Good Morning, All!
A few mos. ago I experienced a wicked, ongoing flare and went to see my GI doc. (For those who don't know, I have had MC for 15 years, treated by diet alone). Going back to my very safest foods had no effect. Had all of the usual tests (C. difficile, serum gastrin, O and P, SIBO, etc.) - all normal. She then suggested a trial of cholestyramine, a bile acid binder. I had an immediate clinical response! I have been reviewing the literature, and it appears that a bile acid sequestrant like cholestyramine may be the best first line of treatment for MC. In the study below, patients with CC responded well to it - and this is the interesting point - ALL with documented bile acid malabsorption (BAM) responded favorably, but many with without it also did:
http://gut.bmj.com/content/46/2/170.full
Notice that this is a British study. The Brits have done far more research with BAM, mainly because they routinely use a test called the 75SeHCAT test to determine BAM. There is no readily-available test for BAM in the U.S. In those with BAM, it is thought that the excess bile acids continually damage the colon, resulting in D, and that if they can be bound up by a sequestrant, the damage stops.
Other studies have documented an even greater incidence of BAM in patients with LC, compared with CC. I have also seen studies where many with longstanding IBS can be successfully treated with sequestrants.
In the above study, they were able to avoid prescribing steroids to any patient. Sequestrants like cholestyramine are thought to be safe, given that they are not absorbed systemically at all. And cholestyramine is a heck of a lot cheaper than the other meds used for IBD!
Now, here is what intrigues me..........if we can figure out why sequestrants work so well, we may gain a better understanding of the mechanisms involved in MC.
It makes sense that those with documented BAM respond well, but why do many without it respond so well? My GI believes that sequestrants might be removing toxins from the intraluminal contents. (toxins that cause inflammation of the colon). Interesting, no? Many of us here have long wondered about an infectious cause of MC. Perhaps part of the problem is that the altered gut bacteria are releasing toxins that continually damage the gut.
Anyway, perhaps this is a key to further unlocking the mysteries of MC. I am not advocating any changes to what we currently recommend - especially related to diet. However, I am now thinking that folks should ask their docs for a sequestrant first....before trying Pepto, sulfasalazine, Entocort. The best way to know if it will work is to TRY it, since we don't have a good test for BAM (and since it often works even if you don't have BAM). It works almost immediately, so it is a godsend for people who have lingering D for months waiting for diet to kick in.
Polly
A New Way to Look at MC
Moderators: Rosie, Stanz, Jean, CAMary, moremuscle, JFR, Dee, xet, Peggy, Matthew, Gabes-Apg, grannyh, Gloria, Mars, starfire, Polly, Joefnh
A New Way to Look at MC
Blessed are they who can laugh at themselves, for they shall never cease to be amused.
Polly,
Thank you, I'm going to check into it with my PCP. I still have loose stools 1-2 x/day and sometimes more despite close adherence to diet.
How much did you find helpful, what is the best way for a prescription to be written so that the dose can be adjusted?
Thank you, I'm going to check into it with my PCP. I still have loose stools 1-2 x/day and sometimes more despite close adherence to diet.
How much did you find helpful, what is the best way for a prescription to be written so that the dose can be adjusted?
Donna
Diagnosed with CC August 2011
Diagnosed with CC August 2011
Donna,
I can relate. Over the years I never felt like my MC was in perfect control. Even at my best, I often had "puff poopies" - you know, the poop that looks fine in the toilet but disappears into a cloud when you flush. LOL! That's why I did the MRT a few years ago to further tweak my diet.
And some members here just couldn't seem to achieve remission, no matter what they did or how determined they were. I suspect now that they would have been good candidates for a sequestrant.
Good luck with your PCP - I don't think many U.S. docs are familiar with this approach. Oh, there is an excellent review article on BAM I will share with you. Let me go find it. Here it is:
http://www.medicine.virginia.edu/clinic ... Oct_12.pdf
But be sure to let your PCP know that sequestrants often work even if BAM is not present, as noted in the article in my original post.
Polly
I can relate. Over the years I never felt like my MC was in perfect control. Even at my best, I often had "puff poopies" - you know, the poop that looks fine in the toilet but disappears into a cloud when you flush. LOL! That's why I did the MRT a few years ago to further tweak my diet.
And some members here just couldn't seem to achieve remission, no matter what they did or how determined they were. I suspect now that they would have been good candidates for a sequestrant.
