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Irritable Bowel Syndrome in the Brain

July 23, 2010 -- Irritable bowel syndrome (IBS) may be in the brain, not in the mind.

IBS patients tend to suffer anxiety and depression, but they tire of being told their symptoms of diarrhea, constipation, and/or pain are all in their minds.

Now there's evidence that their underlying problem may be due to the structure of their brains, says Emeran Mayer, MD, professor of medicine, physiology, and psychiatry at the University of California, Los Angeles.

"Discovering structural changes in the brain ... demonstrates an 'organic' component to IBS and supports the concept of a brain-gut disorder," Mayer says in a news release. "The finding removes the idea once and for all that IBS symptoms are not real and are 'only psychological.' The findings will give us more insight into better understanding IBS."

Mayer, David A. Seminowicz, PhD, and colleagues at UCLA and Canada's McGill University used sophisticated scans to compare the brain anatomy of 55 women with moderate IBS to 48 age-matched healthy women.

The finding: Thinning grey matter -- the part of the brain rich in neurons -- in specific areas of the brain. The affected areas involve:

  • Dampening the brain's arousal system. IBS patients tend to be over-sensitive to (and hypervigilant for) bowel sensations.
  • Controlling emotion. Symptom-related worries and ineffective coping strategies play an important role in chronic pain syndromes.
  • Controlling pain. Brain thinning in this region was seen only in patients who listed pain as their most bothersome IBS symptom.

Importantly, brain areas linked to anxiety and depression were no different in IBS patients than in anxious or depressed people without IBS.

The findings, Seminowicz and colleagues suggest, point to a difference between IBS and chronic pain syndromes such as fibromyalgia.

In chronic pain syndromes, nerves constantly send increased pain signals to the brain. But in IBS, the brain itself seems to be amplifying pain signals it receives from the bowel.

The researchers say future studies should look at family members of IBS patients, to see if they inherited the same brain anatomy that may increase a person's risk of IBS. If so, the studies may reveal genetic components of IBS and point the way to new treatments.

The study appears in the July issue of the journal Gastroenterology.

IBS effects up to 50 million Americans, mostly women. Sign-up for the GI Disorders newsletter and start getting the latest news on treatments & management of IBS from WebMD - the health information provider you trust.

日期:2010年7月24日 - 来自[Health News]栏目
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Efficacy, safety, and tolerability of fructooligosaccharides in the treatment of irritable bowel syndrome

Merete Olesen and Eivind Gudmand-Høyer

1 From the Department of Medical Gastroenterology F, Copenhagen County Hospital, Hellerup, Denmark.

2 Supported by Ferrosan A/S, Soeborg, Denmark.

3 Address reprint requests to M Olesen, Department of Medical Gastroenterology F, KAS, Gentofte, Niels Andersens vej 65, DK-2900 Hellerup, Denmark. E-mail: j.hounsgaard{at}mfi.ku.dk.


ABSTRACT  
Background: Interest in fructooligosaccharides as a health-promoting food component is increasing. Fructooligosaccharides are mainly indigestible and large amounts in the colon may provoke gastrointestinal symptoms.

Objective: The symptoms of irritable bowel syndrome (IBS) may be provoked by large quantities of carbohydrates in the colon. The objective of this study was to determine whether regular consumption of fructooligosaccharides worsens gastrointestinal symptoms in patients with IBS.

Design: A multicenter, prospective, randomized, double-blind, placebo-controlled parallel group comparison was conducted at 24 sites. The study consisted of a 2-wk, single-blind run-in phase and a 12-wk, double-blind comparative phase. Subjects were randomly assigned to receive 20 g fructooligosaccharides powder/d (n = 52) or a placebo (n = 46). Efficacy was based on the patients' overall response to treatment at completion of the study and on the severity and duration of individual symptoms (abdominal distension, abdominal rumbling, abnormal flatulence, and abdominal pain).

Results: Data from 96 patients (16 men and 80 women) were analyzed. After 4–6 wk of treatment, IBS symptoms improved more in the placebo group than in the fructooligosaccharide group. After completion of the study, there were no significant differences between the 2 groups: symptoms improved in 58% of the fructooligosaccharide group and in 65% of the placebo group and symptoms worsened in 8% of the fructooligosaccharide group and in 13% of the placebo group.

Conclusion: Although symptoms worsened in patients with IBS at the onset of treatment with 20 g fructooligosaccharides/d, continuous treatment for 12 wk resulted in no worsening of symptoms.

Key Words: Fructooligosaccharides • irritable bowel syndrome • placebo-controlled clinical trial • efficacy


INTRODUCTION  
Several new types of oligosaccharides have been developed as bulking sucrose substitutes and are claimed to have beneficial health effects. These compounds are of interest as low–glycemic index and low-energy bulk sweeteners, especially for use in patients with diabetes mellitus, and as noncariogenic sucrose substitutes (1–3). Oligosaccharides were shown to improve the bioavailability of calcium, magnesium, and iron in rats (4) and in humans (5, 6) and may affect human lipid metabolism (7). Oligosaccharides are used in processed foods such as table sugar, candies, chocolate, soft drinks, yogurt, and chewing gum. In the area of nutritional sciences, oligosaccharides are attracting interest and debate.

A prebiotic is a nondigestible food ingredient that beneficially affects the host by selectively stimulating the growth, activity, or both of one or a limited number of bacteria in the colon and thus improves the health of the host (8). Of the natural nondigestible oligosaccharides (and polysaccharides) that fulfill the criteria of a colonic food, fructooligosaccharides are the only products currently recognized and used as food ingredients that meet all criteria allowing classification as prebiotics.

