What’s the deal with gluten sensitivity?

Gluten has been getting a lot of attention lately—both from people who avoid it and from others who scoff at them. In fact, when my husband brought a review of recent research to my attention on certain social media site (follow me here!), it sparked a passionate debate between folks with self-diagnosed non-celiac gluten sensitivity (NCGS), as it has recently been named, and others opposing the idea.   I promised an in-depth assessment of the study.  So I’ve read about 15 papers and now have some perspective to share.

It turns out that in the last 3-4 years, NCGS has gotten its name, its own acronym, and a whole lot of scrutiny.  This attention is good.  Because despite heavy-handed articles like this one that claim one study can close the book on a subject, it is actually by looking at the weight of evidence that we can begin to understand a subject.  Right now, NCGS research is in its infancy.  Researchers are only just now starting to believe in this new entity, so please don’t expect me to give you a definitive answer. I will say though: it is looking like wheat sensitivity is a real thing, although the details need to be sorted out.  I’ve seen this clinically for years, but now the research is starting to support my experience.

In 2011, Jessica Biesiekierski et al published one of the first studies since the early 1980s to examine possible negative effects of gluten.  It was decisively titled Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind Randomized Placebo-Controlled Trial.  After ruling out celiac disease, this group followed the gold standard for identifying food sensitivities: double blind, placebo-controlled challenge. The subjects were a small group of 34 irritable bowel syndrome (IBS) sufferers whose symptoms were controlled by avoiding gluten. They were split into two groups: one given gluten in the form of 2 bread slices and a muffin per day, the other given placebo as gluten-free forms of bread and muffins.  After 6 weeks, the gluten-free group was doing significantly better than the gluten group.  The results of this study showed that the subjects who ate gluten had more pain, more fatigue and worse stool consistency “over the entire study period.”

If you’ve ever tasted gluten-free—well, gluten-free anything, it is hard to miss. The team accounted for that. All the bread and muffins were made with the same flour base, but commercially prepared pure gluten was added back in to the test breads.  And in a mini-pre-test test, 10 subjects could not tell the difference.

Surprised by their results, the group followed up with two more specific—but still small—studies to investigate where these effects were coming from.  They used many of the same people with IBS who did not have celiac disease. (By the way, folks, it is not celiacs.  No “s.”)  In both, they rigidly controlled the subjects’ diets to eliminate the “background noise” of their regular diets, as much as possible.   After two weeks on a diet low in Fermentable Oligo-Di-Monosaccharides and Polyols (FODMAPs), all the subjects felt better: this was the baseline where they started giving the gluten and placebo baked goods.  In contrast to the previous study, the results of this first follow-up study did not show an association between gluten and symptoms of pain, fatigue, bloating, or wind, as they say in Australia.  In other words, gluten wasn’t the problem.   Curious why the subjects decided to stay gluten-free despite these results, they investigated again and found that gluten did significantly increase symptoms of depression (not by a lot, but it was statistically significant).

There are some issues with their approach, including the use of whey protein as a placebo.  Whey protein is problematic because dairy is often a trigger in people with IBS.  However, they looked at this, by following up with a trial that included a GFDF placebo arm in both of these follow-ups and their results did not change.

Another problem with this study was with their selection of participants.  They carefully ruled out celiac disease, as they should, and had specific criteria for subjects who were on a GF diet and whose symptoms were adequately controlled. However, a number of these people who met the criteria reported that while they felt better on a GF diet, they still had symptoms.  This suggests they these people may have had other sensitivities. There may have been an unintentional selection bias for people who were indeed sensitive to gluten, but perhaps also to the FODMAPs—most likely to the fructans contained in wheat.  The mood issues may be due to exorphins–mood-changing opioid-like peptides derived from gluten and other proteins.  Also, they may have also excluded people with allergy/sensitivity to gluten and ended up with a very specific population.  This is part of the trouble with small studies of tens rather than thousands of people: it is very difficult to extrapolate results to the general population.  Read more about this issue here if you like.

Despite these problems, this is a very interesting paper that really does help us to understand what may be going on for a lot of people.  Many folks who believe they are sensitive to gluten may indeed do better on a gluten-free diet, but they may actually be sensitive to the fructans or other FODMAPs in wheat, rye, and barley.  Biesiekierski et al suggested another interesting point: perhaps FODMAPs and gluten work hand in hand to create symptoms.  Perhaps in some people the FODMAPs are the main irritant but when take with gluten, things get worse.  Interestingly, in a 2013 review, the same group points out, “Cereal products with the lowest FODMAP contents are mostly gluten-free, based on rice, oat, quinoa and corn ingredients,” so that people on a GF diet may end up feeling better whether its the gluten or the FODMAPs that were the original problem.

In the research that I have reviewed, it is pretty well accepted that some kind of reaction that is currently being called NCGS does exist, at least in some populations.   Antonio Carrocio and his buddies suggested that non-celiac wheat sensitivity would be a better name. I agree.  Even this name is not perfect, but no one is going to say Non-Celiac Wheat-Rye-Barley-Triticale sensitivity.  As it stands right now, we do not know for sure what it is in these grains that people are reacting to.  In addition to the aforementioned gluten, FODMAPs, and exorphins, there are other potential problems.  Non-gluten wheat proteins including α-amylase/trypsin inhibitors have recently been shown to cause inflammation in the gut.  And then there is the little-recognized, but well established wheat allergy (most common in bakers).  We also do not yet understand the underlying mechanism, although this has also been the subject of recent research.  Remember that part about me not being able to give you a definitive answer?  Yeah, here it is.

Before I wrap up, I have to offer a brief word on avoidance diets in general. It is not all about gluten. Many people do not tolerate gluten, but gluten is not the only food people do not tolerate.  If you have persistent digestive issues, a gluten-free trial is a reasonable approach, but if that does not resolve your issues, do not give up. There are many foods that I have found irritate people and cause symptoms. Discovering what these are is best done under supervision, as questions usually arise during the process, and it can be tricky to get adequate calories and sound nutrition.   I do find value in books like David Perlmutter’s Grain Brain.  But I am frustrated by the current laser focus on gluten and grains. The link between inflammation, chronic disease, and overconsumption of refined carbohydrates is important.  But in addition, in my practice, I find many people are sensitive to other foods, commonly dairy, soy, and corn, among others.  Food is a major culprit in the epidemic of chronic disease in the USA, beyond obesity, diabetes and cardiovascular disease.


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