Is Glyphosate the Toxic Chemical that’s Making Us All Sick?

Stephanie Seneff May 2, 2015

“It's difficult to get a man to understand something if his salary depends on his not understanding it."

Upton Sinclair

A Frightening Trend*

*K. Weintraub, Nature 479, Nov. 3 2011, 22-24.

??

12 years

Exponential Growth!

Percentage of children with Autism in the US

50%

2032

1970 1980 1990 2000 2010 2020 2030 2040 2050 20600.01

0.1

1

10

Percentage of Children with Autism in US

Percentage of Children with Autism in USExponential (Percentage of Children with Autism in US)Exponential (Percentage of Children with Autism in US)Exponential (Percentage of Children with Autism in US)

Percentage of children with Autism in the US

50%

2032

1970 1980 1990 2000 2010 2020 2030 2040 2050 20600.01

0.1

1

10

Percentage of Children with Autism in US

Percentage of Children with Autism in USExponential (Percentage of Children with Autism in US)Exponential (Percentage of Children with Autism in US)Exponential (Percentage of Children with Autism in US)

A linear extension of the trend line says that 1 in 2 children born in 2032 will end up on the autism spectrum.

Outline

• Glyphosate’s Biological Effects• Glyphosate and Folic Acid• Glyphosate, Oxalate and Anemia• Glyphosate and Vaccines• Summary

Glyphosate’s Biological Effects

Poison Spring• Author E.G. Vallianatos worked for

the US EPA for 25 years.• Corruption and misuse of science

and public trust has turned EPA into a "polluters' prtection agency."

• Repeatedly endorsed deadly chemicals, often against the advice of their own scientists.

• Botched field investigations.• Turned a blind eye to toxic disasters.

Adoption of “Roundup Ready” Crops*

* N. Swanson et al., Journal of Organic Systems 20145;9(2): 6-37.

SoyCorn

CottonCanolaAlfalfa

Tobacco

Is Glyphosate Toxic?• Glyphosate is the active ingredient in the

pervasive herbicide, Roundup• Monsanto has argued that glyphosate is

harmless to humans because our cells don’t have the shikimate pathway, which it inhibits

• However, our gut bacteria DO have this pathway– We depend upon them to supply us with essential amino acids

(among many other things)• Other ingredients in Roundup greatly increase glyphosate’s

toxic effects• Insidious effects of glyphosate accumulate over time– Most studies are too short to detect damage

Main Toxic Effects of Glyphosate*

• Kills beneficial gut bacteria and allows pathogens to overgrow

• Interferes with function of cytochrome P450 (CYP) enzymes

• Chelates important minerals (iron, cobalt, manganese, etc.)

• Interferes with synthesis of aromatic amino acids and methionine– Leads to shortages in critical neurotransmitters

• Disrupts sulfate synthesis and sulfate transport*Samsel and Seneff, Entropy 2013, 15, 1416-1463

The Enhancing Effect of Adjuvants*

“Adjuvants in pesticides are generally declared as inerts, and for this reason they are not tested in long-term regulatory experiments. It is thus very surprising that they amplify up to 1000 times the toxicity of their APs [Active Principles] in 100% of the cases where they are indicated to be present by the manufacturer.”

*R. Mesnage et al.BioMed Research International 2014; Article ID:179691.

*Plot provided by Nancy Swanson, with permissionData sources: autism: US Department of Education; Glyphosate: US Department of Agriculture

R = 0.9972

Autism Prevalence: 6 year olds

Some Biomarkers for Autism

• Disrupted gut bacteria; inflammatory bowel• Low serum sulfate• Methionine deficiency• Impaired methylation: MTHFR • Serotonin and melatonin deficiency• High serum oxalate• Essential iron deficiency• Mitochondrial disorder• Glutamate toxicity in the brain

Some Biomarkers for Autism

• Disrupted gut bacteria; inflammatory bowel• Low serum sulfate• Methionine deficiency• Impaired methylation: MTHFR • Serotonin and melatonin deficiency• High serum oxalate• Essential iron deficiency• Mitochondrial disorder• Glutamate toxicity in the brain

These can all be explained as potential effects of glyphosate on biological systems

Paper on Glyphosate and ManganesePublished March 24, 2015

Manganese Deficiency and Autism*• Glyphosate chelates manganese• Manganese deficiency leads to:– Disrupted gut bacteria anxiety– Impaired dopamine synthesis thyroid disease– Glutamate and ammonium toxicity in the brain as

well as glutamine deficiency– Mitochondrial damage– Impaired bone development and osteoporosis– Impaired development of perineuronal nets

• Many of these pathologies are associated with autism *A Samsel and S Seneff, Surg. Neurol. Int. 2015;6:45.

