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.
Bibliografisk noteFunding Information:
Funding informationThis project was funded by the A.P. Møller Fund (grant nos.19‐L‐0228 and 18‐L‐0032), Odense University Hospital Research Fund (A3675 and A 2971), Direktør Kurt Bønnelyckes og hustru Fru Grethe Bønnelyckes Fund (100 53030), Torben og Alice Frimodts Fund (n/a), and L.F. Foghts Fund (21.844) to CC and the Augustinus Fund (19–2419) to SH. Thermo Fischer (n/a) donated $70 000 and had no influence on the design of the study. CC holds a PhD grant funded by the University of Southern Denmark, the Region of Southern Denmark, and Hans Christian Andersen Children’s Hospital. The Department of Clinical Immunology, Odense University Hospital covered the cost of the Coeliac screening analysis. Professor Christensen acknowledges that the Section for Biostatistics and Evidence‐Based Research, the Parker Institute is supported by a core grant from the Oak Foundation (OCAY‐18‐774‐OFIL). Novo Nordisk Foundation Center for Basic Metabolic Research is supported by Novo Nordisk Foundation (grant number NNF18CC0034900). Dr. Joseph Murray has received study grants from Nexpep/ImmusanT, National Institutes of Health, Immunogenix, Takeda Pharmaceutical, Allakos, Oberkotter, and Cour.
The Danish National Birth cohort was established with a significant grant from the Danish National Research Foundation. Additional support was obtained from the Danish Regional Committees, the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Health Foundation, and other minor grants. The DNBC Biobank has been supported by the Novo Nordisk Foundation and the Lundbeck Foundation.
Follow‐up of mothers and children has been supported by the Danish Medical Research Council (SSVF 0646, 271–08‐0839/06–066023, O602‐01042B, 0602‐02738B), the Lundbeck Foundation (195/04, R100‐A9193), Innovation Fund Denmark 0603‐00294B (09–067124), the Nordea Foundation (02–2013‐2014), Aarhus Ideas (AU R9‐A959‐13‐S804), University of Copenhagen Strategic Grant (IFSV 2012), and the Danish Council for Independent Research (DFF‐4183‐00594 and DFF‐4183‐00152).