Bile acid malabsorption; an unrecognised cause of IBS-diarrhoea
Bile acids are nature’s laxatives. So said Dr Alan Hoffman, for many years a world expert on bile acids. So might malabsorption of bile acids be a major factor in IBS diarrhoea?
Bile acids are synthesized from cholesterol in the liver and are released along with other components of bile into the small intestine, where they disperse fat rendering it capable of being digested by pancreatic juice. They then convey the digestive products to the cells lining the small intestine and assist their absorption, before shuttling back to pick up more fat. In this way they are key players in ensuring adequate fat absorption.
Bile acids continue to do their conveyancing as the meal travels the 20 feet of small intestine, but when they get to the last section, which is called the ileum, they combine with a receptor and are themselves transported across the intestinal wall into the veins that drain into the liver and are used again to help digest the next meal. Under healthy conditions, only about 5% of bile acid is lost into the colon, where it is converted by bacteria into highly irritant secondary bile acids, which stimulate secretion and peristalsis – nature’s laxative. This entero-hepatic circulation of bile acid is disrupted if the ileum is inflamed by Crohn’s disease, has been surgically resected or if the passage through the ileum is too quick for complete absorption to take place. Then the secretion and peristalsis caused by an excessive influx of larger amounts of bile acid, can overwhelm the ability fo the colon to salvage salt and water and diarrhea can ensue. This is know as bile acid malabsorption (BAM).
The most frequent method of testing for BAM is to administer by mouth a small dose of radioactively tagged bile acid, which mixes with the circulating pool of bile acid. Then after a week the body is scanned to determine the amount retained. This is known as the SeHCAT test. Normally upwards of 20% of the label is retained after a week but anything less than 15% indicates bile acid malabsorption.
Although this test has been available for about thirty years, few diagnostic centres use it. The reason for this is not clear. Perhaps it is considered too cumbersome, perhaps there is some anxiety over the dose of radioactivity (which is actually less than background radiation), perhaps doctors do not appreciate that BAM is so common.
Bile acid malabsorption as detected by SeHCAT testing occurs in a third to a half of patients with idiopathic/IBS diarrhoea, and most people with low SeHCAT retention (49 to 83%) respond to bile acid sequestrants, resins that adsorb or stick to bile acids and remove them from the body without causing irritation. There are several sequestrants available: colestyramine (questran), colesevelam and colestipol. Colestyramine is the one that is most commonly used. I prefer to prescribe it since patients learn to take it half an hour before a meal and can easily subdivide the dose titrating it with the size of the meal and the response of the symptoms. Not everybody likes Questran, finding it gluey or gritty in the mouth, but if it is mixed with orange juice and swallowed quickly, it goes down well.
So to use common parlance, we might say that treating IBS diarrhoea with Questran or other bile acid sequestrants is a ‘no brainer’. Not so! Questran is licensed for reducing cholesterol, not for treating diarrhea, yet when IBS diarrhea is associated with urgency, it can work very well. Those of us , who believe that BAM is a major factor in IBS-diarrhoea, might often use a trial of Questran as a diagnostic therapy, but we would struggle to convince other medical practitioners without evidence that the patient has BAM. But how can we prove that BAM is a significant factor if the SeHCAT test is not generally available or recommended by NICE and the treatment is not licensed for that indication? It’s not just a double bind, but a triple bind.
The water has been rather muddied in recent years by the discovery of a ‘gut hormone’, FGF-19, which is released from the ileum when bile acid is absorbed and inhibits bile acid synthesis in the liver, providing negative feedback. Bile acid malabsorption from whatever cause will therefore reduce FGF-19 and stimulate additional synthesis of bile acid, which might enter the colon in larger amounts causing more diarrhoea. This discovery has led to the notion that IBS might be associated with a primary defect in production of FGF-19 instead of reduced absorption due to rapid ileal transit, yet it has been know for many years that IBS-diarrhoea is associated with rapid small bowel transit.
So if you have diarrhoea associated with IBS and it does not respond to restricting FODMAPs, do consider whether food and bile acids are passing too quickly through your small intestine and irritating the your sensitive colon and whether you would be better treated with Questran.
Most studies and many letters received by The IBS Network would support the use of colestyramine and other bile acid sequestrants, but doctors are unlikely to prescribe these unless there is evidence of bile acid malabsorption. If the NICE committee could acknowledge that bile acid malabsorption as detected by SeHCAT testing is common in IBS-diarrhoea and responds to bile acid sequestrants, it might allow patients to receive an effective treatment, doctors to use an effective test and clinic investigators to carry out more research.
The Sensitive Gut 
Would treating the symptoms with Questran or similar that removes bile acids from the body also in itself result in a reduction of the absorption of the bile acids via the usual pathway, so resulting in the increase in the action of FGF-19 and so the production of yet more bile acids?
