Having recently discovered that an anti-histamine
drug like Claritin can markedly reduce autistic behaviours, I have been looking
into exactly why this might be and to see if there could be any other related
interventions. Here are the results and they pull together
all sorts of related comorbidities and in the end I seem to have found a better
solution for managing summertime autism flare-ups.
What I recently noticed in Monty, aged 10 with
ASD, were some of these behavioural problems, but with only the slightest outward sign of an
allergy.
Most histamine in the body is generated in granules in mast cells or in white blood cells called basophils. Mast cells are especially numerous at sites of potential injury — the nose, mouth, and feet, internal body surfaces, and blood vessels.
It is also used by body builders. They are using another asthma drug called Clenbuterol. This drug has the side effect of reducing your body mass index (BMI), so it makes you more muscular if you take enough of it for long enough. Such use of Clenbuterol has side effects, the body builders are using Ketotifen to reduce these and allow them to use Clenbuterol for longer. The misuse of Clenbuterol affected beta-adrenergic receptor functions, for those who are curious. Ketotifen blocks this from happening.
It turns out that the H2 antagonists can reduce this degradation of the BBB, but H1 antagonists like Claritin have only a marginal effect. This is all based on research in rats.
and from way back in 1988:-
Behavioral effects of histamine and its antagonists: a review
Research studies in to the use of H1 and H2 antagonist in autism
Famotidine treatment
of children with autistic spectrum disorders: pilot research using single
subject research design. H2 receptor antagonists
Allergies have long been linked to aggressive
behaviours
It seems to be well known among allergists, that
children with allergies may exhibit challenging behaviours. It goes beyond the simple fact that the child
with an allergy will be irritable and therefore behave badly; the allergy
itself is affecting the behaviour.
Allergies tend to worsen behaviour and the science can explain exactly
why this happens. This applied to
pollen type allergies, food allergies and even asthma.
In the case of asthma, I found several studies,
one is called: Prevalence of Behavior Problems in US Children With Asthma
The study concluded with:
Clinicians caring for children with asthma and their families
should be aware of the relationship between asthma and emotional and/or behavioural
problems and anticipate that a substantial number of their patients may have
mental health services needs.
One alternative health website, gives a list of
symptoms they believe histamine allergies produce in kids with ASD.
Some different types of responses to histamine seen in ASD children: If
histamines become too high, you can see hyperactivity, compulsive behaviors,
depression, abnormal fears, intense mood swings, runny nose, itchy eyes,
sneezing, perfectionism, strong wills, explosive anger, anxiety, hair pulling,
lack of focus, scripting (repeating commercials or television programs, etc.),
high libido, giggling (which can be a sign of yeasty behaviors), aggression,
change in bowel movements, a craving for salt, frequent urination and rashes.
Those who have seasonal allergies tend to see a worsening of these symptoms
during spring time.
Food allergies causing autism-like behaviours
I was surprised to find one allergy site listing
the behavioural effects of food allergies, it reads like a long list of
autistic behaviours. This made me wonder
if many of the milder cases of autism and the so-called autism epidemic may
just be unresolved food allergies. Many
of the DAN interventions are about “healing the gut”, so maybe they are really
more about treating food allergies. Many
cases of classic autism appear to have no problem with their digestive system
at all.
Here is a list of behaviours from one site on
food allergies:
• Poor coordination
• Trouble
communicating
• Self-destructive
behavior
• Staring
• Difficulty in
group games or sports
• Obsessions
• Nonsense talk
• Inability to
read tones of voice and/or body language
The best studied/documented allergies
Asthma is the best researched allergic condition
that I found, followed by food allergies and the rare condition of
mastocystitis; this condition is rare but sufferers write extensively about it
on the internet. They also report on the
effect of different drug combinations in managing their conditions. Mastocystitis is also a comorbidity of
autism that has been researched by Theoharides, who proposes his NeuroProtek
supplement.
