Yet Another Highly Unethical and Socially Irresponsible “Genes-Only” Study Fails to Show that Autism is 80% “Genetic”

Yet Another Highly Unethical and Socially Irresponsible “Genes-Only” Study Fails to Show that Autism is 80% “Genetic”

In a WebMD article, the results from a large genetic-factor-only study gleefully reports that the newest, highest-ever estimate of the percent liability of autism risk that can be attributed to “genetics” is 80%, leaving the remaining 20% to environmental factors.

The article also claims that this new, highest estimate is reported by the study authors to be “…roughly in line with those from prior, smaller studies on the issue, further bolstering their validity“.

Consistent Results From Invalid Methodology Does not Make Those Results “Valid”.  It Makes Them “Consistent”.

The “roughly in line with” is an appeal to consistency.  But the Liability Threshold Models differ from other approaches methodologically. Previous studies, one of which was conducted by the same group of researchers, had estimates that ranged from 0 to 99% heritability.  The average, until this group started using liability-threshold models, was around 40% attribution to genetics. Their studies increased the average, but it still hovered around 50% liability.  Only the liability threshold models, used by this group, show results around 80% liability.  So their method is consistent with itself.  No surprise there. But that’s nowhere near “roughly in line” with all prior studies.

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One of those studies is discussed in the article “Non-genetic factors play surprisingly large role in determining autism, says study by group“.

Why Autism is Not “Genetic”

The article skips over the fact that the newest, latest study, like the prior studies, fails to actually measure the contribution of a single environmental factor.  While the article rails against “anti-vaxxers”, the study ignores the vaccination status of those involved in the study.  The mantra of so many studies never showing association has to be tempered with a mature, responsible and realistic interpretation in the context of how those studies were conducted: restricted to one vaccine (MMR), and then there is this:

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Assumptions Without Measurement Lead to Assumptions as Conclusions

Their entire methodology is based on familial correlations. In the current study under consideration, no exposure levels to pesticides, medical exposures in utero, smoking history, nothing environmental was measured.  And yet somehow the study authors pretend they can estimate the % liability from environmental factors.  How do they pretend to achieve such a feat?

The first problem is that they have not measured any interaction between genetics and environmental factors.  There is, in fact, established knowledge of special risk of autism that involves combined risk of specific genes and specific environmental factors.  Check out, for example, Bowers and Erickson (2014):2

Their Liability Threshold Model Approach is Both Under- and Mis-Specified

You really have to understand population genetics a bit to get this next part, so I apologize to the lay public, but please take what understanding you can from this:

Their model (generically represented) is

ASD risk  =  “Genetics” + e

where = measurement error, leaving whatever variation appears to be unexplained to Environment.  That’s unusual because the usual interpretation of such unexplained variation is “Error” and “Unknown Variation”.   In technical terms, their model is underspecified.  Environmental variation is not “Error” in a genetic model, it’s “Environmental Variation”.

If they HAD measured environmental factors, say, vaccination exposure, their model form would be

ASD risk = “Genetics” + “Environment” + e

but this model would still be underspecified.

The more fully specified model would be

ASD risk = “Genetics” + “Environment“+ “(Genetics x Environment)” + e

And if the interaction term “(Genetics + Environment)” is more highly significant than “Genetics” or “Environment“, a reasonable interpretation would be that we cannot interpret genetics in a vacuum, that the significance of many ADK risk alleles must be modified by environmental factors.  If during model selection, G or E is significant, but then in the full model G x E is significant, we attribute liability to both G and E working together.

Instead of this standard approach to studying genetic and environmental contribution to phenotypic variation (ASD phenotype), they do something very odd.

In the Supplementary Material, they report that they made assumptions about environmental factors.  Non-specified “Shared Environmental” effects are ASSUMED to be 1.0 for siblings and 0 for cousins.  Families quite often stop vaccinating after an older sibling experiences seizures.  The study authors also EQUATE “Non-Shared Environmental Factors” with “residual errors”, which is patently absurd.  That’s “e“, which is unspecified variation (error), not designated environmental factors.

If I had conducted an analysis of environmental factors and their contribution to ASD, and used their methodology, I would be able to attribute any unexplained variation to “Genetics” after allowing “Environmental Factors” to consume most of the variation.  I might arbitrarily add in some assumptions, such as assuming that risk from dominant alleles were 1.0 (which they are not, if the impact of those alleles are modified by environmental factors) and all recessive risk alleles contributed zero risk, which would be, as described, arbitary.  Their conclusions draw directly from their assumptions.

Evidence? What Evidence?

The WebMD article cites the entire team of researchers as saying “the current study results provide the strongest evidence to our knowledge to date that the majority of risk for autism spectrum disorders is from genetic factors,” [‘said a team led by Sven Sandin, an epidemiological researcher at the Karolinska Institute in Stockholm, Sweden’] – as quoted by WebMD.

Evidence?  What evidence? If you assume no contribution of environment, measure no environment, and conclude no contribution, there is no evidence.

There are over 850 genes that have been determined to contribute to ASD risk – and not one of them explains >1% of ASD risk individually.  Most of these are Common Variants – meaning they are ancient – as in, they pre-date both the ASD epidemic (and yes, there is an epidemic) and vaccination.  Here’s a figure from my book, which reviews all of the genetic and environmental studies published to mid-2016:

 

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This explains why ASD pedigrees look like humanity dipping its toes into a toxic soup:

pedigree

The study also does not explain why >20% of children with ASD have higher copy number variation – de novo genetic variation – compared to the rest of the population, nor why people with ASD – and their mothers – have anti-brain protein antibodies – nor why people with ASD have strange misfolded proteins, lifelong microglial activation, why studies of replacing the microbiome show a reduction in the severity of autism traits by 50%… a feat for a diagnosis that is allegedly 80% “genetic”… and so on, and so on.

Then There is Phenomimicry

The study ignores the fact that environmental factors can impact genes, proteins and biological pathways in a manner that is identical to the effects of genetic variation. This is called Phenomimicry – a term so cool I wish I had invented it.  Examples of Phenomimicry are known in science relevant to ASD.

3“Guess What? Being Human is Heritable”

It’s worth pointing out that thousands of human “traits” are heritable, and that includes traits that contribute to sociality, language ability, intellect, and even perhap tendency toward repetitive motion.  That means that genetic studies must subtract the heritability of these traits in the non-ASD population from the estimate of heritability in their contribution to ASD.

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The WebMD article, and the research report itself, lauds the study for involving over 2 million people from five countries.  This is not impressive because the study falls into the category of “Science-Like Activities“.

No More YAHUGS

It is highly unethical – and socially irresponsible  – for “Genes-Only” studies to be conducted that claim to rule out environmental factors.  All “Yet Another Highly Unethical Genes-Only Study”s – YAHUGS – should be replaced with fully and correctly specified models. That means measuring and studying both vaccination patterns and genetics.

WebMD article on archive.is

James Lyons-Weiler

Allison Park, PA

Note: A layman’s example will help.  Let’s say you want to understand thumb injuries among carpenters,and you specify a model

Risk of Injury = Hammer Size

You SHOULD also include Length of Nail, i.e.,

Risk of Injury = Hammer Size + Length of Nail

but it is socially unacceptable to conduct science on the Length of Nail.  So you leave it out.  You then model

Risk of Injury = Hammer Size + e

and incorrectly attribute variation in the “Length of Nails” to “e“.

You SHOULD specify

Risk of Injury = Hammer Size + Length of Nail + (Hammer Size x Length of Nail) + e

But that pesky social pressure to ignore Length of Nail goes a long way.

So you don’t know “(Hammer Size x Length of Nail)“because you do not know Length of Nail.

So you attribute everything to “Hammer Size”, totally ignorant of any direct or interactive effect of the “Length of Nail“and “Hammer Size“.

So you conclude “Hammer Size explains more than Length of Nails” when you should publish

“We Do Not Know the Effect of Length of Nails in Isolation nor with Interaction with Hammer Size”.

You can support me in my initiatives – going live in the fall with the WWDNYK Studios – join on Patreon where these and other pressing issues will be discussed with live guests.

 

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A Tale of Three Metals and The Fate of Western Civilization

A Tale of Three Metals and The Fate of Western Civilization

1200px-MadlHatterByTenniel

Biff: LET’S DIG UP TOXINS, PURIFY THEM, AND INJECT THEM INTO OURSELVES! AND BABIES! AND PREGNANT WOMEN! AND LET’S PUT THEM INTO PAINT THAT WE USE IN OUR HOMES WE LIVE IN, AND PUMP THEM INTO THE AIR WE BREATHE! AND LET’S MAKE SURE THAT THE WATER WE DRINK COMES INTO OUR HOMES IN PIPES THAT LEACH LEAD!
Buff: ARE YOU MAD?
Biff: NO, BUT WE WILL BE!

The Romans drank beverages prepared in lead vessels, and brought spring water into their homes through lead pipes. Lead poisoning undoubtedly hastened the fall of the Roman empire. So when we think about the evidence that we are harming ourselves, and our children, with lead in the water, mercury in the air, mercury in flu vaccines, and aluminum in many other vaccines, one has to wonder: what are the likely effects on society?

  1. African Americans will suffer the most. Due to Vitamin D deficiency, African Americans at northern latitudes can be expected to be most sensitive to toxins because they rely on dietary Vitamin D to drive their cellular detoxification systems. The fix? Measure blood Vitamin D levels, and absent any mutation that would preclude increased doses of Vitamin D, improve brain health via addition Vitamin D supplementation.
  2. Young adults (millenials) will have different sociality, and higher rates of early-age psychological disorders such as schizophrenia. They may also experience higher rates of early age of onset Parkison’s disease, Alzheimer’s disease, and other neurodegenerative diseases. The fix? Filter aluminum out of the water, try silica-rich mineral waters, silica drops, with a preference for sources with the more biologically available silicic acid. In short, detoxify their food, water, and everything in their environment, and more (see below).
  3. Young children with special education needs will tend to be more violent and brain studies will show increased presence of amyloid precursor protein, the kind responsible for Alzheimer’s disease.
  4. There will be a population-wide downward shift in IQ.
  5. There will be a plague of multiple chemical sensitivity.
  6. Academics will be stretched thin and the curriculum dumbed down to the point where schools will have to stop giving grades. When 20% of the class can no longer function academically to take and exam, the rest will be asked to “help” their classmates learn.
  7. Families will become increasingly stressful social units. Divorce rates will skyrocket.
  8. People will become increasingly dependent on the State (Nanny State).
  9. Those most able to withstand the toxic effects of accumulating neurotoxins will become increasingly taxed because their income and property will have to sustain an increasingly demanding medico-government empire.
  10. When they, too, begin to fall apart, the tax base will falter.
  11. Violence will become increasingly common. Those most damaged will tend to kill and injure those who are capable.
  12. America will tear itself apart from within.

This doomsday scenario is not inevitable. So what can we do to prevent this?

  1. Listen to the mothers. They have experience in what works. NIH has avoided real research on neurodevelopment disorders that address neurotoxic metal exposure since the CDC worked so hard to defraud the public on the vaccine/autism link. They gambled, lost, and we now pay the cost.
  2. These solutions must be tested in combinations in clinical studies to insure safety, and also to validate them (if they do help). They must be studied NOW, before it’s too late.

Option 1. Environmental Detoxification. Remove all neotoxins from your home. Use reverse osmosis water filters, and use filtered water for everything – even cooking – because aluminum is used to condition the water coming from the tap. Fluoride is another issue, and your filtration should also remove fluoride. Eat organic foods and nothing out of aluminum containers. Certainly never cook in aluminum pots.

