• The bile production system
• How can you tell the difference between acid and bile reflux?
• What can I do to relieve bile reflux?
• PPIs and bile
• PPI withdrawal causes bile reflux
• PPIs can damage the gall-bladder
• Gall stones
• A list of links, with comments, to relevant www papers

The bile production system.

Bile is produced in the liver and stored in the gall bladder. When food is eaten, bile is released into the duodenum (the upper part of the small intestine) via the sphincter of Oddi (Google will show you some interesting pictures and much more information) to mix with the food as it leaves the stomach.

This timing is very complicated: there is a hormonally-controlled feedback and timing system involving several hormones. It seems this system is not entirely understood – and few doctors seem to know anything about it!

The main hormone involved in bile reflux seems to be cholecystokinin, which itself is intimately controlled by Gastrin. Gastrin is secreted into the blood stream by the stomach. It’s secretion is triggered by the presence of food – in particular peptides, certain amino acids and calcium. Certain compounds in coffee, beer and wine are also potent. See Colorado State University’s ebook Pathology of the endocrine system for more detail.

Gastrin causes acid to be secreted into the stomach. Its production is switched off again when the pH in the stomach falls – i.e. when the acidity gets high. This is why hypergastrinaema (excess blood gastrin levels) is a well documented side effect of long-term PPI usage.

Gastrin also interacts with many other hormones. It relaxes the lower oesophageal sphincter. It probably also relaxes the pyloric sphincter (via other hormones) and it (also via other hormones) triggers bile production and release.

So interfering with acid production by taking PPIs and, probably, also H2 receptor antagonists (Ranitdine and similar drugs) is likely to affect the bile system allowing bile to flow at the wrong time and also allowing bile back into the stomach via a relaxed pyloric sphincter.

I found when I first started on PPIs that I could taste bile as the PPI dosage wore off. See my page Hiatus Hernia, Bronchiectasis, Barrett’s oesophagus, so I was well aware of bile. Later (as I lost weight) I would not taste refluxate and differentiating between bile and acid reflux became more difficult.

There is a documented link between PPI usage and gall-bladder malfunction. See: Gallbladder function before and after fundoplication from which a quote:

Unexpectedly, 58% of patients with GERD demonstrated gall bladder motor dysfunction prior to fundoplication, with improvement to normal occurring in most of those studied postoperatively.

The authors reladid thatt it could be the PPIs that caused the malfunction! Naturally, after fundoplication, PPIs are withdrawn – hence the gallbladder recovery. So they did another test. See their paper Proton pump inhibitors reduce gallbladder function.

How can you tell the difference between acid and bile reflux?

This is usually difficult: the symptoms of both are generally extremely similar. However sodium bicarbonate in water almost always brings immediate relief from acid indigestion. It does absolutely nothing for bile reflux.

Sodium bicarbonate (SodiBic) also releases carbon dioxide as soon as it hits stomach acid – so is quite likely to cause almost immediate belching. This is not 100% – it depends on the amount of acid and bicarbonate. SodiBic has no such reaction with bile!

If you are unlucky enough to regurgitate stomach fluids, you will easily know the difference between acid and bile. Bile is hugely more unpleasant, being very bitter!

What can I do to relieve bile reflux?

Immediate relief seems impossible. However once you realise that bile flow is triggered by reduced stomach acidity and switched off by acids, it seems logical that an acid drink will help. Diluted vinegar – cider vinegar is generally the most palatable and said to be the most healthy – or lemon or lime juice or plain citric acid may therefore help. I found they did indeed help when I experienced bile reflux, but the relief is not immediate.

PPIs and bile

The digestive system is hugely complicated: there are many known hormones – Gastrin, Secretin, Cholecystokinin, Ghrelin, Motilin – and probably more to be discovered. They interact with stomach acidity in ways that are still being explored.

Switching off stomach acid by any means is like throwing a spanner into a complex machine. Amazingly it does not cause much trouble: it is reputed to be one of the safest drugs around. However – its long term use is evidently problematical.

I was lucky enough to realise it was affecting my bile system. I was luck enough to be able to withdraw from the drug – totally against medical advice – before any damage was done! I did not listen to the doctors – chiefly because I found they were nor prepared to listen to me! My father was a consultant surgeon, and he always said that any doctor who was not prepared to openly listen and discuss their views was not to be trusted. Very good advice!

However – once you suspect PPI usage is affecting your bile production, there is enough evidence in papers on the www to be totally convincing. Long term PPI usage is dangerous!