The result is that there has been a great deal
of research and many established drug therapies exist. The link between allergies and behaviour was
investigated in the 1980s, but there has not been much written since, which is
a pity.
Mastocystitis
The Mastocystitis Society of Canada have a good website. It defines Mastocytosis as a myeloproliferative
neoplastic (mpn) stem cell disorder, caused by an over-abundance of good immune
system cells called mast cells and the release of mast cell mediators.
What that really means is that when the mast
cells encounter an allergen they overreact and release too much histamine and
also inflammatory messenger, such as cytokines.
These chemical disperse throughout the body. The histamine activates the four types of histamine
receptors around the body. The pro
inflammatory cytokines react in a different way, but promote an excessive
inflammatory response.
To grossly simply the condition, mastocystitis
is an extreme form of allergic response.
Mastocystitis is a comorbidity of autism and the
mast cell response has been proposed to be a key part of autism. It is interesting to look at how mastocystitis
is treated. Click the link here.
Note the use of both H1 and H2 histamine
antagonists, many asthma drugs including the steroid Prednisone, and the mast
cell stabilizer Ketotifen.
Histamine & Histamine Antagonists
Histamine is a chemical in your body with three distinct functions:-
Histamine is a chemical in your body with three distinct functions:-
1.
Histamine triggers the inflammatory
response
2.
Regulates physiological function in the
gut
3.
Acts as a neurotransmitter
Most histamine in the body is generated in granules in mast cells or in white blood cells called basophils. Mast cells are especially numerous at sites of potential injury — the nose, mouth, and feet, internal body surfaces, and blood vessels.
Histamine functions in
coordination in 4 types of receptors (H1, H2, H3 and H4). In the central nervous system H1 and H3
receptors. H1 is involved in allergies
and asthma. H2 is mainly involved
invasodilation and gastric acid secretion.
H3 controls neurotransmitter release (histamine, acetylcholine,
norepinephrine,
serotonin). H4 Plays a role in chemotaxis.
Histamine antagonists are drugs that inhibit the
action of histamine by blocking specific receptors in specific parts of the
body. The most common drugs are H1
antagonists that block the H1 receptor in summertime allergies. H2 antagonists reduce gastric acid secretion
to heal peptic ulcers.
Histamine is the link between allergies and
behavioural change
Histamine in the brain has been shown to directly
influence behaviour (see later in this post for links). There is also plenty of anecdotal evidence
from allergists, as shown earlier in this post.
In addition histamine has been shown to weaken
the blood brain barrier. This would
then let into the brain pro-inflammatory agents that might then cause a spike
in neuroinflammation and oxidative stress.
This in turn leads to more challenging behaviours.
The disruption to the BBB can be best reduced by
the use of H2 antagonist. H1 antagonists have a much smaller effect. See this study, which concludes:
It is concluded that histamine
causes an increase in blood-brain barrier permeability which is mediated via
endothelial H2 receptors,
Ketotifen
Ketotifen is an H1 histamine antagonist. It is a 40 year old antihistamine drug that
is available over the counter in Europe.
Not only can it be used to treat
allergies (it is the active ingredient in many eye drops) and help
control asthma, but it has some additional benefits. It acts as a mast cell stabilizer, reducing
the amount of histamine released by the mast cells when they encounter
allergens. It is the only H1 histamine antagonist that does this. In
addition it also blocks H1 receptors like the other widely used H1
histamine antagonists.It is also used by body builders. They are using another asthma drug called Clenbuterol. This drug has the side effect of reducing your body mass index (BMI), so it makes you more muscular if you take enough of it for long enough. Such use of Clenbuterol has side effects, the body builders are using Ketotifen to reduce these and allow them to use Clenbuterol for longer. The misuse of Clenbuterol affected beta-adrenergic receptor functions, for those who are curious. Ketotifen blocks this from happening.
Celebrities, like a certain very well-known footballer’s
wife, take Clenbuterol to stay thin.
Maybe they also take Ketotifen?