Option 2. Get the Aluminum Out. Consider using high silicic acid mineral water, or adding silicic acid drops to your filtered water to bind any aluminum from food. Other possibilities include malic acid, magnesium, and acetoacetic acid:

Principles of Orthomolecularism. R.A.S. Hemat: “Aluminum can be effectively complexed and excreted with silicon, a complex of malic acid and mg, and acetoacetic acid.”

Precise combinations that work best and are safe are not yet determined. That’s why we need studies.

Doctor Toni Bark, MD informs me that ketogenic diet can also help reduce brain inflammation and reduce the effects of toxic metals from the body and the brain – including the reduction of brain amyloid. And Dr. Richard Frey’s research on intranasal insulin and intranasal deferoxamine seems very promising for the actual removal of iron and aluminum from the brain. Care should be taken to conduct any such research under the direct care of a physician.

Option 3. Up the Vitamin D3, watch the A, Avoid Folic Acid. Dr. Keith Baggerly, MD, has determined that the FDA flubbed in it recommended daily Vit D intake. As a result, most Americans are Vit D deficient. Increased Vitamin D3 can be expected to improve many aspects of health by helping our cells properly fold proteins. Vits A and D are antagonistic, and so watch all sources of Vit A and make sure you and your child are not taking in too much Vitamin A. Read The Big Vitamin D Mistake. and Grant Genereux’s resources on Vit A toxicity [1] [2].

Much of our population has MTHFR mutations that cause problems with Folic Acid. Moms taking prenatal vitamins should seek methyl folate or folinic acid instead of folic acid. Children’s vitamins with methyl folate are also available.

Option 5. Reduce Brain Inflammation. Chronic low-grade inflammation is a hallmark of autism. Powerful brain antioxidants include N-acetylcysteine and glutathione. It seems likely that everyone with a brain could benefit from less brain inflammation.

Option 6. Improve the Gut. The commensal (helpful) bacteria in the large intestine can become significantly altered after antibiotic use to treat ear infections, most likely caused by harm from to the immune system from thimerosal. Pro-biotics may help, as will eating organic.

Option 7. Keep This Handy for Bad Head Days. Brain dysfunction from metal-induce excitotoxicity involves high glutmate levels in the brain. Oxaloacetate can reduce blood glutamate levels, allowing the excess glutamate in the brain to spill into the blood. Oxaloacetate is used after stroke to reduce the exitotoxic brain injury. Research is needed to determine if it should be used after vaccination to reduce the incidence of vaccine-induced excitotoxicity. And aluminum should be removed from vaccines because the schedule results in toxic doses in infants.

Option 8. HBOT is HOT. Consider Hyperbaric Oxygen Therapy (HBOT). HBOT can increase de novo neurogenesis. If the brain has suffered a loss of neurons due to toxic exposure, increased neurogenesis – at the right time in development – could ultimately be shown to increase IQ.

Option 9. Avoid Thimerosal. If you choose to use a flu vaccination, ask the doctor for the type of flu shot that does not contain thimerosal.

Option 10. Tell Congress You Want Research Reform.

No studies of the synergistic toxicity of aluminum, lead and mercury have been conducted at doses reflecting the vaccine schedule and daily exposure due to leaching of lead from pipes into homes.

We know which homes have lead pipes. Departments of Health should consider telling parents of children in those homes to avoid exposures to mercury and to aluminum – in other words, to skip vaccines that contain these neurotoxic metals. The children will become more educated, better behaved, make better decisions, commit fewer crimes, and overall have better lives. Toxicity of lead, aluminum and mercury is synergistic.

No studies of the options and combinations of options listed above have been conducted to determine if we could improve overall brain health in children and adults. This research is badly needed. YOU can make it happen.

Make an appointment with your Congressional Representative and ask them to create the Brain Health 2030 initiative designed to reverse the ill effects of the past 30 years of industry and medicine on brains, and on our childrens’ brains. These interventions are not intrusive. Studies could be done also with the Department of Education to determine whether reports of violence decrease, grades increase, drop-out rates decrease if entire SCHOOLS – including administrators – are enrolled in Healthy Brain programs, which could incorporate aspects of mindfulness.

You can join the Neurodevelopment Research Reform group on Facebook where ideas on the Brain Health 2030 initiative are shared. And you can support our efforts to compile the most promising evidence-based approaches to improving brain health by supporting IPAK’s Neurodevelopment Research Reform Initiative.

This article is a call for research reform. These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Check with your physician before changing any mode of medical treatment for your child, or yourself.

Further Reading:

Lyons-Weiler, J and R. Ricketson. 2018. Reconsideration of the Immunotherapeutic Pediatric Safe Dose Levels of Aluminum. Journal and Trace Elements in Medicine and Biology 48:67 73.

https://www.sciencedirect.com/science/article/pii/S0946672X17300950

Thanks to Tim Lundeen for the Vit A information and of course to the outstanding medical doctor, Dr. Toni Bark, MD for permission to cite her expertise.

Neuroimmune Toxicity of Aluminum Adjuvants 1: Safety studies of aluminum in vaccines lack immunotoxicity analysis of this immunological adjuvant: Ignorance or deception? -Vinu Arumugham

This article is part of a series of guest articles to jameslyonsweiler.com on the neurological and immunological toxicity of aluminum-containing adjuvants in vaccines.  These articles appear by invitation to the authors.  -JLW

The safety studies most often referred by vaccine regulators when making claims about the safety of aluminum in vaccines, have ignored the immunotoxicity of aluminum.

Vaccinologists admit that they neither understand the general immunological mechanisms involved in vaccination nor do they understand the mechanisms involved in aluminum adjuvant action.

Thus vaccine regulators have no scientific basis to make vaccine safety claims. Given this situation one would expect that vaccine regulators would be very cautious about making vaccine safety claims. Instead, they collude with vaccine makers to actively hide vaccine safety problems and mislead the public.

The dual role of immunotoxicity and neurotoxicity of aluminum in autism is also covered. Cow’s milk contaminated aluminum adjuvanted vaccines cause the synthesis of folate receptor antibodies. These antibodies block folate uptake causing cerebral folate deficiency and autism. The folate deficiency in turn, causes aluminum accumulation in the brain, resulting in neurotoxicity and exacerbation of autism.

Background

Vaccine safety authorities such as the US Food and Drug Administration (FDA) and the Australian National Centre for Immunisation Research & Surveillance (NCIRS) use studies such as Mitkus et al. 1 and Jefferson et al.2 to claim that aluminum adjuvants in vaccines are safe.

Discussion

Mitkus et al.1 provide the following description of the effect of aluminum adjuvants on the immune system:

“Aluminum adjuvant are important components of vaccines, since they stimulate the immune system to respond more effectively to protein or polysaccharide antigens that have been adsorbed to the surface of insoluble aluminum particles. Specifically, these coated particles are phagocytized by cells of the innate immune system (e.g., macrophages) and activate intracytoplasmic sensors of pathogen-associated molecular patterns located within the cells, such as the nucleotide-binding domain leucine-rich repeat-containing family of sensors ([6]; Schroder and Tschopp [30]). The functional consequence of activation of this intracellular system is the activation of certain enzymatic caspases that cleave pro-interleukin (IL)-1β to interleukin (IL)-1β. The secretion of the mature cytokine, IL-1β, leads to an inflammatory reaction and a downstream Th2-dependent antibody response [7], which amplify the immune response to the antigen. Adjuvanted aluminum, therefore, plays a vital role in facilitating the response that underlies the immunoprotection afforded by vaccines.”

 

The rest of the Mitkus et al. review focuses on body burden of aluminum after it is absorbed from the muscle into the blood. They completely ignored any negative immunological effects that aluminum can have while it is still in the muscle (following intramuscular vaccine administration).

The quoted paragraph above assumes that the only proteins in the vaccine are viral/bacterial target proteins required for immunoprotection. In that case, as they state, the stimulation by aluminum plays a vital role in generating immunoprotection.

But obviously, vaccines contain numerous other proteins including food proteins (ovalbumin, milk, soy, yeast, oils from sesame, peanut, fish etc.)3,4, culture medium cell proteins (Vero monkey kidney cell proteins, calf serum proteins, WI38/MRC5 fibroblast cell proteins, chick embryo cell culture proteins etc.)3, non-target viral/bacterial proteins5, that are also adsorbed on to the surface of insoluble aluminum particles. As they state then, aluminum adjuvants stimulate the immune system to respond more effectively to ALL these proteins as well. The result is off-target immune responses that includes synthesis of antibodies against any and all of these proteins as well as cell-mediated immune responses.

The result of such a response of course includes food allergy6-9, asthma10, autism11,12 and autoimmune diseases13,14.

How can they perform a safety assessment of aluminum in vaccines while completely ignoring this immunological effect?

Jefferson et al.2 reviewed eight studies (listed in Table 2 of Jefferson et al.) on the effect of aluminum adjuvants. Any vaccine will need about 3-4 weeks to take effect. That’s how long it takes for the immune system to develop the appropriate immune response and antibodies. For this reason, vaccine effectiveness investigators wait at least one month post vaccination to assess effectiveness.15

Aluminum compounds are of course an immunological adjuvant in vaccines.16. So their immunological effect (positive or negative) can only be assessed if the follow-up period is greater than 4 weeks. However, only two out of eight studies in Jefferson et al. had a follow up period of >4 weeks. So rest of the studies they included were useless to assess immunological safety of aluminum adjuvants. Even those two studies ignored immune disorders such as allergies, asthma, autism or autoimmunity. As previously described, each of these immune disorders can be initiated by IgE mediated allergy11 or the Th2 response, which aluminum adjuvants are known to produce.1,17

So not only were the original studies flawed, Jefferson et al. made the mistake of including these flawed studies in their analysis. To really evaluate the safety of aluminum salts in vaccines, one would have to account for all known/potential immunological mechanisms involved with aluminum adjuvants. What are the potential negative outcomes due to that mechanism? What tests are needed to check for those outcomes? Would the outcomes be overt disease or will they be sub-clinical effects for years? This would determine follow-up times and decision on serological examination. For example: to assess if aluminum may be increasing the risk of sensitization to cow’s milk proteins contaminating the vaccine, one would not only have to wait for 4 weeks after vaccination, but also challenge the patient with cow’s milk, pre- and post- vaccination, to assess the impact. Similarly, to check if aluminum induced an autoimmune disease that may only show up years later, one would have to perform autoimmune serology pre- and post-vaccination checking for changes in autoantibody levels, as suggested by Wraith et al.18

These studies have never been performed. Why?  In fact, vaccine makers seem to go out of the way to obscure the adverse effects of aluminum adjuvants by injecting aluminum adjuvant into control subjects during vaccine clinical safety trials.15

Given this situation, the Jefferson et al. conclusion: “Despite a lack of good-quality evidence we do not recommend that any further research on this topic is undertaken.” is inexplicable, and raises serious questions about the manner in which vaccine safety investigations are conducted.

Evidence of aluminum adjuvant dangers

Morris et al.19 have called for the elimination of aluminum adjuvant in vaccines. Prof. Franco Celada, Dept. of Pathology, NYU School of Medicine, called for safety studies of aluminum adjuvant induced innate immune system activation (personal email communication, Oct 2017) in the context of low affinity self reactive (LASR) T cell mediated autoimmune diseases13,14 caused by animal protein contaminated vaccines.

Anders et al.20 have called for the re-evaluation of aluminum adjuvants in vaccines due to its role in boosting IgE mediated responses. In other words, a Th2-dependent antibody response as described by Mitkus et al.1 and Terhune et al.21 Terhune et al.22 further link Treg dysregulation in atopic disease to aluminum adjuvants.  Shoenfeld et al.23 describe aluminum adjuvant-induced autoimmunity.

