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Monday 27 July 2015

Verapamil, Autism, Summertime Allergy, Asthma and Eczema


















As the symptoms get stronger, so does the therapy, 
going up in steps from May to July/August and then down to October


Today’s post is a practical one.  There is an interesting scientific one in preparation all about applying the emerging science of gene silencers and enhancers. 

I discovered in previous years that the summertime raging exhibited by Monty, now aged 12 with ASD, could be prevented using a small dose of the L-type calcium channel blocker, Verapamil.  Verapamil is also a mast cell stabilizer and blocks potassium channels linked to some inflammatory response.

This summer the story has repeated itself.  As the amount of airborne allergens increases from spring to summer the same seemingly mild allergy symptoms return.  So in late spring there was some sneezing and by mid-summer some eczema (atopic dermatitis) behind the knees and finally a very mild amount of asthma (slight wheezing); all of which were easily treated.

This apparently mild allergy triggers a flare-up in autism that is anything but mild.  To treat that the “silver bullet”, so to speak, is Verapamil.  It has a short half-life and so after 3-4 hours, depending on the initial dose, the effect is lost.  So in the peak of the allergy season, 20 mg every 4 hours provides near guaranteed protection.  Skipping a dose, like first one in the morning, will almost guarantee a mood change to agitation and then extreme anger.  That mood reverses within a few minutes of treatment again with Verapamil.

In late spring and early summer the use of allergy treatments (Azelastine, plus quercetin) and verapamil twice a day keeps things all under control.  But once the first faint signs of asthma reappear, due to the growing allergy effect, the only way to maintain normalcy is to make more frequent use of small doses of verapamil.  Using more antioxidants (NAC) does not have any effect; the verapamil addresses a summertime need.

In a previous post I did mention that I tried verapamil on a winter-time flare-up, just to see.  It had no effect whatsoever.  That problem was traced back to losing milk teeth and was solved with some ibuprofen, which was later replaced with Sytrinol/Tangeretin, the PPAR gamma agonist.  

Some children with autism are treated long term with Ibuprofen, or other NSAIDs, on a daily basis.  I have no doubt that it can be effective in specific cases, but the known side effects made me look for a safe alternative, which turned out to be Sytrinol.  Sytrinol has exactly the same effect as Ibuprofen, for this kind of flare-up, with no apparent side effect. Sytrinol is not a painkiller.

Since the roots of the final four milk teeth take several months to melt away and all the time levels of the inflammatory cytokine IL-6 are raised, there will be recurring behavioral flare-ups in those with the kind of over-activated immune system common in autism.  It seems plausible that the PPAR gamma agonist is down regulating  the activated microglia and thus blunting the immune over-reaction.  Anyway it works, for whatever reason.

The mast cells, degranulating due to allergens, release histamine and IL-6, the histamine causes further subsequent release of IL-6. Verapamil blocks this process.  The IL-6 released by the body to signal teeth to dissolve clearly is not reduced by Verapamil. 

The amount of inflammatory cytokines (IL-6 etc) produced by allergy is logically over a different order of magnitude to that used to signal milk teeth to dissolve.  The effect of Sytrinol is perhaps too mild to sufficiently dampen the response to the IL-6.   Maybe it helps somewhat, but I really cannot say one way or the other.

There seems to be a good case for Sytrinol year round and then Verapamil as required.  When I next update my Polypill formulation, Sytrinol will be included.

I think Verapamil likely has beneficial pleiotropic effects and so, in those who well tolerate it, it might be useful year round.  A small number of people do experience side effects.
     







8 comments:

  1. Hello.
    My autistic son gets better from his symptoms every time he takes Allegra D. His vocalization, stimming and hyperactivity all improves with this drug. A 23andme test showed that he has the genes for histamine intolerance. Others anti-histamines don’t work as good as Allegra.
    My question is: is safe to use this medication long term? Is there a natural alternative?
    The only, but bad sad-effect is loss of appetite and he is already a thin boy.
    Thank you!

    ReplyDelete
  2. There is a great deal of information on this blog about allergies and mast cells. Since your son has histamine intolerance, it is worth reading up on the subject. Quercetin is natural and may also help, but also can have side effects. Plenty of people with mast cell issues are taking various drugs on a daily basis, since benefits outweigh any minor side effects. A mast cel stabilizer is likely to be even more effective than Allegra, there is plenty on this blog about those. Since you have a spefiic genetic piece of analysis, why not go and see an Allergist/immunologist?

    The most effective treatment may indeed be verapamil. It is certainly worth a trial.