Ketotifen is extremely cheap and widely
available in Europe and Canada. In the
US it is much more difficult to get hold of and so seems to have great rarity
value.
In the US, some DAN doctors give Ketotifen to
autistic children as a therapy for Gastrointestinal problems. The well-known DAN doctor, with an audio
lecture on this subject, states that Ketotifen is “mainly active in the
gut”. He obviously has not read the
research, since the opposite is actually true.
Based on my limited research, it appears that some of these kids may
just have autistic-like symptoms causes by the excess histamine in their brain.
In other words they may just have a case of food intolerance / Irritable bowel
syndrome rather than autism. That would
certainly be a relief to the parents concerned.
Other H1 Antagonists
You will know these drugs by their brand names
: Claritin, Zyrtec, Benadryl, Allegra,
Phenergan etc. There are several types of these drugs. The early examples passed into the brain and
so made people drowsy. The second
generation are the current big sellers, based on their non-drowsy effect. When you dig deeper, you will see that they
are all slightly different, and some work better than others in different
people. They also vary in which part of
the body they have the most affect.
The older types are off patent and sold cheaply
as generic over the counter drugs.
Mast
cell stabilizers and irritable bowel syndrome
It has been long known that certain drugs reduce
the allergic reaction in food intolerance.
Remarkably the same drugs are today also used to treat asthma. The expensive drug I was prescribed as child called
Intal (Cromoglicic acid)
for food intolerance, is today called a mast cell stabilizer and used in asthma therapy.
Mast cell stabilizers prevent the release of
inflammatory chemicals like histamine from mast cells.
Another insight courtesy of the Mastocystitis
Society of Canada:-
“Mast Cell Stabilizers -
Ketotifen is preferred as most effective for entire body, Cromolyn mainly targets
gastrointestinal system”
So it looks like the DAN doctors have chosen the
wrong treatment for their GI problems, they should be using Intal not
Ketotifen.
Modern second generation anti-histamines do not
enter the CNS
First generation H1 antagonist crossed the blood
brain barrier and had a sedative effect, making sufferers drowsy. As a result there was a big search made of
drugs that could relieve allergy symptoms but not make sufferers drowsy. These second generation drugs are the current
big sellers, although the first generation drugs are still widely available.
These modern drugs should therefore have less
impact on histamine driven challenging behaviours than the old ones.
Most anti-histamines block the receptor rather
reducing the amount of histamine
The popular H1 antagonist like Claritin do not
reduce the amount of histamine produced in the body, they rather block the
receptors used to detect it. The amount
of histamine flowing through your body remains the same. That histamine weakens the blood brain
barrier, allowing in things that might be better kept out.It turns out that the H2 antagonists can reduce this degradation of the BBB, but H1 antagonists like Claritin have only a marginal effect. This is all based on research in rats.
Sufferers of mastocystitis take copious amounts
of H1 antagonists and H2 antagonists plus a whole host of other drugs. H2 antagonists are old drugs like Tagamet,
that were designed to reduce acidity in your stomach for treating ulcers and
GERD. It appears that also have
unforeseen effects in your brain and elsewhere.
Histamine in the Brain
For those scientists among you, the areas to
read up on are mast cells and how histamine functions in the brain. Many of the papers on histamine in the brain
are not available without payment. Here
is a short paper that is available.
Other good ones, not available free include:
and from way back in 1988:-
Behavioral effects of histamine and its antagonists: a review
Research studies in to the use of H1 and H2 antagonist in autism
From my recently acquired insight, the H1
antagonist improved behaviour by blocking some of the unwanted response to
histamine in the brain and the H2 antagonist help restore the blood brain
barrier and keep out those unwanted pro-inflammatory agents like cytokines and perhaps
even some histamine.
