Cover Story

Low FODMAPs Diet in IBS: Experts Disagree on Evidence of Efficacy

Interest in dietary interventions for irritable bowel syndrome has seen a recent revival, prompted by randomized controlled trial data suggesting elimination diets — namely, the gluten-free diet and the low fermentable oligo, disaccharides, monosaccharaides, and polyols, or low FODMAPs, diet — may be effective for treating patients. Emerging data on the potential efficacy of probiotics in IBS have also sparked increasing interest as the role of the gut microbiome in GI disorders becomes better understood.

This interest is not only limited to the scientific community, but also extends to patients; experts interviewed by Healio Gastroenterology estimated around three-quarters of their patients with IBS either ask about how diet may be affecting their symptoms, or have already tried a restrictive diet.

There seems to be a consensus that dietary therapies show promise for the treatment of patients with IBS, but data from rigorous randomized controlled trials, while compelling, remain sparse. The low FODMAPs diet currently has the greatest amount of available data, yet experts continue to disagree on whether or not enough is known about its efficacy to justify strong recommendation to patients with IBS.

Emerging Data

Last year, Paul Moayyedi, MBChB, PhD, MPH, director of the division of gastroenterology at McMaster University in Ontario, Canada, along with Eamonn Quigley, MD, chief of the division of gastroenterology and hepatology at Weill Cornell Medical College at Houston Methodist Hospital, and colleagues published results from a systematic review of randomized controlled trials published through December 2013, evaluating the efficacy of dietary restriction in patients with IBS. Based on three eligible trials — each respectively evaluating the low FODMAPs diet, the gluten-free diet and another exclusion diet — they concluded that elimination diets in general cannot be strongly recommended to patients with IBS until more evidence is accumulated.

Paul Moayyedi

 

In the first trial, 41 patients with IBS were randomly assigned to the low FODMAPs diet or their normal diet for 4 weeks, and while 68% of the low FODMAPs group reported adequate symptom control compared with 23% of controls (P = .005), the trial had a high risk of bias due to the unblinded design, Moayyedi and colleagues wrote. “The bottom line is most of these studies don’t give you the information you need to know whether [these dietary restrictions] are truly working in terms of improving patients’ overall symptoms,” Moayyedi told Healio Gastroenterology. “We simply don’t have enough evidence to say whether this works or not.”

William D. Chey

William D. Chey, MD, professor of medicine and nutrition sciences at the University of Michigan health system, director of the Digestive Diseases Center for Nutrition and Behavior at the University of Michigan, and Healio Gastroenterology Peer Perspective Board Member, said he disagrees with the authors’ conclusion that elimination diets cannot be recommended to patients with IBS. “While I agree at the time of their [study] it was fair to make that statement, a lot has happened in that intervening period of time,” he said in an interview. “First, people have gained a lot of clinical experience with diet therapies, and in general, I think the people who have been working with diet therapies would claim that a substantial proportion of their patients improve at least somewhat with diet strategies, whether you’re talking about the low FODMAPs diet or gluten-free diet. But more important than anecdotal clinical experience is the presentation of a number of different studies ... that seem to indicate a benefit for diet therapies.”

In one such study presented by Staudacher and colleagues at last year’s UEG Week, 104 patients were randomly assigned to receive low FODMAPs or sham dietary advice, and to the probiotic VSL#3 or placebo, for 4 weeks in a 2x2 factorial design. Intention-to-treat analysis showed 57% of the low FODMAPs group reported adequate symptom relief vs. 38% of the sham group (P = 0.05), as did 57% of the probiotic group vs. 37% of the plaebo group (P = 0.05). Mean IBS Symptom Severity Scale scores were also lower in the low FODMAPs vs. sham group (P < .001).

