Gluten Free’ Really 100% Gluten Free? Why It Matters

21/07/2020

Is ‘Gluten Free’ really 100% Gluten Free? Why it matters

Dr. Kim Faulkner-Hogg Dietitian, Advanced APD BSc, Post Grad Dip Nut & Diet, PhD

[email protected] http://www.glutenfreenutrition.com Brought to you by

Talk Overview: Gluten

▪ Coeliac Disease & Non-Coeliac Gluten Sensitivity (NCGS) ▪ Defining gluten 3 ways ▪ Gluten digestion ▪ Tests to measure background gluten in a gluten free diet ▪ Accidental and contaminant gluten quantified ▪ Toasters, pastas and cakes with shared cooking equipment ▪ In supermarket and restaurant foods ▪ Impact on Quality of Life ▪ Non-Diet therapies to combat contamination ▪ Enzyme therapies to break down undigested gluten ▪ Proposed role alongside the gluten-free diet. ▪ Dietitians role ▪ Points & resources to reduce background gluten exposure

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Who is avoiding wheat or gluten? 28% of Australians monitor their gluten intake 1 ▪ 4 % avoid it all together Coeliac Disease: ▪ 1 in 80 males and 1 in 60 females in Australia1 ▪ Villi damage and symptoms ▪ Lifelong avoidance of all gluten Non-Coeliac Wheat/Gluten Intolerance ▪ Common: 11 %2 ▪ Symptoms vary over time ▪ Varying avoidance of possible wheat triggers2 ▪ Gluten ▪ Fructans ▪ Lectins ▪ Amylase/trypsin inhibitors

Defining Gluten

1. Bakers definition: 2. Todays definition: Gluten:- is the elastic substance that Gluten:- is the causative agent for forms when water is added to villi damage in those with coeliac flour….which stretches and traps disease. gas….allowing the product to rise and be light and porous.

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GLUTEN Containing Grains

▪ Wheat (Spelt, Atta, Durum, Burghul, Khorasan) ▪ Triticale (Hybrid of wheat and rye) ▪ Rye (Pumpernickel) ▪ Barley

Listed in decreasing order of gluten quantity

▪ Possibly oats: controversial

WHEAT STARCH 3. How Science Defines Gluten ~<0.02 % gluten

PROTEIN

Water ALBUMINS

Sodium Chloride GLOBULINS Ethanol WHEAT PROLAMIN (Gliadin) GLUTEN

   ω GLUTELIN (Glutenin)

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Amy C Brown (2012) Expert Review of Gastroenterology & Hepatology, 6:1, 43-55, DOI: 10.1586/egh.11.79

How Coeliac Disease Defines Gluten

1940’s

Dr. Willem-Karel Dicke, discovered that something in the gluten portion of the wheat grain caused villi destruction in those with coeliac disease

Today the definition of gluten is synonymous with the physiological damage seen in coeliac disease

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What is Gluten?

Proline Glutamine Gluten

Protein

Gluten is a protein Proteins are strings of amino acids Amino acids are linked together in different repeating patterns Glutenin Gliadin Gluten containing grains, that can cause damage, have a high proportion of proline and glutamine amino acids in the prolamin portion

Picture from: Alessio Fasano. Sci Am. 2009 Aug;301(2):54-61. Surprises from celiac disease.

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Gluten Digestion

Gluten

After consumption It is divided into

Glutenin Gliadin

GIP: Gluten Immunogenic Peptide ▪ Remains toxic to the gut in some Enzymes in our gastrointestinal track digest proteins into peptides and single amino acids Peptides

SHUT SHUT Enterocytes

Small intestine – Digested food

Pass through

SHUT

Inside the lining of the small intestine

Bloodstream

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Enterocytes

Small intestine – Digested food

Intestinal damage

TTG Inside the lining of TTG the small intestine TTG

Bloodstream

Coeliac Disease

Gluten Ingestion

Symptoms Diagnoses CD Raised coeliac-specific blood antibodies Inflamed small intestinal mucosa: Villous atrophy

Strict Gluten Free Diet (20ppm)

Restoration of Health3 ▪ ↓ symptoms ▪ ↓ antibodies ▪ Villi recovery

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Gluten Free Internationally The term gluten free defines a quantity of gluten that is thought to do no harm While the details of the standards differ4

<20ppm United States, Canada and Europe + gluten free oats 20mg gluten/1kg of food