Contrary to most dietary fibers, which act mainly as bulking agents, fructooligosaccharides are osmotic laxative agents. However, fructooligosaccharides exert their osmotic effect in the colon and are similar to other dietary fibers in that they enter the colon virtually unchanged. Contrary to most dietary fibers, once in the colon, fructooligosaccharides are rapidly fermented to short-chain fatty acids, especially by bifidobacteria, whose growth is consequently promoted. The breakdown of fructooligosaccharides by bacterial fermentation is followed by a pronounced increase in hydrogen concentrations, which promotes peristalsis of the colon. These effects of fructooligosaccharides are similar to the effects of lactose in people with lactose maldigestion, a condition that produces symptoms similar to those of irritable bowel syndrome (IBS): bloating, flatus, abdominal rumbling, and an irregular defecation pattern (9). Thus, although fructooligosaccharides may have health-promoting effects, they can also have adverse effects; therefore, the usefulness of fructooligosaccharides as a functional food has its limitations. IBS comprises a group of functional bowel disorders in which abdominal discomfort or pain is associated with defecation disorders (10). IBS is one of the most common disorders in the Western population. Symptoms consistent with IBS are reported by 5–25% of the population (11–14). In this population, the general health condition can worsen if fructooligosaccharides are consumed unknowingly, resulting in additional health care costs.

Because the portion of the population with IBS is so large, and because the use of fructooligosaccharides will probably increase, we found it of interest to study the effect of fructooligosaccharides on patients with IBS.


SUBJECTS AND METHODS  
Subjects
The study was conducted in accordance with the Helsinki Declaration II and was approved by the local ethical committee. Participants were recruited from general practice and were well known to their primary care physicians. Subjects had to be white, 18–70 y of age, and attending a general practice for treatment of IBS. Symptoms of IBS had to have been present for 12 wk before visit 1. Furthermore, the results of a physical examination had to be normal and the following laboratory variables had to be within normal ranges: blood hemoglobin, C-reactive protein, serum alkaline phosphatase, serum acetylornithine transaminase, and serum creatinine.

Exclusion criteria included a history of severe chronic medical disease, including colorectal disease or surgery, anal disease, and other gastrointestinal diseases; severe abdominal discomfort; severe obstipation (<2 defecations/wk); abnormal dietary habits; regular use of strong analgesics or strong laxatives; use of medication that might influence bowel function; foreseen introduction of the regular use of new medication during the trial period; alcohol abuse; known or suspected lack of compliance with the study protocol; and abnormal results of a physical examination.

IBS is defined according to the Manning criteria (15) as 1) mild-to-moderate abdominal discomfort relieved by defecation, accompanied by 2 of the following symptoms: abdominal distension, abdominal rumbling, abnormal flatulence, or abdominal pain; and 2) a defecation pattern that is irregular >25% of the time, accompanied by 2 of the following symptoms: a change in defecation frequency, a change in the consistency of the feces, or discharge of mucus. The subjects discontinued the study under the following conditions: voluntary withdrawal, unacceptable treatment response, medical deterioration, adverse events, and exclusion criteria becoming apparent during the study. All participating patients signed informed consent forms after receiving written and oral information of the aim, course, and potential hazards of the trial.

Trial medication
A white, crystalline fructooligosaccharide powder (Idolax; Orafti, Tienen, Belgium) certified by Ferrosan A/S (Soeborg, Denmark) and provided in 10-g sachets was used. The product was a semisynthetic carbohydrate produced by the hydrolysis of inulin and extracted from chicory root. The hydrolysis of inulin produces linear oligomers of the Gfn type, in which one glucose moiety is bound to (ß2–1) fructooligosaccharides by a (1–2)-type linkage, and of the Fm type, in which the homopolymers of fructose are bound by a (2–1) linkage. The placebo was a powdered, dry, glucose syrup (Ferrosan A/S, Soeborg, Denmark) and was provided in 10-g sachets identical in appearance to those of the fructooligosaccharide.

Study design
The study was designed as a prospective, randomized, placebo-controlled, parallel group comparison. The study was divided into 2 phases.

2-wk Single-blind run-in phase
A total of 114 patients received 10 g placebo powder. The main purpose of this phase was to wash out any effect of medication or dietary supplements that the patients had received for IBS before their participation in the study. Medication that might influence the outcome of the study was stopped at the screening visit (eg, psyllium, wheat bran, and laxatives). During this phase, the patients were offered optional treatment with 5 mg bisacodyl (Toilax; Ercopharm, Kvistgaard, Denmark). The tablets were returned at the second visit and if >2 were used over 2 wk, the patient was considered to have severe obstipation and was excluded from the study. Sixteen patients withdrew from the study during or at the completion of this phase.

12-wk Double-blind comparative phase
Ninety-eight patients were randomly assigned to receive either fructooligosaccharide (n = 52) or a placebo (n = 46), 10 g/d for the first 2 wk and 20 g/d for the following 10 wk. Efficacy, safety, tolerability, and compliance were recorded at 2, 4, 6, 8, and 12 wk. The patients were advised to take the powder with their morning meal, dissolved in either milk or juice. The primary efficacy endpoint was the patient's overall response to treatment at completion of the comparative phase. Secondary efficacy endpoints were the investigator's overall assessment of the patients' response to treatment, changes in individual symptom scores, changes in total symptom scores, and changes in defecation frequency. All changes are changes from baseline (the end of the 2-wk run-in period). At each visit, any adverse event that occurred since the previous visit was recorded. The adverse events were graded by the investigator as mild, moderate, or severe and as probably, possibly, or unlikely related to the trial medication. Patients were asked to return any unused sachets at each visit, which were counted by the investigator and by the trial monitor.

Randomization procedure
Only patients who complied with the protocol of the run-in phase were eligible for the comparative phase. Patients were admitted in consecutive order at each trial site and were assigned a code number in that order. Randomization was in balanced blocks according to a computer-generated list of random numbers. The randomization list was generated by Unikem, Copenhagen, and was retained until the study code was broken.

