New Treatment for Irritable Bowel Syndrome (IBS)

 

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“A critical weekly review of important new research findings for health-conscious readers”


NEW TREATMENT FOR IRRITABLE BOWEL SYNDROME (IBS)

An estimated 10 to 20 percent of the population suffers from a complex of gastrointestinal symptoms that are collectively referred to as Irritable Bowel Syndrome (IBS).  Irritable Bowel Syndrome affects women three times more commonly than men, and has historically been considered a “wastebasket” diagnosis for patients with functional gastrointestinal (GI) complaints when no other specific diagnosis can be found. 

While the precise causes of IBS are not well understood at this time, various theories have been proposed.  These include abnormal responses to infections of the GI tract, abnormal hormonal and neurological function of the GI tract, hypersensitivity to certain types of foods, abnormal motility of the colon, a “hyper-awareness” of bodily functions, and certain psychiatric conditions, in addition to other hypotheses.  (It is almost certain, however, that there is more than one cause for IBS.)

There are a variety of symptoms that have been associated with IBS, and the incidence, severity and frequency of each of these symptoms varies considerably from one IBS patient to another.  Typically, however, IBS-associated symptoms include bloating, crampy abdominal pain, diarrhea alternating with periods of constipation, and the passage of clear or white mucus from the rectum.  In many cases, IBS symptoms are more pronounced after eating, and patients with IBS often experience a powerful urge to move their bowels after meals.  IBS symptoms are also more frequent and more severe during times of stress.  In women with IBS, these distressing GI symptoms may become more intense around the time of their menstrual periods.  Other symptoms that have been commonly observed in patients with IBS include heartburn, nausea, and vomiting.

Because the precise causes of IBS are poorly understood, there have been a wide range of treatments recommended for this syndrome.  For example, exercise and other stress-reducing activities may be helpful for some IBS sufferers.  Giving up tobacco, and reducing or eliminating alcohol consumption may also help to reduce IBS symptoms, while promoting improved overall health at the same time.  Keeping a food diary can also help to identify foods that tend to provoke or worsen IBS symptoms in many patients.  Finally, dietary fiber supplementation has been almost universally advocated by most IBS experts.  Unfortunately, for many IBS sufferers, these and other recommended treatments for IBS are often ineffective. 

A new prospective, randomized, placebo-controlled clinical research study, just published in the journal Gut, has evaluated a new medical treatment for IBS that may hold promise for some of the millions of people who suffer from the unpleasant symptoms of this condition.  This small clinical research study included 60 patients with IBS.  Half of these IBS patients were randomized to receive an antihistamine medication (ketotifen) that prevents inflammatory “mast cells” from releasing inflammatory substances.  (Mast cells are present throughout the body, including the respiratory tract and the GI tract; and when stimulated, they release histamine and other substances that cause swelling and inflammation of adjacent tissues.)  The remaining half of this group of study volunteers was secretly randomized to receive an identical placebo (sugar) pill.  This study lasted for 8 weeks, altogether. 

At the start of this prospective clinical study, the 60 patient volunteers with IBS underwent an initial “barostat” study of the rectum.  This test involves the insertion of a balloon-like device into the rectum.  The balloon is then slowly inflated, which distends the rectal wall.  Prior studies have shown that many IBS patients perceive rectal discomfort with significantly less rectal distension than patients without IBS, a response that has been termed “visceral hypersensitivity.”  One theory as to why IBS patients experience visceral hypersensitivity relates to the abnormal activation of mast cells in the GI tract which, in turn, release multiple substances, including histamine, that generate an inflammatory response.

The 60 IBS patient volunteers also underwent biopsies of the rectum, and the results of these biopsies were compared with rectal biopsies taken from 22 age- and gender-matched “control” patients without IBS.  These biopsy specimens were then assessed for the number of inflammatory mast cells present, as well as the extent to which these mast cells spontaneously released inflammatory substances such as histamine and tryptase.

