MERCURY, SCIENCE AND POLITICS

January 2009

Dr. Boyd Haley

Professor Emeritus of Chemistry/Biochemistry

University of Kentucky

• From: www. uninformed concent.com

• David Kennedy’s IAOMT tape

IN SPITE OF THE OBVIOUS EMISSION OF Hg VAPORS FROM DENTAL AMALGAM THE FDA HAS STEADFASTLY REFUSED TO TEST THEM FOR SAFETY!

Visualization of Mercury Vapor Escaping from an Aged Dental Amalgam

Amalgam is 50% Mercury, inches from your brain and olfactory tissues.

Mercury from Dental Amalgam1. Pro-amalgam ADA spokespersons “estimate” that

about 0.03 mcg mercury are emitted from a single amalgam per day. Estimate that it would take several hundred amalgams to provide a toxic

exposure.

2. A new IAOMT study shows that different amalgam types emit more mercury and that a

single spill (very small amalgam) emits between 4.0 to 20 mcg of mercury per day at room

temperature and without abrasion of any sort. This is about 133 to 666 times more than was

estimated by the ADA!

IAOMT AMALGAM STUDY PROCEDURE• Nine dentists across the USA volunteered to make 10

cylindrical, one spill amalgams in a provided plexiglass mold.

• The IAOMT provided new amalgam kits directly from the manufacturers to each dentist.

• The amalgams in the molds were sent to Dr. Haley at the University of Kentucky for Hg analysis.

• The amalgams were allowed to age for over one month to eliminate any surface mercury.

• The amalgams were placed in 10 ml of distilled water which was changed daily.

• Aliquots of this water were removed at days indicated and analyzed for mercury content.

DENTISTS BRAND DAY1 DAY4 DAY8 DAY11 DAY15 DAY18 DAY22 DAY25

BASCIANO Valiant 9.921 9.677 9.580 9.463 8.700 8.873 9.392 9.311

    9.751 9.262 8.886 8.202 8.074 8.014 9.563 10.322

    8.075 7.288 7.054 7.288 7.558 7.311 7.315 6.956

ECCLES Dispersalloy 9.966 9.620 10.851 10.590 11.260 9.070 9.280 9.014

    7.322 7.922 9.913 9.279 8.639 6.809 7.542 8.672

    9.206 8.685 8.599 8.480 7.783 8.270 7.936 8.997

FISCHER Valiant 5.958 5.829 4.408 4.533 4.266 4.473 5.136 4.460

    5.280 4.762 4.492 4.279 4.801 4.505 4.300 4.862

    4.596 4.704 4.929 4.867 6.147 5.798 5.936 5.468

GRUBE Valiant 6.841 6.904 6.788 5.782 8.158 7.740 7.893 8.026

    12.458 11.878 11.771 12.404 12.146 10.693 10.484 10.221

    13.911 13.421 12.618 11.176 11.669 13.439 13.208 13.090

MESSERMAN Dispersalloy 11.357 11.238 11.887 12.086 15.335 14.712 14.473 15.859

    17.796 17.484 16.765 19.584 19.321 20.716 20.696 19.995

    15.336 14.602 14.086 18.625 17.759 12.389 16.285 15.580

Micrograms Hg released/24hrs/cm2 at 25oC from amalgams kept in a sealed test tube.

BOYS

GIRLS

J. Woods, et al., Environmental Health Perspectives (2007) 115;10, 1527-1531.

From a study funded by NIH done on orphans in Lisbon, Portugal.

• The previous slide shows that prolonged exposure to mercury vapor decreases the child’s ability to excrete mercury through their kidneys. Especially affects BOYS.

• This is consistent with the well known toxic effects of mercury on kidneys.

• This explanation is consistent with the reports by the EPA and National Academy of Sciences that 8 to10% of American women have such high Hg body levels that would render increased susceptibility to neurological damage any child they would give birth to.

ELEVATED MERCURY IN IDIOPATHIC DILATED CARDIOMYOPATHY (IDCM).

WHERE DOES THE Hg COME FROM?

LEVELS ng/g Hg SbControls 8.0 1.5IDCM 178,400 19.260Frustaci et al., J. of American College of Cardiology, 33, (6) 1578, 1999. Controls were patients with valvular or ischemic heart disease. ATHLETIC YOUTH DIE OF IDCM. WHY HASN’T NIH REQUESTED PROPOSALS FOR RESEARCH TO STUDY THIS??THIS IS PROOF THAT MERCURY CAN CONCENTRATE IN SPECIFIC TISSUES OR ORGANS OF THE BODY, EVEN IF Hg BLOOD LEVELS ARE FOUND TO BE IN THE NORMAL RANGE.

