Gluten not the cause of GI symptoms and ‘brain fog’

Coeliac disease

2 Aug 2022

Two new studies have added more support to the notion that gluten is not the trigger for GI symptoms and ‘brain fog’ in people without coeliac disease, an Australian expert says.

While previous studies of so-called Non Coeliac Gluten Sensitivity (NCGS) have provided mixed results, a new placebo-controlled trial has shown that people whose GI symptoms improve on a gluten elimination diet do not show recurrence when rechallenged with gluten in a blinded fashion.

The results therefore suggest that there may be some other factor in a gluten elimination diet that is triggering the GI symptoms, according to Professor Jason Tye-Din of the Department of Gastroenterology, The Royal Melbourne Hospital, and Melbourne University.

In a recent Danish study, 54 young people who had multiple GI symptoms  such as abdominal pain, bloating and constipation – but without coeliac disease – were enrolled to an initial phase of a trial in which they undertook gluten free diet for two weeks. Those who showed significant improvement in GI symptoms (n = 33) continued into the next phase in which they were randomised to receive either a blinded rechallenge with additional gluten (10g/day) of placebo for seven days, followed by a crossover to the other intervention.

The results showed that while 36% of the group  reported significant worsening of GI symptoms with gluten re-challenge, this was the same rate as seen with placebo. One in four participants (24%) reported no difference between gluten and placebo.

Overall, gluten was no more likely to induce gastrointestinal symptoms than placebo. The findings support several DBPCGC that fail to show overall deterioration with gluten and demonstrate high nocebo effects.

The trial participants had HLA DQ2 and/or DQ8 frequency comparable to the general population and there was no significant difference in the frequency of HLA DQ2 and/or DQ8 among either the gluten or placebo-responders.

There were also no differences between gluten and placebo for individual GI symptoms, nor for the secondaty outcome of mental health measures.

Similarly findings from an Australian study published in the same journal also showed no detrimental effect of gluten re-challenge in 16 adults with self-reported NCGS who had shown improvement on a gluten elimination diet.

During 14 days of follow up, researchers at the Department of Gastroenterology, Monash University, observed no differences between gluten and placebo in GI symptoms or mental health (depression, anxiety, stress,) fatigue or quality of life.

In a linked editorial Professor Jason Tye-Din said the findings from these and other studies  suggested it was time to ditch the ‘gluten’ from ‘non-coeliac gluten sensitivity’.

“[The] findings greatly strengthen the notion that gluten is not a driver of gastrointestinal symptoms in people without coeliac disease and that symptomatic improvement on a gluten-free diet poorly predicts subsequent symptoms to a ‘pure’ gluten challenge,” he wrote.

“NCGS may be better substituted with ‘non-coeliac wheat sensitivity’ although this fails to encompass people avoiding wheat, rye and barley,” he added.

Other putative triggers of NCGS, such as amylase–trypsin inhibitors or FODMAPs,  will require further studies and research examining novel mechanisms, said Professor Tye Din.

The articles are published in Alimentary Pharmacology and Therapeutics.

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