A low FODMAP diet plus traditional dietary advice versus a low-carbohydrate diet versus pharmacological treatment in irritable bowel syndrome (CARIBS): a single-centre, single-blind, randomised controlled trial.

Dietary advice and medical treatments are recommended to patients with irritable bowel syndrome (IBS). Studies have not yet compared the efficacy of dietary treatment with pharmacological treatment targeting the predominant IBS symptom. We therefore aimed to compare the effects of two restrictive dietary treatment options versus optimised medical treatment in people with IBS. This single-centre, single-blind, randomised controlled trial was conducted in a specialised outpatient clinic at the Sahlgrenska University Hospital, Gothenburg, Sweden. Participants (aged ≥18 years) with moderate-to-severe IBS (Rome IV; IBS Severity Scoring System [IBS-SSS] ≥175) and no other serious diseases or food allergies were randomly assigned (1:1:1) by web-based randomisation to receive a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) plus traditional IBS dietary advice recommended by the UK National Institute for Health and Care Excellence (hereafter the LFTD diet), a fibre-optimised diet low in total carbohydrates and high in protein and fat (hereafter the low-carbohydrate diet), or optimised medical treatment based on predominant IBS symptom. Participants were masked to the names of the diets, but the pharmacological treatment was open-label. The intervention lasted 4 weeks, after which time participants in the dietary interventions were unmasked to their diets and encouraged to continue during 6 months' follow-up, participants in the LFTD group were instructed on how to reintroduce FODMAPs, and participants receiving pharmacological treatment were offered diet counselling and to continue with their medication. The primary endpoint was the proportion of participants who responded to the 4-week intervention, defined as a reduction of 50 or more in IBS-SSS relative to baseline, and was analysed per modified intention-to-treat (ie, all participants who started the intervention). Safety was analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02970591, and is complete. Between Jan 24, 2017, and Sept 2, 2021, 1104 participants were assessed for eligibility and 304 were randomly assigned. Ten participants did not receive their intervention after randomisation and thus 294 participants were included in the modified intention-to-treat population (96 assigned to the LFTD diet, 97 to the low-carbohydrate diet, and 101 to optimised medical treatment). 241 (82%) of 294 participants were women and 53 (18%) were men and the mean age was 38 (SD 13). After 4 weeks, 73 (76%) of 96 participants in the LFTD diet group, 69 (71%) of 97 participants in the low-carbohydrate diet group, and 59 (58%) of 101 participants in the optimised medical treatment group had a reduction of 50 or more in IBS-SSS compared with baseline, with a significant difference between the groups (p=0·023). 91 (95%) of 96 participants completed 4 weeks in the LFTD group, 92 (95%) of 97 completed 4 weeks in the low-carbohydrate group, and 91 (90%) of 101 completed 4 weeks in the optimised medical treatment group. Two individuals in each of the intervention groups stated that adverse events were the reason for discontinuing the 4-week intervention. Five (5%) of 91 participants in the optimised medical treatment group stopped treatment prematurely due to side-effects. No serious adverse events or treatment-related deaths occurred. Two 4-week dietary interventions and optimised medical treatment reduced the severity of IBS symptoms, with a larger effect size in the diet groups. Dietary interventions might be considered as an initial treatment for patients with IBS. Research is needed to enable personalised treatment strategies. The Healthcare Board Region Västra Götaland, the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, AFA Insurance, grants from the Swedish state, the Wilhelm and Martina Lundgren Science Foundation, Skandia, the Dietary Science Foundation, and the Nanna Swartz Foundation.

Nybacka S ，Törnblom H ，Josefsson A ，Hreinsson JP ，Böhn L ，Frändemark Å ，Weznaver C ，Störsrud S ，Simrén M ... -  《The Lancet Gastroenterology & Hepatology》

Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: a randomized controlled trial.

A diet with reduced content of fermentable short-chain carbohydrates (fermentable oligo-, di-, monosaccharides, and polyols [FODMAPs]) has been reported to be effective in the treatment of patients with irritable bowel syndrome (IBS). However, there is no evidence of its superiority to traditional dietary advice for these patients. We compared the effects of a diet low in FODMAPs with traditional dietary advice in a randomized controlled trial of patients with IBS. We performed a multi-center, parallel, single-blind study of 75 patients who met Rome III criteria for IBS and were enrolled at gastroenterology outpatient clinics in Sweden. Subjects were randomly assigned to groups that ate specific diets for 4 weeks-a diet low in FODMAPs (n = 38) or a diet frequently recommended for patients with IBS (ie, a regular meal pattern; avoidance of large meals; and reduced intake of fat, insoluble fibers, caffeine, and gas-producing foods, such as beans, cabbage, and onions), with greater emphasis on how and when to eat rather than on what foods to ingest (n = 37). Symptom severity was assessed using the IBS Symptom Severity Scale, and patients completed a 4-day food diary before and at the end of the intervention. A total of 67 patients completed the dietary intervention (33 completed the diet low in FODMAPs, 34 completed the traditional IBS diet). The severity of IBS symptoms was reduced in both groups during the intervention (P < .0001 in both groups before vs at the end of the 4-week diet), without a significant difference between the groups (P = .62). At the end of the 4-week diet period, 19 patients (50%) in the low-FODMAP group had reductions in IBS severity scores ≥50 compared with baseline vs 17 patients (46%) in the traditional IBS diet group (P = .72). Food diaries demonstrated good adherence to the dietary advice. A diet low in FODMAPs reduces IBS symptoms as well as traditional IBS dietary advice. Combining elements from these 2 strategies might further reduce symptoms of IBS. ClinicalTrials.gov ID NCT02107625.

