Abstract
Introduction
The prevalence of irritable bowel syndrome (IBS) varies depending on the criteria used to diagnose it, but it ranges from about 5% to 20%. IBS is associated with abnormal gastrointestinal motor function and enhanced visceral perception, as well as psychosocial and genetic factors. People with IBS often have other bodily and psychiatric symptoms, and have an increased likelihood of having unnecessary surgery compared with people without IBS.
Methods and outcomes
We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of dietary modification (gluten-free diet, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols [FODMAPs]) in people with irritable bowel syndrome? We searched Medline, Embase, The Cochrane Library, and other important databases up to June 2014 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review).
Results
At this update, searching of electronic databases retrieved 33 studies. After deduplication and removal of conference abstracts, 19 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 14 studies and the further review of five full publications. Of the five full articles evaluated, three RCTs were included. Based upon their own search, the contributor(s) added two additional RCTs that did not meet BMJ Clinical Evidence inclusion criteria; these have been added to the Comment section. We performed a GRADE evaluation of the quality for two PICO combinations.
Conclusions
In this systematic overview, we categorised the efficacy for two interventions based on information relating to the effectiveness and safety of dietary modification (gluten-free diet or a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols [FODMAPs]).
Key Points
The key features of irritable bowel syndrome (IBS) are chronic, recurrent abdominal pain or discomfort, associated with disturbed bowel habit, in the absence of any structural abnormality to account for these symptoms.
The prevalence of IBS varies depending on the criteria used to diagnose it, but it ranges from about 5% to 20%.
IBS is associated with abnormal GI motor function, enhanced visceral perception, abnormalities in central pain processing, and altered gut flora, as well as psychosocial and genetic factors.
People with IBS often have other bodily and psychiatric symptoms, and have an increased likelihood of having unnecessary surgery compared with people without IBS.
A positive symptom-based diagnosis and a graded general treatment approach are cornerstones in the management of people with IBS.
Pharmacological agents, including antispasmodics, antidepressants, and secretagogues, are effective therapies in IBS, but none have been shown to alter the long-term natural history of the condition.
Some people with IBS believe that certain foods trigger their symptoms and would, therefore, rather try dietary modification as a first-line approach instead of taking drugs, which may have side effects.
We searched for RCTs and systematic reviews of RCTs on gluten-free diets or diets low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (low- FODMAP diet) compared with normal diet or general dietary advice, or compared with standard usual care (e.g., antispasmodic treatment).
We don't know if a gluten-free diet is more effective than a normal gluten-containing diet in controlling symptoms in IBS, as there were few studies, and results were inconsistent.
RCTs recruited people with IBS, in whom coeliac disease had already been excluded by either serological testing or small intestinal biopsy. The RCTs were conducted in specialist centres, so the results may not be generalisable to patients seen in primary care.
Adverse events are unlikely in the short-term and, for people who are keen to avoid pharmacological therapies due to concerns about side effects (particularly those in whom pain or bloating is the predominant symptom), a trial of a gluten-free diet, instituted with the help of a trained dietitian, may be worthwhile.
We don't know if a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (low-FODMAP diet) is more effective than a normal diet in controlling symptoms in IBS, as there was only one trial providing evidence of low quality for a clinically significant benefit.
As with gluten-free diets, adverse events are unlikely in the short-term and, for people who are keen to avoid pharmacological therapies due to concerns about side effects (particularly those in whom pain or bloating is the predominant symptom), a trial of a low-FODMAP diet may be worthwhile.
Clinical context
General background
Irritable bowel syndrome (IBS) is a highly prevalent chronic condition. The key features of IBS are chronic, recurrent abdominal pain or discomfort, associated with disturbed bowel habit, in the absence of any structural abnormality to account for these symptoms.
Focus of the review
While some pharmacological therapies (including antispasmodic drugs, antidepressants, and secretagogues) are effective, none have been proven to alter the long-term natural history of the disorder. Some patients with IBS would rather try out alternative non-pharmacological therapies. Partly as a result of this, over the last 5 years or so, interest has turned towards assessing the efficacy of dietary interventions in IBS. This overview has focused on examining the evidence available for two such dietary modifications, a gluten-free diet and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs).
Comments on evidence
There is, as yet, insufficient evidence to make firm judgements on whether gluten-free diet is more effective than a normal gluten-containing diet in controlling symptoms in IBS. Ideally, larger RCTs are required, although conducting dietary intervention trials in large numbers of patients is difficult. The RCTs we found included small numbers of participants and were conducted in specialist centres, so the results may not be generalisable to patients seen in primary care. For diets low in FODMAPs, there is equally insufficient and low-quality evidence; although, one small cross-over RCT suggests that they may be more effective at improving gastrointestinal symptoms in people with IBS compared with a normal diet.
