ON GLUTEN FREE AND
CASEIN FREE DIET IN AUTISM
AND THE OPIOIDS
EXCESS THEORY: ANOTHER PERSPECTIVE
Renato COCCHI, a neurologist and a
medical psychologist
Abstract
An extensive review of gluten free
and casein free diet in autism, as outlined in Reichelt writings, was carried
out. Given that such a diet works in some autistics, the opioids excess theory,
as an explanation of this fact, has been found rather debatable. Opioids excess
seems closely linked to the stress of the illness itself, being not a primary
but a secondary phenomenon, as for importance and occurring time. As causal
factor, opioids excess appears poorly related to most symptoms in autism.
Moreover, gluten and casein free diet's results accord better to this opinion.
The role of gluten and casein in autism could be related to very large amounts
of glutamate these two food components possess.
Key words: Gluten; casein; diet;
autism; opiates; stress, glutamate; glutamine; GABA.
There is a growing interest on
gluten free and casein free (G/F & C/F) diet among parents of people
affected by various chronic psychiatric disorders. This kind of therapy sets
itself into the field of "natural" therapies, which is a strong
current trend in health care of western countries.
Mainly children with autism seem to have
some benefits by using that diet, and this is an unexpected coming out when
other therapies do not reach but slight results. In particular the discussion
groups "celiac@sjuvm.stjohns.edu" e
"autism@sjuvm.stjohns.edu" have become what sociologists call the
tam-tam way to spread news, among celiac people or parents of autistic
children. One partecipant to this discussion groups is Kalle Reichelt, a
Norwegian pediatrician who is today the major advocate of the use of G/F &
C/F diet. Another one is Paul Shattock, an English pharmacologist, who says
himself as an obsessive supporter of this diet. On this topic Reichelt posted
original texts on Internet, then collected by followers that he authorized to
give them a free diffusion (Reichelt on Internet (ROI), 1995, 1996).
After about two-years-following the
autism's newsgroup (also called "list") I convinced myself that this
diet works, because of my long experience in treating childhood psychoses by
drugs. That is: I know the symptoms, and the possible ways by which they can
modify themselves.
But for the same reason I have many
doubts as for the explanations that support these results. This paper aims to
discuss the rationale of G/F & C/F as given by Reichelt himself and to
propose another one.
Reichelt
on gluten free and casein free diet.
It is not easy - or, at least, I did not
find easy - to give a whole information on this topic by using mainly what
Reichelt itself wrote on it.
Many are the guidelines Reichelt affords
in the same time, by merging information coming from several fields, often
interconnected by analogy. My attempt had the aim to arrange a tidy statement
of his assertions, with the references he quoted. I hope I could make it and
did not miss any important point.
Gluten and celiac disorder.
"There are at least two types of
intolerance. Celiac disease is one where certain peptides from gliadin and
gluten are toxic to the gut mucousa due to lack of breakdown. Usually these
people have certain major histocompatability
genes or surface molecules on cells that
bind peptides." (ROI, 1995)
"Also intact proteins are taken up
from the gut postprandially [after meals] (Husby et al., 1985)."
" ... everybody takes up bioactive
peptides and also trace amounts of protein from the gut (Gardner 1994)"
(ROI, 1995).
"When some other people eat this
gluten, the little, finger-like villi (that stick up from the inner walls of
the small intestine, and wave around, and absorb food) get severely flattened and
damaged and therefore cannot absorb food normally. It is not well understood
how exactly the gluten causes the damage.
People with that particular type of
reaction to gluten are diagnosed as having something called celiac syndrome. A
malabsorption of food with symptoms of diarrhea and fatty stools, and failure
to thrive and grow at normal rates are often the symptoms first noticed in
children with celiac syndrome.
Fairly often doctors miss the diagnosis.
When successfully diagnosed, people with celiac syndrome are advised to
eliminate all gluten and dairy [because casein acts like gluten] from their
diets and when they do so, it is usually the case that the villi in their small
intestine recover and their digestion normalizes." (ROI, 1995)
"They show IgA often IgG antibodies
to gluten and gliadin as well as endomysium antibodies ( Wieser et al., 1984;
Cornell, 1988). IgA and endomysium bodies together may make biopsies
superfluous, but as of today, biopsies are probably necessary." (ROI,
1995).
Actually the only serum test used to
diagnose celiac disease is the endomysial test that detects antibodies to
endomysium. That test is calibrated for about 3-5% false negatives.
