The effect of a controlled gluten challenge in a group of patients with suspected non‐coeliac gluten sensitivity: A randomized, double‐blind placebo‐controlled challenge

Dale, Hanna Fjeldheim; Hatlebakk, Jan Gunnar; Hovdenak, Nils; Ystad, S.O.; Lied, Gülen Arslan

doi:10.1111/nmo.13332

Cited by 37 publications

(41 citation statements)

References 25 publications

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“…Methodological issues related to short wash‐out periods between challenges contribute to complicate interpretation of results. Subsequent studies, including the one by Dale et al., failed to show symptomatic responses to gluten, when the challenge is introduced in a blinded fashion. Although the study had a rigorous double‐blind placebo‐controlled design, FODMAPs were not specifically removed from the treatment.…”

Section: Introductionmentioning

confidence: 99%

“…There have been several randomized clinical trials (RCT) addressing this issue with different design, controversial results and which are subject to many limitations inherent to dietary intervention trials. In this issue of Neurogastroenterology and Motility, Dale et al 7 performed a double-blind placebo-controlled randomized trial, to evaluate whether symptomatic response in a suspected NCGS population on GFD, could be reproduced after gluten intake compared to placebo. Diagnostic criteria for NCGS included the presence of gastrointestinal and/or extra-intestinal symptoms related to food intake, which improved on a GFD.…”

Section: Introductionmentioning

confidence: 99%

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Non‐celiac gluten or wheat sensitivity: It's complicated!

Sánchez

Verdú

2018

Neurogastroenterology Motil

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In the last 30 years, non‐celiac gluten sensitivity (NCGS) has emerged as an intriguing and controversial topic in gastroenterology. The diagnosis of NCGS/NCWS requires a symptomatic reaction to gluten, or wheat‐containing food, and remission of symptoms with gluten or wheat challenge, in patients in whom celiac disease and wheat allergy have been excluded. There have been several randomized clinical trials (RCT) addressing this issue which have produced controversial results. In this issue of Neurogastroenterology and Motility, a double‐blind placebo‐controlled randomized trial in patients with suspected NCGS on GFD, did not reproduce symptoms after gluten intake compared to placebo. This mini‐review addresses outstanding issues related to the diagnosis of NCGS/NCWS as well as areas of interest for future studies that could explain, in part, the controversy in this area.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Non‐celiac gluten or wheat sensitivity: It's complicated!

Sánchez

Verdú

2018

Neurogastroenterology Motil

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“…Furthermore, the actual dietary triggers and the putative mechanisms underlying GI symptoms and extra‐GI manifestations in NCG/WS patients remain still poorly understood. The role for gluten in GI and extra‐GI symptom generation is still controversial . As non‐gluten proteins and fermentable short‐chain carbohydrates have also shown similar effects although mainly in the GI spectrum .…”

Section: Introductionmentioning

confidence: 99%

Mast cell‐nerve interactions correlate with bloating and abdominal pain severity in patients with non‐celiac gluten / wheat sensitivity

