Expert Commentary -- Bloating, Distension, and the Irritable Bowel Syndrome

Richard Lea, MD; Peter J. Whorwell, MD

Editor's Note

Please note: The following announcement supersedes any information contained in this article. On March 30, 2007, Novartis, in compliance with an FDA request, suspended marketing and sales of its irritable bowel/constipation drug tegaserod maleate (Zelnorm) after an analysis of its clinical database pointed to a higher incidence of myocardial infarction, stroke, and unstable angina among patients taking the drug. For updated information on this issue, see the Medscape Alert Center on tegaserod.

Definition of Bloating and Distension

In the literature, the terms "bloating" and "distension" are largely used synonymously, relying more on patient descriptions rather than on any attempt to record an actual change in girth. However, it has recently been suggested that the term "bloating" should be reserved exclusively for the subjective symptom of abdominal enlargement, with the term "distension" being used only when there is an actual change in girth. The situation is further complicated by the fact that in some languages there is not necessarily an exact equivalent of the word "bloating." For the purposes of this review, when a particular study uses the descriptors of either bloating or distension, they are strictly adhered to because there is usually no way of further refining their precise meaning.

The Epidemiology of Bloating

The symptom of bloating is extremely common and has been experienced by most people at some stage in their lives. Indeed, one recent population survey reported that 16% of apparently healthy individuals experience bloating at least once a month,[1] and bloating within the previous 3 months was reported by 30% of respondents in the US Householders' survey.[2] Despite not being a requirement of the current Rome II diagnostic criteria,[3] bloating is even more prevalent in patients with irritable bowel syndrome (IBS), with at least 75% of patients reporting bloating as part of their symptom complex.[4] Patients with IBS typically suffer from bloating 25% of the time compared with pain 33% of the time.[5] Furthermore, nearly two thirds of patients seen in tertiary care centers rate bloating as their most severe symptom, compared with approximately one third who feel that pain is their worst symptom.[6] Bloating does not appear to be age-related,[2,7,8] although it is more prevalent in women than in men[1,9-11] and this may be because men sometimes refer to it as a "tight sensation" in the abdomen. Typically, bloating tends to become worse as the day progresses and after ingestion of food,[4,12] and is sometimes relieved by the passage of stool or flatus.[4]

Some studies show that patients with IBS with predominant constipation experience more bloating,[13] with up to 90% of constipated IBS patients reporting the symptom.[14] However, other studies report that bloating is equally common in patients with IBS with diarrhea.[15,16] Approximately 40% of female IBS patients report that bloating is related to their menstrual cycle, usually being exacerbated perimenstrually[4,12,17]; however, bloating is not limited purely to the perimenstrual time of the cycle.

Although abdominal distension formed part of the original diagnostic criteria for IBS described by Manning and colleagues,[18] later studies have suggested that bloating/distension is not a reliable indicator of the disease, especially in men,[9,11] and this was confirmed in factor analyses leading to the development of the current Rome criteria.[11,19,20]

The Relationship Between Bloating and Distension

Chang and colleagues[4] recently conducted a questionnaire study investigating the relationship between bloating and distension and found that three quarters of patients with IBS with bloating also described physical abdominal distension, whereas only one quarter had bloating alone. Several factors were reported to influence this relationship: for example, bloating and distension were more frequently associated with constipation and female sex. Furthermore, although bloating without distension was rarely described as an intrusive symptom, bloating with distension was frequently ranked as one of the most bothersome symptoms of IBS.