Aluminum immunotoxicity followed by neurotoxicity in autism

Many vaccines contain casein or casamino acids of bovine milk origin and are thus contaminated with all bovine milk proteins.3,24 One such protein is the bovine folate receptor (FR) protein25. Such aluminum-adjuvanted, bovine FR protein contaminated vaccines can cause IgE mediated sensitization to the FR protein (aluminum adjuvant induced Th2 response1).4,6,10

Since FR concentration in bovine milk is low, the patient can still consume bovine milk without developing an allergic reaction.25,26 It has been shown that consuming milk when sensitized (via an oral immunotherapy protocol, for example) will result in the synthesis of IgG4 antibodies specific to milk proteins.8

In this case, bovine milk consumption causes FR specific IgG4 synthesis. These IgG4 antibodies cross-react with human folate receptors. Human and bovine FR proteins have 90% amino acid sequence homology.27  IgG4 specific to FR is the main antibody involved in binding/blocking folate receptors in the choroid plexus, blocking folate uptake to the brain.27

This results in cerebral folate deficiency and autism.28 Folate deficiency in turn, results in aluminum accumulation in the brain and aluminum-induced neurotoxicity.29-31

The source of the aluminum could of course be the diet, pollutant inhalation and aluminum-adjuvanted vaccines. Mold et al.32 have demonstrated such aluminum accumulation in human autistic brain tissue.

Conclusion

The FDA makes a mockery of science by comparing aluminum in vaccines to dietary aluminum.33 In that case, we should be drinking our aluminum adjuvanted vaccines, instead of intramuscular injection. The FDA’s Mitkus et al. study1 is entitled “Updated aluminum pharmacokinetics following infant exposures through diet and vaccination.”. They studied pharmacokinetics – how aluminum moves through the body. While aluminum pharmacokinetics related safety needs to be understood, they cannot ignore aluminum adjuvant immunotoxicity, if they were really interested in vaccine aluminum adjuvant safety. If the FDA is incapable of even determining the appropriate lines of safety investigations required, how can they be in charge of vaccine safety? How can we expect vaccines approved by the FDA to be safe?

Safety needs engineering not tinkering

For decades, vaccinologists have been reluctant to understand the immunological mechanism of how vaccines work, fail or hurt the body.

Pulendran et al.37 wrote:

“Despite their success, one of the great ironies of vaccinology is that the vast majority of vaccines have been developed empirically, with little or no understanding of the immunological mechanisms by which they induce protective immunity. However, the failure to develop vaccines against global pandemics such as infection with human immunodeficiency virus (HIV) despite decades of effort has underscored the need to understand the immunological mechanisms by which vaccines confer protective immunity.”

Mojsilovic16: “Some of the first adjuvants discovered back then, on empirical basis of trial and error, are still in widespread use today, but only recently some light on the molecular mechanisms of their action has been shed.”

There seems to be little interest among vaccine developers and regulators in understanding the mechanisms of immunoprotection or immunotoxicity of vaccines and adjuvants. This is no way to build a safety critical product, centuries after its invention.

Since the immunological mechanisms of vaccines are not understood, one would expect that vaccine makers and regulators will be extremely cautious about making vaccine safety claims. One would expect that they will thoroughly investigate even the slightest indication of vaccine-induced adverse events.

Instead, we find vaccine makers and regulators collude to hide vaccine safety problems. The ShingrixTM vaccine was recently approved after an inadequate safety evaluation.35 The FDA briefing document (Sep 2017) describes serious adverse events (SAEs) including supraventricular tachycardia following Shingrix vaccination in clinical studies. The Shingrix vaccine package insert (revised 10/2017)36 has no reference to supraventricular tachycardia at all.

Acknowledgment

Elizabeth Hart, Adelaide, South Australia, suggested this review and provided background material.

References

1. Mitkus RJ, King DB, Hess MA, Forshee RA, Walderhaug MO. Updated aluminum pharmacokinetics following infant exposures through diet and vaccination. Vaccine. 2011 Nov 28;29(51):9538–43.

2. Jefferson T, Rudin M, Di Pietrantonj C. Adverse events after immunisation with aluminium-containing DTP vaccines: systematic review of the evidence. Lancet Infect Dis. United States; 2004 Feb;4(2):84–90.

3. Vaccine Excipient & Media Summary [Internet]. 2015 [cited 2016 Jan 16]. Available from: http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/B/excipient-table-2.pdf

4. Arumugham V. Professional Misconduct by NAM Committee on Food Allergy [Internet]. 2016. Available from: https://www.zenodo.org/record/1034559

5. Ahmed SS, Volkmuth W, Duca J, Corti L, Pallaoro M, Pezzicoli A, et al. Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2 (ABSTRACT ONLY). Sci Transl Med. 2015;7(294):294ra105–294ra105.

6. Arumugham V. Evidence that Food Proteins in Vaccines Cause the Development of Food Allergies and Its Implications for Vaccine Policy. J Dev Drugs. 2015;4(137):2.

7. Platts-Mills TAE. The allergy epidemics: 1870-2010. Journal of Allergy and Clinical Immunology. 2015. p. 3–13.

8. Hoyt AEW, Schuyler AJ, Heymann PW, Platts-Mills TAE, Commins SP. Alum-Containing Vaccines Increase Total and Food Allergen-Specific IgE, and Cow’s Milk Oral Desensitization Increases Bosd4 IgG4 While Peanut Avoidance Increases Arah2 IgE: The Complexity of Today’s Child with Food Allergy. J Allergy Clin Immunol. Elsevier; 2017 Jul 7;137(2):AB151.

 9. Alice Hoyt, Peter Heymann, Alexander Schuyler, Scott Commins TAEP-M. Changes in IgE Levels Following One-Year Immunizations in Two Children with Food Allergy [Internet]. 2015. Available from: https://wao.confex.com/wao/2015symp/webprogram/Paper9336.html

10. Arumugham V. Medical muddles that maim our children with allergies, asthma and autism [Internet]. Unpublished; 2017. Available from: https://www.zenodo.org/record/1034595

11. Arumugham V. Autism Spectrum Disorders: A special case of vaccine-induced cow’s milk allergy? [Internet]. 2017. Available from: https://www.zenodo.org/record/1034557

12. Arumugham V. Strong protein sequence alignment between autoantigens involved in maternal autoantibody related autism and vaccine antigens [Internet]. 2017. Available from: https://www.zenodo.org/record/1034571

13. Arumugham V. Cancer immunology, bioinformatics and chemokine evidence link vaccines contaminated with animal proteins to autoimmune disease: a detailed look at Crohn’s disease and Vitiligo [Internet]. 2017. Available from: https://www.zenodo.org/record/1034777

14. Arumugham V. Bioinformatics analysis links type 1 diabetes to vaccines contaminated with animal proteins and autoreactive T cells express skin homing receptors consistent with injected vaccines as causal agent [Internet]. 2017. Available from: https://www.zenodo.org/record/1034775

15. Gardasil Package Insert [Internet]. Available from:

http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM111263.pdf

16. Mojsilovic SB. Immunological effects of adjuvants, their mechanisms, and relevance to vaccine safety. Cent Eur J Paediatr Vol 13, No 1 Cent Eur J Paediatr. 2017;

17. Lindblad EB. Aluminium compounds for use in vaccines. Immunology and Cell Biology. 2004. p. 497–505.

18. Wraith DC, Goldman M, Lambert P-H. Vaccination and autoimmune disease: what is the evidence? Lancet (London, England). England; 2003 Nov;362(9396):1659–66.

19. Morris G, Puri BK, Frye RE. The putative role of environmental aluminium in the development of chronic neuropathology in adults and children. How strong is the evidence and what could be the mechanisms involved? Metab Brain Dis. United States; 2017 Oct;32(5):1335–55.

20. Markt A, Björkstén B, Granström M. Immunoglobulin E responses to diphtheria and tetanus toxoids after booster with aluminium-adsorbed and fluid DT-vaccines. Vaccine. 1995;13(7):669–73.

21. Terhune TD, Deth RC. How aluminum adjuvants could promote and enhance non-target IgE synthesis in a genetically-vulnerable sub-population. J Immunotoxicol. England; 2013;10(2):210–22.

22. Terhune TD, Deth RC. A role for impaired regulatory T cell function in adverse responses to aluminum adjuvant-containing vaccines in genetically susceptible individuals. Vaccine. Netherlands; 2014 Sep;32(40):5149–55.

23. Shoenfeld Y, Agmon-Levin N. “ASIA” – autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. England; 2011 Feb;36(1):4–8.

 24. Kattan JD, Cox AL, Nowak-Wegrzyn A, Gimenez G, Bardina L, Sampson HA, et al. Allergic reactions to diphtheria, tetanus, and acellular pertussis vaccines among children with milk allergy. J Allergy Clin Immunol. 2011;Conference(var.pagings):AB238.

25. Nygren-Babol L, Sternesjö , Björck L. Factors influencing levels of folate-binding protein in bovine Å milk. Int Dairy J. 2004;14(9):761–5.

26. USDA Food Composition Databases [Internet]. Available from: https://ndb.nal.usda.gov/ndb/

27. Ramaekers VT, Sequeira JM, Blau N, Quadros E V. A milk-free diet downregulates folate receptor autoimmunity in cerebral folate deficiency syndrome. Dev Med Child Neurol. 2008;50(5):346–52.

28. Arumugham V. Epidemiological studies that ignore mechanism of disease causation are flawed and mechanistic evidence demonstrates that vaccines cause autism [Internet]. 2017. Available from: https://doi.org/10.5281/zenodo.1041905

29. Baydar T, Nagymajtenyi L, Isimer A, Sahin G. Effect of folic acid supplementation on aluminum accumulation in rats. Nutrition. United States; 2005 Mar;21(3):406–10.

30. Yassa HA, George SM, Mohamed HK. Folic acid improve developmental toxicity induced by aluminum sulphates. Environ Toxicol Pharmacol. 2017;50(Supplement C):32–6.

31. Zhu M, Li B, Ma X, Huang C, Wu R, Zhu W, et al. Folic Acid Protected Neural Cells Against Aluminum- Maltolate-Induced Apoptosis by Preventing miR-19 Downregulation. Neurochem Res. 2016;41(8):2110–8.

32. Mold M, Umar D, King A, Exley C. Aluminium in brain tissue in autism. J Trace Elem Med Biol. 2018 Mar;46:76–82.

33. FDA. Study Reports Aluminum in Vaccines Poses Extremely Low Risk to Infants [Internet]. Available from: https://www.fda.gov/biologicsbloodvaccines/scienceresearch/ucm284520.htm

34. Pulendran B, Ahmed R. Immunological mechanisms of vaccination. Nat Immunol. United States; 2011 Jun;12(6):509–17.

35. Arumugham V. SHINGRIX vaccine is unsafe and its approval must be revoked [Internet]. 2017. Available from: https://www.zenodo.org/record/1038302

36. FDA. SHINGRIX vaccine package insert [Internet]. 2017. Available from:

https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM581605.

 

When is “Genetic Autism” Not Genetic?

THE FOCUS ON THE CONTRIBUTION OF GENES to the risk of diagnosis of autism seems warranted, if you look at the press.  Each week, sometimes each day. a new study comes out about a gene that is an important contributor, the stories go, to our understanding of autism.  Here’s one that touts the gene SCN2a as a “Rosetta Stone” for understanding risk of autism.  It’s poorly written because it misrepresents the full knowledge base. The media’s coverage is, to some extent, dependent on their ability to comprehend genetics, and what they are told by investigators.  I get hype for research; it’s a form of marketing that is essential to communicating our the value of our activities to the public.  But the story conveys a sense that autism “is genetic”. It also makes no reference to other studies of a similar gene, SCN1a, related to Dravet’s syndrome and seizures. Here’s one I cite in “Causes”. We’ll come back to that later.