Two study populations were analyzed: the intention-to-treat (ITT) population and the per protocol (PP) population. The ITT population consisted of all patients (n = 98) randomly assigned to the study who received at least one treatment dose. The PP study population consisted of all patients who were randomly assigned to the study and who did not violate the protocol inclusion or exclusion criteria and who received treatment for 2 wk, taking 70% of the prescribed powder while participating in the study. Two patients, both belonging to the fructooligosaccharide group, failed to comply with the protocol requirement to take 70% of the prescribed powder during the first 2 wk of the double-blind phase of the study. Both left the study within 4 wk because of adverse events and were excluded from the PP analysis.

Statistical analysis
For all baseline patient characteristics, the between-group difference and the SE of this difference were calculated. For categorical data, all tests were performed by using chi-square tests or Fisher's exact test. The exact test was used when one cell had an expected count <5. For continuous data, tests were performed by using two-sample t tests. Before tests were carried out, the assumptions underlying the tests (normality and homogeneity of variance) were examined. If the assumptions were not met, Wilcoxon's rank-sum test was used. The significance level for all tests was 5%.

The statistical analysis of efficacy endpoints was conducted in the PP population. If efficacy data were missing at completion of treatment, the last observed values were used. The 2 treatment groups were compared by using the two-sample Wilcoxon's rank-sum test. Changes in individual symptom scores were categorized on a 5-point scale: 1, major improvement; 2, minor improvement; 3, no change; 4, minor deterioration; and 5, major deterioration. Changes in feces consistency and in discharge of mucus from visit 2 to end of treatment were analyzed by using Fisher's exact test. All changes are individual changes from baseline to the end of the study.

Reported adverse events were tabulated and the 2 treatment groups were compared by using Fisher's exact test and the chi-square test. Changes in serum lipids and lipoproteins from baseline to the end of the study were analyzed by using Student's t test.


RESULTS  
Study discontinuation
2-wk Run-in phase
The reasons subjects discontinued the study during the run-in phase are listed in Table 1. The exclusion criteria that became apparent were a lack of compliance with the study protocol (n = 3), abnormal results of a blood test that required further examinations (n = 3), regular use of H2-receptor antagonists (n = 2), and severe constipation (<2 bowel movements/wk; n = 1).


View this table:
TABLE 1. Reasons for study discontinuation during the run-in phase1  
12-wk Comparative phase
During the comparative phase, 23 patients (n = 14 in the fructooligosaccharide group and 9 in the placebo group) discontinued the study. The reasons for discontinuation are listed in Table 2. Seventy-five patients (n = 38 in the fructooligosaccharide group and 37 in the placebo group) completed the 12-wk comparative phase. Ninety-six patients (n = 50 in the fructooligosaccharide group and 46 in the placebo group) were eligible for the PP analysis.


View this table:
TABLE 2. Reasons for study discontinuation during the comparative phase1  
Comparability of subjects at baseline
A comparison of the 2 treatment groups at entry to the study is shown in Table 3. The 2 study groups were compatible except for sex (11 men in the fructooligosaccharide group compared with only 5 in the placebo group), although this difference was not significant.


View this table:
TABLE 3. Comparability of treatment groups at entry to the study1  
Symptoms of IBS
2-wk Run-in phase
Of the 96 patients eligible for the PP analysis, 1 patient reported marked improvement, 14 reported moderate improvement, 25 reported slight improvement, 54 reported no changes, and 2 reported worsened symptoms. Thus, 41% of the patients reported an improvement of their symptoms after completion of the 2-wk period of placebo treatment.

12-wk Comparative phase
The patients' overall assessment of their response to treatment at completion of the comparative phase—the primary efficacy endpoint—is delineated in Table 4. Fifty-eight percent of the patients in the fructooligosaccharide group and 65.2% of the patients in the placebo group experienced some improvement in their symptoms. Because the results might be influenced by sex and because the study was unbalanced in this respect, we assessed the response in men only (Table 5).


View this table:
TABLE 4. Patients' overall assessment of treatment response at completion of the comparative phase  

View this table:
TABLE 5. Overall assessment of treatment response at completion of the comparative phase in the male participants1  
The investigators' overall assessment of treatment response was not significantly different from the patients' overall assessment of treatment response. The patients' assessment of their response to treatment at the different time points is shown in Table 6. The placebo group had fewer symptoms at weeks 4 and 6 than did the fructooligosaccharide group; the differences were nearly significant. At weeks 8 and 12, there were no significant differences between the groups. The effect of fructooligosaccharides on the different symptoms of IBS (abdominal distension, abdominal rumbling, abnormal flatulence, and abdominal pain) is shown in Table 7. The patients in the fructooligosaccharide group complained more of abnormal flatulence than did the patients in the placebo group; however, the difference was not significant. There were no significant differences in the effect on IBS symptoms between the fructooligosaccharide and placebo groups. Changes from baseline in defecation frequency are presented in Table 8. The defecation frequency was significantly greater in the fructooligosaccharide group than in the placebo group at weeks 4 and 6, but there was no significant difference between the groups at the end of the study.


View this table:
TABLE 6. Mean changes from baseline in total symptom scores during the comparative phase of the study  

View this table:
TABLE 7. Effect of placebo and fructooligosaccharide (FOS) treatment on the irritable bowel syndrome  

View this table:
TABLE 8. Mean changes from baseline in weekly defecation frequency  
Serum lipids
Serum lipids and lipoproteins were measured at baseline and again at the completion of the comparative phase. There were no significant within-group or between-group changes or differences observed.