Several studies have attempted to objectively determine whether bloating is actually associated with abdominal distension. In one of these investigations, Sullivan[12] showed that in patients with bloating, abdominal girth during symptomatic episodes was greater than that measured in controls. In another study, Maxton and colleagues[21] also demonstrated increased abdominal distension in patients with IBS. However, both of these studies used tape measures and could have been unintentionally influenced either by the patient or investigator. Abdominal inductance plethysmography is a technique that overcomes these problems by allowing objective, continuous measurement of girth in ambulatory patients -- if necessary, over prolonged time periods. The technique was validated by Lewis and colleagues[22,23] in healthy volunteers and showed a high correlation with girth measurements made with tape measures, being accurate to within 1 mm. Additional studies using this technique have objectively demonstrated that abdominal distension is indeed increased in patients with IBS compared with controls, and furthermore, that the symptom of bloating correlates with the degree of abdominal distension.[24] Another technique that has recently been validated in healthy volunteers is an extensometer based on ultrasound, although this is not currently capable of measuring girth in ambulatory patients.[25]

The Pathophysiology of Bloating

Patients and some physicians believe that excessive quantities of intestinal gas are the reason for bloating and/or distension. However, studies attempting to measure gas volumes have not consistently supported this theory. One such study, by Lasser and colleagues,[26] using a gas washout technique, found no differences in gas volumes between patients with bloating and their volunteer counterparts; several more recent studies using labeled sulfurhexafluoride have supported this finding.[27] Using CT scanning to estimate gas volumes, Maxton and colleagues[21] also found no definitive evidence of excess gas in IBS patients, despite demonstrating increased lateral abdominal profiles in these patients. In contrast, Koide and coworkers[28] used plain abdominal radiographs to show that gas volumes were greater in patients with IBS compared with controls. In another study, King and colleagues[29] found that although patients with IBS produced more hydrogen, total gas production was not significantly increased. Thus, the balance of evidence is against excessive gas being the sole cause of abdominal distension.

An alternative approach to determining whether bloating/distension is related to excessive amounts of intestinal gas is to assess whether attempting to modify gas volumes alters the severity of these complaints. One such study administered lactulose, a fermentable fiber (psyllium), and a nonfermentable fiber (methylcellulose) to healthy volunteers. Although lactulose ingestion resulted in an increase in flatus, all 3 materials resulted in an increase in bloating. Gas production as measured by breath hydrogen concentrations only increased following lactulose. This interesting study suggests that whereas gaseous symptoms (ie, passage of flatus) are probably related to an increase in gas production, bloating may not be.[30] Another approach to altering gas production is the modification of colonic flora. Two studies found that treatment with antibiotics improved gastrointestinal symptoms other than bloating in patients with IBS thought to have bacterial overgrowth,[31,32] and another reported similar results in patients with functional gastrointestinal disorders without bacterial overgrowth.[33] Other studies using probiotics have also failed to demonstrate any improvement in bloating, although one study did report an improvement in flatus production.[34,35] Taken together, these studies also suggest that excessive quantities of intestinal gas may be associated with gas-related complaints (flatus volume and frequency), although not necessarily be related to the symptom of bloating.

Accumulating evidence from the Barcelona group, headed by Professors Azpiroz and Malegalada, has suggested that while gas volumes may be normal in bloated patients, intestinal gas handling is abnormal. Following a study validating their "gas challenge" technique (the gas challenge test involves infusing gas at 12 mL/min into the subject's jejunum, while recording symptoms, abdominal girth, and gas volumes) in healthy volunteers,[36] Serra and colleagues[27] found that during jejunal gas infusion, 18 of 20 IBS patients retained gas, had distention, or developed abdominal symptoms, whereas 16 of 20 healthy volunteers failed to do so. These changes could be augmented by enteral infusion of lipid, providing one possible rationale as to why bloating frequently worsens in the postprandial period.[37] Another study by the same investigators suggested that the physical component of a meal (simulated by an intragastric balloon) may induce bloating, but the chemical component (simulated with an enteral lipid infusion) causes distension.[38] This is of considerable importance because it lends experimental support to questionnaire data suggesting that bloating and distension are not always synonymous, and that each may arise from distinct but overlapping pathophysiologic mechanisms. This idea was also supported by another study showing that bloating could be induced by voluntary inhibition of gas passage, while gut relaxation (induced using glucagon) caused asymptomatic distension.[39] Using abdominal inductance plethysmography, we have recently shown that patients with IBS, who complain of bloating in the absence of distension of the abdomen, have lower rectal sensitivity thresholds to balloon distension compared with patients who have both bloating and distension.[40] These patients with bloating alone may have primary perceptual abnormalities, and attempts to modify gas volumes therefore may not be expected to affect their symptoms. In contrast, patients with bloating who exhibit marked abdominal distension, as defined using abdominal inductance plethysmography, may have reduced gut sensitivity (hyposensitivity),[41] and taken together, these 2 observations may provide a possible explanation for the studies inducing bloating in the absence of distension or vice versa.

