Back in college, I had a friend who was severely reactive to MSG. Once he figured this out and eliminated MSG from his diet, he stopped having daily headaches and his asthma improved. (Apparently our food service relied heavily on MSG to make the food halfway edible, so he’d been consuming a whole lot of the stuff.) Our senior year, I ran across some info about a study on MSG reactivity — they were having a lot of trouble recruiting participants because people would find out they were going to be deliberately fed MSG and immediately drop out of the study.
“Would you participate in a study like that?” I asked Curtis.
“No,” he said glumly. “For one thing, I’m pretty sure I could talk myself into a headache if they gave me the placebo.”
And therein lies one of the major problems with any study like this. Can you set off nausea by thinking hard about the last time you had food poisoning? If asked to log whether you have a headache, will you probably have one by the end of the logging period? Do you already know that you have a robust placebo response?1 If you also have a food sensitivity, then you are an excellent candidate for creating problematic data in a double-blind, placebo-controlled study of that sensitivity.
There have been a series of contradictory studies on non-celiac gluten sensitivity.2
In 2011, there was a paper in The American Journal of Gastroenterology titled ” Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind Randomized Placebo-Controlled Trial.” The authors introduced the abstract with obvious skepticism that non-celiac gluten sensitivity was even actually a thing: “Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism.” They had a study group of 34 patients: 19 in the gluten group, 15 in the control group. All of these patients had IBS and had been controlling it with a gluten-free diet. Of the patients being fed gluten, 13 reported that their symptoms were no longer well-controlled; only 6 of the 15 placebo patients said this.
This was allegedly a double-blind, placebo-controlled study. I say “allegedly” because within the study, they fed everyone two slices of bread and a muffin. Do you think that in a blind taste test you’d have a good shot at identifying gluten-free baked goods? Especially if you’re already on a gluten-free diet and have had a reason to try a wide variety of gluten-free breads and try to identify the ones that the most edible?3
Anyway, this study concluded that maybe non-celiac gluten intolerance really did exist, but they had no real idea what the mechanism was.
In 2013, the study that made lots of headlines was officially titled “No Effects of Gluten in Patients With Self-Reported Non-Celiac Gluten Sensitivity After Dietary Reduction of Fermentable, Poorly Absorbed, Short-Chain Carbohydrates” but since this was apparently too unwieldy for the mainstream press, it got reported as “Unless You Have Celiac Disease, Gluten Sensitivity is Probably Just in Your Head,” even though that was totally not the point of the study.
The question this study was asking was actually, “so, those people who think they’re reacting to gluten — are they maybe having trouble with something else?” Which is an interesting and complicated question.
FODMAPs are Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols. Those are all varieties of carbohydrates that are relatively hard to digest. Some people have a whole lot of trouble with them: they can’t absorb them properly, and the result is bloating, cramping, and other types of digestive distress. And, here’s the really interesting thing: wheat-based products like pasta and bread have a whole lot of FODMAPs in them. So if you have trouble with FODMAPs and you try a gluten-free diet, you will almost certainly see an improvement in your symptoms.
Imagine that you got sick every time you drank a glass of milk. You’d probably conclude you were lactose intolerant because lactose intolerance is relatively common. Lactose is the milk sugar; if you were actually reacting to the milk proteins, avoiding lactose would mostly also keep you away from the milk proteins, as well — you’d be eating some stuff you’d be better off avoiding, and avoiding some stuff you’d be fine eating, but overall, probably the main thing you’d notice would be how much better you felt. If you then participated in a dietary study where they fed you pure lactose to see if it made you sick, the researchers might conclude that your problems were all in your head. They’d be wrong; the problem was that you identified the wrong specific culprit in the first place.
Most people who have trouble with FODMAPs do not need a diet that is free from FODMAPs, they just need a diet that is low in FODMAPs. Wheat is full of FODMAPs, so eliminating gluten will probably drop your FODMAP intake by default. If you were to switch from a gluten-free diet to a low-FODMAP diet, that would allow you more dietary flexibility while also being much more annoying in some ways, since sitting down at a restaurant and saying “what do you have that’s gluten-free?” may not always get you a helpful response, but it’s at least straightforward, unlike saying “hi, I need to avoid legumes, wheat, cruciferous vegetables, and onions and all the onion-like things. And dairy except for hard cheeses which are okay. Although I can have some of all of those things, just not a whole lot.”
