Probiotics – Science and Pseudoscience

Once anyone starts to make claims that some autism is treatable, people respond in different ways.  Those applying what has always been taught in medical school, that autism is untreatable,  will either think you are making it all up, or worse, you are some evil person taking advantage of parents in emotional distress.

The very few people who read the research about things like metabolic errors and intracellular signaling may well take a different view. Also the oncology/cancer researchers who themselves think about sub-types of disease that are induced by specific signaling pathways (like RAS-induced cancers for example), may well see the sense in experimentation like that in this blog.

Medicine does indeed say that autism, Down Syndrome and ID/MR are untreatable; however current science does not support this.  Your local doctor applies medicine; he is likely totally out of his depth when it comes to where science is in 2016.

My posts are just my take on the science, I am well aware that some clever neurologists have looked at this blog and think it is all fantasy.  The doctors who have a child with autism and read this blog tend to look from a different perspective and with a much more open mind.  Once you find one therapy that is truly effective, bumetanide in our case, then there can be no turning back.

There are all kinds of diets, supplements and therapies promoted by various people, I wish them all well.

The problem any future science-based autism clinicians will have is that they inevitably get mixed up with other types.  In the US they already go to the same autism conferences, which surprises me. People then think, "Oh well if Professor X is here from Ivy League college Y, then everyone must be legit".  Big mistake. You need to be on really top form to separate out all the pseudoscience, and on occasion you may get it wrong. 

Probiotics

I used to be a skeptic of probiotic bacteria, that is until I was prescribed some little glass vials about a dozen years ago.  I had some side effect from an antibiotic prescribed for an ear infection.  I still recall the ENT doctor calling out (not in English) and asking what to prescribe for the GI side effects.  When I took his prescription to the pharmacy I received a pack of glass vials and a small saw blade.  You used the saw to cut the neck of the vial then you added water to the white fungus growing in the vial and poured into a glass of water, which you then drank.

It most definitely worked.

Even today when I tell my doctor relatives in the UK that probiotics work wonders for diarrhea, all I get is strange looks.

So I am already sold on the fact that probiotic bacteria can do great things for stomach problems.

I spoke to a friend in Denmark this week who has been ill much of the year and finally his problems have been diagnosed as stemming from Ulcerative Colitis.  His first symptom was actually a blood clot.  It turns out that inflammatory bowel diseases (IBD), like ulcerative colitis, increase your risk of blood clots.

So I told my friend to read up on VSL#3 and Viviomixx, which do seem to help IBD, and also to read up on melatonin in the IBD research.

Probiotics and Inflammatory Disease

Looking at immune health more generally we saw how the probiotic Miyairi 588 is used to produce butyric acid which can improve immune health.  This is why cost conscious farmers put it in their animal feed to produce healthier, faster growing animals.

We saw that an alternative is just to add sodium butyrate to the food.  This is done is both livestock and some humans.

Butyrate is an HDAC inhibitor and so is thought to have epigenetic effects.

Probiotics and the Brain

You might be able to convince your doctor that a probiotic bacterium can be good for your stomach, but would you convince him that it could be good for the brain?

I must admit I also would like to see some scientific evidence, beyond anecdotes - even my own anecdotes.

So finally today’s featured scientific study:-

Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve

 There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABA_B1b mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced GABA_Aα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABA_Aα2 in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut–brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression.

The study is interesting because it shows that a bacterium can modify GABA subunit expression in the brain, but when the vagus nerve is removed the effect is lost.  So it is pretty likely that in humans the vagus nerve is the conduit to the brain, as has many times been suggested, but here we have some pretty conclusive supporting evidence.

For a less science heavy explanation of the study:-

Belly bacteria boss the brain

Gutmicrobes can change neurochemistry and influence behavior

I did a post about the vagus nerve a while back and there is an easy to read article here:-

Viva vagus: Wandering nerve could lead to range of therapies

My old posts:-

The Vagus Nerve and Autism

Cytokine Theory of Disease & the Vagus Nerve

Conclusion

Individual GI bacteria have very specific effects.  In people with neurological dysfunctions the possibility genuinely exists to delivery therapies to brain via the gut.  This might have been seen as pseudoscience a decade ago, but now it is part of science, but not yet medicine.

Many other clever things going on in your gut.  The long awaited CM-AT pancreatic enzyme therapy, from a company called Curemark, is now entering its phase 3 trial (thanks Natasa). Click below. 