It’s not just deficiency!

Vagus Nerve

Too much manganese in the brain stem

Too little manganese in the cortex

Balancing the Scales

Autism

Alzheimer’s

ADHD

Parkinson’s

ironmanganese iron

manganese

Glyphosate disrupts the body’s ability to distribute the minerals safely: Everybody walks a tight rope between deficiency and toxicity

Glyphosate and Folic Acid

A Bit of History

The US first considered adding folic acid supplements to grains in 1996, and introduced the mandate in 1998

GMO “Roundup Ready” crops were just beginning to be introduced in 1996 and had obtained

widespread adoption by 1998

Spina bifida is a very rare genetic disorder that is linked to folate deficiency

Adoption of “Roundup Ready” Crops*

* N. Swanson et al., Journal of Organic Systems 20145;9(2): 6-37.

Folic Acid and/or Iron Fortification!!*

*B Handforth and S. Zimmerman, Sight and Life 27 (1); 70-75, 2013

Folic Acid and/or Iron Fortification!!*

*B Handforth and S. Zimmerman, Sight and Life 27 (1); 70-75, 2013

Europe has steadfastly refused to adopt policy of folic acid supplementation!

Generating Methionine from Homocysteine

Methionine HomocysteineRequirements:Working MTHFR enzymeCobalaminZincVitamin B6Methyl tetrahydrofolate

Folate trap: One or more of these requirements are

missing; Methyl group stays stuck on folate (inactive)

There is a belief that elevated serum homocysteine is bad, but the homocysteine is desperately

needed to produce sulfate

Nitrous Oxide Inhibits Methionine Synthesis

• Methionine synthase is inhibited by nitrous oxide

• Excess serum ammonia is a source of nitrous oxide

• Glyphosate likely induces ammonia synthesis by gut microbes (disrupts uptake of nitrogen into proteins)*

*SO Duke et al., Plant Physiol 1980; 65: 17-21.

Nitrogen

Ammonia Protein

Nitrous Oxide

Inhibition

Homocysteine

Methionine at the Crossroads

Methionine

MethylationMethylation

Methionine

Homocysteine

Too much folate drives methionine towards methylation and depletes homocysteine

Transsulfuration Pathway*

*Figure 1, DA Geier et al., Neurochem Res (2009) 34:386–393.

Transsulfuration Pathway*

*Figure 1, DA Geier et al., Neurochem Res (2009) 34:386–393.

Three very important molecules!!!

What’s the difference between folic acid and folate???

• Folic acid is a synthetic molecule, and it’s stable

• Folate is typically methylated• Folic acid is missing four hydrogen ions –

THIS IS VERY IMPORTANT!!!

Folic acid is oxidized, and to convert it to folate is costly for the body

A Problem with Folic Acid

DihydrofolateDihydrobiopterin

Tetrahydrobiopterin TetrahydrofolateHHHH

HH

HHHH

HH

+HH -HH

Dihydrofolate

Tetrahydrobiopterin

REDUCED

OXIDIZED

BH4

Excess folic acid drives biopterin towards the reduced form, which is not good!

A Problem with Folic Acid

DihydrofolateDihydrobiopterin

Tetrahydrobiopterin TetrahydrofolateHHHH

HH

HHHH

HH

+HH -HH

Dihydrofolate

Tetrahydrobiopterin

REDUCED

OXIDIZED

BH4

Low BH4 in the cerebrospinal fluid is linked to autism*

*RE Frye et al., Neurotherapeutics. 2010 July ; 7(3): 241–249.

“High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism,

and liver injury in mice”*

• Fed mice excessive amounts of folic acid

• Reduced methylation capacity in liver

• CYP7A1 level was dramatically reduced. (rate limiting enzyme in bile acid synthesis)

• Caused liver damage and fatty liver disease*KE Christensen e tal., Am J Clin Nutr 2015;101:646–58.

