Two research papers have been published recently which have opened the door to a better understanding of what causes Autistic Spectrum Disorder (ASD) and what we can do to try to reverse the process.

The first paper, published in Japan in November 2003 dealt with the devastating effect that ethyl mercury has on cellular development and how it can cause cellular death [ * ]; the second, published in January 2004 by Dr Richard Deth and others explored in detail the disruption of cellular signalling that follows exposure to toxic levels of Mercury, Aluminium and other ’heavy’ metals[ * ].

Taken together these papers have significantly increased our understanding of the cause of this syndrome.

A third publication, by Dr Rashid Buttar in the form of Testimony to Congress turns the view of ASD on its head, when he states that there is ’no such thing’ as ASD - that it (ASD) is in fact a form of chronic Mercury toxicity - nothing more, nothing less [ * ].

This view, while radical is largely supported by his own research and by the pooled knowledge of many Physicians internationally, who have found that removal of Mercury underpins the successful management of ASD.

The development of ASD appears to be due to a combination of

Genetic susceptibility, and

Exposure to toxins in the environment ( including toxic metals in some vaccines )

This has been calculated by Dr Jill James and by Dr Bernard Rimland to affect approximately 1 in 100 children with a male:female sex ratio of 4:1.

Genetic susceptibility + Toxin causes

Cell death ( apoptosis ) and

Disruption of Cellular signalling ( DNA Methylation ) and this leads to

Metallothionein ( Methionine synthase ) dysfunction

Immune system damage ( T1 to T2 shift - external to internal policing - auto-immunity)

GI system damage ( acquired gluten and/or casein intolerance - peptide formation, dysbiosis )

Copper overload (learning defects, hyperactivity, anxiety & loss of behaviour control) and

These in turn lead to a cascade of symptoms and problems which is the

I have represented this in a flow chart, which is attached.

Note: Over the years, it has been repeatedly noted that there are biochemical similarities between ASD and Alzheimer’s Disease ( and some similarities with Schizophrenia as well ) It is thought that Alzheimer’s may be an ‘adult’ form of ASD due to toxicity with Aluminium - the second commonest toxic metal overload found in ASD.

The first thing to do is to make a full and accurate

We now recommend management on the following lines:

Stool analysis to seek dysbiosis

Hair analysis to estimate toxic metal burden and nutrient mineral deficiencies

Genomic studies chromosome analysis

Genomic studies are relatively expensive and not all parents can afford to have these done. Genomic studies are the headlights on the car - they indicate in which direction therapy should proceed, and can be of immense value.

We then commence therapy, based on the initial assessment of a particular child. Any or all of the following may be recommended.

Then we give

Then we add

Vitamin A as Vitasorb A

Then

Vitamin B as Vitasorb B

By this time, the results of the hair and stool analysis are usually available and this determines the order of priority of further management, either

Chelation therapy (Please see Removal of toxic metals)

And / or

Dysbiosis therapy which varies depending on the lab. Analysis

Then

The extent and duration of therapy and the exact protocol followed will depend on the stool and hair analysis results and of course, the child’s response.

What we are trying to do is effectively to work ’backwards’ - unravelling the chain of events that have occurred in a particular child, addressing their specific needs such as

Toxic metal overload

‘Kick start’ DNA methylation ( cellular signalling)

- and all this time, monitoring the removal of toxic metals, and the child’s response to therapy.

I would now like to go into more detail with regard to each item outlined above:

The gene pool has been more than 5 million years in the making. The second Ice-Age ended 10,000 years ago and it has been calculated by DNA sampling that all Caucasians are descended from just 6 women - 6 women who survived in caves in the South of France. Since then mankind has passed through approximately 200 generations, adapting all the time.

Between 1996 and 2004 the entire DNA structure of our Chromosomes has been mapped in a world-wide joint collaboration and we now know what most genes are there for.

Through a process of ‘adaptation’ we represent the state-of the-art that is Homo Sapiens today. But ‘victory’ (over the environment) comes at a price and we are not perfect. Imperfect genes lurk in all of us - within the DNA structure of our cells’ nuclei.

We have 46 chromosomes, approximately 1250 genes on each chromosome and 214,816 genomes per gene.