Blüm is the study of CM-AT, a biologic, for the treatment of Autism.

  

The Curemark lady, Joan Fallon, has collected numerous patents regarding various mixtures of pancreatic enzymes and even secretin.  Secretin was an autism therapy that was written off many years ago, but is still used by some DAN type doctors.

Some comments on this blog from parents of kids in the early CM-AT trials are supportive of its effect.

Pancreatic enzymes (e.g. Creon) are already used as a therapy for people who lack pancreatic enzymes and many people with autism have taken them.

Curemark have never published any of their trial data which annoys at least one of our medical researcher readers.  If you have so many patents, why not share your knowledge?

Antibiotics and Autism(s) – Pass the Bacteroides Fragilis?

Today’s post allows me to cross off several topics from my to-blog list, since I can link them all together.

N = 1 or N > 1

If you are the parent of one of more children with autism, you will have a very specific view of autism, since your kind is the only kind that affects you.  This is natural and so for most readers it is case of N = 1.

When it comes to everyone else, and what they (should) teach medical students, it is the big picture that matters.  So large clusters of people behaving in a certain way is more significant that any outliers.  If you are the outlier, this is not much consolation.

In the world of autism, rather strangely, it is the very rare types that have an established medical therapy.  This ranges from the types caused by rare metabolic disorders to the more common PANDAS/PANS.

The large cluster that is classic autism remains untreated.

Polypill N = 3

To date I am aware of only a handful of people who have implemented the majority of my suggested Polypill for classic autism.  Three parents found major improvements and one found no impact; but the no impact case was not classic autism, it was very late regressive autism, later diagnosed as mitochondrial disease.

Many parents have implemented 1-2 elements of the Polypill with good results; these usually are elements that are the non-prescription drugs.

Three is not many, but it is more significant than one; and three out of four is a pretty good success rate.

As it stands, the Polypill will be a therapy for some children whose parents happen to be doctors, or own a pharmacy.

What does this have to do with antibiotics?

The other day I wrote a post about a recent 6 month clinical trial of Minocycline, an antibiotic.  The hope was that drug would reduce microglial inflammation and improve autism; but it did not.

Then I received a comment from Seth, a regular reader of this blog, to say that in his son tetracycline antibiotics really do improve autism.

I just read about John, another Dad, who found his child’s autism improved greatly while on antibiotics.  He has started his own charity N of One (N = 1) to raise funds for autism research and published an account of what he noticed.

An n=1 case report of a child with autism improving on antibiotics and a father’s quest to understand what it may mean

There are many other accounts of certain antibiotics improving certain people’s autism.

In the case of PANDAS/PANS antibiotics are just the initial part of the therapy, but unless you live in the US you are unlikely to get diagnosed with PANDAS/PANS, let alone treated for it.

I will not be able to solve this puzzle today, but I will make my observations, for what they are worth.

First of all, Seth is talking about tetracycline-class antibiotics, one of which is Minocycline, the subject of that six month autism trial.  Now as we saw in a recent post, that trial was deemed a failure, but that was a trial of 10 children with regressive autism.  

Note that what people mean by "regressive autism" varies widely; most autism has some degree of regression.  In classic autism, the person is born different and then gradually becomes more evidently "autistic" during early childhood. Regressive autism, as defined by Chez, is when things are normal for at least the first 12 months.  Language can be normal or abnormal and then lost.  

I should also highlight that are other reports of Minocycline being beneficial in Schizophrenia and other neurological disorders.

Minocycline: therapeutic potential in psychiatry.

Abstract

Pharmacological interventions to treat psychiatric illness have previously focused on modifying dysfunctional neurotransmitter systems to improve symptoms. However, imperfect understanding of the aetiology of these heterogeneous syndromes has been associated with poor treatment outcomes for many individuals. Growing evidence suggests that oxidative stress, inflammation, changes in glutamatergic pathways and neurotrophins play important roles in many psychiatric illnesses including mood disorders, schizophrenia and addiction. These novel insights into pathophysiology allow new treatment targets to be explored. Minocycline is an antibiotic that can modulate glutamate-induced excitotoxicity, and has antioxidant, anti-inflammatory and neuroprotective effects. Given that these mechanisms overlap with the newly understood pathophysiological pathways, minocycline has potential as an adjunctive treatment in psychiatry. To date there have been promising clinical indications that minocycline may be a useful treatment in psychiatry, albeit from small trials most of which were not placebo controlled. Case reports of individuals with schizophrenia, psychotic symptoms and bipolar depression have shown serendipitous benefits of minocycline treatment on psychiatric symptoms. Minocycline has been trialed in open-label or small randomized controlled trials in psychiatry. Results vary, with findings supporting use in schizophrenia, but showing less benefit for nicotine dependence and obsessive-compulsive disorder. Given the limited data from rigorous clinical trials, further research is required. However, taken together, the current evidence suggests minocycline may be a promising novel therapy in psychiatry.