Considering autism genetics can be complex. When there are genes that are found to contribute to the risk of autism, and individual genes are headlines, and yet there are hundreds of genes that contribute, none of which are known to contribute to more than 1-2% of the cases of autism, what is really going on?

Much of the landscape of autism genetics, the roles of environmental factors, and, importantly, the role of the interactions between genes and environment is mapped out in “Causes”.  I reviewed over 2,000 studies on autism to come to grips with a number of important unanswered questions, not the least of which is “which is more important in autism: genes, or environment?” It may appear to be a simple question, for given the dramatic rise in autism diagnosis, we cannot expect that such an increase in less than a generation to be attributed to genetics.  And that view is nearly 100% correct.  But at the risk of incurring the wrath of individuals who may fear that today’s post, and my book, is another attempt to make people think “autism is genetic”, let’s proceed.

pedigree

First, we need to contrast some definitions.  Here is a list of similar terms that, importantly, the autism community must keep clear in their minds if they are to communicate meaningfully, say, with genetics researchers, or even with genetic counselors:

  1. risk vs. liability
  2. genetic risk vs. familial risk
  3. mutation vs. variation
  4. heritability vs. concordance

RISK vs. LIABILITY

To say “autism is genetic” is to make very specific claim about where the risk of autism came from. In the vast majority of people’s minds, it means that the risk of autism in children comes from their parents. And to the extent that our genetic information comes from our parents in the form of our DNA, usually packaged into 23 pairs of chromosomes in our genome, some of the risk of autism is surely “genetic”. However, much of that risk was not present in past generations, because a high proportion of the genetic information that appears to contribute to autism has been found to be in form of de novo mutations.  They are new mutations that occur in the formation of the sperm and the egg, in the parent’s body during cellular division leading to gamete formation (meiosis).

This is where the distinction between risk and liability is important. (First, be clear, we are on journey toward understanding: “Liability” is a not synonymous with “Blame”. We’ll see why later). Truly genetic risk exists because the parents not only shared the genetic variation that contributed risk, but they also shared, to a lesser or greater degree, the risk of autism due to that genetic variation.  The “lesser or greater” degree here is meted by two important factors:

(A) Dominance, and Heterozyosity/Homozygosity. Some truly genetic traits are expressed regardless of whether we have one or two copies of the specific variation leading to the trait; these traits are considered dominant, and the risk of seeing the trait is 100% if one carries the variation from either mother, or father, or both.  Other traits require the specific variant (or similar enough variant) from both parents to be observed in the offspring; these are called recessive traits.

(B) Single vs. Multi-locus Traits. Some traits seem more blended than other.  When multiple genes contribute to these traits, the inheritance of risk still exists, but the resulting pattern of the appearance of traits in offspring may be considerably more variable than for simple genetic traits. These are called ‘multi-locus’ traits because genetic information located at multiple positions on chromosome are observed to contribute to the trait of interest.

I already hinted at the fact that hundreds of genes have been found that “contribute to autism”, and therefore you likely have figured out that much of the behavioral traits seen in autism are not simple traits encoded by individual genes.  In fact, in “Causes”, citing the results of numerous genetic studies, I conclude because any individual genetic variant that is truly genetic (with both variant and risk of trait seen in the parental generation) is so low in frequency in the population, purely “genetic” autism is perhaps never seen in our species. Each variant is so low in the population, usually much less than 1%, that the odds of 2, 3, or 4 of these variants being inherited in any individual in our species is vanishingly small.  So while the beautifully conducted Pinto et al. (2014) study show that the odds of autism increases with the number of these inherited variants, the actual and the expected rates of seeing individuals who inherit 2-3 variations from their parents leading to autism approaches zero.  Although there are a very large number genes that encode proteins involved in synaptic transmission (as this image adapted from Pinto et al. shows:

synapsepinto

And there are myriad other pathways involved in autism, the risk of “genetic” autism due to “multiple hits” is very, very low:

pintomultiplehit

So the risk of purely genetic autism is very low, and yet the two largest genetic studies conducted to date conclude that overall genetic liability of autism is around 50%.  They attribute the remainder of the risk to environmental causes.  So what’s the difference between RISK and LIABILITY?

Risk is an inherent characteristic of an individual; each of us have an individual risk of developing cancer. Liability is the degree to which genetics, or environmental factors, can be said to ‘explain’ the incidence of a trait (usually a disease trait) in a population.  So with hundreds of genes each contributing “to autism” in small percentages, the total population-wide occurrence of increases in traits can be explained, in part, by “genetics”.  I use “genetics” in quotes here because I mean the combined total population risk due to both inherited genetic variations, and de novo mutations.  Up to 20% of autistics show increases in new genetic variations, not found in either of their parents.  And thus while the information is carried in the gametes in the genome sequence, the trait “risk of diagnosis of autism” is not inherited, because it is not shared by the parents.

Many of the other conceptual contrasts can now also be made clear. GENETIC VS. FAMILIAL RISK, for example, is seen as the risk of a trait appearing in offspring due to inherited risk of the disease trait due to genetic information seen in either or both the parents and in the children, whereas FAMILIAL RISK is seen as the overall risk found in children born to the same parents whether the source of that risk is genetic, or due to a common environment. It should be noted that it is possible that some families are at overall higher GENETIC RISK of having de novo mutations (such as mutations in post-replication mismatch repair genes active in meiosis), and therefore the GENETIC RISK of de novo mutations may be shared among siblings.  This characteristic would tend to be shared among siblings both with, and without autism, but may be expected to be higher (more concordant) in twins and in siblings with autism.

The distinction between CONCORDANCE vs. HERITABILITY is an important one to make.  CONCORDANCE is the rate of shared occurrence of traits among siblings in the same family, and is a mix of genetic contributed liability and liability due to shared environment, whereas HERITABILITY is the rate of share occurrence of traits between parents and offspring.  Obviously, since parents of most autistics born since 2005 do not have autism themselves, the pattern of traits across millions of pedigrees indicates that the evidence of autism risk cannot come from HERITABILITY of risk, again, implying a large role for shared environments explaining any studies with high rates of CONCORDANCE of autism or traits associated with autism.

Autism Risk is No More than 50% Genetic, and AT LEAST 50% Environmental

I outline very strongly in “Causes” that genetic studies, as conducted thus far, cannot truly estimate that relative contribution of genes and environmental factors as long as they only study genes.  “Geneticists are doomed to find genes” is the phrase I drop. However, it can be seen in the largest studies, because they have not studied environmental exposures, that if the apparent contribution of genes is estimated at 50%, leaving around 50% liability for environmental factors, but the studies could not estimate the GENETIC X ENVIRONMENT interactions, that the real contribution of environmental factors is likely GREATER than 50%, because if the genetic liability (inherited variants attached to inherited risk) is G, and the environmental liability is E, then

TOTAL LIABILITY = G + E + (G x E)                                                      (1)

Where G X E is the interaction between environmental and genetic factors.

Clearly (G x E) is not zero in autism, given that purely genetic autism is perhaps no more than 1-2% of cases of autism. So if E+(G x E) = >98% of autism, either E is huge, or (G x E) is huge, or both are huge.

But we cannot forget the “genetic” contribution of de novo variations.  Let’s distinguish between inherited risk tied to inherited genetic information (G1) from risk newly derived from new variation (G2):

TOTAL LIABILITY  = G1 + G2 + (G1,G2 x E)                                           (2)

Now we can see that if G2 is being increased, the importance of the apparent “genetic” contribution of de novo variations cannot be known until they are studied in the context of environmental factors.  We should expect that environmental factors, and both G1 and G2 type genetic factors are causal; and none are mere ‘triggers’.

What is Causing Increased Rates of G2 de Novo Variation in Autistics?

So where is the genetic contribution to the “genetic” liability coming from?  This is an important question, because if 20% or more of autistics have increased numbers of de novo copy number variations, effecting apparently hundreds of genes, whatever is causing those increases of copy number variations must be identified.  Some hypotheses are being looked into, from, as I indicated, the DNA repair genes involved in meiosis. Scant evidence exists one way or the other (many readers will appreciate that careful distinction, can I get an “Amen!” for Science?), but it is interesting that there appears to be decreased risk of cancer in autistics.  To me, this implies the loss of individuals with cancer risk from the population of autistics, perhaps in the womb, due to excessive genetic load.  Variations (inherited and de novo) that contribute “to autism” may (I speculate) already pose such difficulties for developing embryos that variation in the critical DNA repair genes may simply be screened out by lethality of genetic (G1 + G2) burden.  It would be interesting to see if siblings of children with autism have a higher overall incidence of cancer risk or increased variations known to contribute to cancer risk because they represent individuals who survived embryonic development with mutations.

Another hypothesis that could explain the increased rates of de novo variations, posed by radiologist Dr. Edward Fogarty, is the increase in the use of pelvic CT scans.  No evidence exists yet (again, a call FOR SCIENCE, not a call for No More Science), but straightforward looks at the rates of pelvic CT and other radiologic exposures in parents with of autistics compared to parents of neurotypicals could be critically important.  Two lines of evidence make this compelling. The first is the association detected between access to health care and rates of autism.  There could be other obvious contributors to the association of access to healthcare and rates of autism, including exposures to neurotoxins in vaccines (mercury, aluminum) and more likely diagnosis.  But neither of those factors can be expected to lead necessarily to increases in de novo variations.  The other line of evidence is the association of the age of parent with autism; older parents are more likely to have had multiple exposures to medical diagnostic radiation.  Dr. Fogarty and I will be looking into these environmental factors in 2017.

The final thought on when “genetic” autism is actually not genetic derives from my knowledge of biological pathways.  In canvassing the 2,000 studies on autism, including hundreds of genetic studies and way fewer environmental studies, it became apparent to me that understanding the role of genetics and environment (and their interaction) requires putting “autism genes” into three categories

(1) Autism Risk Genes – Genes that contribute directly to G1 (inherited trait risk)

(2) Environmental Susceptibility Genes – Genes that contribute to increased susceptibility of neurological disorders due to environmental toxin (developmental and otherwise)

(3) Autism Phenotype Modifier Genes – Genes that contribute to traits often associated with autism in the population, but that also show heritability in the entire population, not just the autistic population (language skills, some social skills, intellectual ability).

I offer examples of each of these three categories in “Causes” as hypotheses. Recognizing these three categories of genes will be essential for a fully understanding not only of autism, but of the many conditions that are thought to be co-morbid with autism, especially seizures, intellectual ability, and propensity for anger. Because many of these traits or tendencies involve pathways that clearly overlap with pathways that influence the core characteristics of language and communication, social abilities, and repetitive motions used to diagnose autism, it is very clear (to me at least) that every child with autism, or on the spectrum, and every child with a familial risk should have their genome sequenced and studied and their particular constellation of variants determined to be inherited (G1) or de novo (G2) studied to see if they are at risk of these other traits, and to see if they are at risk of suffering due to specific environmental exposures.

We have a long way to go before we can tell families which environmental exposures individual families or individual family members should avoid.  See this remarkably clear study by Scott Faber and colleagues at the Children’s Institute in Pittsburgh, PA that shows that the severity of behavioral traits associated with autism increases in autistics with cumulative exposures to environmental toxins:

faber

And some of the suspects they found:

faber2

They did not study vaccines. Autism is, for the most part, environmental. Our species did not evolve in a world with highly irradiated pelvises, and a toxic soup that challenges a growing identifiable minority of individuals who will get sick, or die, or whose normative neurologic development program will be altered.  And as we (all) become increasingly sick, what is the logical outcome of increasing the baseline of toxic exposures by packing the untested CDC schedule with increasing numbers of vaccines?

