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Wednesday, 16 July 2014

Verapamil for a Broader sub-group of Autism and even Diabetes?



This blog is about science rather than medicine, and believe me there is a much bigger difference than you might hope for.
Many aspects of the research literature indicate the potential of certain calcium channel blockers, like Verapamil, to be useful in treating autism.  As we have seen, there are many different causes of autism and what treatment works in one type may be totally ineffective in another type.

For almost a year Monty, now age 11 with ASD, has taken Verapamil to control the behavioural effects of allergy that are driven by so called “mast cell degranulation”.  His pollen allergy makes his summertime behaviour dramatically worse; a reaction that is almost entirely reversed by Verapamil.

In my page in this blog on Allergies and Autism I raised the question as to whether Verapamil would be effective in treating the many people with autism who have food allergies leading to gastrointestinal (GI) problems.  Many people with autism have symptoms like Irritable Bowel Syndrome (IBS) or Inflammatory Bowel Disease (IBD) and these are widely associated with worsening autistic behaviours.  Monty has no GI issues or food intolerance.  I was very interested to receive some lengthy comments from a mother with a son who does have autism plus GI problems.  She found Verapamil highly effective in treating both his GI problems and the autism.  This is rather significant, since while I do receive the odd comment that H1 antihistamines have an unexpected beneficial effect on autism, which supports some of my own findings and theories, the issue of GI problems is very common in autism.  Could a pill called Verapamil be the little wonder for them as well?  The science does indeed support this, even if current medicine does not.

 

How can medicine be so disconnected from science?  It does seem to happen far more often than it should.

I did wonder if I was missing something about Verapamil.  It is an L-type calcium channel blocker and in autism there is a known genetic dysfunction (CACNA1C) that affects the calcium channel (Cav1.2) blocked by Verapamil.  It also turns out that Verapamil has been shown to be a highly effective mast cell stabilizer.  I did a little more digging and found something very surprising, the effect of Verapamil on the pancreas.  The pancreas makes all kinds of enzymes as well as insulin.  In some people with an auto-immune dysfunction the body destroys its own insulin producing cells and diabetes results.  In some people with autism (also an auto-immune condition) the pancreas seems not produce some of the other enzymes and there are various DAN-type treatments for this; and the new CUREMARK drug CM-AT seems to target this dysfunction.

Science has remarkably shown that Verapamil had the potential to reverse diabetes, if intervention is early.  Given that type 1 and type 2 diabetes are becoming increasingly common and account for a substantial part of national healthcare costs, it seem odd that medicine has not taken full note.



It appears that older people on Verapamil for hypertension, strangely do not develop type 2 diabetes, which supports the claim for Verapamil.

There is no mystery as to why this is happening.  Calcium channels are widely expressed in pancreas, just as they are in the heart and the brain.  The effect of aberrant calcium channel signalling does no good for the brain in autism and in some other people, with a tendency to auto-immune problems, it would appear to be the pancreas that suffers.

You will recall that autism is amongst, other things, an auto-immune condition.  If you look at the extended family you will likely notice other auto-immune conditions like diabetes, thyroid problems, and arthritis.  (I would myself add fibromyalgia and even some types of chronic headaches to this list)

Recall that several drugs that help autism have a beneficial effect in diabetes and that the key type 2 drug for diabetes seems to have a positive effect on autism.

PPAR alpha, beta and gamma in Autism, Heart Disease and Diabetes


In the above post we saw that PPAR gamma (PPARγ) is a nuclear hormone receptor which modulates insulin sensitivity.  The following autism study looked at the effect of a common diabetes drug, pioglitazone (Actos), an FDA-approved PPARγ agonist used to treat type 2 diabetes, with a good safety profile. 
 

Pioglitazone is currently in Phase 2 trials for autism.

Another comorbidity of autism that is an auto-immune condition is asthma.  Here again, Verapamil was shown many years ago to hold promise.

Verapamil in the prophylaxis of bronchial asthma

A single oral dose of verapamil 80 mg was shown significantly to inhibit histamine-induced bronchoconstriction in 8 out of 16 asthmatic subjects (maximum increase in PD20FEVHi 416%). There was still significant protection (Δ PD20FEV1Hi>100%) in the responders 5 h after the oral dose.

I also noted in earlier posts that anti-oxidants seem to reduce the insulin required by diabetics and also improves one of the big problems that occurs along with diabetes that is peripheral neuropathy.  These antioxidants, like ALA, NAC, Thioctacid etc are also chelators of heavy metals.  While the planned study of chelators in autism in the US was effectively “banned”, a large study was carried out on heart patients.  Chelation was shown to be remarkably beneficial, but chelation is really just a shock dose of antioxidants.

