Allergies are often a topic of discussion in the autism community. Much of the alternative- medicine approach works from the point of acting on allergies. I saw this paper and found it interesting, but wasn’t going to blog it until the PETA campaign (Got Autism) came up using the proposed sensitivity of autistics to casein.
The paper is Atopic features in early childhood autism, by B. Bakkaloglu, B. Anlar, F.Y. Anlar, F. Oktem, B. Pehlivantürk, F. Una, C. Ozbesler, and B. Gökler. As you might guess from the author list, this isn’t a U.S. or western European group. They are from Turkey. I have no reason to doubt the group’s quality, but that fact, together with the fact that the sample size is relatively small (30 autistic and 30 controls), suggests to me that this isn’t going to be the final word on this subject.
That said, the paper looks for allergic hypersensitivity (atopy) in a group of children with autism.
Here’s the abstract:
BACKGROUND: Autism is a developmental disorder of unknown etiology. Sensitivity to dietary and environmental antigens has been considered in its pathogenesis.
AIM: To examine immediate hypersensitivity in early childhood autism.
METHODS: We investigated 30 autistic children (23 boys, seven girls 2-4 years old) for atopic history, serum IgG, IgA, IgM, IgE levels, and skin prick tests (SPT) with 12 common antigens.
RESULTS: Nine/30 autistic children (30%) and 1/39 (2.5%) age-matched neurological controls from the same hospital had a family history suggestive of atopy (p<0.005). No patient in the autism and 28% in control group had symptoms of respiratory allergy (wheezing or asthma) (p<0.005), and 6/30 (20%) autistic vs. 7/39 (17%) control children had history suggesting other allergic disorders (p=ns). Eleven/23 (47.8%) autistic children had at least one positive skin test, similar to age-matched population controls. Serum IgG, IgA, and IgM levels were within age-appropriate limits. Serum IgE was elevated in four patients (13.3%). Specific IgE levels were negative in four cases with multiple SPT positivity.
CONCLUSIONS: This study suggests allergic features based on history, skin tests, and serum IgE levels are not frequent in young autistic children despite family history. This discrepancy between predisposition and manifestation might imply immunological factors or environmental condition
That gives away the punch-line: they don’t see a correlation between allergic features and autism. It’s still worth looking a bit closer at the paper.
They recognize that autism is a broad spectrum, so they attempted to look at a group that was fairly similar:
Many studies examined hypersensitivity or intolerance to environmental and food antigens in autism: however, their interpretation and comparison may be difficult due to methodological differences or anecdotal nature of the information. In addition, autistic spectrum disorders are a mixed group: inclusion of patients of various ages and clinical phenotypes can cause discrepancies, which we intended to avoid by studying newly diagnosed cases with idiopathic childhood autism in a narrow age range.
The study looked at very young children, ages 2-4. Autism was measured by a CARS test. Autistic children had scores from 33-50, with a median of 44.5. Since a score of 30-36.5 is considered “mild/moderate” autism, these data indicates that the children were largely in the “severe” range.
They found that 30% of the autistic children had familial history of atopy, compared with only 2.5% of the control children. However, autoimmune disease was not present in high numbers in the parents. Those two facts are interesting on their own, and if that was the end of the study, I wouldn’t be surprised if it popped up in autism discussion forums. But, another interesting finding is that the atopy is not found in the autistic children.
The questionnaire for allergic symptoms indicated familial atopy in 30% of autistic children and 2.5% of hospital controls (p<0.005) (Table 1). Taken together, 3/30 children of the autism group (10%) and 15/39 of the hospital controls (61%) had a score of at least 1 (p<0.005), and the rate of reported allergic symptoms was 6/30 vs. 7/39 (p:ns). Groups did not differ significantly in early-life environmental factors likely to affect allergic state: area of residence, day care attendance, breast feeding, and birth order. Parental autoimmune disease was present in two autism (vitiligo, psoriasis) and one control case (arthritis) (p:ns). CARS scores of the autism group were 33–50, mean 43.6, and median 44.5.
But, given that my interest level was higher due to the PETA ads using the proposed casein sensitivity of autistics, I wanted to see what sensitivities they found:
Of total 276 skin tests applied, 27 (9.7%) were positive, most commonly against aspergillus and grass antigens, followed by cat fur and D. farinae. Eleven/23 (47.8%) of children who received skin tests had a positive result with at least one antigen and five of them, with multiple antigens. House dust mite sensitivity was seen in three (13%), pollen, five (21.7%), and mold, in six (26%) children.
Serum IgG, IgA, and IgM were within age-appropriate limits according to laboratory standards. Serum IgE was elevated in 4/30 cases (13.3%), all associated with allergic symptoms in the patient or in a family member, or SPT positivity. Antigen-specific IgE tests done in four out of five children with multiple SPT positivity were negative.
So, mold (aspergillus), grass, cat fur and dust mites (D. farinae) were the top. Not casein, not gluten.
Again, do I think this is the last word on autism and allergies? No. But, I do think it is a good example of newer studies than, say, PETA’s reliance on a 1995 paper.
