The Science Behind Going Gluten-Free

by Katherine Pett

“Gluten-Free” may be a fad diet buzzword, but we shouldn’t dismiss the science of gluten digestion.

Gluten1These days, everyone who’s anyone is “gluten-free.” A recent New Yorker article noted that one in three Americans say they are trying to reduce their gluten intake. The fad is polarizing, with just as many people deriding it as there are trying it. Jimmy Kimmel sums it up nicely. “Some people can’t eat gluten for medical reasons, which I get…But a lot of people don’t eat gluten because someone in their yoga class told them not to.”

Diet trends aren’t subject to the laws of science; they can and do spread with no proof of their efficacy. So once a diet becomes a fad, it’s natural for “experts” (doctors, nutritionists, the media, bloggers) to dismiss the health kick as fantasy. Going gluten-free is one such trend.

And, yes, it’s likely that for up to 93% of the population, gluten isn’t causing medical or dietary issues. But unlike forgoing all other foods for cabbage soup or a mix of maple syrup and cayenne pepper (both fads that make no medical sense), there is a reason gluten is problematic. It can’t be fully digested by anyone.

The Atkin’s diet was once so vilified that when the low-carb craze ended, people didn’t realize much of his message was correct: highly processed carbohydrates aren’t healthy, and maybe fat isn’t causing heart disease.*

Gluten is another case where the science has been buried by the craze. And once the gluten-free mania ends, as it most surely will, we should remember the scientific research that predated Gwyneth Paltrow’s swearing off gluten.

What makes gluten different?

Gluten is a protein made up of glutenin and gliadin and found in grains. Its signature property is its ability to stretch, allowing bread to rise and giving pastries their light, airy texture. The lower the gluten content, the denser the muffin (as those who have tried gluten-free baking have likely experienced).

Until recently gluten has flown under the radar, only a problem for those with celiac disease, an autoimmune disease in which gluten is the trigger. However, new research on gluten digestion along with the climbing number of celiac diagnoses have given the protein its infamous status.

Dr. Alessio Fasano, Chief of the Division of Pediatric Gastroenterology at Massachusetts General Hospital for Children, and the author of the book Gluten Freedom, has spent his career, somewhat by accident, investigating the effects of gluten in the body. Intent on designing a vaccine for cholera, his team was thwarted when cholera bacteria, though mitigated by the vaccine, still caused diarrhea in subjects. Instead of giving up the project, he looked for the mechanism that allowed cholera to bypass the vaccine. In 1991, his team discovered the cholera protein “zot,” or zonula occludens toxin. Zot somehow managed to create gaps between the cells of the gut and cause the intestine to become permeable.

The human gut, from the mouth to the colon, is generally thought of in biology as being “outside” the body. The entire length of it, from mouth to, well, rear end is a closed tunnel that keeps the food we eat and bacteria that live in our intestines from indiscriminately getting in. By segregating food “outside” the body, the gut breaks it down into particles and mediates what comes in and what stays out. The desired particles are taken in directly by these “guarding” cells and then properly packaged for delivery elsewhere in the body.

For a long time, it was assumed that these guarding cells lining our gut were permanently glued together, like cemented brick walls, and didn’t allow anything to pass through. Zot, however, caused these normally cemented cells to simply open and allow water and electrolytes to seep into the intestines, creating diarrhea, the major symptom of cholera infection. The discovery of zot led to the groundbreaking discovery by Dr. Fasano and his team of zonulin, a natural human protein that, like zot, can “open” the gut and let particles pass directly into the bloodstream.

Gut_Microbes_leaky-gut2 copy

From The Scientific American

Oddly enough, zonulin is triggered by gluten consumption. Every time you eat gluten, the cells of your gut lining become more permeable and allow particles to sneak directly into your bloodstream. For most people this isn’t a problem; their bodies easily clear the protein away. But for people with celiac disease or gluten sensitivity, this causes an immune response.

Nobody can efficiently digest gluten. Because of the composition of the protein, it is impossible for the enzymes in our guts to break down the protein into small enough parts to absorb. Those undigested protein strands, called peptides, can be misrecognized as foreign invaders and provoke our immune system.

In fact, gluten has an unusual number of peptides that can cause an immune cell response. Dr. Fasano’s lab, and others, have uncovered up to 50 potentially immune triggering sequences of amino acids, or “motifs,” in gluten alone. Dr. Fasano notes, “It is unusual for any given protein to have so many toxic domains.” 

If one develops celiac disease, the bits of gluten protein that get into the blood cause the body to form antibodies to fight the invading gluten. But the body, for some reason, creates an antibody that fights the cells of his or her gut instead, and the immune system begins to attack a human protein called transglutaminase. This attack, sustained for as long as the person continues eating gluten, causes destruction of the cells that line the gut wall. Eventually, this leads to symptoms like diarrhea and weight loss because the gut’s damaged lining can no longer ingest nutrients from food.

However, it is possible to be affected by gluten even if you don’t have celiac disease. In Gluten Freedom, Fasano points out, “Research conducted recently through the [celiac] center indicates that gluten sensitivity is controlled by the oldest immune reaction, which is our innate immune response.” This means that though people with gluten sensitivity don’t form antibodies, they do experience a strong immune response to the presence of gluten, which can manifest in many symptoms.

Fasano makes the conclusion: “I am now convinced that our immune system mistakenly interprets gluten as a component of a dangerous bacterium or bacteria. When this happens, it unleashes an immune response similar to that triggered by bacteria to rid the body of the attackers.”

