Wednesday 24 July 2013

Histamine, allergies and reducing challenging “autistic-like” behaviours

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.

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.

 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.
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


Difficulty in group games or sports


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.

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:-

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 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
I was pleased to find that I was not the first to look into the use of histamine drugs in autism.  I did find two studies, and both were positive.  It is strange that in the 12 years since these studies were carried out, the research effort has not been followed up.
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.


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).


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.

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


  1. How do you obtain the Ketotifen? are you in Canada. My gut feeling is that my son would benefit from this. He has symptoms year round (dust mite allergies) but things are particularly bad in the spring and late summer.

    1. In the US, we can get ketotifen eye drops (Zatidor or generic) over the counter in various pharmacies. We also have access to oral ketotifen, but only through compounding pharmacies. It's an expensive drug here, so it's better to work with a compounding pharmacy that deals with ketotifen for many patients which will lower your cost.

      Also beneficial is the mast cell stabilizer cromolyn sodium, which is available orally as a prescription and nasally (Nasalcrom or generic) as an over the counter drug.

    2. Thanks for the comments. There are some later posts about mast cell stabilizers. Also useful are quercetin and palmitoylethanolamide (PEA) which do stabilize mast cells but count as supplements. Rupatadine and Azelastine are two drugs that in theory work better than ketotifen and cromolyn; but it is clear that what works well in one person may have little impact in another person. So it is a case of trial and error.

  2. Just curious if you have tried Lutimax or Neuroprotek supplements? Seems like one of these might help.

  3. I did buy some Neuroprotek to trial. This does include quercetin, luteolin and rutin. You do need a lot of it and it apparently does take months to have an effect. In the end my final solution was a very cheap drug called Verapamil, it works in front of your eyes. Within minutes the allergy driven aggression, anger and awful behaviors vanish. It is a total solution in a tiny pill. The two jars of Neuroprotek remain in the cupboard.

  4. .
    Do Allergies Exacerbate Epileptic Status ?

    Per Below = YES.


    If You suffer from Epilepsy and also suffer from Enviro Allergies …

    Or your Allergies have exacerbated to Allergic Asthma …

    Pls consider the following …

    Today’s Allergy = Tomorrow’s Allergic ASTHMA.

    Allergy is a Cumulative Progressive Allergy SnowBall that begins Rolling at Birth > Gaining Speed ( Frequency ) & Mass ( Severity ) as it Rolls Down Life’s Hill toward Allergic Asthma …

    Disease sequence caused by ALLERGY SnowBall is called ALLERGY March.

    Allergy MARCH = Allergy / Allergic Asthma Parents > Pregnancy / Birth > Eczema ( Food Allergy ) > Colic Baby ( Food Allergy ) > Ear Issue Baby ( Allergy moving to Respiratory ) > Wheezing Baby > Child who “Always” has a Cold i.e. Allergy > Child Rhinitis > Congrat’s You now have Allergic Asthma.

    Pls remember that there are TWO Sides to the Allergy Coin..

    Food & Environmental

    That the Cumulative Progression of Allergy MARCH begins with Eczema and Colic Infant due to FOOD Allergy ..
    before it mitigates to Respiratory / Enviro Allergy with Ear Issues > Wheezing > Child who always has a Cold > Rhinitis > Quite possibly Allergic Asthma.

    While “ Some “ Children do outgrow their Food Allergies ( actually Allergy has just Reinvented itself from Food to Enviro ) ..the Aero-Enviro Allergy Side of the Coin often remains and exacerbates to …

    Thus said, it is Important to Stop & Melt the Allergy SnowBall from Rolling Bigger & Faster to ???

    How ?

    STOP a LifeTime of Masking Symptoms with Pharma ..

    And Target the Source of Allergy by = Building Internal Immune Tolerance to the very Enviro Sources that are causing you to Achoo ...

    }} Why not Build Tolerance to 14 Major Aero-Enviro Sources via a GOOy CHEWy Honey Treat ..

    You have Tried EveryThing for your Allergies UnTil Now ..

    May we suggest .. RELIEF

    And If You have an Itchy Allergy Sad DOG …


    For over 3.5 Yr Doggy GOO has been building Immune Tolerance to 15 Major Enviro allergy Sources in our Itchy Allergy Dogs.

    Pet Parents Luv Doggy GOO ..
    And so do their Animals

    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.

  5. This comment has been removed by a blog administrator.

  6. Will diamine oxidase be helpful at all?

  7. Will diamine oxidase be helpful at all?

    1. Thanks for the comment.

      It could be helpful if the person has DAO deficiency and therefore cannot inactivate histamine. This is really connected with food allergy and histamine in the gut, where DAO should be present.

      So if the person appears to be histamine intolerant and responds to changes in diet, DAO would be a logical thing to try.

      In the case of airborne allergy, increasing DAO in the gut probably will not help.

  8. Hi Peter, I will see the neurologist in july, first days, in BsAs, I am a bit worried because my son is having episodes of upgazes, as if it was having mini seizures.This could be a valproat effect, due to gabaergic hyperextitacion? think that s crazy but i read this could happen with the susteined use ,in some children. In addition he isnt bearing bright and fast tv lights, he covers his face with his hands, he never did it. I will ask him about bumetanide, but iam afraid that my son s case is more complicated, as you told me last time. He never had a seizure but i fell this like threats.
    About flare ups, know that you refer to allergies but now he has strep throat, that is his other weak point, that is causing a lot of tics and obssesive bahaviour. Could this alter nac effect?

    1. Valentina, there are many different possibilities. In your case you have high functioning autism but you see a risk of seizures.

      It does seem that the first seizure makes it easier for further seizures, via some mechanism like an epigenetic change. So I would prioritize not having a seizure.

      It looks like some people have tics and obsessive behavior for a different reason than people with classic autism have stimming/stereotypy. So there are drug treatments like Clonidine that seem to reduce tics, ask your neurologist about these.

      In my son the stimming and OCD is caused by oxidative stress and responds to NAC. He has no tics.

      In your case the tics might not be caused by oxidative stress. If they do not respond to NAC in a couple of days, then you have your answer.

      OCD is well studied and the strep-associated PANDAS also causes tics.

      I think NAC will have either a good effect or no effect.

    2. imagine how scared i am,he had aquired a lot of skills, as an example, he reads fluently, better than all of the classroom, and perfect handling of electronic devices.This is before and after the first seizure, i know that. I think he is a rare case, and unfortunatly, autism is evolutive.

  9. I have been trying nac since two days, i dont see positive effects but as he is with strep thorat, perhaps is not a good moment, or this has nothing to do with nac effect? I am also giving him propolis 180 mg, I see an overall improvment, also in stimming and tics but the effect reduces after a few hours. I started a week ago.Could it be? Stopped clonidine, he was already taking it but it has a tiny effect on tics or hyperactivity, at least in my son,.valentina

    1. It is best to make one change at a time otherwise you will not know what has shown a positive effect. So give the propolis for a week and look for an effect. Then stop the propolis and start the NAC.

      It is best to do this when your son is his best health, since his strep throat may very well disrupt things.