Giancola

Volta

Repossi

et al. 2020

Neurogastroenterology Motil

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Tack and De Giorgio share co-last authorship.Abbreviations: CD, celiac disease; FD, functional dyspepsia; GFD, gluten/wheat-free diet; GI, gastrointestinal; IBS, irritable bowel syndrome; MC, mast cells; NCG/WS, non-celiac gluten/ wheat sensitivity. Abstract Background: Gastrointestinal (GI) and extra-GI symptoms/manifestations represent key clinical features of patients with non-celiac gluten/wheat sensitivity (NCG/WS). This study aimed to investigate neuro-immune (focusing on mast cells, MCs) interactions in the duodenal submucosa of patients with NCG/WS. Methods: Submucosal whole mounts from duodenal biopsies of 34 patients with selfreported NCG/WS, 28 with celiac disease (CD), 13 with functional dyspepsia (FD), and 24 healthy controls (HC) were analyzed by immunohistochemistry. Quantitative data on neuronal and MCs density and the percentage of MCs in close vicinity to nerves were obtained, and correlations among neurons, MC density and MC-nerve distance (D), and symptoms were assessed in the three groups.Key Results: The number of submucosal neurons was not different among groups.In NCG/WS, MC density was not different from HC, while it was slightly increased vs. CD (P = .07) and significantly decreased vs. FD (P < .05). The percentage of MCs close to nerves (D < 15 µm) was similarly increased in all three pathological groups vs. HC (P < .001). In NCG/WS, MC infiltration correlated with bloating (P = .001) andabdominal pain severity (P = .03) and the percentage of MCs in proximity to neurons correlated with the number of GI symptoms (D < 5 µm; P = .05), bloating and abdominal pain severity (D < 15um; P = .01). Conclusions and Inferences: Submucosal MC infiltration and the close (within 15 µm)MC-to-nerve proximity in the duodenum of NCG/WS patients are features providing a histopathological basis to better understand GI symptoms in this condition. K E Y W O R D Sfood sensitivity, functional abdominal pain, functional bloating, functional dyspepsia, glutensensitive enteropathy

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“…We recommend a ratio of placebo to active of at least 2:1 in controlled challenges. This approach has been successfully utilized in a current study, determining that the majority of patients with suspected NCGS cannot identify gluten as trigger of their symptoms [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Non-celiac gluten/wheat sensitivity (NCGS)—a currently undefined disorder without validated diagnostic criteria and of unknown prevalence

Reese¹,

Schäfer

Kleine‐Tebbe³

et al. 2018

Allergo J Int

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Within the last decade, non-celiac gluten/wheat sensitivity (NCGS) has been increasingly discussed not only in the media but also among medical specialties. The existence and the possible triggers of NCGS are controversial. Three international expert meetings which proposed recommendations for NCGS were not independently organized and only partially transparent regarding potential conflicts of interest of the participants. The present position statement reflects the following aspects about NCGS from an allergist’s and nutritionist’s point of view: (A) Validated diagnostic criteria and/or reliable biomarkers are still required. Currently, this condition is frequently self-diagnosed, of unknown prevalence and non-validated etiology. (B) Gluten has not been reliably identified as an elicitor of NCGS because of high nocebo and placebo effects. Double-blind, placebo-controlled provocation tests are of limited value for the diagnosis of NCGS and should be performed in a modified manner (changed relation of placebo and active substance). (C) Several confounders hamper the assessment of subjective symptoms during gluten-reduced or gluten-free diets. Depending on the selection of food items, e.g., an increased vegetable intake with soluble fibers, diets may induce physiological digestive effects and can modify gastrointestinal transit times independent from the avoidance of gluten. (D) A gluten-free diet is mandatory in celiac disease based on scientific evidence. However, a medically unjustified avoidance of gluten may bear potential disadvantages and risks. (E) Due to a lack of diagnostic criteria, a thorough differential diagnostic work-up is recommended when NCGS is suspected. This includes a careful patient history together with a food-intake and symptom diary, if necessary an allergy diagnostic workup and a reliable exclusion of celiac disease. We recommend such a structured procedure since a medically proven diagnosis is required before considering the avoidance of gluten.

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The effect of a controlled gluten challenge in a group of patients with suspected non‐coeliac gluten sensitivity: A randomized, double‐blind placebo‐controlled challenge

Abstract: The present study showed that the majority of patients with suspected NCGS are not able to identify when challenged with gluten in a double-blind placebo-controlled food challenge, indicating that gluten is not the cause of their symptoms.

Cited by 37 publications

References 25 publications

Non‐celiac gluten or wheat sensitivity: It's complicated!

Non‐celiac gluten or wheat sensitivity: It's complicated!

Mast cell‐nerve interactions correlate with bloating and abdominal pain severity in patients with non‐celiac gluten / wheat sensitivity

Non-celiac gluten/wheat sensitivity (NCGS)—a currently undefined disorder without validated diagnostic criteria and of unknown prevalence

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