management of non coeliac gluten sensitivity
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MANAGEMENT OF NON- COELIAC GLUTEN SENSITIVITY Dr Sue Shepherd - PowerPoint PPT Presentation

MANAGEMENT OF NON- COELIAC GLUTEN SENSITIVITY Dr Sue Shepherd B.App.Sci. (Health Promotion), M. Nut & Diet., PhD. Advanced Accredited Practising Dietitian REPRESENTATIONS AND AFFILIATIONS DISCLOSURE Author of Cookbooks for Coeliac


  1. MANAGEMENT OF NON- COELIAC GLUTEN SENSITIVITY Dr Sue Shepherd B.App.Sci. (Health Promotion), M. Nut & Diet., PhD. Advanced Accredited Practising Dietitian

  2. REPRESENTATIONS AND AFFILIATIONS

  3. DISCLOSURE • Author of Cookbooks for Coeliac Disease and IBS. – “ Irresistibles for the Irritable ”, “ Two Irresistible for the Irritable ”, “ Gluten Free Cooking ”, “The Gluten Free Kitchen”, “Allergy Free Cooking”, “Food Intolerance Management Plan”, “Gluten and Wheat Free Diabetes”, “Low FODMAP Recipes”, and “The Complete Low FODMAP Diet”. • Co-author of “ Gastrointestinal Nutrition ”. – Resource manual for dietetic management of gastrointestinal conditions. • Consultant to Gluten Free Food Show in Melbourne, Sydney, Brisbane, Launceston. – for coeliac disease, low FODMAP diet. • Consultant dietitian to food companies for development of specialty food products. • Co-ownership of FODMAP Friendly certification trademark. • Co-director of company producing FODMAP Friendly food products.

  4. CHARACTERISTICS OF PATIENTS WITH NON-COELIAC GLUTEN SENSITIVITY • Functional gut symptoms (IBS-like) e.g., abdominal bloating, excess wind, altered bowel habits, abdominal pain. 1,2 • Systemic manifestations e.g. “foggy head”, headache, fatigue, joint and muscle pain, leg or arm numbness, dermatitis, depression. 1,2 • Symptoms improve on gluten withdrawal. • Symptoms worsen on gluten consumption. 1. Ludvigsson et al, Gut 2012. 2. Catassi et al, 2013

  5. CHARACTERISTICS OF PATIENTS WITH NON-COELIAC GLUTEN SENSITIVITY No standard diagnostic approach to NCGS. 1,2 • Systematic evaluation recommended. • Exclude CD (either normal duodenal histology on • gluten or absence of HLA DQ2 or DQ8 genotype). Exclude wheat allergy; and • Exclude other inflammatory disorders as appropriate. • No major complications of untreated NCGS have been • described. Natural history data lacking. 2 1. Ludvigsson et al, Gut 2012. 2. Catassi et al, 2013

  6. CHARACTERISTICS OF PATIENTS WITH NON-COELIAC GLUTEN SENSITIVITY • Non-coeliac gluten sensitivity has been estimated to affect 0.5-6% of the population. 1,2 • In Australia, it is estimated that for every person with diagnosed coeliac disease, there are twenty others eating gluten-free food. 3 1. www.massgeneral.org/children/services/celiac-disease/gluten-sensitivity-faq.aspx 2. Catassi et al, 2013. 3. Vinning & McMahon. Rural Industries Research & Development Corp, Aust Govt, 2006.

  7. DOES NON-COELIAC GLUTEN SENSITIVITY EXIST? 1 Ludvigsson et al, Gut 2012.

  8. NON-COELIAC GLUTEN SENSITIVITY – THE LITERATURE A mixed bag!..... Some studies have had inappropriate inclusion criteria e.g., • patients with increased density IELs. 1 Increasing risk that patients with latent coeliac disease were included in • study. IBS cases may be classified as NCGS. 2 • Terminology issues – “wheat sensitivity”, “gluten sensitivity”, • “gluten intolerance”, “non-coeliac gluten sensitivity”, etc. Wheat contains many constituents that could play a role in • triggering symptoms – amylase-trypsin inhibitors (new area of interest – release pro-inflammatory cytokines), fructans (FODMAP), proteins (allergy). These need to be controlled for in studies. 1. Wahnschaffe et al, 2001. Catassi et al, 2013

  9. DOES NON-COELIAC GLUTEN SENSITIVITY EXIST? Carroccio et al conducted a study in 2012 in a cohort • of 920 patients with IBS. Participants undertook a 4 week gluten free • (elimination) diet then double-blinded crossover rechallenge with wheat or placebo capsules. 276 participants (30%) had “wheat sensitivity”. • 206 of these (75%) had multiple food sensitivities.  Confusion re: terminology. • Uncertain if it was gluten withdrawal or other factor • that benefited participants. Carroccio et al 2012

  10. DOES NON-COELIAC GLUTEN SENSITIVITY EXIST? Biesiekierski et al conducted a double blinded, • randomised, placebo-controlled rechallenge trial on 34 patients (29-59y, 4 men) with IBS (self-controlled on a GFD) 1 . CD excluded: negative coeliac serology AND either an • HLA DQ2/8 negative or normal duodenal biopsy. Patients were given either gluten (1 muffin and 2 slices • bread = 16g gluten) or placebo for 6 weeks. These were also low FODMAP . Background diet not controlled. • 1. Biesiekierski JR, et al 2011

