Important role of expectation effect in complaints of non-celiac gluten sensitivity

Important role of expectation effect in complaints of non-celiac gluten sensitivity
Important role of expectation effect in complaints of non-celiac gluten sensitivity

Part of the general population experiences complaints after taking wheat products, without celiac disease or wheat allergy. Gluten is often seen as the cause of these complaints, also called non-celiac gluten sensitivity (NCGS). “However, we currently have no clear indications that specific biological factors lead to complaints in NCGS,” says Prof. DMAE (Daisy) Jonkers, professor of Intestinal Health at Maastricht UMC+. That is why we investigated whether psychological factors may play a role in this. The central question is: can the expectation of developing complaints after eating gluten contribute to the experience of NCGS complaints? And this appears to be the case, according to Jonkers.

In the Western world, wheat is a staple food, Jonkers explains the reason for the research. “We associate whole grain products in particular with positive effects on health, including lower risks of obesity, type 2 diabetes, cardiovascular disease, cancer and death in general.”1 But wheat products can also have negative effects such as celiac disease or wheat allergy. In addition, some people with gastrointestinal complaints avoid taking wheat products because they feel that gluten is the cause of these complaints. NCGS is often a self-reported diagnosis. “But avoiding wheat products can mean that the diet of these people is generally of insufficient quality,” says Jonkers. “We would therefore like to understand where these complaints come from so that we can provide these people with good nutritional advice.”

Psychological factors

To date, there is little evidence for the role of gluten in complaints of NCGS. An influence of psychological factors cannot be ruled out. For example, a double-blind, placebo-controlled study showed that people with NCGS had an increase in gastrointestinal complaints and abdominal pain, regardless of whether they received an intervention with high gluten, low gluten or placebo.2 Jonkers: “All participants received these 3 interventions, in a random order. In addition to the fact that the researchers actually saw no difference in complaints between the interventions, they also saw that most complaints occurred with the first intervention that the participants received, regardless of whether this was placebo or one of the interventions with gluten. These findings triggered us: it seemed as if the expectation that people would eat gluten contributed to the development of complaints.” The role of this expectation effect was subsequently investigated in a randomized, double-blind, placebo-controlled study (conducted at the University of Leeds, the University of Maastricht and Wageningen University & Research).1


This study included people with self-reported NCGS who reported developing gastrointestinal complaints (such as abdominal pain, diarrhea, flatulence) within 8 hours of eating gluten. But extra-intestinal complaints such as fatigue, concentration problems and headaches were also examined. People with celiac disease were explicitly excluded from participation; this was tested first if it had not already been done. Jonkers: “We told the participants that we wanted to investigate the effect of bread with or without gluten on their complaints. On the test day itself, we informed each participant whether they would receive the gluten-containing or gluten-free bread. But what they did not know was that an additional randomization took place. In the group that expected to receive gluten-containing bread, half actually received bread with gluten and the other half received gluten-free bread. The same was done with the group that expected not to receive gluten-containing bread.” The study population ultimately consisted of 4 groups: people who expected to get gluten and did get it, people who expected to get gluten but didn’t get it, people who expected not to get gluten but did get it, and people who expected not to get gluten. and they didn’t get it either. Jonkers: “We misled the participants a bit, but this way we could properly investigate the role of the expectation effect in the development of complaints.” Prior permission for this was requested from the medical ethics committee.

Significantly more complaints

The results showed that the group that expected to receive gluten and actually received it reported the most complaints and also had significantly more complaints than the group that did not expect to receive gluten. Jonkers: “This was regardless of whether they actually ate gluten or not. And interestingly enough, we hardly saw any complaints arising in the group that did not expect to receive gluten, even in the people who did eat gluten. Based on this, we concluded that the expectation of receiving gluten plays an important role in actually developing complaints. But because we saw the greatest effect in the group that had a positive expectation and also received gluten, we cannot rule out that there is also an actual effect of gluten on the complaints.”

No posturing

It’s all quite complex, Jonkers agrees. “What we can conclude from this is that there is an important interaction between the brain and the intestines and that this may also play a role in NCGS. Many people recognize this: for example, they get a stomach ache when they are tense about something.” An important point that Jonkers emphasizes is that people with NCGS do not pretend, but that they experience real complaints. “It is therefore important to take these complaints seriously.” Her advice is to explain to people with NCGS that concerns about complaints can contribute to experiencing complaints, and then to try to remove those concerns. “It can also be helpful to advise patients to try different types of bread, if they are willing to do so. We have seen in another study that people can often tolerate a different type of bread. And if people do not want this, they may be advised to see a dietician to ensure that they have a healthy food intake despite avoiding gluten.”

But the study also showed that there are major differences between people and their complaints. Jonkers: “For some, the expectation effect will be more prominent in the development of complaints, while for others it will be gluten or possibly other components of grains. Unfortunately, we cannot provide general advice. I also do not expect that there is one generic mechanism underlying the complaints. In short: there is still plenty to investigate.”


  1. De Graaf MCG, Lawton C, Croden F, et al. The effect of expectancy versus actual gluten intake on gastrointestinal and extra-intestinal symptoms in non-celiac gluten sensitivity: a randomized, double-blind, placebo-controlled, international, multicenter study . Lancet Gastroenterol Hepatol. 2024;9:110-23.
  2. Biesiekierski JR, Peters SL, Newnham ED, Rosella O, Muir JG, Gibson PR. No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterology. 2013;145:320-8.

Well on wheat

The study into the expectation effect in non-celiac gluten sensitivity was conducted in the context of the international ‘Well on wheat’ project. Several studies are being conducted in the project into the health aspects of wheat consumption and the avoidance of wheat and gluten. For example, the biochemical composition of different types of wheat is analyzed, after which it can be investigated whether and which wheat components cause complaints.

As part of this project, breads from different grain types (wheat, spelt and emmer) were also biochemically analyzed and the effect of soil types and climate on the grains was examined. Jonkers: “We saw that the biochemical differences between the breads of the same grain in a different soil type or different climate were greater than the differences between the 3 grain types. This means that people who tolerate a grain type well one year may still experience problems with it the next year because it may have been a drier or wetter year than before. So it may be worth trying a loaf of the same type of wheat from a different bakery, for example, simply because there is so much variation.”

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The article is in Dutch

Tags: Important role expectation effect complaints nonceliac gluten sensitivity


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