Systematic review of safe level of gluten for people with coeliac disease

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Coeliac disease is a systemic autoimmune disease characterised by histological abnormalities of the small bowel mucosa. The mainstay of treatment of coeliac disease is a strict lifelong ‘gluten-free’ diet, although total avoidance of gluten can be difficult and there is individual variability in tolerance to gluten. Objectives To undertake a systematic review to determine if there is a threshold level of intake of gluten that is safe for people with coeliac disease to consume. Search methods We searched MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, trial registers, grey literature sources and key websites for relevant systematic reviews and primary studies. We conducted forward citation searches of key systematic reviews and eligible studies, and checked reference lists. Searches were conducted in November and December 2015. Selection criteria We selected studies that assessed the effects of different amounts of gluten on small-bowel histology, serology and clinical symptoms in adults or children with confirmed coeliac disease. Dietary intervention or gluten exposure were of any duration. Gluten source included gliadin and wheat-starch based glutenfree products but excluded oats. Randomised trials, non-randomised, cohort and cross-sectional studies that investigated safe levels of gluten were included. We excluded challenge studies that assessed mucosal change using high levels of gluten. Data collection and analysis Two reviewers were involved in study selection, data collection and risk of bias assessment. Discrepancies were resolved by discussion within the review team. In the absence of quantitative analysis, results were synthesised narratively and grouped according to study design. The GRADE principles were used in considering the overall quality of the evidence. Main results We included 18 studies involving 1754 participants; nine were intervention studies (including five randomised trials) and nine were observational. Studies were very heterogeneous with respect to the type, amount and duration of exposure to gluten, populations studied, how outcomes were assessed and types of study design included. The risk of bias of the randomised trials was judged to be low or unclear, and high for the non-randomised studies. Only one study aimed to establish the safety threshold of prolonged exposure to small amounts of gluten and thus provided the most direct evidence for this review. This was a placebo-controlled randomised trial of 39 patients that found mucosal damage occurred in patients receiving 50 mg gluten/day (percentage change in villous height/crypt depth: -20% (95% CI: -22% to -13%) 13 participants; moderate quality evidence) but was of uncertain effect in those receiving 10 mg gluten/day (-1% (95% CI: -18% to 68%) 13 participants). From the limited randomised and other evidence available, mucosal deterioration was commonly present in patients receiving about 50 mg gluten/day but robust evidence was lacking for the effects of gluten consumption in the critical range of 2 to 10 mg gluten/day. The evidence in relation to the effect on clinical symptoms was inconsistent and was difficult to interpret because of the uncertainty and variability over how this outcome was measured across studies. Authors’ conclusions There is moderate evidence based on one randomised trial that patients with coeliac disease develop mucosal damage following consumption of 50 mg gluten/day, but the evidence of effect is uncertain for lower levels of consumption. The studies highlight the individual variability in tolerance to gluten and the difficulty this raises for setting a safe threshold. The overall evidence included in the review is 2 characterised by a high level of heterogeneity and consequently most studies provide only low quality indirect evidence of an association between gluten consumption and mucosal change. In the absence of larger randomised trials that compare small amounts of gluten intake, the current evidence precludes establishing a definitive threshold level of gluten that is safe for all people with coeliac disease to consume.
Original languageEnglish
PublisherCochrane Australia
Commissioning bodyCoeliac Australia
Number of pages40
Publication statusPublished - 5 Feb 2016

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