PPI

[DDK]

Does anyone know the mechanism by which PPI's cause atrophic gastritis? What specifically are they doing that causes gastritis (which is a known, and very common side effect).

 

[aguilaroja]

Beg pardon, I have not followed the issue closely. AFAIK the orthodox notion is currently that PPI’s do not cause atrophic gastritis, though they can raise serum gastrin and cause cell apoptosis.

Are proton pump inhibitors a double-edged sword in the treatment of Helicobacter pylori infection? | Ge | Annals of Gastroenterology
“PPIs do not cause atrophic gastritis [3], although they may mildly increase serum gastric concentration and induce apoptosis [4,5].”

There has been concern for a while that PPI’s increase the risk of atrophic gastritis when there is H.Pylori infection:
Long Term Proton Pump Inhibitor Use and Gastrointestinal Cancer
“…PPI use was associated with an increased risk of development of atrophic gastritis, the acknowledged primary risk factor for development of gastric cancer (15-18). Their landmark studies prompted a number of additional investigations; although the final word has yet to be written, most agree that PPI use in H. pylori-infected patients is associated with an increase in corpus inflammation and atrophy (eg, (17;19-23))."

AFAIK, the usual medical therapy with H. Pylori associated atrophic gastritis is pharmaceutical “triple therapy” treatment to remove H. Pylori.

As @haidut and others have noted, PPI’s have side effects outside of the digestive system, that may be extremely concerning.

 

[haidut]

AFAIK the orthodox notion is currently that PPI’s do not cause atrophic gastritis

That is the official version but in the original animal trials (preceding the human ones) they did and also increased risk of gastric cancer for which the atrophic gastritis (but no the regular one) is a risk factor.

http://www.mdedge.com/jfponline/art...ogy/long-term-use-proton-pump-inhibitors-safe
"...Atrophic gastritis with intestinal metaplasia is associated with gastric adenocarcinoma. Because PPIs can theoretically cause atrophic gastritis, there is a concern that this could lead to gastric cancer. The evidence regarding atrophic gastritis is contradictory. A nonsystematic review identified 1 cohort study and 1 randomized controlled trial of patients taking omeprazole from 1 to 4 years, which showed no association between PPI use and atrophic gastritis.1 The same review reported that another cohort study of patients using omeprazole for 1 year showed an increase in atrophic gastritis. None of the studies reviewed showed an association between omeprazole use and intestinal metaplasia or its progression to gastric adenocarcinoma.1 Three other nonsystematic reviews support these findings.2,3,5 The available evidence indicates that PPI use is not clearly associated with atrophic gastritis, or with progression from gastritis to metaplasia or cancer."

This study is especially telling.
Long-term proton pump inhibitor therapy accelerates the onset of atrophic gastritis in Helicobacter pylori -positive patients
"...Together with the demonstration of powerful inhibition of acid secretion came the concerns about any related side-effects of this acid inhibition. These concerns were, in particular, fed by the observation of development of gastric carcinoids in rats after prolonged treatment with very high doses of omeprazole. For this reason, maintenance treatment in humans was initially allowed only in clinical trials with monitoring of serum gastrin levels and gastric histology by repeated endoscopy with biopsy sampling. These trials showed that gastric argyrophil cell hyperplasia developed in a proportion of patients in relation to hypergastrinaemia, but also confirmed that carcinoid formation did not occur. These trials did not focus on gastritis, but did report that a subgroup of patients developed active body gastritis after the start of omeprazole treatment, which was accompanied by development of gland loss during follow-up4. No explanation was given for these observations, and they were considered to relate to the normal progression of gastritis with ageing5,6. However, insight into these observations gradually came with the increasing knowledge of Helicobacter pylori and its effect on gastritis."

Just as with the SSRI drugs, Germany refused to (initially) approve PPI drugs for use in its health care system until more was known about their long term safety. Eventually, the powerful lobbying by Merck (which maintains very strong roots in Germany given its heritage) led to approval anyways.
I have spoken to a number if people who work in gastroenterology and to them the link between lack of acid and atrophy is clear. Famotidine is the only drug that was shown to both reduce GERD while at the same time protecting from atrophic gastritis. Famotidine is somehow anabolic for the gastric mucosa, and the mechanism is not fully known yet. I posted a study somewhere on the forum showing only famotidine stimulated mucosa renewal after strong insult with formaldehyde and acetic acid, in the absense of gastric acid. The PPI and other H2 antagonists simply reduce acid secretion but do nothing to regenerate tissue of there is another insult. So, for people with already atrophied epithelial layer famotodine and gelatin would be what I would try first.

 

[Regina]

That is the official version but in the original animal trials (preceding the human ones) they did and also increased risk of gastric cancer for which the atrophic gastritis (but no the regular one) is a risk factor.

http://www.mdedge.com/jfponline/art...ogy/long-term-use-proton-pump-inhibitors-safe
"...Atrophic gastritis with intestinal metaplasia is associated with gastric adenocarcinoma. Because PPIs can theoretically cause atrophic gastritis, there is a concern that this could lead to gastric cancer. The evidence regarding atrophic gastritis is contradictory. A nonsystematic review identified 1 cohort study and 1 randomized controlled trial of patients taking omeprazole from 1 to 4 years, which showed no association between PPI use and atrophic gastritis.1 The same review reported that another cohort study of patients using omeprazole for 1 year showed an increase in atrophic gastritis. None of the studies reviewed showed an association between omeprazole use and intestinal metaplasia or its progression to gastric adenocarcinoma.1 Three other nonsystematic reviews support these findings.2,3,5 The available evidence indicates that PPI use is not clearly associated with atrophic gastritis, or with progression from gastritis to metaplasia or cancer."

