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Barrett's oesophagus, Omeprazole dosage and bile reflux: links
This is a listing of URLs relevant to Barrett's oesophagus, Omeprazole dosage and bile reflux. The search reveals some interesting pages!
PPIs are the conventional cure, but there are other possibilities
- Modulation of Gastric Acid Secretion by Hypnosis. The brain is deeply involved in the feedback loop that controls acidity. This paper shows that hypnosis can affect acid secretion. It should therefore be possible, if some biofeedback system could be found, to learn to reduce acidity. Certainly it is well known that worry increases acid levels. Learning not to worry is indicated: my own experience is that with sufficient time and practise, one can significantly lower ones own acidity by willpower alone. I must write up my experiences in this sometime!
Manipulation by a skilled chiropractor or osteopath may help some hiatal hernia sufferers. A Google search is informative, including a few YouTube videos. There are also self-help exercises that can help.
However it seems that, with advancing age, the phrenoesophageal ligament relaxes and allows a sliding hiatal hernia, so manipulation is only likely to have useful effect in the young.
I did a search of Google search which prove that an inflamed oesophagus is more sensitive than a normal oesophagus, so Barrett's oesophagus sufferers are more prone to GERD pain than normal, at least in the early stages while their is still inflammation. There are other pages in the search that show the same results. I find no information on sensitivity after the inflammation has abated
Barrett's oesophagus occurs in animals other than humans:
Columnar epithelial oesophageal cells (as develop in Barret's oesophagus) are apparently normal in reptiles. So Barrett's appears to be an atavism to a reptilian / piscine (and probably avian) cell structure. As such it seems to be an atavism to a pre-mammalian structure. If so, it is probably possible in all mammals!.
A Google search for - omeprazole causes bile reflux -
is of interest. However see also the section below Gall bladder and PPI usage
- Omeprazole induces altered bile acid metabolism by K Shindo, M Machida, M Fukumura, K Koide, R Yamazaki
Without a subscription, only an abstract is available. The study was aimed at jejunal flora and found effects which it ascribed to the altered flora affecting the bile mechanism. It was not looking for bile production changes so its conclusions as to mechanism involved are suspect. The bile mechanism could just have easily be caused by the medication rather than the flora changes!
- Effect of omeprazole 20 mg twice daily on duodenogastric and gastro-oesophageal bile reflux in Barrett's oesophagus
Study was based on a 20mG twice daily study. However my findings are that a 20mG dose is in fact a massive overdose!
- Bile Reflux and a defective lower esophageal sphincter
Misses the point that for bile to be refluxed it must be present in the stomach in the absence of food - so something is interfering with the bile release mechanism!
- GERD patients inadequately controlled with PPIs: New Drugs
An interview with professor Jean-Paul Galmiche, MD, PhD, Gastroenterology Unit, College of Medicine, University of Nantes, Nantes, France.
Again - misses the point that nobody seems to have realised - problems with any drug are likely to be minimal if the minimum necessary dose is administered. Nobody has researched minimum dosage of PPIs, but see the paper on the effect of low-dose omeprazole!
- PPIs increase bile reflux
A quote from this paper:
"Finally, recent research has demonstrated that the use of proton-pump inhibitors (PPIs) in treating acid reflux actually increased the occurrences of bile reflux. The reason for this result isn't fully understood, but it does help explain why some people on PPIs don't appear to show a reduction of their acid reflux episodes."
well spotted - but they have not thought to try minimal dosing!
- Heartburn Treatment May Increase Bile Reflux an article from Science Daily.
- Omeprazole Side Effects on the Liver. Page says that PPIs disturb bile production!
- United States National Library of Medicine page entitles "Effects of rabeprazole, a gastric proton pump inhibitor, on biliary and hepatic lysosomal enzymes in rats." Rats may not be humans, but many humans on PPI feel like lab rats!
- Effect of omeprazole 20 mg twice daily on duodenogastric and gastro- oesophageal bile reflux in Barrett‘s oesophagusby REK Marshall, A Anggiansah, DK Manifold. They found that Omeprazole reduces bile: again, only an abstract, but Omeprezole can alter bile flow by mechanisms unknown
- Determination and pharmacokinetic profile of omeprazole in rat blood, brain and bile by microdialysis and high-performance liquid chromatography by F. C. Chenga, Y. F. Hob, L. C. Hungc, C. F. Chenc and T. H. Tsai
They found that omeprazole can penetrate the blood—brain barrier. Could be cause of some of its side effects
So there seems to be few references to Omeprazole promoting bile reflux - but at more than one paper realises that it probably does. My own experience is that it certainly does!