PETA appears to have wanted just enough data to justify their billboard. I join many in the blogging community who found the use of people with autism–the misuse, I should say–abhorrent. Kev has already responded in his own way. It took me a while to find my own, rather obscure, method of response.
I am grateful that the billboard has been pulled. I would hope that PETA would issue an apology as well. I’m not holding my breath.
B BAKKALOGLU, B ANLAR, F ANLAR, F OKTEM, B PEHLIVANTURK, F UNAL, C OZBESLER, B GOKLER (2008). Atopic features in early childhood autism European Journal of Paediatric Neurology, 12 (6), 476-479 DOI: 10.1016/j.ejpn.2007.12.008
Left Brain Right Brain 
My eldest son does not have an ALLERGY. He has an INTOLERANCE to casein protein.
Never, have I claimed it to be the cause of his autism, nor it’s removal a cure. But it did stop the daily nightmares/terrors and daily diahhrea and vicious rashes that started around 4mths of age that kept being blamed on teething.
It did stop the tripping over things and not putting his hands out. Had some dandy goose-egg’s from the fireplace and other pieces of furniture.
It did make him feel much better, within 48hrs with the nighmares/terrors and diahhrea stopped.
It did cause a 24hr meltdown, head-slamming nightmare, complete with night-terrors after his nap and middle of that night, one week later when he was fed a tiny bit of butter on a freezer pancake.
So… tell me… since it’s well known that foods will upset someone’s “system” why much children with autism fall under the catagory of “some children with autism are like that”… and their IBS go untreated.
Had he been NORMAL… the Dr’s first comment would have been “somethings upsetting his stomach… lets start pulling foods and find out which one it is”.
And…. since this is the NLD one… it did nothing for the severe, non-verbal one… FWIW….
S.
My autistic son is healthy and has no allergies, but I have to say, the Turkish study although interesting, has a small sample. I believe there is a smaller subset of autistic children where allergies and intestinal problems are co-morbidities of their autism, which is not to say that a GFCF diet will cure the disorder even for this group. There are universities such as UC Davis trying to come up with specific phenotypes of autism, to try to make sense of those differences and contribute to more effective treatments for each phenotype.
FWIW, my autistic daughter is probably the healthiest in the family and has a relatively mild lactose-intolerance (as do I) and no allergies. From 10 years of trialing restricting and allowing certain foods we have seen no discernable effect on her behavior, so at this point her diet might be characterised as “typical”. Even with the lactose, the most we’ve seen is the gastric upset that one would expect…easily remediated with a lactase product. Just an anecdotal data point of one.
I’m waiting to see what the results are from the U. of Rochester study on the effects of diet. My understanding is that they should be announcing some kind of result in the near future.
Thanks for posting this Sullivan, and for walking through the results. Interesting article.
The MIND Institute at UC Davis has been looking at all the biomed stuff, to some degree, at least considering it, from the get go. They have been doing loads of studying and taking detailed histories of ASD kids. But for some reason, they don’t have an endoscopist on staff. They don’t even have a Gastro-intestinal expert on staff.
They don’t have exactly have a geneticist on staff, but they have one that sees kids at the MIND Institute clinic, he’s just not there all the time seeing all the ASD kids, from what I understand. They have people studying genes, but not geneticists, in the sense of people who try to figure out for each kid what genes or other factors might be at work in a particular child (like if you take your kid to see a geneticist for a diagnosis).
Anyway, you’d think that if they thought there was anything to the presence of gut problems in autism they’d be writing papers on it, they’d have a GI doc on staff like they have behaviorists/researchers on staff and they have brain researchers on staff.
I’m guessing that they see some kids with say Smith Lemli-Opitz, in which case those kids will probably have specific gut problems associated with SLOS. I would guess that they might know that IBS is being caused in the ASD kids who have it by plain old fashioned stress.
Then there might be kids who have lactose intolerance (that’s common in the whole population) and on top of lactose intolerance, stress might make problems much worse.
Also, intellectually challenged kids of all sorts tend to have problems with figuring out when to go to the bathroom, that can cause constipation, and then overflow diarrhea, that is just overflow diarrhea, not some exotic problem from a xenobiotic or a food sensitivity… the kid is just backed up with feces and so their body “gets around” the feces by creating diarrhea.
I have to say I find it odd that many people will say, “gut issues are considered to be a part of autism, so doctors don’t treat it” while another group (with some overlap) will say, “doctors don’t recognize that gut issues are a part of autism”. One can’t have it both ways.
Yes, some people, autistic and not, have sensitivities to certain foods. Has anyone ever made a convincing argument, using real data, that autistic people are more sensitive or that these sensitivities are connected to the autism somehow?
There is another brief report that I saw recently about GI issues with autism. They claim a result that GI issues are linked to autism–but the information given doesn’t support the idea at all. In the report, they looked at a number of people with GI issues and autism–a large fraction of which were on the GFCF diet. For those individuals, it didn’t appear that gluten or casein were the main problems with the GI issues, just based on the fact that they still had issues.
On the other side, there is the recent Hornig paper. They showed a statistically significant larger fraction of the young kids with GI issues also had autism. They stated that they have future papers on that coming out.