<10ppm Argentina + no oats 10mg gluten/1kg of food

<3ppm Australia, New Zealand and Chile + no oats 3mg gluten/1kg of food

Coeliac Disease Recovery

Gluten Free Diets before the year 2000 5,6,7,8,9 ▪ daily gluten intake between 5-150mg

▪ Wheat starch

people Number of of Number

0mg 2mg 10mg 30mg 50mg (aim for <20ppm) Potential small bowel damage Mg gluten/day

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Coeliac Disease Recovery

10mg gluten daily9 ▪ Generally safe for those with CD ▪ International Food Standard aim Regular ingestion of 50mg daily9

▪ Leads to damage of the small bowel

people Number of of Number

0mg 2mg 10mg 30mg 50mg (aim for <20ppm) Potential small bowel damage Mg gluten/day

Coeliac Disease Recovery

10mg gluten daily9 ▪ Generally safe for those with CD Biopsy ▪ International Food Standard aim ≤7mg gluten 9

people Regular ingestion of 50mg daily per day10 Number of of Number ▪ Leads to damage of the small bowel Symptoms 0.15mg gluten There is a high variability of per day10 sensitivity among those with coeliac disease

0mg 2mg 10mg 30mg 50mg (aim for <20ppm) Potential small bowel damage Mg gluten/day

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Gluten Quantities

Using the figure of ~2.5g gluten in a slice of wheat bread (=2,500mg gluten)

~50mg gluten = 1/50 of a slice of wheat bread

~400-500 mg

Gluten Quantities

~ 2.5 g gluten in a slice of wheat bread Average gluten intake on 20 ppm GFD 10 is 66 – 108 mg gluten/day ~ 10 mg gluten = 1/250 slice of bread

Several crumbs ≡ 6 -10 mg gluten

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Recovery of Coeliac Disease Stats vary from paper to paper Villi ▪ Most suggest between 30-50% of patients have ongoing villi damage on a GFD 11,12,13,14,15 ▪ Slow recovery ▪ 4-15% were not recovered at 5 years16,17,18

Symptoms ▪ Despite adherence, there is a high rate of GI symptoms in people on GFD’s 19 . ▪ 25-40% of patients have ongoing symptoms despite the GFD20,21,22 ▪ Generally those diagnosed as kids have the best outcomes

Probably from trace sources of gluten

Adherence to a GFD

Adherence to the GFD varies from 36-96%23 New tests: detect Gluten Immunogenic ▪ Demographic Peptides in faeces and urine ▪ Psychosocial ▪ Clinical factors Made the theory of background gluten a reality

Adherence has 2 main components ▪ Deliberate choice to eat a gluten product GIP ▪ Inadvertent ingestion of gluten ▪ Trace backwards and find the gluten ▪ Background contamination

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GIP Detection Kits Morenos’ 2017 study reports11

GIP: Gluten Immunogenic peptides ▪ GIP’s can be detected in urine ▪ Make it through the intestine unabsorbed ▪ 4-6 hours after ingesting gluten ▪ Excreted in stool and urine ▪ Remain detectable for 1-2 days

50% of the study group Developing tests to measure this suggest…. ▪ Had positive urine GIPs ▪ Stool: ▪ Detects gluten intakes greater than 40mg/day Patients with no villi damage: ▪ Could be positive ~2-7 days after ingestion ▪ 89% had negative urine GIPs ▪ Detects a more chronic exposure ▪ Urine: Patients with villous damage ▪ Detect from about 40-500mg of gluten /day ▪ All had detectable urine GIP’s ▪ Detects a more accurate exposure

GIP Detection Kits

Syage 2018 study reports 24

▪ Background gluten ingestion on a GFD was ▪ Between 200-400mg gluten/day ▪ Moderate symptoms :- significantly more than 200mg/day

More research is needed to define ▪ Cut off points ▪ Conversion factors to gluten consumed ▪ Potential gut microbiota influences on GIPs ▪ Best uses

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Uses for the GIP test

Caution with use as they could create anxiety

Do not want people to use them after eating at restaurants to say ▪ You glutened me!!! ▪ Socially and emotionally damaging leading to isolation

Useful in refractory CD if obvious gluten has been excluded ▪ measure if background gluten could be a contributing factor

Research clinical trials ▪ Measure compliance

Typical Western Diet 10-20g gluten/day25 (ie 10 000- 20 000 mg)

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Accidental & Inadvertent Gluten Ingestion May be a reason for symptoms and villi damage