Several additional non-gas-related mechanisms have been suggested as being relevant to the pathogenesis of bloating and/or distension. Two studies have examined abdominal muscle function and reached different conclusions. One found that patients with bloating were able to perform fewer sit-ups compared with controls,[12] and the other used the more sophisticated technique of surface electrode electromyography (EMG) to show that there were no significant differences in recordings taken from IBS patients and volunteers.[42] A more recent study from the Barcelona group also used EMG recordings; these investigators found subtle changes in recordings from the abdominal oblique muscles in patients with experimentally induced bloating and distension.[43] Although the exact clinical significance of surface EMG recordings on the abdominal wall remains unclear, it does seem reasonable to assume that some form of "accommodation reflex" involving relaxation of the anterior abdominal musculature is likely to be associated with the consumption of a meal. Thus, an exaggeration or abnormality of such a reflex might partly explain the phenomenon of distension in patients with IBS. Therefore, abdominal wall function is certainly worthy of further investigation to assess its possible role in this setting.

Carbohydrate malabsorption is also sometimes cited as a possible factor causing bloating in a subgroup of patients with IBS. Whereas lactase deficiency is relatively prevalent, and therefore frequently found when specifically looked for in patients with IBS, whether this is of clinical importance is disputed. One placebo-controlled study supplementing patients' diet with lactase found that IBS symptoms were independent of treatment with this enzyme,[44] suggesting that there was no causal link between lactose intolerance and IBS symptomatology. Sorbitol and fructose have also been implicated in some patients,[45] although malabsorption of these sugars is also probably equally common in healthy controls. Finally, fluid retention has been proposed as a possible cause of bloating; however, no changes in body weight have been found during bloating episodes, and therefore this mechanism seems unlikely to be of major importance.[12] The study by Maxton and colleagues[21] using CT scanning largely excluded the previously "popular" theories of abnormal diaphragmatic descent, increased lumbar lordosis, or voluntary abdominal protrusion. A study that directly compared anxiety levels between patients with functional bloating and inflammatory bowel disease suggested that anxiety was also an unimportant factor.[46]

How to Manage Patients With Bloating

The majority of patients complaining of bloating are ultimately diagnosed as suffering from one of the functional gastrointestinal disorders. However, it is important to exclude organic explanations when indicated. When extreme, distension can cause concern that conditions such as ascites or subacute obstruction are being overlooked, but it is usually possible to distinguish these conditions from bloating clinically, especially if the characteristic diurnal pattern associated with functional distension is present. Approaches to the diagnosis of functional gastrointestinal disorders have been reviewed in detail elsewhere and will not be discussed at length here.[47] Whether tests for bacterial overgrowth or carbohydrate malabsorption should be routinely undertaken in patients with bloating is controversial, although these are unlikely to harm the patient and may sometimes be useful for symptomatic management. The possibility of celiac disease also needs to be considered, especially in high prevalence areas, and serologic testing, which is now widely available, has made screening for this condition much easier. Very rarely, specific tests for other forms of malabsorption, such as pancreatic insufficiency, may be necessary, although overinvestigation should be avoided.

