Comments on Natural Variation - Autism Blog: Effectiveness of Chelation Therapy

for regular (and supportive) reports on chelation ...

2006-06-17T03:34:00.000-07:00

for regular (and supportive) reports on chelation check the www.acresusa.com issues from the nineties (a voice for eco-agriculture).

Now that I am passing out tips, may as mention a maverick sociologist of autism: Andrew Lehman, reviewed here:
http://29marbles.blogspot.com/2005/09/natural-selection-and-prevalence-of.html review of serpentfd.org

Re Dateline and hype, I came across a precedent:"I...

2006-06-07T07:35:00.000-07:00

Re Dateline and hype, I came across a precedent:

"In 1998, a case series (1) and television program (NBC Dateline) described children whose symptoms of autism improved remarkably after secretin infusion for a gastrointestinal procedure. These and other testimonials sparked a huge demand for off-label secretin use."

I happened to come across an article by Wing where...

2006-06-06T11:55:00.000-07:00

I happened to come across an article by Wing where she discusses the early prevalence study Mike commented on:

"One of us (LW) was involved in the planning of the study by Vic Lotter of 78,000 children aged 8, 9, and 10 years living in the former English county of Middlesex. This was the study in which the 4-5 in 10,000 prevalence rate was first found. I (LW) know what sorts of children were included as classically autistic because I was one of the small group (Neil O'Connor, John Wing, Vic Lotter and myself) who decided on the criteria. In those days we were interested only in really classic Kanner's syndrome and Vic was determined to keep the criteria as narrow as possible. Later, in the Camberwell study described above, Vic was shown case histories of the children Judy Gould and I thought fitted Kanner's descriptions - to our surprise, Vic said we ought to exclude some because they were not classic enough! I think it is fair to say that, when Vic specified narrow criteria, they were NARROW.

When Judy Gould and I started the Camberwell study, we still thought that Kanner's autism could easily be differentiated from other developmental disorders.. By the end of the study our ideas had been turned upside down. We had learnt from direct experience that the psychological dysfunctions underlying autism were manifested in many different ways, far beyond the boundaries of Kanner's syndrome. We developed the hypothesis of an autistic spectrum based on the triad of impairments of social interaction, communication and imagination. Because we concentrated on the children with learning disabilities (IQ under 70) we saw very few with the pattern described by Asperger. We had to wait for the study by Christopher Gillberg in Gothenberg to find out how many children with IQ of 70 and above were also in the autistic spectrum. As described above, combining the results of these two studies gave an overall prevalence rate for the whole autistic spectrum, including those with the most subtle manifestations, of 91 per 10,000 - nearly 1% of the general population."

There you have it: 91 in 10,000 for the whole autism spectrum. As I've said before, I think it's about 150 in 10,000 if you count those who might escape a diagnosis for various reasons, such as being too high functioning.

María,I think some line breaks got in your URLs. S...

2006-06-06T10:03:00.000-07:00

María,

I think some line breaks got in your URLs. Sorry for not answering right now. It's a lot of information.

Hi JosephAlthough the links were shown when I incl...

2006-06-06T09:51:00.000-07:00

Hi Joseph
Although the links were shown when I included them, in the page the links do not work. Sorry
María Luján

Sure María. You have my address. (Blogger should a...

2006-06-06T09:48:00.001-07:00

Sure María. You have my address. (Blogger should allow b, i and a tags).

Hi JosephI think you pointed out to the discussion...

2006-06-06T09:48:00.000-07:00

Hi Joseph

I think you pointed out to the discussion several key points, when you answer to me my prompt

I think that the first step to clarify the issue is to find a trustable and complete way to detect/discard HM poisoning in autistic people.

Is it different with autistic people?

I think we must go back to this point, before to go to the discussion of the tests, and less to the discussion of the chelation treatment, that IMHO, must be based on appropiate tests.

Therefore the questions are

1-Are autistic people different as population in terms of HM susceptibility to poisoning, based on genetics-epigenetics-proteomics-metabolomics? Are there any evidence of bioaccumulation of HM in autistic people?

2-What are the appropiate tests to detect HM poisoning in this subgroup of autistic people?

I will begin with the first because I think that the second is related to the first. If the autistic people are different in the management of xenobiotics, tests must be different and “common tests” are not trustable or give no information. If bioaccumulation in tissues is possible-because of lack of excretion-, no common tests in blood, urine, fecal or hair would provide evidence at least at the best of the published literature in the topic, after the initial exposure.