Safety and tolerability of fructooligosaccharide treatment
Twenty-one patients in the fructooligosaccharide group experienced a total of 32 adverse events and 22 patients in the placebo group experienced a total of 29 adverse events. Seven patients in the fructooligosaccharide group and 1 patient in the placebo group complained of abdominal pain (P = 0.063; Fisher's exact test). Ten patients in the placebo group and 3 patients in the fructooligosaccharide group reported some type of infection (P = 0.020; chi-square test). Otherwise, adverse events reported in the study were few and not significantly different between the fructooligosaccharide and placebo groups.


DISCUSSION  
The use of low-energy bulk sweeteners has become increasingly popular. In the area of nutritional sciences, fructooligosaccharides are currently attracting interest as a functional food with beneficial health effects. It might be anticipated that an increased use of fructooligosaccharides would enhance symptoms similar to those associated with IBS in the general population. The clinical tolerance to regular consumption of fructooligosaccharides was studied in healthy volunteers (16, 17). Both of these studies found that tolerance did not improve during 12 or 15 d of regular fructooligosaccharide use. The main complaint related to all doses of fructooligosaccharide was excessive flatulence, but daily doses of <20 g resulted in only minor complaints. Doses >40 g/d resulted in abdominal rumbling and bloating; doses >50 g/d resulted in abdominal cramps and diarrhea (17). Pronounced gastrointestinal distress may be provoked in IBS patients because of the malabsorption of small amounts of fructose, sorbitol, and mixtures of fructose and sorbitol (18) and by lactulose and fructooligosaccharides in people with lactose maldigestion (19). The treatment most widely recommended for IBS patients is an increased intake of dietary fibers (9). This recommendation has been modified in recent years (20). Although dietary fiber consumption has been proven to increase stool volume and reduce colonic transit time (21), there are serious doubts about the effect of a high-fiber diet on IBS symptoms. According to Klein's (22) literature review of placebo-controlled clinical trials, the only beneficial effect of bulking agents on IBS symptoms was the alleviation of constipation; abdominal pain and bloating did not improve. Francis and Whorwell (23) found that 55% of patients who answered a questionnaire about the effects of bran consumption reported that their IBS symptoms worsened, specifically bowel disturbance, abdominal distension, and abdominal pain.

In the present study, we found that the symptoms of IBS patients did not worsen significantly after daily ingestion of 20 g fructooligosaccharides for 12 wk; however, 7 fructooligosaccharide-treated patients reported abdominal pain compared with only 1 placebo-treated patient. These patients were all included in the final statistical analyses (Tables 4, 6, and 7). At weeks 4 and 6, the total symptom score improved in the placebo and fructooligosaccharide groups, more so in the placebo group (NS), but at weeks 8 and 12, this difference in symptom score reduction leveled out.

Prolonged ingestion of lactulose or lactose in lactose-intolerant persons may result in colonic adaptation and a reduction in symptoms indicating intolerance (24, 25). This same phenomenon may have occurred in the present study. For example, the laxative effect of fructooligosaccharide changed during the study because the defecation frequency was significantly greater in the fructooligosaccharide group than in the placebo group at visits 4 and 5, whereas the difference was not significant at visit 7 or at the end of the study (Table 8).

Men constituted only 16.6% of the participants in the present study. This reflects well the proportion of men among IBS patients seeking medical advice for their problems (10, 22). The mens' responses were not significantly different from those of the population as a whole in both the placebo and fructooligosaccharide group. Whether fructooligosaccharides have a beneficial effect on IBS symptoms is impossible to evaluate from the present study. Both the placebo and fructooligosaccharide groups improved significantly during the 12-wk study, which was expected. In a comparative analysis, Klein (22) found that >50% of IBS patients responded positively to placebo in 15 of 28 placebo-controlled studies. Whether fructooligosaccharide consumption has an effect on IBS symptoms different from traditionally recommended dietary fibers could not be deduced from the present study. The results obtained may simply indicate that the symptoms of IBS fluctuate and whether they fluctuate due to or despite a given diet is unknown.

In conclusion, in most patients with IBS, symptoms are not constant but return intermittently for years and may worsen transiently at the onset of fructooligosaccharide ingestion. The disappearance of this effect after continuous ingestion of 20 g fructooligosaccharide/d for 12 wk may be a result of the adaptation.


ACKNOWLEDGMENTS  
We acknowledge Bente Brünner for motivating and encouraging the primary care physicians to participate in the study and UNI-C (Aarhus, Denmark) for providing statistical support.