So, gluten causes an immune reaction in everyone. Doesn’t that mean no one should eat it? Not quite. Humans come into contact with many potential inflammatory triggers every day. We eat more harmful bacteria than we’d like to imagine. Very rarely, however, do we “lose the fight,” as Dr. Fasano calls it, and suffer from an infection. The same is true with gluten consumption. Though everyone’s body probably treats gluten as if it is a bacterium, the vast majority of people dispose of it efficiently and without excess inflammation. In fact, it seems over 90% of the population have no negative response to gluten.

With “data from our center,” Dr. Fasano explains in the book, “We estimate that 6%, or almost 20 million, are affected by gluten sensitivity.”

While that is an undeniably large number, it leaves most of the population unharmed by gluten. For those people, glutinous bread and pastries can continue to be part of the diet.

If it doesn’t hurt me, why does it matter?

The discovery of zonulin and the effect of gluten on the intestines have implications outside of celiac disease. In fact, the “gut permeability” caused by increased zonulin levels are implicated in other autoimmune diseases including type I diabetes. It has also been less conclusively linked to conditions such as autism and schizophrenia.

This doesn’t mean that gluten causes these diseases, but that gut permeability is a precursor to the development of some autoimmune diseases. With the rate of autoimmune diseases, including celiac disease, growing substantially and for unknown reasons, the interactions between our food and our gut create a crucial point of interest.

800px-Bread_rollsDr. Fasano and other researchers are working on treatments that inhibit zonulin expression, decrease gut permeability and prevent people with celiac from having to forgo all gluten for a lifetime. While some people may laud the idea of a lifetime of no-gluten, for people with celiac, serious symptoms return if they ingest a tiny amount of gluten accidentally. This limits their ability to do things like eat school lunches, go to restaurants, or even cook using the same utensils as the rest of their family. A drug that prevents gluten proteins from getting into the body could prevent major relapses in people with celiac disease.

There is broader potential for this type of treatment if intestinal permeability is definitively shown to be a major contributor to the development of autoimmune diseases. By preventing permeability, drug therapy could prevent someone with familial risk of autoimmune disease from developing the illness.

Dr. Fasano notes that his goals are to help those with celiac and gluten sensitivity live healthier, more fulfilling lives, not to prevent everyone from eating gluten.

“Although I have contributed to the discoveries of some of these inappropriate immune responses elicited by gluten in humans, I do not share the position of the proponents of a ‘gluten free world,’ who often cite my work to support their position.”

Who should go gluten-free?

It’s easier to say who doesn’t need to go gluten-free: 93% of people. However, limiting highly processed white flour, sugary baked goods, and snack-foods is good for everyone.

Dr. Dariush Mozaffarian, Dean of the Friedman School of Nutrition, notes that some benefit can come from a fad.

“Like Dr. Atkins theory of ketogenesis, it remains unclear if gluten per se is harmful in people not documented to be gluten-sensitive,” he said. “Yet, if going gluten free helps in reducing refined grains, starches, and sugars, it could be a helpful approach.”

For most people who swear by a gluten-free diet, they likely feel better because they are eating fewer highly processed foods. Most baked sweets and snacks are out-of-bounds for the gluten-free set, and they turn to healthier alternatives. It’s important, however, not to find gluten-free alternatives that are just as unhealthy as the originals. A cupcake made without gluten is still a cupcake.

Dr. Alice Lichtenstein, D.Sc., Director of the Cardiovascular Nutrition Laboratory at Tufts University, points out the eventuality.

“Over the years I have seen people focus on low-fat diets, low-carb diets, and now gluten free diets,” she said. “Eliminating any category of food will help restrict calories until the market place catches up, and people find a way around the restriction. We saw that with low-fat: the proliferation of foods like fat-free brownies, cookies, and ice cream. We saw that with low-carb with the proliferation of foods like low carb pasta, bagels, and pizza. Now we see the same thing with gluten-free, with a remarkable array of gluten-free products, from breads, cookies and pies, to pizza.”

If you think you have celiac disease or non-celiac gluten sensitivity, consult with your physician to rule these conditions out. If you self-diagnose and start a gluten-free diet, you may be needlessly restricting or, worse, missing out on a different condition altogether. Symptoms characteristic of one autoimmune disease are often characteristic of many, so if you think you may have issues with gluten, it’s important to rule out diseases like hypothyroidism or rheumatoid arthritis first. Also, in order for celiac blood tests to be accurate, you must be consuming gluten at the time of the test. 

If you partake in a gluten-free diet because someone in your yoga class recommended it, and not for medical reasons, more power to you! Just keep in mind that the health benefits (for the 93%) likely come from making healthier choices overall, and not just the lack of bread in your diet.

*Correction:
The downsides of saturated fat are still up for debate: Notably, Dr. Lichtenstein does not agree that saturated fat is not related to heart disease risk.  “There is strong evidence that saturated fat intake is positively related to LDL cholesterol concentrations and LDL cholesterol concentrations are positively related to heart disease risk. When considering diet the devil is in the details.  Substituting polyunsaturated fat for saturated fat is associated with decreased risk of heart disease, substituting carbohydrate for saturated fat has not been associated with risk of heart disease.  The point is with macronutrients one should not consider each in isolation but in terms of an exchange. It would be unfortunate if the message was that it is now okay to eat saturated fat with abandon as some news articles have implied.”

Katherine Pett is a Master’s student at Friedman studying Biochemical and Molecular Nutrition. She can be reached at Katherine.docimo@tufts.edu or on twitter @smarfdoc

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Comments

  1. This article provides a very clear and informative overview of Gluten and its impact on health. It made me wonder if gut flora may play a role in this process. Might some gut flora actually buffer the gut lining to prevent or mitigate the permeability caused by zonulin? This might occur by somehow preventing the production of zonulin, or my protecting the gut from its effects. Conversely, might the wrong gut flora reduce the body’s ability to suppress zonulin’s production or impact? It will be interesting to see where the science leads in the coming years as we gain a more complete picture of the biology.

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