 In 1980, researchers in England reported a series of women who suffered from chronic diarrhea that resolved on a gluten-free diet, yet did not have evidence of celiac disease, the autoimmune disorder associated with gluten intolerance. The medical profession was skeptical at the time, and even 30 years later. So much so that, much like patients who had irritable bowel syndrome, patients claiming non-celiac gluten sensitivity were commonly referred to psychiatrists because they were believed to have an underlying mental illness. Psychological testing of such patients, however, found no evidence as they were suffering from some kind of psychosomatic hysteria. The medical profession has a history of dismissing diseases as all in people's heads—PTSD, ulcerative colitis, migraines, ulcers, asthma, Parkinson's, MS. Despite resistance from the prevailing medical community at the time, these health problems have subsequently been confirmed to be credible physiologically-based disorders rather than psychologically-based confabulations. On the flip side, the internet is rife with unsubstantiated claims about gluten-free diets, which has spilled over into the popular press to make gluten the diet villain du jour, with claims like, 17 million Americans are gluten-sensitive. However, it must be remembered that this is also big business. When literally billions of dollars are at stake, it's hard to trust anybody. So is always best to stick to the science. What sort of evidence do we have for the existence of a condition presumed to be so widespread? Not much. The evidence base for such claims was unfortunately very thin because we didn't have randomized controlled trials demonstrating that the entity even exists. The gold standard for confirming non-celeac gluten sensitivity requires a gluten-free diet followed by a double-blind, randomized, placebo-controlled food challenge, like you give someone a muffin, and they're not told if it's a gluten-free muffin or a gluten-filled muffin to control for placebo effects and see what happens. The reason this is necessary is because when you actually do this, a number of quote-unquote gluten-sensitive patients don't react at all to disguised gluten, and instead react to the gluten-free placebo, so it truly was in their heads. But we never had that kind of level of evidence until 2011, when a double-blind, randomized, placebo-controlled trial was published, which tested to see if patients complain of irritable bowel type symptoms, who claimed they felt better on a gluten-free diet, despite not having celiac disease, actually could tell if they were given gluten-free bread and muffins or gluten-containing bread and muffins. They started out gluten-free and symptom-free for two weeks, and then they were challenged with the bread and muffins. Here's what happened to the 15 patients who got the placebo, meaning they started out on a gluten-free diet and continued on a gluten-free diet, they got worse. Just a thought that they may be eating something that was bad for them made them feel all cramping and bloated. This is what's called a nocebo effect. The placebo effect is when you give someone something useless and they feel better. The nocebo effect is when you give someone something harmless and they feel worse. But the small group that got the actual gluten felt worse still. So, they concluded this non-celiac gluten intolerance may actually exist. It was a small study, though, and even though they claimed the gluten-free bread and muffins were indistinguishable, maybe at some level the patients could tell which is which. So, in 2012, researchers in Italy took 920 patients that had been diagnosed with non-celiac gluten sensitivity and put them to the test with a double-blinded wheat challenge by giving them not bread and muffins, but capsules filled with wheat flour or filled with placebo flour, or kind of placebo powder, no flour at all. And more than two-thirds failed the test, like they got worse on the placebo or better on the wheat. But of those that passed, there was a clear benefit to staying on the wheat-free diet, confirming the existence of a non-celiac wheat sensitivity. Now, note they said wheat sensitivity, not gluten sensitivity. Gluten itself may not be causing gut symptoms at all. See, most people with wheat sensitivity have a variety of other food sensitivities. Two-thirds are sensitive to cow's milk protein as well, then eggs were the most common culprit after that. So if you put people on a diet low in common triggers of irritable bowel symptoms and then challenge them with gluten, there's no effect. Same increase in symptoms with high gluten, low gluten, or no gluten. Calling into question the very existence of non-celiac gluten sensitivity. Interestingly, despite being informed that avoiding gluten wasn't apparently doing a thing for their gut symptoms, many participants opted to continue following a gluten-free diet as they just subjectively described feeling better. So the researchers wondered if avoiding gluten might be improving the mood of those with wheat sensitivity, and indeed, short-term exposure to gluten appeared to induce feelings of depression in these patients. But whether non-celiac gluten sensitivity is a disease of the mind or the gut, it is no longer a condition that can be dismissed.