*DavidsonandSeneff,Entropy14,1399-1442,2012.

Rouleaux–InsufficientNega5veCharge*

*Dr.MarcialVega;h)ps://www.youtube.com/watch?v=9vhHe55s9rg

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ArteryCrossSec5on

ExpandedView

SulfateandtheGlycocalyx

SulfateisCrucialtoMaintainStructuredWaterintheGlycocalyx

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LipidPar5clesinblooddependoncholesterolsulfateto

protectthemfromoxida5veandglyca5ondamage

CholesterolSulfateinPlacentalVilli•  Placentalvilliarehighlyenrichedincholesterolsulfate,especiallyinthirdtrimesterofpregnancy

•  Mother’sserumcholesterolsulfatesteadilyrisesthroughpregnancy

•  Inthirdtrimester,villicontain24picomol/mgofcholesterolsulfate,comparedtoonly1.5inbloodserumofanon-pregnantwoman

Linetal.,JournalofChromatographyB,704(1997)99–104

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SulfateinFetalDevelopment*•  Fetusdependsonmotherforsulfatesupply•  SulfateisessenWalfortransporWngsterols(likeestrogenandDHEA)andsupplyingextracellularmatrixproteinseverywherewithsufficientnegaWvecharge

•  SulfatedetoxifiesxenobioWcslikeacetaminophen(Tylenol)andisessenWalforexcreWngtoxinslikealuminumandmercury

•  SulfateisseverelydeficientinauWsWcchildren(1/3thenormalleveloffreesulfateinbloodstream)

*Dawson,“SulfateinFetalDevelopment,”SeminCellDevBiol2011

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HeparanSulfate:WonderWorker

Polymersofsugarswitha)achednitrogenandsulfates:safeglucosestorage

SulfatedGlycosaminoglycans(GAGs)

•  Prominentinglycocalyx:extracellularmatrixofcells

•  Amountofsulfatedependsonavailability

•  Regulatesignalingandnutrientuptake

Heparansulfate

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'Bo\lebrush'moleculestructures-proteincentered,carbohydratebristlestermina5ngwithsulfate/water'ac5vityareas'

Mul5pleRolesofHeparanSulfateProteoglycans(HSPGs)*

*Figure3.FEPoulainandHJYost.Development2015;142:3456-3467.

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HeparinProtectsfromROSduetoIron*FreeradicalproducWon(FentonreacWon):Fe(II)+02+20H--->Fe(III)(OH)2+02-

But,intheacidenvironmentofheparin:4Fe(II)+02+4H+-->4Fe(III)+2H20

superoxide

water

*M.A.Rossetal.,Biochem.J.1992,286:717-720.

HeparinProtectsfromROSduetoIron*FreeradicalproducWon(FentonreacWon):Fe(II)+02+20H--->Fe(III)(OH)2+02-

But,intheacidenvironmentofheparin:4Fe(II)+02+4H+-->4Fe(III)+2H20

superoxide

water

*M.A.Rossetal.,Biochem.J.1992,286:717-720.

Iron’sreacWonwithoxygenisamajorcontributortothearterydamagecausedbyinflammaWon

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DisruptedSignalingwhenHSPGsareDepleted*

*Figure5inPMullerandAFSchier,DevelopmentalCell21,July19,2011,145-158.

HSPGs=HeparanSulfateProteoglycans

“Theuniversalnon-specificmesenchymalreac5on”*

•  StudiedincorporaWonofsulfurintoGAGsinconnecWveWssuesurroundingarterywalls,inhumansandinrats

•  ShowedthatagingleadstoareducWoninuptakeofsulfurANDslowerrecyclingofGAGs

•  ShowedalsothatatherosclerosisisaspecialcondiWonwheremuchmoresulfuristakenupspecificallyattheregionswherecholesterolandfathaveaccumulated

*WHHaussetal.,AnnalsNYAcadSci156,207-218,1969.

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Incorpora5onofsulfurintoGAGsinarterywall*

*Figure6,WHHaussetal.,AnnalsNYAcadSci156,207-218,1969.

AtheroscleroWcarteries

Age

Sulfu

rIncorpo

raWo

nHugeamountspostnatally

Incorpora5onofsulfurintoGAGsinarterywall*

*Figure6,WHHaussetal.,AnnalsNYAcadSci156,207-218,1969.