Evidently not. I think there’s something to be said, though, about the fact that autistic children are not as good at communicating these types of complaints. On the one hand, many real issues could be missed. On the other hand, it’s possible the parents are getting tests and having disproportionate worry over issues that wouldn’t be given a second thought when it comes to normal kids.
Hello Sullivan –
Has anyone ever made a convincing argument, using real data, that autistic people are more sensitive or that these sensitivities are connected to the autism somehow?
Well, I’m not sure if this paper speaks precisely towards your question, but it may:
http://foa.sagepub.com/cgi/content/abstract/23/3/176
Specific IgA, IgG, and IgE antibodies to food antigens in 35 participants with autistic disorder and 21 of their siblings in the Republic of Macedonia were examined. Statistically significant higher plasma concentration of IgA antibodies against alpha-lactalbumin, beta-lactoglobulin, casein, and gliadin were found in the children with autistic disorder. Plasma concentrations of IgG antibodies against alpha-lactalbumin, beta-lactoglobulin, and casein in participants with autistic disorder were significantly higher. IgE-specific antibodies (alpha-lactalbumin, beta-lactoglobulin, casein, and gluten), as well as plasma concentration of total IgE, also were statistically significantly higher in the participants with autistic disorder. Gender differences were found for select IgA, IgG, and IgE (but not for total IgE) food-specific antibodies (kU/L) in the participants with autistic disorder and their siblings.
I suppose the question is, can you have higher levels of immunoglobulins without being more sensitive to certain kinds of foods? If you can, then I guess this paper might not be what you are looking for; though it is still a set of quite strange findings. This is, in my mind, also indirect evidence of a leaky gut; though I suppose there is some other mechanism to develop sensitivity without proteins passing through the gut wall. (?) [does anyone have any ideas on this?]
There are several others with similar findings:
IgA antibodies in Rett syndrome. (Reichelt KL, Skjeldal O.) – The level of IgA antibodies to gluten and gliadin proteins found in grains and to casein found in milk, as well as the level of IgG to gluten and gliadin, have been examined in 23 girls with Rett syndrome and 53 controls. Highly statistically significant increases were found for the Rett population compared to the controls.
Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder – (Jyonouchi H, Sun S, Itokazu N.) – Abstract is cumbersome to paste, but essentially more reactivity to common dietary proteins among autism group compared to controls; similar to neurotypical children with dietary protein intolerances.
Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders. – (Jyonouchi H, Geng L, Ruby A, Reddy C, Zimmerman-Bier B.) – Cumbersome abstract.
Does this help?
– pD
So, we have Turkey vs. Macedonia with possibly conflicting results?
Statistically significant higher values for the autstic children in the Macendoian study. Doe they state that these are outside the normal range? I realize that is a variation on the question you already posed.
I honestly can’t see how the Macedonian study would indicate a leaky gut.
Hi Sullivan –
So, we have Turkey vs. Macedonia with possibly conflicting results?
Well, we might be mixing wheat and dust mites here, which could be a source of confusion.
Did the Turkey even study common food allergens, or just common allergens? Listed above I see: aspergillus, grass, cat fur, d. farinae, dust mite, pollen, and mold. So out of 12 allergens studied at least seven were not dietary proteins; one might think they’d mention that they were testing for these, if they did. I’m betting that dietary proteins like beta-lactoglobulin are not considered a ‘common’ allergen.
Another possible problem is that I don’t think that the Turkey study studying plasma, but rather serum and skin pricks. I’m not knowledgeable enough to understand if there is a good reasoon why both results can be accurate based on this difference. If it was statisically higher than controls, isn’t that higher than normal? And we still have many other studies indicating the differential responses to dietary proteins from the autism cohort than normal, don’t we?
I honestly can’t see how the Macedonian study would indicate a leaky gut
Well, my reasoning was admittedly simple; how does one develop reactions to proteins commonly found in milk without it coming through the gut wall in the first place? I sort of thought that is what the gut wall was for; keeping the big particles out and only letting the small ones in.
I suppose one develops reactions to things like grass, pollen, and pets without eating them. I guess it might be possible to develop reactions to the common dietary proteins without the mucosal wall being the point of entry; I’m just not seeing it. If you aren’t seeing evidence of a leaky gut, do you have an idea of why / how the reactions that have been observed can be explained (?).
– pD
How this manuscrip may add to the situation when it does not consider the state of the art knowledge in food allergy /intolerance testing?
This manuscript did NOT measured the four IgG…, did not measured eosinophilic activation did not considered non-Ig E allergies…, did not consider the known food allergens.I do not understand how they can conclude what they conclude….especially because there are non-invasive methods to look at. For example
Some selected info
Link
.
Link
Link
Link
I remain surprised at the lack of large multi-centred clinical trials in autism considering the prevalence of autism. These small studies seem to muddy the waters further.
pd
A question for you, courtesy of what I think Dr Offit wrote in false prophets: If there was any substance at all to the leaky gut phenomenon, you would expect the leaks to go both ways, that is opioid like proteins to the blood and blood proteins to the gut. Well they went looking intensively for blood proteins in the gut and found zip, niets, nada. This looks like another sunk theory.