Anyway. This particular study started out by putting everyone on a low-FODMAP diet and then fed them a high-gluten supplement, a low-gluten supplement, and a non-gluten (whey-based) supplement to see if they had symptoms. They found, first off, that nearly everyone improved significantly on a low-FODMAP diet — lots of people who’d seen improvement in their IBS symptoms on a gluten-free diet got even better on the low-FODMAP diet. They also found very little consistent response to the gluten — lots of study participants got worse when they took the gluten supplements, but they got worse on the placebo supplements as well. Everyone rotated through the three diets, but they took two weeks or more between each diet, until whatever symptoms they were having on it fully resolved.
There were a few people who reacted just to the gluten in the first part of the trial, but then they did a shorter “re-challenge” and none of them reacted specifically to it in the second trial. There were, however, people who reproducibly reacted specifically to the whey.
So, it’s hard to know for sure what was going on here. I am pretty sure that my own nocebo response would be as robust as my placebo response, so if I were in a study like this, I would totally react to the whey if I were expecting to react to the gluten. They also note that it’s possible that a lot of the people reacting to the gluten also have trouble with whey. It was chosen for being easily digestible, but I’ll note that many of my friends with non-celiac gluten sensitivity also have issues with dairy products. The researchers also note that the gluten in the re-challenge portion of the study came from a different source, and may have been qualitatively different.
I’m not including in this list of possibilities that the people with non-celiac gluten sensitivity are imagining their symptoms and/or feeling better with the elimination of gluten entirely due to a placebo response to a special diet: I don’t believe that’s what’s going on.
Speaking of “all in your head,” though, someone in 2014 published a study on whether gluten causes depression. They again focused on patients with IBS. In the study, they supplemented diets with gluten, whey, and a placebo. They found that all three challenges resulted in gastrointestinal symptoms…but they also ran all the patients through the Spielberger State Trait Personality Inventory (STPI) and found that depression went up during the gluten challenge, but not during the other challenges.
Since I couldn’t find the full paper online anywhere that I could get to it, I’m not sure what they disclosed to the patients, but I would find this study particularly revealing if they had the patients logging and focusing on the gastrointestinal symptoms, and ran them through the STPI along with some other tests. I’m pretty sure I’m more likely to develop a nocebo response if I’m focused on the nocebo response I think the researchers are looking for.
Depression is, by its very nature, happening (at least partly) inside your head, but that doesn’t mean it’s not a physical response. Numerous drugs can cause depression as a side effect, for instance. “Feeling better” when you’re not eating gluten because the gluten is making you depressed is a legit physical response. If someone says “that’s all in your head,” they are technically correct only if you’re snorting the gluten rather than eating it.
In February of this year, a new paper came out that did yet another “is this actually a thing?” double-blind placebo-controlled cross-over test on gluten sensitivity. Things they did differently: (1) They used rice starch instead of whey as the placebo. (2) I think they may have excluded IBS sufferers, or at least they did not restrict themselves to IBS sufferers.4 (3) They looked at all the symptoms people complained about, not just gastrointestinal symptoms.5 What they found: a significant number of the gluten-sensitive patients in the study saw a worsening of their symptoms when they consumed gluten and not when they consumed the placebo.
So. Does science think that non-celiac gluten sensitivity is a thing? It really depends on the study, but on balance, I’d say that science thinks it’s a thing while still being very unsure what sort of thing it actually is. It could be something other than the gluten that’s actually setting people off. Or people could be reacting to multiple ingredients.
Should you try a gluten-free diet to treat whatever ails you? Maybe. With non-celiac gluten sensitivity, no one is really sure what’s going on. Don’t eliminate it if it’s not making you sick; that’s just silly. If you’ve got a robust placebo response, maybe target something else with your elimination diet first, like high-fructose corn syrup, because avoiding gluten is kind of a pain. But whatever diet you choose — if you feel better when you’re not eating (pick one: gluten, dairy, refined sugar, FODMAPs, high-fructose corn syrup, red dye #40…) then trust your body.
[Illustration via Shutterstock]
Technically, when you react badly to a neutral substance, that’s a “nocebo” effect. It’s only a “placebo” effect if you get better instead of worse. ↩
Whether gluten is bad for people who have celiac disease is not in question. ↩
I suppose the real question isn’t whether it’s possible to bake gluten-free bread that takes like regular bread, it’s whether you can make bread and muffins that contain gluten but have the spongy texture or weird aftertaste that so many gluten-free baked goods have. ↩
I can’t see the whole paper; that’s based on what I read in a discussion of this paper elsewhere. ↩
In the abstract, they mention bloating and pain but also foggy mind, depression, and canker sores. ↩