The logic around vaccine safety science has been replaced by a shell game, mixed with false dichotomies. Remember SCN1a, which I promised we would come back to?  It turns about that because a few studies found that Dravet syndrome patients with encephalopathy were conducted, and they found and reported small numbers of patients w/mutations in SCN1a. Because they existed in these patients, the studies concluded that the encephalopathy could (potentially) be due to the mutations. Prior to these studies, vaccines had been (and still is) attributed as the cause of encephalopathy in these patients.  Do those mutation case series exonerate vaccines?

No.

It requires science to rule out vaccines. Mutations do not exonerate vaccines as a cause of encephalopathy simply because the mutations were found second.  The studies had no control groups (patients with Dravet’s with no history of vaccination), so it is certainly plausible that, as in many complex disorders, the risk is additive, or these mutations (or others) interact with toxins from vaccines in identifiable way.  We need multifactorial thinking in vaccine safety science, not merely “either/or” contrasts.

magic

Due in part to this errant “either/or” thinking about autism risk factors,  we can’t yet specifically predict which families should avoid which toxins.  Therefore, in the meantime, let us all adopt an attitude of tolerance and respect for individuals who wish to reduce their risk by reducing their own, or their child’s exposures to environmental toxins, including the neurotoxins in vaccines.  Let us stand firm on informed consent and require a full accounting of risks (as required by law) in each and every encounter in the clinic on vaccines.  Let us stop the draconian practice of destroying careers of medical professionals and journalists who become aware that with vaccines, we are taking some of the most toxic parts of our environment, and injecting them into babies. Let us use Science to formalize our approaches to using known risk factors of adverse events.  Let us use Science to develop biomarkers for serious adverse events.  Let us stop public shaming, and name-calling, and let’s get down to the business of public health considering all dimensions of risk of illness and disease.   If we are all protected from infectious diseases from vaccines, we owe everything to those who have taken the hit in the form of vaccine injuries. Let us not deny vaccine-injured children and their families justice, and due compensation. They are STILL trying to protect us, every day, by increasing  Vaccine Risk Awareness. Let us stop minimizing the perception of risk, while doing nothing to minimize the actual risk. That is a recipe for disaster. Vaccine court Special Masters, stop obfuscating with broken logic and give awards to kids whose toxin tolerance was pushed over the edge by vaccines (“via”, as you say, encephalopathy):

conditional2

And please stop using non-sequitur molecular excuses like “channelopathy” to hide “autism”. The damage done to sodium channel functioning via mutation, or via environmental exposures, is identical.  It’s called “phenomimicry”.

Journal editors, stop retracting papers because a vocal minority of individuals say they cannot live with those published results.  Journalists, #bebrave and report on the environmental factors, including vaccines. Let us have #the conversation, so we can enact a sea change.  If you all start reporting at once, Pharma will not pull their funding from everyone.  Mass resistance WILL WORK.  Parents, continue to tell your stories, to Polly at #vaxxed and any outlet you can find.

For heaven’s sake, let’s stop using Thimerosal in flu shots for pregnant women (and for everyone, while we’re at it) and stop vaccinating pre-term babies altogether.  This study shows that Thimerosal specifically inhibits a protein called ERAP1, which is responsible for proper shortening of ALL proteins during translational expression.  Who in their right mind would want to alter protein editing processes in anyone, not to mention developing fetuses?  And why in the world is 850 micrograms of aluminum the safe dose limit for a 150 pound adult, and the same dose limit for a 7.5 pound baby?  Why is 5 micrograms the limit of aluminum in biologics other than vaccines, and yet pre-term infants receive 250 micrograms after a few days?  Where is pediatric dosing in vaccines?  Where is the vaccine safety science? More importantly, where is the integrity in vaccine safety science?

If we return to Science, we can make vaccines safer.  Totally safe? Maybe not. Much safer? Certainly. Spacing out vaccines is not a crime. It’s informed caution. We can screen for epitopes that make vaccines unsafe for some because they match human proteins. We can develop and use means of artificial immunization that elicit dendritic cell responses – without aluminum. Vaccine safety science must look at tallied cumulative exposures, not vaccinated vs. vaccinated. Clinicians, petition Medicare to count medical exemptions TOWARD, not AGAINST, the 60% rate you need to enjoy your bonuses.  Were it not for their medical conditions, after all, they would be on schedule! Researchers, stop burying associations and model overfit.  CDC, publish all of the comments on the proposed weakening of the risk of MMR, and uncensor my comment. Oh, and fix your website, it looks like there are zero comments.  Congress, one last time, PLEASE  subpoena William Thompson. We all know what happened. It’s getting embarrassing.  We’re moving on. Either way, you’ll be hearing from us.

All of this can be done. All of it MUST be done.

week

I dedicate this blog article to The World Mercury Project, and I wholeheartedly endorse Mr. Kennedy as Chairperson for the Vaccine Safety Science Commission.  Their logo here is used without permission, and WMP has nothing to do with my blog, or any of its articles.

 

wmp

I am grateful for everyone who has helped me to this point. There are so many.  You know who you are.

smiley

Protect Baby’s Brain from Aluminum Neurotoxicity – It’s Not Just the Vaccines

Anyone who reads my writings will know that I tend to not hold back in the “should” department – because ethics and morals in society depends not only in the proper conduct of science, but also in the proper translation into general knowledge and public health policy.  Those with their hands on the reins of public health policy appear to be more interested in defending flawed policies, and those of us who have come to learn of flaws in the science used to bolster those policies are bound by moral contract with a duty to warn our fellow human beings.

Well, at least some of feel that way.

I would be worthy of being labeled hypocritical, therefore, if I did not shout from my blog the news that there are other sources of aluminum that pregnant and nursing moms may well expose their developing babies to – one that is so commonly available, and the dose of aluminum so high that I shudder to think of any pregnant woman or nursing mom (or individual who likes their brain) taking a single dose.

That product is antacids.

In a chapter reviewing aluminum neurotoxicity (yes, Dr. Offit, aluminum is a long-known neurotoxin), Dr. Robert Yokel in 2012 reviewed estimates of the amount of aluminum absorbed from exposure from various sources, and the results certainly do not bode well for vaccines.  Here is a screen shot of the chapter:

Yokel1

And here is a screenshot of his Table 1, with aluminum from vaccines at 0.07ug daily exposure and aluminum from antacids at 80ug per day:

yolkel1

The low amount calculated “per day”from vaccines, however, is misleading: the dose from a vaccine is given in a single day – and the body has to deal with 100% absorption in real time.  So the numbers to compare are 12-300µg/dose in a day to 80µg/day.  Se the “up to 5,000,000 µg” ingested?  The fact that only 80µg are absorbed per day shows you how little aluminum a normal-functioning GI tract actually absorbs. But that’s a lot for a mom to have in her body while she’s pregnant.  So much for the dismissive position that babies get more aluminum from baby formula. Mothers should breastfeed anyway – unbelievable, CDC recently said moms should not breastfeed to give the vaccines a chance to be more effective.

Add to the 80 from antacids and aluminum in the vaccines offered during pregnancy (bad idea in the first place), and add later aluminum to the baby after via vaccines after birth, you can see we may successively and repeatedly dose our youngest with a neurotoxicant. Aluminum (in a wide variety of forms) causes chronic microglial activation, which occurs when certain cells (microglia) in our brains get stuck in the “destroy” mode and take out dendrites trying to make connections and baby nerve cells (neural precursor cells).

Expectant moms, lactacting moms, throw your antacids away and look at your aluminum intake.  Other foods potentially high in aluminum include pre-prepared pancake mixes and other foods that are kept powdery and dry.  Look at the ingredients and save your baby’s brain from chronic and prolonged exposure.   Get an air filter and filter out the dust that can introduce aluminum into your baby’s body via the lungs or GI tract.

Aluminum is certainly not the only toxin that can induce microglial activation. But 10% of the aluminum absorbed stays in the brain for decades.  Moms and dads, look at the table an find ways to reduce aluminum exposure, and we might just be able to reduce the rates of autism/ASD worldwide.

The full chapter is available from the University of Kentucky website.

http://uknowledge.uky.edu/cgi/viewcontent.cgi?article=1030&context=ps_facpub

baby brain

 

Dr. Lyons-Weiler is the author of three book, the latest of which is “Environmental and Genetic Causes of Autism”, which can be ordered online or from your local independent bookseller. A companion website to the book includes over 1,000 references to studies on autism.

causes

My Journey from Ignorance

WHILE RETURNING from the United Nations building where I heard NYU Professor Mary Holland (School of Law) nail the issues of constitutional and international law on the right to informed consent to the floor, to a standing ovation, I received an email from Mary ( To my delight). I read, in part:

“I  started reading your Ebola book last night.  Wow, you have evolved a lot in your thinking on vaccines in a VERY short period, based on your definition of ‘antivaxxers’ at bottom of 206, top of 207.  Have you written up how your views evolved so quickly?  It might be a helpful roadmap towards turning others around.  Was this all in connection with the autism book, or did your views changing precede that book?”

Looking at my book this morning, I turned to page 206, with trepidation, to find the younger, knowing me, trying to save the world by chiding and deriding people whom I have come to learn much more about in the past two years:

“Again and again with Ebola we see, from Guinea to the US, societies struggling with the ethical problem of the needs (and wants) of a few vs. the safety (and lives) on the many”.

Ok, that’s not too bad.  A bit uppity, but I cannot disagree. But it gets worse.

“With over 100 cases confirmed, the US is, at the time of this writing, at high risk of an epidemic of measles because the herd immunity is lacking due to a dogmatic antivaccination movement”.

I warned you.

Deplorably, I continue:

“The efficacy of the measles vaccine in protecting children against terrible diseases should be reason enough for parents to insist on vaccinating their children, but the so-called ‘anti-vaxxers’ (people who believe vaccines place their children at risk of developing autism) fail to consider the greater good: They put others at risk by not participating in national programs for the greater good.”

I really do not like my former self. Naturally, I continue, because I knew SO much before I actually looked into the studies and the data:

“This perspective is more than mere 20:20 hindsight; such occurrences of cultural and institutional amnesia are certain to recur as our society becomes more reliant and trusting in technology, and we forget to respect the awesome power of biology and Nature”.

I really don’t know this guy, I swear.

Mary Holland will certainly be remembered as one of the most staunch defenders of human rights, well, in the history of abuses in medicine. So back to Mary’s question:

“Have you written up how your views evolved so quickly?  It might be a helpful roadmap towards turning others around.  Was this all in connection with the autism book, or did your views changing precede that book?”

Here’s how and why my views have changed. First, I was really rather upset about the fact that CDC Director Thomas Freiden stated in his testimony to Congress that there were no mutations in the Ebolavirus that was driving the epidemic.  I was upset because I had the 396 mutations on my laptop at the very moment he testified to Congress.  I capture that moment in “Ebola“. My anger at the CDC increased when I attended a secret White House conference call, held by the Ebola Czar, in which I asked about the 396 mutations – whether they influenced the ability of tests to detect Ebola, or altered its virulence or transmissibility. In that call, the entire scientific community was lied to again by a CDC Scientist who claimed that the virus was “99.9999% identical to the strain from Zaire in 1995”, which was not true at all.  I capture both of those events in “Ebola”, as well as how the White House then asked the Associated Press to stop covering potential cases of Ebola in the US.  I even ask in that book whether that was “fascism”.

Fast forward a couple of months to where I had decided to write “Cures vs. Profits“. I felt that we had bungled our response to Ebola so badly that I wanted to cheer myself up and write a book on the successes in biomedical research.  Having participated in so many studies over the past two decades, I knew of many reasons that the public should continue to support biomedical research, and I was going to share all that I knew, and discover more. The first two chapters deal with “the bad stuff” – the doctors who cheat at medicare fraud, which robs other patients of needed funds for real medicine – and the biomedical researchers who cheat at their research studies.