First, no complete study on the issue of HM genetic susceptibility/predisposition to bioaccumulation because of metabolic disruption in metal transport/excretion in autistics is available today (even when some metabolic studies on some biomarkers-such as glutathione and the pathway of gluthathione transferase and other enzymes are available-but are partial). Therefore I consider these studies on genetic susceptibility in the general population and autistic people almost not done yet. If we think in ASD as a genetic predisposition distributed in the general population and see the interaction with the environment as important, the importance of some key polymorphisms in the HM management can give clues to look at in ASD people.
To give some insight to this question 1- that I consider is far from being solved from the published available science, I will present some studies about some polymorphisms in general population that have been detected that would be important to study in ASD vs controls to evaluate importance-beyond the ApoE that has been published with contradictory results.

Transport of toxic metals by molecular mimicry points the importance of transport of toxic metals

Transporters of divalent cations

-DCT1 (divalent cation transporter-1; also known as NRAMP2 or DMT1) is considered to be a major cellular uptake mechanism for Fe(2+) and other essential divalent metals, but this protein also mediates uptake of Cd(2+), Pb(2+), and possibly of other toxic divalent metals (Hg+2 ??)

-the apically located MRP2 (multidrug resistance-associated protein 2) transporter, a member of the adenosine triphosphate-binding cassette protein superfamily.

Personally it intrigues to me the nature of the heavy metals considered as insults in autism:
-Hg, Pb, Cd ( all of them with the possibility of +2 oxidation state in inorganic form)
-Al , that presents the +3 oxidation state

Adverse reactions after injection of adsorbed diphtheria-pertussis-tetanus (DPT) vaccine are not due only to pertussis organisms or pertussis components in the vaccine

Nielsen AO, et al. [Aluminum allergy caused by DTP vaccine]. Ugeskr Laeger. 1992 Jun 29;154(27):1900-1. Danish.

-As, that also has available the +3 oxidation state and others. Arsenite (As+3) compounds are lipid soluble. Within 24 hours of absorption, arsenic distributes over the body, where it bind to the SH groups of tissue proteins. As can replace phosphorus in bones (from Textbook of modernToxicology Hogdson)

“We know that the toxicity of arsenic is dependent on its oxidation state, chemical form and solubility in the biological media and that the scale of toxicity decreases in the order: arsine > inorganic As(III) > organic As(III) > inorganic As(V) > organic As(V) > arsonium compounds and elemental arsenic. We also know that the toxicity of As(III) is about ten times that of AS(V) “

-Ni, Cu (both of them have +2 as oxidation state available)

Main elements in the body are present as +2 (Mg, Ca and Zn). Molecular mimicry is worrisome in these circunstances, as a possibility, with the potential of disruption of Ca channels and Zn ”fingers”,beyond a lot of enzymes and metabolic paths involving Mg.

Transport of toxic metals by molecular mimicry points the importance of transport of toxic metals

Heavy metals can have impact in the regulation of genes

Transcriptional regulation of the NAD(P)H:quinone oxidoreductase 1 and glutathione S-transferase ya genes by mercury, lead, and copper.

Transporters can be cationic or anionic

Research on Metal transport

Identification of polymorphisms in the promoter region of the human NRF2 gene..

Polymorphisms in xenobiotic metabolism genes and autism.

“We performed family-based association studies of polymorphisms in metal-regulatory transcription factor 1(MTF1), a multispecific organic anion transporter (ABCC1), proton-coupled divalent metal ion transporters (SLC11A3 and SLC11A2), paraoxonase 1 (PON1), and glutathione S-transferase (GSTP1) genes in 196 autistic disorder families. There was deviation from the expected pattern of transmission for polymorphisms in MTF1 (Single nucleotide polymorphism database reference identification number, dbSNP rs3790625, P = .02) and divalent metal ion transporter SLC11A3 (dbSNP rs2304704, P = .07) genes. Although these results might represent chance finding, further investigations of genetic variations of metal metabolism in autism are warranted.”

The possibility of chance finding must be analyzed with care

Chronic low-level mercury exposure, BDNF polymorphism, and associations with cognitive and motor function..

Chronic low-level mercury exposure, BDNF polymorphism, and associations self-reported symptoms and mood..

Mutation screen of the brain derived neurotrophic factor gene (BDNF): identification of several genetic variants and association studies in patients with obesity, eating disorders, and attention-deficit/hyperactivity disorder..

DMT1: which metals does it transport?

Phenotypic variation in xenobiotic metabolism and adverse environmental response: focus on sulfur-dependent detoxification pathways.

The association between a genetic polymorphism of coproporphyrinogen oxidase, dental mercury exposure and neurobehavioral response in humans.

