Gastroenterology

Gastroenterology

Volume 145, Issue 2, August 2013, Pages 320-328.e3
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
No Effects of Gluten in Patients With Self-Reported Non-Celiac Gluten Sensitivity After Dietary Reduction of Fermentable, Poorly Absorbed, Short-Chain Carbohydrates

https://doi.org/10.1053/j.gastro.2013.04.051Get rights and content

Background & Aims

Patients with non-celiac gluten sensitivity (NCGS) do not have celiac disease but their symptoms improve when they are placed on gluten-free diets. We investigated the specific effects of gluten after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates (fermentable, oligo-, di-, monosaccharides, and polyols [FODMAPs]) in subjects believed to have NCGS.

Methods

We performed a double-blind cross-over trial of 37 subjects (aged 24−61 y, 6 men) with NCGS and irritable bowel syndrome (based on Rome III criteria), but not celiac disease. Participants were randomly assigned to groups given a 2-week diet of reduced FODMAPs, and were then placed on high-gluten (16 g gluten/d), low-gluten (2 g gluten/d and 14 g whey protein/d), or control (16 g whey protein/d) diets for 1 week, followed by a washout period of at least 2 weeks. We assessed serum and fecal markers of intestinal inflammation/injury and immune activation, and indices of fatigue. Twenty-two participants then crossed over to groups given gluten (16 g/d), whey (16 g/d), or control (no additional protein) diets for 3 days. Symptoms were evaluated by visual analogue scales.

Results

In all participants, gastrointestinal symptoms consistently and significantly improved during reduced FODMAP intake, but significantly worsened to a similar degree when their diets included gluten or whey protein. Gluten-specific effects were observed in only 8% of participants. There were no diet-specific changes in any biomarker. During the 3-day rechallenge, participants’ symptoms increased by similar levels among groups. Gluten-specific gastrointestinal effects were not reproduced. An order effect was observed.

Conclusions

In a placebo-controlled, cross-over rechallenge study, we found no evidence of specific or dose-dependent effects of gluten in patients with NCGS placed diets low in FODMAPs. www.anzctr.org.au. ACTRN12610000524099

Section snippets

Patients

Patients were recruited between January 2010 and January 2011 via advertisements in e-newsletters and community newspapers in metropolitan Melbourne, Australia and by referrals from private dietetics practice or gastroenterology clinics. The inclusion criteria were age older than 16 years; symptoms of IBS fulfilling Rome III criteria that self reportedly improved with a GFD; symptoms well controlled on a GFD; and adherence to the GFD for at least 6 weeks immediately before screening as assessed

Study Population

Subject flow is shown in Supplementary Figure 1. After randomization for the 7-day trial, 3 patients were withdrawn due to poor symptom control during the run-in period. Thirty-seven patients completed the 7-day trial as per protocol. Twenty-two subjects returned to complete the 3-day rechallenge. The details of those patients are shown in Table 1.

Dietary Adherence

For the 7-day trial, all 37 patients adhered to the GFD during the study and undertook all 3 treatment arms. Nearly all (98%) of the main meals

Discussion

Generally, NCGS is viewed as a defined illness, much like celiac disease, where gluten is the cause and trigger for symptoms. In such a case, it would be anticipated that removal of gluten from the diet would lead to minimal symptoms and subsequent exposure to gluten would lead to specific triggering of symptoms. The results of the current study have not supported this concept. First, some of the patients were not minimally symptomatic, despite apparent adherence to and previous considerable

Acknowledgments

The authors thank Dr Jason Tye-Din (Walter and Eliza Hall Institute) for material support and technical help. The authors also thank chef Mrs Debbie King (Monash University) for her assistance with food preparation and menu design, Dr Ferenc Bekes (George Weston Foods) for completion of protein characterization studies and George Weston Foods for performing the radioallergosorbent test analyses.

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    Conflicts of interest Peter R. Gibson discloses the following: He has published a book on a diet for irritable bowel syndrome. The remaining authors disclose no conflicts.

    Funding This study was supported by George Weston Foods as part of a partnership in an Australian Research Council Linkage Project and the National Health and Medical Research Council (NHMRC) of Australia. Jessica R. Biesiekierski and Simone L. Peters were supported by scholarships from the Faculty of Medicine, Nursing and Health Sciences, Monash University. Evan D. Newnham was supported by a scholarship from the Gastroenterological Society of Australia.

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