      I found that NAC works very fast, but also the effect only really last for 3 hours. In some people it has zero effect.

    2. Hi Peter, which brand of NAC do you use ?

    3. I use an effervescent tablet form of NAC called Fluimucil. It is made in Switzerland and available in most countries, except the English speaking ones. For people in the US the equivalent would be Pharmanac, which I am told they now actually buy in from India.

      We also use NAC Sustain which is a time released NAC. This does seem to be the most potent product.

      There are also gelatin capsules with NAC. These are much cheaper. They do work, but do not seem to be as potent as it says on the label.

      NAC oxidizes and gives off a smell of rotten eggs.

  10. Any comment on Hardy Nutritionals? Is it really safe for children with autism?

  11. Coincidentally, I've just noticed this with my 23 yr old autistic son. On 3 occasions during the past month, a 10 mg loratadine tablet has dramatically improved behaviour in about 30 minutes. The first time I gave it was in response to what I thought was a seasonal allergy, the next two times in response to behaviour. Fascinating.

    I've also found a "patent" application ( that seems to corroborate our experience.

  12. I just stumbled on your site after hitting Google trying to figure out why we are having a "behavior burst" days after removing him from Benadryl, after more than a year of continuous improvement. Wow. So, food allergy? And how do I figure it out? Or does he just take allergy meds forever? (Not that that would be a bad thing) I have noticed an upswing in behavior issues during spring and fall.

    1. You can think of autism as being, in part, an allergy of the brain. So in your son's case, any kind of allergy, be it food, pollen, cats, dust etc, is likely to make his autism worse.

      You either remove the allergen, treat the allergy or just live with the allergy.

      There are drugs called mast cell stabilizers, which are like super antihistamines. They should work even better than Benadryl. Cromolyn Sodium is a well known example. Some readers of this blog are using Verapamil off-label.

      Mast cell stabilizers block a calcium channel essential for mast cell degranulation, stabilizing the cell and thereby preventing the release of histamine and related mediators. Verapamil is a calcium channel blocker, used primarily to low blood pressure, but seems to work great in some people with autism.

  13. This group in Australia has given us very helpful information about food and additive allergies which kids with ASD often have. It is helping us to chase down hidden allergies instead of just masking the symptoms. Taking my daughter off of berries, for instance, seems to make a real difference.

  14. I'm in Sweden. Ketotifen is prescription only here unfortunately. I do feel that thus drug could very well help my son. I found he responded well to quercetin but unfortunately it proved to be too phenolic for him. We can get ketotifen eye drops here but I'm not sure if this would be safe to administer orally?

    1. Trying the eye drops in his eyes might make more sense than you think, since your eyes are part of CNS. If you want to affect the brain it should be much more potent than taking it orally. It depends where you want the ketotifen to act.

  15. Interesting. He seems to be very sensitive to all histamine containing foods, especially liberators, causing all sorts of gastrointestinal discomfort. But it's more the effect of this reaction on his brain that is most worrying as he can go from being a fairly competent 5 year old to being very anxious and displaying much more autistic behaviour in no time. Probiotics is an example of something that could cause him to feel very unwell. Apart from a pollen allergy, no other allergies have been detected. Clarityn has some good effects but he doesn't seem to handle the lactose in it too well. It feels as though when he eats something that causes mast cell degranulation in his stomach something terrible is released into his brain causing headache, confusion, anxiety and increased autistic behaviour. I haven't found a doctor who will take me seriously on this yet and have thus ordered some ketotifen from Japan. I shall of course test the drug on myself first. It's definitely interesting regarding the eyedrops. I wonder if they would have any effect in his case? Thanks for your reply. Would be grateful for any more info you might have.

    1. Nick, Our son shows similar behavior after eating some food...these food did not show up in the ige allergy testing 8-9 months back but in a more recent testing have shown up... most likely he was having a non-ige mediated reaction.. our son also started regurgitating with the offending food items almost within an hour and than behavior would deteriorate in the next few hours.. he had an endoscopy recently and he was diagnosed with EoE (effectively asthma of food pipe).. we are seeing a gastroentologist and allergist here in london. If you like you can reach me on ..

  16. Hello Peter,
    I would love to share our experiences this past week with you and all your other readers looking for answers, in case it resonates with anyone else's situation--Just a few days on NAC brought on another bout of yeast overgrowth for my son which was seen immediately in behavior yesterday morning--almost no speech, cracked toes, gazing and general "zoned out" behavior. Discontinued it and started olive leaf extract. Honestly did not see much improvement or speech on NAC despite my hopes, it made him lethargic at first and then the yeast set in. I tried it as well and felt immediate drowsiness. B12 needed perhaps? Another issue has been allergies, as you and others know very well. I live near DC, USA, and lately pollen/environmental allergies have worsened for entire family, especially my youngest with ASD. Symptoms are ferocious tantrums, red eyes, eczema, and lack of interest in learning. Tried 1 mg Ketotifen a few day ago and saw immediate improvement, plus the solution has no taste and is a small dose. Speech was amazing, attention at least 50% improvement-success! Said goodnight to his brother for the first time ever. However...and I say this with a heavy heart, after reading about prevalence of seizures, especially in younger children, I decided to discontinue simply because we are still in diagnostic phase and do not yet know if he is a higher risk for seizure activity. So despite wonderful progress with Ketotifan I cannot keep giving it to him. Otherwise, we have tried all other OTC H2 antihist. with no improvements. Allegra was decent but a pain to actually get a toddler to drink and often resulted in hyperactivity at too small a dose. Plus all of them have a bitter taste therefore dosing is a challenge. However, (finally, I get to my point!:)) children's chewable Advil tablets have been a godsend. For the past two days it has not only brought my son's inflammation down, but also calmed his demeanor and brought his engagement and speech to above "normal" levels, for us, within 30 minutes after dosing. I read the label today and found that each tablet has 4.2 mg of phenylalanine per tablet. However, I did not see it listed on the Advil website for other forms of the drug but will try the liquid in the next week to see if the addition of phenylalanine, even such a small dose, plays a role in the cognitive improvement I have seen. My son often shows signs of a headache, discomfort from his allergies--naturally--so just overall pain relief is likely a big part of the solution to his behavior.

    1. Some people's autism is highly variable. If you can identify what causes the flare-ups then you are on your way to bringing the autism back to the "base level". Many people find that during these flare-ups previously useful drugs "stop working". So there is no point trialing a new drug like bumetanide during a flare-up, it will show no benefit.

      If you have pollen allergies or other mast cell dysfunctions these have to be treated first.

      Pollen allergy caused my son to exhibit violent raging. Now this problem is fully managed and we have no summertime raging. The allergy can be controlled by conventional mast cell stabilizers and we find the biogaia probiotic reduces the immune response that is part of the allergic reaction. The raging itself can be stopped within a few minutes using a small dose of the calcium channel blocker, Verapamil. For about 4 hours after verapamil there is no raging. If you fully treat the allergy, if that is possible, there is no raging anyway.

      The activated mast cells do cause pain and this is why the person may hit their head or whichever part of the body is hurting. If they are verbal they can tell you about it, "spray the fire in my head" etc.