"Classic works on autistic symptoms
in celiac disease have been published ( Asperger, 1961) and also on depression
( Hallert et al., 1982). But of course not in all (is there ever something that
applies to all?)" (ROI, 1995)
"Furthermore a series of
neurological conditions have been related to gluten intolerance. Thus
spinocerebellar degeneration, neurological symptoms, cerebellar syndromes and
degeneration of the CNS have all been implicated (Ward et al., 1985; Cooke et
al., 1966; Finelli et al., 1980; Kinney et al., 1982). Gluten provocation in
young children with celiac disease can cause long lasting EEG changes in spite
of normal vitamin levels (Paul et al., 1985). In adults gluten intolerance,
occipital calcifications and a parietal epilepsy have been found (Gobbi et al.,
1992)." (ROI, 1995).
"It is worthy to pay
"attention to the fact that the celiac inducing peptide isolated from
gliadin (Wieser H et al, 1984) contains the gliadinomorphin sequence
Y-P-Q-P-Q-P-F." (ROI, 1995)
"The only certainly established
peptide problem so far is gliadin, gluten and casein. However, people can be
allergic (IgE mediated) to almost anything." (ROI, 1995)
Opioid peptides.
"The other type of intolerance is
due to psychoactive peptides formed in the gut such as exorphins, opioids [ie.
opioid peptides] formed in the gut. Especially important are casein, gliadin
and gluten." (ROI, 1995)
" ... gluten contains at least 15
opioid sequences per molecule (Fukudome and Yoshikawa (1991) It is therefore
clear that one molecule could theoretically give 15 opioids. This means that
trace amount of peptide could quickly become very important." (ROI, 1995)
"Although little (2-5 nanomles per
ml blood) insufficient break-down may end in peptide build up over time with
psychoactive effects. It is easy to see that this may develop into a problem if
the breakdown is insufficient or inhibited." (ROI, 1995)
"Usually peptide increased in the
urine. Peptiduria is of course a sign of hyperpeptidaemia. We do not really
need increased uptake to get into trouble although that would accelerate the
process and if sufficiently large it could overwhelm even normal breakdown
capacity.
All we need is a decreased breakdown,
something that regularly causes peptiduria and peptidaemia (Wright et al.,
1979; Blau et al., 1980; Lunde et al., 1982; Abassi et al., 1992; Watanabe et
al., 1993.)" (ROI, 1995)
Proteins, opioids and mothers milk.
"Peptides are in general very good
peptidase (break down enzyme) inhibitors (La Bella et al., 1985) and this means
that as peptides accumulate increasing nonspecific peptidase inhibition may
cause a vicious circle." (ROI, 1996)
This process may even start before [??;
perhaps better: soon after] birth because intact antigens have been found in
mothers milk too." (ROI, 1995).
" ... there is gut to blood to
mother milk transport of intact food proteins is illustrated by papers where
intact antigens were found in mothers milk (Axellson et al., 1986; Kilshaw and
Cant, 1984; Troncone et al., 1987; Stuart et al., 1984)" (ROI, 1995).
"Because we have isolated bovine
casomorphin 1-8 immunoreactive peptides from the urine and dialysis fluid of
schizophrenics and autistics (eg Reichelt et al., 1991) and also find an
increased frequency of IgA antibodies higher than the upper normal limit
(Reichelt et al., 1994; Reichelt and Landmark, 1994), there is reason to
believe that opioids from the diet are important. The mucosa is normal in these
cases as are endomysium antibodies." (ROI, 1995)
Exogenous opioids and autism.
"Already Asperger, 1961, in Austria
noticed that many (not all) celiac children showed psychiatric problems A similar
relationship of malabsorption to autism was also suggested in the USA (Coleman
1976)".(ROI, 1995).
In 1991 Reichelt et al. suggested that
increased levels of a group of urinary peptidases in autistic syndromes
indicate that genetic disposition could be a defect of peptidases. The quantity
of peptides excreted and the effect of diet pointed to casein and gluten as
possible etiological factors.