Hi Alyric –
Some questions for you.
Can you provide a reference to this ‘intensive’ analysis for blood proteins in the intestine?
Did any of the abstracts I posted above have anything to do with opiods?
In order for the immune system to react, it must understand the proteins; something that shouldn’t be happening if they were restricted to the correct side of the intestinal wall.
If you, or Dr. Offit for that matter, have any idea of why children with autism seem to differentially react to food proteins that doesn’t involve the transport of these proteins through the gut wall at one time or another, I am all ears.
We could be lookoing at a case of molecular mimicry, but what agents could be responsible for this?
Or maybe there is another reason. (?) If you have ideas other than random sniping, please, please expound on them.
What isn’t a sunk theory is that children with autism have been observed to react differently to food proteins than their non diagnosed peers.
– pD
MsClark… how does a child under 2yrs of age have STRESS that would cause IBS??? In our family it is a genetic trait… My Father, my bro and I, all suffer from it in varying degrees. None of us can have large quantities of dairy products without stomach upset. My bro – none… myself… I pop a pill before having a bagel with cream cheese, pizza, processed meats.
And yes… the first Dev Ped we saw said to my face… who was also nearing retirement age… “Some children with Autism are like that”. He did not care at all that the child had a very nasty, full time stomach ache… he also… does not believe that Aspergers, NLD and other forms of “high” functioning Autism… are Autism.
Which is why… the next visits – for the eldest and the little one… were to another Dev Ped.
http://www.cbc.ca/health/story/2007/12/10/autism-mouse.html
The Cdn version.
S
http://www.cbc.ca/health/story/2007/09/27/autism-study.html
Sorry… grabbed the wrong link
Well, the leaky gut as a problem under study is not “sunk” I would say
The leaky gut is studied in a context where intestinal microbiota and the immune system function are also considered -together.
I’m not saying there are no kids with food intolerances, celiac is fairly common, lactose intolerance is fairly common. Parents may be attributing gut problems to something exotic when it is something common, like lactose intolerance.
So far, there’s no evidence that lactose intolerance and celiac are more common in autistic kids than in other kids.
A widely ignored possible cause of IBS in babies/toddlers is stress.
It’s totally obvious that children have stress, even a great deal of stress, from birth onward. They aren’t stressing over their bank accounts, or whether or not they’ll get to sit next to the boss at the company party. But babies experience pain and can’t tell parents where it is. Toddlers are expected to hear and understand and to be able to speak their needs. An autistic kid might not be hearing the world normally, or might not be able to speak, and yet the world demands that he speak.
Some parents are good at guessing what the kid wants, some are not. So being a non-verbal toddler/pre-schooler could be extremely stressful.
If the kid is autistic and has the kind of stress response that Dr. Blythe Corbett found in older kids, the infant or toddler may be having his intestines assaulted with unusual amounts of cortisol.
Parents haul their kids to day-care these days before the babies are old enough to get a diagnosis, and I can only imagine how stressful it is for the baby to be taken to different places and left behind by mom. A typical baby may find that harsh, but get used to it, maybe it’s much harder for an ASD kid.
Then there may be undiagnosed genetic disorder is ANY autistic kid. Maybe not yours, but in any other kid it could be that he has undiangnosed Smith-Lemli-Opitz or Cornelia de Lange syndromes, or other genetic problems that are as yet misunderstood. Not all of these would be mediated by the kind of food you give the kid as celiac and lactose intolerance are.
The most common digestive problem in autism is not diarrhea, like that caused by lactose intolerance, but it’s constipation. The kids in Wakefield’s study had constipation. Constipation can cause the lymphoid nodular hyperplasia that Wakefield wanted to attribute to measles.
Hi Farmwifetwo –
Children with autism have been found to have highly exagerated chemical responses to new situations, the same chemicals that are associated with stressful events. So, as Ms. Clarke states, it isn’t necessarily about the bank account, but any new situation might cause them at a chemical level to release stress hormones; and having a bunch of excess cortisol is bad for your stomach.
http://cat.inist.fr/?aModele=afficheN&cpsidt=17376689
The children with autism, but not typical children, showed a more variable circadian rhythm as well as statistically significant elevations in cortisol following exposure to a novel, nonsocial stimulus.
I’m not discounting your familial history; it seems likely this plays a role too.
This is also not meant in any way to defend the treatment you received from your pediatrician, something that is not an uncommon tale among autism parents.
– pD
pd, I wasn’t sure what the heck you were talking about with immune response, which isn’t a pillar of the leaky gut theory, so I went back to see why you were looking for one. I think you may be quite wrong about proteins having to be on one side of the gut to be reacted against (if indeed they are) because peyer’s patches are on the gut side.
The reference cited in AFP, page 44 and Offit credits it to Gershon, cited in Fitzpatrick, MMR and Autism, page 146. Offit also gives three other reasons why the leaky gut theory is definitely dead.
Hi Alryic –
pd, I wasn’t sure what the heck you were talking about with immune response, which isn’t a pillar of the leaky gut theory, so I went back to see why you were looking for one
LOL! So you decided to read through the thread? Very impressive.
