Italians eat a lot of wheat

[Aytundra]

Thank you RRM,for highlighting this article.
Very Much Appreciated!

[Ducky]

The new link you gave me once again is on autistic children. Im more interested in experiments on healthy individuals.

I dont know what is wrong with willing to verify what I hear? Do you expect others to believe everything blindly?

I wanna see exactly how those experiments was conducted and want the details. How much Glumorphin B5 they found for example?

[Aytundra]

Questions this study.

Quote 1: "Finally we can demonstrate that overloading a normal person with gluten and gliadin for three days resulted in finding Glumorphin B5 in urine. The peptide was determined to four decimal places and showed identity through spiking with synthetic glumorphin B5."
Reichelt KL et al

Quote 2: "Overloading normal person with gluten and gliadin for three days resulted in a demonstrable glumorphin B 5. Topp trace is spiked with standard peptide, bottom trace urine pattern after three days excessive gluten exposure."
Reichelt KL et al

Quote 3: "Overloading normal person with gluten/and gliadin for 3 days gave a measurable peak for glumorphin B5, which could be spiked with B5 (Fig. 5)." Reichelt KL et al

I like how they did this study with "overloading a normal person", to serve as a mindframe of reference to compare to their autistic individuals.
I like how they kept "four decimal places", to say they paid attention to their numbers.
However, they only overloaded 1 person, "overloading a normal person".
We don't know how much really normal that 1 person is, or if it is just 1 case, or 1 odd ball, or 1 fluke in testing.
I would have liked this study more, if they had included more normal people, increased sample size of their controls.

I am not sure what they overloaded that 1 person with.
Quote 1 said they spiked "with synthetic glumorphin B5"
Quote 2 said they overloaded "with gluten and gliadin"
Quote 3 said they overloaded "with gluten/and gliadin"
This seems wishwashy writing to me, what did they overload the normal person with?

To my knowledge, a), b) ,c) are different molecular structures, see molecules on pubCHEM.
a) gluten
b) gliadin
c) synthetic glumorphin B5 (can't find this molecule on pubCHEM)

All it showed was ingestion and excretion of synthetic glumorphin B5 (whatever that is, as there is no structure in pubCHEM).
Even then, their graph is poor photography, I can't display the fine prints of the lines and axis on the graph to read the units of Fig 6.
Also, this study did not say if the overloaded normal person had any brain effects from their molecular addition.

[RRM]

The new link you gave me once again is on autistic children. Im more interested in experiments on healthy individuals.

Me too. A large group preferrably.
At least this study demonstrated that glumorphin B5 may show up in the urine of a healthy individual if overloaded with gliadin.
And that is a opioid peptide that is 5 amino acids long.
Something you claimed it does not get absorbed.
Apparently, it may.
Even in a healthy individual.

To my knowledge, a), b) ,c) are different molecular structures, see molecules on pubCHEM.
a) gluten
b) gliadin
c) synthetic glumorphin B5 (can't find this molecule on pubCHEM)

Glumorphin B5 is a peptide (of 5 amino acids) that is contained in gliadin.
Gliadin is a fraction of gluten protein. This gluten-protein fraction contains the most active opioid peptides sequences.

All it showed was ingestion and excretion of synthetic glumorphin B5 (whatever that is, as there is no structure in pubCHEM).

Ingestion of gliadin.
The glumorphin B5 is contained in the gliadin, and set free by digestion of this protein fraction,
as is demonstrated by its appearance in urine. (its not digested itself as its resistant to the intestinal proteinases trypsin and
chymotrypsin.Zioudrou C et al)
All glumorphin B5 is exactly the same molecule, regardless of how you extract it from a longer protein.
Its a peptide of 5 amino acids linked to eachother:
Tyrosine-Glycine-Glycine-Tryptophane-Leucine

[Ducky]

At least this study demonstrated that glumorphin B5 may show up in the urine of a healthy individual if overloaded with gliadin.