“Cerebral folate deficiency with developmental delay, autism, and

response to folinic acid”*

Folinic acid is a form of TETRAHYDRO-folate

* P Moretti et al., Neurology March 22, 2005 vol. 64 no. 6 1088-1090

“Cerebral folate deficiency with developmental delay, autism, and

response to folinic acid”*

Folinic acid is a form of TETRAHYDRO-folate

* P Moretti et al., Neurology March 22, 2005 vol. 64 no. 6 1088-1090

Folate receptor antibodies due to excess folic acid in the blood???

Recapitulation

• The timing of mandatory folic acid enrichment is uncanny: hide pending epidemic in spina bifida?

• Folic acid is synthetic, and it leads to excessive oxidation in the liver and/or depleted BH4

• Glyphosate depletes methionine– Folate drives methionine towards methylation rather than

sulfation– This causes severe systemic sulfate deficiency

• Folate receptor antibodies in the brain may be an attempt to protect the brain from sulfate deficiency

Glyphosate, Oxalate and Anemia

Autism Linked to Oxalate Crystals*• Crystals of oxalate

form kidney stones and cause great discomfort

• Study has shown at least 3-fold higher serum and urinary levels of oxalate in autistic kids***William Shaw, The Role of Oxalates in Autism and Chronic

Disorders WAPF, March 26, 2010

**J Konstantynowicz et al., European Journal of Paediatric Neurology 16(5), 2012, 485-491.

*http://www.greatplainslaboratory.com/home/span/oxalates.asp

“Oxalate crystals in the bone may crowd out the bone marrow cells, leading to anemia and immunosuppression”*

Plot produced in collaboration with Dr. Nancy Swanson from US Government data

*K Froberg et al., Clin Toxicol (Phila). 2006;44(3):315-8.

“Cerebral edema, and perhaps injury to other organs, could result from oxalate crystal

deposition in small blood vessels in the brain and other organs.”*

Glyphosate Metabolism*

*Figure 3 in L. Polligioni et al., FEBS Journal 278 (2011) 2753–2766

Oxalate Metabolism*

*http://www.greatplainslaboratory.com/home/eng/oxalates.asp

Monsanto Patents: 2002-2010:Pesticide Compositions Containing Oxalic Acid

“[origin: WO02069718A2] Pesticidal concentrate and spray compositions are described which exhibit enhanced efficacy … More particularly, the present invention relates to a method of enhancing the herbicidal effectiveness of glyphosate concentrate and tank mix formulations containing one or more surfactants through the addition of oxalic acid.”

Monsanto Technology, St. Louis, MO

Monsanto Patents: 2002-2010:Pesticide Compositions Containing Oxalic Acid

“[origin: WO02069718A2] Pesticidal concentrate and spray compositions are described which exhibit enhanced efficacy … More particularly, the present invention relates to a method of enhancing the herbicidal effectiveness of glyphosate concentrate and tank mix formulations containing one or more surfactants through the addition of oxalic acid.”

Monsanto Technology, St. Louis, MO

Oxalic acid and oxalate are essentially the same thing!

Oxalate Enhances Glyphosate’s Toxicity to Plants at Small Concentrations*

*Figure 1, Monsanto Patent #US 7,771,736 B2, Aug. 10, 2010

Hypothesis: flooding with oxalate prevents metabolism of glyoxylate to oxalate. Glyoxylate is a very potent

glycating agent, leading to widespread damage.This also inhibits glyphosate breakdown to glyoxylate.

sec.gov/Archives/edgar/data/1110783/000103570403000400/c77652exv99w2.htm

sec.gov/Archives/edgar/data/1110783/000103570403000400/c77652exv99w2.htm

WEATHERMAX!!

“In 2004, this powerful new formulation was chosen by more western Canadian growers than any other non-selective herbicide on the market. Grower satisfaction with the performance in the field has reached newheights - 99% of growers who used Roundup WeatherMAX were satisfied with their experience.”