AtheroscleroWcarteries

Age

Sulfu

rIncorpo

raWo

n

Hugeamountspostnatally

IncreasedturnoverofsulfatedGAGs

inregionswithatherosclerosis

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HeparanSulfateDeficiencyandAu5sm*

•  Experimentwith“designer”mice:impairedheparansulfatesynthesisinbrain

•  MiceexhibitedalltheclassicfeaturesofauWsm–bothcogniWveandsocial

*F.Irieetal.,AuWsm-likesocio-communicaWvedeficitsandstereotypiesinmicelackingheparansulfate.PNASMar.27,2012,109(13),5052-5056.

Recapitula5on•  Cholesterolsulfateissuppliedtothevasculaturebyred

bloodcellsandendothelialcellsinresponsetosunlight–  eNOSperformsthemagic

•  Sulfateplaysanimportantroleinthevasculaturetoinduceflowandprotectfromdamageduetoiron

•  Theglycocalyxisacomplexstructurecontainingabundantheparansulfate,whichregulatescellularsignalingandprotectsthecellmembranefromdamage

•  HeparansulfateistakenupbycellsalongwithnutrientsanditsupportsacidificaWonofthelysosometodigestnutrientsandclearcellulardebris

•  HeparansulfatedeficiencyisassociatedwithauWsminamousemodel

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BileAcids:ABriefTutorial•  Bileacidsaresynthesizedintheliverfromcholesterol,andcirculatebetweentheliverandthedigesWvetract,withabout5%beinglosttothefeceswitheachcycle–  BileacidsynthesisdependsoncytochromeP450enzymes

•  Bileacidsareconjugatedwitheithertaurineorglycineando{ensulfatedbeforebeingsecreted

•  Conjugatedbilesaltssitatthelipid/waterinterfaceand,attherightconcentraWon,formmicellesandsolubilizelipids

•  Bileacid-containingmicellesaidlipasestodigestlipidsandbringthemneartheintesWnalbrushbordermembrane,promoWngfatabsorpWon.

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Acartoondepic5onofbilecircula5on

Bacteriastripofftaurine/glycineandconvertprimarytosecondarybileacids

Bileacidsareconjugatedtoeithertaurineorglycineandthensulfatedbeforebeingshippedoutbytheliver

Modifica5onsofBileAcids

Eitherglycineortaurine

Sulfateiso{enaddedhere

Secondarybileacids

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Taurolithocholicacid3-sulfate

Taurine

Sulfate

AHypothesis:Liverdeliverstaurineandglycinetobacteriatosynthesize

methionineandsulfateforthehost

Taurine

GlycineGlycinecleavagesystem

Methylfolate

Folate

Sulfite

Serine

MethionineAssimilatory

sulfitereductase

SulfateSulfiteoxidase

Methionineistheuniversalmethyldonor

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Bifidobacteriamodifybileacidstoincreasegellingpoten5al*

•  BifidobacteriaarethemostsignificantmicrobesinthegutfordeconjugaWngtaurineandglycinefrombileacids

•  ReleaseofdeconjugatedbileacidsbyBifidobacteriacausestheaqueousmediumtogel

“IfsuchaphenomenonoccursinphysiologicalcondiWonsofhumangut,itmayimprovebacterialabilitytocolonizethegastrointesWnaltractandtheirsurvivalinthisspecificecologicalniche.”

*PJarockietal.PLOSONEDecember3,2014;9(12):e114379.

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MainToxicEffectsofGlyphosate*•  Killsbeneficialgutbacteriaandallowspathogenstoovergrow–  BifidobacteriaareespeciallysuscepWble

•  InterfereswithfuncWonofcytochromeP450(CYP)enzymes

•  Chelatesimportantminerals(iron,cobalt,zinc,manganese,etc.)