At the end of the 8-week study, the 60 IBS patient volunteers underwent a repeat barostat study of the rectum.  Among the IBS patient volunteers who experienced visceral hypersensitivity at the time of their initial barostat study, ketotifen significantly reduced the severity of visceral hypersensitivity when compared to similar patients who had been secretly randomized to receive placebo pills.  (There was no apparent change in visceral sensitivity associated with ketotifen among the IBS patients who had a normal response to initial barostat testing, however.)  More importantly, the IBS patients who had secretly been randomized to receive ketotifen reported significant improvement in abdominal pain and the other classic symptoms of IBS, when compared to the patient who had been randomized to receive placebo pills.  At the same time, the results of the rectal biopsies actually revealed fewer mast cells in the rectal biopsy specimens of IBS patients when compared to the control patients.  Moreover, there was only a very slight increase in histamine release by these rectal mast cells observed in IBS patients, when compared to the control patients.  (These latter two observations call into question the theory that increased numbers of mast cells, or/and an increased release of inflammatory substances from these mast cells, are responsible for visceral hypersensitivity in IBS patients, or for other symptoms commonly associate with IBS.  They also suggest that the favorable effects of ketotifen on the symptoms of IBS among these patient volunteers are likely occurring by a mechanism other than inhibition of mast cells within the GI tract.)

As I have noted in previous columns on this topic, there are likely multiple causes of IBS, and, therefore, individual treatments for this condition are not likely be equally effective in every patient with IBS.  However, the results of this small, early-phase study offer the hope that ketotifen (and, perhaps, other so-called “H1 antihistamines”), may be able to relieve the distressing symptoms of IBS in at in least some patients with this chronic GI syndrome.

 

To review previous columns on IBS, please select the following links:

Irritable Bowel Syndrome (IBS), Diet & Fiber

Irritable Bowel Syndrome: Cause Discovered?

 

Watch for the publication of my new landmark evidence-based book, “A Cancer Prevention Guide for the Human Race,” in September of this year.



 

Disclaimer: As always, my advice to readers is to seek the advice of your physician before making any significant changes in medications, diet, or level of physical activity


Dr. Wascher is an oncologic surgeon, a professor of surgery, a cancer researcher, an oncology consultant, and a widely published author



For a different perspective on Dr. Wascher, please click on the following YouTube link: 

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I and the staff of Weekly Health Update would again like to take this opportunity to thank the more than 100,000 health-conscious people, from around the world, who visit our premier global health information website every month.  As always, we enjoy receiving your stimulating feedback and questions, and I will continue to try and personally answer as many of your inquiries as I possibly can.



 

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Irritable Bowel Syndrome: Cause Discovered?

 

Welcome to Weekly Health Update


“A critical weekly review of important new research findings for health-conscious readers”


IRRITABLE BOWEL SYNDROME: CAUSE DISCOVERED?

Irritable bowel syndrome (IBS) is a poorly understood cluster of gastrointestinal (GI) tract symptoms that typically includes varying degrees of abdominal bloating and crampy pain, diarrhea, constipation, and the frequent discharge of mucus-like stools from the rectum.  At any one time, an estimated 10 to 20 percent of all Americans chronically experience one or more of these intestinal symptoms.  In most patients with IBS, these symptoms begin in childhood.  In the United States, and in most other Western countries, IBS is at least 3 times more common in women than in men although, interestingly, in Southeast Asia, men are 2 to 3 times more commonly afflicted with IBS.

Numerous theories about the cause(s) of IBS have been proposed, but none have been definitively proven to cause this common syndrome, thus far.  Because the precise cause(s) of IBS has not yet been determined, there is no specific medical test available to diagnose this condition.  Likewise, there is no specific treatment available for IBS, although fiber supplements and careful attention to dietary “triggers” are often helpful.  Moreover, as IBS is frequently associated with chronic depression and/or anxiety, the use of some types of antidepressant medications has also been associated with an improvement in IBS symptoms.