Effect of Disodium EDTA Chelation Regimen on Cardiovascular Events in Patients With Previous Myocardial Infarction The TACT Randomized Trial


My take on this is that in many medical conditions, oxidative stress is present and therefore any antioxidant will be beneficial, but some more so than others.  In the well-researched world of asthma they concluded that the most potent, safe antioxidant was NAC (N-acetylcysteine).  NAC is my choice for autism.


Conclusion

If you have autism and suffer from chronic GI problems, Verapamil might well offer significant relief.

If you have unexplained autism flare-ups, like aggression, in summer this may well be driven by a pollen allergy, Verapamil is likely to help.

If your older relative has hypertension already and looks likely to be heading towards type 2 diabetes, maybe suggest they talk to their doctor about Verapamil;  it may well treat both.

Incidentally, if you have a child with autism and suffer yourself from chronic headaches or fibromyalgia, you might want to try some Verapamil yourself.

Verapamil is a very cheap generic drug; one tablet cost a couple of cents/pence. 


Opinion

I continue to be surprised how far medicine is behind science.

In the case of autism there is now a great deal of “actionable” research that is available for anyone to read.  This blog is about autism, but it seems that in many other areas of medicine the same is true, for example diabetes and types of cancer.   

The idea is that you should wait for clinical trials.  But who do you think is going to do them? There is no financial incentive for drug firms to do trials on old generic drugs for new uses.  Prepare for a long wait.

The medical practitioners involved with autism, mainly psychiatrists if anyone, show little interest in any novel treatment that has not yet been approved.  With such little interest from clinicians, novel treatments will remain well kept secrets for decades to come.

The “alternative” practitioners dealing with autism, like DAN doctors, are mainly in the US; but they are not fully grounded in science and seem overly interested in unorthodox expensive lab tests and costly supplements.

So you really do have to figure out autism for yourself, if you want to control it.  



16 comments:

  1. Peter, have you tried the verapamil gel? I wondered if it might be useful for those who have difficulty with pills

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    1. Interesting idea, but this gel has been designed so that the Verapamil does not enter the bloodstream.

      "The gel has been designed to carry the verapamil through the skin and deliver it to the fibroma. The proprietary formula allows for minimal absorption into the blood, while maximizing the concentration of verapamil in the fibroma and surrounding plantar fascia."

      As a result it would not be very effective.

      The Verapamil tablets are very small and can be crushed and added to a drink or even food.

      Delete
  2. Peter,
    I had upped the quercetin when I saw that my son's skin was beginning to clear but he was unable to handle it. Very loud and overexcited. Then agitated. We are trialing verapamil. This is the 3rd day. He started getting loud and active last night and it has morphed into escalated and SIB this morning. Yet, his skin looks even better. I am stopping the verapamil. I have been giving 40 mg 3X a day since Monday night.
    Thoughts?
    Nancy

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    1. Nancy, in some people there is a negative response to things that work well in others, but there has to be a reason. How does he respond to common anti-histamines like Claritin? Do they give a negative reaction?

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    2. I tried Zyrtec (I think that's what it was called). Same thing happened. Could it be a slow build up dosing process that I am not honoring? I jumped in with 40 mg 3x a day of verapamil.

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    3. Nancy, I just looked things up on google and a rare side effect of antihistamines is aggression. This is how your son reacts to things that clear up his skin. If you have the chance to see an immunologist, you could ask how do I treat my son's skin condition when he cannot tolerate antihistamines, quercetin etc. Maybe they know what to do. I would think solving this will help your son more generally.

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    4. Nancy, the same thing happened to my son on a very tiny dose of verapamil after three days...may I ask... is your son verbal?

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  3. Peter, what do you make of this paper/case studies, just out:

    "... reporting on two cases - "one with ASD [autism spectrum disorder] and the other with developmental delay, congenital deafness, and other multiple congenital anomalies" - attending a pediatric allergy/immunology clinic for "non-IgE mediated food allergy" and "delayed type food allergy around 4–5 years of age" respectively. In both cases treatment was made using "the second line allergy treatment, omalizmab" (also known as omalizumab), a humanised monoclonal antibody that "inhibits binding of IgE to the IgE receptor expressed on effector cells... and blocks allergen induced immune responses." Normally indicated for patients with 'convincing' IgE-mediated asthma (at least here in Blighty), both children were offered this treatment when first line allergy medications (steroid nasal inhalers, a leukotriene receptor antagonist, and topical ophthalmic solutions for ocular allergy) did not seem to be as effective as they should. Some quite surprising effects are detailed as and when omalizumab was started including a "marked attenuation of their problematic neuropsychiatric symptoms and subsequent improvement in the cognitive development, once respiratory allergy symptoms were under control."
    http://questioning-answers.blogspot.co.uk/2015/12/allergy-symptoms-affecting-autistic-symptoms.html

    What caught my eye of course was the fact that the children did not have an IgE-mediated allergy to start with, so why would omalizumab be helping...