•  InterfereswithsynthesisofaromaWcaminoacidsandmethionine–  LeadstoshortagesincriWcalneurotransmi)ersandfolate

•  Disruptssulfatesynthesisandsulfatetransport

*SamselandSeneff,Entropy2013,15,1416-1463

*PlotprovidedbyDr.MarWnMichener

Clostridia Salmonella

PathogenOvergrowthinPoultryMicrobesExposedtoGlyphosate*

Bifidobacteria

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Glyphosatecontamina5oninbileacids*

•  Monsanto’sownearlystudiesfoundglyphosatecontaminaWoninbileacids

•  Likelymechanismisitsroleasaglycineanalogue:– Glyphosateconjugatestothebileacidsinplaceofglycine

•  ThiswouldbeespeciallydamagingtoBifidobacteria,becausetheydeconjugatethebileacids,thusimporWngandfreeingglyphosate

*AnthonySamsel,personalcommunicaWon

•  ompF,involvedintaurinetransport,wasthemostreducedenzymeintheenWretable

•  Enzymesinvolvedinbothtaurinetransport/metabolismandassimilatorysulfiteincorporaWonintomethionineweresuppressed

*AppendixinWLuetal.MolBioSyst20139:522-530.

GlyphosateimpairstaurinemetabolismbyEcoli*

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Inhibi5onofCytochromeP450Enzymes(CYPs)byVariousPes5cides*

Studyinratson2,4-D,clofibrate,MCPA,andglyphosate

*EHetanenetal.,ActaPharmacol.EtToxicol.1983,53,103-112.

Bifidobacteria,acetate,NaClandSO4-2

inau5sm•  AuWsWcchildrenhavelowBifidobacteria(p=0.002)*•  AuWsWcchildrenarehyponatremic(lowsodium)**–  Recurringdiarrhea(glyphosateinducesleakygut)***–  DepleWonoftaurine(taurine-conjugatedbileacidslosttofeces)

•  AuWsWcchildrenhavelowgutacetate(p=0.00002)*–  Lossofacetate-producingmicrobesthatfeedonbileacids

•  AuWsWcchildrenhavesulfatedeficiency****

*JBAdamsetal.BMCGastroenterology2011;11:22.**PGood.MedicalHypotheses2011;77:1015-1021.***JJGildeaetal.JournalofClinicalNutriWon&DieteWcs2017;3:1.1).****RHWaringandLVKlovrza.JNutrEnvironMed2000;10:25-32.

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ABTBRMouseModelofAu5sm*Thesemicehadallthemousefeaturesofau5smTheywerefed“standardrodentchow”–glyphosatecontaminated?Somefeaturesinthegut:•  Reducedlevelsofbileacids(duetoimpairedCYP7A1acWvityin

theliver)•  Furtherreducedlevelsofsecondarybileacids(impaired

metabolismbygutmicrobes)•  ReducedlevelsofLactobacillusandBifidobacteria–  ThesemicrobesarepreferenWallykilledbyglyphosate

•  Serotonindeficiency–  Serotoninisderivedfromtryptophan,aproductoftheshikimatepathwaywhichglyphosatedisrupts

*AVGlubevaetal.EBioMedicine.2017Oct;24:166-178.

ABTBRMouseModelofAu5sm*Thesemicehadallthemousefeaturesofau5smTheywerefed“standardrodentchow”–glyphosatecontaminated?Somefeaturesinthegut:•  Reducedlevelsofbileacids(duetoimpairedCYP7A1acWvityin

theliver)•  Furtherreducedlevelsofsecondarybileacids(impaired

metabolismbygutmicrobes)•  ReducedlevelsofLactobacillusandBifidobacteria–  ThesemicrobesarepreferenWallykilledbyglyphosate

•  Serotonindeficiency–  Serotoninisderivedfromtryptophan,aproductoftheshikimatepathwaywhichglyphosatedisrupts

*AVGlubevaetal.EBioMedicine.2017Oct;24:166-178.

TheseBTBRmicealsohadheparansulfatedeficiencyinthebrainventriclesandamissingcorpuscallosum

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HormonesEnhanceSulfateLevels*•  Sulfateisthefourthmostcommonanioninthebody

•  Serumsulfateiselevatedininfants,youngchildrenandpregnantwomen.

•  Estrogen,progesterone,growthhormoneandinsulin-likegrowthfactorallenhancetheexpressionofthesodium-sulfatecotransporter,increasingserumsulfatelevels.

*HJLeeetal.ProcSocExpBiolMed.2000;225(1):49-57.

HormonesEnhanceSulfateLevels*•  Sulfateisthefourthmostcommonanioninthebody

•  Serumsulfateiselevatedininfants,youngchildrenandpregnantwomen.