Search and appraisal summary
The literature search was carried out in June 2014. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the overview, please see the Methods section. Searching of electronic databases retrieved 33 studies. After deduplication and removal of conference abstracts, 19 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 14 studies and the further review of five full publications. Of the five full articles evaluated, three RCTs were included. Based upon their own search, the contributor(s) added two additional RCTs that did not meet BMJ Clinical Evidence inclusion criteria to the Comment section.
Additional information
Despite the lack of evidence, for people who feel that their symptoms are worse with gluten-containing foods, a trial of a gluten-free diet is not unreasonable; particularly. in a patient who is keen to avoid drugs and their potential side effects. This would need the involvement of a trained registered dietitian. Similarly, as adverse events are unlikely, a trial of a low-FODMAP diet may be worthwhile in patients with IBS who are keen to avoid pharmacological therapies due to concerns about side effects in the short-term, although it should be noted that the long-term consequences of restrictive diets such as these, in terms of their effect on nutritional status and general health, is unknown.
About this condition
Definition
Irritable bowel syndrome (IBS) is a chronic functional condition of the lower GI tract characterised by abdominal pain or discomfort and disordered bowel habit (diarrhoea, constipation, or fluctuation between the two). There is no known structural or biochemical explanation for the symptoms. Symptom-based criteria, such as the Manning criteria (see table 1 ) and the latest revision of the Rome criteria, the Rome III criteria (see table 2 ), aid diagnosis, but their main use is in recruiting patients for clinical trials. The Rome III criteria subcategorise IBS according to predominant symptom (diarrhoea, constipation, or alternating bowel habit). In practice, the division between constipation-predominant and diarrhoea-predominant IBS may not be clear-cut in all people, particularly as individuals often change subcategory during follow-up. Restriction of trial entry to a subcategory of IBS limits the generalisability of some RCT results.
Table 1.
Manning criteria
| Recurrent abdominal pain and 2 or more of the following: |
| - Relief of pain with defecation |
| - More frequent stools at the onset of pain |
| - Looser stools at the onset of pain |
| - Visible abdominal distension |
| - Passage of mucus per rectum |
| - A sensation of incomplete evacuation |
Table 2.
Rome III criteria
| Recurrent abdominal pain or discomfort at least 3 days a month in the past 3 months, with symptom onset at least 6 months before diagnosis, associated with 2 or more of the following: |
| - Improvement with defecation |
| - Onset associated with a change in frequency of stool |
| - Onset associated with a change in form (appearance) of stool |
Incidence/ Prevalence
Estimates of incidence and prevalence of IBS vary depending on the diagnostic criteria used to define the condition. One cross-sectional survey conducted in the UK defined IBS as recurrent abdominal pain on more than six occasions during the previous year plus two or more of the Manning criteria (see table 1 ). It estimated prevalence in the UK to be 17% overall, with 23% among women and 11% among men. An Australian study reported the prevalence to be 14% using the Manning criteria, 7% using the Rome I criteria, and 4% using the Rome II criteria. A cross-sectional survey of almost 4000 individuals in the UK with 10 years of follow-up estimated the incidence of IBS, defined using the Manning criteria, to be 1.5% a year.
Aetiology/ Risk factors
The pathophysiology of IBS is uncertain, and it is unlikely that a single unifying mechanism explains the condition, but abnormal GI motor function, enhanced visceral perception, and abnormalities of central pain processing seem important. Other determinants include psychosocial factors such as a history of childhood abuse, genetic predisposition, a history of exposure to acute enteric infection, so-called post-infectious IBS, and abnormalities in gut flora.
Prognosis
A retrospective study reviewed the medical records of people with IBS (112 people aged 20–64 years when diagnosed with IBS at the Mayo Clinic, US, between 1961 and 1963). IBS was defined as the presence of abdominal pain associated with either disturbed defecation or abdominal distension, and the absence of organic bowel disease. Over a 32-year period, less than 10% of people developed organic GI disease subsequently, and death rates were similar among people with IBS compared with age- and sex-matched controls. In another study conducted in the US, individuals meeting diagnostic criteria for IBS were followed up for between 10 and 13 years, during which time almost 50% had undergone subsequent investigation of the lower GI tract, yet this had not led to a revision of the diagnosis of IBS in any of the patients. Other investigators have reported that people with IBS are two to three times more likely to undergo unnecessary surgical procedures, such as cholecystectomy, hysterectomy, or appendicectomy.
Aims of intervention
To improve symptoms and reduce disability, with minimal adverse effects.