Some potential sources of contamination of gluten free foods Hidden in Foods26 Farm, Factory & Market Kitchen/Restaurant/Take-away Soy sauce Share transport trucks with wheat Self-serve buffets Beer battered chips Share storage facilities with wheat Toasters Boost low protein flour Share equipment with wheat Chopping Boards Salad dressing Unlabelled fresh food Shared cupboard & fridge space Thickeners Open bulk container foods Shared food crumbs:-jam, butter Imitation crab Self serve outlets Shared food preparation areas Gravies and marinades Ambiguous food labels Knives Confectionary Pasta colanders Pharmaceutical tablets

Contamination Potential

Weisbrod V et al. Gastroenterology 2020 Jan;158(1):273-275. doi: 10.1053/j.gastro.2019.09.007

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Contamination Summary27

▪ Shared pop-up toasters OK ▪ Be wary of GF pasta and GF cut cakes ▪ Restaurants ▪ School fetes

OVERALL Cross contamination when cooking is not a huge risk for most people

Food labelled Gluten Free

Gluten Free in Gluten Free Not Gluten Free Australia Internationally Country Ref # of products Under 5ppm <20ppm Over 20ppm

n (%) n (%) n (%) Canada Gelinas 2008 28 77 70 90% 7 9%

Canada Koerner 2013 29 268 265 99% 3 1%

Europe Gibert 2013 30 205 193 94% 10 with detectable gluten

USA Sharma 2015 31 275 265 96%

Australia Forbes & Dods 169 imported GF 169 100% Not R5-Eliza 2016 32 foods Italy Verma 2017 33 93 91 98% 2 2%

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Gluten free by ingredient but not labelled Gluten Free Gluten Free in Gluten Free Not Gluten Free Australia Internationally Country Ref # of products Under 5ppm <20ppm Over 20ppm

n (%) n (%) n (%) Finland Collin 2004 34 59 46 75% 13 22%

Canada Gelinas 2008 28 71 55 74.5% 16 22.5%

USA Thompson 2010 35 22 15 68% 7 32%

USA Sharma 2015 31 186 138 74% 12 6% 36 19%

Italy Verma 2017 33 107 99 93% 8 7%

Canada Koerner 201329 298 30 10%

Conclusions

▪ Foods labelled gluten free are quite safe ▪ Foods not labelled gluten free, but are gluten free by ingredient, are concerning

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Restaurant Meals

Melbourne21: ▪ 158 meals sold as gluten free ▪ Meals tested in a laboratory 91% were gluten free USA22: ▪ 5624 meals sold as gluten free ▪ Meals tested by NIMA 68% were gluten free

Most contaminated (USA) ▪ Dinner (35%) and breakfast foods (27.2%) ▪ GF pizza meal 53%) ▪ GF pasta meals (50.8%) GF pizza and GF pasta not good choices to order when eating out

Contamination build up

Unknowingly, gluten can creep into the background of your diet over a day

Personal symptom Personal villi damage tolerance level tolerance level

The gluten threshold for inflammation, symptoms and villi damage 10mg ▪ varies between people and ▪ may vary over time.

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QUALITY OF LIFE: QoL

Strict Gluten Free Diet Adherence QoL is a major reason for non-compliance 23, 24

▪ Motivation ▪ Psychological and emotional needs 4, 24 ▪ Symptom or villi damage…. ▪Hypervigilance and anxiety presence/absence ▪Less socializing ▪ Long-term medical outcomes ▪More self-isolation

▪ Economic ▪ Social ▪Cultural/Religious ▪ GF food availability and cost ▪Spontaneity ▪Travel

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Socialising

NCGS and CD struggle with social gatherings

▪ Hypervigilance ▪ More self-isolation and home cooking ▪ Less restaurants and social food gatherings ▪ Also impacts loved ones Ref: 24, 25, 26,27

Quality of Life on a Gluten Free Diet QoL is a balance between ▪ Adherence to a GFD and ▪ Social and emotional well-being

To live a good QoL for many:- Diet slip ups and unintentional gluten exposure means the GFD as we live it, is not sufficient to control symptoms and prevent mucosal damage in some people with coeliac disease and noncoeliac gluten sensitivity

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Quality of Life on a Gluten Free Diet QoL is a balance between ▪ Adherence to a GFD and ▪ Social and emotional well-being

Non Dietary Therapies 28

▪ To assist a gluten free diet ▪ Help to improve quality of life ▪ More socialization ▪ Less symptoms

Enzyme Therapy 30,31,32

Enzyme Therapies Under Development

Enzymes can be ▪ engineered or ▪ made from recombinant technologies or sourced from ▪ Fungi ▪ Plants; eg ▪ Barley ▪ Papaya Current enzymes in research overseas31,32,33 ▪ ALV003 ▪ AN-PEP ▪ Kumamax

