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Today, December 2012, as I write this, I am no longer taking Omeprazole or any other drugs. Reflux symptoms are minimal - barely noticeable in practise. This is the story of my experiments to find out the correct PPI dosage, why I needed to experiment, what I learned about PPIs and my own body on the way. It is also about why I believe that long-term PPI use van be possibly more dangerous than the plain acid reflux. It is also about how I weaned off the drug.
I am not medically trained: my writing is as a result of curiosity and awareness of my own symptoms and, as a result, seeking facts that give consistent and rational explanation. Such a scientific approach should lead to experiments that can be tested: not possible for me, but they do leas to more questions, so to more information seeking. I have done much research in scholarly papers on the www and a list of some of these scholarly papers is available so you can read and draw your own conclusions.
A foreign chemical such as a drug (a xenobiotic - see a Wikipedia article on xenobiotic) in the body is eliminated, generally by the liver. The rate at which it is eliminated is directly dependant on the concentration in the blood plasma. There is an article in Wikipedia on drug metabolism.
So if the dose of a xenobiotic is doubled, the rate of clearance is doubled. This gives rise to a useful measurement: the drug's half-life. This is the time it takes the liver (or other clearance system) to reduce the concentration in the blood to half the original level.
Drug clearance is a specialist subject called pharmacokinetics.
Omeprazole has a short half-life.
The U.S. Food and Drug Administration Center for Drug Evaluation and Research says
The half-life of omeprazole is short, 0.5-1 hour. There is also a slow pharmacodynamic onset, with acid inhibition only 50% of maximum at 24 hours, and a long-acting pharmacodynamic effect of acid secretion reduction to baseline over 3-5 days. It is these effects that make Prilosec ineffective in acute relief and make it beneficial for 24-hour prevention.
A Wikipedia article says half-life is 1-1.2 hours. That Wikipedia article quotes a number of references.
So Omeprazole is metabolised very quickly in the liver, but the exact half life quoted seems very variable. Reasons for that variation are not stated, so below I offer my own explanation.
When first diagnosed, I was prescribed 40mg once per day. 8 weeks later I was re-scoped and told the ulcers were still present. 40mG was not enough - it lasted about 20 hours. I should take 2 doses per day. This got me thinking - and experimenting.
It seemed that the correct dosage was a matter of opinion! So I started checking exactly how long a dose lasted. As the effects wore off the first thing I noticed was a tickly cough. Then I would taste bile in the regurgitated fluid. Then it would start to taste acid.
This taste of bile worried me: why should bile be present in the stomach? But that's a digression: see the page on bile reflux.
In those days, I was not what the doctors consider overweight. However in retrospect it's clear that I was then sufficiently overweight (my BMI was then 23.6 - top end of the range considered normal) to exacerbate the reflux and to cause quite frequent regurgitation. In one way that regurgitation has been helpful as it has enabled me to better monitor my stomach fluids.
I found that indeed, I started getting the cough about 20 hours after a single dose. So I halved the dose, expecting a 20mG dose to last half the time. It didn't! Instead 20mG lasted about 18 hours: two hours less that a 40mG dose. It was at this point that I learned about half-life. I found, experimentally that
For a long time I was om 10mG taken every 8 hours. Then I decided to experiment with 5mG doses. Very tentative, I also tried ranitidine at the same time. Eventually (September 2010 - so 2 years after starting the Omeprazole) I settled om a 5mG dose every 8 hours. These caused the tickly cough to come after about 10 hours. A bit shorter than I expected) which I will explain later). But oddly, 37 days after starting this dose I had a massive nocturnal regurgitation of strong bile. If you have ever tasted that - it's far, far worse that acid and very difficult to rinse out of your mouth. I had another such attack after 46 days, 52 days. Then again 90 days after the regime change: this after eating a curry. And another at 108 days, after eating guacamole & taramasalata. No further major bile events happened until I stopped PPIs completely, but that's to follow.