I wrote my chapters out on grapefruit, on cancer vaccines, on prostate cancer robotic surgery, and then something happened: I wrote a chapter on ADHD overdiagnosis. I tell the story of the destruction of a promising career of Dr. Gretchen Watson.  Pharma sent a “Key Opinion Leader” to EVMS to debate her over her study, and the next day she was told her case load was canceled, that her colleagues were told that she no longer worked at EVMS, and that she was to expected to resign.  She refused, and won an appeal to HR.  But then someone floated a rumor that she manipulated her data in the 1996 study showing overdiagnosis.

The investigation revealed no flaw – well, a typo in an appendix – but the damage to her career was done. The good news is that Dr. Watson has decided to write of book of her own after reading my chapter on ADHD.  She now also serves on the Board at IPAK.

When I finished writing the rest of “Cures“, including chapters on the history of hormone receptor status in breast cancer, chemosensitivity assays, characteristics of good research scientists, and cancer vaccines, I found the book missing something.

So I decided to write a chapter on Vaccines.

I’ll let the chapter on vaccines speak for itself- it begins with tales of how wonderful vaccines are, how they save lives.  I went back to review the autism/vaccine link, fully expecting to review the Andrew Wakefield issue briefly, how his claims that MMR were linked to vaccines. I read the retracted study.

I found that Andrew Wakefield never claimed that the MMR might cause autism.  Instead, I found the study to suggest that it was a question worth looking into.

My digging around then led to my discovery of reports that someone at CDC had revealed that CDC had manipulated data on the studies designed to disprove Wakefield by omitting results with a positive association.

The more I dug into the issue, and then into the literature, the more I found the science of vaccines falling far short of the science needed to insure public health via any medical procedure given to millions. And this is where I leave the issue in “Cures“. I added an addendum that reviews four open controversies in vaccines that cause me to question whether vaccines can be called an unmitigated success in translational research.

In retrospect, I see that position as something of an understatement.

My understanding of vaccines was (obviously) limited, and I needed to grasp the risks involved. I needed resolution. So after I completed “Cures“, I began writing about what I had learned. I spoke with people with an open mind. I started to listen not only to what these evil, selfish “anti-vaxxers” had to say, I started to really think about the consequences of the additives. I began to question the over-arching claims of safety.

And via some new contacts, I made connection with Tony Lyons of Skyhorse Publishing. After a few chats, he, Louis Conte and I agreed that I should write a book on the Genetics of Autism. (I love Louis – and knowing what I know of him now, my bet is that he thought I was a good prospect – but somehow I can hear him telling Tony that Jack has ‘a way to go, but I think he’ll get there’. Thank you Louis for the confidence.

So in I dove, into 3,000 research articles on autism.  Not on vaccines – on autism.  I wanted to know if the basic science could in any way reasonably support a hypothesis that vaccines or their additives cause autism. The answer is a resounding “Yes, yes, and yes”. Other articles in this blog will give you an idea of some of the evidence that exists on the role of chronic microglial activation and autism, for example.

To the readers of “Ebola” who feel confused or hurt by my, and others’ ignorance, please remember that there is a Great Unknowing, even among professionals.  Think about it – all “Anti-vaxxers” with vaccine-injured children were once pro-vaccine. As I advised some 500 participants at the VIALs Health Summit in Atlanta, GA, do not argue with them – educate them. Your anger and frustration is warranted, but help them move from ignorance to awareness and understanding.

I took it upon myself to consider 3,000 articles on autism for “Causes” (available at Amazon.com and in your local Barnes and Noble or indie bookstore).  (I skimmed 3,000, read >2,000, and cite >1,000). Look at what knowledge can do to a scientist who themselves feel cheated and lied to, someone who entrusted the CDC to perform objective science (See “The Tyranny of Pseudoscience“):

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The author at a CDC Rally, April 22nd, 2016.

 

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Educating the public and calling for Congress to Subpoena Dr. William Thompson at the CDC on the true nature of so-called “Science” conducted at the CDC on the link between vaccines and autism.

To My Fellow Scientists and Medical Health Care Professionals

I wrote “Ebola” in good faith, assuming that the position of the CDC on vaccines was based on sound science. It was unfathomable to me that

-Upon finding positive associations, CDC would routinely over-analyze data from studies until they could make associations go away, and when they could not succeed in doing that, they would simply omit the results;

-CDC would suspend an employee who drew these practices to the attention of then CDC Director Dr. Julie Gerberding (who subsequently took a position in charge of vaccine development at Merck);

-After CDC published these studies they called for an end to research on vaccine safety with regard to potential links to autism;

-CDC would ignore nearly all of the basic science that shows mechanisms of how neurotoxins in vaccines (not just MMR) could reasonably be expected to cause autism in some people;

-CDC’s position is based on ecological association studies, not randomized prospective clinical studies with proper controls.

-Our knowledge of vaccine safety is based on post-market surveillance;

-CDC would ignore all of the post-market surveillance on vaccine safety, claiming that the passively collected data in VAERS did not provide causal evidence;

-CDC would lie repeatedly under oath to Congress about the State of Science on the link between vaccines and autism;

-No one has ever conducted a vaccinated vs. unvaccinated study for association with negative health outcomes, including autism.

-CDC would communicate to the public that “Vaccines Do Not Cause Autism” on their website knowing full well that 6/12 vaccines on the schedule before the age of 7 have 0 studies one way, or the other, on whether they indeed may (or may not) contribute to the risk of autism.

I, like the rest of the world, relied on the CDC to be a reliable source of information on vaccine safety.  Yes, I vaccinated my children. I will not allow them to get the HPV vaccine. Here is why.

To the Parents of Vaccine-Injured Children who Regressed Into Autism

Your observations are the basis of a new era in vaccine science.  All science begins with observations. Help and relief is on the way. And there is nothing that can stop it.

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Dr. Lyons-Weiler (right) meets Marcella Piper-Terry (left) at the 2016 CDC Rally.
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Fellow Vaccine Risk Aware Protestors Calling for Congress to Subpoena Dr. Thomspson
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Dr. Lyons-Weiler meets the future Director of the CDC.

After the Rally, we enjoyed a summit at Life University hosted by VIALS. Here was our audience:

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Here I presented the CDC Schedule as backed by “Magic”, because no science exists on any link between 6 vaccines and autism, whereas some vaccines do, in fact have some studies that support association:

no science 2no science

That was a good day in Atlanta, GA. Here are the slides to share with your pediatrician:

VIALs health summit slides James LyonsWeiler MAGIC

CDCSCHEDULE
“MAGIC!!!”

 

 

Next stop, the United Nations:

 

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Dr. Lyons-Weiler attends a UN Session on Toxins in Our Children, April 26th, where Dr. Thompson’s revelations were shared with the world.


 

Mary Holland standing up for your rights to refuse medical procedures as a basic human right. To watch the unprecedented UN Session on Toxic Contamination of Children (4/26/2016), follow this link.

Mary Holland’s question to me was an important one:like many, if not most other professionals, I had argued my position on the vaccine/autism question from a position of ignorance.  They simply have not done their homework, and many have bought the CDC’s lies hook, line and sinker. They count on CDC to be honest and forthright. This include the AAP, the AMA, and, very likely, your pediatrician.

Most of them probably have not read a single study. They likely have never read the following words that Dr. William Thompson said to Dr. Hooker:

Thompson: “They don’t really want people to know that this data exists.”

Thompson: “…among the blacks, the ones that were getting vaccinated earlier, were more likely to have autism.”

Thompson: “It appears in the final publication is that race in general is downplayed. Of course it is.”

Thompson: “I actually think the most interesting results are the isolated, ones that don’t have their co morbid conditions. The effect is where you would think it would happen.”

Thompson: “I was just looking at—I was like, oh my God, I cannot believe we did what we did. But we did.”

Thompson: “The higher ups wanted to do certain things and I went along with it. In terms of chain of command, I was number four out of five. “

Thompson: “…Literally, everyone else got rid of all their documents, and so the only documents that exist right now from that study are mine.”

Thompson: “There are things that I haven’t even shared with you because I can’t prove it, and that’s what I struggle with. I don’t want to share things with you that I can’t prove, that there aren’t hard records. I am worried that the other four people will collude and say no, that’s not true.”

Thompson: “That’s what I keep seeing again, and again, and again where these senior people just do completely unethical, vile things and no one holds them accountable. “

Thompson: “The reason you don’t see anything else circulating on the study, it was five of us behind closed doors for two years.”

Thompson: “It’s the lowest point in my career that I went along with that paper.”

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Dr. William W. Thompson

My book “Cures vs. Profits” tells more of the story of Dr. Thompson and Hooker. At this point, I am willing to go on the record and say that I have zero – ZERO confidence in any science coming out of the CDC Immunization Safety division. And no one else should trust their research, either.

In fact, nothing they publish can be trusted. Not merely because of what Thompson said.

I’ve read their studies.

They are atrociously unsafe ventures in data cooking, model overfit, sad excuses for “control variables”, use of multicollinear variables, the product of repeated data analysis to a desired result (no association). They are a mess.

The individual people in question include

RADM Anne Schuchat, Principal Deputy Director of CDC

Dr. Frank DeStefano, Director of the Immunization Safety Office

Dr. Coleen Boyle Director, National Center on Birth Defects and Developmental Disabilities (NCBDDD)

Dr. Poul Thorsen (co-author on suspect CDC studies, wanted by HHS for embezzling over $1Million in funds that were to be used for autism research, living openly in Denmark).

and others.

In my research, I strive to remain objective. However, since 2004, when the research fraud at the CDC occurred, there have been over 1,000,000 cases of autism that potentially could have been prevented simply by splitting up the MMR into three vaccines, spacing the vaccines out, giving non-adjuvanted vaccines with 1 adjuvanted, screening for safe epitopes, removal of mercury from all vaccines, giving medical exemptions to parents who already have one autistic child (to avoid the genetic x environment interaction), dropping HepB until adulthood… so many simple things that could have been done to reduce early exposures to toxins. Where is the science for biomarkers to indicate which children might be most at risk of ASD due to vaccines?  Not done.  CDC called for no more science.

We Want Evidence-Based Public Health Policies, not Policies Based on Subjective Belief (aka “Magic”)

Right now, the so-called “Anti-vaxxers” I so woefully admonished in “Ebola” are not all “Anti-Vaxxers”. They do consist partly of some people who believe no safe vaccine could ever exist. I respectfully remind them that until the science is done to show that non-adjuvanted vaccines without mercury, aluminum, formaldehyde, etc are tested, their knowledge claim is an untested generalization about all vaccines. Out of well-deserved distrust, they call for no more science on vaccine safety – because they know that some will be injured by that very research.

But the Vaccine Risk Aware movement also includes people who are 100% Pro-Vaccine Safety. They suspect that safe and effective antigen presentation systems can be designed, that use exposure at the skin (microdermal abrasion), with epitopes that do not induce autoimmunity. They believe that taking the toxins out will likely make vaccines safer. But they do not make such claims.  They call for more science, not less, but on newer options for inducing immunity.

To watch my presentation at the VIALS Health Summit State of Science on Vaccine Safety: Autism, in which I explain how the CDC’s claims that vaccines do not cause autism must be based on magic, follow these links: (Part 1, Part 2, Part 3).

Calls for Retraction of CDC “Studies”

Because CDC committed scientific fraud, the studies they performed should be retracted. IPAK has informed the journals of this, and we have sent them copies of “Vaccine Whistleblower, by Kevin Barry, Esq.