    2. MKate.

      Your mention of phenylalanine is very interesting. Are you still giving home the Advil and have you researched this any further?


    3. Olive leaf extract is also a calcium channel blocker

  17. Hi Nick--Have you tried digestive enzymes in addition to probiotics? We have had great luck with Houston Trienza enzymes in limiting casin and gluten allergy response. They also help with phenolic foods. A bit expensive but they work. Yes, we had a good experience with ketotifen also but feel the risk of possible seizure activity is not worth it at this time. Also, we are tryng L. reuteri in addition to a completely dairy free probiotic complex, due to my son's severe dairy allergy. Most OTC antihistamines do not work for my son but children's advil has been great for seasonal allergies and the overall inflammation, discomfort that it brings. Just a few thoughts, best of luck in all the trial and error! :)

    1. Ibuprofen (Advil) is an NSAID used by many people with autism. It reduces inflammatory cytokines like IL-6. It is also a PPAR gamma agonist. In some people you can get a similar benefit that you get from ibuprofen using Sytrinol. It is flavanol with no apparent side effects that is a mild PPAR gamma agonist, so people take it every day.

      Prolonged use of ibuprofen can cause GI side effects.

      RG just left a comment that after a year on sytrinol, there are no allergies.

  18. Hi Mkate,

    I was keeping nac, b12 and potassium on the hold and waiting for the biogaia. But your experience seems to make me question my intention to introduce all these interventions as my son is fortunately in a very aware, peaceful and contented phase right now, giving us unbridled affection.

    He does not have much expressive speech but otherwise doing OK. My major problem right now is cognition and language as other autistic behavioural problems and comorbidities are not an issue for us at present. So I am really nervous about starting something which takes us backwards. Please keep on updating on your experience as I plan to start with the safest and probably most broadly acting treatment, biogaia.

    From my personal experience, whatever releives the child of physical discomfort, an anti inflammatory, anti histamine, probiotic or diuretic, whatever the mechanism of action, is going to jumpstart improvement. I think you are making the same point.

    All the best

  19. Hi Kritika,
    Sorry I took so long in replying. We are having lots of changes in our lives right now too. I initially had my son (who also has speech apraxia, uses word approximations and sign language) on NAC, sulphorafane, citocholine, L Carnitine. Too much. Really saw improvement with sulphorafane...until allergies hit us hard! So at that point I stopped all of the above and just concentrated on stopping the allergic response, and we started on just probiotic regimen plus quecertin about four days ago. He's done very well. Honestly I think your son will only benefit from the L. reuteri. I wish I'd given them to my son earlier. I see a LOT more social interaction and speech attempts, he's coming up to us, pointing out things on TV or ipad. It may be the other probiotics I've included, it could be a collective result of all 4 supplements, I don't know. But I've definitely seen a big change for the better.
    I actually tried the biogaia tablets but my son would not take them. So I bought some cheaper brand of Lreuteri drops from, Bioamicus. I'm also using Cytoflora drops which also has lreuteri included in it's ingredient list. Also give one capsule Klaire Labs Therbiotic every other day. It has inulin which is another form of prebiotic. This may/may not work for others, it's good so far for us. But it could change anytime, you know? If your son is happy but if you think maybe he wants/needs to communicate more, try the drops or the drops in conjunction with Cytoflora, which has wonderful reviews --the reason I bought it, was recommended for speech in ASD. Biogaia might be better than Bioamicus, I will probably switch to that brand after this bottle, to get a different strain. If he reacts you will know what caused the change. Again, I give quecertin also for allergies, which seems to really help with reducing gut inflammation/histamine response. I think he feels better since the gut-brain inflammation is reduced and thus the social changes are that much more pronounced.

    Good luck and keep in touch! :)


  20. Hi Mkate,

    It's so wonderful that your son responded well to l.reuteri. I am sure, he is going to make great progress, not withstanding the minor bumps, fingers crossed.
    Actually you did a big favour by just reinforcing my treatment plan, starting with biogaia as its supposed to modulate immnue responses, inflammations, allergies, gastric troubles as well as upregulation of certain hormones. So I am still waiting for my tablets which btw cost me a lot. Next I plan to introduce nac and bumetanide/diamox. Also will look up for cytoflora and the prebiotic you have mentioned.

    Incidentally, my son has been displaying lot of awareness, picking out a soft t for me to wear at night. And yesterday, he was doodling numbers on our wall and out of irritation I asked him to draw a spoon on paper. And there it was, a long robust horizontal line curved like a sickle at one end and an oval on top of it for the depth factor. And then a car, two wheels under a horizontal line and a vertical line in the center. It looked like a cubist impression of daily objects. So something is going on in his tiny muddled up brain and I hope he does not regress. So taking supportive as well as preemptive drug intervention really seriously.
    Thank you so much and do keep posting.
    Best wishes for the little one.

    1. No worries, Kritika. He sounds like a deeply imaginative soul, and he will get to where he needs to be, just as my son will. We are not going to allow anything less than the best for our children. I know it's become my mission in life--no hobbies, no weekends spent indulging museums or movie, I spend my time reading, searching, discussing treatments, making appointments, etc for my son...there is no greater priority than getting him closer to recovery (both my children are my priority I should say, as I have an older son). It sounds like you are very much of the same mind so just keep on doing what you are doing. You will find the right answers.
      Next month I'm hoping to have my son seen by a neurologist that specializes in traumatic brain injury (he had some birth complications, surgeries as an infant, etc) and in neuroplasticity at KK at Hopkins, maybe get an MRI if it is not too traumatic an undertaking for a 3 year old. With his speech apraxia being the presenting symptom, along with other motor apraxia issues, I feel that an expert in pediatric neurology would be the best place to start asking questions as to what may be happening in his brain. Perhaps a visit to a neurologist could help your son, or at least ease your mind a bit about his symptoms? Has he been diagnosed with autism and/or verbal apraxia? Even if he hasn't, it's never too late to start working with him yourself. That has been what I have been doing the past few months. Youtube videos are the best way to quickly learn ABA and Verbal Behavior techniques. Also Peter recommended some books that I also have read, in addition to The Verbal Behavior Approach by Mary Barbera. It teaches you how to use ABA techniques to guide your child to realize that speech is how he gets his needs and wants met, among many other concepts. Mary Barbera's book is the least confusing version of VB basics, I really recommend it. (Also, you could probably find it online on a reference site to read for free if you don't want to buy a hard copy)
      Best of luck!
      PS- Oh, and if possible look into a sensory therapy swing to hang indoors. Ours has been a lifesaver! I bought a long stretchy type "yoga silk" and it hangs in his playroom. Wonderful way for him to decompress, calm himself from sensory overload (which helps concentration), and it's just a lot of fun for him...after all, ASD or not, that's what all kids want and need--fun! :)

    2. Hi Mkate,
      Thanks for the uplifting and empathetic message. And don't even get me started on this obsession with the A thing. In fact I suspect I have become quite a bore lately, maneuvering all attempts at a decent conversation into one about autism.