In another randomized controlled trial presented by Piacentino and colleagues at last year’s DDW, 75 IBS patients were blindly assigned to one of three 4-week diets: low FODMAPs and gluten-free, low-FODMAPs and normal gluten, or normal FODMAPs and normal gluten (controls). Patients were assessed during the last 2 weeks and again after a mean follow-up of 16 months. Patients in the two test diet groups had greater improvements in symptoms compared with controls, and a trend favoring the normal gluten vs. gluten-free group was observed. Compliance was lower in the gluten-free group, and at follow-up, 72% of the low FODMAPs and normal gluten group continued the diet with benefit vs. 52% of the low FODMAPs and gluten-free group and 40% of controls.

The long-term adherence to the low FODMAPs diet in this study is significant, Chey said. “The low FODMAPs diet is not intended to be a long-term strategy for patients; it’s important to try to expand the number and types of foods that a person can eat if they respond ... but initial concerns that the diet was too complicated and that people couldn’t comply to it actually haven’t born out to be true.”

Also notable, Chey said, is that available data suggest the low FODMAPs diet improves abdominal pain and bloating more than bowel-related symptoms like diarrhea or constipation. “That’s not to say that it doesn’t make some patients with diarrhea better, but if you look at bigger groups of patients ... there’s a more consistent benefit for abdominal pain and bloating — in fact ... it’s fair to say that based on available data, at least half [of] patients with IBS in randomized controlled trials get benefits for abdominal pain and bloating with the low FODMAPs diet.”

Despite new positive evidence, Moayyedi maintains that data are conflicting, and that the jury is still out on whether the low FODMAPs diet works in IBS.

“The largest and best randomized trial out there was published after our systematic review,” he said, “which basically showed no difference between the low FODMAPs diet and the standard diet for IBS.”

In this multicenter, parallel, single-blinded trial, Böhn and colleagues randomly assigned 75 patients with IBS to a low FODMAPs diet or traditional dietary advice for 4 weeks, and found that while both groups had significant improvements in symptom severity (P < .0001), there was no significant difference in symptom improvement between groups.

“I think we need to be cautious before pushing hard on this, because we’ve got to know whether this diet works or not — but of all of them out there, this is the most restrictive, so if anything is going to work, it will be something like this,” Moayyedi said. “Even if it doesn’t have an effect, the very restrictive nature of it means that there is going to be a high placebo effect.”

Eamonn Quigley

 

While the trial by Böhn and colleagues did not show the low FODMAPs diet was superior, Quigley said the fact that both interventions were effective is significant.

“I think more evidence has accrued to support the low FODMAPs diet [since our systematic review],” Quigley said. There are “quite a bit of data to show that it’s effective, and there’s also been quite a bit of clinical research to provide a scientific basis for why it does work, so I do recommend the low FODMAPs diet to patients, but I do ask that they see a dietician, because it is quite a complex diet, and I want to make sure ... their diet is balanced and they are not missing out on any essential nutrients.”

Safety Concerns

Moayyedi agreed long-term adherence to a low FODMAPs diet can be “quite dangerous,” as a nutritional deficiency is possible “given the amount of foods you can’t eat, so it’s very important to use a dietician who can systematically re-introduce foods to see which aggravate symptoms and which don’t.”

Chey also agreed a dietician is essential to administer a low FODMAPs diet correctly, but emphasized that “if administered correctly, it can be administered safely.”

In addition to the possibility of nutritional deficiencies and difficulty in adherence, Quigley said a more recent safety concern is that the low FODMAPs diet may negatively alter the gut microbiota, which is “not all that surprising. If you restrict the diet in a way that reduces the amount of carbohydrates that get to the colon, you’re going to affect the bacteria there, so that’s an issue in terms of the long-term use of this diet.”

“FODMAPs are important prebiotics that ... encourage the growth of potentially beneficial strains of bacteria, particularly within the colon, and it’s been observed that the low FODMAPs diet decreases the number of strains of bacteria that produce a potentially beneficial short chain fatty acid, butyrate,” Chey said. “So that’s raised red flags in terms of whether the diet is potentially dangerous when somebody’s left on the full low FODMAPs diet for extended periods of time.”