Total genomic variation is therefore 1.235 billion, with each genome being capable of up to 1 million different ’expressions’.

Genomic expression potential variation is therefore 1.235 million, billion or

1, 235, 000, 000, 000, 000, 000

- we are concerned with just one !!

On Chromosome no.6 there is a fault in the expression of the genome for Methionine Synthase activity ( MS ) - these kids have a low level of MS activity, which impairs

DNA Methylation and Cellular Signalling.

They are therefore unable to make adequate amounts of

Glutathione within their cells.

Glutathione, Vitamin C and Vitamin E are the three ‘weapons’ our cells have to combat ( neutralise and remove ) cellular toxins, such as heavy metals - Mercury, Aluminum, Arsenic, Lead, Tin, Antimony and so on.

The major intracellular anti-oxidant is Glutathione and a deficiency places the cell in a state of potential ‘Oxidative Stress’ - but all is well, until the cell is ‘attacked’ by an oxidative challenge, such as Thimerosal or Aluminum.

Mercury passes quickly into the cell - brain cells particularly, and the cellular production team - the Mitochondria, immediately produce Glutathione which attaches itself to the molecule of Mercury. Once this happens Glutathione + Mercury are then excreted out of the cell and the complex passes to the kidneys and liver and is voided in the urine and bile.

Most children can easily deal with the Mercury ‘hit’ provided by a vaccine containing Thimerosal; however for the (estimated) 1 in 100 children ( M: F ratio of 4 : 1 )who have extremely low Methionine Synthase activity and therefore impaired capacity for Glutathione production - it is catastrophic.

Once MS capacity ( to produce methyl groups and Glutathione ) is exceeded, there is a back-up and SAH is converted to Adenosine. ADA activity is in turn swamped then Adenosine binds to SAH Hydrolase - once this happens, no more SAM can be processed, no more methyl groups can be produced and Methylation ceases. This leads to

The CDC in Atlanta have recommended a maximum daily intake of Mercury for an adult to be 1 microgram ( one millionth of a gram ). For a 10lb. Infant this equates to 0.05 micrograms.

With the routine childhood vaccinations now standing at 22 up to age 2 years there comes 237.5 micrograms of Ethylmercury; that is 12 times the ‘safe’ limit for every day of their life!

In the USA the CDC and Congress called for removal of all Mercury from vaccines in 2001. In California this was done immediately, and now three years later the official figures from the Department of Developmental Services ( DDS ) for California show for the first time in 35 years - a reduction in numbers of new cases of Autism.

[ Note: All of the above comments apply to a slightly lesser extent to all of the other ‘heavy’ metals ]

Laboratory studies can be done to determine the genetic susceptibility of an individual. The study - a Detoxigenomic Profile - can be done on a blood or saliva sample. The DNA is analysed and the genomic profile determined and this provides information on the status of the various enzyme systems in that individual and enables retrospective diagnosis of the cause of that individual’s ASD and therefore indicates the therapeutic priorities. This study is of immense pro-spective value in the determination of siblings’ susceptibility to toxic metal exposure.

Hair analysis is an important baseline investigation because hair is an excretory pathway for so-called ‘heavy’ ( or toxic ) metal elimination. Because hair grows slowly it is a more accurate representation of the metal burden than say, blood where values can change on a day-to-day basis. With one exception ( Mercury ) the higher the toxic metal level in hair the greater the whole-body burden.

The exception - Mercury - works in the opposite sense. Genetically-vulnerable children are unable to rid themselves of Mercury. They are Mercury-retainers. The Mercury has got into their cells and become (almost) irreversibly bound to elements within each cell ( the Lysosome ). Once this happens Mercury causes some cell death and disrupts a process within the cell called DNA methylation. The cell no longer gets instructions from the nucleus, instructions which tell the cell how to develop - what type of cell to develop into - and how to function. A cell content of 1 x 10- 9 ( 1 part per 100 million ) of Mercury is sufficient to disrupt DNA methylation.

DNA methylation and the effect this has on expression of genes can best be understood by the following analogy:

Think of a flute - place your fingers over some of the holes and blow - and you get one sound. Now move your fingers around and place them over other holes and blow again - a different sound will be emitted. Same flute - different notes.