Böhn L ，Störsrud S ，Liljebo T ，Collin L ，Lindfors P ，Törnblom H ，Simrén M ... -  《-》

Low fermentable oligo-di-mono-saccharides and polyols diet versus general dietary advice in patients with diarrhea-predominant irritable bowel syndrome: A randomized controlled trial.

Recent evidence indicates that new approach of the diet with low fermentable oligo-di-mono-saccharides and polyols (FODMAPs) may have an effective role in management of the patients with irritable bowel syndrome (IBS). We compared the results of low FODMAP diet with current dietary treatment, general dietary advices (GDA), on the clinical response in patients with diarrhea subtype of IBS (IBS-D). In this randomized, controlled, single-blind trial, we included 110 patients with IBS-D in two intervention groups. Participants were randomly assigned to the low FODMAP diet (n = 55) and GDA (n = 55) for 6 weeks after a 10-day screening period. Gastrointestinal symptoms and bowel habit status were evaluated using a symptom severity scoring system and Bristol stool form scale pre-intervention and post-intervention. Patients completed 3-day food diary before and after the intervention. Of 110 patients, 101 completed the dietary interventions. At the baseline, the nutrient intake, severity of symptoms, and demographic data were similar between two groups. After 6 weeks, the low FODMAP diet improves significantly overall gastrointestinal symptoms scores, stool frequency, and consistency versus GDA group (P < 0.001, P < 0.001, and P = 0.003, respectively). Compared with the baseline, both intervention groups expressed a significant reduction in overall scores of symptom severity scoring system, abdominal pain, distension, consistency, and frequency, but this reduction is greater in low FODMAP diet group. Both low FODMAP diet and GDA in patients with IBS-D led to adequate improvement of gastrointestinal symptoms for 6 weeks. However, the low FODMAP diet has greater benefits in IBS improvement.

Zahedi MJ ，Behrouz V ，Azimi M 《-》

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.

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. 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). 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. 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. 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.

Nordin E ，Brunius C ，Landberg R ，Hellström PM ... -  《-》

The Impact of a 4-Week Low-FODMAP and mNICE Diet on Nutrient Intake in a Sample of US Adults with Irritable Bowel Syndrome with Diarrhea.

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) has gained increasing acceptance for the treatment of irritable bowel syndrome but safety concerns have been raised regarding nutritional adequacy. Changes in nutrient intake during the elimination phase of the low-FODMAP diet remain predominantly unknown. To determine changes in the mean reported daily nutrient content before and after 4 weeks of a low-FODMAP diet vs modified National Institute for Health and Clinical Excellence (mNICE) dietary intervention and to identify nutritional inadequacies based on comparison to the Dietary Reference Intakes in patients with irritable bowel syndrome-diarrhea subtype. Post hoc analysis of a randomized controlled trial entailing a 4-week trial period comparing the low-FODMAP and mNICE diets. A total of 78 patients (41 low FODMAP and 37 mNICE) meeting the Rome III criteria for irritable bowel syndrome-diarrhea subtype were consecutively recruited from gastroenterology and primary care clinics at the University of Michigan Medical Center between October 2012 and November 2015. Participants randomized to the low-FODMAP arm were instructed to decrease their dietary intake of FODMAPs, whereas participants randomized to the mNICE intervention arm were instructed to eat small frequent meals, avoid trigger foods, and avoid excess alcohol and caffeine. Post hoc evaluation for presence of micronutrient deficiencies per Dietary Reference Intakes when implementing low-FODMAP vs mNICE dietary interventions. Dietary intake was analyzed via 3-day food diaries at baseline and during the final week of the assigned diet. A post hoc analysis utilizing either a t test or χ2 analysis was conducted between before and after data. Both diets resulted in fewer daily kilocalories consumed, fewer number of daily meals consumed, and less daily carbohydrate intake. Among the patients following the low-FODMAP diet, there was a statistically significant decrease from baseline in several micronutrients, which was not observed in the mNICE cohort. However, these differences in the low-FODMAP group remained significant only for riboflavin after correcting for calorie-adjusted nutrient intake. Comparing Dietary Reference Intakes of participants pre- and postintervention, fewer patients met the Dietary Reference Intakes for thiamin and iron in the low FODMAP group, and for calcium and copper in the mNICE group. During a 4-week dietary intervention, the mean daily intake of most micronutrients remained stable and within the Recommended Dietary Allowances for both diets. Although decrease in several micronutrients was observed with implementation of the low-FODMAP diet relative to the mNICE diet, most of these disappeared after adjusting for energy intake.

Eswaran S ，Dolan RD ，Ball SC ，Jackson K ，Chey W ... -  《Journal of the Academy of Nutrition and Dietetics》