Hypochlorhydria and autism?

I'm in speculative mode in this post so you will have to humour me a little. I know, I know, this is a blog which is supposed to be about autism research, so why the tangent? Well, let's just say that there are a few ideas for further study potentially included in this post should anyone care. The caveat as always is that no medical advice is intended or given. So, got your pinch of salt ready?

Part of the title of this post - hypochlorhydria - refers to a state rather than a condition, whereby the level of gastric acid is low and potentially below that required to fulfil certain gastrointestinal duties optimally. Gastric acid is predominantly composed of hydrochloric acid (HCl) alongside various other buffer solutions which moderate the pH or acidity of the mix. It's main task is to digest and aid in the digestion of food. Where there might be issues with the appropriate level of HCl, hypo- or achlorhydria (an absence of acid) can arise with several potential consequences.

There are several reasons why hypochlorhydria might be present. Perhaps one of the more widely discussed relates to the use of a certain class of medications under the umbrella of proton-pump inhibitors whose main aim is to reduce gastric acid production in the treatment of things like dyspepsia.

There have been rumblings down the years that gastric acid might require a little more study with autism spectrum conditions in mind. Finegold and colleagues* (full-text) reported on cases of hypochlorhydria during their study looking at intestinal flora in autism. Indeed, Finegold's findings *could* tie into quite a large body of evidence which seems to implicate overgrowth of intestinal bacteria such as Clostridium difficile and gastrointestinal acid suppression as per reviews like this one from Chun Shin Kwok and colleagues**.

I first heard about hypochlorhydria with autism in mind quite early on in my research career alongside a few potentially positive anecdotal reports following the use of preparations such as betaine hydrochloride (trimethylglycine). Betaine HCl (for which I offer no endorsement) is a source of HCl, for which, to coin a phrase of a mentor of mine, "there is general consumer resistance to drinking neat HCl". The theory went that betaine HCl was a way to prop up any issues with HCl generation in the stomach, which subsequently relates back to the function of pepsin, an enzyme whose main aim is to chop up food proteins. Pepsin and its parent pepsinogen rely on acidic conditions to 'spread its wings' in terms of protein degradation.

Some people might have heard about trimethylglycine (TMG) and dimethylglycine (DMG) with autism in mind. DMG is the daughter product of TMG after the loss of a methyl group which might very well take us back to the issue of methylation noted in a few research papers on autism like this one from Melnyk and colleagues on impaired methylation capacity.

I know that this has been a bit of a speculative post and hope that readers will see it in that light. There are lots of other potential links which I could go on about such as the knock-on effects of hypochlorhydria and downstream peptide chemistry which litter the autism research landscape. I note for example, that the current interest in the CM-AT preparation by Dr Joan Fallon's company Curemark which continues with protein digestion in mind (see also a presentation at IMFAR 2012 here).

Indeed I'm going to end with a paper from Cater*** published twenty years ago and some more speculation on the links between hypochlorhydria, intestinal bacterial overgrowth and a triad of amino acids (tyrosine, tryptophan, phenylalanine) which might prove very interesting...

* Finegold SM. et al. Gastrointestinal microflora studies in late-onset autism. Clinical Infectious Diseases. 2002; 35 (supplement 1): S6-S16

** Kwok CS. et al. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. American Journal of Gastroeneterology. April 2012.
DOI: 10.1038/ajg.2012.108

*** Cater RE. The clinical importance of hypochlorhydria (a consequence of chronic Helicobacter infection): its possible etiological role in mineral and amino acid malabsorption, depression, and other syndromes. Medical Hypotheses. 1992; 39: 375-383.