There is no completely satisfactory treatment for bloating in patients with functional gastrointestinal disorders, although in most cases, some improvement in this symptom can be achieved. Patients seen in hospital practice have often been advised to take a high-fiber diet that is frequently detrimental,[48] and consequently, we routinely recommend a trial of wheat-fiber withdrawal which seems to reduce bloating and distension in a good proportion of cases. Other dietary modifications may also help -- for example, limitation of fat intake, avoiding carbonated drinks, and excluding artificial sweeteners. A discussion of dietary treatments for IBS can be found elsewhere.[49] It is not known whether exercises to strengthen the anterior abdominal musculature would be helpful despite evidence that these muscles may be weak in patients with IBS.[12]

A number of medications aimed at limiting intestinal gas volumes have been suggested for use in patients with bloating, although experience with these agents has largely been disappointing. Simethicone, an antisurfactant is frequently used by patients, but there appears to be little objective evidence of benefit over placebo.[50] Beano, which is an alpha-galactosidase preparation capable of digesting complex sugars, has been shown to reduce flatus volume and frequency, but not bloating.[51] Activated charcoal is frequently recommended for gas-related complaints, but evidence for any beneficial effect has largely been conflicting.[52,53] Rifaximin, which is a nonabsorbable antibiotic, has been shown to reduce gas production, flatus events, and abdominal distension, although, paradoxically, no improvement in bloating was reported in this study.[33] In another study from the Barcelona group which is of potential therapeutic importance, it was reported that intravenous neostigmine was capable of reversing both gas retention and symptoms following the gas challenge test.[54]

Antispasmodics warrant a trial, although there is little evidence that they have particular utility in reducing bloating.[55] Treating constipation can be helpful, but it is important to note that some laxatives such as lactulose and fermentable fiber preparations may actually worsen bloating and gas-related symptoms. Approximately one third of patients with functional gastrointestinal disorders improve with antidepressants, yet again, no studies have specifically addressed the effect of this class of drug on bloating.[56] Various psychological therapies have also been found to be helpful in improving IBS symptomatology and there is evidence that hypnotherapy can improve bloating.[57,58] However, these treatments vary considerably in their local availability and by their very nature can only be offered to restricted numbers of patients with more severe symptoms.

Finally, it is of considerable interest that tegaserod, a new 5-HT4 receptor partial agonist, has been shown to improve the symptom of bloating. Several large randomized, controlled trials have consistently demonstrated an improvement in bloating with this drug in patients with IBS,[59-61] and pooled data from a number of trials have confirmed this effect, suggesting that tegaserod may have specific utility for this indication.[62]


Bloating and distension may occasionally occur in apparently healthy individuals, but are much more common in patients with functional gastrointestinal disorders. Although it has been suggested that the term "bloating" should be used to describe how the patient feels, whereas the term "distension" is reserved for an actual increase in girth, it is important to appreciate that the 2 phenomena may not be precisely the same. Despite the prevalence of these symptoms, the pathophysiology is only just beginning to be discerned and is likely to be much more complex than attributable to just the accumulation of excessive quantities of gas. Until the underlying mechanisms are better understood, treatment will remain challenging; however, modification of diet, use of antidepressants, psychological therapies, or tegaserod may lead to improvement.


  1. Sandler RS, Stewart WF, Liberman JN, Ricci JA, Zorich NL. Abdominal pain, bloating, and diarrhea in the United States: prevalence and impact. Dig Dis Sci. 2000;45:1166-1171. Abstract

  2. Drossman DA, Li Z, Andruzzi E, et al. U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact. Dig Dis Sci. 1993;38:1569-1580. Abstract

  3. Drossman DA, Talley NJ, Thompson WG, Corazziari E, Whithead WE. Rome II: The functional gastrointestinal disorders: Diagnosis, pathophysiology and treatment; A multinational Consensus. McLean, Va: Degnon and Associates; 2000.

