Cut out FODMAPs, cut out IBS symptoms?

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that affects approximately 11% of the global population^[1]. It is associated with abdominal pain, bloating, excessive flatulence, and altered bowel habits, severely lowering a person’s quality of life. Functional gastrointestinal disorders like IBS are not caused by structural abnormalities such as ulcers or tumors. Rather, they occur as a result of an abnormally functioning GI tract. This makes it difficult to accurately diagnose a person because no biomarker can indicate whether or not someone is suffering from IBS. Thus, clinicians have to rely on the reports of patients and on a set of criteria that have evolved over time for diagnosis.

Although the cause of IBS is still not well understood, researchers have put forth several hypotheses. Some of these theories include infections of the GI tract^[2], psychological stress^[3], abnormalities in gut motility^[4], and gut-brain axis problems. Unfortunately, no cures currently exist for IBS. It is managed through various treatments such as 5-HT agonists/antagonists, antispasmodics, and antidepressants. These drugs can improve primary symptoms in some people, but they are unable to fully resolve disorders like IBS that are characterized by multiple symptoms. In addition to their limited use, there are several side effects associated with these drugs, so long-term use is not ideal.

As a result of these issues, researchers have investigated several alternative treatments as potential treatments for IBS. Patients suffering from IBS often report that particular foods worsen their symptoms more than others. Therefore, researchers have investigated various dietary interventions.

Dietary interventions that restrict specific food components, such as low-FODMAP diets, have been explored in several trials. FODMAP is an acronym that stands for "Fermentable, Oligo-saccharides, Di-saccharides, Mono-saccharides, and Polyols." These are short-chain carbohydrates that are poorly digested and absorbed^[5] in the small intestine. As a consequence, they travel to the large intestine, where they are fermented by the bacteria that colonize it. This breakdown of carbohydrates by bacteria results in the formation of gasses such as hydrogen and methane in all individuals. However, this phenomenon seems to be excessive in IBS sufferers. Therefore, restricting foods that are rich in these short-chain carbohydrates (some of these are listed in Figure 1) can potentially alleviate many of the symptoms prominent in people with IBS.

Source: The Monash University Low FODMAP diet

A previous systematic review^[6] conducted in 2015 showed that a low-FODMAP diet was somewhat effective in reducing the severity of symptoms associated with IBS. Six studies were included in that review and of those six, three were randomized controlled trials. The authors concluded that although a low-FODMAP was somewhat effective in treating IBS symptoms, more controlled trials with longer durations were needed to gauge the efficacy and safety of a low-FODMAP diet in treating IBS symptoms. The current study extends upon that review with further research, and also performs a meta-analysis to quantitatively summarize the findings.

Irritable bowel syndrome is a functional gastrointestinal disorder associated with abdominal pain, distension, and altered bowel habits. It is theorized to have a variety of causes. It is currently considered incurable by most medical practitioners, and is most commonly managed through the use of pharmaceuticals. Several alternative treatments have been explored as a result of this and one of these treatments, a low-FODMAP diet, has shown some effectiveness in reducing the severity of the symptoms associated with IBS.

This study was a systematic review and meta-analysis of six randomized controlled trials and sixteen non-randomized studies, which evaluated the effectiveness of a low-FODMAP diet in reducing symptoms associated with IBS. In the controlled trials, a low-FODMAP diet was generally compared to a control diet, which varied from study to study. In some studies, the control diet was a diet typically prescribed to IBS patients by healthcare professionals. In other studies, the control diet was the normal diet of the participants.

The duration of the RCTs ranged from three to six weeks. The age of the participants ranged from 18 to 74 and most were female. The duration of the non-randomized studies ranged from two days to 35 months, with the number of participants ranging from 19 to 82.

The three primary outcomes in both the randomized and non-randomized interventions were the number of participants with symptom improvement after the intervention, IBS Severity Scoring System (IBS-SSS) scores, and/or the IBS Quality of Life (IBS-QOL) scores, which were measured pre- and post-intervention.

Pooled odds ratios and confidence intervals were calculated for the reduction in IBS-SSS scores, the increase in IBS-QOL scores, and for the number of patients who reported improved functional gastrointestinal symptoms for both randomized and non-randomized interventions.

The goal of a meta-analysis is to pool together the results of multiple studies. It is impossible for all of the studies to be identical because there will always be differences in the study designs, measured outcomes, and results. This is known as heterogeneity. When there is high heterogeneity amongst the studies, a meta-analysis is usually not appropriate. Therefore, researchers usually quantify the heterogeneity amongst the studies before proceeding with a meta-analysis. In this meta-analysis, heterogeneity was calculated using the I² statistic, study quality was assessed using the Jadad scale for reporting RCTs, and publication bias was measured using the Egger’s regression model.