*www.highbeam.com/doc/1P2-13686824.htmlJANUARY 3, 2005

New Roundup Transorb'R' Herbicide Formulation to Hit Retail Shelves in Eastern Canada*

This Detoxification Scheme is Essential in Red Blood Cells

Depends on selenium

Inhibited by glyphosate

Depleted by glyphosate

Product of shikimate pathway

Induced by excess folic acid

This Detoxification Scheme is Essential in Red Blood Cells

Depends on selenium

Inhibited by glyphosate

Depleted by glyphosate

Product of shikimate pathway

G6PD Deficiency Leads to Hemolysis and Anemia

Anemia leads to low oxygen which induces chronic low grade encephalopathy linked to autism

Oxalate, Iron and Autism• Agricultural workers exposed to glyphosate suffer

from high rate of kidney failure due to tubular interstitial diseases*– Tubules depend on transferrin to supply iron– Oxalate interferes with transferrin iron delivery**

• Autistic children also have intractable iron deficiency• Child with defective gene for transferrin receptor had

developmental delay and intractable seizures***

*C Jayasumana et al., Int. J. Environ. Res. Public Health 2014**AN Luck et al., Biochemistry. 2013 November 19; 52(46)

***Stockler et al. Orphanet Journal of Rare Diseases 2014, 9:141.

Autistic Children are Sensitive to Iron Overload*

*A Chauhan et al., Life Sciences 2004; 75: 2539–2549

Children with autism have low levels of transferrin,

which protects from oxidative damage due to

free iron in the cells

Recapitulation• Oxalate is elevated in association with autism• Oxalate can cause crystals to form in tissues

which is very damaging• Monsanto has patents on oxalate as an additive

to enhance toxicity to plants• Oxalate can work synergistically with glyphosate

and folic acid to cause essential iron deficiency• Anemia can lead to low oxygen supply and

encephalopathy (linked to autism)

Glyphosate and Vaccines

Case Study: Evidence that Glyphosate Penetrates the Brain Barrier*

• 58 year old woman ingested glyphosate (suicide attempt)

• Glyphosate showed up in blood (1294 μg/mL) and cerebrospinal fluid (122 μg/mL)

• Associated with both disseminated intravascular coagulation (DIC) and aseptic meningitis

*C Sato et al., Clinical Toxicology (2011) 49, 118–120

Glyphosate Suppresses Melatonin Synthesis!

• Glyphosate interferes with shikimate pathway in plants and microbes tryptophan depletion*

• Tryptophan is sole precursor to melatonin

• Melatonin binds to aluminum, cadmium, copper, iron and lead, reducing their toxicity**

• Melatonin is produced by the pineal gland and regulates the wake/sleep cycle **J. Limson et al. J. Pineal Res. 1998; 24:15–21.

*N. de María et al., J Agric Food Chem 2006, 54, 2621-2628.

How Glyphosate Depletes Serotonin and Melatonin

Tryptophan

Dietary Sources

Synthesis by Gut Microbes

Kynurenine NAD+ Metabolized to ATP

(Liver)

TDO

Kynurenine (Macrophages)

IDO Kynurenine (Endothelial Wall)

IDO

Serotonin melatonin (Brain)

Protein Synthesis(Tissues)

G G G

G

G *S.L. Connors et al., Plasma Serotonin in Autism. Pediatric Neurology 35(3), Sep 2006, 182-186.

Serotonin deficiency is linked to not only autism but also obesity, depression, Alzheimer’s disease and violent behavior*

Sleep Disorder, Aluminum, and the Pineal Gland

• Sleep disorder is linked to many neurological diseases: – Autism, Alzheimer’s, ADHD, depression, schizophrenia, ALS,

Parkinson’s disease, etc.• Insomnia occurs much more frequently as an adverse

reaction to vaccines containing aluminum than to those not containing aluminum (p < 0.0025)*

• Insomnia also occurs much more frequently in ALL adverse reactions after the year 2000 compared to before 2000 (p < 0.009)*

• Pineal gland is heavily perfused and outside of the blood brain barrier– Susceptible to aluminum toxicity*Seneff et al., Entropy 2012, 14, 2227-2253.