REFERENCES  

  1. Oku T, Tokunaga T, Hosoya N. Nondigestibility of a new sweetener, "Neosugar," in the rat. J Nutr 1984;114:1574–81.
  2. Oku T. Oligosaccharides with beneficial health effects: a Japanese perspective. Nutr Rev 1996;54:S59–66.
  3. Hidaka H, Eida T, Takirawa T, Tokunaga T, Tashoiro Y. Effects of fructooligosaccharides on intestinal flora and human health. Bifidobact Microflora 1986;5:37–50.
  4. Delzenne NM, Eaertens J, Verplaetse H, Roccaro M, Roberfroid M. Effect of fermentable fructooligosaccharides on energy and micronutrients absorption in the rat. Life Sci 1995;57:1579–87.
  5. Coudray C, Bellanger J, Castiglia-Delavoud C, Rémésy C, Vermorel M, Rayssiguier Y. Effect of soluble or partly soluble dietary fibres supplementation on absorption and balance of calcium, magnesium, iron and zinc in healthy young men. Eur J Clin Nutr 1997;51:375–80.
  6. van den Heuvel EGHM, Muys T, van Dokkum W, Schaafsma G. Oligofructose stimulates calcium absorption in adolescents. Am J Clin Nutr 1999;69:544–8.
  7. Van Loo J, Cummings J, Delzenne N, et al. Functional food properties of non-digestible oligosaccharides: a consensus report from the ENDO project (DGXII AIRII-CT94-1095). Br J Nutr 1999;81:121–32.
  8. Gibson GR, Roberfroid MB. Dietary modulation of human colonic microbiota: introducing the concept of prebiotics. J Nutr 1995;125: 1401–12.
  9. Sleisinger MH, Fordtran JS, eds. Gastrointestinal disease, pathophysiology, diagnosis/management. 5th ed. Philadelphia: WB Saunders, 1993.
  10. Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Müeller-Lissner SA. Functional bowel disorders and functional abdominal pain. Gut 1999;45(suppl):1143–7.
  11. Talley NJ, Zinsmeister AR, Van Dyke C, Melton LJ. Epidemiology of colonic symptoms and the irritable bowel syndrome. Gastroenterology 1991;101:927–34.
  12. Heaton KW, O'Donnell LJD, Braddon FEM, Mountford RA, Hughes AO, Cripps PJ. Symptoms of irritable bowel syndrome in a British urban community: consulters and nonconsulters. Gastroenterology 1992;102:1962–7.
  13. Jones R, Lydeard S. Irritable bowel syndrome in the general population. BMJ 1992;304:87–90.
  14. Kay L, Jørgensen T, Jensen KH. The epidemiology of irritable bowel syndrome in a random population: prevalence, natural history and risk factors. J Intern Med 1994;236:23–30.
  15. Manning APM, Thompson WG, Heaton KW, Morris AF. Towards a positive diagnosis of the irritable bowel syndrome. Br Med J 1978; 2:653–4.
  16. Stone-Dorshow T, Levitt MD. Gaseous response to ingestion of poorly absorbed fructo-oligosaccharide sweetener. Am J Clin Nutr 1987;46:61–5.
  17. Briet F, Achour L, Flourié B, et al. Symptomatic response to varying levels of fructooligosaccharides consumed occasionally or regularly. Eur J Clin Nutr 1995;49:501–7.
  18. Rumessen JJ, Gudmand-Høyer E. Functional bowel disease: malabsorption and abdominal distress after ingestion of fructose, sorbitol, and fructose-sorbitol mixtures. Gastroenterology 1988;95:694–700.
  19. Teuri U, Vapaatalo H, Korpela R. Fructooligosaccharides and lactulose cause more symptoms in lactose maldigesters and subjects with pseudohypolactasia than in control lactose digesters. Am J Clin Nutr 1999;69:973–9.
  20. American Gastroenterological Association. American Gastroenterological Association medical position statement: irritable bowel syndrome. Gastroenterology 1997;112:2118–9.
  21. Müeller-Leisner SA. Effect of wheat bran on weight of stool and gastrointestinal transit time: a meta analysis. Br Med J 1988; 296:615–7.
  22. Klein KB. Controlled treatment trials in the irritable bowel syndrome: a critique. Gastroenterology 1988;95:232–41.
  23. Francis CY, Whorwell PJ. Bran and irritable bowel syndrome: time for reappraisal. Lancet 1994;344:39–40.
  24. Flourié B, Briet F, Florent C, Pellier P, Maurel M, Rambaud JC. Can diarrhea induced by lactulose be reduced by prolonged ingestion of lactulose? Am J Clin Nutr 1993;58:369–75.
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Received for publication August 25, 1999. Accepted for publication April 24, 2000.


日期:2008年12月28日 - 来自[2000年72卷第6期]栏目

Antibiotic May Aid Irritable Bowel

Oct. 16, 2006 -- Ten days' treatment with the antibiotic Xifaxan reduces symptoms of irritable bowel syndrome (IBS), a small clinical trial suggests.

IBS is a condition of the intestinal tract that causes symptoms of bloating, gas, abdominal cramping, diarrheadiarrhea, and constipationconstipation.

Xifaxan, now approved for the treatment of travelers' diarrhea, kills bacteria living in the gut. Experts disagree over the cause of IBS. Some suspect the root cause to be overgrowth of gut bacteria.

One of these experts is Mark Pimentel, MD, director of the gastrointestinal motility program at Cedars-Sinai Medical Center in Los Angeles. In prior studies, Pimentel used breath tests to show that about 80% of IBS patients may have serious bacterial fermentation going on in their gut.

This led him to wonder what would happen if he used a powerful antibiotic to shift the balance between overgrowth of these theoretically harmful bacteria and normal bacteria living in the gut.

So Pimentel and colleagues gave a 10-day course of Xifaxan or inactive placebo to 87 IBS patients. Seventy-two patients finished the study. As is common in IBS studies, those who got placebo felt a bit better. Those who got Xifaxan reported even more improvement -- especially less bloating.

"Xifaxan was superior to placebo for control of IBS," Pimentel tells WebMD. "It suggests we are finally tackling a sustainable cause of IBS. If it is bacteria, we have changed the environment so that IBS is better on a semipermanent basis."

The study, funded by Xifaxan maker Salix Pharmaceuticals, appears in the Oct. 17 issue of Annals of Internal Medicine. Pimentel is a consultant to Salix and has received speaking fees from the company. Cedars-Sinai Medical Center has a licensing agreement with Salix.

Change of IBS Treatment?

Is Xifaxan a new treatment for IBS? Not yet. A larger study, looking at IBS patients treated by their own doctors with Xifaxan, is already underway. Until those results are known, Xifaxan is not an officially approved treatment for IBS.

But Pimentel says he's treated "thousands" of IBS patients with Xifaxan -- and he says now the word is getting out.

"The gem here is you have a sustained effect in IBS. The larger, longer studies will show how well this works," he says. "We've reported these results at professional meetings, and it has changed the way IBS is treated. Sixty percent of gastroenterologists in the country are starting to do it this way."

