Omeprazole dosage and side effects – experiments with dosage
Contents – this page
- Omeprazole dosage and clearance
- My journey through PPIs and out
- Minimum Effective Dose
- Bile reflux
- Side effects of PPIs
- How can I tell bile reflux from acid reflux?
- Can the body grow tolerant of PPIs?
- How can I wean myself of PPIs?
- Interesting www pages on Barrett’s oesophagus, Omeprazole dosage and bile reflux
This page is currently being re-written
In July 2008 I was diagnosed with acid reflux, an ulcerated oesophagus and a 9cm long Barrett’s oesophagus. I was immediately prescribed Omeprazole.
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 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
- 40mG lasted 20 hours.
- 20mG lasted 17½ hours.
- 40mG lasted 15 hours.
although times were not exact and exact measurements were difficult.
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. <p)then 49=”” days=”” after=”” stopping=”” ppis=”” i=”” had=”” another=”” massive=”” nocturnal=”” bile=”” event.=”” and=”” at=”” 59=”” days,=”” 75=”” 88=”” 104=”” (this=”” a=”” meal=”” high=”” in=”” meat).=”” then=”” they=”” stopped.=”” <p=””>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.
One of the thoughts that struck me is that surely any medicine that is prescribed should have a known minimum effective dosage that is properly researched and well known. Surely if you are going to give patients a drug you need to know how little is going to be effective? That seems so obvious (to a layman) that is seems not worth saying.
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!
Side effects can be divided into three categories:
- Secondary effects due to reduced stomach acidity. These do not seem to be of statistically great importance.
- Direct effects of PPIs on the system which may be common in lots of users. I find these more alarming, tough they do not seem to be realised by most doctors.
- Other side effects. Few and far between. I have no experience so cannot comment.
These are well-known and I won’t cover them in detail as you can surely find information for yourself:
- Brittle bones
- Caused because acid helps the ingestion of minerals, calcium being one.
- Caused because acid helps with the ingestion of iron also.
- Stomach acid kills most bacteria that are ingested. With no acid, food-poisoning and other diseases that are caught via the gut become more likely.
- Mentioned in Bile reflux above. Gastrin in an important hormone that controls the digestive system. It relaxes the lower oesophageal sphincter and causes th gall-bladder to release bile. Its production is switched off by acid levels in the stomach. If you aren’t acid, you can get excess gastrin in the blood.
- Nausea and vomiting
- Since PPIs interfere with gall bladder function, PPIs may cause symptoms of gall bladder disease. These symptoms include abdominal pain, nausea and vomiting.
It seems that it has taken the medical trade a long time to find out about primary effects. moreover if the main primary effect is as serious as I find the evidence proves. PPIs are not an effective tool to prevent reflux progressing towards cancer. Indeed PPIs may even be causing some of that progression.
- Bile reflux
- I experience bile reflux as a direct result of taking PPIs. If you search the www there is plenty of mostly anecdotal evidence of bile reflux occurring. See the references page on bile reflux.
- Gall bladder malfunction
- Disturbingly there are two reports by the same team that seem to prove that gall bladder malfunction is very common – almost the rule rather than the exception. However they tested only a small sample. See references page on gall bladder.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.
- Gall bladder damage
- If PPIs cause gall-bladder malfunction, can continued use lead to actual damage? This is a matter of speculation, but there are people on the internet who have had their gall bladders removed, after continued long term PPI use. Whether the PPIs were given as a result of gall bladder problems, or whether the problems followed the PPI use, I cannot say. However it would be wrong to deny the possibility and in view of the report on gall bladder malfunction, I find the possibility disturbing.
Generally speaking the symptoms of bile reflux and acid reflux are identical. I found that (after I had lost weight) the main remaining symptom was a tickly cough. There are cough receptors on the oesophagus and this cough was clearly a result of irritation. In the early days I could taste the refluxed fluid, so telling bile from acid was easy. Both bile and acid caused me the cough, probably bile more so than acid. However if I took a dose of the original antacid, sodium bicarbonate, an acid induced cough would be quenched. Sodium bicarbonate does nothing whatsoever for a bile-induced cough.
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.
Drug tolerance is a well-known problem with many drugs, where, over the course of continued administration, the drug becomes less and less effective as the body learns how to cope with it. There are several mechanisms whereby tolerance can occur.
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!
I cannot give you a definitive answer. I weaned myself off in effect by reducing the dose gradually and simply seeing what happened.
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 explains!
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: Wed, 11 May 2016 10:38:47 BST
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