Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge
Elli L, Tomba C, Branchi R et al
Nutrients 2016; 8: 84; doi:10.3390/nu8020084
Non-celiac gluten sensitivity (NCGS) is a syndrome characterised by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food. Currently, available blood tests and histology do not help towards making the differential diagnosis, hence response to a gluten free diet in the absence of celiac disease (CD) or wheat allergy (WA) is the fundamental principal of diagnosis for NCGS.
Nutrients 2016; 8: 84; doi:10.3390/nu8020084
Non-celiac gluten sensitivity (NCGS) is a syndrome characterised by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food. Currently, available blood tests and histology do not help towards making the differential diagnosis, hence response to a gluten free diet in the absence of celiac disease (CD) or wheat allergy (WA) is the fundamental principal of diagnosis for NCGS.
Unfortunately, the placebo effect, in addition to the presence of other active compounds within wheat, e.g amylase trypsin inhibitors (ATIs), and FODMAPs, may act as confounding factors when analysing the impact of gluten withdrawal amongst potential NCGS sufferers. A correct diagnosis is essential in order to avoid unnecessary dietary restriction, provide effective treatment options, and to reduce the need for drugs in order to manage the symptoms of patients reporting functional bowel disorders including IBS.
The aim of this study was to identify patients with NCGS from those reporting an improvement of gastrointestinal symptoms while following a gluten free diet (GFD), through a double-blind placebo-controlled gluten challenge with crossover. The study was carried out in 15 gastrointestinal out-patients centers in Italy. The study enrolled 140 adult patients routinely attending gastrointestinal outpatient clinics and meeting the Rome III criteria for functional gastrointestinal disorders. All were following a gluten-containing diet and had negative IgA anti-tTG, normal total IgA and negative IgE mediated WA. Amongst patients with high clinical suspicion of CD, a duodenal biopsy was also performed in order to identify any seronegative patients.
Phase one of the trial investigated subject response to a GFD. Symptoms and quality of life were evaluated using a series of 10cm visual analogue scales (VASs) and a SF36 questionnaire. Following this initial evaluation, patients were asked to follow a GFD for 3 weeks. Subjects were provided with detailed information and support regarding the diet by an expert nutritionist. At the end of phase 1, patients repeated the VASs and SF36 questionnaire. Only those patients reporting a significant improvement in well-being (VAS ≥ 3cm, n=101) were defined as ‘gluten responsive’ and were enrolled in to phase 2 of the study.
Gluten responsive patients were asked to maintain their strict GFD for phase 2 of the trial (placebo-controlled double-blind gluten challenge with crossover). Ninety eight subjects were enrolled in this phase of the study (3 subjects refused to proceed owing to fear of symptom relapse during challenge). Patients were randomised to receive either purified gluten capsules (5.6g/ day, equivalent to 80g of dried pasta) or the same volume of placebo capsules (rice starch) for 7 days. A 7 day washout period was scheduled between the cross-over periods, hence the total duration of phase 2 was 21 days (subjects followed a gluten free diet throughout). Subjects completed the VASs and SF36 questionnaire at the end of each 7 day period (gluten challenge, cross over and placebo). Overall, subjects reported a greater deterioration in well-being during the gluten challenge rather than during placebo administration (p=0.05). Twenty eight of the randomised patients were identified as being ‘positive’ to the DBPCC (ie with symptomatic relapse during gluten ingestion) and 69 were found to be ‘negative’ to the DBPCC (ie without any symptomatic reaction during gluten administration). No demographic, clinical or biochemical factors were found to be associated with the gluten challenge response. Among positive patients, there appeared to be no significant effect of capsule sequence. Notably, 14 of the 28 positive patients were also considered to be placebo responsive, indicating a significant ‘placebo effect’, as would be expected.