  4. Chang L, Lee OY, Naliboff B, Schmulson M, Mayer EA. Sensation of bloating and visible abdominal distension in patients with irritable bowel syndrome. Am J Gastroenterol. 2001;96:3341-3347. Abstract

  5. Hahn B, Watson M, Yan S, Gunput D, Heuijerjans J. Irritable bowel syndrome symptom patterns: frequency, duration, and severity. Dig Dis Sci. 1998;43:2715-2718. Abstract

  6. Lembo T, Naliboff B, Munakata J, et al. Symptoms and visceral perception in patients with pain-predominant irritable bowel syndrome. Am J Gastroenterol. 1999;94:1320-1326. Abstract

  7. Johnsen R, Jacobsen BK, Forde OH. Associations between symptoms of irritable colon and psychological and social conditions and lifestyle. Br Med J (Clin Res Ed). 1986;292:1633-1635. Abstract

  8. Heaton KW, Radvan J, Cripps H, Mountford RA, Braddon FE, Hughes AO. Defecation frequency and timing, and stool form in the general population: a prospective study. Gut. 1992;33:818-824. Abstract

  9. Smith RC, Greenbaum DS, Vancouver JB, et al. Gender differences in Manning criteria in the irritable bowel syndrome. Gastroenterology. 1991;100:591-595. Abstract

  10. Chang L, Heitkemper MM. Gender differences in irritable bowel syndrome. Gastroenterology. 2002;123:1686-1701. Abstract

  11. Thompson WG. Gender differences in irritable bowel symptoms. Eur J Gastroenterol Hepatol. 1997;9:299-302. Abstract

  12. Sullivan SN. A prospective study of unexplained visible abdominal bloating. N Z Med J. 1994;107:428-430. Abstract

  13. Talley NJ, Dennis EH, Schettler-Duncan VA, Lacy BE, Olden KW, Crowell MD. Overlapping upper and lower gastrointestinal symptoms in irritable bowel syndrome patients with constipation or diarrhea. Am J Gastroenterol. 2003;98:2454-2459. Abstract

  14. Schmulson M, Lee OY, Chang L, Naliboff B, Mayer EA. Symptom differences in moderate to severe IBS patients based on predominant bowel habit. Am J Gastroenterol. 1999;94:2929-2935. Abstract

  15. Ragnarsson G, Bodemar G. Division of the irritable bowel syndrome into subgroups on the basis of daily recorded symptoms in two outpatients samples. Scand J Gastroenterol. 1999;34:993-1000. Abstract

  16. Lee OY, Mayer EA, Schmulson M, Chang L, Naliboff B. Gender-related differences in IBS symptoms. Am J Gastroenterol. 2001;96:2184-2193. Abstract

  17. Heitkemper MM, Jarrett M, Cain KC, Shaver J, Walker E, Lewis L. Daily gastrointestinal symptoms in women with and without a diagnosis of IBS. Dig Dis Sci. 1995;40:1511-1519. Abstract

  18. Manning AP, Thompson WG, Heaton KW, Morris AF. Towards positive diagnosis of the irritable bowel. Br Med J. 1978;2:653-654. Abstract

  19. Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Muller-Lissner SA. Functional bowel disorders and functional abdominal pain. Gut. 1999;45(suppl 2):II43-II47. Abstract

  20. Taub E, Cuevas JL, Cook EW, III, Crowell M, Whitehead WE. Irritable bowel syndrome defined by factor analysis. Gender and race comparisons. Dig Dis Sci. 1995;40:2647-2655. Abstract

  21. Maxton DG, Martin DF, Whorwell PJ, Godfrey M. Abdominal distension in female patients with irritable bowel syndrome: exploration of possible mechanisms. Gut. 1991;32:662-664. Abstract

  22. Lewis MJ, Reilly B, Houghton LA, Whorwell PJ. Ambulatory abdominal inductance plethysmography: towards objective assessment of abdominal distension in irritable bowel syndrome. Gut. 2001;48:216-220. Abstract

  23. Reilly BP, Bolton MP, Lewis MJ, Houghton LA, Whorwell PJ. A device for 24 hour ambulatory monitoring of abdominal girth using inductive plethysmography. Physiol Meas. 2002;23:661-670. Abstract

  24. Lea R, Houghton LA, Reilly B, Whorwell PJ. Is abdominal bloating related to physical distension in patients with irritable bowel syndrome (IBS)? Gastroenterology. 2003;124:A14.

