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PPIs increase gastrin levels

PPIs work by 'poisoning' a very specific enzyme that produces hydrochloric acid in the stomach. So they appear to be 'safe' (and that is how the medics see them!).

However acid production is part of a complicated biological feedback mechanism. If you interfere with any feedback mechanism, be it mechanical, electronic or biological, you can expect odd things to happen.

In the case of PPIs, what seems to happen is that the hormone that triggers the acid production increases over time as the body tries harder and harder to produce stomach acid. That hormone is Gastrin. It is interesting that MedlinePlus - A service of the U.S. National Library of Medicine says "Greater-than-normal levels (of Gastrin) may also be due to: ... Use of antacids or medicines that suppress stomach acid". Several other authoritative www sites give similar information.

Gastrin secretion is primarily inituated by the presence of certain foods in the stomach. Gastrin secretion is inhibited when the stomach pH falls below about 3.

A Google scholar search for "proton pump" gastrin reveals some interesting papers.

Apparently gastrin it is more than one chemical, a family of similar chemicals. An excess of gastrins in the body is a state called hypergastrinemia. There are other hormones also involved, for instance Secretin..

An interesting page on gastrins is from Colorado State University who have a series of biomedical hyperbooks.

Gastrin see Wikipedia on Gastrin)

So high levels of gastrin, as a side-effect of PPIs, may actually make reflux worse by relaxing the lower oesophageal sphincter and causing bile to be released when the stomach is empty, thus causing bile reflux rather than acid reflux! Certainly it explains to me why and how PPIs cause, in myself at least, bile reflux!

Gastrin, Secretin and bile release

There is also a second hormone that is involved: secretin. I have not yet discovered sensible research on exactly how these two hormones interact with acid and bile release, but from my own experience the interaction is complex and there are long-term factors involved. When on high (normal!) dose PPIs I would occasionally get huge bile release incidents, usually at night. There was also a background bile taste in the refluxate which got worse as the PPIs wore off.

I gradually reduced the PPI intake (see page on PPI dosage) unlit I was taking 10mG at 12 hourly intervals. But 10mG lasted about 15 hours, I had found, so I was sure that I could cut down to 5mG doses at 8 hourly intervals.

On the first two occasions that I took a 5mG dose (both were last thing at night, on retiring) I failed - rebound acidity, which is a common problem on reducing PPI dosage. The third time I tried reducing the dosage - success! All seemed well and the background bile taste disappeared. However some 30 days after starting the reduced doses I had fairly bad nocturnal bile. Again a worse episode, 8 days after that. Then a third, even worse 6 days later. Since that, nothing. So it is evident that there is a long-term upset factor in PPI usage, in addition to the rebound acidity that occurs almost immediately.

I cannot explain the long-term effects on bile release, however since going on the reduced dose, my general health is much improved. Regurgitation of solids is rare - presumably my Lower Oesophaheal Sphincter is less lax. Also the latest endoscopy shows islands of normal cells in the Barrett's area, so things were mending.

Afterword Wednesday the 17th of October, 2012
Having frequently experimented with the time a single dosage lasted, I eventuall found that I was becoming tolerant to PPIs - presumably my liver had learnt to extract the chemical as a foreign sustance. o I weaned myself off PPIs completely - bile reflux stoped - although it took about 90 days to do so!

I have also learnt that gall-bladder dysfunction - and even its removal as a result, is linked to long term PPI usage. See Gall bladder and PPI usage on the page of links.

Other relevant pages


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Page first published: Sunday the 20th of February, 2011
Last modified: Thu, 18 Oct 2018 10:18:36 BST
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