Mitochondria, autism and thimerosal

18 Apr

The whole mitochondria/autism thing is pretty fascinating. A Dr Shoffner presented the results of a study he conducted (‘Mitochondrial Dysfunction May Play a Role in Autism Spectrum Disorders Etiology‘ – its free registration at Medscape to read the whole thing) in which he noted:

a retrospective analysis of 41 children with ASD who were being evaluated for suspected mitochondrial disease showed that 32 (78%) had defects in skeletal muscle oxidative phosphorylation (OXPHOS) enzyme function and 29 of 39 (74%) harbored abnormalities in the OXPHOS proteins.

The numbers kind of leap out at you don’t they?

Except, we need to remember that this is a heavily skewed population. As SL has pointed out:

I can’t state it enough: this is NOT a random sample of autistic individuals. These are children who were already suspected of having a mitochondrial disorder.

Which is a bit like looking for wet kids at a swimming pool. It doesn’t really tell us anything about autism aetiology. It tells us that some kids who are autistic also have mitochondrial dysfunction. Reading anything concrete into that is just like reading anything concrete into the fact that autism symptoms become clear around the time vaccines are administered – correlation does not equal causation after all.

Dr Shoffner is unavailable right now but I have dropped an email off with him asking if he would be kind enough to make his presentation available. We’ll see.

In the meantime it should be noted that there are other highly respected mitochondrial researchers who are not pleased with the way that Dr’s Poling and Shoffner have conducted themselves. A researcher I am talking with commented:

….more harm than good has been done this time by Shoffner’s and Poling’s whipping up controversy but not providing the hard data that everyone needs….. Therefore, again, I ask that you serve the public good by not trying to ferret out partial data and incomplete statements from me or others, trust that nothing is being hidden by anyone, and wait for the full story to appear in a medical journal……offer assurance to your readers that the true story will be told and that misstatements of the legions of the uninformed and conspiracy mongers who are pursuing their own selfish aims will ultimately be revealed.

Strong words from someone who clearly feels that Shoffner and Poling are doing what they’re doing solely to be controversial.

So that seems to be the state of research regarding a mitochondrial aetiology for autism. Patchy and sensationalist with a clear agenda to serve personal interests.

However, as we all know, there are a group of people who want to take the autism/mito thing one step further and blame vaccines for triggering an occluded mitochondrial dysfunction which in turn causes autism. Its like a minor league domino effect with only three domino’s. Again, it reminds me very much of the early days of the thiomersal/MMR hypotheses – look for a direct cause and when one can’t be found, look for an indirect one and twist, twist, twist until you can argue for one.

Our old friend Ginger Taylor has, for example, been hopping from online newspaper to online newspaper saying in their comments section that:

The debate is over. Our highest health authorities have stated that vaccines are a cause of autism.

When in fact no such statement exists. Ginger is arguing that ‘features of autism’ is the same as a diagnosis of autism. Back in the real world of autism diagnostics, that is not the case.

So – what can we do to examine the hypothesis that thimerosal triggers mitochondrial dysfunction which in turn triggers autism? We could search for papers that mention thimerosal and mitochondria. When we do we get:

1: Yel L, Brown LE, Su K, Gollapudi S, Gupta S.
Thimerosal induces neuronal cell apoptosis by causing cytochrome c and apoptosis-inducing factor release from mitochondria.
Int J Mol Med. 2005 Dec;16(6):971-7.
PMID: 16273274 [PubMed - indexed for MEDLINE]

2: Humphrey ML, Cole MP, Pendergrass JC, Kiningham KK.
Mitochondrial mediated thimerosal-induced apoptosis in a human neuroblastoma cell line (SK-N-SH).
Neurotoxicology. 2005 Jun;26(3):407-16.
PMID: 15869795 [PubMed - indexed for MEDLINE]

3: Makani S, Gollapudi S, Yel L, Chiplunkar S, Gupta S.
Biochemical and molecular basis of thimerosal-induced apoptosis in T cells: a major role of mitochondrial pathway.
Genes Immun. 2002 Aug;3(5):270-8.
PMID: 12140745 [PubMed - indexed for MEDLINE]

4: Collin HB, Carroll N.
In vivo effects of thimerosal on the rabbit corneal endothelium: an ultrastructural study.
Am J Optom Physiol Opt. 1987 Feb;64(2):123-30.
PMID: 3826286 [PubMed - indexed for MEDLINE]