"Opioids may very well be important
to the development of autism because they modulate trophically CNS development
(Zagon and McLaughlin 1987; Zagon and McLaughlin 1989)". (ROI, 1995)
There is "a paper which highlights
exactly autism and large stools [as it happens in celiac disease]"
Shattock, 1988)" (ROI, 1995)
"Because gluten can cause
neurological problems it is not strange at all that it may also give
behavioural problems. The opposite would be improbable. We believe (Reichelt et
al., 1994) that the mediators of these problems are peptides and specifically
exorphins that do have inhibition of nerve development as one of their effects
(Zagon and McLaughlin, 1987).(ROI, 1995)
"We and others have isolated bovine
casomorphin from urines and dialysis fluid of autistic patients. About 1/4 of these
children have IgA antibodies against gliadin, gluten and or casein higher than
the upper normal limit but without celiac disease. Furthermore we do not claim
that this pertains to all but to some, probably many." (ROI, 1996).
Gluten free and casein free diet in autistic people.
"The effect of food proteins are
also manifest from our data on diet and autism (Reichelt et al., 1994)."
(ROI, 1995)
"In autistic children we have very
good results as documented with strict diet (Knivsberg et al (1990) and also
Reichelt et al (1991)."(ROI, 1995)
"Double blind on autistic children
is very hard to do. Howver, we have run the urines blind and applied the
strategy of two independent persons to carry out functional tests and
evaluation. The results cannot possibly be placebo because they last for 4
years and those that quit diet show regression. In spite of ordaining longer
time to complete the tests the children off diet could not complete tests
easily finished when on diet ( Kvinsberg et al., 1990; Reichelt et al., 1990;
Reichelt et al., 1994)." (ROI, 1995).
"For autistic children and
schizophrenics it is best to stick with gluten, gliadin and casein, because
that is what we have studied. After all we all need proteins of some sort to
develop normally and it is important to warn against overenthusiastic slashing
of this and that in an arbitrary way. Growth is a good variable to monitor
adequate nutrition."(ROI, 1995)
An open trial of G/F and C/F diet was
applied to 15 Ss (aged 6-22 years) with autistic syndromes and pathological
urine patterns with increased peptide levels. After 4 years normalisation of
urine patterns was found, and a decrease in odd behaviour and improvement in
the use of social, cognitive, and communicative skills were registered
(Kvinsberg et al., 1995).
"The effect of diet takes a long
time because the kidneys are very well adapted to preserve peptides and
proteins. We found that it took 28 weeks of strict diet to normalize the
urinary excretion of peptides in a double blind study of diet followed with
urine analysis and rating scales (Reichelt et al, 1990)" (ROI, 1995)
"Diet is however, not easy and may
be experienced as a socially isolating procedure [ Sponheim 1991]. It must also
be strict. Finally the opioids make it difficult to quit the food in question
as in all addictive states."(ROI, 1995)
"The problem is usually that diet
is tried as a last resort, and because there are strong indications that
opioids inhibit the normal maturation of the CNS (Zagon and Mclaughlin
(1987)." (ROI, 1995)
"Therefore a strict diet (gluten
and milk protein free) ameliorates but does not completely solve the problem of
opioid break down." (ROI, 1966)
"When you quit an opioid source you
will after a few days have abstinence problems. (Getting worse). The reason for
this is that because of increased sti-
mulation the number and sensitivity of
the receptors decreases. When the stimulus is removed the receptors will
inversely increase in numbers and sensitivity.
Therefore it takes time to reach a new
equilibrium. Usually about 3-8 weeks.
Therefore you have to be patient."
(ROI, 1966)
"Removal of casein and gluten
effects are very individual, and I suspect (do not know) if there are treshold
effects.
There are four probable variables: 1:
Uptake of proteins and peptides from the gut; 2: Rate of break down; 3:
Transport through the blood-brain barrier. 4: The receptor sensitivity on
target neurones and cells." (ROI, 1966)
Opioid peptides and other mental
troubles.
Schizophrenia:
As for gluten and schizophrenia, Reichelt
wrote: "Epidemiology: I would like to draw your attention to two papers
that are extremely well done: Lorenz and Lee (1977) and Lorenz (1990)."
(ROI, 1995)
"Clear-cut effect of diet in
schizophrenia was found by Dohan and Grasberger (1973); Singh and Kay (1976);
Cade et al. (1990) (he uses our urine screening too)." (ROI, 1995).
"We found that it took 28 weeks of
strict diet to normalize the urinary excretion of peptides in a double blind
study of diet followed with urine analysis and rating scales (Reichelt et al.,
1990)." (ROI, 1995).