•  Estrogen,progesterone,growthhormoneandinsulin-likegrowthfactorallenhancetheexpressionofthesodium-sulfatecotransporter,increasingserumsulfatelevels.

*HJLeeetal.ProcSocExpBiolMed.2000;225(1):49-57.

Aromatase,anenzymethatconvertstestosteronetoestrogen,isaCYPenzyme

thatisinhibitedbyglyphosate.

ThiscouldparWallyexplaintheincreasedrisktoauWsminboys.

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SulfateDeficientMice*Micemissingthesodiumsulfatecotransportergene(NaSi-/-mice)survivedinuterobutexhibitedseveralmetabolicproblems:•  Severelyreducedserumsulfatelevels(75%reducWon)•  Significantlyreducedli)ersizeandmiscarriages•  Aseizuredisorder•  Stuntedgrowth•  Increasedliversize•  1.5to2-foldincreasedphenolsulfotransferaseacWvity

*PADawsonetal.PNAS2003;100(23):13704-13709.

SulfateDeficientMice*Micemissingthesodiumsulfatecotransportergene(NaSi-/-mice)survivedinuterobutexhibitedseveralmetabolicproblems:•  Severelyreducedserumsulfatelevels(75%reducWon)•  Significantlyreducedli)ersizeandmiscarriages•  Aseizuredisorder•  Stuntedgrowth•  Increasedliversize•  1.5to2-foldincreasedphenolsulfotransferaseacWvity

*PADawsonetal.PNAS2003;100(23):13704-13709.

Toxicphenol-sulfatemetabolitesareimplicatedinauWsm**

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eNOSisVeryVulnerable*

*S.Seneffetal.,Entropy2012,14,2492-2530

•  eNOSdependson:– Cobalamin(vitaminB12,cobalt)– Hemeiron,sulfur,zinc,oxygen– Glutathione– Sunlight/melanin– Tryptophan:sourceofNAD

•  eNOSisacytochromeP450enzyme:– Highlyvulnerabletovariousenvironmentaltoxicantslikemercury,aluminum,glyphosate,etc.

*S.Seneffetal.,Entropy2012,14,2492-2530.


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•  eNOSdependson:– Cobalamin(vitaminB12,cobalt)– Hemeiron,sulfur,zinc,oxygen– Glutathione– Sunlight/melanin– Tryptophan:sourceofNAD

•  eNOSisacytochromeP450enzyme:– Highlyvulnerabletovariousenvironmentaltoxicantslikemercury,aluminum,glyphosate,etc.

*S.Seneffetal.,Entropy2012,14,2492-2530.

GlyphosatedisruptseNOSfuncWoninmulWpleways


GlyphosatedisruptseNOS!•  Glyphosatechelatescobalt,zincandiron,makingthemunavailable

•  Glyphosateinterfereswiththesynthesisofpyrrole,theprecursortoheme(ineNOS)

•  Glyphosatedepletesglutathionebyinterferingwithmethioninesynthesisbygutmicrobes

•  Glyphosatedepletesmelaninintheskin(productofshikimatepathway)–  ImpairedconversionofUVlighttovisiblelight

•  Glyphosatedisruptstryptophansynthesis,depleWngNAD•  eNOShastwohighlyconservedglycineresidues–  EssenWalfora)achingtothemembraneandformingadimer

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1990

1991

1992

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Hospital Discharge Diagnoses of Hyperlipidemia (ICD 272.0-4)& Glyphosate applied to corn & soy crops

R = 0.9662, p<1.797e-5Sources: CDC; USDA

hyperlipidemia per 10,000

Total glyphosate / total acreage (lb/acre; corn & soy)

Year

Nu

mbe

r o

f d

isch

arg

e d

iag

no

se

s o

f h

ype

rlip

ide

mia

pe

r 1

00

00

Tota

l g

lyph

osa

te a

pplica

tio

ns/ T

ota

l a

cre

ag

e (

lbs/a

cre

)

HighSerumLipidsisCorrelatedwithGlyphosateUsageonCornandSoyCrops

CollaboraWonwithDr.ChenLiandDr.NancySwanson

1990

1991

1992

1993

1994

1995

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1999

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2001

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Hospital Discharge Diagnoses of Hyperlipidemia (ICD 272.0-4)& Glyphosate applied to corn & soy crops