If a drug is affecting you negatively – clearly you must withdraw from its usage! This is not easy with PPIs! Rebound acidity is a known and admitted problem. In my case – I found the main rebound was bile – not acid. This intermittent bile reflux occurred chiefly at night (as is widely admitted for acid rebound). However as few people can tell the difference between acid and bile reflux symptoms, the rebound acid reflux reported may indeed be rebound bile reflux rather than acid.

PPI withdrawal causes bile reflux

I found that, after ceasing PPI usage, it look a very long time – 100 days or so – for bile reflux episodes to subside completely. The mechanism for that escapes me completely! I experimented to find ideal PPI dosage: elsewhere I have written up more about my experimentation with PPIs. On both occasions I had severe bile nocturnal reflux which was clearly to do with the PPI withdrawal. Whilst the above link on experimentation does explain some of the mechanisms, it cannot explain the extremely long time it took for my system to settle!

I kept a diary of these events and the timing was

• 15 Sept 2010: stared on 3 x 5mg Omeprazole per day. It is (in retrospect) clear this was inadequate at that time to completely suppress acid.
  • 22 Oct 2010 (37 days) Nocturnal bile reflux event. Not severe.
  • 31 Oct 2010 (46 days) Nocturnal bile reflux event. Fairly strong.
  • 6 Nov 2010 (52 days) Strong nocturnal bile reflux event.
  • 14 Dec 2010 (90 days) Strong nocturnal bile reflux event. This was also after eating a curry. However now, totally weaned of PPIs, I can eat hot curry with no problem!
  • 1 Jan 2011 (108 days) Strong nocturnal bile reflux event after eating guacamole an taramasalata in the evening. Again – these foods do not affect me now.
    In July 2011 I had another such curry and a barbecue at which I ate Czech cheese in oil – both of which should have caused bile events were they caused by food alone. No such bile reflux occurred.
• 27th April 2012. Stopped taking Omeprazole (after 3 years 9 months)
  • 15 Jun 2012. (49 days). Bad nocturnal bile reflux.
  • 25 Jun 2012. (59 days). Bad nocturnal bile reflux.
  • 9 Aug 2012 (108 days). Bad nocturnal bile reflux after a large meal at a Brazilian restaurant in Prague.
    Since then, I have had no such bile events.

<p?the above=”” is=”” anecdotal=”” and=”” proves=”” little.=”” however=”” the=”” extreme=”” similarity=”” of=”” two=”” scenarios=”” strong=”” indication.=”” <p=”” style=”color: #000000;”>Of course – my system may be atypical. However the various papers I have found on the www and the contacts I have had lead me to fear that such bile interference is the norm for PPI usage, especially as the liver learns to metabolise the drug quicker, so it becomes less effective, and with PPI withdrawal. However there are several papers that prove it’s not uncommon

• Heartburn treatment May Increase Bile Reflux.
• Omeprazole Liver Side Effects
• Effects of rabeprazole, a gastric proton pump inhibitor, on biliary and hepatic lysosomal enzymes in rats. Which, of course does not prove much about humans.
• Proton Pump Inhibitors: The Culprit for Barrett‘s Esophagus?
• Proton pump inhibitor use may not prevent high-grade dysplasia and oesophageal adenocarcinoma in Barrett’s oesophagusThis paper concluded (based on 9883 cases): No cancer-protective effects from PPI’s were seen. In fact, high-adherence and long-term use of PPI were associated with a significantly increased risk of adenocarcinoma or high-grade dysplasia.

PPIs can damage the gall-bladder

Furthermore – if as I found, tolerance does develop to PPIs, then bile flow interference and gall-bladder damage are probable effects of any long-term usage of PPIs.

There are, on the www two papers of relevance. The first entitled Gallbladder function before and after fundoplication. found that gall-bladder functioning actually improved after fundpolication. This unexpected finding clearly set the team thinking as they later tested the gall-bladder functioning of 19 healthy volunteers. Then the volunteers took a course of PPIs and had their gall-bladder function retested. In 15 out of the 19 volunteers, gall-bladder functioning had indeed been affected. The paper is Proton pump inhibitors reduce gallbladder function.

These two papers are strong evidence that PPIs do compromise gall-bladder function. If mine was compromised I would theorise that the bile reflux events after PPI withdrawal were my gall-bladder recovering from the effects of the PPIs.

Gall stones

There is much thought that PPIs might cause gallstones, but there is little real evidence that I can find. If you are a person whose ball bladder is affected by PPIs, it seems that cholestasis is the result – so bile would not be released as it should, but would stay in the gall bladder longer and could then, in theory, concentrate and form stones.

Gall stones (according to wikipedia) have four main constituents:

• Cholesterol
• Bilirubin
• Calcium carbonate
• Palmitate phosphate

I would be interested to hear more on this subject, so please contact me if you can add anything.

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