This observation was made in an Australian single-blinded, randomized cross-over trial performed by Halmos and colleagues, in which 27 patients with IBS and six healthy participants were randomly assigned to one of two 21-day diets that differed only in FODMAPs content. Participants then crossed over to the other diet after a 21-day washout period. Stool sample analysis showed the low FODMAPs diet was associated with higher fecal pH, similar short-chain fatty acid concentrations, greater microbial diversity and reduced total bacterial abundance compared with the standard diet. Specifically, the low FODMAPs diet was associated with reduced relative abundance of butyrate-producing Clostridium cluster XIVa, mucus-associated Akkermansia muciniphila, and Ruminococcus torques.

Further study on the long-term consequences of the low FODMAPs diet on the microbiome and subsequent metabolomic effects are ongoing, with some forthcoming results expected in the coming months, Chey said. “At the end of the day, these concerns are exactly the reason why it’s important for doctors and patients to realize the low FODMAPs diet is not intended to be a long-term solution for IBS patients; it’s intended to be a blunt instrument to determine whether somebody is sensitive to FODMAPs or not,” he said. The diet should be discontinued if a patient does not respond, and if they do respond, a dietician-guided, structured re-introduction of FODMAP-containing foods should occur “to determine which foods are most likely to trigger their symptoms,” he said. “At the end of 6 months, of the patients I start on a low FODMAPs diet, virtually nobody is still on a full FODMAPs exclusion. Almost everybody is on some variation of a low FODMAPs diet — they’re on their low FODMAPs diet, not the generic low FODMAPs diet, and that’s something I think, unfortunately, is not happening in clinical practice at the current time.”

These and other safety issues continue to drive Moayyedi’s reservations about recommending the low FODMAPs diet to patients. “Why am I making a fuss? ... The feeling out there is, ‘Let’s just do it because it might work, and what’s the harm?’ It can be harmful because there can be nutritional issues, but just as importantly, this can affect a patient’s quality of life. Because they believe they need to take this very restrictive diet [they] ironically may be worse off in terms of their general well-being on this diet than they were to start with,” he said. “So to think this is harmless ... may be misleading.”

More Rigorous Trials Needed

Despite conflicting data on the low FODMAPs and other dietary interventions in IBS and the resulting controversy, Quigley said there is “absolutely” promise for them in the future, though much still remains to be elucidated. “First of all, we need a lot more information on the basic role of diet in IBS,” he said. “I don’t think anybody believes diet causes IBS, but I think it’s quite clear that diet is a major factor in precipitating symptoms and making them worse.” Ultimately, high quality, large trials of dietary interventions in IBS to conclusively demonstrate efficacy are needed, he said. However, all of the experts interviewed agreed that such studies are uniquely difficult to perform.

Nonetheless, “we should do them,” Moayyedi said, and they need to be adequately powered, properly randomized, have proper concealment of allocation and have sensible endpoints. “The problem with dietary interventions is that it’s difficult to blind people. ... Diet is a more complex intervention than drugs, and blinding is a key issue here. It’s possible for individual food groups, but almost impossible for a complex kind of diet like low FODMAPs, and therefore, you can just do the best you can.”

A “neat trick would be to randomize people to a low FODMAPs diet vs. a high FODMAPs diet, and see if you can make symptoms worse with a high FODMAPs diet,” he added.

Looking toward the future, Chey speculated in a recent review article about the potential of improving outcomes to diet therapies using biomarkers. “There may come a day when our rapidly expanding knowledge of the gut microbiome and/or the functional consequences of these changes through measurement of short-chain fatty acids or volatile gases can be leveraged to identify patients more or less likely to improve with different dietary interventions,” he wrote. Recent data already support this possibility, he added.

In the short-term, the scientific community can expect new data from a number of randomized controlled trials evaluating the low FODMAPs diet in patients with IBS in the coming months, these experts said, including the first U.S. randomized controlled trial performed by Chey and colleagues, which will be presented at DDW in May. – by Adam Leitenberger

Disclosures: Chey reports he has a research grant and is a consultant for Nestlé. Moayyedi and Quigley report no relevant financial disclosures.