" ... we have (Reichelt and
Landmark, 1994) found IgA antibody increases in schizophrenics diagnosed after
DSM-III and sex and age matched controls. These IgA antibodies were mainly
against gliadin, gluten, lactoglobulin and casein." (ROI, 1995).
"I would like to draw your
attention to a wee paper from us (Reichelt et al., 1990) on diet and
schizophrenia, where we followed completely blind 10 semichronic (not the best
starting point) male schizophrenics for one year.
We could conclude: a. That both urinary
peptide excretion and rating scales (Comprehensive Psychopathological Rating
Scale and Whitaker Index of Schizophrenic Thinking) as well as clinical state
improved slowly on diet, with regression in those off. This was a crossover
study. b.It is not unreasonable that changes will be slow because the kidneys
are efficient peptide, amino acid and protein preserving organs." (ROI,
1995)
"We have recently been able to
demonstrate the presence of at least 5 (five) peptides with opioid activity in
urines and dialysis fluid from schizophrenics, which react to antibodies
against bovine casomorphin 1-8. One of these co-chromatographs has the same
amino acid composition as bovine casomorphin 1-8. (Reichelt submitted).
NB: The biopsies were normal so that
this is not celiac disease, but a state with increased transmucosal
protein/peptide transport." (ROI, 1995)
Post-partum psychosis.
"In post-partum psychosis, which is
one of the most vivid psychotic conditions known, the Swedes have shown that
human casomorphin is the mediator and accumulates in blood, spinal fluid and
urine (Lindstrom et al., 1984). Human casomorphin is present as a family of
peptides and has the structure Y-P-F-V-E-P-I-P and exists as 1-8,1-7,1-6 etc.
It has long been known that stopping
milk production fast (before receptor changes take place) alleviates the
psychotic condition." (ROI, 1995).
Hyperkinesia
" ... we have found peptide
increases (possibly phosphorylated/glycosylated?) in hyperkinesia (Hole et al.,
1988.) (ROI, 1995).
"It should also be noted that
concentrated glucose can increase the paracellular uptake in the gut. That is
also more proteins and peptides can be taken up (Pappenheimer and Madara
1993)." (ROI, 1995).
"The intestinal permeability can be
increased through the paracellular route by hyperosmotic solutions (Madara and
Pappenheimer, 1987; Madara, 1988; Travis and Menzies, 1992) such as
concentrated sweets etc. would be. This would increase proteins and peptides
uptake as reviewed by Gardner, 1994. So you see there are definitely
possibilities related to a concentrated carbohydrate intake especially if
hyperosmotic." (ROI, 1995)
Down's syndrome
"It is extremely relevant that we find
very high IgA antibodies against food proteins in Downs syndrome (Reichelt et
al. 1994)." (ROI, 1995)
"Many Downs syndrome children have
very high levels of IgA and also IgG antibodies to food proteins (Kanavin et
al., 1988; Reichelt et al., 1994) even if most of these do not have endomysium
antibodies and a normal gut lining. We have interpreted this as indicating
increased gut permeability but in most cases not a celiac condition.
There is an inverse relationship between
the size of the children and the level of these antibodies (Kanavin et al.,
1988). It also is very relevant that Shattock found peptide increases in the
urine of such patients (Shattock et al., 1990)." (ROI, 1995)
Depression.
In reply to a quotation of a paper
(Saelid et al., 1985) that shows a variation in urinary peptides in psychotic
depression, Reichelt wrote: "Depression causes an increase in pain
sensitivity. Endorphins are what your body uses to regulate pain. It would be
more surprising if people with depression didn't produce more of them."
(ROI, 1996).
Although Saelid et al., 1985 have
reported what appear to be the same peptides in the urine of depressed people,
in greater quantity than normal, Rechelt explains:
"They are not *causatively*
involved; drugs affecting the opiate-receptor system have been around for
decades and none of them has any effect on
depression, except as a means of
temporary escape. Drugs affecting dopamine, serotonin and noradrenalin do have
such effects.
(And if there were any way of making an
endorphin-related drug for depression that actually worked, you can bet the
drug industry would be selling it. It's 11 years since that paper; where's the
product? Retrovirus replication inhibitor drugs came from nowhere to a nice
little earner in half that time)." (ROI, 1996)
Saelid et al., 1985 asserted that these
peptides could not have any clear link to diet. In fact, they seemed to believe
that the peptides were endogenous, and a peptidase insufficiency was at the
root of the problem.