The question was asked if there was evidence to suppor the notion that children with autism are sentitive to foods. If we didn’t have scads of people with stories just like farmwifetwo; wherein their child had a drastic reaction to removal of these types of foods, a differential immune reaction might be of little consequence; however, we have the opposite.
In any case, it matters quite little. I was quite specific in that I felt the evidence was indirect, and indeed, there may be other mechanisms.
This is, in my mind, also indirect evidence of a leaky gut; though I suppose there is some other mechanism to develop sensitivity without proteins passing through the gut wall. (?)
The relative leakiness (or not) has no impact on what has been observed, different immune responses to proteins in milk and wheat in children with autism when compared to children without that diagnosis.
Your note in regards to Peyer’s patches is quite interesting. Thank you.
I looked for a while, but could not find anything resembling a search for blood proteins in the intestine of children with autism, by Gershon or anyone else. Can’t you just give me the pubmed link? I am geniunely interested in looking at that study.
– pD
There never was any reason to suspect that autistic kids had leakier guts than anyone else. It’s a part of the whole “measles in the gut” fraud. Which is all about Wakers and his desire to sell his own measles vaccine and his taking money from lawyers to prove that some kids with “gut problems” that were resolved with a cleaning out of their intestines prior to colonoscopy. The kids had this “great improvement” in their behavior because they felt better after their intestines were cleaned out of lots of backlogged feces.
They didn’t feel better because someone took away the dairy or wheat.
There’s no reason to think that autistic kids have more and more serious reactions to wheat or dairy. And there’s every reason to believe in parent passing on to parent the belief system that you can get a big change in the kid by changing the diet.
The parent can go from having no hope, to having hope and that can make a massive change in the anecdotes coming from the parents.
I don’t believe that the GFCF diet is a going to help any but a tiny, tiny minority of autistic kids, and maybe no more than would be helped of a random group of non-autistic kids.
There’s no reason to think that there would be a connection between dairy/gluten and autism.
There’s every reason to suspect that it’s an offbranch of quackery promotion because the anti-wheat anti-dairy thing is old and very common among alt med. It’s a cure for everything, just like chelation is a cure for everything and everything is caused by yeast, and everything improves with a “liver cleanse” and high-colonics, and spinal manipulation and moxibustion.
Cancer, diabetes, baldness, excema, arthritis, high blood pressure, bad breath, they are all treated by quacks and believers with whatever that quack specializes in and one thing that is a recurrent recommendation from them is a wheat free/dairy free diet.
Been there, done that. Tried the diet myself a few years ago for a totally not-autism-related issue. I couldn’t do it and as it turned out it was stupid to think that the diet would have had an effect on what I was trying to improve.
Exactly. What is the provenance of the idea, as Skeptico would point out? When there’s no sound provenance, that’s a red flag. It means we’re likely dealing with pseudoscience.
New reports on the topic of allergies and ASD
From the same authors
Stress management-emotional and physiological – is being more and more studieda; it requires immune dysregulation
Link
In fact
Link
pd
Have to ask Offit, or Fitzpatrick. There are 3000+ references on pubmed to gershon and it may not be him that wrote it but one of his minions since he’s the head honcho. I’d like to see the original here too.
Alyric,
I left you a reply on the possible source of the Gershon statement over at ScienceBlogs Bookclub , as well as a slight hint to Dr. Offit to corroborate whether that’s the source.
If that’s the cause of a (non demonstrated) increased rate of leaky gut in autistics, that would tend to argue it’s not an autistic characteristic per se; meaning that the right phenotype to focus on for this issue is the stress, not the autism. Also, it would not be the leaky gut that causes stress, but the other way around.
But in reality, I don’t think the leaky gut hypothesis comes from this. I think it was completely made up.
Note that it predates Wakefield. Search Usenet.
This is how I think it went down. A mom takes an autistic kid to the doctor for digestive complaints. The doctor tests the kid and finds the kid has leaky gut. The mom wonders, “is this common in autistic kids?” Tells friends. The rest is history.
Essentially a non-existent provenance.
]
Gut or brain mast cells can also be triggered by many non-immune molecules; you may find them in table 3 of this manuscript
Trends Pharmacol Sci. 2008 Aug;29(8):375-82. Epub 2008 Jul 6. Links
Novel therapeutic targets for autism.Theoharides TC, Doyle R, Francis K, Conti P, Kalogeromitros D.
Hi Ms. Clarke –
There’s no reason to think that autistic kids have more and more serious reactions to wheat or dairy.
What about the abstracts posted above clearly showing a differential immune response to those proteins? Does this not qualify as a serious reaction? Why not?
What reason do we have to assume that this is a benign reaction; especially considering what we have thousands of parents telling us about their childs behavior when these agents are removed?
Forget about leaky gut. You are right. There is no such thing as a leaky gut. It is non existent in autism. You have all convinced me.
This admission does absolutely nothing to discount was has been observed at a clinical level in terms of immune responses to dietary proteins, however. The mechanism by which this immune response is generated is a different question than if there is a difference in response.