Interest in dietary interventions for irritable bowel syndrome has seen a recent revival, prompted by randomized controlled trial data suggesting elimination diets — namely, the gluten-free diet and the low fermentable oligo, disaccharides, monosaccharaides, and polyols, or low FODMAPs, diet — may be effective for treating patients. Emerging data on the potential efficacy of probiotics in IBS have also sparked increasing interest as the role of the gut microbiome in GI disorders becomes better understood.

This interest is not only limited to the scientific community, but also extends to patients; experts interviewed by Healio Gastroenterology estimated around three-quarters of their patients with IBS either ask about how diet may be affecting their symptoms, or have already tried a restrictive diet.

There seems to be a consensus that dietary therapies show promise for the treatment of patients with IBS, but data from rigorous randomized controlled trials, while compelling, remain sparse. The low FODMAPs diet currently has the greatest amount of available data, yet experts continue to disagree on whether or not enough is known about its efficacy to justify strong recommendation to patients with IBS.

Emerging Data

Last year, Paul Moayyedi, MBChB, PhD, MPH, director of the division of gastroenterology at McMaster University in Ontario, Canada, along with Eamonn Quigley, MD, chief of the division of gastroenterology and hepatology at Weill Cornell Medical College at Houston Methodist Hospital, and colleagues published results from a systematic review of randomized controlled trials published through December 2013, evaluating the efficacy of dietary restriction in patients with IBS. Based on three eligible trials — each respectively evaluating the low FODMAPs diet, the gluten-free diet and another exclusion diet — they concluded that elimination diets in general cannot be strongly recommended to patients with IBS until more evidence is accumulated.

Paul Moayyedi

 

In the first trial, 41 patients with IBS were randomly assigned to the low FODMAPs diet or their normal diet for 4 weeks, and while 68% of the low FODMAPs group reported adequate symptom control compared with 23% of controls (P = .005), the trial had a high risk of bias due to the unblinded design, Moayyedi and colleagues wrote. “The bottom line is most of these studies don’t give you the information you need to know whether [these dietary restrictions] are truly working in terms of improving patients’ overall symptoms,” Moayyedi told Healio Gastroenterology. “We simply don’t have enough evidence to say whether this works or not.”

William D. Chey

William D. Chey, MD, professor of medicine and nutrition sciences at the University of Michigan health system, director of the Digestive Diseases Center for Nutrition and Behavior at the University of Michigan, and Healio Gastroenterology Peer Perspective Board Member, said he disagrees with the authors’ conclusion that elimination diets cannot be recommended to patients with IBS. “While I agree at the time of their [study] it was fair to make that statement, a lot has happened in that intervening period of time,” he said in an interview. “First, people have gained a lot of clinical experience with diet therapies, and in general, I think the people who have been working with diet therapies would claim that a substantial proportion of their patients improve at least somewhat with diet strategies, whether you’re talking about the low FODMAPs diet or gluten-free diet. But more important than anecdotal clinical experience is the presentation of a number of different studies ... that seem to indicate a benefit for diet therapies.”

In one such study presented by Staudacher and colleagues at last year’s UEG Week, 104 patients were randomly assigned to receive low FODMAPs or sham dietary advice, and to the probiotic VSL#3 or placebo, for 4 weeks in a 2x2 factorial design. Intention-to-treat analysis showed 57% of the low FODMAPs group reported adequate symptom relief vs. 38% of the sham group (P = 0.05), as did 57% of the probiotic group vs. 37% of the plaebo group (P = 0.05). Mean IBS Symptom Severity Scale scores were also lower in the low FODMAPs vs. sham group (P < .001).

PAGE BREAK

In another randomized controlled trial presented by Piacentino and colleagues at last year’s DDW, 75 IBS patients were blindly assigned to one of three 4-week diets: low FODMAPs and gluten-free, low-FODMAPs and normal gluten, or normal FODMAPs and normal gluten (controls). Patients were assessed during the last 2 weeks and again after a mean follow-up of 16 months. Patients in the two test diet groups had greater improvements in symptoms compared with controls, and a trend favoring the normal gluten vs. gluten-free group was observed. Compliance was lower in the gluten-free group, and at follow-up, 72% of the low FODMAPs and normal gluten group continued the diet with benefit vs. 52% of the low FODMAPs and gluten-free group and 40% of controls.