Maybe a Google search for Barrett's bile will reveal more?
The astute reader will have noticed my own belief that Barrett's oesophagus is a protection against acid reflux and is not protective against bile. So to be fair, I quote some papers that disagree. I Googled for Proton pump inhibitor bile
Whatever the truth about PPis causing bile reflux, ther is growing evidence that bile is more damaging to th oesophageal (and, presuably the syomach) lining. PPIs cause definite malfunction of the gall bladder in the majority of cases and as this is lukely to cause gile release at the wrong time it is likely thatPPIs can cause bile reflux: certainly they did so in myself.
Until the medical profesion understand this - and reference to bile as a contributory cause of Barrett's is a clouded view! But I hav no doubt that bile us a contributory cause of progression to cancer.
- Columnar Mucosa and Intestinal Metaplasia of the Esophagus is a long article from the nnals of Surgery, dated 2000. This admits the picture is cloudy but, well down the article, has a secion on Bile salts. It also disusses how the definition of "Barrett's oesophagus" is not exactly fixed, and its prevalence is not known! One estimate is that, for every known case, there may be 20 or more undiagnosed!
Barrett's oesophagus is said to be a cancer risk, sometimes leading to oesophageal cancer. However cats and dogs get Barrett's and it has been experimentally induced in rats - with great ease. So it is an evolved response to acid reflux and is probably possible in all mammals. This hardly satisfies me that Barrett's is any real cancer risk!
The actual figure of incidence of cancer developing in Barrett's oesophagus is open to doubt: figures have been quoted as high as 5% of Barrett's sufferers develop cancer per year, but other studies have shown the risk to be far smaller than that. 0.5% to 0.9% or even as low as 0.2% per year! In other words, the experts simply do not know!
It seems certain that whatever causes oesophageal adenocarcoinoma also causes Barrett's oesophagus on its way to full-blown cancer. So Barrett's is a danger sign and the cause of it should be reduced. However - Barrett's seems not to be the actual cause. See my own page on
Cancer risk is also linked variously to certain foods: some foods reduce the risk of cancer, others seem to increase it. See my own thoughts on Cancer.
- Esophageal cancer risk overblown, study suggests a CBS news page.
- Esophageal Cancer Risk Higher in Medically Treated GERD Patients With Fewest Symptoms
- GERD not helpful in esophageal cancer screening. Statistics are confusing: Successful management of symptoms with PPIs apparently increases the chances of cancer developing!
- Risk for Progression to Cancer in Barrett's Esophagus. This is a study based on some 8,522 Barrett's 'sufferers' in Northern Ireland over a 7 year period. It found that only 0.22% of Barrett's cases progressed to HGD or cancer per year. That is one person in every 450! Hardly a risk at all!
- Risk Factors in the Development of Esophageal Adenocarcinoma reviews various factors which can increase/decrease risk of adenocarcinoma.
Incidentally, Medscape is worth subscribing to - you can get email alerts of any papers relevant to your condition.
- Diet, reflux and the development of squamous cell carcinoma of the oesophagus in Africa - interesting. This is not about Barrett's progressing but non-Barrett's related cancer. It proves that cancers can be diet-related. It links cancer to linoleic acid (a known cancer inducer if in excess in the diet, but linoleic is common in a lot of foods - see Wikipedia's article on linoleic acid - many of which have strongly recognised health benefits!
- Some Observations on the Epidemiology of Barrett's Oesophagus and Adenocarcinoma of the Oesophagus is a long document. It assesses risk at about 0,5% per year.
- Bile, not Acid, is Bad Guy in Triggering Precancerous Condition Associated with Reflux Disease so causing bile upset is the last thing that should be done! Put that together with the report on PPIs causing gall-bladder dysfunction ... I leave the obvious an an exercise for the reader!
- Precancerous Condition Associated With Reflux Disease Triggered By Bile - Not Acid this backs up the previous article. Add these to the fact that PPIs cause gallbladder malfuction in most people and that erratic gallbladder fuction could well lead to bile in the stomach.