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Enzyme Therapies

Caricain in bread making reduced gluten by 90% 49

Caricain Enzyme

Caricain can break down the GIPs left undigested by human gastrointestinal enzymes 50, 51

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Enterocytes

Small intestine – Digested food

Inside the lining of the small intestine

Bloodstream

Enterocytes

Small intestine – Digested food

Inside the lining of the small intestine

Bloodstream

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Enterocytes

Small intestine – Digested food

Inside the lining of the small intestine

Bloodstream

Clinical Trials: GluteGuard in Coeliac Disease

2014 & 2016: Trials using GluteGuard ▪ Assessed GluteGuard in Dermatitis Herpetiformis35 ▪ Assessed GluteGuard use in Coeliac Disease36 Proposed protection against background gluten contamination People with Coeliac Disease on a gluten-free diet ▪ 1 gram gluten (1000 mg) ▪ daily for 42 days (6 weeks)

➢ Group 2 received GluteGuard daily ➢ Group 1 received placebo/dummy tablet daily

▪ Symptom and well-being scores were collected throughout ▪ Intestinal biopsies and blood TTG antibodies collected before and after https://glutagen.com

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Clinical Trials: GluteGuard in Coeliac Disease

No adverse effects of GluteGuard were recorded during the trial

GluteGuard tablet daily Dummy/Placebo tablet daily 12 of 14 (93%) 4 of 6 (67%) STOPPED after 14 FINISHED the 42 days days due to symptoms

Clinical Trials: GluteGuard in Coeliac Disease

Study Conclusions

No harmful effects of GluteGuard were recorded during the trial

Significantly less symptoms in the group receiving GluteGuard

Fatigue - Nausea/vomiting - Stomach pain - Stomach cramps

Mucosal damage was no worse after 42 days of ingesting 1g gluten daily

8 of 13 who completed 42 days had lower TTG antibodies at the end

https://glutagen.com

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Survey

98.5% of GluteGuard users amongst the nearly 300 participants find GluteGuard helpful in providing peace of mind from symptoms caused by gluten cross-contamination

https://glutagen.com

Living with Coeliac Disease

▪ Women have more trouble emotionally adapting to a gluten-free diet but, with time, were more accepting of it than men52.

▪ People need to be provided with appropriate support and resources to enhance their emotional quality of life 53

▪ Difficulties and negative emotions were experienced less often, after more than 5 years on GFD52 ▪ Frustration and isolation because of the diet were ongoing negative emotions ▪ Food labelling and eating away from home remained very problematic.

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Dietitian teaching points

Patients need to know Patients need to know What their disease is and what are the long term Set up a gluten free kitchen implications for health Join Coeliac Australia Suggest tips for eating out and travel What is gluten and how it may affect them Alternative product and meal substitutions Gluten content of ingredients & alternative names Balance the gluten free diet, correct nutrient deficiencies Teach how to read and interpret a food label Discuss nutrient of concern on a long-term GFD

Purchase Coeliac Australia’s Ingredient List -Mobile App Know the story about oats

Consequence of non-adherence Investigate food intolerances if symptoms persist long term

RESOURCES Take home: Tips to reduce accidental gluten handout

https://glutenfreenutrition.com.au/

https://www.coeliac.org.au/join-now/

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THIS IS WHAT WE NEED TO AVOID

Finding balance in your gluten free life

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References

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References

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References 28. Gelinas et al. Gluten contamination of naturally gluten-free flours and starches used by Canadians with celiac disease. Int J of Food Sc & Tech, 2008;43:1245-1252. 29. Koerner TB et al. Gluten contamination of naturally gluten-free flours and starches used by Canadians with celiac disease. Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 2013; 30(12):2017–2021. doi:10.1080/19440049.2013.840744 30. Gibert A et al. Might gluten traces in wheat substitutes pose a risk in patients with celiac disease? A population-based probabilistic approach to risk estimation. Am J Clin Nutr, 2013;97:109-116. 31. Sharma et al. Gluten detection in foods available in the United States - a market survey. Food Chem, 2015;169:120-6 32. Forbes & Dods. Gluten content of imported gluten-free foods: national and international implications. MJA, 2016;205(7):316 33. Verma et al. Gluten contamination in naturally or labelled gluten-free products marketed in Italy. Nutrients, 2017,9:115;doi:10.3390/nu9020115 34. Collin P et al. The safe threshold for gluten contamination in gluten-free products. Can trace amounts be accepted in the treatment of coeliac disease? Aliment Pharma & Therapeutics 2004;19:1277-1283. doi: 10.1111/j.1365- 2036.2004.01961.x 35. Thompson T. Gluten contamination of grains, seeds, and flours in the United States: a pilot study. NEJM 2010;110:937- 940. 36. Halmos et al. Gluten in “gluten-free” food from food outlets in Melbourne: a cross-sectional study. MJA, 2018;209(7):1-2. 37. Lerner B et al. Gluten Contamination of Restaurant Food: Analysis of Crowd-Sourced Data. The American Journal of Gastroenterology, 2019;114(5):792–797. DOI: 10.14309/ajg.0000000000000202