The long-term adherence to the low FODMAPs diet in this study is significant, Chey said. “The low FODMAPs diet is not intended to be a long-term strategy for patients; it’s important to try to expand the number and types of foods that a person can eat if they respond ... but initial concerns that the diet was too complicated and that people couldn’t comply to it actually haven’t born out to be true.”

Also notable, Chey said, is that available data suggest the low FODMAPs diet improves abdominal pain and bloating more than bowel-related symptoms like diarrhea or constipation. “That’s not to say that it doesn’t make some patients with diarrhea better, but if you look at bigger groups of patients ... there’s a more consistent benefit for abdominal pain and bloating — in fact ... it’s fair to say that based on available data, at least half [of] patients with IBS in randomized controlled trials get benefits for abdominal pain and bloating with the low FODMAPs diet.”

Despite new positive evidence, Moayyedi maintains that data are conflicting, and that the jury is still out on whether the low FODMAPs diet works in IBS.

“The largest and best randomized trial out there was published after our systematic review,” he said, “which basically showed no difference between the low FODMAPs diet and the standard diet for IBS.”

In this multicenter, parallel, single-blinded trial, Böhn and colleagues randomly assigned 75 patients with IBS to a low FODMAPs diet or traditional dietary advice for 4 weeks, and found that while both groups had significant improvements in symptom severity (P < .0001), there was no significant difference in symptom improvement between groups.

“I think we need to be cautious before pushing hard on this, because we’ve got to know whether this diet works or not — but of all of them out there, this is the most restrictive, so if anything is going to work, it will be something like this,” Moayyedi said. “Even if it doesn’t have an effect, the very restrictive nature of it means that there is going to be a high placebo effect.”

Eamonn Quigley

 

While the trial by Böhn and colleagues did not show the low FODMAPs diet was superior, Quigley said the fact that both interventions were effective is significant.

“I think more evidence has accrued to support the low FODMAPs diet [since our systematic review],” Quigley said. There are “quite a bit of data to show that it’s effective, and there’s also been quite a bit of clinical research to provide a scientific basis for why it does work, so I do recommend the low FODMAPs diet to patients, but I do ask that they see a dietician, because it is quite a complex diet, and I want to make sure ... their diet is balanced and they are not missing out on any essential nutrients.”

Safety Concerns

Moayyedi agreed long-term adherence to a low FODMAPs diet can be “quite dangerous,” as a nutritional deficiency is possible “given the amount of foods you can’t eat, so it’s very important to use a dietician who can systematically re-introduce foods to see which aggravate symptoms and which don’t.”

PAGE BREAK

Chey also agreed a dietician is essential to administer a low FODMAPs diet correctly, but emphasized that “if administered correctly, it can be administered safely.”

In addition to the possibility of nutritional deficiencies and difficulty in adherence, Quigley said a more recent safety concern is that the low FODMAPs diet may negatively alter the gut microbiota, which is “not all that surprising. If you restrict the diet in a way that reduces the amount of carbohydrates that get to the colon, you’re going to affect the bacteria there, so that’s an issue in terms of the long-term use of this diet.”

“FODMAPs are important prebiotics that ... encourage the growth of potentially beneficial strains of bacteria, particularly within the colon, and it’s been observed that the low FODMAPs diet decreases the number of strains of bacteria that produce a potentially beneficial short chain fatty acid, butyrate,” Chey said. “So that’s raised red flags in terms of whether the diet is potentially dangerous when somebody’s left on the full low FODMAPs diet for extended periods of time.”