- ... rat oesophageal squamous cell dysplasia and Barrett‘s metaplasia induced by duodenal contents reflux says "It is known that bile acids can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis." Rats aren't humans - but rats are used a lot to test theories. It is also known that PPIs induce bile reflux in a too-high proportion of users - see Gall bladder and PPI usage
- Antireflux Surgery and the Risk of Esophageal Adenocarcinoma. I quote a passage: "The authors noted an almost 3-fold increase in cancer risk in people who used medications for reflux.".
I found that PPIs caused, in myself, bile reflux - something I never experienced before taking medication. As PPIs are known (but not generally admitted) to cause gall-bladder malfunction in a large number of people, bile reflux seems likely to be a common effect of taking PPIs. It seems likely that this increase in cancer risk is likely to be due to the bile reflux.
This passage is from the first part of the report, based on a population study over 1995-1997, when PPI usage was common.
There is an interesting series of biomedical hyperbooks at Colorado State University. two that are of particular relevance are:
- Models of enzyme inhibition
This is part of a university course on Biochemistry by Dr. Jakubowski. It explains why such inhibitors are almost a switch: either the action is inhibited, it it is not. Increased dosage of PPIs won't result in lower acidity. A higher dose will last longer and will likely cause more side-effects.
A couple of correspondents emailed me with huge problems with bile reflux and gastritis. Both have had their gall-bladders removed. Both have been on long-term PPIs. So is there a link?
A Google Scholar search for Gall bladder PPI turns up:
For more evidence of bile problems see the links above on:
- Potential adverse effects of proton pump inhibitors
- Omeprazole side effects on the liver One side effect mentioned Cholestasis - bile draining slowly from the gall-bladder.
- Gallbladder function before and after fundoplication from which a quote:
Unexpectedly, 58% of patients with GERD demonstrated gallbladder motor dysfunction prior to fundoplication, with improvement to normal occurring in most of those studied postoperatively.
- Proton pump inhibitors reduce gallbladder function is a follow-up to the above paper. The authors realised the effects might be due to PPIs so tested 19 volunteers before and after a course of PPIs. 15 of the volunteers had reduced gallbladder function after taking PPIs.
This report was first published in "Surgical Endoscopy And Other Interventional Techniques" in September 2006, Volume 20, Issue 9, pp 1364-136. Authors are M. A. Cahan, L. Balduf, K. Colton, B. Palacioz, W. McCartney, T. M. Farrell.
Although 19 is too small a sample to be statistically useful - but it appears to be the only such research. Surely there is such a link and at the very least caring doctors should have heard alarm bells and investigated! Am I glad I took my own health into my own hands and did not listen to the doctors - mainly because they would not listen to me!
- Proton Pump Inhibitor May Reduce Gallbladder Function adds a bit more to the above report and explains why some people on PPIs feel nauseous.
- Genetic Determinants of Drug-induced Cholestasis and Intrahepatic Cholestasis of Pregnancy mentions PPIs as one of the drugs that can cause cholestasis.
- Larygopharyngeal Reflux
Something I used to suffer so I am well aware of how much nastier bile reflux is than mere acid: at one time (before I was diagnosed, shouting would cause me to cough violently!
- The Dreaded Diagnosis of Laryngopharyngeal Reflux Disease
Apparently the damage to the larynx etc is caused not by acid but more by pepsin in the presence of acid. I myself have experienced refluxed fluid which did not taste particularly acid, nor did it have the bitterness of bile, but it did burn in my larynx. I had hypothesised that this might be pepsin, but could find no confirmation before this paper.
PPIs are cleared from the blood by the liver, so the metabolic products end up in the bile. If these products are toxic - this could explain the apparent link between long-term PPI usage and gall-bladder dysfunction. There is little reference to the metabolic end-products on the www, but the following are of interest.
- Proton pump inhibitors--PPI differences emerge in hepatic metabolism. This states that
Omeprazole and, more markedly, esomeprazole, differ from the other proton pump inhibitors in that their bio-availability increases over the first week of treatment. This is due to a progressive reduction in their hepatic clearance with repeat dosing.
- Omeprazole side effects on the liver One side effect mentioned is terminal liver failure, which has occurred in some cases! Another reported effect is Cholestasis - bile drains slowly from the gall-bladder.