DNA Methylation is like the fingers - it ‘stoppers’ genes and prevents their expression; so genes which are methylated are ‘silent’ and their characteristic is not seen. The genome for Methionine synthase has eleven ‘repeats’ - so ten of them need to be methylated (silenced) leaving the genome repeat for optimal Methionine synthase activity to be expressed. Not enough Methyl groups = impaired gene silencing and more likelihood that an imperfect genome might be expressed.

Hair analysis also provides important information on the nutrient mineral levels - of Iron, Copper, Zinc, Manganese, Magnesium and so on. Any mineral deficiencies or imbalances can be rectified by appropriate supplementation. One very common imbalance is an excess of Copper in relation to Zinc and aggressive Zinc supplementation is needed to correct this.

Well over 80% of children with ASD have some form of Dysbiosis. Dysbiosis is any overgrowth of any one, or group of bacteria or yeasts in the intestine ( usually the colon) and the significance of this is that some of these bacteria and yeasts use up essential nutrients (thereby depriving the body of these nutrients) and in return, they manufacture waste products. These waste products are almost 100% peptides (derived from dietary protein) - notably

Caso-morphin (from dairy products) and

Gluteo-morphin ( from Wheat products)

- as their names imply, these are chemically- related to the morphine-like group of chemicals called Opioids.

Opioids effectively block some neural pathways and many of these are located in an important area of the brain - the Thalamus - which in turn houses a ‘computer micro-processor - the Amygdaloid body. The Amygdaloid body is an important relay station in neural pathways from the frontal lobes of the brain - this part of the brain is concerned with personality, learning and deductive reasoning. The Amygdaloid also relays and processes signals from the occipital cortex ( concerned with vision ) and the auditory cortex ( concerned with hearing )

Malfunction of the Amygdaloid effectively stops the process of neural integration that is started at birth and only stops in senescence. The early years of neural integration is also termed ‘Neuro-Linguistic Programming’ (NLP). NLP is pretty much the same as hard-wiring a computer. By making neural connections, we allow different parts of the brain to communicate more effectively with each other and eventually this becomes integrated to the extent that an individual can be said to be ’learning from experience’ and ’using their judgement’ - just as a computer can become self-aware.

From the moment of birth, everything we see, hear, feel or are told - adds to the database which is ’knowledge’. Imagine then what confusion is caused when this process mal-functions.

Everyday sights and sounds become confusing, facial expressions convey no meaning (one possible reason why ASD children don’t look at peoples’ faces) and every time a child with ASD encounters a situation in life it is as though they have never met that situation before.

Is it any wonder then that speech is absent or delayed, eye contact is seldom made and these kids clap their hands over their ears and shut their eyes tight - it’s a confusing world when you’re on the Autistic Spectrum.

We live between two worlds - the world outside and the world within; and so we have two main ‘arms’ to our immune system. One polices the external environment looking out for aggressors in the form of bacteria, viruses, pollen and so on trying to get in; while the other polices the internal environment looking for rogue cells, bacteria, viruses and so on that have managed to get past the Th1 system

The External arm is termed Th1 ( Th = ‘T’ helper cells)

The Internal arm is termed the Th2 system.

Normally, the T1 system is the more active; however after the ’big bang’ - Mercury toxicity - the Th1 system (which is PLM and therefore MS-dependent) is shut down and the Th2 system predominates - a real increase in activity over the baseline.

For this reason, children with impaired MS activity - exposed to toxic doses of heavy metals - have increased susceptibility to infection and increased incidence of Auto-immune disease.

Some viruses ( example - measles in MMR ) have another trick ‘up their sleeve’ termed ‘antigen mimicry’ - their antigenic ‘signature’ can be altered to resemble that of the host cell - perfect camouflage - not quite - we make antibodies anyway but these don’t just target the virus, they hit the host cell as well - like shooting a crow sitting on a fence with a shotgun - you get the crow and take out the fence ! When this happens in the gut, it causes immense damage to the lining, and in the brain leads to demyelisation and nerve cell death. Raised levels of anti-MBP antibodies are found in over 80% of children with ASD and this indicates an auto-immune response against cerebral neurons.

In the GI system antibodies have been found in lymph follicles - Ileal Lymph Node Hyperplasic (ILNH) - this was the work of Dr Andrew Wakefield at the Royal Free Hospital, London.