This study is especially telling.
Long-term proton pump inhibitor therapy accelerates the onset of atrophic gastritis in Helicobacter pylori -positive patients
"...Together with the demonstration of powerful inhibition of acid secretion came the concerns about any related side-effects of this acid inhibition. These concerns were, in particular, fed by the observation of development of gastric carcinoids in rats after prolonged treatment with very high doses of omeprazole. For this reason, maintenance treatment in humans was initially allowed only in clinical trials with monitoring of serum gastrin levels and gastric histology by repeated endoscopy with biopsy sampling. These trials showed that gastric argyrophil cell hyperplasia developed in a proportion of patients in relation to hypergastrinaemia, but also confirmed that carcinoid formation did not occur. These trials did not focus on gastritis, but did report that a subgroup of patients developed active body gastritis after the start of omeprazole treatment, which was accompanied by development of gland loss during follow-up4. No explanation was given for these observations, and they were considered to relate to the normal progression of gastritis with ageing5,6. However, insight into these observations gradually came with the increasing knowledge of Helicobacter pylori and its effect on gastritis."

Just as with the SSRI drugs, Germany refused to (initially) approve PPI drugs for use in its health care system until more was known about their long term safety. Eventually, the powerful lobbying by Merck (which maintains very strong roots in Germany given its heritage) led to approval anyways.
I have spoken to a number if people who work in gastroenterology and to them the link between lack of acid and atrophy is clear. Famotidine is the only drug that was shown to both reduce GERD while at the same time protecting from atrophic gastritis. Famotidine is somehow anabolic for the gastric mucosa, and the mechanism is not fully known yet. I posted a study somewhere on the forum showing only famotidine stimulated mucosa renewal after strong insult with formaldehyde and acetic acid, in the absense of gastric acid. The PPI and other H2 antagonists simply reduce acid secretion but do nothing to regenerate tissue of there is another insult. So, for people with already atrophied epithelial layer famotodine and gelatin would be what I would try first.

Still waiting on Ulcerban.....

 

[ecstatichamster]

PPIs cause huge problems. They inhibit magnesium and calcium absorption. They may interfere with cellular turnover. They elevate parathyroid hormone. Peat has said lowering PTH is Very very important. The PTH effect may cause the atrophic gastritis.

http://medicine2.missouri.edu/jahm/wp-content/uploads/2017/07/PTH-Final.pdf

A Proton Pump Inhibitor’s Effect on Bone Metabolism Mediated by Osteoclast Action in Old Age: A Prospective Randomized Study

Digestive manifestations of parathyroid disorders

 

[Dezertfox]

What is the best way to reduce PTH??

 

[aguilaroja]

PPIs cause huge problems....They elevate parathyroid hormone....The PTH effect may cause the atrophic gastritis.
http://medicine2.missouri.edu/jahm/wp-content/uploads/2017/07/PTH-Final.pdf
A Proton Pump Inhibitor’s Effect on Bone Metabolism Mediated by Osteoclast Action in Old Age: A Prospective Randomized Study
Digestive manifestations of parathyroid disorders

Thanks, these are interesting points. I have been dismayed for so many years by many adverse possibilities about PPI's. PPI's have so many confounding effects that it is helpful to re-think which parts are upstream of the downstream badness.

 

[ecstatichamster]

What is the best way to reduce PTH??

Peat says high dietary calcium relative to phosphorus.

 

[haidut]

What is the best way to reduce PTH??

Vitamin D, niacinamide, calcium, thyroid, progesterone, anti-prolactin drugs, famotidine, etc all reduce PTH.

 

[DDK]

The worst part about PPI's, at least in my own experience, is that the side effects do not cease upon discontinuation of the drug. They are permanent and remain until intervention is taken to address them.

 

[haidut]

The worst part about PPI's, at least in my own experience, is that the side effects do not cease upon discontinuation of the drug. They are permanent and remain until intervention is taken to address them.

Sounds like Finasteride or PFS to me What worked for you to reverse those long term symptoms?
I wonder how many people in the PFS thread have actually taken or still taking PPI... What do you think @Drareg?

 

[DDK]

Sounds like Finasteride or PFS to me What worked for you to reverse those long term symptoms?
I wonder how many people in the PFS thread have actually taken or still taking PPI... What do you think @Drareg?

Nothing has worked so far Haidut, and it's been 1.5 years since I discontinued Omeprazole. I sent you a PM couple of days ago, remember? We talked about correcting my vitamin D, Pepzin GI & famotidine; so those are the three things I am going to try soon. Hopefully, they work, and if they do I will be sure to post.

 

[Drareg]

Sounds like Finasteride or PFS to me What worked for you to reverse those long term symptoms?
I wonder how many people in the PFS thread have actually taken or still taking PPI... What do you think @Drareg?

I think it’s cocktail city in that thread,just like cocktails it’s hit and miss,let’s hope it’s a hit this time.

I actually know of a 74 year old prescribed protium after really bad chest pains at Christmas,over eating and wine,family thought it was a heart attack,his GP continued a prescription of protium for over 2 years daily,they said in the ER just 2 months needed.
Fast forward to 2 years time he collapses from what they think is low sodium,2 weeks later they think prostate cancer,1 and half months later stomach cancer and prostate not sure which is causing which.
They castrate him with injections for prostate and swallow radium for the stomach,they still prescribe a ppi but a different one even though a "specialist" said his doctor was an idiot for prescribing ppi’s for so long.Throw in morphine,a sleeping pill,an ssri and Xanax we have edema of neck area and lower legs,throw in edema tablet,there could be more....
50/50 chance of 2 more years to live,no history of cancer in family not that means anything but they told the family this as it was unusual.