Reichelt strongly rejected the
contribution of exogenous peptides.
"The obvious reason why not, is
that removing such peptides from the diet has absolutely zero effect on the
great majority of cases of depression. (It is more likely to work in schizophrenia, but still only in a minority
of instances)." (ROI, 1996)
Discussion
Dr Reichelt is an eminent researcher,
but I have some doubts on the primary role of gluten and casein in PDD. I
believe that gluten and casein can exacerbate some psychotic symptoms, and
their cut off from the diet can reduce these symptoms. The reasons justifying
my doubts come out from different places.
First, I am an inhabitant of a country
where the national foods are bread and pasta, both made with a gluten rich
wheat flour. My work on drug therapies in psychotic Down and non-Down children
started 14 years ago. Till now I did not have any notice that the rate of
Italian psychotic children is different from 4-6/10000 usually found in other
countries.
One may argument that there should be
less gluten intolerance in Italy because of a natural selection. The people
with a genotype to produce gluten intolerance could have been largely put out
from the population because the Italians have been eating wheat for centuries.
I can hardly agree with this objection. Part
of Italians is largely eating wheat products since about one century only (I
think only since the first decade of our century). In Southern Italy people
always consumed bread on a daily base but the same did not happen in the whole
country.
Most of them were very poor and the main
food in northern and middle Italy was the Polenta (An Indian corn pudding),
with epidemic diffusion of Pellagra (Jacini 1878-84). The Darwinian natural
selection does not work so quickly.
Although I have been consulted for autistic
children coming from all Italian regions, I did not notice any difference in
rates of autistic prevalence between North-central and Southern Italy.
If we would maintain the opinion of a
favourable genetic selection among Italians, we have to assume the same also
for casein in many other countries of Europe.
Since centuries European peoples surely
consumed dairy casein on a daily base because milk was a very accessible
product also by the poorer. We come from a long lasting agricultural society
where milk and derivatives were easy to find and low price products, often in
home products.
Sheep and cows were eating grass that
grows also without being cultivated. Somewhat different is the case of wheat or
corn or oats, all too rare as spontaneous products. They need cultivation to
have enough amounts to feed people.
Second, as I said previously, I am
working on drug therapies in psychotic Down and non-Down children since 14
years. (Cocchi 1990-1996).
My experience in drug therapies in
autistic children went on without considering the opioids' problem, save a
trial on naltrexone, already published (Cocchi, 1991).
Always the parents reported some
improvements at first check-up, soon after three-months drug therapy (see, for
a detailed case: Cocchi 1995; 1996a; 1996b).
On the other hand I have a large
experience in Downs, even psychotic Downs, and until now - 31th of October 1996
- I have seen 537 of them. As for food habits I made special research in Downs
non-treated and treated by drugs (Cocchi 1994, 1995).
I was very attentive to defecating
habits, before and after drug therapies. On this topic I recently got out a
paper on toilet habits in 492 Down children (Cocchi, 1996), where I reported
only one case of celiac syndrome. I collected as well toilet habits in autistic
children, I did not count the reports but they hardly agree with celiac
syndrome as the primary cause.
Third, Reichelt pointed up on exorphins
produced by gluten and/or casein malabsorbption. Now it is not clear if this
pathological action of gluten and casein malabsorption works as a primary
mechanism, or a secondary one. In this latter case, there are many steps before
the body produces endogenous opiates and increases its sensitivity to very
small doses of exogenous opiates (exorphins).
Now, being the counterpart of
endorphins, exorphins belong to a class of opiates that act throughout opiates'
mu and delta receptors in the brain. So, we can block these opiates' receptors
by naloxone and naltrexone.
The naltrexone trials in autistic
children - I refer also to myself (Cocchi, 1991) - had very controversial
results, if not at all. So, I cannot agree with a prominent role of exorphins,
because if so, we have had more favourable results using naltrexone.
Of course, this one is not an isolated
assertion. Alexander (1996), in a recent survey on drug therapies on autism,
adding to them her own trial, referred inconsistent results of naltrexone even
on self-abuse.
This fact suggests two hypotheses: 1.
Gluten and casein opioids are not exorphins and do not work throughout these
receptors, but throughout other receptors. Are they kappa receptors for
dynorphins-like opioids? 2. Gluten and casein produce another active byproducts
and the opioids' uptake from gut has not such significant effect in autistic
children.