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References 38. Dorn S.D et al. The development and validation of a new coeliac disease quality of life survey (CD-QOL). Aliment. Pharmacol Ther, 2010 31, 666–675. 39. Wolf RL et al. Hypervigilance to a Gluten-Free Diet and Decreased Quality of Life in Teenagers and Adults with Celiac Disease. Dig Dis Sci, 2018; 63, 1438–1448. https://doi.org/10.1007/s10620-018-4936-4 40. Lee A & Newman JM. Celiac diet: its impact on quality of life. J Am Diet Assoc, 2003;103:1533–5. 41. Silvester et al. Living gluten-free: adherence, knowledge, lifestyle adaptations and feelings towards a gluten-free diet. Journal of Human Nutrition and Dietetics, 2016; 29(3):374–382. DOI: 10.1111/jhn.12316 42. Vis, E. & Scheepers, P. Social implications of celiac disease or non-celiac gluten sensitivity. International Journal of Celiac Disease, 2017; vol. 5(4), p.133-139. doi: 10.12691/ijcd-5-4-3 43. Alhassan E et al. Novel Nondietary Therapies for Celiac Disease. Cell Mol Gastroenterol Hepatol, 2019;8:335–345 44. Finlay Macrae. Enzyme Therapy that Can Digest the Toxic Motifs of Gluten as an Aid in the Management of Celiac Disease International Journal of Celiac Disease, 2018, 6(1), 4-6. DOI: 10.12691/ijcd-6-1-3 45. Ido H et al. Combination of Gluten-Digesting Enzymes Improved Symptoms of Non-Celiac Gluten Sensitivity: A Randomized Single-blind, Placebo-controlled Crossover Study Clinical and Translational Gastroenterology, 2018;9:181. DOI 10.1038/s41424-018-0052-1 46. Lähdeaho ML et al. Glutenase ALV003 attenuates gluten-induced mucosal injury in patients with celiac disease. Gastroenterology 2014, 146: 1649-58. 47. König J et al. Randomized clinical trial: Effective gluten degradation by Aspergillus niger-derived enzyme in a complex meal setting. Scientific Reports, 2017. DOI:10.1038/s41598-017-13587-7

References

48. Gordon SR et al. Computational Design of an α-Gliadin Peptidase. J. Am. Chem. Soc. 2012, 134, 20513−20520. dx.doi.org/10.1021/ja3094795 49. Buddrick O, Cornell HJ, Small DM. Reduction of toxic gliadin content of wholegrain bread by the enzyme caricain. (2015) Food Chem. 170:343-7. 50. Zebebrowska A et al. The Effect of Enzyme Therapy on Skin Symptoms and Immune Responses in Patients with Dermatitis Herpetiformis. International Journal of Celiac Disease, 2014, Vol. 2;(2):58-63. DOI:10.12691/ijcd-2-2-7 51. Hugh J. Cornell et al. The Effect of Enzyme Supplementation on Symptoms and Duodenal Histology in Celiac Patients. International Journal of Celiac Disease, 2016;Vol 4;(2):40-47. DOI:10.12691/ijcd-4-2-2 52. Zarkadas M et al. Living with coeliac disease and a gluten-free diet: a Canadian perspective. J Hum Nutr Diet.2012; 26, 10–23. doi:10.1111/j.1365-277X.2012.01288.x 53. Harnett JE & Myers SP. Quality of life in people with ongoing symptoms of coeliac disease despite adherence to a strict gluten-free diet. Scientific Reports, 2020;10:1144. https://doi.org/10.1038/s41598-020-58236-8

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Thank you for attending!

Dr. Kim Faulkner-Hogg Dietitian, Advanced APD BSc, Post Grad Dip Nut & Diet, PhD

[email protected] http://www.glutenfreenutrition.com