Abstract
Niaprazine is a
histamine H1-receptor antagonist with marked sedative properties. It
has been employed in subjects with behavior and sleep disorders. No data
concerning the use of niaprazine in subjects with autistic disorder are
reported in the literature. The authors performed an open study to assess
niaprazine efficacy in a sample of 25 subjects with autistic disorder and
associated behavior and sleep disorders. Niaprazine was administered at 1
mg/kg/day for 60 days. A
positive effect was found in 52% of patients, particularly on hyperkinesia,
unstable attention, resistance to change and frustration, mild anxiety signs,
heteroaggressiveness, and sleep disorders. Statistical comparison
between responders and nonresponders showed no influence on niaprazine effect
by age over or under 12 years, presence of neurologic signs, epilepsy, or
abnormalities seen on brain imaging. Niaprazine was more efficacious in
subjects with a mild or moderate degree of mental retardation. No side effects
were observed. Because of its sedative effects and good tolerability,
niaprazine can be used as a first-choice drug to improve behavior and sleep
disorders in patients with autistic disorder. (J Child
Neurol 1999;14:547-550).
Abstract
Using single subject research design, we performed pilot research to
evaluate the safety and efficacy of famotidine for the treatment of children
with autistic spectrum disorders. We studied 9 Caucasian boys, 3.8-8.1 years
old, with a DSM-IV diagnosis of a pervasive developmental disorder, living with
their families, receiving no chronic medications, and without significant
gastrointestinal symptoms. The dose of oral famotidine was 2 mg/kg/day (given
in two divided doses); the maximum total daily dose was 100 mg. Using
single-subject research analysis and medication given in a randomized,
double-blind, placebo-controlled, cross-over design, 4 of 9 children randomized
(44%) had evidence of behavioral improvement. Primary efficacy was based on
data kept by primary caregivers, including a daily diary; daily visual analogue
scales of affection, reciting, or aspects of social interaction; Aberrant
Behavior Checklists (ABC, Aman); and Clinical Global Improvement scales.
Children with marked stereotypy (meaningless, repetitive behaviors) did not
respond. Our subjects did not have prominent gastrointestinal symptoms and
endoscopy was not part of our protocol; thus, we cannot exclude the possibility
that our subjects improved due to the effective treatment of asymptomatic
esophagitis. The use of famotidine for the treatment of children with autistic
spectrum disorders warrants further investigation.
Conclusion
Several important conclusions can be drawn based
on a few hours of research on Google Scholar.
·
Your child may be subject to an allergic
response that is outwardly hardly visible
·
The allergic response may be visible
first as challenging autistic-like behaviour, rather than sneezing, runny nose,
red eyes or wheezing
·
H1 antagonists can supress both the
autistic-like behaviours and the typical allergic reactions
·
People do not all react the same way to
H1 antagonist drugs. A little
experimentation is in order. A drug that
should work 24 hours can be effective for only 4 hours.
·
To avoid excessive use and possible side
effects, allergists often combine different H1 antagonists, even though the
information from the drug firm warns not to do this.
·
In some people the old H1 antagonists,
that make you drowsy, work better than the new 2nd and 3rd
generation drugs.
·
One old H1 antagonist called Ketotifen,
seems to work wonders for some people.
It is both a mast cell stabilizer and a histamine receptor blocker.
I have ended up with a combination of Ketotifen
and Claritin. Claritin has an effect on
behaviour within 20 minutes, Ketotifen had no apparent impact in the short term
whatsoever. You cannot keep giving
Claritin every 4 hours. It is supposed
to be 10ml per day.
The day after taking Ketotifen things did
change, and without having to overuse the Claritin.
The allergy is still mildly visible, but the challenging behaviours have gone.
I wish I had known about this last summer. When Monty was aged 9, he went completely
berserk on an aircraft and so as to restrain him, I was almost sitting on top of him, holding arms, legs and head;
the flight attendant was asking if he would like a glass of water. This year I will be well prepared with my
Ketotifen/Claritin combo and anticipate no such problems.
Related Post:-
More on anti-histamines in Autism and introducing H4
Related Post:-
More on anti-histamines in Autism and introducing H4