Forth, I do not have any doubts about
the presence of gluten and casein peptides in the urine of autistic children.
So I never denied the possibility of finding in these children more exogenous
opioids from gluten and/or casein. On the other hand I never said that gluten
or casein free diets are without usefulness. I precisely think the opposite.
The presence of gluten and casein
opioids in the urines of some psychotic children means only that gluten and
casein increase opioids as their by-products. Very little we can infer about
the pathological relevance of these opioids upon autistic symptoms, and only by
analogy or indirect way. What I am maintaining is that opioids' excess could be
a secondary phenomenon and not a primary one.
In other terms: I think the opioids'
excess does not produce the autism but in some autistics, by a cascade
reaction, there is also an opioids' excess, when they have dietary gluten and
casein.
Of course, it is possible that the
opioids' excess, in its turn, causes some peculiar symptoms, but we lack
evidence of it, save perhaps increased analgesia.
If so, we can interpret this excess in
two different ways. 1. We could view the excess transformation of gluten and
casein into exorphins as only a derouting malfunction of the small intestin
(malabsorption, according to Reichelt).
I do not very much believe in it,
because nature goes on according to the minimal effort rule, also said the
economy criterion. Nevertheless it is a secondary phenomenon and not a primary
one, being this latter the malabsorption.
2. The opiates' increase in urine too
could also stay for an antipain mechanism to protect the body against the pain
induced by excitatory aminoacids like the glutamate. Here too, it is a
secondary phenomenon.
Fifth, the extension of opioids' excess
mechanism to other psychiatric troubles is surely a valuable idea, but I have
two points to discuss.
Where it has been found, the datum of
opioids increasing rates into urines cannot be without any meaning. I was
unable to check it in the post-partum psychosis too, but I should wonder if
not. This increase has been found out in depression but there are doubts that
this opioids' excess comes from diet, namely from gluten and casein.
Although attributing it to an excess of
endogenous opiates, Reichelt asserts it as due to an antipain reaction of the
depressed body. He rejects any "causative" result of this excess
incretion of opiates because drugs affecting dopamine, serotonin and
noradrenalin do have therapeutic effects on depression. The same did not prove
to be true for drugs acting upon opiates. It is a curious fact that endogenous
opiates in the post-partum psychosis are highly pathological, but not
endogenous opiates in depression.
The second point I should have to
discuss is the pathological relevance of endogenous opiates in Down's syndrome.
As I early wrote, I am working on drug
therapies in Downs since nearly 18 years. These therapies act modulating stress
reactions and correcting possible neurochemical imbalances directly linked to
the "dosage effect" of the third functioning chromosome 21. (Cocchi,
1993).
Although in Downs too I did not consider
opiates and diet modification, the parents reported improvements after 3-6
months of therapy in most people (Cocchi 1987; 1989; 1990d; 1990e; 1991g; 1992;
Cocchi and Favuto 1993; 1995; Lamma and Cocchi, 1988). There is also a
mitigation of the so-called typical mongoloid face (Cocchi, 1985a; 1985b;
1986).
These results could hardly have a link
with either endogenous or exogenous opioids, as causal agents of some symptoms
in Down's syndrome. Moreover because no one drug I use specifically acts on
opiatesThis fact appears like what happens in drug therapies of depression.
.Eventually there is also another
opposite finding: Children so treated eat even more bread and pasta, two foods
very rich in wheat flour gluten (Cocchi 1995c).
How
gluten and casein free diet works: A more complex perspective.
Said that G/F & C/F diet works - and
I have no doubts on it - since I refuse the opioids' excess theory I shall try
to see about a different explanation. To build it, I think we shall refer to
stress and antipain mechanisms.
Although I do not fully agree with it,
this is the more recent definition of stress. " .... it generally refers
to physical or psychological alterations capable of disrupting
homeostasis." (Cullinan et al., 1995).
Homeostasis seems to me the key point,
from where we have to start. Any type of external stressors can disrupt it as
everybody knows, but also internal stressors, as most researchers often forget.
The more frequent internal stressor (except the cyclic fall of progesteron in
fertile women) is an illness, which also produces stress. The extent of this
stress depends on 1. The type of illness itself; 2. The course of the illness
itself; 3. The ability to react to stress of that particular body in that
moment of its biological cycle.
This means that every illness, besides
its peculiar symptoms, could also have stress symptoms, and in many cases we
need to treat these ones as well.