  25. Basilisco G, Marino B, Passerini L, Ogliari C. Abdominal distension after colonic lactulose fermentation recorded by a new extensometer. Neurogastroenterol Motil. 2003;15:427-433. Abstract

  26. Lasser RB, Bond JH, Levitt MD. The role of intestinal gas in functional abdominal pain. N Engl J Med. 1975;293:524-526. Abstract

  27. Serra J, Azpiroz F, Malagelada JR. Impaired transit and tolerance of intestinal gas in the irritable bowel syndrome. Gut. 2001;48:14-19. Abstract

  28. Koide A, Yamaguchi T, Odaka T, et al. Quantitative analysis of bowel gas using plain abdominal radiograph in patients with irritable bowel syndrome. Am J Gastroenterol. 2000;95:1735-1741. Abstract

  29. King TS, Elia M, Hunter JO. Abnormal colonic fermentation in irritable bowel syndrome. Lancet. 1998;352:1187-1189. Abstract

  30. Levitt MD, Furne J, Olsson S. The relation of passage of gas an abdominal bloating to colonic gas production. Ann Intern Med. 1996;124:422-424. Abstract

  31. Pimentel M, Chow EJ, Lin HC. Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome. Am J Gastroenterol. 2000;95:3503-3506. Abstract

  32. Pimentel M, Chow EJ, Lin HC. Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. a double-blind, randomized, placebo-controlled study. Am J Gastroenterol. 2003;98:412-419. Abstract

  33. Di Stefano M, Strocchi A, Malservisi S, Veneto G, Ferrieri A, Corazza GR. Non-absorbable antibiotics for managing intestinal gas production and gas-related symptoms. Aliment Pharmacol Ther. 2000;14:1001-1008. Abstract

  34. Nobaek S, Johansson ML, Molin G, Ahrne S, Jeppsson B. Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with irritable bowel syndrome. Am J Gastroenterol. 2000;95:1231-1238. Abstract

  35. O'Sullivan MA, O'Morain CA. Bacterial supplementation in the irritable bowel syndrome. A randomised double-blind placebo-controlled crossover study. Dig Liver Dis. 2000;32:294-301. Abstract

  36. Serra J, Azpiroz F, Malagelada JR. Intestinal gas dynamics and tolerance in humans. Gastroenterology. 1998;115:542-550. Abstract

  37. Serra J, Salvioli B, Azpiroz F, Malagelada JR. Lipid-induced intestinal gas retention in irritable bowel syndrome. Gastroenterology. 2002;123:700-706. Abstract

  38. Serra J, Azpiroz F, Malagelada JR. Gastric distension and duodenal lipid infusion modulate intestinal gas transit and tolerance in humans. Am J Gastroenterol. 2002;97:2225-2230. Abstract

  39. Serra J, Azpiroz F, Malagelada JR. Mechanisms of intestinal gas retention in humans: impaired propulsion versus obstructed evacuation. Am J Physiol Gastrointest Liver Physiol. 2001;281:G138-G143. Abstract

  40. Lea R, Reilly B, Whorwell PJ, Houghton LA. Abdominal bloating in the absence of physical distension is related to increased visceral sensitivity. Gastroenterology. 2004;126:A53.

  41. Lea R, Houghton LA, Reilly B, Whorwell PJ. Abdominal distension in irritable bowel syndrome (IBS): is there a relationship to visceral sensitivity? Gastroenterology. 2003;124:A398.