This meta-analysis and systematic review investigated the effectiveness of a low-FODMAP diet in reducing symptoms associated with IBS. The analysis included six randomized trials and sixteen non-randomized trials. The main outcomes of the studies were IBS-SSS scores, IBS-QOL scores and the number of participants who reported improved gastrointestinal symptoms.

In the randomized controlled trials, participants in the experimental groups reported abdominal pain and abdominal bloating as the symptoms with the greatest improvement. The low-FODMAP diets were found to be superior in providing overall relief of gastrointestinal symptoms compared to the diets in the control groups. In the non-randomized interventions, abdominal pain was reported to be the symptom with the greatest amount of improvement, followed by gas, diarrhea, nausea, and constipation.

All participants had a baseline IBS-SSS score that was greater than 232, which is considered to be moderate. In the RCTs, the average decrease in IBS-SSS scores for the low-FODMAP groups was 122.64. In the control groups, the average decrease was 69.64. In the non-randomized interventions, the average decrease in the IBS-SSS scores was 118.7. For a change in IBS-SSS score to be designated as clinically meaningful, it must be over 50 points. So, both the control diets and the low-FODMAP diets led to clinically meaningful decreases in IBS-SSS scores. However, it is also important to note that the difference in the mean decrease in scores between the experimental and control groups was over 50 points. Thus, the low-FODMAP diets were far more effective in reducing IBS-SSS scores than were the control diets, as shown in Figure 2.

In the randomized trials, the experimental group had an average improvement of 10 points in IBS-QOL scores while the control group had an average increase of 0.4 points. In the non-randomized trials, there was an average improvement of 10.5 points. While none of these improvements were deemed clinically meaningful (due to being less than 14), there was a difference in the mean increase in scores between the experimental groups and the control groups.

The authors did not find any evidence of publication bias. The authors also did not find any statistically significant heterogeneity in the RCTs. However, there was large heterogeneity in the non-randomized interventions.

In this analysis, the authors pooled together the results from multiple other studies, and found that adhering to a low-FODMAP diet resulted in clinically meaningful changes in IBS-SSS scores and led to a reduction in abdominal pain and bloating. Adhering to a control diet also resulted in symptom improvement. However, the low-FODMAP diet was superior in reducing symptom severity.

This is the first meta-analysis to investigate the effectiveness of a low-FODMAP diet in reducing symptoms associated with IBS. The analysis shows that low-FODMAP diets are effective and superior to control diets in reducing gastrointestinal symptoms.

The results also indicate that even though the low-FODMAP diets were associated with better outcomes, adhering to a control diet still resulted in improved outcomes. This suggests that simply adhering to any diet may offer symptom relief in certain individuals. However, this could also be a result of patients adhering better to diets while enrolled in trials.

Meta-analyses are only as good as the studies they include. When there are significant differences between the studies being analyzed, also known as heterogeneity, a meta-analysis is not always appropriate. While the authors of this meta-analysis tested the RCTs for heterogeneity using the I² statistic and found low to no heterogeneity, they noted that there were differences in the RCTs that could be confounding factors and that quality assessment of the RCTs yielded mixed results.

For example, the durations of the randomized interventions differed, ranging from three to six weeks. The blinding techniques of the RCTs also tended to vary, with four randomized trials being single-blinded and two being unknown, due to the original study authors not providing this information.

The authors also noted that the control diets in the RCTs varied, with some comparing low-FODMAP diets to the standard diets of IBS patients, while others compared a low-FODMAP diet to dietary advice that is prescribed to IBS patients. However, each of these studies has shown the low-FODMAP diet to be superior to the control diets. Another limitation of the RCTs included was that the longest RCT was only six weeks in duration. In the context of a chronic disorder like IBS, six weeks may not be long enough to determine how a diet would affect symptoms in the long-term.

An important shortcoming of this meta-analysis was that most of the studies included did not report on IBS subclassification such as diarrhea predominant (IBS-D), constipation predominant (IBS-C), both diarrhea and constipation (IBS-M) and neither diarrhea or constipation (IBS-U). Thus, it remains unclear how a low-FODMAP diet affects these particular symptoms.

This meta-analysis provides strong evidence to support the use of a low-FODMAP diet in treating IBS symptoms. Both the low-FODMAP diets and the control diets resulted in improved symptoms. Unfortunately, the control diets between the studies differed, thus it is difficult to accurately determine how effective each one is in reducing IBS symptoms. The RCTs included were also not very long in duration, which limits conclusions about long-term efficacy.