Since 1975 there has been a 700% increase in the number of vaccinations required by a child up to the age of 2 years, a 700% increase in the incidence of ASD and a 700% increase in the incidence and prevalence of Auto-immune disease. Coincidence? [ figures from the Autism Research Institute ]

The ‘Big bang’ - the heavy metal ‘hit’ - especially where Mercury is concerned; initiates a cascade of events within the intestinal mucosal cells resulting in

Cell degeneration ( through apoptosis )

Loss of villi ( and therefore absorptive surface )

Increased gut permeability ( leaky gut syndrome ) and

Formation of auto-antibodies ( to mucosal cells )

In addition, Glutathione is ‘delivered’ to the intestine via bile - and bile production is almost universally defective in children with ASD.

It is also thought that the resultant inflammation from the antibody attack damages the bicarbonate-producing cells which are Secretin-responsive. This Secretin resistance lowers the pH ( more acidic ) which causes further inflammation and favours the growth of undesirable bacteria and yeasts.

The undesirable bacteria are almost any An - aerobic bacteria but particularly

Clostridia and

Aerobic Gram negative bacilli ( AGNB) such as

Enterococcus, and

Klebsiella, and others

Undesirable yeasts are usually

We have over a kilogram of bugs in our intestines !

… and as we have seen these organisms generously supply the body with toxic waste in the form of Peptides ( Gluteo- and Caso- morphin )

As I have already said, one of the effects of Mercury is to shift immunity from Th1 to Th2 - and increase auto-immunity. The additional problem of reduced availability of Glutathione ( and therefore anti-oxidant capacity ) worsens the effect of all of the above and exacerbates the cellular degeneration.

Against this background multiple food intolerances develop and incomplete digestion of various food groups adds fuel to the flames in the form of incompletely-digested proteins which act as ‘fertiliser’ for further abnormal bacterial and yeast growth.

We use a ‘weed, feed and seed’ approach using a tailored regime for each child, depending on the stool report.

Certain minerals act as ‘fertiliser’ to promote the growth of beneficial bacteria in the colon and Pro-biotics are used to ‘seed’ the intestine with ‘good’ bacteria, such as Bifidobacterium and Lactobacillus

Almost 100% of children with ASD have some food-related problems. This can take the form of

True allergy eg. Peanuts - causes wheezing or hives, anaphylaxis. Skin tests.

Food Intolerance eg. Gluten, casein, soy - GI distress, behaviour. Blood test (RAST)

Peptide-uria Leaky gut - behaviour. Urine/blood tests (Chromatography)

Incomplete digestion of proteins from the diet ( gluten and/ or casein ) leads to an increase in peptides ( the -morphins ) in the blood. These cross the blood-brain barrier and switch ‘on’ the opioid receptors.

The child becomes a drug-addict, habituated to these -morphins and seeking them out at every opportunity to get a ‘fix’.

The more a child craves a particular food, the more likely he/ she is to be getting this ‘fix’ from that food.

The sooner a child can be started on a Gluten-free and/ or a Casein-free diet, the better. If they have this food intolerance - every mouthful of that food is further damaging their brain.

A GF or CF diet must be 100% gluten and/or casein - free. And some children are intolerant of Soy as well …

The best sequence is as follows:

1. Casein withdrawal - you should see improvement within 3 weeks - if so

Continue, if not - stop.

Then

2. Gluten withdrawal - this may need up to 3 months to take effect. Children may show increased stimming behaviour at first - this is a good sign ! Try to tolerate it.

Time of response may be as short as a few days in

children below 5 years of age, months in older children.

Also, the condition of the gut and presence or absence of dysbiosis may affect time needed.

As before - if improved - continue; if not - stop.

Then

3. Allergy elimination - allergy screen ( blood test ) or trial and error

Then

Digestive enzymes

Yeast - free diet

Grain - free diet

And finally

Specific Carbohydrate Diet ( SCD )

The SCD involves allowing only mono - saccharides ( short chain sugars) such as honey and fruit sugars. This ‘starves’ out harmful bacteria and yeasts and is best accompanied by Pro-biotics.

Changes within the cells of the small intestine render the environment within the bowel hostile to many ( favourable ) bacteria and favour the growth of other ( toxin-producing ) bacteria.