1. Where does it say that there were one healthy individual?

2. Do you base your diet on the result of one individual overloaded with gliadin?

And that is a opioid peptide that is 5 amino acids long.
Something you claimed it does not get absorbed.

I find it strange that we are in 2014 and the scientific community still doesnt know what size of proteins can pass through the small intestine.

[RRM]

Where does it say that there were one healthy individual?

One 'normal' person, as in 'not autistic'.
Whatever absence of illness defines healthy.
Maybe you think that we should exclude every person with somewhat increased intestinal permeability.
But the level of intestinal permeability will be individually different anyway.
This means that some may absorb very little opioid peptides, whereas others absorb a little more, substantially more, or even far more.
What is your absorption rate?
You dont know.
I dont know.
Nobody knows.
But we do know some of the possible influences of opioid peptides.
And how easy it is to avoid them.

Do you base your diet on the result of one individual overloaded with gliadin?

This diet is based on minimizing the intake of toxins such as HCAs, oxysterols, acrylamide and so on,
and on minimizing the intake of anti-nutrients. (and still getting all required nutrients)
Opioid peptides are neither.
Opioid peptides are just one foot note in this diet.
Even without opioid peptides, wheat products would be excluded from this diet, because of the toxins that result from cooking.

But there is a very solid argument against consuming wheat and other grains.
1. Wheat gluten contains many opioid amino acid sequences
2. These opioid peptides get released by digesting gluten in our intestines
3. As such, they may cause constipation
3. They are relatively resistant to intestinal proteases
4. They get absorbed in such great numbers in a small group of people (with increased intestinal permeability), that they may contribute to schizophrenia and autism.
5. They may get absorbed in smaller numbers in people who are not autistic / schizophrenic.

How do you know how many opioid peptides are absorbed by your intestines?
Similarly, you dont know how susceptible you are to cancerous HCAs.
Some people may smoke 2 packs of cigarettes a day all their life, and have healthy lungs at the age of 90.
In advance, you dont know how susceptible you are.
When you get lung cancer, thats when you know your susceptibility.

And that is a opioid peptide that is 5 amino acids long.
Something you claimed it does not get absorbed.

I find it strange that we are in 2014 and the scientific community still doesnt know what size of proteins can pass through the small intestine.

So, if we find in, say 1985, that from various foods 4-amino-acids-long peptides may get absorbed, and longer peptides will not,
science has to adhere to that no matter what other studies demonstrate?
This happens a lot in science: we think that something is true,
but later on (or even before), with more sophisticated techniques and methods, or just different, it appears that its a little different after all.
That is science.
Science is constantly evolving.
What may seem true in 1985, may look very different in 2014.
And will probably yet again be somewhat different in 2020.
Thats not strange.
That makes a lot of sense.

That also applies to the Wai diet.
Originally, we were making protein recommendations based on amino acid requirements established by various institutes and scientists.
Then several studies stimulated the WHO to radically change (from 1985 to 2002) the amino acid requirements,
and thus our recommendations.
Another example is the wealth of new information about autophagy, which radically changed our view on fasting and meal frequency.

Also, let us not forget what is the main reason that gluten opioids get absorbed.
That main reason is that wheat opioids are resistant to the intestinal proteinases trypsin and
chymotrypsin.
So, if you do experiments with 'normal' dietary proteins, you will find that virtually no peptides longer than 4 amino acids get absorbed,
for the simple reason that dietary protein 'normally' gets cleaved in free amino acids and very short (mainly di- and tri-) peptides.
Except for wheat (and milk-derived) opioid peptides.
On top of that, milk contains substances that increase intestinal permeability (lactose, substance P) to maximize uptake of milk-opioids (and nutrients) by the suckling.
Which may also favour the absorption of wheat-opioids when you have a glass of milk with your sandwich.

[Ducky]

3. They are relatively resistant to intestinal proteases

Where did you see that?

