Betaine HCl stomach pH

Question

It seems betaine HCL is often recommended for those suffering from "low stomach acid" -- which, as I understand, is having too high stomach pH for proper digestion (especially for proteolysis via pepsin). However, I have a few questions then -- though I'm not sure if my reasoning is correct here:

Understandably, one wouldn't want to drink pure or highly concentrated HCl by itself to increase stomach acid! But then, what role does the betaine play?

I'm guessing betaine HCl probably does not dissolve in water to give the same pH as just straight (or concentrated) hydrochloric acid -- since then it would seem just as dangerous as drinking plain HCl!

In that case, if it doesn't decrease the pH as much, making it safe for oral consumption, what value does it bring for "lowering stomach pH" anyway? I mean, one could just drink a little vinegar or citric acid for the same effect?

Or, perhaps, is betaine-HCl just a means of some "delayed release" of HCl to lower stomach pH without hurting the mouth and esophagus during its initial consumption? Betaine may just be a useful carrier here, given it's quaternary ammonium and carboxylic acid groups (e.g., a zwitterionic carrier)

Alternatively, could the value of betaine HCl simply be in providing a source of Cl- anions, possibly for increased pepsin activity? (I'm not sure if pepsin requires merely low pH or specifically also needs Cl- anions as well) Betaine-HCl does seem to be often formulated with additional pepsin enzyme(s) as well...

Answer 1

Betaine HCl (trimethylglycine) was present in over the counter "stomach acidifiers" but the US FDA says there is no evidence for its efficacy and has banned its use for this indication (source: US FDA) - it may be freely available elsewhere, I am unaware of the regulatory status in other jurisdictions.

There is no biological reason to expect the "HCl" portion for most drugs to have any substantial effect on stomach acid. Lots of drugs are packaged in an acidic form as "drug HCl" - this is usually because the acidic form of the drug is more soluble. Drug doses are commonly in the microgram to milligram range (though obviously this varies for different drugs) - at those concentrations, the stomach acid is much too concentrated to be affected by the small amount of acid added from the drug.

The catch with Betaine HCl is it looks like websites are advocating for taking several grams to provide enough HCl to affect stomach acid. I suspect that supplement makers suggesting these high doses is what led the FDA to ban the drug OTC in the first place. Although betaine is produced as part of normal metabolism, there are some side effects reported, mostly mild.

Note that anhydrous betaine is prescribed (and approved by US FDA) for homocystinuria, and used as a supplement to animal feed, but neither application is related to stomach acidification (and the anhydrous form is not acidified).

One recent study supports use of Betaine HCl with patients who are being treated with acid-suppressing drugs such as proton-pump inhibitors, to be given along with other drugs that require an acidic environment to function/be absorbed. However, it is important to note that this study was in fasted patients: they consumed nothing but a little water with the betaine HCl. In this circumstance, the little bit of HCl in a moderate to large dose of betaine was sufficient to lower stomach pH. However, the results likely would have been very different if the patients had eaten a recent meal.