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In 2008 I was diagnosed with a hiatal hernia, 9cm section Barrett's oesophagus, and, above that, severe oesophageal ulceration. I also had mild bronchiectasis which can sometimes be caused by gastro oesophageal reflux disease (GORD) due to inhalation of the refluxate.
I suddenly became interested in health matters and have discovered a lot about GORD, Barrett's and the PPIs used to control reflux. This page is essentially a summary of information I have learnt.
I am not medically trained so these facts must not considered as medical advice. However it has become clear to me that a lot of doctors know very little about the drugs they prescribe and if their advice is inconsistent with the facts presented herein, you will better know what questions to ask them to clarify their reasons!
A - Special stomach cells, called stomach parietal cells, have mechanisms called 'proton pumps' which can produce acid and which can be turned on and off by hormones in the blood stream. The proton pumps contain an enzyme called Hydrogen potassium ATPase (shortened to H+K+ATPase which does the actual work and which is killed by the drugs called Proton Pump Inhibitors or PPIs
The italicised terms above will furnish more technical information of you use them in a Google search.
A - The parietal cells bear receptors for three stimulators of acid secretion, reflecting a triumvirate of neural, paracrine and endocrine control:
However other chemicals and hormones in the blood stream can stimulate production. These include calcium, enkephalin and bombesin. The process is complex and probably not fully understood. Certainly worry can trigger acid production, as can hunger or the mere thought or smell of food.
A - Many hormones can turn off acid secretion. These include:
A -This seems to be a major problem with PPIs. It seems to be unpredictable: sometimes it is cured and sometimes it is caused by PPIs. So the doctors think that if a high dose doesn't work - they try a higher dose. They are literally shooting in the dark - with your body! They do not seem to realise that PPIs actually upset the bile production mechanism. Elsewhere I have explained one of the ways PPIs can upset bile release.
Yes. Bile is produced more or less continuously by the liver and stored in the gall bladder. It should be released as ingested food leaves the stomach ater processing to mix with this chyme (as the processed food is called) on its entry to thr small intestine. However this release of bile from the gall bladder is only a part of a long chain of hormonal events which control acid production, bile production and release, pancreatic secretions and even the feeling of fullness after a meal. The chain is controlled by the brain so even the thought, smell, or sight of food can start things happening!
The liver also metabolises most drugs - including PPIs so it may not be surprising if some of these drugs upset liver function. My own experience was that high PPIs caused problems in this respect.
If your doctor can think of any reason - please let me know! However the medicines that are prescribed to control stomach acidity can and apparently often do cause bile reflux. There is a complicated biological feedback system involved which controls acid production, bile production, pancreatic secretion, stomach action, intestinal action and even the feeling of being full after a meal. Completely preventing one step in the process (for instance, the production of stomach acid) can and does upset the general balance of these events, leading to various possible side effects.
Since writing up the above, two paprs have come to my notice: the first found that (I 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.
See the list of references on gall-bladder.
Acid reflux symptoms are likely tp be rapidly quenched by a drink of sodium bicabonate - about 1/4 teasoop in a glass of water is usually effective. It does absolutely nothing for bile!
Sodium bicabonate - baking soda - is a harmless chemical and a stronger dose is unlikely to harm. Excess sodium bicarbonate over a period could possibly trigger acid release as the body tries to compensate and this might eventually cause blood alkalinity. Also of course it's not helpful to a low sodium diet, but for the average person it's a lot less harmful that PPIs!
The granules are then put into an outer capsule.
The following ingredients list is taken from Dr Redy's capsules. Links are to wikipedia on the chemical.
The granules contain
The outer capsule contains
If diarrhoea persists, medical advice should be sought as some gut infections can be harmful.
One major side effect (which is generally not admitted by the profession) is that PPIs, in most people, affect the gall-bladder (see Gall bladder and PPI usage, causing cholestasis (slow bile release). Poor gall-bladder function can cause effects such as nausea, abdominal pain, vomiting etc. so these may be experienced as a side-effect of PPI usage.
Minimum effective doses of most drugs do not seem to be published, researched or even known! Drug companies are more interested in selling the maximum safe dose ad safety is a matter of opinion. So minimum effective dose is not generally known! To a layman the concept of minimum effective dose seems fundamental and common-sense. Not so, apparently to the drug trade in general.