Pimentel says the average patient needs re-treatment every two or three months, but that response varies greatly from patient to patient.

[page]

Controversy Over IBS Treatment

Not all experts are convinced that bacterial overgrowth is a root cause of IBS, or that antibiotics are the best treatment. One of these experts is Douglas A. Drossman, MD, co-director of the University of North Carolina Center for Functional GI and Motility Disorders, Chapel Hill.

In an editorial accompanying the Pimentel study, Drossman notes that IBS is a complex disorder that springs from the complex interplay of an oversensitive gut and the brain.

Breath tests, he says, aren't reliable for diagnosing bacterial overgrowth. And Pimentel's study, he says, does not prove that treating bacterial overgrowth helps.

Drossman is not impressed by Pimentel's finding that IBS patients reported an average 36.4% improvement in the 10 weeks after treatment with Xifaxan, while those given placebo treatment reported an average 21% improvement.

"Only bloating improved, and abdominal pain, diarrheadiarrhea, and constipationconstipation did not improve," Drossman notes. "The benefit of using antibiotics is not fully proven and must be balanced with potential risks in terms of side effects, high costs ? and the need for recurrent treatment."

Pimentel says new studies now coming out will support the bacterial-overgrowth theory of IBS. He does, however, say people with IBS have "movement disorders of the small bowel." He is hoping that a drug to promote movement in the small bowel will improve outcomes for IBS patients treated with antibiotics.


SOURCES: Pimentel, M. Annals of Internal Medicine, Oct. 17, 2006; vol 145: pp 557-563. Drossman, D.A. Annals of Internal Medicine, Oct. 17, 2006; vol 145: pp 626-628. Mark Pimentel, MD, director, gastrointestinal motility program, Cedars-Sinai Medical Center, Los Angeles.

日期:2006年10月18日 - 来自[General Health]栏目
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Irritable Bowel, Pain Syndromes Linked

Sept. 28, 2006 -- Doctors have long suspected a link between irritable bowel syndrome, pain syndromes, and depression. New data now strongly support this theory.

The findings come from data on 97,593 people with irritable bowel syndrome enrolled in a large U.S. health plan from 1996 to 2002. J. Alexander Cole, DSc, MPH, and colleagues at Boston University compared these patients with 27,402 people seeking routine health care.

Their results show that people with irritable bowel syndrome are:

  • 80% more likely to suffer fibromyalgiafibromyalgia
  • 60% more likely to suffer migraine
  • 40% more likely to suffer depression
  • Overall, 60% more likely to suffer fibromyalgia, migraine, or depression

"Perhaps what is driving the relation between irritable bowel syndrome and these other conditions is some underlying biological disorder," Cole tells WebMD. "Nobody is sure what this could be. But people suggest that there is this constellation of symptoms among people with irritable bowel syndrome, fibromyalgia, migraine, and depression that might present in different ways."

Cole and colleagues report their findings in the Sept. 28 issue of the online journal BMC Gastroenterology.

Common Cause of Pain Syndromes?

Cole, now an epidemiologist with i3 Drug Safety, is not an expert on irritable bowel syndrome. Reza Shaker, MD, is. Shaker, chief of gastroenterology and hepatology at the Medical College of Wisconsin, was not involved in the Cole study.

"Clinical observations of patients with pain syndromes indicate that we are dealing with a syndrome bigger than a single organ," Shaker tells WebMD. "These findings confirm these previous observations."

Shaker says people with irritable bowel syndrome and people with pain syndromes such as fibromyalgia and migraine have something in common. They all have nerve pathways which somehow have become vastly oversensitive to pain signals -- a process doctors call sensitization.

Perhaps, Shaker suggests, there's a common problem at the crossroads where these nerve pathways intersect.

"Is it possible that there is an event -- possibly an early life event -- that affects the crossroads of all these nerve pathways?" he asks. "In areas where these nerves cross, it could be that there is sensitization occurring, affecting different neural circuits."

Cole suggests that different doctors looking at the same underlying illness might make different diagnoses. A gastroenterologist, for example, might diagnose irritable bowel syndrome, while a rheumatologist might diagnose fibromyalgia.

This sounds a lot like the blind men who, on first encountering an elephant, declare it to be like a snake or a tree depending on whether they are touching the elephant's trunk or its leg. Shaker says this analogy is apt. But most doctors, he says, will examine the whole elephant, not just its parts.

"A professional doesn't just focus on one symptom. If we see irritable bowel syndrome along with noncardiac chest pain or fibromyalgia, then we tackle this," he says. "But we doctors need to have a more global picture of this, instead of pigeonholing our diagnosis according to our own specialty or subspecialty."


SOURCES: Cole, J.A. BMC Gastroenterology, Sept. 28, 2006; vol 6: pp 26. J. Alexander Cole, DSc, MPH, epidemiologist, i3 Drug Safety. Reza Shaker, MD, chief, division of gastroenterology and hepatology, Medical College of Wisconsin, Milwaukee.

日期:2006年9月29日 - 来自[General Health]栏目

Irritable Bowel Syndrome: Herbal Help?

Jan. 25, 2006 -- Some traditional Chinese, Tibetan, and Indian herbal medicines may improve irritable bowel syndrome (IBS) symptoms, researchers report.

The finding comes from a review of 75 studies on irritable bowel syndrome. The herbal medicines that stood out in the review were:

  • Standard and individualized Chinese herbal formulations including "STW 5" and "STW 5-11"
  • A Tibetan herbal formula called "Padma Lax"
  • An Indian formula of two unnamed herbs used in Ayurveda, a traditional Indian health system

However, the review doesn't endorse or recommend any herbal medicines for irritable bowel syndrome, since many of the studies weren't of top-notch quality.