      And why not when I have an autistic son, a dog with anxiety disorder and a husband whose aspergers started emerging just prior to our wedding to descend into autism after marriage with a second hit when fatherhood came calling. So life is quite a circus with the A list males surrounding me.
      We have not had much medical examinations for done as my paed and therapist feel that it's prudent to conserve time, energy and finances and tackle pathologies ad and when they appear.
      About the literature, well, I have pretty much covered ground, Greenspan to Patricia lemer. In fact after purchasing hard copies I started downloading via Kindle to cut cost and as well as to be able to read on the move. And my leisure activity..reading autobiographical accounts mothers with kids on the spectrum.

      Mkate, your son is still very young with an added advantage of having a sibling, so if you not already gone through it, please read rdi books, specifically the one for young kids which has lots of helpful activities. Some of the son rise program ideas are very insightful. Koegel's Overcoming Autism on pivotal response and Sally Roger's Early start for child with autism, based on early start Denver program are crisp with practical examples. Another book which is an easy but useful read is Spectacular Bond by Marion Blank.

      Mkate, in the end it ultimately boils down to a lot of common sense and as intelligent and perceptive parents I think we all design our own protocols as we know our child like nobody does.

      My best wishes for your family

      And take care

    3. Hi Mkate,
      Forgot to mention that my son has been assessed as being borderline/mild autistic with a CARS score of 28 and I suspect verbal apraxia could be a an issue here although his therapist has not suggested that. Someone suggested social communication disorder which again indicates that he is somewhere on the spectrum. I think these labels are pretty subjective and we have to work on multiple deficits..I cannot deny my child perceives the world in a non typical manner, has communication issues as well as cognitive differences..So there it is.

    4. Peter would you give suggestions on a H2 antagonists as Tagamet cannot be prescribed for a child that is 7 years .H1antagonists have been a life saver thank you ever so much for your write up in this area thank you Peter

    5. Many young children have GERD/GORD/reflux and are treated with H2 antagonists like ranitidine (Zantac). Ask your doctor.

      I would first try the OTC probiotic Biogaia, which greatly reduced my son's allergy and his need for prescription allergy drugs.

    6. I am giving this feedback in order to help others Peter awesome use of ranitidine as suggested by you h1 and h2 with bumetandine are making a good difference more intoned understanding receptive speech ,imitating,any suggestions with h3 my child does not seem to respond well to nac potassium the strain of probiotics Ali suggested might try yours Peter in the future.Must note still aggressive and defiant but will continue to shuffle things aggresion is slightly less H2 was my last addition this has somehow brought about this positive development Peter what are you thoughts child non verbal

  21. As a small warning on first gen antihistamines (benadryl in particular) is that they are typically anticholinergic.

    Basically this means that they may have the inverse effect to galantamine on acetylcholine used for memory etc, especially if used long-term. However, they may be more effective for some causes of ASD irritability.

    Second generation antihistamines don't tend to have this issue, but seem to have lower efficacy from anecdata.

  22. Hello Peter,

    It's been two months wait for the ever elusive biogaia and I think I have to postpone this trial for now, although I was really curious as to its effects on my son. I plan to quickly test the other drugs/supplements starting with NAC but right now, probably due to seasonal changes, most people including my son are facing issues with digestion (acid reflux, bloated tummy) which is affecting his sleep and behaviour. NAC might irritate the GI system a little so my apprehension was that firstly I might exacerbate his digestive issues and secondly, the effects if any of NAC might not get adequately expressed under these conditions.
    Should I wait a is going to ease off a little so wanted to make best use of this time.

    Also, does quercetin works as an H2 antagonist as well? Would you suggest its use during change of seasons and would you suggest trying a probiotic like culturelle for settling his GI issues. Digestive enzymes and probiotics have not really helped my son in the past.

    Lastly, that devided attention seems to help my son focus and divert attention from penile erections, was also confirmed by his occupational therapist. And as you suggested, now it does seem to me anxiety driven leading to circulatory hypoxia which induces NO production. Behavioural therapy to reduce stress should help with this. Could psychological anxiety and hyperexcitability which do have a neurological basis but different from neuronal hyperexcitability be indirectly helped with treatments targeting oxidative stress and E/I imbalance?

    I have a feeling I am making some kind of blunder here.

    1. Anxiety is a consequence of many people's autism, particularly the Asperger's type.

      Emotional distress, particularly extreme forms, can be very damaging to people with autism and can cause a downward spriral. This will have biological underpinnings and might involve change in GABA sub-unit expression, epigenetic changes and even acquired channelopathies (like in epilepsy). I very much doubt you have this.

      I actually think your son may be showing unusual symptoms of the common E/I imbalance. One of the drugs original used to modify E/I imbalance, via GABA, was potassium bromide. A hundred years later bromide was supposedly given to soldiers to subdue sexual desires. It was even given specifically to reduce the arousal that your son is experiencing.

      So it is plausible, but by no means certain, that when you treat your son with bumetanide, and/or baclofen (or potentially even KBr) that your son's issues might well improve.

      I would go rationally through what interventions help other people, one by one. Then you can draw useful conclusions.

      NAC is very easy to try and for us had no side effects of any kind.

    2. Only thing to watch out for with Quercetin is if your child is low in iron (quite common in ASD).

      Quercetin blocks iron absorption, which may exacerbate certain issues.

    3. Hello Peter,

      Now you have got me worried. I was actually convinced that what my son is experiencing might be a common behaviour with young autistic kids, especially boys. The same behaviour is displayed by dogs, at least mine who would get it up all the time as a puppy and would go humping when excited.

      I will definitely have to open up more now. My son was in diapers till 2.8 years of age, partly because i did not try hard enough to toilet training him as i was working more on bonding. After his diagnosis, the first thing they did was toilet train him which he picked up pretty quickly. So off went the diaper but in came the fiddling with his organ part. And after some time rubbing himself on the bed or for floor which his paed dismissed as exploratory and normal. This rubbing process increased usually as a result of sensory overstimulation. Then as he matured, he would come home and de stress by doing this but it was quite controlled..he would stop when told to. This behaviour got almost eliminated as also the visual stims like wiggling fingers in front of eyes and looking through corner of eyes and would rear its weird head during seasonal change, or lack of sleep of when he would get extremely overwhelmed. This was rare though.

      This erection thing has been the latest development in this short little history (4.7 years) of his over sensitive organ and has kept pace with his awareness levels.

      I suspect, it's a combination of stress and sensory seeking behaviour. And I am repeating, all this odd brhsviour, the visual stimming, laughter and finger movements have come back with a vengeance in the past week. This makes me suspicious about hidden allergies as well.

      Hidden allergies, iron deficiency, hypoxia due to stress have all been implicated for inducing NO production. But i think I have to get examined his hormonal profile, specifically androgen levels, as well.

      I will start with steps you suggested but I think it's time to take a referral for an endocrinologist and a urologist.

      Any other suggestion will be most helpful. I also feel its time for some basic blood and urine tests.

      Mossy, yes, my son is deficient in iron. H1 antagonists and most sedatives make my son as well as my self really uncomfortable. GI system is the one which gets most affected in us with environmental fluctuations. Therefore I was curious about quercetin. Thanks for the information.