During this time, I had also noticed acidity: I had also consulted a medical herbalist who (amongst other things) recommended I stop drinking tea as this can increase stomach acidity and cam cause extra reflux. I found that this did indeed seem to make an improvement - I now drink Red Bush team which doesn't have the same effect as the caffeine in tea.
Then I had another endoscopy: the consultant endoscopist did not like the reduced PPI dosage - arranged for pH monitoring. Sure enough, there was acid reflux. I increased the number of 5mG doses, but it looked like 5mG no longer worked at all. So I went back to 10mG. But I was now a bit confused as to why 5mG had ceased to work, when I though it did. And exactly how long did the 10mG dose last? Also - Barrett's seemed like a protection against acid. It seemed like something we had evolved as a protection, why did it progress? More on that later!
So after a bit of indecision, I decided to make some definite experiments with timing of a dose. I had determined that the first noticeable effect was the tickly cough. I was also fairly sure that this was cased by acid and by bile - however an acid attacks was quickly quelled by a drink of sodium bicarbonate (sodibic). Bile was not, so there was a was I could tell what was the most likely cause. 5mG did nothing. 10mg also had reduced effect. I tried Lansoprazole (no change) and went to 20mG.
Then finally after nearly 4 years, I decided to make a final concerted effort to time exactly how long 20mG now lasted. I had a cough, but sodibic didn't help it, nor did an experimental lansoprazole. It was clearly bile. I found I got bile related cough, but apparently little acid - except when I did severe physical exercise. My weight had now reduced so my BMI was now near the low end of normal: I did not often regurgitate fluids.
As I write this I have been off PPIs for nearly 8 months! Curiously the occasional tickly bile-caused cough has gone. It stopped after about 6 months. . I hardly ever get acid-reflux symptoms - when I 'm aware of acid I take conventional antacids. Reflux is clearly still happening but it's acid, not bile. Whether this so called "silent reflux" is dangerous is a matter of opinion: it depends on whether the Barrett's can be prevented from progressing.
The liver produces bile. It is stored in the gall-bladder, from whence it is released as required. Release it triggered by a complicated system of hormones, chief amongst which is gastrin. These hormones are explained in a tutorial on the Endocrine system by Colorado State University.
Bile production and release is normally triggered by food, especially fatty food. Bile is released into the duodenum where it mixes with the food. There is a Wikipedia article on bile which explains it all.
I have suffered from bile reflux. The doctor said that it simply showed a lax pyloric sphincter. But to get bile reflux as I did sometimes in the middle of the night when my stomach must have been empty seemed wrong. This niggled me and needed explaining: I read up on the subject. To get bile reflux when the stomach is empty requires bile to be produced and released at the wrong time. So something other than food must be triggering abnormal bile release.
Yes - a lax pyloric valve will allow bile back into the stomach, but that can only happen if bile is being produced when there is no food present to trigger it! There are also other sphincters that allow the gall-bladder to release bile. These must be operating at the wrong time. So bile in the stomach seems to me an alarming abnormality.
There is lots of anecdotal evidence (if you look hard enough) that bile reflux is apparently not uncommon in people on Omeprazole. It is even said to be one possible reason why PPIs are not always as effective as expected. See some of these papers, links on my page of references.
More seriously, two of the papers quoted on the references page seem to prove unarguably that there is a severe risk of gall-bladder damage from long term PPI use. Any damage from short term use seems to be not permanent.
I have proven to myself that it is indeed Omeprazole that causes bile reflux. Proven by reducing the Omeprazole dosage when the bile reflux stopped. A trial on one individual is hardly scientific proof but it was arrived at by scientific methods: I had a suspicion that the bile reflux and the tickly cough were both caused by Omeprazole.
I put the theory to my doctor: he said that other PPIs were likely to have the same effects, I should try Ranitidine. That did not adequately control acid production. That may be another story - there may be antagonism between Omeprazole and Ranitidine, and long term effects of Omeprazole may mean the 2 week trial was not a fair test. But the discomfort on Ranitidine was generally greater than on Omeprazole, so I decided to continue experiments with reducing Omeprazole levels.