Good luck with your PCP - I don't think many U.S. docs are familiar with this approach. Oh, there is an excellent review article on BAM I will share with you. Let me go find it. Here it is:
http://www.medicine.virginia.edu/clinic ... Oct_12.pdf
But be sure to let your PCP know that sequestrants often work even if BAM is not present, as noted in the article in my original post.
Polly
Blessed are they who can laugh at themselves, for they shall never cease to be amused.
Donna,
My cholestyramine comes in a box of 60 individual foil packets. My GI wrote the Rx for twice a day but told me to start with once a day. Once a day didn't work but twice a day made me constipated! So I now take one one day and two the next.
I don't find it objectionable at all, altho some apparently do. I just mix it with a few ounces of water (it is orange-flavored), but you can use applesauce if you like. It is a little cloudy/gritty but compared to some of the colonoscopy cleanout solutions, I find this to be a breeze.
Polly
My cholestyramine comes in a box of 60 individual foil packets. My GI wrote the Rx for twice a day but told me to start with once a day. Once a day didn't work but twice a day made me constipated! So I now take one one day and two the next.
I don't find it objectionable at all, altho some apparently do. I just mix it with a few ounces of water (it is orange-flavored), but you can use applesauce if you like. It is a little cloudy/gritty but compared to some of the colonoscopy cleanout solutions, I find this to be a breeze.
Polly
Blessed are they who can laugh at themselves, for they shall never cease to be amused.
Hi Lisa,
Yes, the D returns if I skip a day or two or three. Folks who have BAM from gall bladder removal must be on it indefinitely - forever in most cases. Of course, they don't mind, because they get their lives back. I have not seen any studies about the length of time needed for other related issues like CC, LC, IBS. Hopefully, they will be forthcoming.
The good news is that cholestyramine is very safe, with no systemic absorption. The main issue is if you take supplements or medications, since the sequestrant can bind them too, making them ineffective. It is recommended to take meds/supplements one hour before or 4 hours after taking the sequestrant.
Polly
Yes, the D returns if I skip a day or two or three. Folks who have BAM from gall bladder removal must be on it indefinitely - forever in most cases. Of course, they don't mind, because they get their lives back. I have not seen any studies about the length of time needed for other related issues like CC, LC, IBS. Hopefully, they will be forthcoming.
The good news is that cholestyramine is very safe, with no systemic absorption. The main issue is if you take supplements or medications, since the sequestrant can bind them too, making them ineffective. It is recommended to take meds/supplements one hour before or 4 hours after taking the sequestrant.
Polly
Blessed are they who can laugh at themselves, for they shall never cease to be amused.
Hi Polly,
I certainly wouldn't argue what that, since approximately half of all MC patients apparently have bile acid malabsorption when their MC is active.
75Se HCAT test in the detection of bile acid malabsorption in functional diarrhoea and its correlation with small bowel transit.
But the point is, why do the test when it's so fast and easy (with minimal risk) to just try a bile acid sequestrant?
But bile acid malabsorption (and the D it causes) is a symptom, not a disease. So the more important question is, "Why is bile acid malabsorption present in the first place. You've inspired me to dig a little deeper into this issue. 5 possibilities come to mind to explain how this can happen:
1. The terminal ileum is inflamed (which interferes with the reabsorption of unused bile salts).
2. Part of the terminal ileum is missing (due to surgery — which interferes with the reabsorption of unused bile salts).
3. The pancreas is not functioning properly — it isn't producing an adequate amount of either lipase, procolipase, or trypsinogen.
4. The conversion of procolipase to colipase (which takes place in the small intestine) is corrupted.
5. The conversion of trypsinogen to trypsin in the duodenum is corrupted because of insufficient production of enteropedsidase (also known as enterokinase).
Note that colipase is a protein co-enzyme required for optimal enzyme activity of pancreatic lipase. Without it, lipase doesn't work very well (to hydrolyze the fat globules encapsulated by bile). Procolipase is activated in the small intestine by trypsin. Its function is to prevent the inhibitory effect of bile salts on the lipase-catalyzed hydrolysis of dietary long-chain triglycerides (such as animal fat). Trypsin is produced in the pancreas as the inactive protease trypsinogen. And trypsinogen is converted to trypsin in the duodenum by enteropepsidase. And finally, enteropeptidase (also called enterokinase) is an enzyme produced by cells of the duodenum (similar to the way that many digestive enzymes are produced in the duodenum).