      As I am planning to schedule a meeting with his paed, if anybody has any advice as to what examinations I should request for,
      I would really appreciate it.

    4. Peter,

      Actually would not there be different pathways involved in his semi-matusturbatory behaviour which could be linked to arousal if we can use that term for a four and s half year old and which is thankfully not very frequent, and the erection problem which is distressing for him and always takes place in situations where he is anxious. I always thought that stress would create problems with erections but here we have a situation where the neurological and hormonal processes seem to have got mixed up. Sorry, but too many issues are crossing my mind after reading first your depressing post on the historical account of extreme societal indifference and even revulsion towards the atypicals and then looking up KBr.

      I hope the less extreme interventions work for my son.

  23. Hi Peter
    My son has been having skin rashes/hives for the first time, he is 4 years. We had started a sulphur based supplement for a couple of days and stopped, but he seems to be reacting to a lot of stuff now with a rash which he was not previously
    It goes away with Zyrtec or Benadryl
    But I was wondering if had a reaction to a particular supplement should the allergic reaction not go away after we stopped it or is like some thing got activated and now he is sensitive to a lot of stuff which we was not to previously
    He has always been a sensitive kid with eczema,asthma but not skin rash
    Btw we had Chiari surgery on aug 29 which went smoothly his running/stimming almost disappeared, but has come back, but we see some improvement in other sensory stufff like hand clenching

    1. It seems that when you have an immune reaction things can take quite a while to settle back where they were. We also encountered this. You are seeing some kind of mast cell activation, which should just fade away over time. If it does not then go to your pediatrician.

      It is good that it goes away with Zyrtec.

      We have found that a moderate dose of L. reuteri Protectis bacteria seems to reduce these allergic over-reactions. There are other probiotic bacteria strains shown to help some people with allergy, including Bifidobacterium lactis BB-12 and Lactobacillus GG. All of these are commercially available and usually given to babies. They seem to help some people more than others.

      It is good that you had the Chiari surgery.

  24. Hi Peter,
    So it occurred to me that perhaps my son's recent uptick in OCD behavior and increased anxiety really could be from allergies. I read through the information you have on this site and have reached out to my son's doctor to see if he would be willing to trial Verapamil.
    I am currently giving him Zyrtec and BioGaia Gastrus which should be helping but aren't.
    If I am unable to get Verapamil, what else would you suggest we add to help in this regard? Quercetin?
    NAC used to work beautifully for his OCD, but has not only stopped working but seems to be aggravating it. I will go back to it once allergy season is over.
    Thank you for any advice you can provide.

    1. Christine, for us Biogaia Protectis helps a lot, but Gastrus made things worse from the first pill. You could stop Gastrus, wait a week till the bacteria leaves the body and its effects fade and then try Protects.

      Quercetin is well worth a try.

    2. I'm so glad I asked because I added another Gastrus thinking it would help. Ugh!!! I am probably inadvertently making things worse. Thank you for the advice!
      Would you try Quercetin on it's own or Neuroprotek?
      Thanks for your advice.

    3. Quercetin is quite cheap and is effective in many people. Neuroprotek is very expensive and I am not convinced how much it really helps. Verapamil is ultra cheap and works wonders for some people.

      I would try quercetin on its own.

  25. Sorry Peter! One more thing if you can clarify -- wouldn't it seem to make sense that Gastrus with it's anti-inflammatory strain would be more beneficial than Protectis since histamine triggers an inflammatory response?

    1. For most people Gastrus is indeed more anti-inflammatory and is better. In some people, including my son, the mechanism of the second bacteria in Gastrus makes things worse. In a few people even Protectis causes a negative result. In my son the benefit of Protectis was clear from the first day and the surprise negative effect of Gastrus was immediate.

  26. Peter,
    I know I have been writing often, but I got an answer from my son's doctor about Verapamil:
    "In regards to Verapamil, a calcium channel blocker I feel uncomfortable using it to achieve mast cell stabilization as there is no indication for use for allergies at this time and has some potentially serious side effects. I would recommend using Monteleukast instead, which does have an indication for allergies. There are studies that have shown a positive effect in lung inflammation and therefore it has been hypothesized it could have an effect in brain inflammation caused by allergies."
    Any thoughts... Do you feel this could be an effective alternative?
    As always, THANK YOU!

  27. Christine, I do think Montelukast is worth trying as is Ibudilast from Japan. It will not do the same thing as verapamil, but it may be beneficial. Montelukast is widely used in children. Verapamil will not help pollen allergies and asthma, but there is interesting research to show its effect on GI problems. In the brain it has been shown effective in bipolar and various types of headaches. In our case it treats the allergy driven autism flare up, but not the allergy itself. I will write a post on the GI effect, I recently tried it on myself.

    So go ahead and try the montelukast, it is used at Johns Hopkins for people with mitochondrial disease when they are sick to avoid further mitochondrial damage. We tried it but it made our allergy worse not better.

  28. Peter, Thank you for your response. I am discouraged that we can't try Verapamil. I'm a bit confused about his feeling that Verapamil has the potential for serious side effects because I am reading horror stories about Singulair/Montelukast. My son's OCD/anxiety are through the roof right now and Singulair sounds like it makes it worse since it depletes serotonin. Lots of talk about kids becoming very upset and angry.
    I'm wondering if adding in a serotonin booster like tryptophan or 5-HTP would help?
    It seems every step forward, is a step back...
    My sincere thanks for your blog and your feedback.

  29. Very nice article but I am in a dilemma now. Various studies show that Carnosine has beneficial effects on autism particularly with social skills and anger. However, Carnosine is made up of beta-alanine and histidine, so The supplementing with Carnosine increases histamine levels. So the dilemma is: how could carnosine help autism by increasing histamine while, at the same time, antihistamines reduce autistic problems by blocking histamine receptors. Could you please elaborate. Thanks so much.

    1. Carnosine has multiple effects, it does degrade to histamine, but it is also a mast cell stabilizer which will reduce histamine. Histamine is produced by food and the body can deal with normal levels via the enzymes DAO and HMT. So unless you are histamine intolerant (lacking in DAO and HMT) carnosine likely will have no negative histamine relates effects in the doses you are likely to use.

  30. Hello,

    My son seems to be worse lately and I thought it looks like an allergic reaction to something: his nose is full of mucus, he's ithcy, irritable in the morning and more aggressive. I tried Hayleve, which is Chlorphenamine Maleate, with moderate success, but he needs to take half a pill every half hour. What is the difference wih Clarityn and Ketotifen?

    1. Claritin and Ketotifen are both H1 antihistamines, but Ketotifen is better at stabilizing mast cells and so reduces the amount of histamine that is actually released. This effect of Ketotifen can take a couple of weeks to establish. Nasal spray antihistamines are also a good idea. Azelastine is used in some sprays and like Ketotifen is both an H1 antihistamine and a mast cell stabilizer.