Activated Matrix Metallo Proteinase (MMP) is involved in numerous inflammatory diseases. Our new research shows MMP is activated by mercury and organic mercury!1. Atrial fibrillation (AF) produces changes in atrial structure and extracellular matrix composition, which is regulated by matrix

metalloproteinases (MMPs) and often occurs in the setting of congestive heart failure.2. Matrix metalloproteinases (MMPs) are thought to participate in the pathogenesis of coronary artery disease (CAD), particularly

in the occurrence of acute coronary syndrome (ACS).3. Matrix metalloproteases (MMPs) are important in many physiological processes including development, reproduction, and

wound repair. Conversely, aberrant MMPs expression can be detrimental, promoting the pathologic destruction of extracellular matrix components in numerous disease states including breast and squamous cell carcinoma.

4. The significance of circulating matrix metalloproteinases -2 and -9 (MMP-2, MMP-9), as well as their tissue inhibitors -1 and -2 (TIMP-1, TIMP-2) in ovarian cancer were studied to assess the possibility of using them in clinical decision-making. Within malignant neoplasias, high circulating TIMP-1 correlated to the aggressive phenotype and unfavorable prognosis.

5. Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of diseases such as Alzheimer's Disease (AD) and amyotrophic lateral sclerosis (ALS). Increased expression of MMP-9 and TIMPs has been reported in postmortem AD and ALS brain tissue, as well as in ALS cerebrospinal fluid (CSF) and plasma.

6. In active MS patients, both with relapsing-remitting and chronic progressive disease MMP-9 mRNA and plasma protein levels were significantly increased compared to healthy controls.

7. Abdominal aortic aneurysms are characterized by degradation of the extracellular matrix, with a reduction in the elastin concentration of the arterial media. These changes are mediated by increased levels of endogenous metalloproteinases (MMPs) within the aorta.

8. These data suggest that the balance of MMP-2 and MMP-9 to TIMP-1 and TIMP-2 expression is an essential factor in the aggressiveness of renal cell carcinoma.

9. Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs), and recently MMP-inhibitors have entered clinical trials. The obtained results support the hypothesis that MMPs and their endogenous inhibitors participate in the invasive process of human osteosarcoma.

NUMEROUS DISEASES INCLUDING SEVERAL CANCERS AND NEUROLOGICAL ILLNESSES ARE ASSOCIATED WITH THE ACTIVATION OF SPECIFIC MATRIX METALLO PROTEINASES (MMP). Hg2+ AND ETHYL-Hg (as thimerosal) BOTH ACTIVATE A COMMON FORM OF MMP.

BOTH Hg2+ AND THIMEROSAL ACTIVATE MMP-9, AN ENZYME THAT DIGESTS COLLAGEN AND LEADS TO TISSUE BREAKDOWN. Other involvements of mercury:

Amalgams and General Health•The constant release of mercury from dental amalgams would lead to the constant activation of the enzyme MMP (matrix metallo proteinase) that degrades collagen and disrupts cell to cell contacts.

•This would lead to rapid aging and exacerbate the many diseases that are associated with elevated MMP activity.

•Anti-aging treatments should all include the removal of dental amalgams, a fact based on science not irrelevant “estimations”.

Axonal Transport - A Process Essential for the Survival of Neurons

Dendrite

Microtubule

MembraneBound OrganelleDynienAxon

Kinesin

Only Hg2+ Induces Aberrant [32P]8N3GTP-ß-Tubulin Interactions In Normal Brain Mimicking

the Observation seen in AD Brain

Alzheimer’s Disease Brain

Normal Brain without and with Hg2+.

EDTA Prevents Cd, Cu & Zn But Not Hg Inhibition of [32P]8N3GTP Photolabeling of Brain ß-Tubulin

Water in Which an Aged Amalgam has been Soaked Induce Abnormal Tubulin in Normal Brain Homogenates: Mimics the

Observation in Alzheimer’s Diseased Brain

0

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Hours of Amalgam Soak

% Active Tubulin

Placing amalgams in water makes it toxic to brain tubulin just like adding Hg2+.

Degenerating Neurons into Neurofibillary Tangles by Treatment with Nanomolar Levels of Hg2+. Leong et al. NeuroReports 2001,12 (4):733-737.

MERCURY, AND ONLY MERCURY COULD CAUSE THE FORMATION OF NFTs, THE MAJOR DIAGNOSTIC HALLMARK OF ALZHEIMER’S DISEASE!

Immunostaining for Tubulin in Neurons treated with Hg2+. Leong et al. University of Calgary.

Alzheimer's Metal Concentrations in Plasma and Cerebrospinal Fluid in Patients with Disease. Dement Geriatr Cogn Disord. 2008 May 5;25(6):508-515 [Epub ahead of print]Gerhardsson L, Lundh T, Minthon L, Londos E.