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Yes it well might, but the intention is that it would balance out into a new steady state so that there is enough bile acid to help digest the fat but not too much to cause diarrhoea. The proof of the pudding ….. the thing is Questran can be very effective as long as you can take it before meals and titrate it with the size of your meals and the response of your symptoms. You need to control the dose.
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Really enjoyed reading that article. But now I have a question: is NICE more a hindrance than a help to IBS patients?
NICE’s guidelines are useful for offering first line therapies that are the most effective for most people but as IBS is not fully understood and can have many individual manifestations, does the limited advice given by NICE discourage or prevent GPs from taking more investigative or novel therapies to help tackle their patients’ problems? And, if so, what can be done about that?
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Yes, i feel sure you are correct. It is a mistake to think that NICE guidelines are ‘written in stone’; they are quasi political pronouncements that try to balance published evidence with the opinions and practices of a small group of self selected ‘experts’ . With a concept as diverse as IBS, they should be regarded as an indication of good practice as suggested by those on the committee, but not adhered to as a law or religion. NICE has just published its much awaited quality standards for IBS. It will be the subject of my next post. Thanks for your comment.
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Can a person have IBS-D and respond well to the low FODMAP diet but also have further improved symptoms with the bile acid sequestrant? Or is it only that if the low FODMAP diet doesn’t work than bile acid sequestrant can be the next step?
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You may find that a bile acid sequestrant slows bowel transit and allows you to tolerate more FODMAPs. Yes you can take bile acid sequestrants with a low FODMAP diet.
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After seeing numerous local and Harley St consultants, who said I had IBS and gave advice such as not to eat strawberries out of season (really!) I was finally diagnosed with BAM after having a SehCAT at Addenbrookes . A few years later I was in the US and had to see a GI consultant who totally dismissed the test as useless because it’s not licensed by the FDA and thus not used there. This same doctor prescribed not one but 2 cholergenic drugs without mentioning any of the side effects other than drowsiness . The antispasmodic action was a huge relief but they made me stupid to the point where I was seriously concerned that I was developing dementia. It was quite by accident that I mentioned I was taking these meds to a neuroscientist at home who got alarmed and said I should stop. I looked up the class of drugs and found the horrifying side effects
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The daft ideas about treatment of IBS are really frustrating. BAM is a frequent accompaniment of IBS diarrhoea and SeHCAT is a good test, but since BAM is so common in IBS-D, a trial of treatment with Colestyramine saves time. I sometimes wonder whether some American physicians are on the same planet.
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They’re not on the same planet! I live in the USA and they are slowly killing us here.
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Dear Dr Read, thank you for this very interesting article. I have Crohn’s and also BAM (due to a Cholecystectomy in Jan 2000 and then an Ileo-Caecal Resection & Right Hemicolectomy 18 months later). I used Questran (and also Cholestagel) for many years with some success, but I am unable to tolerate either now due to a narrow stricture at the anastomosis. For the moment my best option is Dihydrocodeine 2-3 times per day because it works effectively for diarrhea and pain, but also wears off quite quickly which means that I have diarrhea a few times in the morning or late at night depending on when I take the DHC. I also know that DHC probably isn’t very good for me longterm. Do you know of any other treatments for BAM that I could ask my gastroenterologist about? Many many thanks!
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How frustrating for you. Questran is a specific treatment for Bile Acid Malabsorption and usually works very well, but since it can swell in the gut, it could cause a blockage if you have such a narrow stricture at the anastomosis. Other bile acid sequestrants that come in tablet form include Colestipol and Colesevelam. You could ask your doctor about these. You could also ask about Budesonide to inhibit the colonic irritation/inflammation secondary to BAM.
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Thank you very much for your reply. Unfortunately I’ve had trouble tolerating both Questran and Colesevelam, as they work almost TOO well for a day or so, and then I end up in loads of pain when eventually what’s in my digestive system tries to pass through the stricture. My doctor thinks that the stricture is part scar tissue and part inflammation, so I’m starting Humira next week, and if that doesn’t work to open up the stricture then I’m probably going to have to have surgery. I’m concerned that the BAM will still be a problem even after surgery, as even before the stricture was a problem, I’d sometimes find that Questran or Colesevelam would make me constipated and cause pain. I wondered if you know of any dietary treatments for BAM that I could try? I read that Calcium Carbonate can be helpful for some people – do you have any idea if this is worth a try?
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Apologies for the delay in replying. I had major computer problems last week. Hopefully the Humira will reduce the swelling around the stricture. I think that Questran is the best reatment for BAM but it is critically important to titrate the dose with your response. If you are getting constipated reduce the dose perhaps to just half a sachet half an hour before meals and adjust accordingly. I can’t see how calcium carbonate would help.
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calcium carbonate acts as an acid binder. Try it.