R = 0.9662, p<1.797e-5Sources: CDC; USDA

hyperlipidemia per 10,000

Total glyphosate / total acreage (lb/acre; corn & soy)

Year

Nu

mbe

r o

f d

isch

arg

e d

iag

no

se

s o

f h

ype

rlip

ide

mia

pe

r 1

00

00

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l g

lyph

osa

te a

pplica

tio

ns/ T

ota

l a

cre

ag

e (

lbs/a

cre

)

HighSerumLipidsisCorrelatedwithGlyphosateUsageonCornandSoyCrops

CollaboraWonwithDr.ChenLiandDr.NancySwanson

GlyphosatedisruptsbileacidsynthesisandforceslivertodistributecholesterolasLDLparWclesinstead

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ElevatedHomocysteineandHeartDisease*

•  587paWentswithcoronaryarterydiseasefollowedovermedianperiodof4.6years

•  Homocysteine>15μmol/Literà6.5-foldincreaseindeathratecomparedto

homocysteine<10μmol/Liter

*P.O.Limetal.,JournalofHumanHypertension(2002)16,411–415.

Sulfur

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Hypothesis:Homocysteinebecomeselevatedwhensulfatesuppliesaredepletedbecauseit

canbeasourceofnewsulfate

PathwayfromHomocysteinetoSulfate*

homocysteinethiolactone

VitaminA

thioreWnamide

VitaminC

alphaketobutyrate Sulfite

oxidase

reWnoicacid

sulfate

sulfite

*McCully,AnnalsofClinicalandLaboratoryScience41:4,300-313,2011

WhenfolateandB12aredeficient,nearlyallhomocysteineisconvertedtohomocysteinethiolactone

Superoxide:ReacWveoxygenspecies

(ROS)

PAPS

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PathwayfromHomocysteinetoSulfate*

GAGs=glycosaminoglycans!

*McCully,AnnalsofClinicalandLaboratoryScience41:4,300-313,2011

GAG-sulfate

*Seneffetal.,JournalofBiologicalPhysicsandChemistry17;2017:53-76

*

Paperexplainshowthecomplexsignalingcascadethattakesplaceinthegoutytoejointisacarefullyorchestratedplantosynthesizecholesterolsulfateandsupplyittoinvadingimmunecells.

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*Seneffetal.,JournalofBiologicalPhysicsandChemistry17;2017:53-76

HeparanSulfateDeficiencyinAu5smHumans:“HeparansulfatedeficiencyinauWsWcpostmortembrainWssuefromthesubventricularzoneofthelateralventricles”*Mice:“Hippocampus/amygdalaalteraWons,lossofheparansulfates,fractonesandventriclewallreducWoninadultBTBRT+�/Jmice,animalmodelforauWsm”**

*BLPearsonetal.BehavBrainRes.2013;243:138–145**FMercieretal.NeurosciLe)2012;506(2):208-13.

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Chroniclow-gradeencephalopathy(braininflammaWon)characterizesauWsm.

Signalingcascadeinthebrainleadstotaurinereleaseandhypothesizedsynthesisofsulfate

fromtaurinebymicrobes

VariousFactorsthatIncreaseSulfate*Anincreaseofthe35S-sulfatedepositiseffectedregularlybyinfecWons,byinjecWonsoftoxinsandproteins,byhypoxemia,dieteWcinfluence,muscularover-exerWon,weatherinfluenceandincreaseofthebloodpressure.

SMPS=Sulfatedmucopolysaccharides=glycosaminoglycans

*ReportbyBernhardMuschlien

*FirstpublishedintheGermanlanguageintheSANUM-Postmagazine(17/1991)

SMPS=Sulfatedmucopolysaccharides(GAGs)

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Chlamydiapneumoniae

•  Causepneumoniawhentheyinfectthelungs

•  Showupfrequentlyincardiovascularplaque

•  ShowupfrequentlyinAlzheimer’splaque

Whataretheydoingthere???

ChlamydiaProduceHeparanSulfate!*

•  Chlamydiaareviableonlyinsidehostcells

•  Theysetuphousekeepinginvacuoleswithinthecell(e.g.,amacrophageintheplaque)

•  Theyproduceaglucosamine-containingsulphatedpolysaccharidethatisnearlyindisWnguishablefromheparansulfate

•  Theyhaveauniquesetofenzymesforthis*S.J.Rasmussen-Lathropetal,CellMicrobiol.2000Apr,2(2),137-44.