The homeostasis of essential metals such as copper, iron, selenium and zinc may be altered in the brain of subjects with Alzheimer's disease (AD). Methods: Concentrations of metals (magnesium, calcium, vanadium, manganese, iron, cobalt, nickel, copper, zinc, selenium, rubidium, strontium, molybdenum, cadmium, tin, antimony, cesium, mercury and lead) were determined in plasma and cerebrospinal fluid (CSF) by inductively coupled plasma mass spectrometry in 173 patients with AD and in 87 patients with the combination of AD and minor vascular components (AD + vasc). Comparison was made with 54 healthy controls. Results: The plasma concentrations of manganese and total mercury were significantly higher in subjects with AD (p < 0.001) and AD + vasc (p </= 0.013) than in controls. In CSF, however, the concentrations of vanadium, manganese, rubidium, antimony, cesium and lead were significantly lower among subjects with AD (p </= 0.010) and AD + vasc (p </= 0.047) than in controls. Strong positive correlations were noted between plasma Cs versus CSF Cs in subjects with AD (r(s) = 0.50; p < 0.001), and AD + vasc (r(s) = 0.68; p < 0.001). Conclusion: Besides the raised plasma mercury concentrations, no consistent metal pattern in plasma or CSF was observed in patients with AD.

Maternal amalgam dental fillings as the source of mercury exposure in developing fetus and newborn. Palkovicova L, Ursinyova M, Masanova V, Yu Z, Hertz-Picciotto I. J Expo Sci Environ Epidemiol. 2007 Sep 12. Dental amalgam is a mercury-based filling containing approximately 50% of metallic mercury (Hg(0)). Human placenta does not represent a real barrier to the transport of Hg(0); hence, fetal exposure occurs as a result of maternal exposure to Hg, with possible subsequent neurodevelopmental disabilities in infants. This study represents a sub-study of the international NIH-funded project "Early Childhood Development and polychlorinated biphenyls Exposure in Slovakia". The main aim of this analysis was to assess the relationship between maternal dental amalgam fillings and exposure of the developing fetus to Hg. The study subjects were mother-child pairs (N=99). Questionnaires were administered after delivery, and chemical analyses of Hg were performed in the samples of maternal and cord blood using atomic absorption spectrometry with amalgamation technique. The median values of Hg concentrations were 0.63 mug/l (range 0.14-2.9 mug/l) and 0.80 mug/l (range 0.15-2.54 mug/l) for maternal and cord blood, respectively. None of the cord blood Hg concentrations reached the level considered to be hazardous for neurodevelopmental effects in children exposed to Hg in utero (EPA reference dose for Hg of 5.8 mug/l in cord blood). A strong positive correlation between maternal and cord blood Hg levels was found (rho=0.79; P<0.001). Levels of Hg in the cord blood were significantly associated with the number of maternal amalgam fillings (rho=0.46, P<0.001) and with the number of years since the last filling (rho=-0.37, P<0.001); these associations remained significant after adjustment for maternal age and education. Dental amalgam fillings in girls and women of reproductive age should be used with caution, to avoid increased prenatal Hg exposure.

•Mercury, and only mercury, can mimic the abnormal biochemistry observed in Alzheimer’s Diseased brain as detected in comparison to normal human brain. The vaporous form of mercury is the most effective as it crosses the blood-brain barrier with ease as shown in a study with living rats.

•Amalgams are only inches from the brain and the olfactory nerves and constantly release mercury vapor.

•Yet our FDA and ADA constantly contend that these vapors, shown to accumulate in the brain and other organs, is safe. Today the FDA is reevaluating the safety of dental amalgam. Contact them!

Federal Register / Vol. 73, No. 82 / Monday, April 28, 2008 / Proposed Rules

SUMMARY: The Food and Drug Administration (FDA) is reopening for 90 days, the comment period for the proposed rule, published in the Federal Register of February 20, 2002 (67 FR 7620), on the classification of

encapsulated amalgam alloy and dental mercury, the reclassification of dental mercury, and the issuance of special controls for amalgam alloy.

Consumers Dental Choice lawyers had to sue the FDA and certain officials to get them to take action. The lawsuit is currently underway. It has been over 30 years that the FDA has refused to evaluate and classify dental amalgams. Classification of amalgams is being fought by the American Dental Association.

Thimerosal Is Composed of Thiosalicylic Acid And Ethyl Mercury, A Known

Neurotoxicant

1. The Merck Index, 12th ed., p. 1590, #9451 (1996).2. Martindale The Extra Pharmacopoeia, 30th ed., 804 (1993).

Water insoluble

Water soluble

Organ Mercury Levels in Infants with Omophaloceles Treated with Thimerosal. Fagan et al. Archives of Disease in Childhood 52, 962-64, 1977

• Between 1969-75, 13 cases were treated, 10 died. Mercury analysis of organs ranged from 65 to 2,700 times normal levels. This appears to be from 9 to 48 topical applications of 0.1% thimerosal applications. NOTE; These children were most likely on antibiotics. Consider the effect on their immune system!

• “Paradoxically, (in another study) 3 infants exposed postnatally (Iraq, Methyl-Hg by ingestion) did not exhibit signs or symptoms, though their blood levels were

>1,000ppb, and one was >1,500ppb.” No antibiotics involved! Blood levels are not a measure of toxicity.

