Monday, 24 March 2014

Summertime Raging in Autism – H1 Anti-histamine Effect on Histamine Levels and IL-6

Last summer, I wrote a lot about autism getting much worse in that time of the year and how I found that common “24 hour” anti-histamine drugs seemed to have a magical effect; but one that lasted only 2-3 hours. There were only visible signs of a mild allergy, which could indeed easily be overlooked.

I did later receive a message from a reader who noticed his child’s ASD behaviours were greatly improved by Zrtec and his doctor agreed to prescribe this H1 antihistamine all year round.

Recently, I stumbled upon a blog, rich with many comments of parents of kids with severer types of autism.  Here I noted some parents referring to “summertime raging”, and I thought to myself, I know what they mean.  Fortunately, I found out how to make it go away.

Ant-histamine drugs

The two most common antihistamine drugs are Claritin (Loratadine), its active derivative Aerius (Desloratadine) and Zrtec (Ceterizine) and its active derivative Xyzal (levocetirizine).

The main action of an antihistamine is not actually to reduce the amount of histamine in your blood, rather it is to block the effect of histamine on the H1 receptors.

An H2 antihistamine blocks H2 receptors that are mainly in your intestines, and is used to reduce the amount of acid in the stomach.

This led me on a quest for substances that actually stop the increase in histamine, rather than just blocking some effects.  The only thing that does this is something that can stop so-called mast cells from degranulating and spilling their load of histamine, serotonin, nerve growth factor and cytokines, including IL-6, into the blood; from where, all except serotonin, are free to travel to the brain, across the blood brain barrier (BBB).  Serotonin cannot cross the BBB.

According to the mast cell specialist Theoharides, conventional drugs are not genuine mast cell stabilizers.  There are some partial ones, like Ketotifen, Cromalin, Rupatadine and Azelastine, but Theoharides thinks naturally occurring flavonoids like Luteolin and Quercetin work best.

Last summer in this blog I looked at newly discovered histamine receptors types H3 and H4 which are known to be present in the brain.

So how is it that Claritin and Zrtec can reduce autistic behaviours ?

I did note that both the above drugs did reduce summertime raging and also the Theoharides' research that showed they probably should not, since they are not mast cell stabilizers. 

Since my blog reader also found Zrtec helpful, so much so he gives it to his kid year round and it now seems summertime raging is not an unusual phenomenon in autism, I did some more checking.

In spite of what Theoharides tells us, it turns out that both Claritin and Zrtec do indeed reduce the amount of histamine in the blood.

Also, it turns out that not only is the pro-inflammatory cytokine IL-6 released from mast cells but it is also released from another type of cell, called the endothelial cell.

The endothelium is the thin layer of cells that lines the interior surface of blood vessels and lymphatic vessels, forming an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. The cells that form the endothelium are called endothelial cells. Endothelial cells in direct contact with blood are called vascular endothelial cells, whereas those in direct contact with lymph are known as lymphatic endothelial cells.

And what prompts endothelial cells to release IL-6? Histamine does.

Indeed we have studies showing how Claritin (loratadine) and  Zrtec (Ceterizine) reduce histamine and IL-6; it is the IL-6 from the endothelial cells.


These results demonstrate that both L and DCL are active to reduce the histamine-induced activation of EC. Interestingly, DCL seems to be effective at lesser concentrations especially to inhibit cytokine secretion."

The above study would suggest that Aerius (DCL) should be more effective than Claritin (L) its predecessor.

"Histamine is a major constituent of the mast cell. The effect of histamine on endothelial cells is primarily mediated through H1R

Collectively, our results suggest that mast cell-derived histamine and proteases play an important role in vascular inflammation and calcification in addition to their well-recognized participation in allergic diseases."

This study, and others like it, show how mast cell degranulation contributes to heart disease.  This would suggest that mast cell stabilizers have a much wider role in human health than is realized.  Another example of how a red apple a day (with the skin) may indeed help keep the doctor away and a glass of red wine will do the same.  Both are rich sources of the mast stabilizer Quercetin.  The alcohol increases the bio-availability.


These results suggest that cetirizine exerts its beneficial effects on viral myocarditis by suppressing expression of pro-inflammatory cytokines, genes related to cardiac remodeling in the hearts of mice."