  11. DOES NON-COELIAC GLUTEN SENSITIVITY EXIST? The group given gluten demonstrated a significant • deterioration of symptoms compared to placebo (85% vs 40% p=0.0001). Symptoms included abdominal pain, bloating, • satisfaction with stool consistency, and tiredness. There was no difference between the groups in tests for • intestinal injury (faecal lactoferrin, CRP or sugar test for intestinal permeability) or coeliac serology. We were unable to elucidate a mechanism for the • difference between the groups. Biesiekierski JR, et al 2011

  12. DOES NON-COELIAC GLUTEN SENSITIVITY EXIST? Recently… • A double-blind placebo-controlled cross-over trial in patients with self-reported NCGS has produced contradicting results, raising some doubt about the existence of NCG.

  13. DOES NON-COELIAC GLUTEN SENSITIVITY EXIST? Biesiekierski et al . recruited 37 patients with IBS and • self-reported NCGS. 1 CD excluded: negative coeliac serology AND either • a HLA DQ2/8 negative or normal duodenal biopsy (identical inclusion/exclusion criteria as the 2011 study). 2 Recruits were provided all meals during the study and • undertook all three treatment arms, in a cross-over study with >2 week washout periods between arms. 1. Biesiekierski JR, et al 2013 2. Biesiekierski JR, et al 2011

  14. n=37 – STUDY PART A 7 days 7 days 7 days 14 days Low G Glu luten en Control ol Hig igh g glu luten en (2g g glu luten en/ (0g g glu luten en/ Low Lo (16g/gl glute ten) n) 14g w 14g whey) 16g w 16g whey) FODM DMAP AP Diet Di et ≥ 2 we week wa wash shout ≥ 2 we week wa wash shout ← Low F FODM DMAP Di Diet et → Vis isual A l Analogue S e Scale le ( (VAS AS) symptom scores es Biesiekierski JR, et al 2013

  15. CHANGES IN SYMPTOM SEVERITY * FROM RUN-IN FOR EACH 7 DAY DIETARY TREATMENT Mean + n +/- SEM EM * * * Biesiekierski JR, et al 2013 * = <0.05 from end of low FODMAP run-in to end of treatment arm

  16. CHANGES IN SYMPTOM SEVERITY * FROM RUN-IN FOR EACH 7 DAY DIETARY TREATMENT Mean + n +/- SEM EM * In all participants, gastrointestinal symptoms 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 (serum and faecal markers of intestinal inflammation/injury). Biesiekierski JR, et al 2013 * = <0.05 from end of low FODMAP run-in to end of treatment arm

  17. n=37 – STUDY PART B 3 days 3 days 3 days Glu luten en a arm Whe hey ar arm Control ol (16g g glu luten en/ (0g g glu luten en/ (0g g glu luten en/ 0g w g whe hey) 16g 16g w whey) 0g w g whe hey) ≥ 3 day washout ≥ 3 day day w was ashout ut ← Low F w FOD ODMAP , L , Low F w Food c chemical, D , Dairy F Fre ree D Diet → • No differences across dietary treatment arms for change in overall symptoms (day 3) vs baseline period (PART A). • Changes in individual symptoms (e.g., bloating, satisfaction with stool consistency, wind, pain, tiredness, and nausea) were similar across the 3 dietary periods (all p > 0.209). Biesiekierski JR, et al 2013

  18. RESULTS All participant’s symptoms improved on reduction in • FODMAPs prior to the delivery of treatment arms. There was no difference in VAS symptom scores • between gluten, whey and/or placebo arms. The study demonstrated a significant placebo effect • as all treatment groups experienced an increase in symptoms during each of the treatment arms. Biesiekierski JR, et al 2013

  19. DIFFERENCES IN STUDY DESIGN 2011 VS 2013 Fa Factor Prot otoc ocol ol i in Chang hange i in n 2013 Rational nale 2011 2011 Acce ccess to f food ood Regular diet. All meals provided To reduce “background noise”. duri ring stu study Only muffins – low FODMAP To control for changes in and bread and gluten free participant’s usual diet including provided. FODMAP intake. Considerati ation n Nil Restriction of dairy Ensured that during Part B, the only of o oth ther p puta tati tive products and all difference between treatment arms triggers f rs for g r gut food chemicals. was the nature of the protein intake. symp ymptoms Stu tudy d desi sign Parallel Cross-over To reduce influence of confounders and increase power. Durat ation o n of 6 weeks 1 week – part A Symptoms peaked at day 3, unlikely treatm tment nt 3 days – part B longer time frame would capture delayed response to gluten

  20. DOES NON-COELIAC GLUTEN SENSITIVITY EXIST IN PATIENTS WITH FUNCTIONAL GUT SYMPTOMS? Answer: ?? “In these two double-blind, randomised, placebo-controlled, cross-over trials (Part A and B), specific and reproducible induction of symptoms with gluten could not be demonstrated”. Biesiekierski JR, et al 2013

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