5: Collin HB.
Ultrastructural changes to corneal stromal cells due to ophthalmic preservatives.
Acta Ophthalmol (Copenh). 1986 Feb;64(1):72-8.
PMID: 3083641 [PubMed - indexed for MEDLINE]

6: Van Horn DL, Edelhauser HF, Prodanovich G, Eiferman R, Pederson HF.
Effect of the ophthalmic preservative thimerosal on rabbit and human corneal endothelium.
Invest Ophthalmol Vis Sci. 1977 Apr;16(4):273-80.

Of these, studies 4, 5 and 6 are not relevant – they’re talking about eyes. Its studies 1, 2 and 3 on this list that are articulatory relevant to us in our search for papers touching on vaccines>mito>autism. If anyone else finds any, please let me know in the comments section.

Now, these three studies are not supportive of the vaccines>mito connection. Why? They use frankly massive concentrations of thiomersal, way beyond whats contained in a vaccine. A quote from a scientist about these studies:

all of the studies used “non-physiological” concentrations of thimerosal – concentrations that would not be reached even by giving three or four (or even ten or twenty) high-thimerosal-containing vaccines to a low-weight and/or premature infant.

You can kill mitochondria with glutamate (an amino acid found in chicken soup, among other things), salt, oxygen, and a number of other things, if you use ENOUGH of it. The studies are not relevant…..because the concentrations used are so high – by a factor of at least 100.

So we seem to be back to square one. Whilst the evidence for a mitochondrial aetiology for autism is of mixed provenance and yet seems probable at some level, the evidence for thiomersal and autism-related mitochondrial dysfunction is not good.

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25 Responses to “Mitochondria, autism and thimerosal”

  1. Joseph April 18, 2008 at 12:37 #

    Some people are going around saying that the Poling case has something to do with thimerosal. I fail to see how it is that they reach that conclusion. Is there any reason whatsoever to suspect that is the case? Has HHS said that thimerosal played a role?

    I do look forward to hearing the whole story from the researcher who appears to be suggesting that Poling and Shoffner ripped him off.

  2. Joseph April 18, 2008 at 16:04 #

    Did you know that Ginger’s autistic son did not get a thimerosal-containing vaccine? The things you find sometimes are quite interesting.

    In March of 2002 my son Chandler, who was born one month early, is injected with Hepatitis B vaccine containing a “trace amount” of thimerosal, despite the fact that he has no risk factors for Hepatitis B, and he is still two weeks from reaching his due date. Within days he develops fevers and uncontrollable crying that lasts for three months and bowel problems that persist for two years until he is placed on the GFCF diet. He will go on to be diagnosed with both Autism and mercury poisoning at age 2. I later discover that the “trace amount” of thimerosal is still just over the EPA limit of mercury for his weight.” (source)

    Of course, the story doesn’t match the description she gave recently, nor is it mentioned in the original story of how her son ended up being diagnosed.

    “Trace amount” is what vaccines had after thimerosal was removed. It’s generally understood to be less than 1 microgram, and the EPA limit bit has been debunked countless times before. Just from breathing and eating, a child might get 5 times that amount of mercury into their system every day.

    Ginger’s non-autistic son did get a thimerosal-containing vaccine, but he was 2 months premature. So what do we know about Ginger so far?

    – Husband is autistic.

    – Autistic son was 1 month premature.

    – Non-autistic son has ASD characteristics and was 2 months premature.

    – She has changed her story and altered her own old posts in order to introduce the idea that there was a relationship between vaccines and her kid’s autism.

    Clearly, we’re talking about familial autism when it comes to Ginger’s kids. Her heavy promotion of the idea that the “debate is over” is a sort of denial, really. I’m guessing she’s also hoping to cash in on vaccine injury litigation. But if she’s expecting that a court will rule that, well, all you need to be compensated for vaccine injury is to have a child with an ASD diagnosis, she’s obviously deluding herself. She still needs to demonstrate vaccine injury explains her kids’ issues. Her case is not even weak. It’s non-existent.

  3. Patrick April 18, 2008 at 17:40 #

    Well, if her highest health authorities are DANites and the likes of JMac I’m not surprised that ‘they’ have said a lot of things which don’t reflect what the court documents actually said.