One mechanism that explains some of the bile reflux is gastrin. See the page PPIs increase gastrin levels. Gastrin is the hormone that triggers bile release, and gastrin production by the stomach is switched off when th stomach pH falls below about 3. When I had severe bile regurgitation, did indeed find that an acid drink (dilute vinegar or lemon juice) did indeed give some relief. The gastrin mechanism may explain why, as the PPI wore off, I first tasted bile, not acid. But it does not explain the 3 month period during which I had nocturnal bile regurgitation. I think this was my compromised gall-bladder recovering normal functioning. Of interest is the fact that the tickly cough I mentioned above seemed to stop after about 6 months off PPIs. This presumably means that there is no bile now in my stomach: my gall bladder has presumably recovered fully.
Although gall bladder malfunction had been documented and it is a very common (much more than 50%) side effect of PPIs, other than the two papers concerned very little else has been done about this - although Barrett's (and presumably its progression to cancer) is though to be due to bile as well as cancer and bile reflux is known to be dangerous.
Yet, despite many hours searching the www for information on the minimum effective dose of Omeprazole, I am unable to find any reference to the subject! I have listed some of the more interesting pages I have found on Barrett's oesophagus, Omeprazole dosage and bile reflux. One realises that Omeprazole causes bile reflux. None have investigated MinED!
Seems to me that the profession as a whole know it is a safe drug without side effects so nobody has ever thought along the lines of a MinED!
My own experiments pointed to a very low MinED - maybe 5mg. But it seems that the MinED is likely to depend on the length of time for which you have been taking PPIs.
In fact a Google search for Minimum effective dose is informative in how little information it divulges on any drug!
Even more disturbingly, although this finding dates from 2005, there appears to have been no further work done on this - almost as if the medical profession do not want to know. Since PPIs are the main tool against reflux, if the finding were proven to be general, PPIs would be removed as a useful tool, leaving the doctors fairly powerless.
This was not an easy differentiation to make - there are many different causes of a tickly cough!
However any acid induced symptom is likely to be quickly relieved by sodium bicarbonate which is a very fast-acting antacid. Bile induced symptoms will not be affected.
There appears to be no antidote to bile. However there is a very common statement that cider vinegar can help reflux. This on first thought is a nonsense.
But if the reflux is bile rather than acid it could make some sense: the bile release system is turned off by hormones triggered by acid. So cider (or any other) vinegar could help bile reflux by turning off bile release. I found that there was no immediate relief, but it did appear to make the reflux stop sooner.
There is nothing findable on the www concerning tolerance to PPIs. They are generally assumed to not suffer from tolerance. However my own experiments seem to show that, over the years, a single dose was becoming gradually less effective: its half-life seemed to be decreasing.
This would be consistent with the liver 'learning' to process the xenobiotic and seems to be consistent with the way it is cleared. Such tolerance would also be consistent with the widely variant half lives quoted by various sources. So it cannot be ruled out!
The commonly experienced problem with stopping PPIs is said to be "rebound acidity", happening particularly at night. I suspect that it is often rebound biliousness: I experienced intermittent very severe nocturnal bile reflux events and no severe acid events. I have yet to find any scientific papers where this rebound has actually been measured. It appears to be an assumption that the rebound is acid: it could equally be bile!
When I put this point to my consultant, her response was that PPIs cause a massive upset in the hormonal system. So acid rebound is caused by the hormonal system overshooting when PPIs are stopped. However PPIs (if taken is adequate amounts) kill the proton pumps. Acid can only be produced by the stomach growing new pumps. This happens gradually over time and there seems to be no way an acid rebound could then occur. However PPIs are known to affect the gall-bladder, a study had proven that even short-term use massively reduces the gall-bladder's efficiency. Gall is still produced, and the gall-bladder could (as I experienced) eject gall erratically and spasmodically. Though why at night, I cannot explain!
The effect, either way, is that if you stop PPIs you can expect some very nasty nocturnal reflux events. You will have to go though these.
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Page first published: Sunday the 10th of October, 2010
Last modified: Thu, 16 Nov 2017 14:31:30 GMT
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