Numerous people may be following a gluten-free diet, possibly unnecessarily, say experts after a study suggested that many with self-declared gluten sensitivity experienced symptoms whether or not they ate gluten.
The researchers suggested that people who report being gluten intolerant but do not have coeliac disease may, in fact, be experiencing gut symptoms unrelated to gluten intake.
Associate Professor Jessica Biesiekierski of the University of Melbourne, one of the study’s senior authors, told The Guardian the findings were significant in light of popular blame on gluten as a trigger for various symptoms.
Only about 1% of people in western countries have coeliac disease, an autoimmune condition in which gluten causes an inflammatory reaction in the small bowel.
“Coeliac disease is a well-defined medical condition. It has a clear diagnostic pathway,” Biesiekierski said. For people with coeliac disease, a gluten-free diet is the only effective treatment option.
However, about 10% of the population self-report being gluten sensitive. “We’ve got this large number of people who are following a gluten-free diet, possibly unnecessarily,” she added.
“Gluten is actually a complex mixture of proteins found in wheat, and related proteins are also present in rye, barley and sometimes oats.
“When you follow a gluten-free diet, you’re excluding an entire group of cereals and grains. Over the long term, this can lead to nutritional inadequacies and is often costlier.”
The study involved 16 participants with non-coeliac gluten sensitivity and 20 healthy controls. Researchers gave participants yoghurt containing either 16g of gluten or whey protein. For five days, the participants also consumed two muffins daily, which each contained either 8g gluten, or no gluten.
After a two-week period, participants were then switched to the other intervention but were not aware of which they were ingesting.
Individuals with gluten-sensitivity reported increased fatigue after both the gluten and placebo yoghurt, compared with healthy controls. They also reported increased pain and bloating with both the gluten and gluten-free muffins.
Urine, blood and saliva samples taken for cortisol levels and markers of inflammation showed no differences after gluten ingestion.
“Participants continued to report gastrointestinal symptoms, but these symptoms didn’t appear to be specifically triggered by gluten,” Biesiekierski said.
Researchers believe the response to gluten may be explained by a nocebo effect, the opposite of the placebo effect, in which a negative outcome results from an expectation that the treatment will be harmful.
At baseline, the gluten-sensitive participants had a higher negative effect, the researchers noted.
“From working with these patient groups for more than 15 years, I can say their symptoms are real. It’s just that, for many of them, gluten may not be the specific cause,” Biesiekierski said.
Previous research has suggested that fructan, a type of carbohydrate, may be the culprit for abdominal symptoms in people with self-reported gluten sensitivity.
Rather than immediately turning to a gluten-free diet, the researchers suggest people should consult a dietician to explore whether other dietary triggers such as high Fodmaps (Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols) foods may be involved.
“We have strong evidence supporting psychological treatments like cognitive behavioural therapy and gut-directed hypnotherapy,” Biesiekierski said. “These approaches help to rewire the gut-brain pathways that may be contributing to the symptoms.”
Dr Kerith Duncanson, a research dietician at the University of Newcastle who was not involved in the research, described the study as “very nicely designed” but said the main limitation was its small sample size.
“Much larger numbers are needed for definitive conclusions and application to clinical practice,” she said.
“While the study progresses understanding … it does not provide evidence that non-coeliac gluten sensitivity does not exist.
“As a dietician working clinically in this field, the reality is that people who present with suspected non-coeliac gluten sensitivity may have had considerable medical investigations and procedures or may simply have noticed they felt better when not eating wheat, and been following a gluten-free diet.”
Associate Professor Jason Tye-Din, head of the coeliac research lab at the Walter and Eliza Hall Institute of Medical Research, who was not involved in the study, said despite the small sample size the study added to evidence “that non-celiac gluten sensitivity is most likely not driven or caused by gluten”.
“I think it’s a very positive and important study,” he said. “Future studies hopefully will be larger and explore this concept further.”
The research was published in the United European Gastroenterology Journal.
Study details
Impact of Acute and Sub-Acute Gluten Exposure on Gastrointestinal Symptoms and Psychological Responses in Non-Coeliac Gluten Sensitivity: A Randomised Crossover Study
Julie Iven, Annelies Geeraerts, Tim Vanuytsel, Jan Tack, Lukas Van Oudenhove, Jessica R. Biesiekierski.
Published in UEG Journal on 26 March 2025
Abstract
Background/Aims
Non-coeliac gluten sensitivity (NCGS) is a controversial entity, characterised by symptom improvement with gluten exclusion in the absence of coeliac disease. We primarily investigated the effects of acute and sub-acute gluten on psychological and mood profiles, with secondary outcomes examining gastrointestinal symptoms and biological markers in healthy controls (HC) and individuals with NCGS.
Methods
A randomised, single-blind, crossover study used acute (16 g gluten or whey in yoghurt) and sub-acute (gluten-containing (16 g) or gluten-free muffins per day for 5 days) challenges. (Extra)intestinal symptoms, intestinal permeability, high-sensitive C-reactive protein and cortisol awakening response were assessed. Responses over time were analysed using generalised linear mixed models.
Results
Twenty HCs (15% men, mean age 30 years) and 16 individuals with NCGS (31% men, mean age 33 years) participated. No significant group-by-nutrient interactions were observed. Negative affect scores were higher and positive affect scores were lower in NCGS compared to HC (p = 0.01 and p = 0.04, respectively). Participants experienced higher tension scores after gluten compared with placebo (p = 0.01 acute; p = 0.05 sub-acute) regardless of the group. After acute administration, fatigue scores increased in NCGS (p = 0.03) compared with HC regardless of nutrient intake. After sub-acute administration, abdominal pain scores (p < 0.001) and bloating (p = 0.001) increased in NCGS compared with HC regardless of nutrient intake. No differences were found for biological markers.
Conclusions
These findings reveal that NCGS is characterised by baseline differences in affect, and higher acute fatigue and subacute gastrointestinal symptoms that are not gluten-specific. This may be explained by nocebo effects, warranting research into novel mechanisms and re-evaluating the NCGS definition.
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