Because I found the contrary:

Natural opioid peptides are rapidly degraded
in vivo by several peptidases, such as aminopeptidases, dipeptidyl
peptidase III and IV (DPP III, DPP IV), etc. DPP IV is a
non-classical serine protease which appears to be a major
physiological regulator [30] for some neuropeptides,
regulatory peptides, circulating hormones and chemokines
[31].

Peptidases are
present in the serum, on capillary endothelial cells, and on
the different organs. The presence of several peptidases in
the blood-brain barrier can also constitute a metabolic barrier
for opioid peptides [32].

http://www.science.smith.edu/department ... relief.pdf

[Aytundra]

Peptidases are
present in the serum, on capillary endothelial cells, and on
the different organs. The presence of several peptidases in
the blood-brain barrier can also constitute a metabolic barrier
for opioid peptides [32].

http://www.science.smith.edu/department ... relief.pdf

"[32]" means that Gentilucci, Luca et, al. referenced another paper:
[32] Brownson, E. A.; Abbruscato, T. J.; Gillespie, T. J.; Hruby, V. J.;
Davis, T. P. Effect of peptidases at the blood brain barrier on the
permeability of enkephalin. J. Pharm. Exp. Ther. 1994, 270, 675-
680.http://jpet.aspetjournals.org/content/270/2/675.short

Quote 1: The in vitro BBB model consisted of confluent monolayers of bovine brain microvessel endothelial cells (BMECs). Enkephalin metabolizing enzymes, total aminopeptidase, aminopeptidase M (APM), angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) activities were measured in BMEC monolayers.Brownson EA et al

@Ducky,
Thank you for highlighting this article, I learned something about bovines.
Browson, E.A. et al., used a cow's brain (bovine = cow): "bovine brain microvessel endothelial cells (BMECs)" .
I am not surprised that a cow's brain has peptidases to stop opioid peptides.
Do you have any articles on human BBB and human peptidase?

-----------
Aytundra's thoughts:
Evolutionally speaking,
If a cow's brain contains peptidases, then should it not be logical that these peptidases are present to prevent opioid peptides?
I imagine, to prevent opioid peptides ingested from milk perhaps.
Indirectly this means, that peptides may make it through the intestinal layers of cows.
Why else would there be a production of peptidases on the brains of cows?
It is probably extra work for the cow's body to make enzyme structures, why make peptidases?

Do humans have peptidases on their human brain microvessel endothelial cells?
Is there a population of humans that have peptidases to reduce opioid peptides ingested?
Have humans evolved to have peptidases on their brains?
Or are there populations that have not caught up, like lactose tolerant vs. lactose intolerant population.
Where lactose tolerant populations are more prevelant in human populations that have evolved on dairy farming.

[RRM]

3. They are relatively resistant to intestinal proteases

Where did you see that?

I had already posted that study 2 times. Here is number 3.
Its about the resistance of exorphins (from wheat and milk) to the intestinal peptidases trypsin and chymotrypsin,
and about some of it ending up in the brain (indirect evidence). Zioudrou C et al

Regarding bovine versus human:
Of course the body contains various peptidases to degrade endogenous opioid peptides and there analogues.
That is because the body also produces these peptides.
Everything in our body has checks and balances.
There are circumstances where the body needs to be able to eliminate pain, to enable fleeing for danger when wounded, for example.
These peptidases must prevent those peptides from continueing to float around in the blood endlessly.

Does that mean that opioid peptides have no effect in our body?
No, not at all. The article that you quote does not say so. On the contrary.
It says that such endogenous opioid peptides (and their analogues) have a short-lasting, but strong effect.
When you absorb relatively much of such peptides from food, this may contribute to autism and schizophrenia.

[Ducky]

And I'm telling you for the third time that this source is an experience on animals not humans and in vitro not in vivo.
Im not sure that you can draw a conclusion from this study that the same thing is going on in the human body.
Even this study admits it.