  42. McManis PG, Newall D, Talley NJ. Abdominal wall muscle activity in irritable bowel syndrome with bloating. Am J Gastroenterol. 2001;96:1139-1142. Abstract

  43. Tremolaterra F, Serra J, Azpiroz F, Villoria A, Malagelada J. Bloating and abdominal wall dystony. Gastroenterology. 2004;126:A53.

  44. Lisker R, Solomons NW, Perez BR, Ramirez MM. Lactase and placebo in the management of the irritable bowel syndrome: a double-blind, cross-over study. Am J Gastroenterol. 1989; 84:756-762. Abstract

  45. Fernandez-Banares F, Esteve-Pardo M, de Leon R, et al. Sugar malabsorption in functional bowel disease: clinical implications. Am J Gastroenterol. 1993;88:2044-2050. Abstract

  46. Song JY, Merskey H, Sullivan S, Noh S. Anxiety and depression in patients with abdominal bloating. Can J Psychiatry. 1993;38:475-479. Abstract

  47. Olden KW. Diagnosis of irritable bowel syndrome. Gastroenterology. 2002;122:1701-1714. Abstract

  48. Francis CY, Whorwell PJ. Bran and irritable bowel syndrome: time for reappraisal. Lancet. 1994;344:39-40. Abstract

  49. Lea R, Whorwell PJ. Dietary treatment of the irritable bowel syndrome. Curr Treatment Options Gastroenterology. 2004; in press.

  50. Friis H, Bode S, Rumessen JJ, Gudmand-Hoyer E. Effect of simethicone on lactulose-induced H2 production and gastrointestinal symptoms. Digestion. 1991;49:227-230. Abstract

  51. Ganiats TG, Norcross WA, Halverson AL, Burford PA, Palinkas LA. Does Beano prevent gas? A double-blind crossover study of oral alpha-galactosidase to treat dietary oligosaccharide intolerance. J Fam Pract. 1994;39:441-445. Abstract

  52. Hall RG Jr, Thompson H, Strother A. Effects of orally administered activated charcoal on intestinal gas. Am J Gastroenterol. 1981;75:192-196. Abstract

  53. Potter T, Ellis C, Levitt M. Activated charcoal: in vivo and in vitro studies of effect on gas formation. Gastroenterology. 1985;88:620-624. Abstract

  54. Caldarella MP, Serra J, Azpiroz F, Malagelada JR. Prokinetic effects in patients with intestinal gas retention. Gastroenterology. 2002;122:1748-1755. Abstract

  55. Poynard T, Regimbeau C, Benhamou Y. Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 2001;15:355-361. Abstract

  56. Jackson JL, O'Malley PG, Tomkins G, Balden E, Santoro J, Kroenke K. Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis. Am J Med. 2000;108:65-72. Abstract

  57. Whorwell PJ, Prior A, Faragher EB. Controlled trial of hypnotherapy in the treatment of severe refractory irritable-bowel syndrome. Lancet. 1984;2:1232-1234. Abstract

  58. Gonsalkorale WM, Miller V, Afzal A, Whorwell PJ. Long term benefits of hypnotherapy for irritable bowel syndrome. Gut. 2003;52:1623-1629. Abstract

  59. Muller-Lissner SA, Fumagalli I, Bardhan KD, et al. Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. Aliment Pharmacol Ther. 2001;15:1655-1666. Abstract

  60. Novick J, Miner P, Krause R, et al. A randomized, double-blind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation. Aliment Pharmacol Ther. 2002;16:1877-1888. Abstract

  61. Kellow J, Lee OY, Chang FY, et al. An Asia-Pacific, double blind, placebo controlled, randomised study to evaluate the efficacy, safety, and tolerability of tegaserod in patients with irritable bowel syndrome. Gut. 2003;52:671-676. Abstract

  62. Whorwell PJ, Ruegg P, Earnest D, Dunger-Baldauf C. Tegaserod significantly improves bloating in female irritable bowel syndrome patients with constipation. Gastroenterology. 2004;126:A643.