• CONCLUSION IN 1977: “Organic mercurial antiseptics should be heavily restricted or withdrawn from hospital use, and the fact that mercury readily penetrates intact membranes and is highly toxic seems to have been forgotten.” Result: Merthiolate (thimerosal) was removed from the market by the FDA due to its inherent toxicity to infants.

RAPID BLOOD TO BRAIN MOVEMENT OF [203Hg]-THIMEROSAL. Gasset et al. Tetratogenicities of Opthalmic Drugs. Arch. Opthalomology 93, 52-55, 1975.

• Pregnant rabbits were injected subcutaneous with [203Hg]-thimerosal.

• From hour 1 post injection to hour 6 the cpm of 203Hg in the blood decreased from 100,000 to less than 25,000 cpm, or over 75%.

• From hour 2 post injection to hour 6 there was increased cpm of 203Hg in the fetal brain (2 fold), liver (4 fold) and kidney (3 fold).

• Yet the IOM/CDC/AAP state that the rapid loss of mercury from thimerosal from the blood makes it unlikely to be toxic enough to cause autism. Pichichero et al. Lancet 360:1737, 2002

THE BIG MISTAKE!• YET SOME INDIVIDUALS AT THE CDC AND

FDA DECIDED IT WAS OK TO INJECT THIMEROSAL INTO A NEWBORN INFANT AT LEVELS THAT WOULD BE EPA SAFE IF THE INFANT WEIGHED 275 POUNDS!

• The EPA “safe level” was based on mercury exposure from eating fish and whale meat.

• Most of the heavy metal protection in humans is in the intestinal area as we evolved eating and drinking contaminated food and water. This is bypassed on injection of thimerosal or breathing mercury vapor.

THERE IS A LACK OF OLDER AUTISTICS!

AUTISM IN DIFFERENT AGE GROUPS IN SCOTLAND

Thimerosal is toxic to tubulin and actin. Combinations of Hg2+ and thimerosal would be at least additive.

MOST VACCINES CONTAIN TRACES OF THIMEROSAL EVEN IF IT IS NOT ADDED AS A PRESERVATIVE.

The vaccine thimerosal concentration was (is) 125,000 to 250,000 nanomolar!

Thimerosal in vaccines appeared to be more toxic than pure thimerosal! Most likely due to synergistic effects of other additions like Al3+.

Time (hr) After Treatment

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50 nM thimerosal+10 nM HgCl2

50 nM thimerosal+ 25 nM HgCl2

10 nM HgCl2

25 nM HgCl2

Hg2+ & THIMEROSAL DISPLAY ADDITIVE TOXICITIES TO NEURONS IN CULTURE.

SYNERGISTIC EFFECTS OF HEAVY METALS IS QUITE COMPLEX AND CAN GREATLY ENHANCE

THE TOXICTY OF MERCURY

Shubert et al. Combined Effects in Toxicology--A Rapid systematic Testing Procedure:Cadmium, Mercury & Lead. J. of Toxicology & Environmental Health 4:763, 1978.

1. “the administration of an essentially no response level (LD1) of a mercury salt together with a 1/20 of the LD1 of a lead salt killed all of the animals.” “Generally, a combination was synergistic when the most toxic member was present at or near its LD1 dose in the presence of a much less toxic member.”

2. Conclusion: Mixing borderline toxic levels of two toxic metals (Pb2+ & Hg2+) makes an extremely toxic solution.

Time (hr) After Treatment

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500 nM Al(OH)3

1.75 µg Neomycin/ml

50 nM Thimerosal500 nM Al(OH)3

50 nM Thimerosal1.75 µg Neomycin/ml

50 nM Thimerosal500 nM Al(OH)3

1.75 µg Neomycin/ml

Al:NEOMYCIN:TESTOSTERONE EFFECTS

+ TESTOSTERONE

SYNERGISTIC TOXICITIES

50 NANOMOLAR THIMEROSAL

DR. MARK LOVELL

COLLABORATOR

Estradiol Reduces Cumulative Mercury and Associated Disturbances in the Hypothalamus-Pituitary Axis of

Ovariectomized Rats. Oliveria et al. Ecotoxicol. Environ. Safety Jan.10, 2006

• Methyl-mercury induced a decrease in LHRH in the medial hypothalmus and a decrease in plasma levels of LH. These decreases in LHRH and LH were abolished by estrogenic replacement therapy.

• “The estrogenic effects were associated with a reduction of mercury content of the anterior pituitary gland and medial hypothalmus, suggesting a protective estrogenic effect.”

Mercury Effects on the Immune System• The mitotic spindle is built on tubulin quite similar

to that found in axons of neurons. Therefore, since the cells of the immune system must divide for an effective immune response Hg inhibits this and actively suppresses the immune system.

• Thimerosal is a very potent inhibitor of phagocytosis by mononuclear phagocytes, inhibiting the process at low 1 to 5 nanomolar levels. (Rampersad et al., Transfusion 45(3):384-93,2005). This prevents removal of microbes and ethyl-Hg damaged cells and proteins leading to greater susceptibility for microbe infection and widespread autoimmune problems.