Insomnia is Strongly Correlated with Glyphosate Usage

Plot provided by Dr. Nancy Swanson; Data from CDC Hospital Discharge database

R = 0.98

Aluminum in the Pineal Gland*

*S.B. Lang et al./Bioclectrochemistry and Bioenergetics 41(1996)191—195

Glyphosate and Aluminum: Partners in Crime

• Glyphosate induces pathogens like C. difficile in gut, leading to leaky gut syndrome– C. diff produces p-cresol which promotes

aluminum uptake by cells– p-Cresol is a known biomarker for autism– p-Cresol is an important factor in kidney failure which

leads to aluminum retention in tissues dementia• Glyphosate cages aluminum to promote entry• Glyphosate promotes calcium uptake by voltage-

activated channels– Aluminum gains entry as calcium mimetic

Autism, Glyphosate, Vaccine Reactions*

*Collaboration with Dr. Nancy Swanson

Glyphosate application to corn and soy, US

# Adverse Reactions in VAERS

Children with Autism, US

Autism, Glyphosate, Vaccine Reactions*

*Collaboration with Dr. Nancy Swanson

Glyphosate application to corn and soy, US

# Adverse Reactions in VAERS

Children with Autism, US

Is this steep rise linked to theIntroduction of WeatherMax?

Autism, Glyphosate, Vaccine Reactions*

*Collaboration with Dr. Nancy Swanson

Glyphosate application to corn and soy, US

# Adverse Reactions in VAERS

Children with Autism, US Glyphosate makes the aluminum

(and mercury?) (and glutamate??) in vaccines much more toxic??

Glyphosate enhances aluminum toxicity

Glyphosate interferes with acetaminophen metabolism

Aluminum Glyphosate*

*M. Purgel et al., Journal of Inorganic Biochemistry 103 (2009) 1426–1438

Six different ways two glyphosate molecules can chelate aluminum

ALUMINA

aluminum

Aluminum citrate**

** P. Sianina et al., Clin. Chem. 32/3, 539-541, 1986.

MMR and Autism• Andrew Wakefield found a connection in 1998

in a now retracted publication*• CDC claimed proof of no link in 2004 paper**• Whistleblower, Dr. William Thompson, has just

come forward: – Data supported significant increased risk for

autism in black males with early vaccine– Demand for birth certificate hid this finding

• I believe it has to do with glutamate!*A Wakefield et al., The Lancet 1998; 351 (9103): 637–41. (RETRACTED)

**F DeStefano et al., Pediatrics 2004;113;259-266 .

Glutamine Synthesis Depends on Manganese!

glutamate glutamine

Glutamine synthetase

ammoniumwater

Ammonium and glutamate toxicity in the braincan arise because of insufficient manganese

“Alteration of Plasma Glutamate and Glutamine Levels in Children with

High-Functioning Autism”*

*C. Shimmura et al. PLoSone October 2011 6(1):e25340

Symptoms of Adverse Reactions to MMR before and after 2002*

*Data analyzed from the VAERS database

Symptoms of Adverse Reactions to MMR before and after 2002*

*Data analyzed from the VAERS database

These are all characteristic symptoms of allergies to MSG

seizures

hives

swellingswelling

Joint pain

Facial swellinganaphylactic shock

shortness of breath

eczema

Glutamate is an Additive in Vaccines!• Flu vaccines (FluMist), MMR (measles,

mumps and rubella), Rabies vaccine and Varicella vaccine (chicken pox) all contain glutamate

• Anecdotal evidence links these vaccines with autism

• My own studies on VAERS revealed a correlation between autism and MMR*

• Glyphosate’s depletion of manganese prevents glutamate breakdown

*S. Seneff et al., Entropy 2012, 14, 2227-2253.

Varivax and Hepatitis A Vaccines: Linked to Autism*

Contains Glutamate

Contains Aluminum*TA Deisher et al., Journal of Public Health and Epidemiology 6(9), 271-284, 2014.

Recapitulation• Glyphosate’s inhibition of the shikimate pathway

likely impairs melatonin synthesis– Leads to sleep disorder, associated with many diseases

• Pineal gland is highly susceptible to aluminum• Glyphosate promotes aluminum entry past the

gut and brain barriers and uptake by the cells• Glyphosate also promotes glutamate toxicity due

to manganese deficiency, leading to acute reaction to glutamate in MMR vaccine

Summary

• We face a looming crisis with the exponential rise in autism rates in the US

• There is much evidence to support a link between glyphosate exposure and autism

• Glyphosate is synergistically toxic with excess folic acid supplements, with oxalate, and with aluminum and mercury in vaccines

• Glyphosate is also likely linked to many other diseases on the rise, as evidenced by strong correlations in time trends

• Glyphosate should be banned from the market