This observation was made in an Australian single-blinded, randomized cross-over trial performed by Halmos and colleagues, in which 27 patients with IBS and six healthy participants were randomly assigned to one of two 21-day diets that differed only in FODMAPs content. Participants then crossed over to the other diet after a 21-day washout period. Stool sample analysis showed the low FODMAPs diet was associated with higher fecal pH, similar short-chain fatty acid concentrations, greater microbial diversity and reduced total bacterial abundance compared with the standard diet. Specifically, the low FODMAPs diet was associated with reduced relative abundance of butyrate-producing Clostridium cluster XIVa, mucus-associated Akkermansia muciniphila, and Ruminococcus torques.

Further study on the long-term consequences of the low FODMAPs diet on the microbiome and subsequent metabolomic effects are ongoing, with some forthcoming results expected in the coming months, Chey said. “At the end of the day, these concerns are exactly the reason why it’s important for doctors and patients to realize the low FODMAPs diet is not intended to be a long-term solution for IBS patients; it’s intended to be a blunt instrument to determine whether somebody is sensitive to FODMAPs or not,” he said. The diet should be discontinued if a patient does not respond, and if they do respond, a dietician-guided, structured re-introduction of FODMAP-containing foods should occur “to determine which foods are most likely to trigger their symptoms,” he said. “At the end of 6 months, of the patients I start on a low FODMAPs diet, virtually nobody is still on a full FODMAPs exclusion. Almost everybody is on some variation of a low FODMAPs diet — they’re on their low FODMAPs diet, not the generic low FODMAPs diet, and that’s something I think, unfortunately, is not happening in clinical practice at the current time.”

These and other safety issues continue to drive Moayyedi’s reservations about recommending the low FODMAPs diet to patients. “Why am I making a fuss? ... The feeling out there is, ‘Let’s just do it because it might work, and what’s the harm?’ It can be harmful because there can be nutritional issues, but just as importantly, this can affect a patient’s quality of life. Because they believe they need to take this very restrictive diet [they] ironically may be worse off in terms of their general well-being on this diet than they were to start with,” he said. “So to think this is harmless ... may be misleading.”

More Rigorous Trials Needed

Despite conflicting data on the low FODMAPs and other dietary interventions in IBS and the resulting controversy, Quigley said there is “absolutely” promise for them in the future, though much still remains to be elucidated. “First of all, we need a lot more information on the basic role of diet in IBS,” he said. “I don’t think anybody believes diet causes IBS, but I think it’s quite clear that diet is a major factor in precipitating symptoms and making them worse.” Ultimately, high quality, large trials of dietary interventions in IBS to conclusively demonstrate efficacy are needed, he said. However, all of the experts interviewed agreed that such studies are uniquely difficult to perform.

PAGE BREAK

Nonetheless, “we should do them,” Moayyedi said, and they need to be adequately powered, properly randomized, have proper concealment of allocation and have sensible endpoints. “The problem with dietary interventions is that it’s difficult to blind people. ... Diet is a more complex intervention than drugs, and blinding is a key issue here. It’s possible for individual food groups, but almost impossible for a complex kind of diet like low FODMAPs, and therefore, you can just do the best you can.”

A “neat trick would be to randomize people to a low FODMAPs diet vs. a high FODMAPs diet, and see if you can make symptoms worse with a high FODMAPs diet,” he added.

Looking toward the future, Chey speculated in a recent review article about the potential of improving outcomes to diet therapies using biomarkers. “There may come a day when our rapidly expanding knowledge of the gut microbiome and/or the functional consequences of these changes through measurement of short-chain fatty acids or volatile gases can be leveraged to identify patients more or less likely to improve with different dietary interventions,” he wrote. Recent data already support this possibility, he added.

In the short-term, the scientific community can expect new data from a number of randomized controlled trials evaluating the low FODMAPs diet in patients with IBS in the coming months, these experts said, including the first U.S. randomized controlled trial performed by Chey and colleagues, which will be presented at DDW in May. – by Adam Leitenberger

Disclosures: Chey reports he has a research grant and is a consultant for Nestlé. Moayyedi and Quigley report no relevant financial disclosures.