– pD
Hi Regan –
I left you a reply on the possible source of the Gershon statement over at ScienceBlogs Bookclub , as well as a slight hint to Dr. Offit to corroborate whether that’s the source.
I managed to find the presentation to Congress associated with Gershon, but considering the attitude posters on this board tend to take of treating posters or presentations in the place of peer reviewed, published articles, I figured that this could not be the source for an ‘intensive’ analysis.
Fancy that, the posters on LBRB defining a presentation as actual research. That is rich beyond belief. LOL.
– pD
Hi pD
Even more, the topics of tight junctions in gut and how transport/absorption of nutrients is done (besides complexity)is a topic of continous research
and
Intestinal crosstalk – a new paradigm for understanding the gut as the “motor” of critical illness
What is zonulin?
Link
and…
Gluten sensitivity…
Hi pD,
I posted the Congressional report because that was a source of some statements by Dr. Gershon which bore strong similarity to the quotation in “Autism’s False Prophets”. (There are some citations associated with the Dr. Gershon’s testimony to the Congressional committee.)
There may be more specific citations out there as well; in fact that’s probable. So it may be more the case that that’s what I could find, not necessarily that’s all that there is. Just trying to help Alyric out if that was the source of the quote. Not being sure is the reason for the request for corroboration at ScienceBlogs.
As you always say, “Take care!”
Hi Regan –
But this shouldn’t be difficult to find at all. It really should be simple.
There is no reason at all to search through 3000 abstracts; the literature on intestinal problems and autism is relatively sparse. Goto pubmed and type autism / permiability and you get 14 hits; autism / leaky gets you 5 hits; autism / intestinal gets almost 100.
I was unable to find a single one wherein tissue to intestine transport of proteins or peptides in children with autism was investigated. I very well could be wrong; I’d be very interested in seeing this study.
If you read the quote closely, there may be some clues as to why no one seems to be able to validate if such a study was actually ever undertaken:
No movement of peptides or proteins from the tissue fluid to the intestine has been detected in autism or as a result of MMR vaccination.
Of course, in order for it to be detected, someone must have tried to perform an evaluation. If there have been zero evaluations, the above statement is true by the letter, but utterly deceptive by the nature of what people expect of those crafting public health policy. Now that’s some quality framing of science!
– pD
Look for them in the urine apparently. Courtesy of a very nice person:
http://www.ncbi.nlm.nih.gov/pubmed/18337276?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=1&log$=relatedarticles&logdbfrom=pubmed
Alyric
Things are NOT so simple
A recent manuscript on urine proteomics analysis
Urine proteomics: the present and future of measuring urinary protein components in disease
Now, this manuscript did not take into account the different groups of HFA-MFA and LFA or –better- the DSMIV diagnostic criteria to differentiate Asperger from Autism.
Without concomitant knowledge on the leaky gut presence or not, on the peptidases/other enzymes level and function blocking or not and with the complexity of the proteins digestion, metabolism and excretion through kidney- PLUS the complexity of the testing in the urine of low quantities of opioids- that Dr Reichelt presented in their work.
If children tested were HFA- such as Dr Reichelt presented- no higher amounts of peptides are present- and he also published on the topic. What if there are different combinations of clinical problems ?What if the results are different depending on the subgroup of autistic children?
This manuscript shows that the finding is dependent of the subgroup
It is evident that without further information ( clinical, behavioral, diagnostic and from CMPs) it can not be concluded that in autism as a whole there are not peptides in urine
and not the same but related…
Hi Alyric –
LOL! LOL!
1) The paper you reference seems to have nothing to do with ‘blood proteins in the gut’.
You made this increasingly difficult to verify statement: Well they went looking intensively for blood proteins in the gut and found zip, niets, nada.
The paper you provide here has nothing, at all to do with blood proteins in the intestine, as you stated. It is about opioids. Did you read the abstract? In any case, not having opioids found doens’t mean you cannot have intestinal permiability.
Whoever kindly provided this to you must not have understood what you were trying to prove. How, precisely, would looking for peptides in the urine have anything to do with blood proteins in the intestine?
2) This paper you provided was published in September 2008.
This is also the same month and year that the book by Dr. Offit was published. I’m pretty sure that in the publishing world, it takes a few months from the time you get done writing until the book hits the street. So it seems unlikely that this is the paper Offit (didn’t) reference.
But since you originally told me Gershon was the source, this makes things even more unlikley to be the original material.
The Gershon presentation to Congress kindly provided by Regan was in 2001. If you have a mechanism by which Gershon could have possibly be referencing this paper, seven years before publication, I’m very interested in hearing it. This also forgets the fact that the paper doesn’t have anything to do with “movement of peptides or proteins from the tissue fluid to the intestine”.
Are you sure the source of your information can be trusted? And why rely on a kind person to give you this link; as I stated the papers on intestinal permiability and autism are relatively scarse in pubmed. Why don’t you just post the paper Gershon was referencing?