  31. Thanks, I will try a few different ones and see what happens. He was on NAC for a month, as his hair test came back with high levels of pesticides and hydrocarbon in his body, so it was supposed to increase glutathione. I don't know if it worked, but NAC made his symptoms worse, so either he's allergic to NAC or there is something else going on. I read your post about oxidative vs reductive stress and it was interesting to me: my son can't get anywhere near B12 or B6 supps (he goes mental, basically) and NAC or Theamine didn't do anything good. So far the only thing that has worked, apart from homeopathy, is Cytoflora (pre-biotic), which has improved his speech and social skills enormously and immediately. That makes me think that he does have GI issues and possibly allergies to something (he's had a stuffed nose for ever). I will try to give him paracetamol as well and see what happens. Thanks again, Giovanna

    1. Hello Peter,

      Cytoflora, which basically consists of lysed bacteria has been found to be effective for development of speech and social skilss by quite a number of parents. Giovannas son's good response to homeopathy and not much else except cytoflora does raise my hope on the prebiotic doing something for my son as well.

      I am writing primarily to share that son is displaying mild allergic symptoms starting Oct end which got aggravated in the past ten days. Actually I had been observing irritability during Nov/early December every year and his therapist acknowledged that this happens with seasonal changes in most autistic kids and is mostly a passing phase. But this time, with increased awareness, both mine and my son's, I could observe explicit allergic symptoms. Itchy eyes and nose, and skin (gestures towards itchy areas which seem all over though no external skin condition), which is heightened when he gets up from sleep, early evening, short periods of irritability and a little anxiety (urgent and incessant demand to be played sometjing on you tube ). There is no cognitive decline though, and even the behavioural deterioration is not long drawn. But the propensity towards allergies or behavioural response to them seems to be there so have to keep a close watch.

      As far as potassium is concerned, after reading up a comment from an ADHD sufferer on your blog, I fed my son half an avocado (size of a plum). No miracles there.

      Peter, in your honest opinion can we expect a medical treatment for most autism in another ten years or so?


    2. Hi Giovanna and Mkate, I was intrigued by the Cytoflora thing you mention and did some research. It seems that yes it is possible to get the same benefits from the dead bacteria as from the live ones, but with less or no side effects!

      "In summary, we show for the first time in an animal model that heat-killed LGG has similar effects in modulating splanchnic-derived inflammation that can be reflected in plasma and a distal organ such as the lung. This may be a safer approach than using live microbes in certain situations such as immediately after birth, in premature infants, or in immunosuppressed individuals."

      Live and Heat-Killed Lactobacillus rhamnosus GG

      Alive and Dead Lactobacillus rhamnosus GG Decrease Tumor Necrosis Factor- –Induced Interleukin-8 Production in Caco-2 Cells

      My kid benefits a lot from probiotics, but certain strains he can't deal for long or at all. This may be a safer way for him. You have my thanks.


  32. Jane, I remember our kids had similar reactions to certain strains. If you try cytoflora, can you please share your experience here? or you can email me privately at I am starting to think anything I give to my son that stimulates any arm of the immune system too much - really creates problems.

    1. Hi Tanya, no problem, when I try it I'll let you know how it goes.

  33. Hi Peter,
    My comment may seem all over the place as I am trying to connect some dots and you and your readers seem to always help me do so. Please bear with me.
    My son shows many signs of having high histamine. Many years ago he was tested by a DAN doctor and the results of the test showed this (who knows how accurate that was), but nonetheless he has a constant runny nose and dark circles under his eyes. He also has terrible anxiety which I am always looking to find any help with.
    I was reading your post on histamine and Mastocytosis (disorder of mast cells). The treatment plan according to the Mastocytosis Society Of Canada was broken down into symptoms and under anxiety they list: low dose Clonazepam, Remeron and Lyrica. I remembered reading in your post that one parent used Remeron (which is a tricylic antidepressant) and a powerful antihistamine. I also remembered you mentioning Betahistine which is an H3 antagonist used to treat vertigo. I ended up on a site for vertigo which said they use vestibular suppressant drugs to treat it which fall into three groups: anticholinergics, antihistamines, and benzodiazepines.
    So many kids with Autism have sensory processing issues including vestibular dysfunction. The vestibular system detects movement and gravitational pull, and it provides information regarding the position of our head in space and acceleration and deceleration of movement. It is the first sensory system to fully develop in utero and is located in the inner ear. The vestibular system has strong neurological connections in the brain and is a major organizer of varied sensory input. This system is considered the most influential sensory system and has tremendous impact on one’s ability to function daily. Directly or indirectly, the vestibular system influences nearly everything we do. It is the unifying system in our brain that modifies and coordinates information received from other systems, and it functions like a traffic cop, telling each sensation where and when it should go or stop.
    Help me put this all together as I know that your son as well as many others are having success with low dose Clonazepam and controlling histamine. Perhaps the effects on the vestibular system in organizing the brain and body has a domino effect on overall function???
    Has anyone tried Remeron, or another tricylic antidepressant called Sinequan which also has antihistamine properties?
    Would you suggest a combination approach of an H1 (Claritin)or Remeron, H2 like Zantac and perhaps an H3 like Betahistine?
    Thanks for helping me make sense of this.

  34. Hi Christine, Was just wondering how things were going with your son - i remember a few weeks back you were trying to find something to help with your son's anxiety.....My son is in the mast cell/histamine/gut kid category - if ypu would like to email to compare notes - Obviously not saying I have it all figured out (who does anyway) but with similar kids, perhaps going over some details can give us both ideas. I will say verapamil seems to have kick started a good turn for my son with allergies and anxiety caused by stress. I would say my son has more situational anxiety - and when I focused on cutting out unnecessary stressors that helped a lot with his mast cell and histamine issues. stress is a big mast cell trigger. for my son, an improper school placement made things so much worse - as well as hiring people with ABA backgrounds to do respite for me - I can only see that now. I'm sure the verapamil made this much easier too. My son has DAO snps as well as HMNT snps. And a couple of trips to,the ER in his history for breathing treatments. We tried ketotifen for a couple of yrs and it helped - some. But verapamil has been the best. I have not had to use any antihistamines in many months. Perhaps verapamil has kick started some of the naturals/nutrients we have used for years to work better or just to start working. He is no,longer reactive to B vitamins esp. folinic... Yasmina Ykelenstam and Alison Vickery are very good sources for mast cell/histamine issues - they have compiled a lot of research citations as well as interviews of specialists. Alison writes about her experience with iatrogenic mast cell activation - which i think is the case for my son - he was given cipro for an infection when he was young and afterwards, mast cell symptoms started to appear. By supporting the liver, knowing your cyto p450 mutations and cutting out things that impair that functioning can help. I have commented here that it seems this cyclical red patch of skin above my son's upper lip started after a couple of months on verapamil - but unlike Peter I do not think this is allergy. And I can't say for sure if is is from verap., still testing things out - but overall it has been a huge help is the allergy/histamine area for my son. I did try remeron for a month or so - and it gave him 10 hr sleeps - but in time it caused constipation and I did not want to have to keep giving him senna teas and mess with his gut flora just so he could go. I felt it was just creating another problem and only positive was long sleep.... We have never tried clonazepam. best wishes Christine!

  35. Would it be wise to try aan immunotherapie (hyposensitization) against pollenallergy for a young child who is on the spectrum (mild case) with flare ups in summertime? Thank you!

