The chemistry-based diet that’s treating irritable bowel syndrome

The chemistry-based diet that’s treating irritable bowel syndrome

Trials have shown that eating foods low in specific sugars—the low FODMAP diet—can clear up digestive ailments

By Bethany Halford
February 5, 2018 | Volume 96 Issue 6
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Imagine having an illness so severe that you would give up 15 years of your life if the symptoms would vanish. That was the average amount of time nearly 2,000 people diagnosed with irritable bowel syndrome, or IBS, said they were willing to sacrifice if they could be symptom-free, in response to a 2007 survey (J. Clin. Gastroenterol. 2009, DOI: 10.1097/MCG.0b013e318189a7f9).

In brief

Between 10 and 15% of people in the developed world have irritable bowel syndrome (IBS), which is characterized by unpleasant gastrointestinal symptoms such as bloating and diarrhea. Over the past 12 years, doctors and scientists have systematically studied sugary substances in foods, known as FODMAPs, that they think might be triggering some forms of IBS. Read on to learn more about the low FODMAP diet, which they’ve developed to help people with IBS figure out which foods are responsible for their symptoms.

IBS—a condition characterized by bloating, abdominal pain, flatulence, diarrhea, and constipation—is not the sort of thing most people talk about at the dinner table. But evidence continues to mount that what people eat could profoundly impact their IBS symptoms. Because IBS affects 10–15% of people in the developed world, relieving those symptoms could improve the quality of life for at least 100 million people.

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“IBS isn’t a life-threatening disease. It just makes life miserable,” says Peter Gibson, a gastroenterologist at Monash University. A few years before the 2007 survey, Gibson and colleagues in Australia were beginning to suss out saccharides that may be exacerbating IBS symptoms.

They developed a regimen aimed at helping relieve IBS symptoms and began to study its effectiveness. Known as the low FODMAP diet, the plan begins with people avoiding FODMAPs, otherwise known as fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. People on the diet then systematically reintroduce foods to figure out which of them contains the sugary molecules causing symptoms and which FODMAPs that particular IBS patient can consume without problems.

The diet pulled together a lot of information that doctors had known for years, even decades, but that they had not connected into a cohesive whole that made sense, Gibson says. For example, doctors had known since the 1960s that the disaccharide lactose in milk and in other dairy products can cause IBS symptoms. People with IBS who went on a lactose-free diet, however, rarely found relief from their symptoms because they were still consuming other FODMAPs to which they were also sensitive.

“When we put the diet together, it was much more effective than anything we had seen before,” Gibson says. “This was specifically related to definite molecules in the diet.”

Linking FODMAPs to IBS

The concept of FODMAP sensitivity is simple, Gibson says. These molecules are either very difficult or impossible for the small intestine to digest or absorb. When a person eats enough FODMAPs, the compounds pass through the small bowel mostly untouched into the colon, where bacteria ferment them into gases—hydrogen, carbon dioxide, and methane—as well as short-chain fatty acids, which bring water into the bowel via osmosis, making stool watery and causing diarrhea.

“These things can make the bowel blow up like a balloon and cause pain,” Gibson explains. People with IBS are more sensitive to inflammation and stretching of the bowel, Gibson says, whereas people who don’t have IBS don’t experience the same sensitivity. Scientists don’t yet understand the underlying causes of the sensitivity, whether it’s genetic, related to microbial residents in the gut, or some combination of factors.

“In healthy individuals, FODMAPs may cause a little more flatulence, but not pain, diarrhea, and bloating,” says William Chey, a gastroenterologist at the University of Michigan who studies the low FODMAP diet. FODMAPs also trigger abnormalities in how IBS patients’ bowels function, Chey adds. For example, their colons may be hyperactive after a meal, and FODMAPs might exacerbate that activity.

FODMAPs also seem to influence the microbes living inside the gut. Recently, a team led by Chung Owyang, another gastroenterologist at the University of Michigan, reported that FODMAPs promote the overgrowth of Gram-negative bacteria in the gut. These bacteria have cell walls that contain lipopolysaccharides, a group of molecules that can inflame the intestinal lining (J. Clin. Invest. 2017, DOI: 10.1172/JCI92390).

Owyang says his group is now starting to identify the specific Gram-negative bacteria that are richest in lipopolysaccharides. “Perhaps we can come up with ways to decrease the growth of those particular bacteria,” he says.

Meanwhile, Chey’s patients commonly tell him that ingesting various types of food causes their gastrointestinal (GI) problems. “You would think just logically based upon what patients have been telling us for many, many years that there would be many evidence-based diet strategies for patients with GI problems,” he says. “Curiously, that has not been the case until probably the last 10 years or so.”

Chey says he first learned about the low FODMAP diet in 2008 after reading a paper from Gibson and the rest of the Monash University team (Clin. Gastroenterol. Hepatol. 2008, DOI: 10.1016/j.cgh.2008.02.058). The following year, Chey gave a talk during a postgraduate course for gastroenterologists in the U.S. and asked how many of the gathered doctors had heard of FODMAPs. “Out of an audience of several thousands, fewer than half a dozen hands went up,” he recalls. “People had just never even heard of this concept.”

