Weekly Health Update:
New Treatment for Irritable Bowel Syndrome (IBS)
By, Robert A. Wascher, MD, FACS
The information in this column is intended for informational purposes only, and does not constitute medical advice or recommendations by the author. Please consult with your physician before making any lifestyle or medication changes, or if you have any other concerns regarding your health.
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NEW TREATMENT FOR IRRITABLEBOWEL 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:
Watch for the publication of my new landmark evidence-based book, “ A Cancer Prevention Guide for the Human Race,” in September of this year.
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Disclaimer: As always, my advice to readers is to seek the advice of your physicianbeforemaking any significant changes in medications, diet, or level of physical activity
Dr. Wascher is an oncologic surgeon, professor of surgery, cancer researcher, oncology consultant, and a widely published author
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Robert A. Wascher, MD, FACS
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