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Saturday, 27 July 2013

More on anti-histamines in Autism and introducing H4

In my previous posts on histamine, you would have read that I found that Claritin appeared to reduce autistic behaviours.  Once I had got to the bottom of what was going on, I found out that histamine has a long record of stimulating challenging behaviour in all children.  It also became clear that typical anti-histamines (H1 antagonists) are all slightly different and one may be effective in one person and ineffective in another.  Each one tends to have additional secondary effects.

It now appears that the secondary effect of certain H1 antagonists may actually be more important than the primary intended effect of reducing itchy eyes and runny noses.
There are three generations of H1 drugs.  The fastest working and most potent is still the first generation, the second generation are non-drowsy derivatives of the first generation.  The third generation are the active metabolite of the second generation.  As you will see in today’s central paper, the third generation probably does not warrant the tittle.  For many users they may be just expensive versions of the second generation drug.

The excellent paper  New anti histamines: a critical view is from Brazil, but it has an English version.  It is highly readable.  It tells of the specific secondary effects of certain second generation  H1 antagonists.   (She omits to mention the secondary effects of the first generation. Some people say Ketotifen is 1st generation and other people say 2nd generation, anyway it appears not to be sold in Brazil).  I suggest you read the paper, if you have a child with an ASD. The key section is this:

Antiallergic/anti-inflammatory effects

Originally, studies of the relative potencies of H1 antihistamines were based on the capacity of different compounds to competitively inhibit the H1 receptor binding of histamine, i.e. on their blocking effect on the receptor.8 Nevertheless, it has already been known for some time that, in addition to acting on H1 receptors, many H1 antihistamines, at appropriate doses, are capable of inhibiting not only the release of histamine by mast cells,9,10 but also mast cell activation itself.11 Some of them can even regulate the expression and/or release of cytokines, chemokines, adhesion molecules and inflammatory mediators.5,8

Therefore, the antiallergic properties of H1 antihistamines are generally a reflection of their capacity to affect mast cell and basophil activity, inhibiting the release of preformed mediators such as histamine, tryptase, leukotrienes and others.8 Several second-generation H1 antihistamines have demonstrated antiallergic properties, irrespective of their interaction with the H1 receptor.5,8

Chronic allergic inflammation resulting from the late-phase reaction, exhibits components that are similar to other forms of inflammation, including chemotaxis of inflammatory cells followed by activation and proliferation, with subsequent production and release of many chemical mediators. Among cells involved in allergic inflammation are: antigen-presenting cells (for example, macrophages), mast cells, basophils, T lymphocytes, epithelial/endothelial cells and eosinophils - major effectors of chronic inflammation. Cytokines, chemokines, inflammatory mediators and adhesion molecules also contribute to this process which ultimately leads to dysfunction of the affected organ.8

Many second-generation H1 antihistamines (particularly cetirizine) are capable of inhibiting the influx of eosinophils to the site of allergen challenge in sensitized individuals.5,8 Studies have demonstrated that some of them can also alter adhesion molecules expression on epithelium and eosinophils, and reduce in vitro survival of eosinophils. Finally, some second-generation H1 antihistamines are capable, in vitro and in vivo, of altering the production of inflammatory cytokines (for example, TNF-a, IL-1b and IL-6) and the Th1/Th2 balance regulation cytokines (for example, IL-4 and IL-13).5,8

Therefore, it is well established that, in addition to their effects on H1 receptors, many second-generation H1 antihistamines also manifest antiallergic and anti-inflammatory properties which differ depending upon their molecules and the experiments used for their evaluation.5

 
From my own experience, I have already replaced Claritine (Loratadine) with Cetirizine to see if it will remain active for longer.  Rather than working for 24 hours, Claritine is working for about 5 hours.
I thought Cetirizine might remain active for longer, but the main difference seems to be in how it works, rather than for how long it works.  With Cetirizine autistic behaviour has pretty much returned to where it was at the start of summer, before the allergy season.  With Claritine things improved greatly, but not all the way back to "normal".

Reading the paper and one of its references -
makes me think that the expensive new  version of Cetirizine, called Levocetirizine, might be even better.  It happens to be available locally, but it is seven times as expensive.

The Brazilian paper does rather contradict some of what Dr Theoharides says about stabilizing mast cells.  You can choose who you think has got it right.  The good thing is that both Dr Inês Cristina Camelo-Nunes and Dr Theoharides seem very serious, objective people, which cannot be said about all the people offering their advice on the internet.

In fact, I found an interesting paper on the anti-inflammatory effects of the new version of Claritin, called Aerius/Clarinex (Desloratadine).


It really seems to be the case of trying several antihistamines and selecting the one that works best for you.
 
The H4 Histamine Receptor and Inflammation
You may recall that there is a fourth histamine receptor, naturally called H4.

It was only recently discovered, as you might guess from the short entry in Wikipedia.  It seems that the H4 receptor plays a substantial role in the inflammatory response.  It is seen as playing a key role in conditions ranging from arthritis to asthma.
Here is a full text paper for those interested in the science:-

The role of histamine H4 receptor in immune and inflammatory disorders

 Here is a graphic from that paper:-

I wonder if that H4 is a ticking bomb in autism as well ?

Those more peaceful people among you will be less aware of what C4 is, and hence the sticks of H4 dynamite.





 



 

21 comments:

  1. A year or two ago I gave my son children's Zyrtec for seasonal allergies, and noticed an immediate positive effect in emotional and stimulus regulation and social development. At the time nobody seemed to know what to think, but with the doctors approval, we started him on a daily low dose. I've been willing to sum it up to anxiety management, but now it seems there may be more involved.