He repeated the informal survey at a similar course in 2017. “Probably 80% of the hands went up,” he says. And 60% of the doctors said they were using the low FODMAP diet in their clinical practice. In just nine years, he says, the dietary treatment has become wildly popular.

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Finding FODMAPs

“Food chemistry is really the foundation of this diet,” says Jane Muir, a dietitian and biochemist who is part of the Monash team. “We had to understand what was in the food and identify those trigger carbohydrates.”

These logos, from two certification companies, are used to label low FODMAP foods.

Muir developed a systematic method for analyzing foods for FODMAPs. For example, to determine the FODMAP content of fruit and vegetables, her team will collect 500-g samples from five different supermarkets and five different green grocers. The researchers cut and pool the edible portions of the produce and use a food processor to blend it into a homogeneous mixture. They perform a similar homogenizing process for grains, cereals, and packaged foods.

From the homogeneous mix, they portion out and freeze-dry 100-g samples. They then use hot water to extract saccharides and polyols from those samples. Ultra-high-performance liquid chromatography analysis measures amounts of lactose and galacto-oligosaccharides. The scientists use high-performance liquid chromatography with a different column and mobile phase to measure fructose in excess of glucose and sugar polyols. They also use enzyme assay kits to measure total fructans—oligosaccharides that contain fructose—in food. This procedure employs highly purified and specific enzymes to hydrolyze sucrose, maltose, maltotriose, starch, and fructans. Calculations are then necessary to determine the total fructan content (J. Agric. Food Chem. 2007, DOI: 10.1021/jf070623x; J. Agric. Food Chem. 2009, DOI: 10.1021/jf802700e; J. Hum. Nutr. Diet. 2011, DOI: 10.1111/j.1365-277X.2010.01139.x).

Many of these analytical techniques were in the literature, Muir says, but she had to find the methods that worked best for identifying FODMAPs. “What’s so time-consuming is looking at all these different sugars in the same foods,” she says. “Often people will concentrate on one or two sugars in the same food, but we have to track so many. That’s where it becomes very labor intensive.”

To develop the diet, the team has analyzed more than 1,000 different food products from across the globe in the past 12 years, Muir estimates. In some instances, people have sent them canned and packaged foods from other countries. Because of quarantine restrictions in Australia, the team cannot receive international shipments of fresh fruit, vegetables, or dairy products, so the researchers have developed some work-arounds. For instance, when they wanted to know the FODMAP content of collard greens, a staple in many diets in the American South that isn’t available in Australia, they grew the leafy greens from seeds.

“The highest FODMAP foods are wheat, corn, apples, and onions.”

—Robin Foroutan, spokesperson, Academy of Nutrition & Dietetics,

Credit: Shutterstock

For packaged foods, it’s not always obvious from reading the label if a food is high or low in FODMAPs. Garlic, a high-FODMAP food that’s rich in oligosaccharides, is often added to food and simply labeled as “natural flavor.” To help consumers adopting a low FODMAP diet navigate their way through food labels, Monash University offers a FODMAP certification process for food companies. For example, Nestlé’s ProNourish nutritional drink was certified as a low FODMAP food using Monash’s analysis.

The FODMAP Friendly program, also based in Australia and cofounded by Susan Shepherd, who was previously part of the Monash team, and Timothy Mottin, offers a similar certification system. Products that have received the program’s certification bear a logo that features two shades of green divided by a squiggly line. The program has already certified more than 200 products found in popular supermarkets, such as Woolworths in Australia and Kroger, Hy-Vee, and Wegmans in the U.S.

The Monash team recently assembled the information from all their analyses into the Monash University Low FODMAP Diet app. It tells users which foods are low or high in FODMAPs using a stoplight system. For example, uncooked white onions get a red rating because of their high oligosaccharide content. Experiments have shown that cooking and processing can change food’s FODMAP content. Pickled onions get a green rating in the app. The app also breaks down which specific FODMAPs are present at high or low levels in a particular food. It costs $7.99, and the proceeds go to FODMAP research at Monash, Gibson and Muir say.

Inspiration from gluten

In the process of developing the low FODMAP diet, Muir says she had something of a “light bulb moment” when she discovered that the grains that are high in the protein gluten are also high in the FODMAPs called fructans. She and the Monash team hypothesize that many people who get relief from unpleasant GI symptoms by adopting a gluten-free diet are not actually sensitive to gluten but are sensitive to fructans instead.

The University of Michigan’s Chey says there is an increasing amount of evidence that indicates this is the case. Relief from GI discomfort that’s achieved through a gluten-free diet, he says, probably doesn’t come from eliminating gluten but rather from the restriction of fructans.

“The highest FODMAP foods are wheat, corn, apples, and onions,” says Robin Foroutan, a dietitian at the Morrison Center in New York City and spokesperson for the Academy of Nutrition & Dietetics. “Somebody who is wondering if they’re sensitive to FODMAPs can begin by eliminating just those four foods to see if they get any kind of relief.” But she adds that a person’s GI symptoms could be specific to wheat. “There is a spectrum of wheat sensitivity,” Foroutan says.