Direct evidence that the exorphins will do so is not
yet available, although some peptides have been shown to
cross the blood-brain barrier.

There are circumstances where the body needs to be able to eliminate pain, to enable fleeing for danger when wounded, for example.
These peptidases must prevent those peptides from continueing to float around in the blood endlessly.

And why wouldnt these peptidases prevent it when those peptides come from an outside source and there is no need to flee?
So basically all you have is a theory based on some animal studies done in vitro.

[RRM]

this source is an experience on animals not humans

Thats a lame excuse.
Its about the endopeptidases trypsin and chymotrypsin, which are present in humans.

why wouldnt these peptidases prevent it when those peptides come from an outside source and there is no need to flee?

Peptidases do not prevent.
Peptidases clean up the result, which may take a while.

So basically all you have is a theory based on some animal studies done in vitro.

What we have is that wheat opioid peptides contribute to autism and schizophrenia in humans with a relative high absorption rate.
Thats is quite impressive.
We dont know how high your absorption rate is.

Are you in denial?
Is it because you like to eat wheat products too much?
Is that why you have been pondering this same question over and over again since 2008?
http://www.waitalk.com/viewtopic.php?f=20&t=1898

[Ducky]

What we have is that wheat opioid peptides contribute to autism and schizophrenia in humans with a relative high absorption rate.
Thats is quite impressive.

That is the conclusion you draw from cherry picking the studies that support your theory. There are other studies that didn't find any relationship between autism and gluten.
Shouldn't they be healed by now if its the gluten that caused their condition?
You might be right but as long its not proven by facts it stays a theory.
I think the one who is in denial here is you. Im trying to stay objective.

[RRM]

What we have is that wheat opioid peptides contribute to autism and schizophrenia in humans with a relative high absorption rate.

That is the conclusion you draw from cherry picking the studies that support your theory.

To circumvent cherry picking, meta-analyses are done.
A 2014 meta-analysis (of 12 scientific studies) found that 5 biomarkers of gluten sensitivity were found to be significantly elevated in patients with psychoses. Lachance LR et al
So, no cherry picking here.
Or did you find a meta-analysis that opposes this claim?

... wheat opioid peptides contribute to autism ... in humans with a relative high absorption rate

There are other studies that didn't find any relationship between autism and gluten.

Which studies exactly?
There are no studies that refute the quoted claim.

Wait...
Maybe you are referring to the efficacy of gluten-free/casein-free diets.
But that is about the efficacy of such a diet as a treatment for autism.
I never claimed that the Wai diet may cure autism.
Never. Not even suggested it. Or hinted.
Not on the website, not on this forum. Nowhere.
A diet without opioid peptides does not cure autism.
But that does not validate that there is no role for opioid peptides in the cause.
Are you claiming that?
That is like denying the role of cigarettes in lung cancer because lung cancer is not cured when you stop smoking.
Is that really what you are saying?

Autism does not go away just like that...
Autism is a neurodevelopmental disorder, becoming apparent in early childhood.
Thats is why we are looking at the role of opioid peptides in the cause of autism.
Autism has a strong genetic basis, and one aspect is increased intestinal permeability.Souza NC et al Shattock P et al
Autistic children have significantly higher levels of urine opioids than controls.Reichelt KL et al Free Full Text
The severity of autistic symptoms correlated with concentrations in the urine.

So, again:
Which studies exactly show that there is no such relationship between autism and gluten?

Im trying to stay objective.

Then objectively accept the results of the meta-analysis on psychosis.
And objectively accept a possible role of opioid peptides in the cause of autism.
Or show me a study that demonstrates the opposite.

[Ducky]

To circumvent cherry picking, meta-analyses are done.
A 2014 meta-analysis (of 12 scientific studies) found that 5 biomarkers of gluten sensitivity were found to be significantly elevated in patients with psychoses. Lachance LR et al
So, no cherry picking here.
Or did you find a meta-analysis that opposes this claim?