I urge all of my colleagues to view the movie #Vaxxed.  Call your local theater and ask them to screen the movie. If you consider yourself an objective scientist, read “Whistleblower“, and RFK jr.’s book, “Thimerosal: Let the Science Speak“.  Order “Master Manipulator” by James Grundvig, which tells the story of Poul Thorsen, a CDC collaborator wanted for absconding with autism research cash (given what CDC would have done with the money, Thorsen may be a hero, for all we know).  For a deeper timeline view on how long corporate corruption has eroded science in our most esteemed institutions like the CDC, read “Science for Sale” by David Lewis.

I ask my professional colleagues from all walks of science and medicine then to join us in our calls for retraction of the CDC’s false studies: DeStefano et al., Madsen et al., and Verstraeten et al.  I will not stop educating professionals about the fraud because we need evidence-based medicine, not medicine based on guesses, or hopes, or magic.  Babies are dying in the womb due to mercury in flu vaccine reserved for pregnant women; babies are born autistic due to immunoneuroexcitotoxicity; they are born with seizure disorders; toddlers regress into autism after learning language. And yes, it may be due to cumulative and interactive effects of toxic chemicals from agriculture, industry, our home, etc.  But we can reduce the toxins we expose our children to.  Right now, autism risk is 1 in 68, up from 1 in 3000 in the 1970’s.  Let’s have #theconversation.

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Acknowledgements. I have literally thousands of people to thank for helping move from ignorance to awareness.  You know who you are. Thank you.

Please support VIALs with a generous donation.  Tell them Jack sent you!
To support Dr. Lyons-Weiler and his research associates at IPAK, visit ipaknowledge.org

VIALs health summit slides James LyonsWeiler MAGIC

causes

Aluminum, Alzheimer’s and Autism

TO THE READER: IMPORTANT DETAILS HAVE EMERGED FROM STUDIES ON THE CAUSES OF BRAIN DYSFUNCTION FROM STROKE AND ALZHEIMER’S DISEASE THAT LEAD DIRECTLY TO HOPE FOR EFFECTIVE AMELIORATION OF THE BRAIN-CELL DESTROYING PROCESSES IN AUTISM. READ THE ARTICLE ALL THE WAY THROUGH TO LEARN ABOUT TWO NUTRIENTS THAT CAN HAVE BEEN FOUND TO REDUCE BRAIN GLUTAMATE LEVELS, WHICH CAUSES CHRONIC MICROGLIAL ACTIVATION (CMA). CMA IS KNOWN TO OCCUR IN THE BRAINS OF AUTISTICS FROM AGE 4-44. THE POSSIBILITIES ARE IMMENSE. MORE RESEARCH IS URGENTLY NEEDED. -JLW (April 8, 2016)

THERE ARE TWO MAIN KNOWN PROCESSES involved in the onset of autism. The first is susceptibility to environmental toxins via mitochondrial dysfunction, which can be the combined result of environmental insults and mutations in mitochondrial genes and genes that directly influence mitochondrial function.  This combination of factors exists in as many as 20% of cases of autism.

The second is chronic microglial activation (CMA). Microglia are amazing nerve cells that serve as shepherds of learning, fostering connections at the synapse during reinforcement learning. They also play the role of the white blood cells (WBCs) of the brain, becoming activated due to injury or infection. Upon dying, brain cells release chemicals calls cytokines that activate microglia from tending shepherds to armed killers. They consume bacteria, viruses, and cellular debris, clearing the brain of the dead and dying cells. The eat impaired dendrites in their activated state.

Other cells called astrocytes mop up the chemical signals that cause microglial activation via molecules called receptors. One of these signals is glutamate.  CMA occurs when something causes glutamate build-up in the brain.  CMA can occur in autism patients with or without mitochondrial dysfunction, and both processes may be at work and interrelated in any given patient with autism.

Causes of Excess Glutamate in the Brain

Many environmental factors can cause excess glutamate. Eating it (MSG) is one way to upset the balance between glutamate in the blood and the brain. The higher the concentration of glutamate in the blood, the less able the brains glutamate pumps are able to dump excesses into the blood. Mercury and aluminum, both additives found in vaccines, can cause chronic microglial activation by harming astrocytes’ ability to uptake glutamate. Chronic microglial activation is found in people with autism from age 5 to 44 (Vargas et al., 2005).

Researchers at the Johns Hopkins University in the Neuroimmunopathology lab studied autistics aged 5-44 and found that their brains had widespread microglial hyperactivation and sensitivity to astrocytes, reflecting IL-6 cytokine mediated inflammation (Vargas et al., 2005). The chronic inflammatory conditions were most pronounced in the cerebellum, anterior cingulate and the medial frontal gyrus. The fact that the hyperactivated state persisted for decades is a critical observation from this study.

Reducing Brain Glutamate and Brain Damage from Stroke

A series of important studies have shown that techniques that clear excess glutamate from the brain during stroke reduces brain damage.  Campos et al. (2011a), demonstrated the effectiveness of oxaloacetate  (a known blood glutamate scavenge) in treating rats in which a stroke was induced. The found that intravenous injection of oxaloacetate decreased both blood and brain glutamate levels. This led to an astounding  80% reduction volume of the brain infarct, dramatically reducing brain edema. The neuroprotective effects of oxaloacetate are due to the depletion of blood glutamate levels – which occurs as a consequence of the activation of a blood-resident enzyme glutamate-oxaloacetate transaminase (GOT) (Gottlieb et al, 2003). When blood glutamate levels are low, the gradient across the blood-brain barrier is in the correct ratio to allow rapid glutamate clearing. This will result in a shut-down of microglial activation.

Similar results were found in human studies by the same team. Campos et al (2011b) studied a cohort of several hundred stroke victims at two hospitals. Using the same inclusion and exclusion criteria, they found that blood glutamate levels at the time of admission to the hospitals was a good predictor of outcome from stroke. (Read more at “GOT to ride the body of excess glutamate“.

These studies confirm earlier findings that both oxaloacetate and pyruvate are effective at reducing brain glutamate levels (Boyko et al., 2012).

Read this exciting study in the abstract from Castillo et al. (2015):

“Glutamate excitotoxicity is a primary contributor of ischemic neuronal death and other cellular components of the neurovascular unit. Several strategies have been developed against glutamate excitotoxicity, however none of them have not shown positive results in the clinical practice so far. Nowadays, the concept of blood/brain glutamate grabbing or scavenging is well recognized as a novel and attractive protective strategy to reduce the excitotoxic effect of excess extracellular glutamate that accumulates in the brain following an ischemic stroke. The main advantage of this novel therapeutic strategy is that it occurs in the blood circulation and therefore does not affect the normal brain neurophysiology, as it has been described for other drug treatments used against glutamate excitotoxicity. In this work we report all experimental data from the beginning of our studies, focused on stroke pathology, and we describe new findings about the potential application of this therapy. Future clinical trials will allow to know the real efficacy of this novel therapeutic strategy in stroke patients.”

Microglia, Glutamate and Alzheimer’s Disease

One of the most vocal minds pointing to CMA as a major process involved in autism was Dr. Russell Blaylock, MD.  The abstract above  reads just like studies from autism by Blaylock and others (substitute “stroke” with “autism”). Blaylock’s various writing and videos of his presentations have awakened many to the fact that autism is a medical condition, not a neurodevelopmental disorder per se. The medical aspects of autism mean that reversing the causes of the disorder, such as shutting down chronic microglial activation, should be possible. An important part of that is diet. Some foods (such as those containing MSG) will exacerbate brain trauma caused by the excitotoxicity cycle set up by immunotoxins in vaccines (aluminum and mercury). Tylenol should be avoided as it depletes glutathione, a necessary component of microglial glutamate reduction.

It has only more recently been found that immunoneuroexcitotoxicity is at the causal center of Alzheimer’s disease.  A rich literature exists that shows that CMA is found as a causal factor in Alzheimer’s disease, with specific causal links demonstrated between excess glutamate, and microglial dysfunction.

Here is an example from Solito and Sastre (2012):

Contrary to early views, we now know that systemic inflammatory/immune responses transmit to the brain. The microglia, the resident “macrophages” of the brain’s innate immune system, are most responsive, and increasing evidence suggests that they enter a hyper-reactive state in neurodegenerative conditions and aging. As sustained over-production of microglial pro-inflammatory mediators is neurotoxic, this raises great concern that systemic inflammation (that also escalates with aging) exacerbates or possibly triggers, neurological diseases (Alzheimer’s, prion, motoneuron disease). It is known that inflammation has an essential role in the progression of Alzheimer’s disease (AD), since amyloid-β (Aβ) is able to activate microglia, initiating an inflammatory response, which could have different consequences for neuronal survival. On one hand, microglia may delay the progression of AD by contributing to the clearance of Aβ, since they phagocyte Aβ and release enzymes responsible for Aβ degradation. Microglia also secrete growth factors and anti-inflammatory cytokines, which are neuroprotective. In addition, microglia removal of damaged cells is a very important step in the restoration of the normal brain environment, as if left such cells can become potent inflammatory stimuli, resulting in yet further tissue damage. On the other hand, as we age microglia become steadily less efficient at these processes, tending to become over-activated in response to stimulation and instigating too potent a reaction, which may cause neuronal damage in its own right. Therefore, it is critical to understand the state of activation of microglia in different AD stages to be able to determine the effect of potential anti-inflammatory therapies. We discuss here recent evidence supporting both the beneficial or detrimental performance of microglia in AD, and the attempt to find molecules/biomarkers for early diagnosis or therapeutic interventions.

One of the leaders in this area is Israeli scientist Dr. Vivian Teichberg, Ph.D., who proposed that clearing glutamate from the blood might cause a release of glutamate from the brain into the blood.  In a series of clever studies, researchers at the Weizmann Institute found that transforming glutamate in the blood into another form causes glutamate in the brain to exit – providing protection against glutamate storms associated with stroke.  (Read: “Protecting the Brain from A Glutamate Storm“). More on this exciting epiphany, below.

Aluminum, Alzheimer’s, and Glutamate Uptake

Aluminum has long been suspected to be a plausible causal contributing factor to the risk of Alzheimer’s disease. Geographic correlations of aluminum levels in drinking water (Martyn, et al., 1989), and the finding of high amounts of aluminum in the brains of some patients who died from Alzheimer’s disease (just one example, see Exley and Vickers (2014)  were initial indicators. More recent studies seem to confirm the link. A metaanalysis found a 71% increase in the risk of Alzheimer’s disease in individual with chronic exposure to aluminum (Wang et al., 2016). As people age, their microglia become less efficient at clearing Aβ deposits from the brain parenchyma (Thériault et al., 2015).

Chronic Microglial Activation and Aluminum from Vaccines

Nine of 11 available studies reviewed by Flaten et al. (2001) concluded that Alzheimer’s disease incidence was increased regions with highest aluminum in residential drinking water. Measures of inflammation, particularly in the brain, were also seen to be increased when aluminum was high in drinking water (Campbell et al., 2004) – and, importantly, activated microglial cells were also increased. Aluminum in vaccines is almost certainly a causal factor in chronic microglial activation.

Aluminum is found in most vaccines, and is a serious neurotoxin, in spite of a thwarted misinformation campaign to the contrary (Read “Paging Dr. Offit! Your Aluminum Neurotoxicity Reading Assignments are Ready!“). In mice, subcutaneous aluminum injections resulted in significantly increased apoptosis of motor neurons and increases in reactive astrocytes and microglial proliferation within the spinal cord and cortex Shaw CA et al., 2013). Reduced spatial memory capacity and impairment of motor function was observed after six doses (Shaw et al., 2009). Aluminum also influences other cells than microglia; it results in altered mitochondrial metabolism, globular astrocyte shape and astrocyte dysfunction (Lemire et al., 2009).