– pD
OK, having read Gershon’s statement to Burton’s committee, you will be aware that there is compelling reason to doubt that gut permeability is in any way possible for a living human being. You did read that point didn’t you? I thought they went looking for blood proteins in the gut and still do, because that’s what I remember having read. However, I could be wrong about that. I still have this shocking habit of remembering what I read without remembering where I read it and I still want to follow this up, with Fitzpatrick probably if not Gershon himself. The reference is to Fitzpatrick’s book, not to a peer reviewed paper. The urinary peptide thing is simply that if they’re coming in at all, they’ll end up in the urine. They haven’t. That’s strike two against this benigted theory. Strike three is respectively the liver and the blood brain barrier. Chances of foreign proteins getting past those two are approaching zero. Chances of them managing it to any significant level are zero.
The theories proposed by ‘autism is caused by toxins proponents’ consistently paint a picture of human physiology that is incompatible with life, like this gut permeability theory or the wackier notion that we are somehow overtaxing an infant’s immune system with the current vaccine schedule. Notably, the only evidence the toxin proponents ever come up with are peripheral, secondary if not completely irrelevant to the main issues. If you happen to be wedded to the increased permeability theory, you need references that directly refute Gerahon’s very sensible arguments.
alyric
What??
Starring roles for astroglia in barrier pathologies of gut and brain
Maria, to the list of descriptors of references as secondary, peripheral and irrelevant, i should have added speculative, which your reference is. It is intriguing to speculate whether enteric glial cells perform the same function for the gut barrier as they do for the blood-brain barrier. Apart from the research having been done in transgenic mice, there is the problem of making general references to ‘permeability diseases’, while not specifiying what these entail – permeability to what exactly and without concrete references. This does not constitute evidence of anything and it looks like there is a lot of work to be done to confirm any of the proposed hypothesis. I’d keep an eye on this because it’s interesting.
Which leaves us back at Gershon and the fact that an increased permeability sufficient to admit macromolecules in an uncontrolled manner will undoubtedly have that person dead in short order due to malabsorption and malnutrition issues.
I noted the description of the blood brain barrier function and that degree of control is support for Gershon’s position. Rogue macromolecules aren’t going to make it.
It is likely not the paper since Dr. Offit is referencing Dr. Fitzpatrick’s book, which predates this by a good time.
However, your statement shows a singular lack of understanding of the publication process. Many, if not most, journals do not have “embargo” policies. This means that the authors can distribute the paper in manuscript form. Given the time it takes to get a paper published, it is quite possible that Dr. Offit had access to papers that were published at about the same time as his book.
If this is too esoteric for you, perhaps you might want to look at the “epub ahead of print” statement given for many papers. Electronically published ahead of print publication.
If you want to do your end-zone victory dance on such a minor item at this, do it right. Don’t demonstrate ignorance at the same time.
Let’s see–10 years (plus) and no demonstration of “leaky guts” causing autism. But, if the idea that Alyric didn’t have a good reference in hand eases that lack for you, enjoy.
10 years, tens of millions of dollars spent, countless families put through grief and no demonstration that Wakefield was even close to correct. Quite the opposite–lot’s of information indicating that he ignored conflicting data.
A smart move would be to cut your losses (Wakefield, leaky guts and the MMR) and move on to promising avenues of inquiry.
alyric
A comment was lost…GRH!
I do think that the manuscript is relevant and important, due to the amount of manuscripts on BBB disruption- 700 in pubmed if you put this as search keywords
About the BBB
Link>/a>
and
aPhysiology and pathology of the blood-brain barrier:implications for microbial pathogenesis, drug delivery
and neurodegenerative disorders
sorry,
Other manuscripts
The Blood-Brain Barrier/Neurovascular Unit in Health and Disease
The Blood-Brain Barrier in Neuroinflammatory Diseases
and…
Denial Versus Dualism: The Blood-Brain Barrier as an Interface of the Gut-Brain Axis
Hi MC –
LOL! LOL! Well thank godness someone has set me straight on the publication process! Whew! By the way, do you have any quality ideas on why children with autism are generating immune responses to dietary proteins at different levels than their non diagnosed peers?
I was much more interested in showing that Alyric was basing his rather authoritative statements on assumptions and the lack of investigation, as opposed to actual research. In a similar fashion you seem to spend plenty of time educating me in regards to the esoteric nature of the publication process, and no one seems to want to discuss different immune responses to proteins in one population.
Let’s see—10 years (plus) and no demonstration of “leaky guts” causing autism. But, if the idea that Alyric didn’t have a good reference in hand eases that lack for you, enjoy.
Intestinal permiability, if present, does not need to cause autism to be source of a problem. Phantom argument alert.
There has been precious little investigation into a leaky gut in one way or the other. I believe that there have been two sugar uptake studies with one positive, and one negative result; both studies of which have very small samples sizes. Are you aware of more than two sugar updake studies?
This is a geniune question. Are there more than two studies in autism evaluating for increased permiability? If not, what we have is a relative dearth of evidence, as opposed to the quality analysis.
There have been several opioid studies, again with conflicting results; mostly negative, but this is a different question than if there is increased permiability. Do you agree that you can have one without the other?
Increased permiability is found in conditions like IBD, yet no one seems to be looking for opioids there.