Minocycline is not just an antibiotic; it has several other known modes of action.

Minocycline is the most lipid-soluble of the tetracycline-class antibiotics, giving it the greatest penetration into the prostate and brain, but also the greatest amount of central nervous system (CNS)-related side effects, such as vertigo.

In various models of neurodegenerative disease, minocycline has demonstrated neurorestorative as well as neuroprotective properties

Minocycline is also known to indirectly inhibit inducible nitric oxide synthase (NOS).

As an anti-inflammatory, minocycline inhibits apoptosis (cell death) via attenuation of TNF-alpha, downregulating pro-inflammatory cytokine output.

Early research has found a tentative benefit from minocycline in schizophrenia

Amoxicillin

The antibiotic that John (from N=1) found to have magical properties was Amoxicillin, a very common type of penicillin.  Amoxicillin is a standard therapy for a strep throat.

Streptococcal infections are the initial trigger for PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections)

Amoxicillin seems to be have just one mode of action, that of an antibiotic.  This means it is a type of antimicrobial used specifically against bacteria, and usually used in medical treatment of bacterial infections. Antibiotics may either kill or inhibit the growth of bacteria.

          From the US National Institute of mental Health  (NIMH):-

Can penicillin be used to treat PANDAS or prevent future PANDAS symptom exacerbations?

Penicillin and other antibiotics kill streptococcus and other types of bacteria. The antibiotics treat the sore throat or pharyngitis caused by the strep by getting rid of the bacteria. However, in PANDAS, it appears that antibodies produced by the body in response to the strep infection are the cause of the problem, not the bacteria themselves. Therefore one could not expect antibiotics such as penicillin to treat the symptoms of PANDAS. Researchers at the NIMH have been investigating the use of antibiotics as a form of prophylaxis or prevention of future problems. At this time, however, there isn't enough evidence to recommend the long-term use of antibiotics.

However, a quick “google” will show more n=1 cases, of people claiming their child’s autism/PANDAS improving on Penicillin and then regressing again afterwards.

  

Vancomycin

The other antibiotic that has been researched in autism is Vancomycin.  This drug is not absorbed from the intestine, so for systemic therapy it has to be taken by injection.  

When given orally it is used for things like treating bacterial infections of the intestines that cause colitis.  Orally administered vancomycin is recommended as a treatment for intestinal infection with Clostridium difficile, a common side effect of treatment with broad-spectrum antibiotics.

Vancomycin was first isolated in 1953 at Eli Lilly, from a soil sample collected from the interior jungles of Borneo by a missionary.

.

Short-Term Benefit From Oral Vancomycin Treatment of Regressive-Onset Autism

Abstract

In most cases symptoms of autism begin in early infancy. However, a subset of children appears to develop normally until a clear deterioration is observed. Many parents of children with "regressive"-onset autism have noted antecedent antibiotic exposure followed by chronic diarrhea. We speculated that, in a subgroup of children, disruption of indigenous gut flora might promote colonization by one or more neurotoxin-producing bacteria, contributing, at least in part, to their autistic symptomatology. To help test this hypothesis, 11 children with regressive-onset autism were recruited for an intervention trial using a minimally absorbed oral antibiotic. Entry criteria included antecedent broad-spectrum antimicrobial exposure followed by chronic persistent diarrhea, deterioration of previously acquired skills, and then autistic features. Short-term improvement was noted using multiple pre- and post-therapy evaluations. These included coded, paired videotapes scored by a clinical psychologist blinded to treatment status; these noted improvement in 8 of 10 children studied. Unfortunately, these gains had largely waned at follow-up. Although the protocol used is not suggested as useful therapy, these results indicate that a possible gut flora-brain connection warrants further investigation, as it might lead to greater pathophysiologic insight and meaningful prevention or treatment in a subset of children with autism

What is going on?