So how do Claritin and Zrtec reduce summertime/year round raging in autism?  Well it could be histamine or it could be IL-6, we cannot know for sure.  The science tells us that the brain has many H3 and H4 receptors, so they are possibly to be implicated.  Or, it may just be IL-6;  histamine’s involvement could be just provoking the endothelial cells to release more IL-6.


Claritin/Zrtec/Xyzal are relatively cheap, in theory they are long lasting drugs.  In Monty, aged 10 with ASD, they all work for summertime time raging, but not for long.  Adults should take one per 24 hours.  Monty would need one every 3 hours.

The, supposedly better, mast cell stabilizers like Ketotifen and Rupatadine take a few days before they have any effect at all.  Azelastin is available as a nasal spray and is supposed to be effective quickly as an allergy treatment.

My preferred mast cell stabilizing, IL-6 inhibiting, strategy is to combine PEA (palmitoylethanolamide) which is already naturally in your body, with the flavonoid quercetin, which is found in the skin of red apples and red grapes.  In theory, according to the research, this is both a potent combination and should be free of harmful side effects.

Very frequent doses of Claritin/Zrtec/Xyzal are not going to be good.



On this blog:-


  1. Hi Peter,

    We can attest to the effect of Zyrtec as indeed being 'magical'. It reduces those 'autistic' type behaviours. It completely eliminates all stimming - in our child's case this is hyperkinetic behaviour, skipping/spinning from one side of the room to the other feverishly.

    Why is this? What are the mechanisms behind this? Nothing else comes close. Is Zyrtec doing this for the right reasons. Claritin is not effective whatsoever.

    Zyrtec just seems to calm him down and allow him to focus and increase awareness without turning him into a zombie as Risperdal. We've never had any reason to believe our child has allergies and all blood-work has indicated he is allergy free. So why is this so effective?

    The following is an example of the effects of Zyrtec: We're at a party for a child in our childs' class as recent as today. He first approaches the mother of the new kid and very politely asks for her name because of course he must know her name as he knows the name of every other mother. He then sees a child crying at the table and approaches the mother of that child and politely asks why her child is crying. This might seem insignificant to some but to us it's hope! Most social and behaved he has ever been. It's a platform for hope.

    Without Zyrtec: Run across the room from wall to wall without approaching anyone.

    Peter, can Zyrtec be taken long term? We are giving him 5ml daily (56kg - 9 year old). Is there anything that can augment its effects?

    Very thankful again Peter.


    1. It is almost certainly allergy-related, otherwise Zyrtec would not help.

      It only takes a very minor allergy to produce violent SIB in our son. Nobody noticed the allergy.

      Now you need to figure out the source of this minor allergy. Is it pollen, dust, food etc.

      If it is worse in summer, then pollen is likely. People have allergies to all kinds of things. In typical people you only notice major allergies. In some people with autism, just a tiny rise in histamine/IL-6 can affect behavior.

      It is well known that Claritin does not work at all in some people. It is often recommended to try different anti-histamines to find what works best for you.

      If you know the problem is allergy, then you have to look at mast cells and how to stabilize them. Zyrtec is only a mild stabilizer; there are much better ones, but maybe Zyrtec is enough. I ended up with Verapamil, but that needs a prescription. It is known as a calcium channel blocker and almost nobody would think of using it for allergy.

      You can look on-line for possible effects of long term use of Zyrtec. You are only using a low dose. To match the effect we have from Verapamil I would need to give that dose 6 times a day.

      I would stick with Zyrtec and look for the source of the allergy.

  2. Peter,

    Do you still recommend the PEA/Quercetin combo? We are ready try mast cell stabilizers and/or anti-histamines, but drugs are not an option for us. You haven't written about PEA in while. Do you still think it is worth trying?


    1. If you have allergy I would first try Biogaia Protectis. This had more effect than antihistamines. PEA had no effect, Quercetin does help but produces side effects in some people.

    2. Thanks for your reply. No allergies, but episodic flare-ups have led me to consider histamine as a possible trigger. I was also reading your posts on Acacetin. Any thoughts on this versus PEA/Quercetin as a mast cell stabilizer?

    3. I would try quercetin and if that does nothing during a flare up I would try ibuprofen. NSAIDs like ibuprofen are surprisingly effective in many people with autism for certain types of flare-ups.