    Certainly she cannot mean the real authorities that are supposed to be part of this ‘conspiracy’ to convert everyone in the world into an autistic person, now could she?

  4. Schwartz April 19, 2008 at 01:43 #

    Joseph,

    Not all Thimersol free vaccines have “trace” amounts of Thimersoal, so her child did not have a Thimerosal free vaccine.

    Since no one can tell us what the toxicity level of ethyl mercury is for a newborn, it’s pretty pointless to argue whether “trace” is acceptable or not.

  5. Schwartz April 19, 2008 at 01:53 #

    Joseph,

    Dr. Poling’s initial press conference should explain why people are possibly associating the Poling case with Thimerosal (I’m not stating it’s right, just explaining where people are getting this from). He does state clearly that Thimerosal had no bearing on the HHS decision.

    The second theory which Mr. Shoemaker and colleagues were preparing to present, was that the preservative Thimerosal which contains mercury directly caused mitochondrial disfunciton. There is extensive literature that Thimerosal and mercury do cause mitochondrial disfunction so this is not a… this is certainly not a leap of faith.

    And from his blog entry:

    I don’t want to dwell on mercury, as this theory is not why HHS conceded Hannah’s case (imo). Dr. DiContanzo just wrote an interesting blog about how his opinion of mercury in vaccines has changed (http://drugs.about.com/b/2008/03/08/mercury-in-vaccines-and-autism-the-burden-of-proof-may-shift.htm).

    My opinion is that mercury is a potent neurotoxin. Therefore, don’t inject it into kids! Interestingly, basic research studies have shown that Thimerosal toxicity occurs through mitochondrial pathways. Officials point to the large epidemiology studies as proof that there is no link between thimerosal and autism. However, these studies are not powered to disprove the null hypothesis when considering that the mitochondrial autistic population may be just a small percent of the case totals. Remember that while the CDC sponsored Verstraten study is hyped as a negative study, it DID find a statistically significant increase in childhood tics in those exposed to higher doses of thimerosal.

  6. Schwartz April 19, 2008 at 01:57 #

    Kev,

    I find it interesting that you quote from this Mito doctor…

    offer assurance to your readers that the true story will be told and that misstatements of the legions of the uninformed and conspiracy mongers who are pursuing their own selfish aims will ultimately be revealed.

    … and then proceed to ignore the advice and begin a discussion with the rest of us armchair science critics… Not that I think you should stop the discussion. :)

  7. Kev April 19, 2008 at 08:52 #

    I hold my hands up – you’re right. This docs advice is good and xe is justifiably angry if the rest of what xe’s told me (in confidence) is correct but xe is operating purely from a scientific standpoint. Its unrealistic to suppose we outside that circle won’t discuss it at all – all we have to do is be as non-assumptive and as accurate as we can.

  8. Kev April 19, 2008 at 09:06 #

    I posted a couple of years ago about ‘trace amounts’.

    The idea that a trace amount of anything could cause a neurological disorder seems frankly risible to me purely on common sense grounds. Its not called a trace because there’s a lot of it.

  9. Joseph April 19, 2008 at 13:50 #

    The CDC appears to refer to vaccines with trace amounts of thimerosal as “preservative-free”. For example:

    “Finally, both Novartis and GlaxoSmithKline are producing preservative-free (trace thimerosal) influenza vaccines this season… For children between the ages of 2 and 5 years of age, there are three products available that are thimerosal-free (sanofi’s Fluzone; MedImmune’s FluMist) or preservative-free (trace thimerosal- [Novartis’s Fluvirin])… Most importantly, since 1999, newly formulated thimerosal preservative-free childhood vaccines (Hepatitis B, Hib, and DTaP) have been licensed. With the newly formulated childhood vaccines, the maximum total exposure during the first six months of life will now be less than three micrograms of mercury. Based on guidelines established by the FDA, the Environmental Protection Agency (EPA) and the Agency for Toxic Substances and Disease Registry (ATSDR), no child will receive excessive mercury from childhood vaccines regardless of whether or not their flu shot contains thimerosal as a preservative.” (source).

    It’s non-rational to suppose that exposure to 3 micrograms of thimerosal over a couple years will do anything to anyone. I could go eat a tuna sandwich right now and I’ll get at least 5 times that amount in methyl-mercury.