Secretin returns the gut pH to more normal levels which in turn gives the anaerobic bacteria their notice to quit. As they go, peptide levels begin to fall and the blood and ultimately brain peptide levels reduce.

In addition, Secretin has a direct effect on the Thalamus in the brain, and on the Amygdaloid body in particular. Secretin increases the number of available Retinoid receptors - in effect it creates alternative neural connections - by-passing the damaged and/ or non-functioning pathways in these areas.

The net overall effect of Secretin administration is to produce a fairly rapid improvement in stool consistency and frequency through the direct effect on the bowel; and a global improvement in all symptom categories

Eye contact

Overall awareness

Comprehension

Compliance

Sleep

Concentration

Vocalisation

- and a lowering of elevated pain threshold ( through a decrease in -morphin levels )

Why Vitamin A ? ( Retinol )

Vitamin A is a fat-soluble vitamin (as is Vitamin E ) and since fat cannot be absorbed directly through the intestinal cells it has to be ‘emulsified’ - mixed with bile in order to be rendered soluble.

As already said the production of bile in children with ASD is reduced and the normal response of fat in the intestine triggering bile secretion is impaired - therefore children with ASD cannot absorb fat or fat-soluble Vitamins.

Almost all children with ASD are Vitamin A deficient. Vitamin A is needed by the central part of the retina in the eye ( used for discriminatory vision ) and also by Retinoid receptors in brain cells. Insufficient Vitamin A therefore impairs nerve transmission in certain parts of the brain, notably the Hippocampus, Thalamus and Amygdala.( sound familiar?)

We recommend Vitasorb A which is ‘micellised’. Micellisation is a process which renders fat-soluble substances water-soluble.

[ Dr Mary Megson. Baltimore ]

Why Vitamin B ?

All of the B-vitamin group are water soluble. The problem here is that because of inflammation in the small intestine there is reduced absorption of the B-vitamin group. Additionally, many children with ASD have an extremely restricted diet that is often deficient in B vitamins.

Vitamin B6 is utilised in many enzyme systems (see MT flow chart) as is Vitamin B12 as well as smaller amounts of B 1 & 3.

A recent study ( Dr Hardy, DAN! group study) of 50 children on the Autistic spectrum showed that 100 % were deficient in some or all forms of EFA. The majority were deficient in both Omega-3 and Omega-6

This is highly-significant because EFA - especially Omega - 3 fatty acids such as EPA, DHA and ALA are needed for cell ( and especially neuron ) structure and function. The functions of EFA’s are:

Building blocks of all cell membranes

Nerve transmission

Cell multiplication

Transportation of oxygen

In the immune response, among others.

The Eskimo diet contains 19 grams of EFA per day [Omega 3 & 6]

Our diet contains 1 gram per day !

… and this can be much lower in children with ASD who are ‘fussy’ eaters on a limited diet.

EFA is derived from the diet - we must ‘eat’ it - we cannot make it in our bodies - and the natural sources of EFA are

Fish

Olive oil

Cod liver oil - Cod liver oil supplements were routinely given to children post- WW II and discontinued in the early 60’s - maybe a factor?

Children need EFA in a ratio of Omega-3 to -6 of 4 : 1 and supplements with this ratio are Kirkman’s EFA, Coromega, Omega-Brite and Eskimo 3.

Severe EFA deficiency can mimic Bi-polar Disorder (Manic-Depressive illness) and can lead to:

Rapid cycling mood swings Restlessness

Sleep disturbance Silliness

Giddiness / ataxia Racing thoughts

Rages & explosive temper tantrums Aggressive behaviour

Marked irritability Self-injurious behaviour

Oppositional behaviour Carbohydrate craving/bingeing

Distractibility Risk-taking behaviour

Hyperactivity Tics & OCD

Impulsivity Hypersexuality

Dry, scaly skin Dry hair

Easily broken fingernails Bedwetting/ increased urine

Asthma, Hay fever, eczema, hives Nasal stuffiness/ runny

- does any of this sound familiar … ?

Replacement therapy for a child would be 5 to 10 grams daily, up to 20 grams for an adult.

There are many forms of chelation therapy, many agents used and many different methods of delivery. All have advantages and disadvantages and some are more specific for the toxins encountered in children with ASD.