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  3. Hi Peter,

    Today, a bit after her first meal, my daughter became distressed, with SIB and raging. This was within an hour of taking both Verapamil and magnesium so I followed up with Bumetanide. That took the edge off a little bit, but distress continued. These three are my big guns and any one of them will usually be enough. The only times when she is completely non responsive to verapamil or bumetanide is before a seizure. So, I thought that she must be brewing one. About an hour after the bumetanide, the rage went down in intensity, but a low level irritability and SIB continued for several hours. Then, she had her next meal, and immediately after, the rage and SIB began escalating. By this point I was desperate, and I gave her one capsule, 150mg, of Sytrinol. Within minutes, behavior returned to normal. One hour later, she became happy and began engaging and playing with me. Two hours later, wanted to do class with me and did her toughest one, reading. Did it excellently as well.

    What do you think is a good dose of Sytrinol? I thought 150mg twice a day.

    Btw, I have no idea what caused today's flare. It might have something to do with her food. She has been fantastic the last week since I switched her from 300mg magnesium taurate and 300mg magnesium citrate to all magnesium taurate. It was as if, her emotional regulator was suddenly working. More normal, emotions were not spiraling up.

    ReplyDelete
    Replies
    1. I think Sytrinol 150 mg twice a day is a good idea.

      I would also suggest you add Ibuprofen 200mg to your armory. This is a low dose, but it does have a very prompt impact in some of these crisis situations. Some people with autism are on NSAIDs every day, this does risk the side effects.

      Delete
  4. Would it be safe for 7 year old weighing 40 pounds to take sytrinol? If yes how much dosage would you recommend? ... Did milk teeth falling caused any other symptoms in your son? My daughter is giggling a lot for no reason and suddenly crying thinking about something that happened in the past. Again it's a new symptom that started with milk teeth falling....thank you

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    Replies
    1. I took the view that sytrinol, should be safer than ibuprofen, but you have to make such decisions. The IL-6 produced by loss of milk teeth will affect those people sensitive to it; this is very likely the same people who have allergies that worsen their autism.

      This may change over time, for better or worse.

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  5. Hi Peter. I found an interesting paper on IL-6 elevation causing autistic symptoms.

    http://www.sciencedirect.com/science/article/pii/S0925443912000233

    I found the last section compelling in the context of how Verapamil can be an effective treatment, especially since my ASD son's labs came back showing elevated IL-6:

    "To further investigate how IL-6 elevation affected the balance of
    excitatory and inhibitory processes, we recorded fEPSPs in the CA1
    area of the hippocampus in acute slices. We detected a reduced postexcitatory
    inhibition in Ad-GFP-IL-6 mice. Postexcitatory inhibition
    analyzed by paired-pulse inhibition (PPI) has been suggested to be
    caused by a decrease in the release of excitatory neurotransmitters
    from terminals of afferent axons [73–75]. This effect is likely the result
    of an inhibition of calcium influx through presynaptic receptors
    which play a causal role in the release of glutamate from synaptic
    vesicles on afferent stimulation [50,76]. Thus, the reduced PPI in
    Ad-GFP-IL-6 mice indicates an increased release of excitatory neurotransmitters
    possibly stimulated by calcium influx. Orellana et al.
    [77] demonstrated that IL-6 treatment of rat hippocampal neurons
    increases the calcium influx via the NMDA-receptor and is mediated
    by the JAKs/STATs pathway. We suggest that IL-6 elevation in mouse
    brain could cause a reduced PPI through increasing calcium influx
    and stimulating the release of excitatory neurotanmitters. Decreased
    PPI has also been shown in some other neurological and psychiatric
    diseases including Huntington's disease, schizophrenia and in
    Down's syndrome [50]. Several lines of research have presented convincing
    data demonstrating an association between defects in inhibitory
    capacity and cognitive impairment [50,78].
    In summary, our study supports a critical role of IL-6 elevation in
    modulating autism-like behaviors through impairments on synapse
    formation, dendritic spine development, as well as on neuronal circuit
    balance. These findings suggest that manipulation of IL-6 may
    be a promising avenue for therapeutic interventions."

    Is the calcium influx that these researchers are referring too the same calcium signalling that Verapamil blocks? Moreover, perhaps Verapamil is killing 2 birds with 1 stone (lowering IL-6 and Calcium)?

    ReplyDelete
    Replies
    1. Verapamil blocks one type of receptor, there are many other types, but the type it does affect does influence the broader calcium metabolism via OPG. So there may be a broader effect. It might be that blocking other calcium channels might also be beneficial.

      So verapamil will reduce calcium influx, but only in certain places.

      IL-6 is indeed public enemy number one for autism. Many things can be used to reduce it and what helps arthritis may very well help autism. Ibuprofen can be very useful, but is not suited to long term use.

      Verapamil will lower IL-6 released from mast cells, but IL-6 has many sources. So you would likely need other therapies, such as occasional use of Ibuprofen. One reader, Alli, is using Ibudilast which seems to give the good effects of ibuprofen, but without side effects. Ibudilast is a widely used in Japan.

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