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2-3times loose bowels every morning and urgency, rest of the day fine, can it be bam? If yes, then do i have to take bile acid sequestrant for the rest of my life? Can this medicine give a cure at one stage where i wont have to take any further bam medicine?
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It might be, but I wonder why it is just in the morning. Do you have your last meal late at night. Do you drink very much alcohol in the evening. Do you then to consume a lot of fat in your meals (red meat, dairy, fried food, package meals). If you you could eat earlier and cut down on the fat and alcohol. Or you could try a sachet or two of Questran half an hour before your evening meal and titrate the dose according to your response. No, this is not a life sentence. You may find the changes mentioned above plus leading a more relaxed life style will improve things.
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To be honest, the symtoms start right after i wake up from bed. Even if i have a good bowel movement, then out of nowhere cramps start and have to make few more trips in the bathroom, and the bowels are loose. I never take alcohol and neither i smoke. The symtoms are irrespective of what i eat. The symptoms started 8yrs back when i used to drink lots of hot milk at night and have this trouble in the morning. I stopped milk completely after few days but the symptoms never went away 😦
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Apologies for the delay in replying, Mikey; I have just returned to base after being in the wilds of Scotland. It is interesting that your symptoms started 8 years ago when you used to drink lots of hot milk at night. The bowels can get into bad habits that can last for years, but there is usually a reason for it, like your problems years ago might have been associated with something else that was getting your bowels going on like ongoing stress, and the morning looseness has been recruited to express that. If you think there is anything in that, you could explore it with a counsellor. On the other hand you may find Questran helpful
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You wrote that FGF-19 stimulate more Bile Acid production. But it does the opposite, it inhibits synthesis of new Bile in the liver. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437929/
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Thank you for your comment, which is quite correct. I have amended the paragraph in the above article.
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Thank you so much for this article! I have IBS-D for 9 years now. It’s so bad that I’m 5 out of 7 days bound to my home. I’m 34. No food allergies and nothing was found at my colonoscopy 9 years ago. I have been to so many doctors and each either prescribed depression medicine or told me it’s all in my head. I finally found another doctor and she will do another colonoscopy and then go from there. I will mention BAM as this would really makes sense to me since I also have no gallbladder anymore. I really believe that my gallbladder removal set all this off even tho all doctors told me that nobody needs a gallbladder.
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I think you are right, Sandy. I have found that colestyramine (Questran) is really helpful for many of my patients, who have diarrhoea after cholecystectomy. Colestyramine is, in my opinion, better that other bile acid sequestrants as it comes as granules and can be easily titrated to the severity of your symptoms. I do hope your new doctor will listen to you and give you a trial of Questran.
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I so wish my doctor and consultant would think of this as a possible cause of my IBS-d. I had a Giardia infection last year at the same time as a lot of stress in my work life. The infection was cleared up by antibiotics but the diarrhoea remaind. Went to a specialist had a lots of tests including colonoscopy. Ruled out problems with pancreatic function, Crohn, caeliac disease. Great news! Consultant said the problem would now settle down and go away. A year later and it hasn’t. In the meantime I was diagnosed with anxiety and depression and am now on sertraline. It’s made a huge difference and I am a really positive place but the diarrhoea persists. I do lots of exercise and have a happy home and work life. I notice my stools are yellow and watery or at best type 5. 4 out 7 days a week. I have movements 3 times a day. My doctor says it is the sertraline side effect. It I have been on that for 6 months. Could it be BAM?
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Yes it could, Charlotte. Try to get a prescription for Questran, but titrate with the size of your meals and the response of the symptoms. I usually advice starting with 1 sachet half an hour after the main meal of the day and half a sachet after other meals and adjust the dose up and day according to suit your symptoms. it’s important you take it in the right dose and at the right time.
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After persuading my reluctant gastroenterologist to send me for a SeHCAT scan for my chronic and sudden diarrhoea I discovered I had mild/moderate BAM. I started taking colesevelam and the symptoms completely resolved (within 24 hours) although my wallet has suffered – its not cheap!.
My question is this. If you are taking a bile acid sequestrant does it reduce your ability to digest fatty food ie if the BA is bound by the sequestrant is it no longer available to assist in fat digestion?.
Shortly after taking colesevelam it got a bit carried away with my symptomless gut and had a fatty meal and had quite severe stomach pain the next day.
Thanks in advance for your views.
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Dear Steve,
That would certainly make sense. Best to limit your fat intake while taking colesevelam
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Thank you for this article which makes interesting reading. My ‘IBS’ symptoms started when in my 30’s not long after having my gallbladder removed. I’m now in my 60’s and have been living with bouts of diarrhoea that come on out of the blue with no warning, feeling fine one minute, and rushing to the toilet the next, like someone literally threw a switch. I did read that BAM has been highlighted as being a side effect of cholecystectomy, but when I spoke to my GP about it, he just brushed it off. What do we need to do to get this taken seriously and get this information out into the wider world?
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