The truth is that nobody knows for sure what is going on.  That also applies to PANDAS & PANS, which is why most of the world does not recognize them as genuine diagnosable conditions.

It would seem to me that various different processes are likely involved.  It would not be so hard to do some detective work, on a case by case basis.

For example, both Seth and John were using broad spectrum antibiotics.  If they gave Vancomycin a quick trial, they would find out if the problem was in the intestines, since that is the only place oral Vancomycin can have an effect.

John has written in his paper all about possible changes to the gut microbiome and how repeated antibiotic use early in life could set the stage for the development of autism in some children.  It is very easy to test this hypothesis, just try some Vancomycin.

We know that ulcerative colitis is comorbid with autism.  We know that this will lead to a permeable gut and the flow of unwanted substances to other parts of the body.  We see that Vancomycin is used for treating bacterial infections of the intestines that cause colitis.

So it is no surprise that in some people with autism, Vancomycin will improve behaviors.  You just need to identify which people.

Once apparent that Vancomycin is indeed effective, at least you know where the problem is.  Then it is a question of finding long term solutions to manage the problem.

We already know much about the so-called “leaky-gut” and the many GI problems in autism.  This is very well covered on the SFARI site and blog, so here are some highlights from there.

'Friendly' bacteria treat autism-like symptoms in mice

The new study is the first to show that maternal infection alters the microbiome in the offspring. The finding is significant for autism, as many children with the disorder are plagued by gastrointestinal problems, including diarrhea, vomiting and stomach discomfort. 

Leaky gut is also reported in children with autism and is associated with several other disorders, such as inflammatory bowel disease and Crohn’s disease, and perhaps with Alzheimer’s and Parkinson’s diseases, says Sarkis Mazmanian, professor of biology at the California Institute of Technology.To diagnose leaky gut in the mouse pups, the researchers fed them a carbohydrate molecule attached to a fluorescent molecule. The molecule later turned up in their blood, showing it had escaped through the gut wall. The mice also showed elevated gut levels of an immune molecule called interleukin-6 (IL-6) — a prime suspect in mediating the effects of maternal infection

The researchers then treated the mice with B. fragilis. This strain of bacteria isn’t commercially available, but exists naturally in about 20 percent of the human population. 

Mice treated with B. fragilis at 3 weeks of age don’t have a leaky gut five weeks later, their levels of blood 4EPS and gut IL-6 plummet, and the assortment of bacterial species in the gut reverts to something closer to that of control mice. And the mice do better behaviorally: They stop obsessively burying marbles in their cages, become as vocal as controls and are less anxious.

Probiotic curbs autism features in mouse model

• Guest blog: The case for using 'prebiotics'

• A probiotic therapy for autism

Sarkis K. Mazmanian, Ph.D.California Institute of Technology

Most research into autism spectrum disorders has focused on genetic, behavioral and neurological aspects of the illness, but people with autism also show striking alterations in immune status.

What’s more, a significant subset of children with autism spectrum disorders show chronic intestinal abnormalities, such as loose stool and altered bacterial microbiota (the collection of beneficial bacteria within the intestine). Antibacterial treatments are reported to provide behavioral improvements in some cases.

In addition, many children with autism have been diagnosed with food allergies and are on special diets. Societal advances (including 'Western' diets and antibacterial products) may have paradoxically compromised human health by reducing our exposure to health-promoting gut bacteria.

The connection between gut bacteria, intestinal disease and autism is a promising area of investigation. Sarkis Mazmanian and his team at the California Institute of Technology used mouse models that show autism-like features to evaluate the efficacy of probiotics.

They found that specific probiotic bacteria ameliorate autism-like behaviors in both environmental models of ‘induced’ disease (by mimicking viral infection of the mother during gestation), as well is in two genetic models of autism spectrum disorder.

These studies are an important step in furthering research that addresses the connection between the gut microbiome and altered behaviors, a link suggested by studies in humans. Finally, Mazmanian’s findings may help validate the use of probiotics as a safe and effective treatment for autism when it is accompanied by gastrointestinal abnormalities.

   

What it means?

It certainly appears that some people with ASD and GI problems have a something similar going on to my case of “N=1” (ASD + pollen allergy).  An allergic reaction has caused mast cells to degranualate releasing histamine and  IL-6.  That histamine causes further release of IL-6 elsewhere.  IL-6 is a pro-inflammatory cytokine and “public enemy number one” in the case of autism flare-ups.

