The effect of gluten in adolescents and young adults with gastrointestinal symptoms: a blinded randomised cross‐over trial

Abstract

Background The popularity of the gluten‐free diet and sales of gluten‐free products have increased immensely. Aims To investigate whether gluten induces gastrointestinal symptoms, measured by self‐reported questionnaires, as well as mental health symptoms in adolescents from a population‐based cohort. Methods The eligible participants (n = 273) were recruited from a population‐based cohort of 1266 adolescents and had at least four different gastrointestinal symptoms. Phase one (n = 54) was a run‐in phase where the participants lived gluten‐free for 2 weeks. If they improved they continued to phase 2 (n = 33), a blinded randomised cross‐over trial. Participants were blindly randomised either to start with 7 days of gluten, eating two granola bars containing 10 g of gluten or to 7 days on placebo, eating two granola bars without gluten, followed by the reverse and separated by a 7‐day washout period. The effects of the intervention on gastrointestinal symptoms and mental health symptoms were assessed. Results In total, 54/273 participants entered the run‐in phase and 35 were eligible for randomization. A total of 33 were randomised and 32 completed the trial. The median age was 20.3 (IQR 19.2–20.9) and 32/33 participants were females. Compared with a placebo, gluten did not induce gastrointestinal symptoms. The difference in the average VAS was −0.01 (95% confidence interval −2.07 to 2.05). Nor did we find a difference in the outcomes measuring mental health. Conclusion Compared with placebo, adding gluten to the diet did not induce gastrointestinal symptoms or worsened mental health in adolescents recruited from a population‐based cohort. The trial registration number is NCT04639921.

Nonceliac gluten sensitivity

“…The triggering effect of a single dietary component like gluten is difficult to prove in controlled studies, because of an unavoidable, strong nocebo effect. This has been confirmed by a recent blinded, randomized cross-over trial, performed on adolescents and young adults affected with multiple gastrointestinal symptoms that responded to the GFD: in these subjects, the ingestion of 10 g of purified gluten for 1 week, as compared with placebo, did not elicit gastrointestinal symptoms or worsened the outcomes measuring mental health [7 ▪ ]. On the other hand, it is becoming increasingly clear that wheat components different from gluten may cause symptoms of NCWS.…”

Letter: progressive weakening of the concept that gluten has a detrimental effect on mental health and gut symptoms in the absence of coeliac disease

“…We read with interest the study of Crawley et al 1 who demonstrated the lack of effect on mental health of 7-day blinded rechallenge with gluten (10 g/day) in 33 adolescents whose gastrointestinal symptoms improved over 2 weeks' gluten-free diet. This seemed to be in contrast to the findings of an exploratory study in 2013 (not cited by Crawley) in which 16 g/day gluten over 3 days appeared to specifically induce current feelings of depression in 22 subjects with self-reported gluten sensitivity; whey protein or placebo did not.…”

Editorial: lack of gastrointestinal symptoms caused by gluten in patients without coeliac disease—time to ditch the ‘gluten’ from ‘non‐coeliac gluten sensitivity’

“…As a result, trials employing DBPCGC have failed to resolve if gluten is the trigger in NCGS although several have implicated fermentable carbohydrates (FODMAPs) 5,6 . Crawley and colleagues applied a rigorous DBPCGC approach in an adolescent/young adult cohort 7 . To minimise nocebo confounding, they recruited participants with gastrointestinal symptoms and a subsequent response to a gluten‐free diet, as opposed to those with self‐reported NCGS.…”

“…5,6 Crawley and colleagues applied a rigorous DBPCGC approach in an adolescent/young adult cohort. 7 To minimise nocebo confounding, they recruited participants with gastrointestinal symptoms and a subsequent response to a gluten-free diet, as opposed to those with self-reported NCGS.…”