I lean toward item number 5 on this list — a problem with the availability of enteropedsidase, so that a problem exists with the conversion of trypsinogen to trypsin. Why? Because we know that one of the first effects of enteritis is the loss of adequate enzyme production capabilities in the small intestine. Loss of pancreatic enzymes typically occurs in a much smaller percentage of patients, and this is a later-stage issue in most cases where it occurs (so it's less likely to be a significant problem for most MC patients, especially early on).
Note that a deficiency of trypsin also interferes with the digestion of proteins and the absorption of vitamin B-12 — 2 problems that are very common with MC. In fact, these problems are so common that I wonder if a trypsin deficiency might be a factor in the development of food sensitivities that so many of us have toward animal proteins such as beef, pork, etc., plus the common B-12 malabsorption/deficiency problem.
Sources of Trypsin
So I'm wondering if a trypsin supplement might work just as well as a bile acid sequestrant, plus resolve additional issues as well. IOW, might this address the cause of the problem, rather than just treating the symptom?
Love,
Tex
I certainly wouldn't argue what that, since approximately half of all MC patients apparently have bile acid malabsorption when their MC is active.
My guess is that happens because it's not that easy to diagnose BAM, and the test used is actually only moderately accurate. IOW, it may yield a significant percentage of false negative results.Polly wrote:It makes sense that those with documented BAM respond well, but why do many without it respond so well?
75Se HCAT test in the detection of bile acid malabsorption in functional diarrhoea and its correlation with small bowel transit.
But the point is, why do the test when it's so fast and easy (with minimal risk) to just try a bile acid sequestrant?
But bile acid malabsorption (and the D it causes) is a symptom, not a disease. So the more important question is, "Why is bile acid malabsorption present in the first place. You've inspired me to dig a little deeper into this issue. 5 possibilities come to mind to explain how this can happen:
1. The terminal ileum is inflamed (which interferes with the reabsorption of unused bile salts).
2. Part of the terminal ileum is missing (due to surgery — which interferes with the reabsorption of unused bile salts).
3. The pancreas is not functioning properly — it isn't producing an adequate amount of either lipase, procolipase, or trypsinogen.
4. The conversion of procolipase to colipase (which takes place in the small intestine) is corrupted.
5. The conversion of trypsinogen to trypsin in the duodenum is corrupted because of insufficient production of enteropedsidase (also known as enterokinase).
Note that colipase is a protein co-enzyme required for optimal enzyme activity of pancreatic lipase. Without it, lipase doesn't work very well (to hydrolyze the fat globules encapsulated by bile). Procolipase is activated in the small intestine by trypsin. Its function is to prevent the inhibitory effect of bile salts on the lipase-catalyzed hydrolysis of dietary long-chain triglycerides (such as animal fat). Trypsin is produced in the pancreas as the inactive protease trypsinogen. And trypsinogen is converted to trypsin in the duodenum by enteropepsidase. And finally, enteropeptidase (also called enterokinase) is an enzyme produced by cells of the duodenum (similar to the way that many digestive enzymes are produced in the duodenum).
I lean toward item number 5 on this list — a problem with the availability of enteropedsidase, so that a problem exists with the conversion of trypsinogen to trypsin. Why? Because we know that one of the first effects of enteritis is the loss of adequate enzyme production capabilities in the small intestine. Loss of pancreatic enzymes typically occurs in a much smaller percentage of patients, and this is a later-stage issue in most cases where it occurs (so it's less likely to be a significant problem for most MC patients, especially early on).
Note that a deficiency of trypsin also interferes with the digestion of proteins and the absorption of vitamin B-12 — 2 problems that are very common with MC. In fact, these problems are so common that I wonder if a trypsin deficiency might be a factor in the development of food sensitivities that so many of us have toward animal proteins such as beef, pork, etc., plus the common B-12 malabsorption/deficiency problem.
Sources of Trypsin
So I'm wondering if a trypsin supplement might work just as well as a bile acid sequestrant, plus resolve additional issues as well. IOW, might this address the cause of the problem, rather than just treating the symptom?
Love,
Tex
It is suspected that some of the hardest material known to science can be found in the skulls of GI specialists who insist that diet has nothing to do with the treatment of microscopic colitis.
Brandy,
The comments I made about trypsin are based on speculation. I was just thinking out loud. I'm not aware of any RCTs that have investigated this possibility, but I believe it is something that certainly might have possibilities.
