Summary of double-blind placebo-controlled trials in non-coeliac patients with IBS symptoms and suspected gluten/wheat sensitivity
| Study design | Inclusion criteria | Mode of administration of gluten/wheat (g/day) | Placebo | Duration of the trial | Results | Reference |
|---|---|---|---|---|---|---|
| Cross-over DBPC | Non-coeliac patients (n=6) with chronic diarrhoea, abdominal pain, bloating, rumbling, malaise, nausea, weight loss, recurrent mouth ulcerations. Improvement after GFD and worsening on gluten challenge. Mean average GFD at DBPC time: 46 months | Tomato soup supplemented with sachets made up of gluten-containing flour (20 g/day) | Tomato soup supplemented with gluten-free flour sachets | 4 weeks with administration of sachets randomly through each day for the first 3 days of weeks 2 and 4 | Significant worsening of overall intestinal symptoms for each patient in the week of gluten-containing flour administration vs the control week (p=0.0025) | Cooper et al52 |
| Randomised DBPC | Patients with IBS (n=34) with symptoms fulfilling Rome III criteria. Improvement of symptoms after GFD for at least 6 weeks before DBPC | Gluten-free bread/muffin supplemented with carbohydrate-depleted wheat protein (16 g/day) | Gluten-free bread/muffin | 6 weeks with daily administration of bread/muffin with or without wheat protein randomly | Significant worsening of overall symptoms (abdominal pain, bloating, satisfaction in stool consistency, tiredness) in patients with wheat protein ingestion vs those without wheat protein ingestion (p=0.047) | Biesiekierski et al53 |
| Cross-over, randomised DBPC | Patients with IBS (n=276) with symptoms fulfilling Rome II criteria. Improvement of symptoms after GFD | Wheat flour-containing capsules (13 g/day) | Xylose-containing capsules | 5 weeks with one type of capsules for 2 weeks, washout in the 3rd week and the other type of capsules in the 4th and 5th week | Significant worsening of overall intestinal symptoms in the weeks of wheat administration vs the weeks without wheat ingestion (p<0.0001) | Carroccio et al37 |
| Cross-over randomised DBPC | Patients with suspected NCGS who fulfilled Rome III criteria for IBS (n=37) Improvement of symptoms after GFD for at least 6 weeks before DBPC | Food with high (16 g/day) or low content (2 g/day) of carbohydrate-depleted wheat protein | Gluten-free food with whey protein (16 g/day) | 2-week-run-in period with a low-FODMAPs diet, then 1 week with high or low-gluten diet or placebo, followed by a 2-week washout before crossing over to the next diet | Significant improvement of overall intestinal symptoms during reduced FODMAP diet (p<0.0001) and significant but similar worsening on a diet with wheat protein or placebo—3 patients with wheat protein-specific response | Biesiekierski et al43 |
| Cross-over randomised DBPC | Patients with suspected NCGS who fulfilled Rome III criteria for IBS (n=22)—subset of population as Biesiekierski et al43 | Food with high content of carbohydrate-depleted wheat protein (16 g/day) | Gluten-free food with whey protein (16 g/day) or placebo | 3 days with high gluten, whey protein or placebo diet with ≥3-day washout before crossing over to the next diet | Significant but similar worsening of abdominal symptoms in all dietary arms—no patient with specific wheat protein-mediated response. Specific increase in current feelings of depression in wheat protein arm (p=0.011) | Biesiekierski et al;43 Peters et al38 |
| Cross-over randomised DBPC | Patients with suspected NCGS (n=61) with intestinal (IBS-like) and extra-intestinal symptoms | Capsules (4.375 g/day) containing purified gluten | Rice starch containing capsules | 1 week with one type of capsules, 1 week washout before crossing over to another week with the other type of capsules | Significant worsening of overall symptoms after gluten ingestion vs placebo (p=0.034) (bloating, p=0.040, abdominal pain, p=0.047, foggy mind, p=0.019, depression, p=0.020, aphthous stomatitis, p=0.025) 3 patients with gluten-specific response | Di Sabatino et al39 |
DBPC, double-blind, placebo-controlled; FODMAPs, fermentable oligo-di-monosaccharides and polyols; GFD, gluten-free diet; NCGS, non-coeliac gluten sensitivity; NCWS, non-coeliac wheat sensitivity;