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ChlamydiaProduceHeparanSulfate!*

•  Chlamydiaareviableonlyinsidehostcells

•  Theysetuphousekeepinginvacuoleswithinthecell(e.g.,amacrophageintheplaque)

•  Theyproduceaglucosamine-containingsulphatedpolysaccharidethatisnearlyindisWnguishablefromheparansulfate

•  Theyhaveauniquesetofenzymesforthis*S.J.Rasmussen-Lathropetal,CellMicrobiol.2000Apr,2(2),137-44.

AretheyassisWngthehostbyboosWngheparansulfatelevelsinthearterywall?

SulfiteMetabolism:SulfurSensi5vity

Sulfite

Sulfiteoxidase

DissimilatorySulfitereductase

AssimilatorySulfitereductase

Methionine HydrogenSulfide

Sulfate

InhibitedinEcolibyglyphosate

Desulfovibrioovergrowth

Dependsonmolybdenumandhemeandahighlyconserved

glycineresidue

VeryToxic!

Sulfite

HydrogenSulfide

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SulfiteMetabolism:SulfurSensi5vity

Sulfite

Sulfiteoxidase

DissimilatorySulfitereductase

AssimilatorySulfitereductase

Methionine HydrogenSulfide

Sulfate

InhibitedinEcolibyglyphosate

Desulfovibrioovergrowth

Dependsonmolybdenumandhemeandahighlyconserved

glycineresidue

VeryToxic!

Sulfite

HydrogenSulfide

DesulfovibrioovergrowthislinkedtoauWsm.

Desulfovibrioconvertmercurytoaverytoxicorganicmethylmercurymetabolite.

ColonCancer*•  Clostridia(overgrowthwithglyphosateexposure)leadstoinflammaWoninthegut

•  AssimilatorysulfitereducWonisdisturbedbyglyphosate,allowingovergrowthofsulfur-reducingbacteriaandexcessiveproducWonofhydrogensulfide

•  ThisincreasesrisktocoliWsand,overWme,leadstocoloncancer,anepidemicinAmerica

*JMRidlonetal.GutMicrobes2016;7(3):201-215.

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•  Suppressescarcinogenesisinskin,stomach,colon,breastandliver

•  Inducesapoptosisinawidevarietyoftumorcells

•  Downregulatesvariousproinflammatorycytokines

*SKVaridetal,CancerEpidemiolBiomarkersPrev2008;17:1411-1417.

ThereisalowincidenceofcolorectalcancerinIndiawherecurcuminisheavilyusedincurries

CurcuminHasManyBenefits*

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*SKVaridetal,CancerEpidemiolBiomarkersPrev2008;17:1411-1417.


Anintractablemyelomawassentintoremissionwithcurcumintherapy(8g/day)and

hyperbaricoxygen

*ZaidiA,etal.BMJCaseRepApril162017.doi:10.1136/bcr-2016-218148

•  Lossofbodyfatandadipose-associatedmacrophages

•  Reducedinflammatory-relatedatherogenesis

•  AnWdiabeWceffect– LowerHemoglobinA1c

•  LowertotalcholesterolandLDL-C•  HigherHDL-C.

*SCuengsamarnaetal.,journalofNutriWonalBiochemistry25(2014)144–150.


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ThreeFormsofCurcumin*

*Figure1inSKVaridetal,CancerEpidemiolBiomarkersPrev2008;17:1411-1417.

CurcuminGoesAroundandAroundDeliveringSulfatetoLiver!

curcumin

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CurcuminPreventsDiabetes*

CONCLUSIONS:“A9-monthcurcuminintervenWoninaprediabeWcpopulaWonsignificantlyloweredthenumberofprediabeWcindividualswhoeventuallydevelopedtype2diabetes.InaddiWon,thecurcumintreatmentappearedtoimproveoverallfuncWonof[pancreaWc]beta-cells,withveryminoradverseeffects.”

*SChuengsamarnetal.,DiabetesCar35,2012,2121-2127

Glucosinolates!