Outcomes
Symptom improvement, in particular, improvement in abdominal pain, constipation, diarrhoea, bloating, and urgency of defecation, measured using validated self-report instruments (including adequate relief, the Irritable Bowel Severity Scoring System, the Gastrointestinal Symptom Rating Scale, the Functional Bowel Disorder Severity Index, and the IBS Symptom Questionnaire); quality of life measured using validated instruments (including Quality of Life and Global Impact of IBS, the Irritable Bowel Syndrome Quality of Life Measurement, the Irritable Bowel Syndrome Quality of Life Questionnaire, the Digestive Health Status Instrument, the Functional Digestive Disorder Quality of Life Questionnaire, and the Irritable Bowel Syndrome Health-Related Quality-of-Life questionnaire); adverse effects.
Methods
Search strategy BMJ Clinical Evidence search and appraisal June 2014. Databases used to identify studies for this systematic review include: Medline 1966 to June 2014, Embase 1980 to June 2014, The Cochrane Database of Systematic Reviews, 2014, issue 6 (1966 to date of issue), the Database of Abstracts of Reviews of Effects (DARE), and the Health Technology Assessment (HTA) database. Inclusion criteria Study design criteria for inclusion in this review were systematic reviews and RCTs published in English, at least single-blinded, with no minimum sample size or maximum loss to follow-up. There was no minimum length of follow-up. We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. BMJ Clinical Evidence does not necessarily report every study found (e.g., every systematic review). Rather, we report the most recent, relevant and comprehensive studies identified through an agreed process involving our evidence team, editorial team, and expert contributors. Evidence evaluation A systematic literature search was conducted by our evidence team, who then assessed titles and abstracts, and finally selected articles for full text appraisal against inclusion and exclusion criteria agreed a priori with our expert contributors. In consultation with the expert contributors, studies were selected for inclusion and all data relevant to this overview extracted into the benefits and harms section of the overview. In addition, information that did not meet our predefined criteria for inclusion in the benefits and harms section, may have been reported in the 'Further information on studies' or 'Comment' section. Adverse effects All serious adverse effects, or those adverse effects reported as statistically significant, were included in the harms section of the overview. Pre-specified adverse effects identified as being clinically important were also reported, even if the results were not statistically significant. Although BMJ Clinical Evidence presents data on selected adverse effects reported in included studies, it is not meant to be, and cannot be, a comprehensive list of all adverse effects, contraindications, or interactions of included drugs or interventions. A reliable national or local drug database must be consulted for this information. Comment and Clinical guide sections In the Comment section of each intervention, our expert contributors may have provided additional comment and analysis of the evidence, which may include additional studies (over and above those identified via our systematic search) by way of background data or supporting information. As BMJ Clinical Evidence does not systematically search for studies reported in the Comment section, we cannot guarantee the completeness of the studies listed there or the robustness of methods. Our expert contributors add clinical context and interpretation to the Clinical guide sections where appropriate. Structural changes in this update At this update, we have removed the following previously reported question from this overview: What are the effects of treatments in people with irritable bowel syndrome?. We have added the following question: What are the effects of dietary modification (gluten-free diet; a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols [FODMAPs]) in people with irritable bowel syndrome? Data and quality To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). BMJ Clinical Evidence does not report all methodological details of included studies. Rather, it reports by exception any methodological issue or more general issue that may affect the weight a reader may put on an individual study, or the generalisability of the result. These issues may be reflected in the overall GRADE analysis. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table.
GRADE Evaluation of interventions for Irritable bowel syndrome: dietary interventions.
| Important outcomes | Quality of life, Symptom improvement | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of dietary modification (gluten-free diet; a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols [FODMAPs]) in people with irritable bowel syndrome? | |||||||||
| 2 (84) | Symptom improvement | Gluten-free diet versus normal diet or general dietary advice | 4 | –2 | –1 | 0 | 0 | Very low | Quality points deducted for sparse data and incomplete reporting of results; consistency point deducted as effect varied with symptom measured and at different time points |
| 1 (30) | Symptom improvement | Low-FODMAP diet versus normal diet | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and for not being able to differentiate pre-crossover and post-crossover results; directness point deducted for artificial situation in trial |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.
Glossary
- Very low-quality evidence
Any estimate of effect is very uncertain.
- Visual Analogue Scale (VAS)
A commonly used scale in pain assessment. It is a 10-cm horizontal or vertical line with word anchors at each end, such as 'no pain' and 'pain as bad as it could be'. The person is asked to make a mark on the line to represent pain intensity. This mark is converted to distance in either centimetres or millimetres from the 'no pain' anchor to give a pain score that can range from 0–10 cm or 0–100 mm.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Alexander Charles Ford, Leeds Gastroenterology Institute, St James’s University Hospital, and Leeds Institute of Biomedical and Clinical Sciences, Leeds, UK.
Per Olav Vandvik, Institute for Health and Society, University of Oslo and Acting Consultant, Department of Medicine, Innlandet Hospital Trust, Gjøvik, Norway.
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