I'll bet a GF cookie that none of us has ever been tested for a trypsin deficiency.
Tex
The comments I made about trypsin are based on speculation. I was just thinking out loud. I'm not aware of any RCTs that have investigated this possibility, but I believe it is something that certainly might have possibilities.
I'll bet a GF cookie that none of us has ever been tested for a trypsin deficiency.
Tex
It is suspected that some of the hardest material known to science can be found in the skulls of GI specialists who insist that diet has nothing to do with the treatment of microscopic colitis.
Since Pineapple breaks down protein, if one was deficient in Trypsin could that make the pineapple cause a person to show reactive on a blood test to pineapple? Maybe I'm reading that article wrong....but it sounds like trypsin helps regulate absorption for things that bromelain or pepsin can't do so if one was deficient in trypsin it could cause problems for the other protein breakers to do their job??
Reason I ponder this question is because I showed over the top reaction to pineapple on my blood tests, besides it being full of natural sugars that probably helped flare my LC I would think the bromelain would have been a helper and not an hinder for me, except if not enough Trypsin was present is how I am putting this puzzle together.
Reason I ponder this question is because I showed over the top reaction to pineapple on my blood tests, besides it being full of natural sugars that probably helped flare my LC I would think the bromelain would have been a helper and not an hinder for me, except if not enough Trypsin was present is how I am putting this puzzle together.
To Succeed you have to Believe in something with such a passion that it becomes a Reality - Anita Roddick
Dx LC April 2012 had symptoms since Aug 2007
Dx LC April 2012 had symptoms since Aug 2007
That would depend on how the test worked — on what mechanism it used to determine sensitivities.
Good point, Gabes. You know, when I looked at the literature, I could find only one report about the teeth concern, and apparently it happened to someone who used a lot of sugar (Koolaid to dissolve the powder). But just to be sure, I sip it with a straw.....and put the end at the back of my throat. Then I swish afterwards.
Brandy, the sequestrants require a script, but it can be from the PCP.
Tex,
Good thinking! I enjoyed reading your ideas. In my case, the GI ordered the fecal pancreatic elastase test (90-100% sensitivity, 93-98% specificity) for pancreatic insufficiency - it was normal.
According to that article on Bile Acid Diarrhea that you and I have referenced here, there are 3 types of bile acid diarrhea:
Type I- due to an ileal problem, like resection (surgical manipulation) or disease (like Crohn's)
Type II - no positive findings - no definitive etiology and no demonstrated ileal disease
Type III - due to issues like SIBO, gall bladder removal, chronic pancreatitis, celiac disease, radiation enteritis, etc.
The most common type is Type II......no identifiable cause. Of course, even with normal ileal biopsies, there could certainly be problems at the cellular level.
Recently, it has been proposed that there may be an altered feedback inhibition of bile acid synthesis, mediated by fibroblast growth factor 19 (FGF19). In Type II, the levels of these fibroblasts were 50% of controls. The speculation is that disrupted feedback control leads to a larger bile acid pool being delivered to the colon......which causes the D. Now, I guess we need to figure out what impairs the FGF19. Any ideas?
Love,
Polly
Brandy, the sequestrants require a script, but it can be from the PCP.
Tex,
Good thinking! I enjoyed reading your ideas. In my case, the GI ordered the fecal pancreatic elastase test (90-100% sensitivity, 93-98% specificity) for pancreatic insufficiency - it was normal.
According to that article on Bile Acid Diarrhea that you and I have referenced here, there are 3 types of bile acid diarrhea:
Type I- due to an ileal problem, like resection (surgical manipulation) or disease (like Crohn's)
Type II - no positive findings - no definitive etiology and no demonstrated ileal disease
Type III - due to issues like SIBO, gall bladder removal, chronic pancreatitis, celiac disease, radiation enteritis, etc.
The most common type is Type II......no identifiable cause. Of course, even with normal ileal biopsies, there could certainly be problems at the cellular level.
Recently, it has been proposed that there may be an altered feedback inhibition of bile acid synthesis, mediated by fibroblast growth factor 19 (FGF19). In Type II, the levels of these fibroblasts were 50% of controls. The speculation is that disrupted feedback control leads to a larger bile acid pool being delivered to the colon......which causes the D. Now, I guess we need to figure out what impairs the FGF19. Any ideas?
Love,
Polly
Blessed are they who can laugh at themselves, for they shall never cease to be amused.