I found that I was almost certainly developing tolerance to PPIs after about 3 years: if so the minimum effective dose will also depend on how long you have been on the drug! There is a blood concentration level below which the drug is ineffective.
Another page on this site deals with how I experimented to find the minimum effective dose of Omeprazole - or at least a very low effective dose!
Age affects the dose you need.
Some time after you take a dose of a drug it will all have been absorbed from your gut and the blood level will be at a maximum. However the body tries to eliminate this 'foreign substance and the rate at which it is removed depends on the concentration in your blood. So if the half life is 2 hours, then, two hours after this maximum blood level, the blood level will be halved. Two hours later it will be halved again (so 1/4 of the peak). Two hours later it will be again halved - so 1/8th its peak level. It follows that a drug with a short half life should be taken frequently and in small doses. Many antibiotics are indeed taken in this way.
PPIs have very short half-life! A paper from the US states it to be 1/2 to 1 hour. My own experiments and experience say it is a bit more than 2 hours (but this is the subjective half-life, see below). So if maximum level is reached 3 hours after ingestion then a dose intended to last 12 hours will have halved 4 times so blood levels will have reduced to ½ x ½ x ½ x ½ or 1/16th of their peak level. If that low level is still effective the 12 hourly dose resulted in a 16 times overdose at the peak level.
The picture is complicated because, as well as the liver clearing the drug, some of it is absorbed properly by the stomach cells that secrete acid. Here is does its work, and there are half life involved in the way these cells can recover and be replaced: that half life is around 50 hours! There is a useful review article on PPIs listed in the links section.
5 different half-lives. Subsequently to writing the above, I learn more. So far I have located 5 different half-life effects:
There are many factors affecting the uptake of the PPI by the parietal cells (these are the cells in the stomach that produce acid). Age is one factor - it affects virtually all metabolic processes! The older you are, then the less PPI you are likely to need. Age presumably also affect how well your liver metabolises the drug in your blood - the better the liver's metabolism, the more drug you will need to take.
Your doctor will have prescribed one or two doses per day. Possibly of 40mg each.
There are a large number of factors involved in optimising dosage, so standard prescriptions are a compromise and are based on two assumptions:
A high dose, such as 40mG, results in a high level of the drug in your blood serum. That high level is metabolised quickly by the liver. See Half-life: what does it mean?, above.
However the effectiveness of PPIs is controlled not by the peak serum level but by the 'area under the serum concentration-time curve'. If you were to measure the serum level and draw a graph showing how the serum level reduced over time - that is the 'serum concentration-time curve'.
If your daily dose is 40mG then this area will be higher if you take the 40mg as two 20mg doses than as a single dose. It will be higher again if you were to take it as 4 times 10mg. However, the peak level will be halved by the 20mg doses and quartered by the 10mg doses. It seems certain that any side effects you may have are caused by the peak level - not by the 'area'.
So if you are having trouble with PPIs you can minimise this by taking little and often. 3 or 4 small doses is going to be far more effective than one or two large doses. Your exact dose will vary with your age and other circumstances but you can minimise the amount you need by small, frequent doses.
It is widely accepted that stopping PPI usage causes rebound acidity. My own experiences suggest the rebound is not acid but bile. Certainly when I stopped, I had intermittent bouts (lasting up to 100 days after stopping PPI usage) of extremely strong nocturnal bile regurgitation. Very unpleasant: bile is far more unpleasant than acid and antacids don't affect it - indeed theory says they could make it worse. See my separate article on bile.
There is very strong evidence that PPIs can actually cause gallbladder damage: if so then my bile attacks were probably my gallbladder recovering from such damage. See references on gallbladder.
With this evidence, I believe the sooner you stop PP usage anfd go through the suffering, the better.
Barrett's oesophagus itself has no real symptoms. The acid or bile reflux that caused the condition can of course have severe symptoms: these are many and varied but the commonest is indigestion or heartburn. The medications that are given to control acidity can also cause side-effects.
Severe reflux can cause other problems such as a hoarseness (if the refluxate gets into the vocal chords), a cough or various chest problems as refluxate can be inhaled and enter the lungs. It's probable that most people will get severe coughing fits and other symptoms before this happens as the cough reflex comes in.