Overall, 14% of the 98 randomised ‘gluten responsive’ patients showed a symptomatic relapse during the blind placebo-controlled gluten challenge (without concurrent response to placebo) and accordingly can be defined as patients with NCGS. This finding confirms that gluten ingestion may induce gastrointestinal symptoms in a sub-set of patients with functional bowel disorders. This study is the first to assess the performance of the Salerno Experts’ diagnostic criteria1 for NCGS in a clinical setting. The large number of patients responsive to a GFD (75%) but negative to gluten challenge is interesting, a possible placebo affect is likely to account for some of this discrepancy, however many patients might also be sensitive to other unspecified wheat components, e.g ATIs or FODMAPs.
Please, find the full original article here.
1 Catassi C, Elli L, Bonaz B et al. Diagnosis of Non-coeliac Gluten Sensitivity (NCGS): The Salerno Experts Criteria. Nutrients 2015; 7: 4966-4977.
The aim of this study was to identify patients with NCGS from those reporting an improvement of gastrointestinal symptoms while following a gluten free diet (GFD), through a double-blind placebo-controlled gluten challenge with crossover. The study was carried out in 15 gastrointestinal out-patients centers in Italy. The study enrolled 140 adult patients routinely attending gastrointestinal outpatient clinics and meeting the Rome III criteria for functional gastrointestinal disorders. All were following a gluten-containing diet and had negative IgA anti-tTG, normal total IgA and negative IgE mediated WA. Amongst patients with high clinical suspicion of CD, a duodenal biopsy was also performed in order to identify any seronegative patients.
Phase one of the trial investigated subject response to a GFD. Symptoms and quality of life were evaluated using a series of 10cm visual analogue scales (VASs) and a SF36 questionnaire. Following this initial evaluation, patients were asked to follow a GFD for 3 weeks. Subjects were provided with detailed information and support regarding the diet by an expert nutritionist. At the end of phase 1, patients repeated the VASs and SF36 questionnaire. Only those patients reporting a significant improvement in well-being (VAS ≥ 3cm, n=101) were defined as ‘gluten responsive’ and were enrolled in to phase 2 of the study.
Gluten responsive patients were asked to maintain their strict GFD for phase 2 of the trial (placebo-controlled double-blind gluten challenge with crossover). Ninety eight subjects were enrolled in this phase of the study (3 subjects refused to proceed owing to fear of symptom relapse during challenge). Patients were randomised to receive either purified gluten capsules (5.6g/ day, equivalent to 80g of dried pasta) or the same volume of placebo capsules (rice starch) for 7 days. A 7 day washout period was scheduled between the cross-over periods, hence the total duration of phase 2 was 21 days (subjects followed a gluten free diet throughout). Subjects completed the VASs and SF36 questionnaire at the end of each 7 day period (gluten challenge, cross over and placebo). Overall, subjects reported a greater deterioration in well-being during the gluten challenge rather than during placebo administration (p=0.05). Twenty eight of the randomised patients were identified as being ‘positive’ to the DBPCC (ie with symptomatic relapse during gluten ingestion) and 69 were found to be ‘negative’ to the DBPCC (ie without any symptomatic reaction during gluten administration). No demographic, clinical or biochemical factors were found to be associated with the gluten challenge response. Among positive patients, there appeared to be no significant effect of capsule sequence. Notably, 14 of the 28 positive patients were also considered to be placebo responsive, indicating a significant ‘placebo effect’, as would be expected.
Overall, 14% of the 98 randomised ‘gluten responsive’ patients showed a symptomatic relapse during the blind placebo-controlled gluten challenge (without concurrent response to placebo) and accordingly can be defined as patients with NCGS. This finding confirms that gluten ingestion may induce gastrointestinal symptoms in a sub-set of patients with functional bowel disorders. This study is the first to assess the performance of the Salerno Experts’ diagnostic criteria1 for NCGS in a clinical setting. The large number of patients responsive to a GFD (75%) but negative to gluten challenge is interesting, a possible placebo affect is likely to account for some of this discrepancy, however many patients might also be sensitive to other unspecified wheat components, e.g ATIs or FODMAPs.
Please, find the full original article here.
1 Catassi C, Elli L, Bonaz B et al. Diagnosis of Non-coeliac Gluten Sensitivity (NCGS): The Salerno Experts Criteria. Nutrients 2015; 7: 4966-4977.
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