Olmos-Alonso et al. (2016) found increased proliferation of microglial cells in human Alzheimer’s disease. Stanford University researchers have reported that a drug called EP2 can reverse microglial activation.

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Chronic microglial activation  (CMA) leads to damage to synapses, loss of neural precursor cells, and neuronal death. The same process of CMA is seen in autism from ages 4-25 (Vargas et al.). Image modified from  Morales et al., 2014. Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches. Front Cell Neurosci. 8:112. doi: 10.3389/fncel.2014.00112. eCollection 2014.).


Now The Most Exciting Part: Oxaloacetate and Pyruvate Supplements Clear Excess Glutamate from the Brain

Oxaloacetate is found in nature – and has numerous healthy benefits. It is non-toxic (similar toxicity to vitamin C) and is found in apples, pears, bananas, and spinach. (Read NDX USA’s easy-to-digest article “Oxaloacetate“.

Pyruvate is also found in nature. Foods containing it include red apples, cheese, dark beer, and red wine.  Here is a well-informed article  by Maia Appleby at SFGate on pyruvate supplements (“What Is Pyruvic Acid?”).

Both Oxaloacetate and Pyruvate are available in capsule form, however, the doses required to replicate the effects per body weight conducted in the studies showing their effects on glutamate levels in the brain are very high.  Here are some sources:

Oxaloacetate Supplement, 250 mg, by Natural Dynamix at Amazon.com

[Oxaloacetate (Oxaloacetic Acid) Mental Health Daily Link]

Pyruvate Supplement, 1000 mg, by Piping Rock Health Products at Amazon.com

According WebMD,  our bodies produce pyruvate when it breaks down sugar (glucose), and is used for weight loss and obesity, high cholesterol, cataracts, cancer, and improving athletic performance.  [WebMD Link]

[Disclaimer: These links are provided to the reader to inform on availability, are not meant as a recommendation. No health claims are made by the author, nor any recommendations. High doses of any supplement can have side effects. Check with your doctor before adding any supplements to your diet].

Conclusion

Chronic and acute microglial activation leads to brain trauma in stroke, Alzheimer’s and autism. By reasonable inference, supplements that reduce glutamate-induce chronic microglial activation in Alzheimer’s are very likely to have the same effects on some patients with autism.  Studies are urgently needed to determine if dietary oxaloacetate and pyruvate supplementation provide neuroprotection against chronic microglial activation in persons with autism.  Studies of glutamate levels and injection of oxaloacetate during severe neurological distress following vaccination should be undertaken immediately.

Dr. Lyons-Weiler is the President and CEO of The Institute for Pure and Applied Knowledge, which conducts basic, translational and clinical research in the public interest (without profit motive), and is author of three books, “The Environmental and Genetics Causes of AutismThe Environmental and Genetics Causes of Autism“,  “Cures vs. Profits“, and “Ebola: An Evolving Story“.

References

Boyko M et al., 2012. The effect of blood glutamate scavengers oxaloacetate and pyruvate on neurological outcome in a rat model of subarachnoid hemorrhage. Neurotherapeutics. 9(3):649-57. doi: 10.1007/s13311-012-0129-6.

Campos F, Sobrino T, Ramos-Cabrer P, Argibay B, Agulla J, Pérez-Mato M, Rodríguez-González R, Brea D, Castillo J. 2011. Neuroprotection by glutamate oxaloacetate transaminase in ischemic stroke: an experimental study. J Cereb Blood Flow Metab. 2011 Jun;31(6):1378-86. doi: 10.1038/jcbfm.2011.3. Epub 2011 Jan 26.

Campbell A et al., 2004. Chronic exposure to aluminum in drinking water increases inflammatory parameters selectively in the brain. J Neurosci Res. 75(4):565-72.

Campos F, Sobrino T, Ramos-Cabrer P, Castellanos M, Blanco M, Rodríguez-Yáñez M, Serena J, Leira R, Castillo J. High blood glutamate oxaloacetate transaminase levels are associated with good functional outcome in acute ischemic stroke. J Cereb Blood Flow Metab. 2011 Jun;31(6):1387-93. doi: 10.1038/jcbfm.2011.4. Epub 2011 Jan 26.

Castillo J et al. 2015. A novel mechanism of neuroprotection: Blood glutamate grabber. J Cereb Blood Flow Metab. 2016 Feb;36(2):292-301. doi: 10.1177/0271678X15606721.

Exley C, Vickers T. 2014. Elevated brain aluminium and early onset Alzheimer’s disease in an individual occupationally exposed to aluminium: a case report. J Med Case Rep. 8:41. doi: 10.1186/1752-1947-8-41.

Flaten TP, 2001. Aluminium as a risk factor in Alzheimer’s disease, with emphasis on drinking water. Brain Res Bull. 55(2):187-96.

Gottlieb M, Wang Y, Teichberg VI. 2003. Blood-Mediated Scavenging of Cerebrospinal Fluid Glutamate. Journal of Neurochemistry  87: 119–126.

Lemire J et al., 2009. Aluminum-induced defective mitochondrial metabolism perturbs cytoskeletal dynamics in human astrocytoma cells. J Neurosci Res.;87(6):1474-83. doi: 10.1002/jnr.21965.

Olmos-Alonso A et al., 2016. Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology. Brain 139(Pt 3):891-907. doi: 10.1093/brain/awv379.

Martyn, C. 1989. Geographical relationship between Alzheimer’s disease and aluminum in drinking water. Lancet 1:59.

Shaw CA and MS Petrik. 2009. Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration. J Inorg Biochem. 103(11):1555-62. doi: 10.1016/j.jinorgbio.2009.05.019.

Shaw CA et al., 2013. Administration of aluminium to neonatal mice in vaccine-relevant amounts is associated with adverse long term neurological outcomes. J Inorg Biochem. 128:237-44. doi: 10.1016/j.jinorgbio.2013.07.022.

Solito E, Sastre M. 2012. Microglia function in Alzheimer’s disease. Front Pharmacol. 3:14. doi: 10.3389/fphar.2012.00014. eCollection 2012.

Thériault, P et al. The dynamics of monocytes and microglia in Alzheimer’s disease Alzheimer’s Research & Therapy 20157:41 DOI: 10.1186/s13195-015-0125-2.

Vargas DL et al., 2005. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 57:67-81.

Wang Z et al., 2016.  Chronic exposure to aluminum and risk of Alzheimer’s disease: A meta-analysis. Neurosci Lett. 2016 Jan 1;610:200-6. doi: 10.1016/j.neulet.2015.11.014. Epub 2015 Nov 27.

Zlotnik A, Gurevich B, Tkachov S, et al. 2007. Brain Neuroprotection by Scavenging Blood Glutamate. Experimental Neurology 203: 213–220.

Books by Dr. Lyons-Weiler

Ebola: An Evolving Story (2015, World Scientific)

Genetic and Environmental Causes of Autism (2016, Skyhorse Publishing)

causes

Cures vs. Profits: Successes in Translational Research (2016)

Related Abstracts

Bondy SC. 2016. Low levels of aluminum can lead to behavioral and morphological changes associated with Alzheimer’s disease and age-related neurodegeneration. Neurotoxicology. 52:222-9. doi: 10.1016/j.neuro.2015.12.002. 

Abstract
Aluminum (Al) is a very common component of the earth’s mineral composition. It is not essential element for life and is a constituent of rather inert minerals. Therefore, it has often been regarded as not presenting a significant health hazard. As a result, aluminum-containing agents been used in the preparation of many foodstuffs processing steps and also in elimination of particulate organic matter from water. More recently, the reduced pH of bodies of water resulting from acid rain has led to mobilization of aluminum-containing minerals into a more soluble form, and these have thus entered residential drinking water resources. By this means, the body burden of aluminum in humans has increased. Epidemiological and experimental findings indicate that aluminum is not as harmless as was previously thought, and that aluminum may contribute to the inception and advancement of Alzheimer’s disease. Epidemiological data is reinforced by indications that aluminum exposure can result in excess inflammatory activity within the brain. Activation of the immune system not initiated by an infectious agent, typifies the aging brain and is even more augmented in several neurodegenerative diseases. The origin of most age-related neurological disorders is generally not known but as they are largely not of genetic derivation, their development is likely triggered by unknown environmental factors. There is a growing and consistent body of evidence that points to aluminum as being one such significant influence. Evidence is presented that reinforces the likelihood that aluminum is a factor speeding the rate of brain aging. Such acceleration would inevitably enlarge the incidence of age-related neurological diseases.

Fanne RA, Nassar T, Heyman SN, Hijazi N, Higazi AA.. 2011. Insulin and glucagon share the same mechanism of neuroprotection in diabetic rats: role of glutamate. Am J Physiol Regul Integr Comp Physiol. 2011 Sep;301(3):R668-73. doi: 10.1152/ajpregu.00058.2011. 

Abstract
In patients with acute ischemic stroke, diabetes and hyperglycemia are associated with increased infarct size, more profound neurologic deficits and higher mortality. Notwithstanding extensive clinical and experimental data, treatment of stroke-associated hyperglycemia with insulin is controversial. In addition to hyperglycemia, diabetes and even early prediabetic insulin resistance are associated with increased levels of amino acids, including the neurotoxic glutamate, in the circulation. The pleiotropic metabolic effects of insulin include a reduction in the concentration of amino acids in the circulation. In this article, we show that in diabetic rats exposed to transient middle cerebral artery occlusion, a decrease of plasma glutamate by insulin or glucagon reduces CSF glutamate, improves brain histology, and preserves neurologic function. The neuroprotective effect of insulin and glucagon was similar, notwithstanding their opposite effects on blood glucose. The therapeutic window of both hormones overlapped with the short duration (~30 min) of elevated brain glutamate following brain trauma in rodents. Similar neuroprotective effects were found after administration of the glutamate scavenger oxaloacetate, which does not affect glucose metabolism. These data indicate that insulin and glucagon exert a neuroprotective effect within a very brief therapeutic window that correlates with their capacity to reduce glutamate, rather than by modifying glucose levels.

Pogue AI, Lukiw WJ. 2016. Aluminum, the genetic apparatus of the human CNS and Alzheimer’s disease (AD). Morphologie. 2016 Mar 8. pii: S1286-0115(16)00024-2. doi: 10.1016/j.morpho.2016.01.001.

Abstract
The genomes of eukaryotes orchestrate their expression to ensure an effective, homeostatic and functional gene signaling program, and this includes fundamentally altered patterns of transcription during aging, development, differentiation and disease. These actions constitute an extremely complex and intricate process as genetic operations such as transcription involve the very rapid translocation and polymerization of ribonucleotides using RNA polymerases, accessory transcription protein complexes and other interrelated chromatin proteins and genetic factors. As both free ribonucleotides and polymerized single-stranded RNA chains, ribonucleotides are highly charged with phosphate, and this genetic system is extremely vulnerable to disruption by a large number of electrostatic forces, and primarily by cationic metals such as aluminum. Aluminum has been shown by independent researchers to be particularly genotoxic to the genetic apparatus, and it has become reasonably clear that aluminum disturbs genetic signaling programs in the CNS that bear a surprising resemblance to those observed in Alzheimer’s disease (AD) brain. This paper will focus on a discussion of two molecular-genetic aspects of aluminum genotoxicity: (1) the observation that micro-RNA (miRNA)-mediated global gene expression patterns in aluminum-treated transgenic animal models of AD (Tg-AD) strongly resemble those found in AD; and (2) the concept of “human biochemical individuality” and the hypothesis that individuals with certain gene expression patterns may be especially sensitive and perhaps predisposed to aluminum genotoxicity.

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