It does appear that some people with autism + GI problems improve somewhat with supplemental digestive enzymes, like Creon/Kreon.  This does appear to be the basis of CM-AT, the long awaited therapy from Curemark.

However, based on feedback from this blog, it appears that blocking the calcium channel Cav1.2 with Verapamil may be even better.  It will certainly be much cheaper.

The standard treatment for this type of allergy related GI problem, is Cromolyn Sodium, a mast cell stabilizer.  Verapamil is also a mast cell stabilizer, among other properties.

Interestingly, some people “do grow out” of some allergies.  I myself, as a child, was prescribed Intal (Cromolyn Sodium) for GI problems of unknown origin.

You will find countless reports on the internet of children with “autism” who, on various diets, “recovered”.  You will hear plenty of people saying that young children will “grow out of” their autism.  It is generally accepted that most people’s autism does moderate as they become adults, just like many people’s asthma.

There is some sense in all of this.  Allergies can seriously aggravate autism.  So if you have someone with very mild autism, but a severe allergy, when you control the allergy you will see dramatic behavioral improvement.

Some readers of this blog have found that common allergy treatments like Zyrtec (cetirizine), have a profound behavioral improvement on their child, who was supposedly allergy-free.

In “my” subgroup of classic autism one underlying problem appears to be a channelopathy (Cav1.2); this might be genetic, or it might be an “epigenopathy”.  In either case, you could detect it, with existing technology, if you really wanted to.

Conclusion

The clever people at the NIMH think that PANDAS/PANS is a kind of Rheumatic Disease, where an autoimmune disorder (triggered by strep throat infections) causes the body to produce antibodies against the invading bacteria, and the antibodies help eliminate the bacteria from the body. However in a rheumatic disease, the antibodies mistakenly recognize and may attack the heart valves, joints, and certain parts of the brain.  When they attack the joints it is called Rheumatic Arthritis, when they attack the brain it is now called PANDAS.

The NIMH thinks that PANDAS/PANS is distinct from autism.

If you regularly read the research in this blog, you may disagree with the NIMH and see that PANDAS/PANS is just another autism variant.  Likely many things, other than strep infections, can also trigger this over-active immune system.

Many strange things occur in autism, one being that adults apparently cannot have PANDAS.  Of course they can; it just would have to be called ANDAS.

If an adult with autism wants to check for some rare for metabolic disorders leading to “autism” he/she may need to get referred to a children’s hospital, like Arkansas Children’s Hospital.  All the while, some of their diagnoses/treatments continue to be regarded as quackery by many other clinicians.

Some people with Schizophrenia, who improved on Minocycline, should try Vancomycin.  If the benefit is lost (as I suspect, it will be), then we would know that the effect was elsewhere than in the intestines.

Having established that Minocycline had no benefit in children with regressive autism, perhaps Johns Hopkins and NIMH should trial it in early-onset autism (classic autism).  It is Johns Hopkins after all, who believe that regressive autism is primarily mitochondrial disease.  The research indicates that mitochondrial disease is but one feature of classic autism.

Vancomycin is a useful diagnostic tool, rather than a long term therapy, but if Vancomycin improves behaviour, then you have plenty of choices:-

·        Cromolyn Sodium

·        Verapamil

·        Digestive enzymes like Creon/Kreon and, eventually, CM-AT

·        Probiotics & Prebiotics  (one day even Bacteroides Fragilis)

·        Exclusion diets

So if your child improves after taking antibiotics, or anything else, my suggestion is to investigate it yourself, rather than found yet another autism charity.

There is actually plenty of existing research and clever people, like those at the Simons Foundation, are funding further work on a prolific basis.

Other than readers of the SFARI blog and the Questioning Answers blog, is anyone actually reading (nearly) all this research? (let alone applying it)   Evidently not.

The academic researchers just read narrowly around their very focused area of interest.  The majority of clinicians read almost none of the research.

If you want to solve a complex problem, collect all the available data, look for connections and then think about it.

You should not have to do this for yourself, but with autism you do.

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.

Preventing β-Cell Loss and Diabetes With Calcium Channel Blockers

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. 
 

Effect of pioglitazone treatment on behavioral symptoms in autistic children

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 PD_20FEVHi 416%). There was still significant protection (Δ PD_20FEV1Hi>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.