  10. isles April 19, 2008 at 14:42 #

    Joseph, I think people are saying that because that’s what the Polings say. They think the thimerosal made Hannah’s mitochondria go wonky. Certainly HHS has made no statement to that effect.

    But then, I’m pretty sure I’ve also heard that they thought it was the varicella vaccine, which makes one wonder why they were ever in the Autism Omnibus, which only concerns DTP/DTaP, Hib, hep B, and MMR.

    I have the strong feeling that there are facts in this case which are not in evidence, so to speak.

  11. Joseph April 19, 2008 at 14:54 #

    Here’s a question. If thimerosal causes mitochondrial dysfunction, why doesn’t it cause it in every person ever injected with a thimerosal-containing vaccine? Is it purely random?

    Or is there a genetic suceptibility? Should we call that mitochondrial dysfunction dysfunction?

    A common theme in these arguments is parents trying to find causes that do not implicate their genetics in any way whatsoever. But that is clearly difficult.

  12. isles April 19, 2008 at 17:27 #

    Whoops, Joseph, that last post of mine probably sounded like a non sequitur. I’d had this post open in a window for quite a while, from when your first post was the only one up. That’s the one I was commenting on.

    The information about Ginger’s family being + for autism and – for thimerosal is a real head-shaker. Talk about cognitive dissonance.

    As to your last question, of COURSE it’s a genetic susceptibility to mitochondria being damaged by thimerosal! Occam’s Razor, who’s ever heard of that?!

  13. Schwartz April 20, 2008 at 00:30 #

    Joseph,

    “A common theme in these arguments is parents trying to find causes that do not implicate their genetics in any way whatsoever. But that is clearly difficult.”

    I’m not getting that impression from all quaters. I’m finding that the majority of reasonable people think that there is genetic component involved (that evidence is hard to ignore), but that the genetic component alone would not result in Autistic regression without further insult to the body.

  14. Schwartz April 20, 2008 at 01:38 #

    Kev, Joseph,

    “The idea that a trace amount of anything could cause a neurological disorder seems frankly risible to me purely on common sense grounds. Its not called a trace because there’s a lot of it.”

    Not a lot is not a scientific measurement.

    Additionally, you’ve switched to neurological disorder, when all Dr. Poling was suggesting was that the level of mercury could result in a mito dysfunction not a neurological disorder.

    As for trace, it appears when referring to Thimerosal, that it means 2000 ppb or 2000 mcg/L. That means .5 mcg for a single dose of vaccine having trace amounts.

    It may be a small amount, but it’s still a real amount. Since you can’t produce a toxicity level for Thimerosal, you can’t scientifically argue, nor can you quantify the odds that it won’t have any effect on a small percentage of children. The reality is that you and I just don’t know.

    There are other compounds that are extremely poisonous at those levels and there are others that are benign. Lead has been shown to have negative effects at blood levels within an order of magnitude of this.

  15. Ross April 20, 2008 at 05:53 #

    “but that the genetic component alone would not result in Autistic regression without further insult to the body.”

    I think parents of girls with Rett’s, for instance, would disagree.

  16. Kev April 20, 2008 at 06:56 #

    _”Not a lot is not a scientific measurement.”_

    Of course its not. But then neither is ‘some unspecified amount that’s never been established to do anything in terms of autism causation’.

    _”Additionally, you’ve switched to neurological disorder, when all Dr. Poling was suggesting was that the level of mercury could result in a mito dysfunction not a neurological disorder.”_

    I was referring to the idea that a trace amount of thiomersal could cause autism.

  17. Joseph April 20, 2008 at 20:09 #

    What I said before raises another question. The in-vitro studies of thimerosal where it is found that it damages brain cells or mitochondria, I don’t believe indicates it only does so if the cells are from specific types of people. So why doesn’t every single person who gets vaccinated with a TCV become brain damaged? That by itself seems to put any claimed implications of said in-vitro studies in serious doubt.

    Of course, it’s not hard to imagine why those in-vitro studies don’t translate well to real life, but that’s another way of thinking about the issue.

  18. Joseph April 20, 2008 at 20:20 #

    It may be a small amount, but it’s still a real amount. Since you can’t produce a toxicity level for Thimerosal, you can’t scientifically argue, nor can you quantify the odds that it won’t have any effect on a small percentage of children. The reality is that you and I just don’t know.