Because celiac disease (an autoimmune disorder related to gluten consumption), nonceliac gluten sensitivity, and FODMAP sensitivity all trigger similar GI symptoms, it can be difficult to make a diagnosis, says Shelley Case, a Saskatchewan-based dietitian and author of “Gluten Free: The Definitive Resource Guide.” But, she says, there are people for whom a gluten-free diet relieves other symptoms, such as chronic fatigue, brain fog, headaches, and joint pain, in addition to GI problems. If celiac disease has been ruled out, it’s possible that these people have a nonceliac gluten sensitivity, not FODMAP sensitivity.

Steven J. Singer knows all about the popularity of a gluten-free diet. He cofounded Glutino, a company that makes gluten-free foods. Most supermarkets in the U.S. now have a substantial gluten-free food selection, featuring pasta, bread, and cookies that lack the wheat-based protein. In fact, global sales of gluten-free food reached $3.5 billion in 2016 and are expected to grow to $4.7 billion by 2020, according to the consumer data group Euromonitor International.

After leaving Glutino, Singer was looking for another opportunity in the food industry that had medical ties and another opportunity to make a difference in the world, he says. Because an estimated 45 million Americans have IBS, the FODMAP-sensitive community is potentially very large, Singer says. So he started doing some research into the low FODMAP diet and in 2016 started Fody Foods, a company that makes certified low FODMAP foods, such as pasta sauce, garlic-infused oil, ketchup, and salad dressing.

“This is about food and science coming together,” Singer says. “I think in the next 12 to 36 months you will see many existing specialty food companies look into their portfolios and ask if any of their products meet these criteria.”

Does the low FODMAP diet work?

Kate Scarlata, a Massachusetts-based dietitian and author of several books, including “The Complete Idiot’s Guide to Eating Well with IBS,” says that her clients’ response has often been “miraculous” when they adopt a low FODMAP diet. “It is so rewarding to see patients who have been suffering for close to a decade almost instantaneously feel better by pulling FODMAPs out of their diets.”

Researchers have published at least 10 trials of the low FODMAP diet, conducted at locations around the world. Their results demonstrate that anywhere from 50 to 80% of people with IBS respond positively to the low FODMAP diet. The Monash team found 75% of people on the diet had fewer IBS symptoms than those who did not restrict FODMAPs (Gastroenterology 2014, DOI: 10.1053/j.gastro.2013.09.046).

In 2016, the University of Michigan’s Chey and colleagues published the first randomized trial of the low FODMAP diet in the U.S. They found that 50% of people who adopted the low FODMAP diet felt better. They also found that 40% of people who adopted traditional dietary recommendations for IBS patients, such as eating small, frequent meals, as well as avoiding binge eating and sugary foods, also felt better. The difference between these two groups was that those on the low FODMAP diet had significant improvement in tough-to-treat IBS symptoms, like pain and bloating, whereas those who used the traditional dietary interventions did not (Am. J. Gatroenterol. 2016, DOI: 10.1038/ajg.2016.434).

Chey says he thinks the difference between his results and those from the Monash team is probably due to how the researchers define their end points—fewer symptoms in the Monash study versus overall relief from symptoms in the Michigan study. “I would love it if 75% of patients with IBS got better on the diet, but that’s not what we’re seeing,” he says. “Am I disappointed that half the patients get better? No, I think that’s still very good.”

Chey points out that his group’s study is revealing in that it also shows that 50% of people don’t respond to the low FODMAP diet, which he says is just as important. “It’s not a silver bullet for IBS. It’s just another arrow in our quiver.” IBS, he notes, is not a single disease, but a collection of ailments with common symptoms, likely caused by multiple mechanisms. It makes sense, Chey says, that there’s no one strategy that will work for everybody.

For those who do find relief with the low FODMAP diet, all the doctors and dietitians who spoke with C&EN emphasize that the stage of the program where people eliminate many foods should last only six weeks or so. It isn’t meant for long-term use.

“This story does not end when you put someone on the elimination diet,” Chey says. FODMAPs are important prebiotics that help grow good microbes, and restricting them affects the gut microbiome. Doctors and scientists don’t yet know if those changes are good, bad, or indifferent, Chey says, but eliminating all FODMAPs forever is probably not healthy and very difficult to comply with. Instead, it’s better to figure out precisely which foods trigger symptoms—the so-called challenge phase of the diet.

Once people’s symptoms have improved on the elimination diet—if they improve—then they “challenge” their diets with different FODMAP-rich foods, explains Shanti Eswaran, a University of Michigan gastroenterologist who works with Chey. “This is where a dietitian is incredibly helpful to slowly reintroduce certain foods with regular intervals, tracking symptoms as they go to figure out what FODMAPs the patient is sensitive to.”

Those food sensitivities are going to be different for everyone, Eswaran says, and once they’ve been established, each person has an individualized iteration of the low FODMAP diet. Straying from that diet may produce IBS symptoms, but people will likely know what the trigger was.

“That alone can really give people a lot of freedom and control over their lives,” Eswaran notes. In fact, it could make them eager to hold on to all the years of their lives.

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