Cholestyramine (Questran) For IBS: Why & when to use it for IBS-D?

Cholestyramine is a bile acid sequestrant. it acts as an antidiarrheal and lipid-lowering medication by binding to bile acids inside the intestine.

Hi, I am Dr. Farahat, and Today, I will explain to you:

  • What is the link between Cholestyramine, IBS, and Bile Acid Malabsorption?
  • Key differences between IBS-D and Bile Acid Malabsorption (BAM)?
  • Why and when to use cholestyramine for IBS?
  • Is cholestyramine effective for IBS (especially IBS-D)?
  • How to take Cholestyramine for IBS?

 

What is cholestyramine (Questran)?

Bile acids are the main target of cholestyramine (Questran):

  • Bile acids are formed inside the liver, secreted through bile into your intestine.
  • Bile acids help the digestion and absorption of fats and fat-soluble vitamins (vitamins A, D, E, and K).
  • Normally, 95% of bile acids inside your intestine are reabsorbed again into the blood, and only 5% is excreted with stool.
  • Failure to absorb these bile acids or excess excretion leads to its accumulation inside your gut.
  • Accumulation of bile acid leads to a severe form of diarrhea (called bile acid diarrhea)

Questran (cholestyramine) binds to the bile acids secreted from your liver into the intestine. This binding prevents leads to:

  • Inactivation of bile acid and prevention of Bile Acid Diarrhea.
  • prevention of its re-absorption, which results in lipid-lowering effects.

Questran (cholestyramine) was originally used to:

  • Treat elevated blood lipids (its role is now limited due to the development of more effective lipid-lowering drugs as statins).
  • Treat itching associated with partial biliary obstruction.
  • Treatment of Bile acid diarrhea and postcholecystectomy diarrhea.

Questran (cholestyramine) and other bile acid sequestrants (as colestipol and colesevelam) are usually taken in a powder form.

 

What is the link between IBS-Diarrhea, Bile acids, and Cholestyramine?

Interestingly, several studies (ref, ref) found that almost 50% of people with IBS-D (Irritable Bowel syndrome-predominant diarrhea) have Bile Acid Malabsorption (BAM).

BAM leads to bile acid diarrhea which usually responds and can resolve completely with cholestyramine or other bile acid sequestrants.

SHOCKING?!!

When I first came into this fact as a gastroenterologist, it changed the way I view my patients who are diagnosed with IBS-diarrhea.

The ROME IV criteria for IBS diagnosis are symptoms-only based criteria. It depends on non-specific symptom patterns to diagnose IBS (abdominal pain, change in bowel habits, and stool frequencies).

See How doctor diagnose IBS in detail in this interesting article

These vague diagnostic criteria may lead to confusing many gut diseases and conditions with IBS.

One of the most evident examples is misdiagnosing Bile acid diarrhea as IBS diarrhea.

The symptoms of bile acid diarrhea are very similar to IBS-Diarrhea. This is especially evident in mild forms of bile acid malabsorption (or bile acid diarrhea).

According to the Mayo Clinic, Bile Acid diarrhea is one of the most common under-diagnosed and overlooked conditions by gastroenterologists.

  • Bile Acid Malabsorption (BAM) present in one-third to half of the people with IBS diarrhea.
  • Up to 50% of people with functional diarrhea have also BAM.
  • Up to 35% of people with a condition called “microscopic colitis“ have BAM.

Why BAM is overlooked by doctors?

  • BAM presents with diarrhea, which is very similar to IBS-D and chronic idiopathic diarrhea.
  • BAM tests negative by colonoscopies, abdominal CT enterography, and other conventional stool studies.
  • Tests for BAM are limited and not available across all centers (for example, Fecal bile acid test and serum 7αC4 test).
  • Another common method to diagnose BAM is a therapeutic test with cholestyramine (If the patient’s diarrhea improves with cholestyramine, then it was BAM).
    But this method is of limited value as the response is variable and some people cannot tolerate cholestyramine side effects.

How to know if you have BAM or IBS-D?

BAM is not easily distinguishable from other causes of diarrhea (especially IBS-D) and Functional diarrhea. However, Here are some tips and signs that raise the odds of the presence of Bile Acid Malabsorption (ref, ref):

  • Extreme urgency: a very common sign suggesting that you may have bile diarrhea is an intense urgency to defecate.
  • May lead to soiling accidents: occasional stool incontinence may occur in severe cases due to the extreme urgency to poop.
  • Night diarrhea: BAM can cause more diarrhea at night. it can awaken you with the urge to poop (night diarrhea is not common with IBS).
  • Poor or Non-response to your IBS antidiarrheals: The most common antidiarrheal medication used for IBS is Imodium (Loperamide). 
    If Imodium fails to control your IBS-diarrhea or has very weak effects, consider BAM as a cause of your IBS-D.
  • Relation to fatty meals: fatty meals trigger bile acid diarrhea. If you are consistently getting diarrhea after fatty meals, suspect BAM.
  • Previous cholecystectomy (development of IBS-D after cholecystectomy): According to the Mayo Clinicabout 5-10% of people undergoing cholecystectomy develop diarrhea due to excess bile acids secreted into their intestines. Postcholecystectomy diarrhea is usually a form of BAM (which can be misdiagnosed as IBS-D).
  • Other associated conditions may raise the suspicion of BAM: such as Intestinal resections (especially the last part of your small intestine; the ileum) and abdominal radiation.
  • Other symptoms such as bloating and abdominal pain may present with BAM which makes it difficult to differentiate from IBS-D.
  • The only way to know if you have BAM is to discuss the issue with your doctor, he will either run a therapeutic test with a bile acid sequestrant (as cholestyramine) or order specific BAM blood or stool test.