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    1. Hi shawn, when you say low dose is it less than whats recommended on the bottle? Are you still continuing with gains noted?

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  2. I think what may be happening is the H1 antihistamines like your one also have an effect on the H3 and H4 receptors in the brain. The amount of histamine released remains the same, since only the receptors are blocked.

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  3. I, too, noticed a positive leap in language development for my 19 month old immediately after starting Zyrtec

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  4. Has anyone tried generic Claritin with their child who has Asberger's? I suspect my son has this and he will lay in bed for two hrs before being able to fall asleep! I've tried many different things, such as having him read, magnesium salt bath, valerian capsules and much more! Nothing seems to help. I worry about giving Claritin on a regular basis, as it can make mucous membranes really dry! I don't like to use many drugs if I can help it. But so far nothing else has worked! Thanks.

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    1. Some readers of this blog are using Zyrtec every day, which works very much like Claritin. For sleep problems in autism a small dose of Melatonin is often used. If histamine is the problem, you can also use the flavonoid Quercetin, which is available as a supplement, it is a "natural anti-histamine".

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  5. I gave my son cetirizine for his allergy and I noticed immediate improvements in his behavior and language, he became more talkative and follows instruction, he even tried other food. I wonder if is safe for daily intake..

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    1. If you look on the internet you will see that many people with allergies use cetirizine year round. It is certainly far safer than the drugs normally prescribed for autism and ADHD, which have well known side effects.

      One idea might be to find another anti-histamine that is effective and then use one for a month and then the other.

      If you can find the source of the allergy, you could then reduce exposure to it.

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    2. thanks Peter!

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  6. Hi Peter, did you try levocitrizine?
    And what are your thoughts on quercetin? I read conflicting repiets that it can have negative effect on GI ?

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    1. I have tried numerous anti-histamines and quercetin. Different people respond to different anti-histamines, you just need to try several, including the old first generation ones.

      Quercetin works in a different way. Some people have no side effects. I tried it on myself and after a while developed tendonitis in one ankle, which resolved when I stopped quercetin, but it definitely did have other positive effects. Some people have no side effects. We had no GI side effects.

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    2. Quercetin can reduce ferritin levels further for children with ASD who are deficient. Great for children who have too much of course.

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    3. Hi Em,

      We can't use quercetin here due to my daughter's epilepsy. Do you know of any other substances that can reduce ferritin? My daughter for years has had very high serum ferritin levels.

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  7. Hi RG, if you don't mind, could you give me some information about your daughter's epilepsy?
    Is she officially diagnosed with epilepsy and if so, what kind of?
    My nephew, from my first cousin, living in the sates was diagnosed with temporal lobe epilepsy, he only had one episode, and has been on Lamotrige XR for several years. He seems to respond quite well.
    Thank you.

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    1. Hi Petra,

      She has a diagnosis of epilepsy, but they could not pinpoint a location as she did not have any seizures while on the EEG, even on the 5 day video EEG.

      Is your nephew autistic? Its great that he has responded well. I have had two friends' autistic children react badly to lamotrigine, pretty severe regressions, so am wary. It is also the reason I went to the ketogenic diet as a first line intervention. Verapamil, Diamox and frankincense have helped the best so far. With verapamil we have had several two month periods free of seizures. Diamox cleaned out almost all the non catamenial ones as well as preventing tonic clonic. Along with the frankincense, most seizures are simple or with some tonic only involvement, fully conscious throughout and no post ichtal phase, immediate clean recovery.

      Radhe

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    2. Hi RG,
      How does frankincense help? How do you use it? Thank you.

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  8. Sorry, the antiepileptic drug is Lamotrigine, Lamictal XR.

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  9. RG, you may have already seen this article, but just in case you missed it, here is a link:
    Suppression of Iron-Regulatory Hepcidin by Vitamin D
    Published online before print November 7, 2013, doi: 10.1681/ASN.2013040355
    JASN March 2014 vol. 25 no. 3 564-572
    It might be relevant.

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    1. Thank you Petra. I had not seen it before.

      Its interesting because my daughter's vitamin D levels tend to be low consistently. In the past we had to give very high doses of around 10000iu to bring it to within normal range. Recently, she has been reacting negatively to supplementation, I have suspected that a couple of seizures were right after trying Vitamin D capsules. So I have let that be, relegated it to the no-explanations-yet pile, along with high uric acid, high fibrinogen, low tyrosine and threonine and citrulline. This reminds me that the one thing I should be doing immediately is test her for creatinine deficiency, she has always tested low on it.

      Its also interesting that serum ferritin has been high irrespective of vitamin d status, off and on supplementation. It has also stayed independent of dietary modifications. She used to eat liver regularly, and it stayed high even when we stopped.

      Apparently, high inflammation will cause serum ferritin to be high. Which makes sense in our case, except to add to the paradox, high IL6 can raise hepcidin which lowers ferritin. I wonder then what it means, that other cytokines are high, just not IL6? Or is it something else entirely?

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  10. Interested in your opinion on this product? My son's behaviors et al irritability/aggression etc diminish on zyrtec. Product: https://www.seekinghealth.com/histamine-block#customer-reviews We have not tried this product, but interested in your opinion, thanks

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    1. Wolf, this product contains DAO which is used to degrade histamine. This product might be suitable for people who have histamine intolerance, because they do not produce enough DAO to degrade histamine. Most people with allergy do not have histamine intolerance.

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