    If we’re talking about the same “thimerosal hypothesis” then the dose matters quite a bit. Maybe you’re talking about a different “thimerosal hypothesis” which I’m unaware of The “thimerosal hypothesis” I’m referring to says that an “autism epidemic” occurred due to an increase in the total thimerosal dose per child from about 70 mcg to about 180 mcg. Perhaps you’ve renounced the idea of an autism epidemic, or at least of an autism epidemic having anything to do with thimerosal?

  19. Nathan April 21, 2008 at 00:50 #

    I am surprised that no one has read the paper by Jalili and Abbasi 1961, it is a study on ethylmercury poisoning in rural Iraq in the 1950s and is the best example of this toxins effect on humans. Papers written after this one deal with the developmental effects of mercury. For more mercury information refer to the “Mercury study report to congress” written in 1997 it is an excellent source of information on mercury. It is free, and on the EPA website I believe

  20. Nathan April 21, 2008 at 00:51 #

    By the way both methylmercury and ethylmercury are written as one word (no spaces).

  21. Nathan April 21, 2008 at 02:27 #

    Nice advert Liz,
    But methylmercury forms a complex with glutathione which is what give methylmercury such a long half-life in the human body (Clarkson 1993) this complex is reabsorbed from the bile. I don’t think that there is any research that suggests that increased levels of glutathione reduces levels of mercury in the body. It may work for other metals, I do not know. Please don’t advertise here.

  22. Schwartz April 22, 2008 at 07:35 #

    Joseph,

    You still haven’t addressed the problem. If you support using Thimerosal in vaccines, how are you determining what the toxicity level is?

  23. Joseph April 22, 2008 at 15:07 #

    You still haven’t addressed the problem. If you support using Thimerosal in vaccines, how are you determining what the toxicity level is?

    I haven’t stated that I support thimerosal in vaccines. I don’t have strong feelings that it needs to stay in vaccines.

    But I think it is you who is avoiding the issue, Swartz.

    You either believe there has been an autism epidemic or you don’t. If you believe there has been an autism epidemic, that means you believe autism was rare in the 80s, and consequently, you must believe a total exposure of about 70 mcg in infancy is quite safe. It follows that a total exposure of 3 mcg must be extremely safe then.

    There are no two ways about it. It doesn’t matter if you believe other things also cause autism. If autism was rare in the 80s, a total exposure of 70 mcg must be quite safe in this context.

    It’s also interesting to note that a number of organization have signed articles of membership in a collaboration of sorts. These organizations include the ASA, Generation Rescue, SafeMinds, etc. Among their statements of agreement, they claim that “There is an autism epidemic.” They also have a claim that seems to indicate that only children are “affected by autism.” That is, autistic adults don’t exist (or they don’t care about autistic adults).

    Clearly, these organizations are stating, by implication, that a total exposure of 70 mcg of thimerosal in infancy is quite safe when it comes to autism. There’s no way to get out of that one without undermining a key premise of their belief system.

  24. Schwartz April 24, 2008 at 06:49 #

    Joseph,

    You have done a great deal to discredit the validity of the prevalence trends (and convinced me to some degree as well). Why does belief suddenly play into it? Sure, I might suspect that there has been an increase although less than published, but I know very well, the data is pretty crappy so I don’t really have a strong belief either way on prevalence. Good data just isn’t available.

    If you want to credibly study a possible correlation between a variable and disease or disorder, you need ALL of the following across the WHOLE time period being studied:

    1) Credible data of prevalence
    2) Credible data of dose
    3) Credible data about confounders

    I think even you doubt we have #1. We certainly don’t have #2. We don’t have #3 either.

    If any of these is missing, credible analysis simply can’t be done on correlation.

    I’m not really avoiding anything here.

    This discussion is revolving around the many that claim that trace amounts of mercury are safe in vaccines. How did they come to that conclusion without knowing what level ethylmercury is toxic to infants?

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  1. Left Brain/Right Brain » Blog Archive » Mitochondra and vaccines - the science - April 26, 2008

    [...] my regular readers will note I have – with some frustration – been blogging the responses of some Mitochondrial heavy hitters in recent [...]

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