Fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), but not gluten, elicit modest symptoms of irritable bowel syndrome: a double-blind, placebo-controlled, randomized three-way crossover trial

Elise Nordin, Carl Brunius, Rikard Landberg, Per M Hellström, Elise Nordin, Carl Brunius, Rikard Landberg, Per M Hellström

Abstract

Background: Irritable bowel syndrome (IBS) has been associated with diets rich in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), and gluten. Most previous studies have been single-blind and have focused on the elimination of FODMAPs or provocation with single FODMAPs. The effect of gluten is unclear, large trials isolating the effect of gluten from that of FODMAPs are needed.

Objectives: The aims of this study were to ensure high intakes of a wide range of FODMAPs, gluten, or placebo, and to evaluate the effects on IBS symptoms using the IBS-severity scoring system (IBS-SSS).

Methods: The study was carried out with a double-blind, placebo-controlled, randomized 3-way crossover design in a clinical facility in Uppsala from September 2018 to June 2019. In all, 110 participants fulfilling the IBS Rome IV criteria, with moderate to severe IBS, were randomly assigned; 103 (90 female, 13 male) completed the trial. Throughout, IBS participants maintained a diet with minimal FODMAP content and no gluten. Participants were block-randomly assigned to 1-wk interventions with FODMAPs (50 g/d), gluten (17.3 g/d), or placebo, separated by 1-wk washout. All participants who completed ≥1 intervention were included in the intention-to-treat analysis.

Results: In participants with IBS (n = 103), FODMAPs caused higher IBS-SSS scores (mean 240 [95% CI: 222, 257]) than placebo (198 [180, 215]; P = 0.00056) or gluten (208 [190, 226]; P = 0.013); no differences were found between the placebo and gluten groups (P = 1.0). There were large interindividual differences in IBS-SSS scores associated with treatment. No adverse events were reported.

Conclusion: In participants with IBS, FODMAPs had a modest effect on typical IBS symptoms, whereas gluten had no effect. The large interindividual differences in responses to the interventions warrant further detailed studies to identify possible underlying causes and enable individual prediction of responses. This trial was registered at www.clinicaltrials.gov as NCT03653689.

Keywords: FODMAPs; crossover trial; diet; double-blind; fermentation; functional gastrointestinal disorder; gluten; irritable bowel syndrome; polyols; saccharides.

© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1
FIGURE 1
Study design with the 3 intervention sequences used. A, FODMAPs; B, gluten; C, placebo in blocks of 12; FODMAPs, fermentable oligo-, di-, monosaccharides, and polyols.
FIGURE 2
FIGURE 2
Flow chart of participants by sequence and food intervention period. A, FODMAPs; B, gluten; C, placebo in blocks of 12; FODMAPs, fermentable oligo-, di-, monosaccharides, and polyols.
FIGURE 3
FIGURE 3
Percentage of participants with an increase in total IBS-SSS score of >50 points, or >100 points, for FODMAPs, gluten, and placebo interventions compared with the respective washout periods. Data were analyzed with McNemar's test. FODMAPs, fermentable oligo-, di-, monosaccharides, and polyols; IBS-SSS, irritable bowel syndrome-severity scoring system.

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