Is cholestyramine an IBS (IBS-D) medication?

Yes.

Bile acid sequestrants (including cholestyramine) can be in patients with persistent diarrhea despite the use of antidiarrheals (such as loperamide “Imodium”). However, its use is limited by the associated side effects as bloating, flatulence, abdominal discomfort, and constipation (ref).

Bile acid sequestrants (including cholestyramine) use a second-line agent in IBS-D is justified by the fact that:

Up to 50% of patients with IBS-D have Bile Acid Malabsorption (refref)

From my personal experience, People with IBS-D who fail to respond to usual IBS treatments and antidiarrheals wroth a trial of cholestyramine.

Many people may have a magical response with complete resolution of their diarrhea.

Also, you can find some amazing testimonials across the internet from patients with IBS-D taking cholestyramine.

The bottom line is that you have to discuss the issue with your doctor if your IBS-D is not under control.

How much cholestyramine is effective for IBS-D?

Your response to cholestyramine depends on two main factors:

  • Whether you actually have BAM as a cause of your IBS-D or not?
  • How much you can tolerate its side effects?

As I explained before, confirming BAM as a cause of your IBS-D can be challenging. It requires your doctor to be oriented by the condition and the availability of tests.

Cholestyramine can provide a very effective solution to IBS diarrhea especially if you’re one of the 50% of IBS-D sufferers who have BAM.

Unfortunately, Cholestyramine can cause side effects such as:

  • Bloating and flatulence.
  • Abdominal pain or discomfort.
  • May induce constipation.
  • Also, it can cause nausea and anorexia.
  • Prolonged or faulty use can result in dental discoloration, and bleeding tendency (due to malabsorption of vitamin K).
  • Also, it may interfere with other medications you take (whether for IBS or other conditions). 
    Don’t take cholestyramine with other drugs at the same time (consult your doctor).

The Gastrointestinal side effects (especially bloating and abdominal pain) are relatively common and can limit its use in IBS patients.

However, cholestyramine worth a trial if your diarrhea is persistent despite the use of other IBS anti-diarrheal.

Always discuss the issue with your doctor. Don’t take actions that may affect your health without medical supervision.

When you should (and shouldn’t) take cholestyramine for IBS?

Your doctor may prescribe Bile acid sequestrants ( as cholestyramine, colestipol, or colesevelam) when:

  • Have IBS with predominant diarrhea
  • And you failed to respond to usual antidiarrheals such as Loperamide (Imodium).
  • Your diarrhea is severe or persistent (especially if it happens after fatty meals or awakens you at night).
  • If you have a history of cholecystectomy or intestinal resection together with your IBS.

When NOT to take cholestyramine for IBS?

  • Cholestyramine is indicated only for IBS-D type. Don’t use it if you have IBS-C or IBS-Mixed types unless prescribed by your doctor.
  • If you cannot tolerate its side effects as bloating, abdominal pain, and constipation.
  • Hypersensitivity to bile acid sequestering resins.
  • If you have a complete biliary obstruction.
  • If you have elevated blood Triglycerides: Bile acid sequestrants (including cholestyramine can cause severe hypertriglyceridemia.

As a general rule, don’t try cholestyramine or any other bile acid sequestrants by yourself. always work with your doctor to determine the best option.

How to take cholestyramine for IBS-D?

your doctor will prescribe cholestyramine at small doses at first to avoid its side effects.  Here is how to take cholestyramine for IBS:

  • It’s available in packets or powder form (usually 4 grams per dose).
  • DON’T take cholestyramine in its dry form, you must prepare it with fluid suspension.
  • You can mix it with plain water or juice.
  • Administer at mealtime, one or two times daily, or as prescribed by your doctor.
  • Start with the lowest dose (4g per day) for one week.
  • Increase the dose by 4 grams at weekly intervals.
  • Take it in one to four divided doses.
  • The maximum dose is 36 grams per day ( 9 packets).
  • DON’T sip or held the solution in your mouth, it may cause tooth discoloration or dental decay.

OTHER ORAL MEDICATIONS SHOULDN’T BE TAKEN WITH CHOLESTYRAMINE. TAKE THEM AT LEAST:

  • ONE HOUR BEFORE CHOLESTYRMAINE, OR
  • 4 TO 6 HOURS AFTER TAKING CHOLESTYRMAINE.

Today's Featured

Michael Camilleri, M.D.

Gastroenterologist at Mayo Clinic, Rochester, Minnesota

“Bile acid diarrhea affects 1 or 2 percent of people in the community, which is the same approximate prevalence of celiac disease in the United States.

Source: Mayo clinic.