A cascade analysis of the interaction of mercury and coproporphyrinogen oxidase (CPOX) polymorphism on the heme biosynthetic pathway and porphyrin production.

Therefore it seems that GMST1, BDNF, CPOX, SLC11A3 and SLC11A2, (ABCC1), (PON1), 1(MTF1) DCT1 would be important to study, considering the anecdotic evidence for science of HM poisoning in autism ( including Hg). Basically, focusing in the xenobiotics metabolism and divalent metal transport, including the aminoacid transport system, I think that some further clues would be provided if a coherent, highly scientific and prudent approach is done. Selective inhibition of BLM carriers implicated the involvement of organic anion transporter(s) (Oat1 and/or Oat3; Slc22a6 and Slc22a8), amino acid transporter system ASC (Slc7a10), the dibasic amino acid transporter (Slc3a1), and the sodium-dicarboxylate carrier (SDCT2 or NADC3; Slc13a3). After this knowledge about the how the bioaccumulation can / is taking place (if any) in a subgroup of ASD children, THEREFORE the best tests to detect can be planned and diagnostic/test research can be designed to confirm HM poisoning.
For example

Analysis of case-parent trios at a locus with a deletion allele: association of GSTM1 with autism

High levels of homocysteine and low serum paraoxonase 1 arylesterase activity in children with autism

Mercuric conjugates of cysteine are transported by the amino acid transporter system b(0,+): implications of molecular mimicry.

Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism.

Plasma amino acids profiles in children with autism: potential risk of nutritional deficiencies. .

Plasma amino acid levels in children with autism and their families. .

Imbalance of plasma amino acids in patients with autism and subjects with attention deficit/hyperactivity disorder .

Low serum tryptophan to large neutral amino acids ratio in idiopathic infantile autism. .

Serotonin and amino acid content in platelets of autistic children.

If we consider that in some group of autistic people it has been published that
1- there are problems with proteins metabolism/aminoacids, with some published evidence of defficiency in essential and non-essential aminoacids
2- there are problems with the enzymes ( concentration and activities), cofactors and regulations of the xenobiotics management from glutathione conjugates , cytochromes , phase I and Phase II of the liver and the excretion as mercapturic acid conjugates (as I posted before) – GSH, GSMT (recently published a positive correlation with ASD, etc)
I think that we need lot more research than current on these issues in ASD.

Some thoughts and questions

1-If aminoacids transporter system is involved, diet/nutrition/biochemistry can be important in the management of HM-and Al- (in terms of digestion/proteins/peptides/aminoacids), especially if GI issues are involved
2-Adequate test of metabolites or biomarkers of disrupted detox system of xenobiotics would allow a better understanding of the issue.
3-Adequate levels of aminoacids could be important in this role (methionine levels).
How would exclusion diet affect the protein/polypeptides/aminaocids balances. IF digestive enzymes are disrupted, what about gluten and casein exclusion and effect in aminoacids balance in the body-without the supposed disruption of peptides as interfirients, if adequate testing for leaky gut is present?
And how these diets (such as GFCF diet) would affect the HM transport in the body (levels of HM in blood, urine, fecal stool) in ASD during diet related to food allergies- celiac disease and milk allergy for example- that are related to protein/polypeptides management and immune answers to them if ALSO leaky gut is present?

Again, with this picture I can not say that the management of xenobiotics is similar in autistics than in non autistics because there are no complete published studies about, but there are a lot of clues that are pointing that the answer is no. How, when and why is another history. The lack of published research in these fields is almost total today.

Finally, in this point, I have more questions than answers (and a lot of anecdotic information for science that has not been adequately analyzed and systematically organized and considered). I think that asking for further research in the issue is the right thing to do, considering the medical research for population of ASD. Meanwhile, many of us must deal with the lack of consideration –only anecdotes- and knowledge about our personal and individual experiences and do the best we can.

BTW, thank you for the link to the hyper link. It was a problem of reordering of the URLs to make them fit correctly in the sentence.
Sincerely

María Luján

Hi JosephI tried to post with hyperlinks but the w...

2006-06-06T08:51:00.000-07:00

Hi Joseph
I tried to post with hyperlinks but the web says that tag is not allowed. Can I e-mail to you?
Sincerely
Ma Luján

Absolutely. Thanks.

2006-06-05T17:48:00.000-07:00

Absolutely. Thanks.

I have Wing's study as a word doc if you want it.

2006-06-05T16:29:00.000-07:00

I have Wing's study as a word doc if you want it.

Thanks for that info, Mike.I think someone should ...