  3. Hello Peter,

    Second day on NAC, 600 mg, once a day. Nothing to report. One of those OK days , when he is not too stimmy and upset, which thankfully is a rare occurrence.
    Thinking of adding another 600 mg in the afternoon or evening but running out if ideas as to how to administer it. He is getting bored of juice, the tablet is big and tastes bad. I think warm cereal or or meal will not be wise as it will accelerate the disintegration provess. Any suggestion?

    Peter, if we control all undesirable behaviour in a growing child with drugs, we will not be able to intrinsically modify the child's development and teach him self regulation, which ultimately has to be our objective. I mean, it's completely justifiable for unregulated SIB or violence or even disengaged stereotypy or even severe hyperactivity. But, if we change everything temporarily with chemicals, there will be no one left to try and change permanently. To give you an instance, few days back my son was looking with that sideways glance, which really makes him look 'out of this world', and I gently asked him what he was looking at? Encouragingly, he looked at me, shook his head and smiled.

    Do I want a bacterium driven hug from my child? I don't think so. Would I like him to learn to be aware and conscious of his behaviour including those stemming out of anxiety? Yes. Would I want him to learn to devise his own coping strategies, probably with a little help, to deal with his issues. Of course.

    My family, immediate and extended, is densely populated with hugely talented but social atypicals, the recluses and rebels, but they did OK for themselves.

    What I really want your opinion on is that in a child who is still developing , how far should we be willing to go in our quest for behavioural modification through pharmacological intervention. What should be our absolute non-negotiables?

    1. Kritika, I think it is perfectly fine to be different. When people's difference becomes disabling, then it is worth trying to change things. This can be by developing coping strategies, behavioral intervention, and in severe cases with drugs. I would not give drugs to typical child with ADHD, but I think all kids with classic autism should be treated by the effective drugs, which ever those might be.

      If a child is deficient in oxytocin and so does not bond with its family, that may make their burden very hard to deal with, if the child is severely disabled. Then it is good to intervene. A person with Asperger's might choose to self administer oxytocin or something else just to make it easier to fit in with the world, that is their choice. They might choose to be a recluse, again it is their choice. Severely affected people with autism cannot choose, so it is up to the parents. People will make different choices.

      I think you should match the level of intervention to the severity of the disability. This is why you need to know how disabled someone is. You can have Aspergers and find it is disabling, or you can be perfectly happy with it. If you have classic autism you are de facto disabled.

    2. Peter, you are right. I am completely in agreement with regards to intense parental involvement and absolute requirement for intervention, including drug therapy, in helping an autistic or any other child with a disability. I was more concerned about the masking of issues which drugs might bring about without really bringing about an inherent change in the core development. I mean..should I make my child inhale oxytocin or play with him a liittle more to encourage bonding. The latter will have a more lasting outcome. Sorry, the example I have cited is really oversimplifying things and they don't work this way but I was visualising a future where my child cannot function without drugs because I did not focus and work hard enough on the issues, while I could, which a cocktail of drugs suppressed but could not resolve.

      Finally, I think pondering on these theordtical concerns and imaginary scenarios is a waste of time and energy. We already have our hands full.

    3. We crush/chop NAC (it usually comes in big tables) and stuff it in an empty gel capsule. This is then easy to swallow, provided child can swallow caps, and doesn't taste bad. Hope this helps.

  4. Hi Peter, I am trying Loratadine this week. You mentioned the dose wearing off after a few hours. I am just trying it to see if it will affect our type of autism. In the spring my daughters IgE was elevated without overt allergy symptoms. I just re-tested her IgE yesterday but will give her the meds until I know the results. If this one does not work I will try the next one as you described. I am wondering if I should dose every 4hours or just once every 24 hours as indicated on the bottle to see if it has any effect, and how many days should I give it a try? Thank you.

    1. Agnieszka, Loratadine is supposed to be effective for 24 hours, but for many people is not. In mast cell disorders very high doses of H1 antihistamines are prescribed. I would try one a day and see if you have an effect and then try two a day. If there is no effect after a week I would assume your daughter is not a responder. I would give at breakfast and in early afternoon. She has to be awake for you to see any positive effects.


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