    1. It is more an allergy question than an autism question.

      It is certainly worth a try. It does work for many people with allergy.

      The therapy encourages the body to produce less IgE antibodies and more Th1 regulatory T cells, which secrete IL-10. That should all help control flare ups in summertime.

  36. I have only just found your blog and found this article incredibly interesting. My son, 9, has 22Q 11.2 deletion syndrome (diagnosed early 2012), so has a lot going on. Although he does not have ASD, he does display some ASD traits, particularly when he is under stress/anxious - stimming, difficulty regulating emotions. I discovered an autoimmune disorder called PANDAS, or PANS, a couple of years back. It seemed to explain a lot about Sam's behaviour changes. Every year, since he was about 5, we have seen major changes in his behaviour between the months of July and October (Winter through Spring here in Australia). Increased stimming, restlessness, more anxious, and he finds it harder to regulate his emotions. We also have noted that this coincides with allergy symptoms - sneezing;runny nose, allergy shiners, and itchy, red eyes. When he first began school in 2012, despite his development delays and learning difficulties, he was relatively happy. Then July hit and everything changed. It was like he was a different child. I removed him from school before Term 4 and we now home school, which was the best thing I could have done for him. He is thriving. But, back to his allergy reactions. Each year, I still noted differences in him during the hayfever allergy season, although not quite as bad now that he did not have the pressures of being in a mainstream school. This year, I tried a child's antihistamine. What a difference it has made! I'm now trying to do some research into histamine levels and their effects neurologically. This research brought me to your page. Thank you. I'd love to find some more research/papers. My son has a couple of hospital appointments coming up in October and November and I want to be prepared to discuss this with them.

    1. Clare, you will find many posts in this blog about histamine, mast cells and various possible therapies. This post is from 4 years ago.

      There are numerous ideas that may help, ranging from a particular probiotic (Biogaia) to a calcium channel blocker (Verapamil).

  37. Hist DA0 and Trienza is working for my son!

    1. Robin, that is great to hear. Can you give some more details? How old is your son, what issues he has and how these supplements have helped. Do you think that DAO and the enzymes are having the same effect, or they each are helping in a different way?

  38. Rachel Nicholson14 March 2018 at 14:21

    Peter, will started our son on the ketotifen drops on Saturday night giving them to him two drops in each eye twice daily. Monday he was a changed child; however, Tuesday he was back to his old self spitting on us, hitting us, hyper, making nests on the floor. Why would the drops only work for one day? We have kept giving them to him same as before. This comment is really brief because I'm having trouble posting them. If this works I'll give more info. They keep disappearing.

    1. Rachel, best to write your comment using a different program and just copy paste it into the comment box. When I use an iPad half my comments get lost. I would keep giving the ketotifen and see if things change again. Oral ketotifen might work better, but it depends where you live whether it is available.

      Many people find autism interventions only work for a few days, which is often likely caused by feedback loops in the body countering the action of the drug.

    2. Rachel Nicholson3 April 2018 at 22:28

      We're still experiencing bad behaviors despite continuing the ketotifen. Can you explain more about the feedback loop? I'm not sure I understand. How do we get out of it? Oral ketotifen isn't available without a prescription. We see an allergist on April 9th.

    3. Rachel Nicholson15 April 2018 at 17:08

      We have now started with oral ketotifen. We still are not seeing what we saw the first day. I've tried looking up feedback loops and can't find anything. Please elaborate.

    4. Feedback loops are an in-built compensatory mechanism, so when you use a drug to change something the body reacts and counters the change you made. This happens quite often. What you see is great effect for a day or two and then it disappears. In some cases the good effect lasts for weeks and then you can just cycle the use of the intervention, this happens with some probiotics for example.

  39. This is the first article that I have found that addresses any of what I was looking to confirm. During Chemo treatment Ranitidine was part of my regimen prior to each infusion to help stave off allergic reactions. Post chemo I have developed and continue to find allergies to things I had previously had no issue with. When I feel an allergy coming on my immediate go to is Ranitidine which is usually enough on it's own to calm the symptoms. With in the first hour is blurred vision and fatigue. As the time passes I find myself going through bouts of uncontrollable laughter verging on tears brought on by completely innate things like a picture on my daughters shirt or a sound etc. I have never understood it. Any other anti histamines knock me out cold lingering for days after just one so I avoid them completely. Has anyone else had or heard of anything like this? My family thinks it's funny as they watch me totally loose it but I'm concerned this maybe the tip of the iceberg to something more serious in the wings.

  40. Hi Peter,
    My son's doctor Dr Michael Chez has prescribed Guanfacine 1mg for his ADHD and extreme hyperactivity.What I fail to understand is how does a blood pressure med help with autism.Any ideas?

    1. SB, Guanfacine is widely used to treat ADHD and the proposed reason why it works is:-

      "Guanfacine works by activating α2A adrenoceptors in the central nervous system. This results in reduced peripheral sympathetic outflow and thus a reduction in peripheral sympathetic tone, which lowers both systolic and diastolic blood pressure. In ADHD, guanfacine works by strengthening regulation of attention and behavior by the prefrontal cortex. These enhancing effects on prefrontal cortical functions are thought to be due to drug stimulation of post-synaptic α2A adrenoceptors on dendritic spines, which inhibit cAMP-mediated opening of HCN and KCNQ channels and thus strengthen prefrontal cortical synaptic connectivity and enhance neuronal firing. The use of guanfacine for treating prefrontal disorders was developed by the Arnsten lab at Yale University based on understanding the needs of the prefrontal cortex."

  41. Hi Peter,
    Being at home with my son has increasingly been a challenge since the heavy pollen season started about a month ago. He has severe daily headaches and has started exhibiting a lot more anxiety and defiant behavior. All progress with speech and other learning tasks has come to a halt, especially with being on lockdown. SIB hasn't been a problem yet, though it's a possibility that I am aware of. He has become much more physically sensory seeking, wanting to have his head pressed hard into mine when it really pains him, and playing/wrestling with his brother and father rougher than usual. In previous years I used quercetin/luteolin during pollen season, but now it seems to just make him more hyperactive and slighly cranky. I'm thinking of asking his pediatrician for a Verapamil trial but have a few concerns after reading through the side effects. Has Monty ever experienced any heart rate problems in all his years on Verapamil? Any side effects at all? I just want to be cautious. My son currently takes daily: bumetanide 1 mg, NAC,K/Mg, Naltrexone 2mg, Clemastine 0.5-0.75mg, claritin 5mg, allegra 30mg. He is around 31kg, 67lbs and 6.5 years old. We are not able to have an EKG performed due to his anxiety (not unfounded of course for a young child) but I do have a handheld heart rate monitor that I bought on amazon that I intend to use to get a baseline and if/when we start Verapamil.

    Any thoughts you have would be very much appreciated. Hope all is well with you and your family during this very extraordinary time.


    1. MKate, Verapamil is usually well tolerated. In some people it can affect their gums and this happened to Maja's daughter. We have not had side effects at all.