10 years, tens of millions of dollars spent, countless families put through grief and no demonstration that Wakefield was even close to correct. Quite the opposite—lot’s of information indicating that he ignored conflicting data.
Strawman alert. I have mentioned neither Wakefield, nor measles.
It is well established that increasing levels of psychological stress can cause distrbances in the gastrointestinal system; up to and including increased permiability.
http://www.ncbi.nlm.nih.gov/pubmed/18537635?ordinalpos=14&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Studies in rodents have revealed that both acute and chronic exposure to stressors can lead to pathophysiology of the small and large intestine, including altered ion secretion and increased epithelial permeability (by both transcellular and paracellular pathways). Prolonged exposure to stress can induce low-grade inflammation, cause ultrastructural epithelial abnormalities, and alter bacterial-host interactions allowing greater microbial translocation.
Likewise, we have evidence that the stress response at a chemical level is greatly increased in autism. Behaviorally, we notice that children with autism have inceased anxiety to new situations. Unless we have some reason to believe that only in children with autism that chronic stress is not generating intestinal distress, we must look for studies one way or the other.
Our insurmountable clinical evidence that this increased stress response has not had an impact on intestinal permiability? A single study with fourteen autistic participants. Or perhaps you can provide more?
You might consider the stregnth of your own argument before throwing about the ignorance tag with such abandon.
– pD
Hi MC –
LOL! LOL! Thanks for that update of the publication process; thank goodness you were there to set me straight. Whew! By the way, do you have any ideas on why or how children with autism display differential immune responses to dietary proteins?
Alyric apparently didn’t even understand that a study regarding opioids or their absence from urine does not speak towards the presence of intestinal permeability. The larger point is that Alyrics rather authoritative statements were made based on assumptions and the lack of analysis and strawmen, as opposed to actual research, very much like your own arguments.
Given the time it takes to get a paper published, it is quite possible that Dr. Offit had access to papers that were published at about the same time as his book.
One then might begin to wonder, if such papers existed, why didn’t he include them as references? Why rely on a congressional hearing from 2001 with all of the quality research available to him? Doesn’t this bother you in the slightest? Maybe there is something about the publication process that caused him to exclude any real references that you can explain to me; with my being simple and all.
Let’s see—10 years (plus) and no demonstration of “leaky guts” causing autism. But, if the idea that Alyric didn’t have a good reference in hand eases that lack for you, enjoy.
The idea is must be casual is a false argument. What if having autism causes you to have increased permeability, instead?
What we see is a distinct lack of studies one way or the other. I believe there are a total of two studies regarding sugar uptake in autism; one negative, one positive. Both studies suffer from very small sample sizes. Are you aware of any others?
This is a genuine question. With the exception of Robertson (2008) and
Deufumia (1996), do we have any other clinical analysis for increased permeability in autism? Myabe you can find that Gershon paper!
There have been studies on opioids, mostly negative; but this is a different concept than increased permeability; something some people seem to have difficulty detangling. There is well established permeability problems in IBD, and no one has denounced the fact that opioids have yet to be found in that population.
10 years, tens of millions of dollars spent, countless families put through grief and no demonstration that Wakefield was even close to correct. Quite the opposite—lot’s of information indicating that he ignored conflicting data.
Strawman alert. Have I mentioned measles, or Wakefield? Your argument is only valid if the only way to get increased permiability is by measles vaccination. However, the idea that chronic stress affects the gastro intestinal system, up to and including increased permiability is not controversial; and in fact, has a basis in chemical anlaysis, animal models, and human studies on conditions with increased permiability (i.e., IBD).
Stress-induced gastrointestinal barrier dysfunction and its inflammatory effects (Lambert, 2008)
Pathophysiological mechanisms of stress-induced intestinal damage. (Gareau 2008)
There are many, many others.
We have solid clinical evidence that at a chemical level, the stress response in autism is increased when compared to non diagnosed peers. Likewise, behaviorally, we notice that children with autism have increased anxiety. In other words, having autism, having a different stress response, predisposes you to having a leaky gut; not the other way around. Unless we have a valid reason to believe that only in children with autism this response does this not lead to gastro intestinal distress, including possible permeability, we must look to the research. Do you have a valid reason why we should believe the stress response in autism would not be affecting the gastro intestinal function of these children?
When we do look at what is available, the insurmountable negative research on permeability in autism consists of a single paper with fourteen autistic participants.
You might consider the strength (and relevance) or your own arguments before throwing the ignorant tag around with such abandon.
– pD
alyric, some of the manuscripts I posted show that recent 5 years a lot of knowledge has been added to the ENS and patological conditions of the gut.
Link
Enteric Glia Regulate Intestinal Barrier Function and Inflammation Via Release of S-Nitrosoglutathione
and again Zonulin
Human ENS regulates the intestinal epithelial barrier permeability and a tight junction-associated protein ZO-1 via VIPergic pathways
Role of enteric glial cells in inflammatory bowel disease
Link
Now, alyric, the only reference I found that fits your comment from Gershon MD is this….. a little old, don´t you think?
and you could be intersted to read this
Development of Intestinal function in mammals
especially pages 14 to 25….
and this
Intestinal Permeation and Gastrointestinal Disease