The report appears in The Cochrane Library, a health care research journal. The scientists included Jianping Liu, MD, PhD.

Liu works at Beijing University of Chinese Medicine's Evidence-based Chinese Medicine Centre for Clinical Research and Evaluation. He is also on staff at the National Research Centre in Complementary and Alternative Medicine at Norway's University of Tromso.

Helpful or Not?

The studies, which were mainly done in China, had a combined total of nearly 8,000 patients with IBS.

"Some herbal medicines may improve the symptoms of irritable bowel syndrome," the researchers write.

For instance, IBS patients in nine studies either got herbal and conventional medicines or conventional medicines alone. Those who got herbal and conventional medicines reported greater improvement of their IBS symptoms, the researchers note.

None of the studies reported serious side effects from any of the herbal medicines. But the researchers note that that doesn't mean that the medicines are safe for everyone.

Liu's team urges "caution" in considering positive findings from studies with poor design, small numbers of patients, and unconfirmed results.

Quality Questions

The researchers' main criticisms were:

  • Most studies were of low quality.
  • Various formulas were used.
  • Many studies didn't check long-term results.

For instance, some studies compared herbal medicines with conventional medicines, not all of which are proven to help irritable bowel syndrome. In other trials, herbal medicines were compared with placebos, which don't contain any conventional or herbal medicine.

Also, herbal medicines were often tailored to each patient, a typical practice in traditional Chinese medicine. Using similar formulas would have made comparisons easier, note Liu and colleagues.

"There is a great need for further rigorously conducted trials that look to see whether it is possible to replicate these positive effects," Liu says in a news release.

"For these trials to be useful, they must also improve the description of the herbal medicines being tested," he says.

The researchers' bottom line: "Some herbal medicines deserve further examination in high-quality trials," they write. Meanwhile, they call it "premature to recommend herbal medicines for routine use in irritable bowel syndrome."


SOURCES: Liu, J. The Cochrane Library, 2006; issue 1. WebMD Medical Reference from Healthwise: "Ayurveda: Topic Overview." News release, John Wiley & Sons Inc.

日期:2006年8月16日 - 来自[alternative medicine]栏目
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Hypnosis for Irritable Bowel

Hypnosis for Irritable Bowel


Aug. 23, 2001 -- Relax, you're getting sleepy ... very sleepy.

That may sound like a Hollywood cliché -- the glassy-eyed subject lulled by a swinging watch -- but some researchers believe the peaceful state achieved in hypnosis can help people suffering from irritable bowel syndrome.

At a meeting this week of the World Congress of Psychosomatic Medicine, gastroenterologist Peter Whorwell, MD, will discuss more than 20 years of research showing that hypnosis can not only improve symptoms of irritable bowel syndrome, or IBS, but can even alter the underlying physical problems that cause the symptoms.

The movie version of hypnosis is not much like the real thing. Instead, says Whorwell, in his practice it is more like meditation, yoga, or guided imagery. For treating IBS, a hypnotherapist guides a patient in relaxation exercises and helps him focus on the muscles of the stomach that are so critical in IBS.

"It's a concentrated form of relaxation where the therapist is teaching the patient to control systems of their body they can't normally control," Whorwell tells WebMD.

IBS is a common disorder of the digestive system that leads to cramps and pain, gassiness, bloating, and changes in bowel habits. Some people with IBS have constipation, others have diarrhea, and some have both.

And many doctors believe there is a psychological component to IBS, in which stress, depression, or other mental states can lead to physical symptoms in the gut. Such symptoms are called "psychosomatic," and Whorwell says they are not confined to IBS. "Every disease has a psychological component," he says.

With IBS it's important for patients to have better control of the contractions of their stomach muscles and the sensitivity of their stomach to stress and other influences. That's where hypnosis can help, Whorwell says.

But it doesn't happen overnight.

"It's a skill the patient has to take the time to learn," he says. "Just as it took time to learn to control bowels as an infant, it takes time to train your body to control your gut."

At the Hypnosis Unit of University Hospitals of South Manchester, in England, where Whorwell practices, patients typically receive twelve half-hour sessions of hypnotherapy, he says.

Hypnotherapy can be used in combination with drugs that ease the pain of stomach contractions, or with changes in diet. But Whorwell believes that for some patients hypnosis can be superior.

"The beauty of hypnotherapy is that once patients are better, they stay better," he says. "Once a person stops using drugs, the symptoms can come back."

Whorwell acknowledges that finding a hypnotherapist who knows what he is doing and -- more important -- knows about IBS, can be difficult. And hypnotherapy remains somewhat outside the mainstream, he believes.

Still, a 1996 statement by the American Gastroenterological Association suggests that hypnotherapy is generally accepted as a treatment for IBS.

"Several psychological treatments have been studied in patients with IBS, including psychotherapy, ... hypnosis, relaxation, and biofeedback," according to the statement. "These seem to be effective at reducing abdominal pain and diarrhea but not constipation, and they also reduce anxiety and other psychological symptoms."

"I'm a believer," says gastroenterologist Cynthia M. Yoshida, MD, director of the Women's GI Clinic at the Digestive Health Center of Excellence at the University of Virginia, Charlottesville. "Most people in the field will tell you it's not just medicine that does it [for IBS]."

At the Women's Clinic, people with IBS may receive a range of "alternative" treatments similar to hypnosis, including guided imagery and relaxation techniques, possibly in addition to drugs and dietary changes.

"It's very individualized depending on what is going on in the patient's life and whether stress is a big part of their symptoms," she tells WebMD. "There is no cookbook for treating IBS."

日期:2006年8月16日 - 来自[alternative medicine]栏目

Hypnosis for Irritable Bowel

Hypnosis for Irritable Bowel


Aug. 23, 2001 -- Relax, you're getting sleepy ... very sleepy.