Most people who have been diagnosed with Barrett's oesophagus will have been prescribed PPIs to control the acid production. Although tolerated well my most, the high doses prescribed will cause side effects in some people and it seems likely that many of the symptoms people ascribe to Barrett's oesophagus are in practise side effects of the drug!
Although Barrett's oesophagus is widely said to have no symptoms, it seems that a feeling under the breastbone is actually a symptom. This is not a pain: more of a sensation of pressure, feeling of heat or a slight itch that you want to rub or scratch. It's easily ignored.
An inflamed oesophagus (as in Barrett's oesophagus) is itself more likely to be sensitive to acid and bile, increasing the incidence og heartburn so this also could be a symptom. There are links to papers finding this increased sensitivity in an inflamed oesophagus elsewhere on this site.
Yes. There is not a lot easily found about the incidence in animals but there are a few studies. For instance a study of Reflux Esophagitis in three cats states that reflux is quite common in dogs and cats. So hiatal hernias, reflux disease and Barrett's oesophagus are not human only diseases. They are clearly an evolved response to excess acid in the oesophagus!
A difficult question! My own opinion is that it depends entirely on why you have Barrett's oesophagus. For instance, if you are overweight you are eating too much and your diet is probably unhealthy. If that has caused your Barrett's then yes, it is a wake-up call to change your lifestyle: the unhealthy diet that lead to your obesity and thence to the reflux that caused the Barrett's could also cause other bad health, even cancer.
It may be true that Barrett's oesophagus can sometimes progress. However most cases do not! Barrett's oesophagus was only described in 1950 but it was surely present before that. Cats and dogs also get the condition. So it is probably best to realise that gastric reflux leads to Barrett's oesophagus and it is also gastric reflux that can leads to cancer. There seems to be no information on which cases of Barrett's progress and which do not. If the causes of Barrett's were studied it might be found that there was a sub set which was not prone to progress and another sub-set which was.
However if your Barrett's is caused by a hiatus hernia which is not related to overweight and diet, then Barrett's is probably not a cause for concern. However with a hernia, the critical level at which your weight affects you could be far lower!
Although Barrett's was first described in the 1950s, it also occurs in cats and dogs. The cellular structure (columnar cells with goblet cells) appears to be very similar to the oesophageal lining found in reptiles, so Barrett's seems to be a sort of atavism. It is then very likely that Barrett's can occur in almost any mammal, when they have hiatal hernias and it must also have been occurring in humans since time immemorial. If a hiatus hernia (or other physical problem) cause acid to be refluxed into the oesophagus, the oesophagus has to protect itself and it does so by the cells changing to the type normally found in the intestine. A cell type that can better cope with the reflux. If the cells did not protect themselves - severe ulceration would result.
Of course if you have a hiatus hernia, or a tendency to form one, then even a small amount of excess weight could make all the difference!
So you should not necessarily be concerned about the Barrett's but you should look to the reasons Barrett' has developed in yourself. The cause of your Barrett's may, indeed, be cause for concern!
There is another reason why you should not be too concerned: the brain controls the digestive system (exactly how far has not been determined yet) and it is well known that worry causes excess acid production. Worry can also affect muscle tone and a stomach knotted by worry can probably make reflux far worse!
The usual answer to this is no and you should expect the change to be permanent. However Barrett's can indeed recede. Short sections can return to normal and, in long sections, islands of normal cells can appear in the changed area.
Unfortunately there seems to be no simple answer to this. It seems that everyone is different in what they can eat and what causes them problems.
This puzzled me for a long time - for surely humans should have similar physiology, so similar foods should have similar effects.
It therefore seems very likely that gastric acid secretion is controlled not only by the foods we consume but also by our brains. If the brain has at least partial control then we would indeed expect to be different, one from another.
Indeed a Google Scholar search for brain gastric secretion reveals a number of papers where research into exactly this brain control has been done on rats. If rats can do it, surely humans can too!
Such 'brain control' would of course explain, for example, how worry can cause duodenal ulcers!
A difficult subject with many unknowns, medicine is beginning to find a few cracks through which light shines. I am not qualified to give sensible advice, but it seems to me that there are three factors which govern your chances of getting cancer - any cancer:
Speaking on this subject to a cancer/Barrett's oesophagus specialist, she said that they had identified three items which did seem essential;