•  Naturalcomponentsofmanypungentplantssuchasmustard,cabbageandhorseradish

•  Contributetoplantdefenseagainstpestsanddiseases

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BroccoliSprouts*

*arWcles.mercola.com/sites/arWcles/archive/2014/06/30/broccoli-sprout-detox.aspx

•  Sproutscontain30xnutrientsoforganicvegetables

•  Growyourownandeatthemraw!

glucoraphaninControlledstudyinChina:•  Benzeneandacroleindetoxedintourine•  Thesearechemicalsindirtyairfromcar

exhaustandburningfuels

Querce5n:ASulfateTransporter*

SulfateGlucuronate

Neteffect:gutdeliverssulfatetotheliver

*IRRowland,ToxicolPathol198816:147-153.

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Cholinesulfate!!*•  Producedbyplants,lichens,algae,fungi,andseveralbacterialspecies

•  ExperimentdemonstratedthatithadsuperiorcapabiliWestoinhibitamyloidformaWoninpancreaWcbetacells– AmyloidinbetacellsisakintoamyloidbetainAlzheimer‘sdiseaseandplaysamajorroleintype-IIdiabetes

*M.Hagiharaetal.,FEBSOpenBio2(2012)20–25.

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MostImportant:GoOrganic!

HowMuchDoesitCost?

Food Organic Conven5onalcelery 2.99 1.99cauliflower 4.99 2.99Bartle)pears 2.69 1.99orangejuice 3.99 2.99eggs 5.69 3.99milk 4.69 2.99cereal 4.56 3.91

TOTAL 29.60 20.85

increasebillby~40%

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Probio5cs!–MaintainHealthyGut

•  Sauerkrautandapplecidervinegarcontainacetobacter,oneoftheveryfewmicrobesthatcanmetabolizeglyphosate

•  Yogurtandkimchiprobablydotoo

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AreWeGepngEnoughSulfurinOurDiet?*

•  Mostabundantmineralelementbehindcalciumandphosphorus

•  ChondroiWnsulfate,glucosaminesulfate,etc.usedtotreatdiseasesofthejoints

“OutofthisstudycameinformaWonthatsuggestedthatasignificantproporWonofthepopulaWonthatincludeddisproporWonallytheaged,maynotbereceivingsufficientsulfurandthatthesedietarysupplements,wereverylikelyexhibiWngtheirpharmacologicalacWonsbysupplyinginorganicsulfur.”

*MENimnietal.,NutriVon&Metabolism2007,4:24

EatFoodsContainingSulfur

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Somesulfur-containingsupplements

•  BioWn•  Taurine•  N-acetylCysteine•  Glutathione•  S-adenosylMethionine•  AlphaLipoicAcid•  DMSO(dimethylsulfoxide)•  MSM(methylsulfonylmethane)•  DMPS(chelaWngagent)•  EpsomSalts

FlavonoidsandPolyphenols!

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Escapetoasunnyplaceinwinter!

IfyouLiveinCanada,UseaSunlamp!

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EpsomSalts!MagnesiumSulfateinhotbathwaterisacheapandeasywaytogetsulfatesupplytotheskin

Infraredheatalsobeneficial!

Trea5ngGlyphosatePoisoninginAnimals(e.g.,cows)*

BentoniteClayFulvicAcid

*HGerlachetal.,JEnvironAnalToxicol2014,5:2

AcWvatedCharcoal

SauerkrautJuice

AcWvatedcharcoal,bentoniteclay,humicandfulvicacids,andsauerkrautjuicehavebeenshowntobeeffecWveinreducingurinarylevelsofglyphosateandimprovinganimalhealth

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Summary•  CholesterolsulfateisanessenWalmoleculeinthebodyto

maintainvascularhealth–  Producedintheskinuponsunlightexposure

•  HeparansulfateplaysmulWplerolesinthebodyanditsdeficiencyislinkedtoauWsm

•  BileacidsplayanessenWalroleinsupplyingtaurinetothebody,andtaurineisanessenWalstorageformofsulfate–  TaurinedeficiencymaybeakeyfactorinauWsm

•  GlyphosateisapervasivetoxicantthatiscausingamajorhealthcrisisintheUS–  MuchofitstoxicityrelatestodisrupWonofgutmicrobes

•  Anorganicwholefoodsdietrichinsulfur,cholesterolandpolyphenolshasmanyhealthbenefits

•  ItisessenWaltogetabundantsunlightexposuretotheskinwithoutsunscreen

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