Effects of Antibiotics, Diet and other Metals on Hg Excretion: Found in Published Literature

• Rats exposed to antibiotics were severely impaired in their ability to excrete mercury.

• Rats on milk versus high protein diets were much less able to excrete mercury.

• The great enhancement of synergistic toxicity with Hg and other heavy metals (e.g. lead) is well documented in the literature. We have many children with other heavy metals in their bodies.

• The above confounders have rarely been considered by those who write articles supporting the safety of thimerosal or dental amalgams.

MERCURY BIRTH HAIR LEVELS VS. AMALGAM FILLINGS IN AUTISTIC AND CONTROL GROUPS

AUTISTICS SEEM LESS CAPABLE OF EXCRETING MERCURY AS INFANTS.

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Hair Hg level(mcg/g)

Number of amalgams:Control: autistic ratio:

4-5 6-7 8-9 >102.64 6.93 6.70 6.32 17.91

N: 15 22 29 30 43

Autistic

Controls

Data from A. Holmes, M. Blaxill & B. Haley, Int. J. of Toxicology v22, 2003

Other Epidemiological Studies• A study on seven-year-old children in the Faeroe Islands found

that blood pressure problems increased with decreased blood Hg. This implies retention toxicity effects of Hg in this comparison.

• In the Sechylles study of >700 children, boys with higher levels of hair mercury performed better on some tests as the Boston Naming test. This implies that ability to excrete increases hair Hg levels, not exposure, in this comparison.

• Healthier children seem to be more exposed to mercury if one believes high blood and hair Hg are measure of exposure.

• CONCLUSION: Blood and hair Hg levels are not a measure of exposure at low levels, but rather a measure of both exposure and ability to excrete mercury.

The involvement of the 2004 Institute of Medicine (IOM) report.

• The 2004 IOM committee was funded by the CDC.• The 2004 IOM report cleared thimerosal as being involved in

autism and recommended that no further research be done on this issue but to investigate other more fruitful areas like genetics—which has failed to find a significant genetic component of autism.

• The 2004 IOM report was based only on 5 epidemiological studies of questionable value, none lead by an American.

• The 2004 IOM report totally dismissed the basic science research on thimerosal toxicity and the resultant aberrant biochemistry possibly caused by mercury-like toxicity reported by several research scientists.

• A congressionally requested NIH committee looked at the 2004 IOM report and gave it a very bad evaluation.

• The CDC is living in a state of denial!

Who did the Epidemiological Studies the IOM depended on??• The Verstraten (Belgium) studies at first showed autism rates were

enhanced by thimerosal exposure but changed with renditions to show no effect. All the CDC data was lost or destroyed after it was published. Verstraten now works for a major vaccine producer in Europe.

• Two studies were done by Danish (Madsen and Hviid) who worked for the Stantens Serum Institute (SSI). SSI makes thimerosal containing vaccines and sells them to other countries because they are not allowed to be used in Denmark since 1992. These studies showed a 20-fold increase in autism on removal of thimerosal! STUPID!

• One study was done in England by E. Miller. After her results were made known at the 20004 IOM meeting the National Health Service removed thimerosal from English vaccines.

• Troubling, that the opinion of the CDC is based totally on foreign, conflicted opinions. Why couldn’t the CDC find epidemiologists in the USA to do these studies???

• The Verstraten studies differed from the Danish and English study in that it did not show the dramatic protection effects of thimerosal against autism!!!!!

Evidence of Harm

Autism Risks From 5 Sequential Studies by Verstraten et al. of CDC

Study1 Study2 Study3 Study4 Study5 7.62(1999)

2.48

1.691.52(2001) 1.00*

(2005) *i.e., no increased risk of autism compared to low exposure group. Also, no evident protective effect of thimerosal or the value would have been much less than 1.0. Yet the Danish studies showed that removal of thimerosal caused a 20 to 25 fold increase in autism. One of these sets of studies has to be wrong.

After publication in 2005 all of the data for this work was “lost” by the CDC!!!

Go to Safeminds.org to read the FOIA material on the Verstraten studies.

Simpsonwood Meeting

Conflicts with other CDC accepted studies from Europe!

Indicates thimerosal is causal for autism.

1. In USA rate was 1/150 or 67/10,000!

2. Outpatients added in 1995.

3. Large Copenhagen Clinic added in1992.

4. Autism classification changed in 1994.

5. Thimerosal removed from vaccine.

DANISH STUDY

Conclusion; exposure to a potent neurotoxin, thimerosal, prevents autism!!! Nonsense!

•The CDC, AAP and many pro-thimerosal proponents quote the Danish Studies as showing that thimerosal is not causal for autism since its removal correlated with about a 20-fold increase in autism. But this study is like looking at the involvement of mosquitos with malaria and doing the research in Alaska!•These studies are quite unbelievable if one looks at the content in detail. The major question to the CDC and AAP is why haven’t the Danes, Swedes and English replaced thimerosal in their vaccines if it is proven, as these studies suggest, that thimerosal prevents autism?????

