Thursday, 23 October 2014

GERD/Reflux, Autism, Head Banging and mGlu5

This brief post addresses one further issue as to why people with autism can often suffer from various nasty gastrointestinal (GI) problems. 

First a recap.

Mast Cell Activation

We have already seen that some people’s GI problems are caused by mast cell activation/degranulation.  These cells are activated by allergens (certain foods in this case) and then they release histamine and other pro-inflammatory agents like IL-6.  Degranulation of mast cells can itself cause pain, but the main problem is the resulting damage/inflammation caused by the IL-6 and histamine.

The effective therapy is a mast cell stabilizer.  These include Verapamil (better known as a calcium channel blocker), Cromolyn Sodium, Ketotifen, Azelastine and to a lesser extent most anti-histamines like Claritin, Zyrtec etc.  Quercetin, the flavonoid, also has an effect.

Pancreatic Dysfunction

We also saw that L-type calcium channel (Cav1.2) dysfunction in the pancreas may disrupt the production of certain digestive enzymes.  The lack of these enzymes will disrupt the digestive process and likely affects other processes elsewhere in the body.  Verapamil blocks the Cav1.2 channel.

Ulcerative Colitis

We saw that inflammation and colitis, as diagnosed by an endoscopy, is another comorbidity of autism; this may be in part caused by the mast cell degranulation, but it does fit with the broader hypothesis of the over-activated immune system.  We saw how the potassium ion channel Kv1.3 was the mechanism behind some useful immuno-suppressive therapies, including those TSO parasites.  For those who are skeptical, here is another recent study, I just found:-


Kv1.3 should then be a target to treat ulcerative colitis and, I believe, autism itself. Some Kv1.3 blockers exist today; one is Verapamil, another is Curcumin, for those who prefer supplements to drugs.

Before I forget to write this down somewhere, it appears that Kv1.3 can also be modulated by PKA and PKC, which decrease its activity. 

We have already come across protein kinase B (PKB) and there will be a post soon of PKA, PKB and PKC.  This all links back to oxidative stress, neuroinflammation and even those dendritic spines.


Today’s post is about reflux, sometimes known as gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD).  Reflux is when the acid from the stomach rises through the esophagus/oesophagus to the mouth.

Many adults suffer from reflux from time to time and there are many OTC and prescription drug treatments. It can cause pain and discomfort, and would be particularly troubling if you could neither verbalize, nor understand your symptoms.

Why this post?

You may wonder why I have jumped from broccoli (the previous post) to reflux.  There is a reason.

I was recently listening to a conversation between doctors about a head-banging child and then came “it’s not autism; he’s got reflux, that is why he was banging his head.”

That sounded very odd to me.

It turns out many people with autism suffer from reflux, so you could say it is a comorbidity.  But why might that be?

mGlu5 receptors and disease

In an earlier, rather complicated, post I introduced the glutamate receptor, mGlu5.  This receptor is at the centre of research into Fragile X at MIT.  Fragile X is the most common single gene cause of autism.  It has been shown that mGlu5 dysfunction appears in many types of autism and indeed schizophrenia (adult-onset autism).
I then chanced upon a recent paper on mGLu5 and came across this section:-

Through contributions to synaptic plasticity, mGlu5 receptors have been implicated in neuronal processes such as learning and memory as well as disorders including Fragile X Syndrome (FXS), tuberous sclerosis, autism, epilepsy, schizophrenia, anxiety, neuropathic pain, addiction, Alzheimer’s disease, Parkinson’s disease, L-DOPA-induced dyskinesias, and gastroesophageal reflux disease

That was quite a surprise, but yet another good lesson of why the comorbidities should all be carefully researched.
The full paper, for anyone with time on their hands is:- 


If you have autism, you may have an mGlu5 dysfunction.  This will become treatable once the needed PAMs (Positive Allosteric Modulators) and NAMs (Negative Allosteric Modulators) have been brought to market.  A great deal of research is ongoing.

In the meantime, mGlu5 dysfunction is quite possible elsewhere in the body.  mGlu5 dysfunction is associated with some very rare disorders, but the common ones are diabetes and reflux.

The head-banging boy very possibly had both autism and reflux; he did develop diabetes.

For more on autism and diabetes, a short, thought provoking, but technical, paper:-

Interestingly, we saw earlier that Verapamil seems to offer protection against type 1 and 2 diabetes. This time it is its calcium channel blocking role that is the mechanism.

No big surprise that Verapamil is an ingredient of the autism Polypill.

Verapamil drug may reverse diabetes-related death of pancreatic beta cells


  1. Dear Peter could you support with this question please non verbal autistic 6 year old daughter has quite bad acid reflux and other gastro issues responds well to nalcrom loratadine,ketotifen,Xyzal ,nystan ,bumetandine,excellent behaviour improvement after treating Hypolori with antibiotics and omeprazole .A year and a bit later gastr issues reflux have emerged again resulting with aggression towards others .Being non verbal hard to explain shes in pain .Our doctor has given omeprazole unfortunately this time around although she has improved less aggression but has also reacted negatively to the drug with rashes and itching This is a side effect I have noted.The same happened with ranitidine some time ago.
    I will have to withdraw the omeprazole unfortunately .
    We would appreciate if there is any suggestion of a medication I can ask our doctor to prescribe .Her diet is quite limited but it not an acid rich one its rather bland she has had reflux issues from birth but we did not understand the magnitude the gastrologist we are under gave orders for the hpylori to be treated as our doctor initially refused.

    1. I would try verapamil 20mg three times a day which I suspect may resolve the GI problem. I will shortly be writing a post to explain one proven reason that verapamil helps with GI problems. Your doctor will wonder how a calcium channel blocker can help GI problems, the post will explain why.

      An alternative to omeprazole is medium dose melatonin, this has been shown effective in a trial. You would need about 3 to 5mg of melatonin at bedtime. A non medical intervention to treat reflux is just to raise the mattress under her shoulders by 10 cm / 4 inches. Then during the night gravity stops the acid rising up from he stomach. This works really well and has been used for many decades to minimize reflux.

    2. Thank you for your prompt response unfortunately she responded negatively to verapamil when introduced .I shall try melatonin
      And the matress I am most appreciative Peter


Post a comment