Among the numerous proposed causes of IBS, an excess of a powerful hormone and neurotransmitter, serotonin, within the GI tract has been the focus of considerable research, lately.  (Serotonin is also commonly known as 5-HT, which is an abbreviated form of serotonin’s chemical name.) 

Serotonin has been shown to have multiple functions within the human body.  Decreased serotonin levels in the brain have been associated with both depression and anxiety, which explains why the most commonly used antidepressant medications, the selective serotonin reuptake inhibitors (SSRIs), are used to treat both chronic depression and anxiety.  (Commonly prescribed SSRIs include Prozac, Paxil, Zoloft, Lexapro and Celexa, among others.)  Because more than 95 percent of the body’s serotonin is found in the GI tract, SSRI drugs also have a profound effect on GI tract function, in addition to their effects on brain serotonin levels.  Indeed, previous observations that certain SSRI antidepressant medications worsen cramping and diarrhea in patients with diarrhea-predominant IBS have at least suggested that serotonin in the GI tract may play an important role in this common form of IBS.

Another serotonin-related disease that is associated with severe abdominal cramping and diarrhea is carcinoid syndrome.  In this relatively rare condition, serotonin-secreting carcinoid tumors of the GI tract cause profuse, watery diarrhea in affected patients after these tumors spread to the liver.

Based upon these apparent clinical links between IBS and serotonin (and for diarrhea-predominant IBS, in particular), additional research into the metabolism of serotonin in the GI tract of IBS sufferers is sorely needed.  Fortunately, a newly published research study, which appears in the current issue of the journal Gastroenterology, sheds further light on the potential link between serotonin and at least some forms of IBS.

In this novel clinical research study, 98 children with chronic GI tract symptoms were evaluated.  Twelve of these children presented with chronic symptoms suggestive of IBS.  Endoscopic GI tract biopsies were performed on these 12 children, and the results of these biopsies were compared with similar biopsies performed on other age-matched children who were undergoing endoscopy for reasons other than IBS symptoms.

When compared with the biopsy results on the “control” children without IBS symptoms, the children with IBS symptoms were found to have significantly elevated levels of serotonin (5-HT) in the mucosal cells lining their GI tract.  At the same time, the children with IBS symptoms were also found to have lower levels of a protein that is responsible for removing serotonin from the GI tract (serotonin transporter protein, or SERT) when compared to the children without IBS symptoms.  Therefore, these two findings, in children with chronic IBS symptoms, further and strongly suggest that an excess of serotonin in the gut may be associated with classic IBS symptoms.

In view of the varying degrees of diarrhea and constipation (and other IBS-associated symptoms) observed among individual patients considered to have IBS, it is highly likely that this syndrome has more than just one cause.  However, the biopsy-proven excess of serotonin in the GI tracts of the 12 children in this study with chronic IBS symptoms is a powerful indication that the abnormal regulation and metabolism of GI tract serotonin likely plays an important (if not causative) role in many, if not most, cases of this chronic and very common GI affliction.  The data from this powerful little clinical study also supports the continued development and clinical testing of serotonin/5-HT blocking (antagonist) agents in patients with diarrhea-predominant IBS.

 

For additional information on IBS, please see my previous column on this topic:

Irritable Bowel Syndrome (IBS), Diet & Fiber

 

 

To learn more about the critical role of diet in the prevention of cancer, look for the publication of my new landmark book, “A Cancer Prevention Guide for the Human Race,” in the summer of this year. 



Disclaimer: As always, my advice to readers is to seek the advice of your physician before making any significant changes in medications, diet, or level of physical activity


Dr. Wascher is an oncologic surgeon, a professor of surgery, a cancer researcher, an oncology consultant, and a widely published author


For a different perspective on Dr. Wascher, please click on the following YouTube link: 


http://www.youtube.com/watch?v=7-Tdv7XW0qg



I and the staff of Weekly Health Update would like to take this opportunity to thank the more than 100,000 new and returning readers who visit our premier global health information website every month.  As always, we enjoy receiving your stimulating feedback and questions, and I will continue to try and personally answer as many of your inquiries as I possibly can.



 

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