    Then this:
    "Perhaps the most dramatic effect, which was not foreseen at the time when the anti-IgE therapy was designed and which was discovered during the clinical trials, is that as the free IgE in patients is depleted by omalizumab, the FcεRI receptors on basophils, mast cells, and dendritic cells are gradually down-regulated with somewhat different kinetics, rendering those cells much less sensitive to the stimulation by allergens.[26][27][28] Thus, in this regard, therapeutic anti-IgE antibodies represent a new class of potent mast cell stabilizers,[25] providing the fundamental mechanism for omalizumab's effects on various allergic and non-allergic diseases involving mast cell degranulation..." (wiki)

    Are there any (safer, cheaper and more accessible) alternatives to omalizumab for depleting free IgE?

    ReplyDelete
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    1. Natasa, thanks. We can add omalizumab to the list of mast cell stabilizer to trial in autism.

      The alternative that comes to mind is Verapamil, which is extremely cheap.

      People with autism, who cannot tolerate Verapamil, might well want to try Omalizumab if somebody else is paying for it.

      In a few years it will be a generic drug and then the price will tumble.

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  4. First dose of verapamil yesterday... My son can be very sensitive to meds... For instance with bumantenide I gave him 1/8 of a pill ( he is 14 kg) and he was extremely hyper ... Verapamil ... He had a great gi day... But woke up at 6 am ... Which is very unlike him he normally sleeps til 8 or 9 ... So we know there is an affect ... But what could be causing the extreme sensitivity I gave him only 5 mg or verapamil

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    1. He is very small and some people metabolize drugs differently. Perhaps it interacts with some other therapy you use. If he responds to a very small dose that is an advantage. Best to see if the good effects are maintained in the coming days. It would be great if you could keep a record so that you can share the experience with others.

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  5. Hi Peter,
    We are trying histidine at your suggestion for my adult son's blistery skin. Within a week, his skin had major improvements. I also upped his supplements containing quercitin. His mood, though slightly more hyper, has been pretty great. So I think we are onto something with treating mast cell issues.
    I am hoping Dr. Rossignol will prescribe verapamil in the near future.
    My son's attention short term memory were severely compromised with his second regression around age 5. It has never come back .
    Any ideas as to what we might try for that? Might verapamil also improve things in that area? Thanks.
    Nancy

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    1. Hi Nancy, I am glad the histidine helps. In some people autoimmunity/allergy makes autism worse and so everything you do to bring the immune system closer to balance will help.

      Verapamil may very well help, if your son is a responder you will know within a few days. It does not require a large dose and most people tolerate it very well.

      We get an allergy benefit from the Biogaia Protectis probiotic. The research does show that it can modulate the immune system. The effect does fade after a while and so people use it in cycles. I would suggest you try it, say two tablets a day. There is also Biogaia Gastrus, which contains an additional bacteria. In my son Gastrus had a negative effect, but Protectis is good and the effect is within a day or two.

      For cognition (making GABA inhibitory) I am using bumetanide, potassium bromide,low dose clonazepam.

      Atorvastatin helps with cognition but in a different way.

      If you have not tried bumetanide, ask Dr Rossignol to prescribe it. It now has plenty of evidence to support it.

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  6. Nancy, Peter, What brand of Histidine do you suggest? And what dose are you using?

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    1. Audrey, I use Bulk Powders histidine. It comes in a bag and looks like white sugar, it dissolves in any drink. The scoop provided equals 1 gram. I give 1 g once a day.

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  7. I started with Douglas Lab L-Histidine 500 mg (2 caps in the morning and 2 in late afternoon.)
    In looking back at my notes, I noticed that my son had tried verapamil 40 mg and behaviorally became escalated and self-injurious. I am wondering if a lower dose to start would prevent that negative reaction.
    We currently are on bumetanide and low dose conazepam, as well , but nothing seems to be affecting the attention piece.

    ReplyDelete

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