That may sound like a Hollywood cliché -- the glassy-eyed subject lulled by a swinging watch -- but some researchers believe the peaceful state achieved in hypnosis can help people suffering from irritable bowel syndrome.

At a meeting this week of the World Congress of Psychosomatic Medicine, gastroenterologist Peter Whorwell, MD, will discuss more than 20 years of research showing that hypnosis can not only improve symptoms of irritable bowel syndrome, or IBS, but can even alter the underlying physical problems that cause the symptoms.

The movie version of hypnosis is not much like the real thing. Instead, says Whorwell, in his practice it is more like meditation, yoga, or guided imagery. For treating IBS, a hypnotherapist guides a patient in relaxation exercises and helps him focus on the muscles of the stomach that are so critical in IBS.

"It's a concentrated form of relaxation where the therapist is teaching the patient to control systems of their body they can't normally control," Whorwell tells WebMD.

IBS is a common disorder of the digestive system that leads to cramps and pain, gassiness, bloating, and changes in bowel habits. Some people with IBS have constipation, others have diarrhea, and some have both.

And many doctors believe there is a psychological component to IBS, in which stress, depression, or other mental states can lead to physical symptoms in the gut. Such symptoms are called "psychosomatic," and Whorwell says they are not confined to IBS. "Every disease has a psychological component," he says.

With IBS it's important for patients to have better control of the contractions of their stomach muscles and the sensitivity of their stomach to stress and other influences. That's where hypnosis can help, Whorwell says.

But it doesn't happen overnight.

"It's a skill the patient has to take the time to learn," he says. "Just as it took time to learn to control bowels as an infant, it takes time to train your body to control your gut."

At the Hypnosis Unit of University Hospitals of South Manchester, in England, where Whorwell practices, patients typically receive twelve half-hour sessions of hypnotherapy, he says.

Hypnotherapy can be used in combination with drugs that ease the pain of stomach contractions, or with changes in diet. But Whorwell believes that for some patients hypnosis can be superior.

"The beauty of hypnotherapy is that once patients are better, they stay better," he says. "Once a person stops using drugs, the symptoms can come back."

Whorwell acknowledges that finding a hypnotherapist who knows what he is doing and -- more important -- knows about IBS, can be difficult. And hypnotherapy remains somewhat outside the mainstream, he believes.

Still, a 1996 statement by the American Gastroenterological Association suggests that hypnotherapy is generally accepted as a treatment for IBS.

"Several psychological treatments have been studied in patients with IBS, including psychotherapy, ... hypnosis, relaxation, and biofeedback," according to the statement. "These seem to be effective at reducing abdominal pain and diarrhea but not constipation, and they also reduce anxiety and other psychological symptoms."

"I'm a believer," says gastroenterologist Cynthia M. Yoshida, MD, director of the Women's GI Clinic at the Digestive Health Center of Excellence at the University of Virginia, Charlottesville. "Most people in the field will tell you it's not just medicine that does it [for IBS]."

At the Women's Clinic, people with IBS may receive a range of "alternative" treatments similar to hypnosis, including guided imagery and relaxation techniques, possibly in addition to drugs and dietary changes.

"It's very individualized depending on what is going on in the patient's life and whether stress is a big part of their symptoms," she tells WebMD. "There is no cookbook for treating IBS."

日期:2006年8月16日 - 来自[alternative medicine]栏目
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Hypnosis May Soothe Irritable Bowel

June 8, 2006 ? Focusing the mind with hypnotherapy may help fix problems in the gut and improve the quality of life for people with irritable bowel syndrome (IBS)irritable bowel syndrome (IBS).

Researchers in a new study found hypnotherapy significantly improved the emotional and physical symptoms of 75 men and women with the common digestive disorder.

"It is estimated that between 10 to 15 per cent of adults may suffer from IBS and that the physical, emotional, social and economic consequences of the illness can be considerable," Graeme D. Smith PhD, of the University of Edinburgh, says in a news release.

"Physical symptoms include altered bowel habits, abdominal pain and bloating, together with other non-intestinal problems such as lethargy, problems sleeping, and indigestionindigestion. Anxiety and psychosocial problems are also common and these can have a detrimental impact on quality of life."

Hypnotherapy Eases IBS

In the study, published in the Journal of Clinical Nursing, 20 men and 55 women received between five and seven half-hour hypnotherapy sessions over a three-month period. During the sessions, each patient was instructed to place his or her hands on the site of maximum abdominal discomfort and induce feelings of warmth and comfort in that region.

The therapist also told patients to imagine their gut as a river that changes how it flows. Constipated patients were told to envision the river as motionless and then freely flowing. Patients with diarrheadiarrhea were told to imagine the river flowing more slowly.

Afterwards, patients reported a 5% reduction in abdominal pain and a 4% reduction in abdominal bloating.

Hypnotherapy produced other significant improvements in both the physical and emotional symptoms of IBS, including:

  • 30% improvement in emotional quality of life
  • 25% rise in energy
  • 21% increase in overall mental healthmental health
  • 18% improvement in sleep
  • 16% increase in overall physical health
  • 14% improvement in diet
  • 12% drop in anxiety
  • 4% decline in depressiondepression

Researchers say the biggest improvements were among women who reported abdominal pain as their primary physical symptom.

"There's no universal agreement about what causes IBS and traditional treatment is often disappointing," says Smith in the news release. "This study shows that hypnotherapy can effectively reduce symptoms and improve quality of life and underlines the valuable role that complementary therapies can play in modern healthcare."


SOURCES: Smith, G. Journal of Clinical Nursing, June 2006; vol 15: pp 678-684. News release, Journal of Clinical Nursing.

日期:2006年7月4日 - 来自[General Health]栏目
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