Dietary Triggers of Abdominal Symptoms in Patients With Irritable Bowel Syndrome: Randomized Placebo-Controlled Evidence

      Background & Aims: Observational studies suggest dietary fructose restriction might lead to sustained symptomatic response in patients with irritable bowel syndrome (IBS) and fructose malabsorption. The aims of this study were first to determine whether the efficacy of this dietary change is due to dietary fructose restriction and second to define whether symptom relief was specific to free fructose or to poorly absorbed short-chain carbohydrates in general. Methods: The double-blinded, randomized, quadruple arm, placebo-controlled rechallenge trial took place in the general community. The 25 patients who had responded to dietary change were provided all food, low in free fructose and fructans, for the duration of the study. Patients were randomly challenged by graded dose introduction of fructose, fructans, alone or in combination, or glucose taken as drinks with meals for maximum test period of 2 weeks, with at least 10-day washout period between. For the main outcome measures, symptoms were monitored by daily diary entries and responses to a global symptom question. Results: Seventy percent of patients receiving fructose, 77% receiving fructans, and 79% receiving a mixture reported symptoms were not adequately controlled, compared with 14% receiving glucose (P ≤ 0.002, McNemar test). Similarly, the severity of overall and individual symptoms was significantly and markedly less for glucose than other substances. Symptoms were induced in a dose-dependent manner and mimicked previous IBS symptoms. Conclusions: In patients with IBS and fructose malabsorption, dietary restriction of fructose and/or fructans is likely to be responsible for symptomatic improvement, suggesting efficacy is due to restriction of poorly absorbed short-chain carbohydrates in general.

      Abbreviations used in this paper:

      FM (fructose malabsorption), FODMAPs (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols), IBS (irritable bowel syndrome), ITT (intention to treat), PP (per protocol), VAS (visual analogue scale)
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        • Drossman D.A.
        • 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
        • Leong S.A.
        • Barghout V.
        • Birnbaum H.G.
        • et al.
        The economic consequences of irritable bowel syndrome: a US employer perspective.
        Arch Intern Med. 2003; 163: 929-935
        • Burton W.N.
        • Conti D.J.
        • Chen C.Y.
        • et al.
        The role of health risk factors and disease on worker productivity.
        J Occup Environ Med. 1999; 41: 863-877
        • Delvaux M.
        Alterations of sensori-motor functions of the digestive tract in the pathophysiology of irritable bowel syndrome.
        Best Pract Res Clin Gastroenterol. 2004; 18: 747-771
        • Robayo-Torres C.C.
        • Quezada-Calvillo R.
        • Nichols B.L.
        Disaccharide digestion: clinical and molecular aspects.
        Clin Gastroenterol Hepatol. 2006; 3: 276-287
        • Gibson P.R.
        • Shepherd S.J.
        Personal view: food for thought—Western lifestyle and susceptibility to Crohn's disease: the FODMAP hypothesis.
        Aliment Pharmacol Ther. 2005; 21: 1399-1409
        • Ravich W.J.
        • Bayless T.M.
        • Thomas M.
        Fructose: Incomplete intestinal absorption in humans.
        Gastroenterology. 1983; 84: 26-29
        • Swagerty D.L.
        • Walling A.
        • Klein R.
        Lactose intolerance.
        Am Fam Phys. 2002; 65: 1845-1850
        • Hyams J.S.
        Sorbitol intolerance: an unappreciated cause of functional gastrointestinal complaints.
        Gastroenterology. 1983; 84: 30-33
        • Bach Knudsen K.E.
        • Hessov I.B.
        Recovery of inulin from Jerusalem artichoke (Helianthus tuberosus L.) in the small intestine of man.
        Br J Nutr. 1995; 74: 101-113
        • Rumessen J.J.
        Fructose and food related carbohydrates: sources, intake, absorption and clinical implications.
        Scand J Gastroenterol. 1992; 27: 819-828
        • Park Y.K.
        • Yetley E.A.
        Intakes and food sources of fructose in the United States.
        Am J Clin Nutr. 1993; 58: 737S-747S
        • Bray G.A.
        • Nielsen S.J.
        • Popkin B.M.
        Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity.
        Am J Clin Nutr. 2004; 79: 537-543
        • van Loo J.
        • Coussement P.
        • de Leenheer L.
        • et al.
        On the presence of inulin and oligofructose as natural ingredients in the Western diet.
        Crit Rev Food Sci Nutr. 1995; 35: 525-552
        • Moshfegh A.J.
        • Friday J.E.
        • Goldman J.P.
        • et al.
        Presence of inulin and oligofructose in the diets of Americans.
        J Nutr. 1999; 129: S1407-S1411
        • Boeckner L.S.
        • Schnepf M.I.
        • Tungland B.C.
        Inulin: a review of nutritional and health implications.
        Adv Food Nutr Res. 2001; 42: 1-63
        • Roberfroid M.B.
        Concepts in functional foods; the case of inulin and oligofructose.
        J Nutr. 1999; 129: S1398-S1401
        • Kaur N.
        • Gupta A.K.
        Applications of inulin and oligo-fructose in health and nutrition.
        Bioscience. 2002; 27: 703-714
        • Vernia P.
        • Ricciardi M.R.
        • Frandina C.
        • et al.
        Lactose malabsorption and irritable bowel syndrome: effect of a long-term lactose-free diet.
        Ital J Gastroenterol Hepatol. 1995; 27: 117-121
        • Fernandez-Banares F.
        • Rosinach M.
        • Esteve M.
        • et al.
        Sugar malabsorption in functional abdominal bloating: a pilot study on the long term effect of dietary treatment.
        Clin Nutr. 2006; 25: 824-831
        • Goldstein R.
        • Braverman D.
        • Stankiewicz H.
        Carbohydrate malabsorption and the effect of dietary restriction on symptoms of irritable bowel syndrome and functional bowel complaints.
        Isr Med Assoc J. 2000; 2: 583-587
        • Shepherd S.J.
        • Gibson P.R.
        Fructose malabsorption and symptoms of irritable bowel syndrome: guidelines for effective dietary management.
        J Am Diet Assoc. 2006; 106: 1631-1639
        • Barrett J.S.
        • Gibson P.R.
        Clinical ramifications of malabsorption of fructose and other short-chain carbohydrates.
        Pract Gast. 2007; 31: 51-65
        • Spiller R.
        Problems and challenges in the design of irritable bowel syndrome clinical trials: experience from published trials.
        Am J Med. 1999; 107: 91S-97S
        • Shepherd S.
        • Willett I.
        • Fone D.
        • et al.
        The value of the ‘fructose malabsorption’ (FM) diet and the fructose breath hydrogen test in patients with irritable bowel syndrome (IBS).
        J Gastroenterol Hepatol. 2003; 18: B126
        • Drossman D.A.
        The functional gastrointestinal disorders and the Rome II process.
        Gut. 1999; 45: II1-II5
        • Gibson P.R.
        • Newnham E.
        • Barrett J.S.
        • et al.
        Review article: fructose malabsorption and the bigger picture.
        Aliment Pharmacol Ther. 2007; 25: 349-363
        • Smith A.
        • Kellett E.
        • Schmerlab Y.
        The Australian guide to healthy eating: background information for nutrition educators.
        Adelaide: Children's Health Development Foundation. 1998; : 18-20
        • Akehurst R.
        • Kaltenthaler E.
        Treatment of irritable bowel syndrome: a review of randomised control trials.
        Gut. 2001; 48: 272-282
        • Klein K.
        Controlled treatment trials in the irritable bowel syndrome: a critique.
        Gastroenterology. 1988; 95: 232-241
        • Truswell A.
        • Seach J.
        • Throburn A.
        Incomplete absorption of pure fructose in healthy subjects and the facilitating effect of glucose.
        Am J Clin Nutr. 1998; 48: 1424-1430
        • Rumessen J.J.
        • Gudmand-Hoyer E.
        Absorption capacity of fructose in healthy adults: comparison with sucrose and its constituent monosaccharides.
        Gut. 1986; 27: 1161-1168
        • Chaudhuri T.K.
        • Fink S.
        Gastric emptying in human disease states.
        Am J Gastroenterol. 1991; 5: 533-558
        • Masden J.
        • Linnet J.
        • Rumessen J.J.
        Effect of nonabsorbed amounts of a fructose-sorbitol mixture on small intestinal transit in healthy volunteers.
        Dig Dis Sci. 2006; 51: 147-153
        • Langlands S.J.
        • Hopkins M.J.
        • Coleman N.
        • et al.
        Prebiotic carbohydrates modify the mucosa associated microflora of the human large bowel.
        Gut. 2004; 53: 1610-1616
        • Piche T.
        • des Varannes S.B.
        • Sacher-Huvelin S.
        • et al.
        Colonic fermentation influences lower esophageal sphincter function in gastroesophageal reflux disease.
        Gastroenterology. 2003; 124: 894-902
        • Ten Bruggencate S.J.
        • Bovee-Oudenhoven I.M.
        • Lettink-Wissink M.L.
        • et al.
        Dietary fructooligosaccharides affect intestinal barrier function in healthy men.
        J Nutr. 2006; 136: 70-74
        • Scholtens P.A.
        • Alles M.S.
        • Willemsen L.E.
        • et al.
        Dietary fructo-oligosaccharides in healthy adults do not negatively affect faecal cytotoxicity: a randomised, double-blind, placebo-controlled cross-over trial.
        Br J Nutr. 2006; 95: 1143-1149
        • Andersson H.
        • Ellegard L.
        • Boseaus I.
        Nondigestibility characteristics of inulin and oligofructose in humans.
        J Nutr. 1999; 129: 1428S-1430S
        • Rumessen J.J.
        • Gudmand-Hoyer E.
        Functional bowel disease: malabsorption and abdominal distress after ingestion of fructose, sorbitol and fructose-sorbitol mixtures.
        Gastroenterology. 1988; 95: 694-700
        • 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
        • Symons P.
        • Jones M.P.
        • Kellow J.E.
        Symptom provocation in irritable bowel syndrome: effects of differing doses of fructose-sorbitol.
        Scand J Gastroenterol. 1992; 27: 940-944