•Perhaps the medical establishments in these countries are more concerned about infant health than ours?

Other Considerations• In England, between 1970-1980, about 14.7% of

children were not vaccinated as suggested. Yet a parental autism group there report (Tony Bateson), on the internet, only two cases of autism in non-vaccinated children were found in their search of autistics born during this time frame.

• The UPI series on autism by Dan Olmstead finds:1. Very little, if any, autism in the unvaccinated Amish! 2. Healthfirst, a Chicago Clinic that does not vaccinate in

the first year of birth reports no autistic children born since 1985 from a population of about 35,000 children.

• The dramatic increase in autism in China following the end of the cold war and the importation of Western vaccines (Evidence of Harm by David Kirby).

CRITICAL EXCLUSIONSTHE CDC IGNORING OF THE EARLY REPORT

BY REPORTER DAN OLMSTEAD OF A GREATLY DECREASED RATE OF AUTISM IN

THE NON-VACCINATED AMISH POPULATION IS CRIMINAL!

THERE IS NO RATIONAL EXPLANATION FOR THIS. THEY HAVE PUSHED FOR RESEARCH IN

OTHER AREAS (GENETICS) TO AVOID FINDING THE POSSIBLE NEGATIVE EFFECTS

OF THE CDC MANDATED VACCINE PROGRAM.

About $25 million has recently been spent to find the “genetic cause of autism” without success!

THE SMOKING GUN STUDY• Done in Paris, France (since the 2004 IOM committee

recommended NIH not fund thimerosal studies) in a large autism clinic.

• Investigated porphyrin profiles in autistic versus normal children because these profiles are the best indicator for heavy metal toxicity, especially mercury toxicity.

• Found porphyrin profiles that indicated 53% of autistic children surveyed were mercury toxic.

• Reversed toxic porphyrin profiles by treating autistics with a mercury chelator. Therefore, the cause was not purely genetic, but involved mercury toxicity.

• Supporting data from Norway has been reported.• Dr. Robert Natal and Dr. Richard Lathe were the lead

researchers in this work published in the International J. Toxicology 2006.

WHAT ARE PORPHYRINS?• Porphyrins are a class of compounds that lead to the

synthesis of heme, the iron binding red compound of hemoglobin that binds oxygen and aids in delivery to cells, where it is used in the mitochondria to help make energy (ATP). Lack of heme or hemoglobin leads to a very pale complexion (ever notice the complexion of autistic children?)

• Heme has other biological uses. It is in the mitochondrial electron transport system that makes ATP. A shortage of heme would prevent adequate energy production and could increase free radical formation.

• Heme is needed for active P450 enzymes, the enzymes that modify organic toxins and aid in removing them from the body. Heme is also needed to remove amyloid protein from human brain to prevent production of amyloid or senile plaques as identified with Alzheimer’s diseased brain.

OXIDATIVE STRESS: The single biochemical abnormality found in essentially all neurological, neurodegenerative, and neurobehavioral diseases is the increased production of oxidative free radical compounds and low glutathione levels. This is reflective of oxidative stress. Oxidative stress is strongly associated with modification of lipids, proteins, and DNA that can lead to membrane structural problem, enzyme inhibition and genetic mutations.James SJ, Cutler P, Melnyk S, et al. Metabolic markers of increased oxidative stress and methylation capacity in children with autism. Am J Clin Nutr. 2004;80:1611–1617.

Ischiropoulos H, Beckman JS. Oxidative stress and nitration in neurodegeneration: Cause, effect or association? J Clin Invest.

2003;111:163–169.

Muravchick S, Levy RJ. Clinical implications of mitochondrial dysfunction. Anesthesiology. 2006;105:819–837.

Kern JK, Jones AM. Evidence of toxicity, oxidative stress and neuronal insult in autism. J Toxicol Environ Health B Crit Rev. 2006;9:485–499.

Larsson HJ, Eaton WW, Madsen KM, et al. Risk factors for autism: Perinatal factors, parental psychiatric history and socioeconomic status. Am J Epidemiol. 2005;101:916–925.

Deth R, Muratore C, Benzercry J, et al. How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis. Neurotoxicology. 2008;29:190–201.

REACTIVE OXYGEN SPECIES (ROSs)

• Superoxide Anion: O2 + e- O2-.

•Hydrogen Peroxide: O2-. HO2

. (hydroperoxyl radical) 2HO2

. H2O2 + O2

•Hydroxyl Radical: O2-. + H2O2O2 + HO- + HO. (Haber-Weiss)

Fe2+ + H2O2 Fe3+ + HO- + HO. (Fenton)The hydroxyl radical is the most damaging!REMOVAL OF ROSs

SOD or Superoxide Dismutase Catalyzed Reaction.2O2

-. + 2H+ H2O2 + O2 (keeps O2-. <10-11M)

*Catalyase Catalyzed Reaction. 2H2O2 2H2O + O2

Peroxidase Catalyzed Reaction. H2O2 + AH2 2H2O + A“A” could be reduced glutathione (GSH)

*Catalyase is the enzyme that converts Hgo to Hg2+!