      Maja mentioned that she is finding Pentoxifylline helpful in conjunction with Bumetanide. Pentoxifylline has several anti-inflammatory effects, including on allergy. Pentoxifylline is used for autism in the US and so your doctor might be happy to prescribe it (there are old clinical trials in children).

      Pentoxifylline or verapamil might well be effective. There is no way to be sure without a brief trial. The effect of Verapamil is from the first pill, so your trial need only be very short.

  42. Thanks very much for the reply Peter.
    So no effect on heart rate whatsoever? I only ask again because those are the major side effects listed online and they sound pretty serious. Im still on the fence about it. Digestive side effects do not worry me as much as complications with heart, heart rate. I did ask my son's dr. about a possible trial but have yet to hear back. Right now he is on two different OTC antihistimines, a small dose of clemastine, and LDN. The naltrexone usually really helps with food allergies as well as neuro-inflammation on some level as it seems to give my son more initiative and spontaneity not unlike what you describe as the effects of statin. But atm the pollen reaction seems to be taking center stage despite all medications, so I can only assume calcium channelopathy might be in play here. I will read up on pentoxifylline.

    Sourcing our medications has become MUCH harder since the covid shutdown. I can no longer purchase Miccil from ebay as I was, so we had to ask our pediatrician for a prescription for that, which he easily gave after I explained the situation, bless him. Also Tavegyl is on short supply from the seller on ebay that I usually buy from...I forsee a prescription required for that in the near future also. I don't know, perhaps this will all blow over soon once the panic has died down a bit and things will go back to normal? Not holding my breath though.

    1. MKate, we have had ECG, heart ultrasound, blood pressure and pulse. All is normal. The most likely side effect should be on blood pressure, but that may be skewed towards those with existing high blood pressure.

      It is always advisable to have medical supervision, but that assumes the doctor reads the literature that underlies why a drug might benefit some people with autism.

  43. Hello Peter,
    I found this when I was looking for my son’s sudden behaviour changes, from being calm to very anxious and then very aggressive. I always suspected that histamine is somehow related as before each behavioural changes he will have some itching episodes.
    I am in Australia and my son is 5 years old. He is currently very aggressive and wants to bite everyone, he looks so distressed, lost and doesn’t know what he wants. His symptoms improve a bit when I give him quercetin but it doesn’t resolve. We have tried neuroprotek lp in past but haven’t seen anything. I am very shocked and scared of his recent aggression, haven’t seen anything like this before. Is there anything we can try?

    1. Duggu, this post is from 2013 and I wrote further posts as I narrowed down the optimal therapy in our case.

      If you cannot remove the source of the allergy, which might even mean moving to a different part of the country, you can block its effects.

      In my son's case the problem of this kind of aggression is 100% resolved using a cheap calcium channel blocker called Verapamil. We have used it for a few years now. Your doctor is higher unlikely to prescribe this for you, but likely would give an anti-psychotic drug, which is treating the symptom not the cause.

      Partial solutions that help some people include mast cell stabilizers (cromolyn sodium, azelastine, rupatadine, ketotifen - these are all drugs).

      Many OTC antihistamines are weak mast cell stabilizers, like ceterizine and claritin.

  44. Thank you Peter for sharing this information. My daughter is 13 years old ( severe autism , and a genetic syndrome). She has been on hydroxizine for about 4 years for sleep . We never used medication during the day, it was managable. Several months ago the rage attacks started like we have never seen. No herbal stuff helped. I tried using hydroxide during the day a few days ago and saw rapid result. Today I didn't give her the morning dose but when rage attack came in the afternoon hydroxizine halted it ( I emptied the capsule in the mouth, risking my fingers being biten off).
    So the question, has anybody here heard or tried hydroxizine ( first generation antihistamine H1 )? Not much is available as to it's effect on GABA or serotonin but an article on science direct does mention it has calcium channel black age properties, which may explained why it worked for us like Verapamil for you.
    Thank you all for your the information you are sharing, I would have never guessed the histamine connection if not for this blog, and was about to start major medications like benzos for her.We never suspected allergies or inflammation, except for bloating that I was managing with enzymes.
    Thank you!

    1. Anastasia, very many different antihistamines are in use by people with autism. The problem with first generation antihistamines is that they will make you sleepy if taken in the morning, so not helpful to learning anything at school. If the drowsiness is not a concern, first generation antihistamines are perfect.

      You have to find what works best in your specific case.

      My son's assistant at school told me this morning that many pupils and teachers are struggling these days with allergies, but Monty has no signs at all. I told her there is a very good reason, he is taking several things to eliminate the allergy problem.

      Hydroxizine can be used to lower blood pressure. It does block some of the same ion channels as Verapamil.

      I think summertime raging is a multi-step process and you only have to block one stage to achieve tranquility.

      In my son Verapamil stops the raging, but not the allergy. In some people Verapamil halts the allergy as well.

  45. Sudhakar Vankamamidi3 April 2023 at 18:52

    Hi Peter,
    H1, H2 antagonist will just block the histamine receptors for sometime, but what substances can reduce the circulating histamine, i read vitamin C can help, can you share details please if more substances are available.


    1. Histamine, including its relevance to autism, is very well explained in Wikipedia.

      Read about DAO and HNMT.

      Some people have a problem with histamine contained in the food they eat (they lack enough DAO). Some people have a problem with histamine released in the body and some by histamine released in the brain. Note that histamine among its many functions is also a neurotransmitter.

      You can read all about the histamine-releasing mast cells here:-

  46. Sudhakar Vankamamidi23 April 2023 at 23:00

    Hi Peter, Verapamil worked wonders for us, we used it for few days successfully. But when child had junk food, he had SIB crash and you suggested it decreases DAO. So any clue how much DAO it may reduce to supplement it. Thanks Sudhakar.

    1. The key may be to just avoid junk food. It may be hard at the start, but a varied healthy diet is the basis on which to build success. Some people are extremely sensitive to what goes into processed food, it can trigger all kinds of issues like ADHD, allergies etc.

  47. Sudhakar Vankamamidi30 April 2023 at 13:12

    I shouldn't have used term junk food. He was eating oil fried snacks and they may be releasing histamines. Life was good when exact 4 hourly verapamil is given ending with neuroprotek. Today we delayed second dose of verapamil and he started SIB with laughter. Dont know how to solve it. Going read your new article again.

  48. Sudhakar Vankamamidi30 April 2023 at 13:55

    Niacin causes flushing and skin iches. I read itching is from histamine release. So can we say that Niacin helps in releasing excess histamine from skin and reduces histamine reactions. Thanks Sudhakar.

    1. Niacin causes blood vessels in your skin to expand allowing greater flow of blood. This causes your skin to turn more red. It is not a histamine reaction.

  49. Hi Peter, Long term use of either ketotifen or citrizine caused excessive food cravings. Are they related, if so how any clue please.

    1. Sudhaker, it is well known that some people put on weight when they take certain antihistamines.

      Association of prescription H1 antihistamine use with obesity: Results from the National Health and Nutrition Examination Survey,effects%20of%20treatment%20(6).

  50. You can get verapamil without a prescription through All Day Chemist. i've ordered from them for years. never that specific drug though.


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