As for autism and Down's syndrome I am
working according to this perspective already clearly specified (Cocchi 1990b,
Cocchi 1993a, Cocchi 1996c). The same I did for pseudodementia (Cocchi, 1996d).
At that point we could review our data,
and redirect the opioids' excess theory to a different target. By modifying
homeostasis, the excess of opioids coming from malabsorption of gluten and
casein in the gut increases a state of stress, already described in this
syndrome (Cocchi 1990b; 1995b; 1996b).
In other words, we could have two lines
of symptoms from opioids' excess. The first line, directly related to opioids
function, could be the increase of analgesia. "One common theme of these
opioid systems is mediation of stress responsiveness. Not surprisingly, the
most intensively studied of the opioid mechanisms influenced by stress is pain
modulation" (Stout, Kilts and Nemeroff, 1995). Reichelt clearly knows this
fact as for depression, but neglects it in autism, where hyperanalgesia is a
fairly common phenomenon.
The second line of symptoms, coming from
an indirect stressor action of the opioids excess, could be an increase of the
current symptoms of stress. Due to a threshold effect, the excess of opioids
could also induce other stress symptoms, to be added to the primary symptoms of
stress of the illness itself.
So we can understand why the opiate
antagonist naltrexone does not work very well in autism, but also why G/F &
C/F diet does not work in every autistic child. When G/F & C/F diet works,
the fact it needs so much time to show its results seems a signal that the diet
acts throughout an indirect mechanism.
Perhaps gluten and casein have other
biological effects on the body of some autistic children.
In a state of stress the reverse pathway
GABA-glutamate is always involved. So because type A receptors of GABA modify
their conformation, by reduction of GABA binding sites and increasing of
benzodiazepine binding sites in the cortex (Horger and Roth, 1995). By feedback
mechanisms there could be a larger availability of brain glutamate, being a
share of it no longer transformed into GABA. Surely stress induces an increase
in extracellular levels of glutamate and aspartate as a common result of stress-induced
experimental procedures showed (Horger and Roth, 1995). Following this
imbalance, where type A GABAergic inhibition is declining and excito-toxic
effects of glutamate and aspartate are growing, gluten and casein bring more
glutamate.
Wheat gliadin (a prolamine occurring in
gluten) comprises of 18 amino acids of which 40% is glutamic acid; casein is
23% glutamic acid (Braverman and Pfeiffer, 1987.)
So gluten and casein in diet can act: i.
As producers of exogenous opiates by gut malabsorption; ii. As suppliers of
glutamate where an existing excito-aminoacids' excess is a nearly sure
condition due to the stress of the illness itself. The pathological increasing
of exogenous opiates, in its turn, seems responsible of both directly
opiatergic symptoms and a share of stress due to opioids excess, by
modification of homeostasis. More stress means more excito-toxic amino acids
and more endogenous opiates.
Gluten free and casein free diet can
partly correct this highly vicious circle in autistic subjects who have more
difficulties in fighting against it.
Conclusion
This in-extent review of opioids excess
theory in autism and Reichelt's research ends in some new opinions. Being
accepted that gluten and casein free diet works in some autistics, the role of
opioids excess as a causal factor of some forms of autism is rather debatable.
Opioids excess seems closely linked to stress, and not a primary but a
secondary phenomenon, as for importance and occurring time. On the other hand,
gluten and casein free diet results accord better to this opinion. However, the
pioneering approach of Reichelt is worthy of appreciation. This is true not
only from parents too longer left at the mercy of inconsistent psychological
explanations throwing the blame on the parents themselves. Who quickly defines
his research as "junk science" does not remember that
acetylsalicilate worked as well for about 80 years before we have discovered
why. We need to keep away from any form of scientism. Before the artificial
satellites' era, astronomy was not an experimental science, but surely not a
"junk science".
Aknowledgements
Many special thanks to listmates Tammy Glaser <tamglsr@sgi.net> and
Don Wiss <donwiss@bondcalc.com>, Cristina Destradi, of the Servizio di
Documentazione Scientifica, GlaxoWellcome, Verona for their valuable help in
collecting Reichelt's writings and references, and to all others whose opinions
led me to a better understending of gluten free and casein free diet's
perspective.
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Author's address:
Renato
COCCHI MD, Via Rabbeno, 3
42100 Reggio Emilia
(Italy)
renatococchi@libero.it