Where are those studies? I want to read them in detail. You only showed me the summary.

That is like denying the role of cigarettes in lung cancer because lung cancer is not cured when you stop smoking.

No, its not the same because you werent sick before started smoking but you were already autistic when you started eating gluten.

Autism does not go away just like that...
Autism is a neurodevelopmental disorder, becoming apparent in early childhood.
Thats is why we are looking at the role of opioid peptides in the cause of autism.
Autism has a strong genetic basis, and one aspect is increased intestinal permeability.Souza NC et al Shattock P et al
Autistic children have significantly higher levels of urine opioids than controls.Reichelt KL et al Free Full Text
The severity of autistic symptoms correlated with concentrations in the urine.

And as I said Im not interested discussing the effect of gluten on sick people I'm interested about its effects on healthy persons.
So please stop bringing it up all the time because its another issue altogether. Its a redherring and just make things even more complicated.

So, again:
Which studies exactly show that there is no such relationship between autism and gluten?

You can google it there are a lot of links that says that there is no direct evidence that it works.
Unless you wanna believe in a world wide conspiracy that wants to hide the results. That would be ridiculous.
http://www.parents.com/toddlers-prescho ... tism-diet/

Then objectively accept the results of the meta-analysis on psychosis.
And objectively accept a possible role of opioid peptides in the cause of autism.

I accept objective studies done on human beings that works every time.
Look up drug development, what you do is equivalent to skipping the stage of the clinical trials and releasing drugs directly to the market after pre-clinical research.
http://en.wikipedia.org/wiki/Drug_development

Or show me a study that demonstrates the opposite.

You are the one making the claims its for you to demonstrate.

[RRM]

You only showed me the summary.

Then also show me only the summary of a meta-analysis that claims the opposite.
Then you match my evidence.

you were already autistic when you started eating gluten.

Actually, they (and we) were exposed to opioid peptides from the moment of conception.

Im not interested discussing the effect of gluten on sick people

You should be.
It is as interesting as discussing the effects of cigarettes on people with lung cancer.
Its revealing.

Sure, people may remain healthy smoking 2 packs a day,
which is due to individual differences in (detoxifying and activating) enzyme activity.
Healthy people are apparently less susceptible.
Heavy smokers may have clean lungs and no cancer.
So, if you study only healthy people, smoking cigarettes may seem not harmful.
The same is true regarding autism.
If you study only healthy people, you may not find any clues at all.
Studying people with autism shows us that susceptibility to opioid peptides has something to do with intestinal permeability.
Intestinal permeability is variable.
There are many, many people with intestinal issues, who are not autistic,
and their intestinal permeability may be affected.

its another issue altogether.

They are not reptiles.
They are humans, like you and me.
Science studies sick people to learn.
Studying people with cancer has learned us about how cancer is caused.
How healthy people eventually may get sick.
Studying only healthy people, you may not learn much about cancer.
If you study only healthy people, you can claim that cigarettes are not harmful.

there are a lot of links that says that there is no direct evidence that it works.

That "it works"?
You mean a gluten-free / casein-free diet?
I was not talking about that.
I am not claiming that the Wai diet, or any other diet may cure autism. Not at all.
If you have lungcancer, you will not get cured when you stop smoking.
I am talking about the cause, not a treatment or cure.
Please show me scientific studies that claim that there is no causal association between opioid peptides and autism.

... wheat opioid peptides contribute to autism ... in humans with a relative high absorption rate

There are other studies that didn't find any relationship between autism and gluten.

Which studies exactly?

You are the one making the claims its for you to demonstrate.

Actually, its you who is making a claim here.
You claimed: "There are other studies that didn't find any relationship between autism and gluten".
That is a claim.
So, please back up your claim.
And remember, this is not about the efficacy of treatments. (such as a gluten-free / casein-free diets).
This is about the causal relationship.
Not treatments.