Ubiquione (Co-enzyme Q) is a mitochondrial mobile electron carrier.

Citric Acid Cycle Reducing equivalents

Both O2-. radical and the quinone radical can leak from damaged mitochondrial

membranes during the electron transport process involved in making ATP requiring GSH to scavenge them decreasing the GSH/GSSG ratio.

Structures and General Chemistry of Glutathione

Note the number of charges on GSH. This makes it unlikely that it could enter any hydrophobic location in a tissue where much of the damaging oxidation occurs as caused by many toxicants.

GOOD

BAD

Structures and General Chemistry of Glutathione

Glutathione (GSH) occurs in all tissues and is the most abundant sulfhydryl (-SH) containing compound in cells. It protects many enzymes from inhibition by reactive

oxygen species (ROS).

1. Enzyme-SH(active) + ROS + RSH Enzyme-S-S-R(inactive) + H2O2

2. Enzyme-S-S-R(inactive) + GSH Enzyme-SH(active) + G-S-S-R

3. Enzyme-SH(active) + Hg2+ Enzyme-S-Hg+(inactive) + H+

4. Enzyme-S-Hg+(inactive) + GSH Enzyme-SH (active)+ GS-Hg+

5. GS-Hg+ + GSH GS-Hg-SG(excreted form) + H+

GSH PROTECTS THE BODY FROM OXIDATION AND HEAVY METAL TOXICITY! GS-Hg-SG is probably the major form of mercury that is excreted from the body by natural means. It leaves through the bilary transport system of the liver into the feces, not through the kidney. Low GSH levels (oxidative stress) in effect cause increased enzyme inhibition by ROS and decreases the ability to remove many toxic metals as well as organic type toxins. YOU CANNOT INCREASE BODY GLUTATIONE LEVELS BY EATING GLUTATHIONE!

oxidized reduced

reduced oxidized

VIT-C GETS INTO ALL CELLS AND MITOS.

REVERSAL OF LIPID PEROXIDATION BY GLUTATHIONE PEROXIDASE (GP)

R = CH3CH=CH-CH=(CH)n-COOH (a poly-unsaturated fatty acid, pufa)

ROOH = CH3CH=CH-CH-(CH)n-COOH (an oxidized fatty acid or O-OH a hydroperoxide)

ROOH + 2GSH GSSG (oxidized glutathione) + ROH + H2O

The ratio of GSH (reduced glutathione)/GSSG (oxidized glutathione) is a measure of oxidative stress, or simply put how much GSH is being consumed relative to how well one can make it. The higher the GSH:GSSG ratio the better one’s redox system is functioning. It appears as if autistic children and many other illnesses need help with their redox system.Toxicity, and especially heavy metal toxicity, can rapidly lower the GSH:GSSG ratio as heavy metals contribute electrons very readily.

Apoptosis, cell death.

It appears as if oxidation of GSH to GSSG precedes cell death in two experimental models.

1. Fibroblasts in culture

2. Regressing mammary tissue after weaning.

Oxidative Damage to mitochondrial DNA and GSH oxidation in apoptosis: Studies in vivo and in vitro. Esteve et al. FASEB J. 1999 V13, 1055-1064

CONVERSION OF GSH TO GSSG PRECEDES CELL DEATH IN CULTURED FIBROBASTIC CELLS

Oxidative Damage to mitochondrial DNA and GSH oxidation in apoptosis: Studies in vivo and in vitro. Esteve et al. FASEB J. 1999 V13, 1055-1064

THE REDOX RATIO OF GSSG/GSH INCREASES BEFORE FIBROBLASTIC CELL DEATH

Oxidative Damage to mitochondrial DNA and GSH oxidation in apoptosis: Studies in vivo and in vitro. Esteve et al. FASEB J. 1999 V13, 1055-1064

GSH DROPS AND GSSG INCREASES DURING FIBROBLASTIC CELL DEATH

Oxidative Damage to mitochondrial DNA and GSH oxidation in apoptosis: Studies in vivo and in vitro. Esteve et al. FASEB J. 1999 V13, 1055-1064

GSSG AND GSH LEVELS IN REGRESSING MAMMARY GLAND CELLS AFTER WEANING.

Oxidative Damage to mitochondrial DNA and GSH oxidation in apoptosis: Studies in vivo and in vitro. Esteve et al. FASEB J. 1999 V13, 1055-1064

CHANGE IN MITOCHONDRIAL GSSG/GSH RATIOS IN REGRESSING MAMMARY TISSUE.

MITOCHONDRIAL GSSG IS INCREASING AND GSH IS DECREASING WITH CELL DEATH.