The conclusions that the authors arrived at fall in line with the results of previous reviews^[6] of low-FODMAP diets, showing that they are effective for treating IBS symptoms. Previous reviews were not able to pool together the results of multiple studies due to high heterogeneity and because many of the trials at the time were quite short in duration. Thus, researchers were unable to quantify how effective a low-FODMAP diet was when compared to other interventions. However, dozens of trials investigating low-FODMAP diets have been conducted since then, many with similar study designs. Many researchers^[8] have proposed that a low-FODMAP diet be the first line of treatment for IBS^[9]. This is the first meta-analysis to examine the effectiveness of a low-FODMAP diet, and it provides strong evidence to support the use of a low-FODMAP diet in reducing gastrointestinal symptoms associated with IBS.

The results from this meta-analysis also provide further evidence that diets high in fermentable substrates can be problematic for people with gastrointestinal disorders^[5]. By restricting these short chain carbohydrates, bacteria in the intestines have less substrate and create fewer byproducts such as gas (as shown in Figure 3), so symptoms such as abdominal pain and abdominal bloating are less likely to be problematic. In fact, this meta-analysis showed that abdominal pain and abdominal bloating were reported to be the two symptoms with the greatest improvement in the RCTs by the low-FODMAP group. This theory is further supported by studies that have shown low-FODMAP diets to be superior to gluten-free diets^[10] in treating IBS. However, the results of this meta-analysis also showed that the control groups experienced some relief. Thus, it is very likely that any dietary intervention^[11] will result in some form of relief whether it be due to placebo or to biochemical reasons.

Source: The Monash University Low FODMAP diet

It is quite clear at this point that diet plays a large role in how a person’s microbiome is shaped. Although research into the microbiome is fairly new, the results of this study show that manipulating one’s diet can have a substantial effect on their health-related quality of life.

Now that there is substantial evidence to support the use of a low-FODMAP diet in reducing IBS symptom severity, it is possible that it may become a first line of treatment. The results of this meta-analysis and the results of other RCTs may convince physicians and researchers to focus more on the microbiome when developing new interventions for gastrointestinal disorders.

Q. How will a low-FODMAP diet affect the microbiota?

Unfortunately, there is a lack of long-term RCTs that have examined this phenomenon. Short-term RCTs have shown that following a low-FODMAP diet for over a month reduces luminal bifidobacteria^[12] and reduces total bacteria counts in the colon when followed for an extended period of time^[13]. However, it is difficult to speculate how adopting a low-FODMAP diet will impact the gut microbiome in the long-term.

Fiber consumption can be more difficult on a low-FODMAP diet, but there are still many plant foods that are low in FODMAPs and high in fiber (such as several types of berries). The consumption of fibrous foods without FODMAPs, that a given individual can handle without symptoms, isn’t something that has been well studied. Part of the reason may be that different people can react quite differently to both FODMAPs and different specific fibers and foods.

Q. What impact will a low-FODMAP diet have on constipation?

Interestingly enough, this meta-analysis found that following a low-FODMAP diet resulted in significant improvements in almost all symptoms associated with IBS with the exception of constipation. Although there was some degree of improvement in constipation, it was the symptom with the least amount of improvement.

It is often believed that constipation is caused by a lack of fiber and that low-fiber diets will exacerbate constipation. So, it is commonly thought that a low-FODMAP diet, which is often a bit low in fiber, will likely worsen constipation. One meta-analysis^[14] concluded that the available evidence supports fiber for the treatment of constipation; however the evidence was not strong. Thus, it is quite difficult to know how a low-FODMAP diet will affect constipation.

Q. What other evidence-based strategies are available for managing IBS?

Peppermint oil has been found in multiple RCTs to be effective in reducing abdominal pain in people with IBS. One systematic review and meta-analysis^[15] also found certain probiotics to be effective in reducing abdominal pain associated with IBS. A low-FODMAP diet and probiotic supplementation may be an effective strategy in dealing with IBS, since previous studies^[12] reported reduced counts of bifidobacteria in people who adhered to a low-FODMAP diet for a month.

IBS is a very difficult chronic disorder to manage. In the past, no one treatment had substantial evidence behind it, and thus first-line dietary treatments were in question. However, this meta-analysis and several other RCTs have shown that a low-FODMAP diet is effective in reducing not just one or two symptoms but many of the symptoms that are associated with IBS. Low-FODMAP diets have the potential to be a first line of treatment utilized by evidence-based clinicians. However, more research is needed to evaluate potentially detrimental effects on gut microflora from long-term diet adoption.