Chelation refers to the ‘leaching out’ of a substance, usually metals from within living cells.

There is no ‘perfect’ chelating agent but in the context of ASD we are concerned with the removal of ‘toxic’ or so-called ‘heavy’ metals. These are

Arsenic Aluminum

Antimony Barium

Bismuth Cadmium

Lead Mercury

Nickel Thallium

Tin Uranium

I am often asked where these metals have come from, since they can be present in high concentration. It is not that these children have necessarily been exposed to higher amounts of these metals, it is more a case that whatever amounts they are exposed to gets into their cells and can’t get out - a one-way street.

The reason why Mercury levels in hair are inversely proportional to the total body burden is that Mercury is taken up preferentially into brain, liver and kidney cells - and can’t get back out, so there’s none left over to appear in hair.

Chelation - Removal of Toxic Metals

Metallothionein Promotion

All of the preceding investigations and therapies are in preparation for the important step of trying to re-start cellular (and in particular DNA and Phospholipid membrane ) methylation.

It was methylation that was interrupted by the advent of the toxic metal(s) and once chelation has removed all traces of these, then provided that the cells have the necessary ‘raw’ materials ( B6, B12, TMG, folinic acid and certain amino acids such as Glycine and Cysteine) then methylation should automatically ‘fire up’.

Metallothionein promotion begins with mineral and vitamin supplementation, continues with chelation and finally needs specific mineral and vitamin ’Primers’ and amino acid ‘Promoters’.

The Pfeiffer Institute have a two-stage ‘Primer’ and ‘Promotion’ protocol which includes supplements of

-transferases and -synthases)

‘Primer’ may need to be given for 3 to 6 months before

Promoter Glutathione Proline

Serine Asparagine

Lysine Glutamic acid

Alanine Methionine

Glycine Glutamine

Threonine Isoleucine

Valine - all essential amino acids or likely to be severely deficient because of poor absorption or restricted diet. All are either used directly (essential) or synthesised within cells to make biologically active compounds ( the non-essential amino acids) that are necessary for the Methionine cycle.

In addition Selenium, Copper and Zinc levels may need adjustment for efficient Metallothionein protein synthesis.

Once ALL of the above has been worked through - then and only then is it worth the time, effort and money involved in providing any form of ‘special’ learning or speech therapy, such as ABA or Son-rise therapy. Unless these deficiencies and imbalances are corrected first a child will derive little benefit from therapies designed to ‘shower’ the brain with input. Any benefit will be hard-won and easily-lost.

Finally …

There are a number of new therapies being introduced …

One is 5 - hydroxytryptophan ( 5HTP) 50 milligrams daily. Tryptophan is an essential amino acid, which most ASD kids are deficient in because of poor diet and mal-absorption. Tryptophan is converted into 5-hydroxytryptamine - 5 HT- or Serotonin - a nerve transmitter. A lack of Serotonin can cause constipation and seriously diminish nerve-to-nerve transmission. Serotonin is converted into Melatonin.

Tryptophan can also be converted into Indolyl - Acrolyl glycol ( IAG - a peptide) which is found in excess in the urine of ASD children. It is thought that they are unable to metabolise Tryptophan to 5-HT, and instead convert Tryptophan to IAG.

Another ’new’ therapy is high-dose Vitamin A.

Vitamin A is a naturally-occurring anti-viral agent. Most ASD kids are deficient in Vitamin A. Many ASD kids have been found to have active measles virus present in the CSF - antigenically identical to the measles component of MMR - and some of these children respond to anti-viral agents (Acyclovir, Famcyclovir)

Doses of 400,000 IU on two consecutive days have been evaluated. This can sometimes produce a rapid and sustained global improvement Research is continuing ..

… and Finally, Finally …

There is continuing research into the cellular biochemistry of ASD and into the immunological and chemical processes that are disrupted by the heavy-metal insult suffered by the majority of these children.

It is hoped that this research will lead to improved therapies and better outcomes for all of them.

What started as a trickle in the early 1930’s and developed into a flood in the 1990’s is beginning to wane. California ( whose State Government insisted on immediate implementation of mercury-free vaccines in 2001) has just reported the first fall in the incidence of ASD in 35 years ! …