Oxidative Damage to mitochondrial DNA and GSH oxidation in apoptosis: Studies in vivo and in vitro. Esteve et al. FASEB J. 1999 V13, 1055-1064

INCREASED DNA DAMAGE WITH INCREASED OXIDATIVE STRESS IN REGRESSING MAMMARY CELLS

Oxidative Damage to mitochondrial DNA and GSH oxidation in apoptosis: Studies in vivo and in vitro. Esteve et al. FASEB J. 1999 V13, 1055-1064

INCREASED H2O2 PRODUCTION IN MITOCHONDRIA FROM APOPTIC MAMMARY GLAND.

H2O2

LEVELS

Oxidative Damage to mitochondrial DNA and GSH oxidation in apoptosis: Studies in vivo and in vitro. Esteve et al. FASEB J. 1999 V13, 1055-1064

GLUTATHIONE ESTER DECREASES APOPTOSIS IN CULTURED FIBROBASTS: THEREFORE THE DEATH IS REDUCED WITH TREATMENT THAT INCREASES INTRACELLULAR GSH

NO GSH-ester PLUS GSH-ester

FCS = fetal calf serum

OLD CONCEPTS: WE NEED TO DIRECTLY TREAT OXIDATIVE STRESS

1. REDUCE THE PRODUCTION OF FREE RADICALS OR SCAVENGE THEM TO SALVAGE GSH. (REDUCING VITAMINS)

2. INCREASE PRODUCTION OF GLUTATHIONE BY PROVIDING PRO-GLUTATHIONE NUTRIENTS (e.g CYSTEINE) AND REMOVING ANY TOXICANTS (e.g. HEAVY METALS) THAT PREVENT SYNTHESIS.

3. PREVENT AND REVERSE THE DAMAGE CAUSED BY OXIDATIVE STRESS FACTORS.

New Antioxidant Partitioning Concept• Most available antioxidants are water soluble because they

carry ionic charges. DMPS, DMSA, glutathione, and Se2- are all charged and are rapidly cleared from the body. Therefore, they are not efficient at removing hydroxyl radicals that are located in fatty (hydrophobic) environments or inside of cells, such as the mitochondria.

• Therefore, most toxin generated reactive oxygen species (ROSs) in the body are not available to DMPS, etc. for binding as they are intracellular or in hydrophobic locations.

• The new antioxidants are needed that enter hydrophobic areas. Entering the hydrophobic regions increases the time spent in the body enhancing the scavenging of hydroxyl radicals.

• Therefore, the antioxidants need to be both effective in the ORAC test (oxygen radical absorbance capacity test) and hydrophobic.

O O

NH NH

SH SH

NO O

NH NH

SH SH

New Hydrophobic Antioxidant Agents

Benzene bis-amido bis-thiol Pyridine bis-amido bis-thiolWater insoluble, but lipid soluble, coupling with glutathione makes this compound water soluble (next slide).

Potent scavengers of hydroxyl radicals in lipophilic areas.

Free radical scavenging sites

OHO

NH2O

NH

O NH

O

OH

S

OO

NH NH

S S

OOO O

CH3 CH3 OH O

NH2O

NH

ONH

O

OH

S

Glutathione derivative of Antioxidant Agents

Glutathione Glutathione

Note: Molecule would be charged and water soluble at pH 7.4.

Very water soluble

OSR compound

CT1 Dose Response

y = 0.1487x + 3.0744

R2 = 0.9994

0

10

20

30

40

50

60

0 50 100 150 200 250 300 350

CT1 uM

Trol

ox E

q uM

AN OXYGEN RADICAL ABSORBANCE STUDY OF ONE OF THE NEW ANTIOXIDANTS DONE IN AQUEOUS SOLUTION.

Toxicity Study of Lipid Soluble Antioxidant

• GroupA B C D• Test 10 100 200 300• Test 20 200 300 400• Test 30 300 400 500• Total 0 600 900 1,200

• Test 40 - 1,500 1,500

• Procedure: Rats were injected under the skin in the stomach area with compound to the amount in μMoles/kg body weight. Three days pause was between each treatment.

• Result: No toxicity or weight loss was observed at any level of exposure

TOXICITY TESTING BY ORAL DELIVERY

•A commercial toxicology laboratory has confirmed that the new antioxidant is not toxic at 5grams/kg body weight when given orally, the highest testing level! This is equivalent to a 100 lb person taking 227grams.

Nor did mice given 1.0g/kg body weight for 28 straight days demonstrate any toxic effects.

•The compounds are not mutagenic as determined by a FDA approved laboratory.

•This research was done for the purpose of submission to FDA.

CONCLUSIONS• A NON-TOXIC, LIPID SOLUBLE, FREE

RADICAL SCAVENGING ANTIOXIDANT HAS BEEN DEVELOPED AND FOUND TO BE WITHOUT TOXICITY IN TEST ANIMALS.

• THESE ANTIOXIDANTS SCAVENGE HYDROXYL RADICALS.

• THIS ANTIOXIDANT IS EFFECTIVE IN HELPING MAINTAIN A HEALTHY GLUTATHIONE LEVEL.