One popular solution to the problems of reflux is a 'fundo' - properly a Nissen Fundoplication operation. When this is successful it appears to be excellent. However as in any operation there can be complications:
- Study on 10mG/day omeprazole PRICHARD, P. J., YEOMANS, N. D., SHULKES, A., JONES, D. B., BUCKLE, P. J., SMALLWOOD, R. A. and LOUIS, W. J. (1986)
The effect of omeprazole on 24 h intragastric pH and fasting plasma gastrin during low dosage (10 mg) in the morning or the evening. Journal of Gastroenterology and Hepatology, 1: 289—295.
Departments of Gastroenterology, Austin Hospital, Melbourne, Australia
One of the lowest dosage studies I have found - yet a 10mG single dose is still an overdose.
Google for PRICHARD, P. J., YEOMANS, N. D., SHULKES, A., JONES, D. B., BUCKLE,
reveals many more pages by these researchers.
- A paper on the effect of low-dose omeprazole on gastric acid secretion in duodenal ulcer patients does deal with a very low dosage of 5mG/day. However it does not deal with the effect of several 5mG doses per day!
- Omeprazole and Other Proton Pump Inhibitors: Pharmacology, Efficacy, and Safety, with Special Reference to Use in Children has much background information, including information on differing responses to the drug in different patients.
- Review article: dual delayed release formulation of dexlansoprazole MR, a novel approach to overcome the limitations of conventional single release proton pump inhibitor therapy tries to suggest ways of overcoming the problems of PPIs not by little and often dosing but by a dual-action delayed release single dose. It is very clear that the doctors do not consider patients capable of taking medicines three or even four times daily so have not considered that. They may be correct. See my own pages for more on 'Microdosing':
A google search for oesophageal cough is revealing
The oesophagus is joined to the diaphragm by a ligament called the phrenoesophageal ligament. A Google search for phrenoesophageal ligament hiatal hernia is informative, though some pages are a bit technical.
Pepsin is little referred to but is a major digestive enzyme. It is requires an acid to neutral environment to function. Pepsin is a major problem if refluxate gets beyond the oesophagus, for instance into the airway. From my own experience bile is by far the worst, then pepsin, then acid. Pepsin, unlike bile and acid, has little taste. So quenching the acid in reflux is only a partial solution.
PPIs are a wonder drug - for short-time use. However long term PPI use can be dangerous. A drug such as a PPI is an "zenobiotic" which is metabolised by the liver. The liver adapts to such toxins by metabolising them quicker, so the effect of a single dose wears off quicker. I experienced noticeable tolerance to PPIs after about 3 1/2 years. PPIs also (in about 75% of people according to the only study that seems to have been made) cause gallbladder malfunction. As a dose wears off the first thing that seems to happen (from my own experience) is that the gall bladder partially recovers and causes bile in the stomach: an unnatural condition. Bile in the stomach probably causes problems there (such as gastritis and even cancer) and will cause bile in any reflux. Bile reflux, from personal experience, is far, far more unpleasant than is plain acid reflux.
A search for PPI cancer or PPI oesophageal canceris revealing:
See also Cancer risk for more papers.
PPIs have a short half life in the blood plasma as they are quickly eliminated by the liver. Their effectiveness is very much down to the area under the curve plotting blood plasma levels variation with time. However liver elimination is not the only time constant involved - see Half-life: what does it mean?
Various sites give various figures:
Incidentally a search for PPI plasma "half life" reveals many attempts to search for PPIS with longer plasma half lives, but nobody seems to realise that the way to deal with a short half-life is to increase the frequency of doses! That also means the doses can be reduced and the total intake also reduced.
- A Norwegian study explain the mechanism The authors of this are Helge L. Waldum, Gunnar Qvigstad, Reidar Fossmark, Per M. Kleveland & Arne K. Sandvik whose names may be rewarding in your searches
Considering how radically PPIs disturb the human metabolism and how different they make the biochemistry, it is remarkable they have so few side effects!
When first diagnosed with Barrett's I suspected that, although I was not overweight (I had a BMI near the top of the so-called healthy range) I was too fat for my own good. I lost weight, by reflux symptoms and general health improved. I suspected that visceral fat was the culprit.
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Last modified: Mon, 02 Dec 2013 10:35:23 GMT