2006-06-05T15:10:00.000-07:00

Thanks for that info, Mike.

I think someone should do a prevalence study on autism using Kanner's criteria; you know, just to settle the issue.

Regarding Prevalence the earliest study cited by W...

2006-06-05T13:48:00.000-07:00

Regarding Prevalence the earliest study cited by Wing is Lotter, V. (1966). Epidemiology of autistic conditions in young children: I. Prevalence. Social Psychiatry, 1, 124-137 which gave a finding of 4.5:10000. This was for Kanner's autism using these two defining criteria
1. a profound lack of affective contact
2. repetitive, ritualistic behaviour, which must be of an elaborate kind.

The transcript of the segment is here.At one point...

2006-06-05T10:29:00.000-07:00

The transcript of the segment is here.

At one point Jim Adams is quoted as saying:

"There have been a number of epidemiology studies looking at [thimerosal], Some showing absolutely no link, some showing a very strong link."

At first I thought, which studies show a very strong link? But then I remembered Geier & Geier. I'm sure that's what he's talking about. Are there any others? In other words, studies that claim VAERS can be used as an indication of the prevalence of autism; studies where it's claimed that incidence can be calculated by substracting administrative caseload one quarter minus that of the previous quarter; and studies that use prevalence by birth year cohort as fixed numbers.

Jim Adams apparently likes to compare oranges with rotten apples.

I missed Dateline, so I appreciate your comments. ...

2006-06-05T08:18:00.000-07:00

I missed Dateline, so I appreciate your comments. I missed it because we went to see the latest X-Men movie.

All the time I was watching this movie about mutants with a possible cure... I could not help think about the "cure autism" discussions I have read on the Autism Hub.

I forgot to mention that Dateline goofed up their ...

2006-06-05T07:41:00.000-07:00

I forgot to mention that Dateline goofed up their prevalence numbers. I heard 1 in 100,000 in the 1980s. I'm sure they wanted to say 1 in 10,000, which is what Generation Rescue claims. The earliest data I've found is Wing (1976) which documented a prevalence of 4-5 in 10,000. Once you note that this was a prevalence of Kanner autism, and the current prevalence of 60 in 10,000 refers to ASD (DSM-IV autistic disorder, PDD-NOS and Asperger's syndrome) the increase claim is not so impressive anymore.

Fore Sam:You forgot to include "Amalgam Illness" b...

2006-06-05T06:10:00.000-07:00

Fore Sam:

You forgot to include "Amalgam Illness" by Andrew Hall Cutler in your suggested reading.

I only listed studies that have a placebo-controlled group. I did post a study on alleged mercury poisoning due to dental amalgams. You're welcome to post a link.

Hi María,I think that the first step to clarify th...

2006-06-05T06:09:00.000-07:00

Hi María,

I think that the first step to clarify the issue is to find a trustable and complete way to detect/discard HM poisoning in autistic people.

Is it different with autistic people?

If you are interested I can post some studies about detection- by the combination of different tests- HM poisoning following available literature (excluding challenge tests).

Go ahead. (I prefer if they are hyperlinks as opposed to URLs).

Hi Kristina,Chelation seems to be a treatment used...

2006-06-05T06:01:00.000-07:00

Hi Kristina,

Chelation seems to be a treatment used for so many different ailments that I wonder at its specific efficacy for certain "symptoms" of autism.

I doubt even that will be the case. It's possible some things used as chelating agents, like ALA, might be helpful for reasons other than chelation of heavy metals. But this study is using DMSA (Succimer).

I was thinking that because developmentally delayed kids tend to have Pica, a positive correlation might be found. But the Succimer studies on lead exposed children have not yielded results.

Joe; You forgot to include "Amalgam Illness" by ...

2006-06-05T02:40:00.000-07:00

Joe;
You forgot to include "Amalgam Illness" by Andrew Hall Cutler in your suggested reading. If you want to seem credible, you should include protocols that actually work.

Hi JosephI think that the first step to clarify th...

2006-06-04T18:47:00.000-07:00

Hi Joseph
I think that the first step to clarify the issue is to find a trustable and complete way to detect/discard HM poisoning in autistic people.
If you are interested I can post some studies about detection- by the combination of different tests- HM poisoning following available literature (excluding challenge tests). I think that in this field the research and the current knowledge is incomplete.Please let me know.
María Luján

Thanks for gathering all this together. Chelation ...

2006-06-04T18:26:00.000-07:00

Thanks for gathering all this together. Chelation seems to be a treatment used for so many different ailments that I wonder at its specific efficacy for certain "symptoms" of autism.