21/07/2020 1 Dr. Kim Faulkner-Hogg Dietitian, Advanced APD BSc, Post Grad Dip Nut & Diet, PhD [email protected]http://www.glutenfreenutrition.com Brought to you by Is ‘Gluten Free’ really 100% Gluten Free? Why it matters ▪ 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 Talk Overview: Gluten 1 2
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Is ‘Gluten Free’ really · Today the definition of gluten is synonymous with the physiological damage seen in coeliac disease 1940’s 7 8. 21/07/2020 5 Gluten is a protein Amino
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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
Defining Gluten
1. Bakers definition:
Gluten:- is the elastic substance that forms when water is added to flour….which stretches and traps gas….allowing the product to rise and be light and porous.
2. Todays definition:Gluten:- is the causative agent for villi damage in those with coeliac disease.
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GLUTEN Containing Grains
▪ Wheat (Spelt, Atta, Durum, Burghul, Khorasan)
▪ Triticale (Hybrid of wheat and rye)
▪ Rye (Pumpernickel)
▪ Barley
▪ Possibly oats: controversial
Listed in decreasing order of gluten quantity
PROLAMIN(Gliadin)
ω
WHEAT STARCH ~<0.02 % gluten
WHEAT
PROTEIN
ALBUMINS
3. How Science Defines Gluten
GLOBULINS
GLUTEN
Water
Sodium Chloride
Ethanol
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
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
1940’s
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Gluten is a protein
Amino acids are linked together in different repeating patterns
Proline
Protein
Proteins are strings of amino acids
Glutamine
Gluten containing grains, that can cause damage, have a high proportion of proline and glutamine amino acids in the prolamin portion
Enzymes in our gastrointestinal track digest proteins into peptides
and single amino acids
Gluten Digestion
GIP: Gluten Immunogenic Peptide▪ Remains toxic to the gut in some
Gluten
Enterocytes
Small intestine – Digested food
SHUT
Pass through
Bloodstream
Inside the lining of the small intestine
SHUT
SHUT
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Enterocytes
Small intestine – Digested food
Bloodstream
Inside the lining of the small intestine
TTG
Intestinal damage
TTG TTG
Restoration of Health3
▪ ↓ symptoms ▪ ↓ antibodies▪ Villi recovery
SymptomsRaised coeliac-specific blood antibodiesInflamed small intestinal mucosa: Villous atrophy
Strict Gluten Free Diet (20ppm)
Diagnoses CD
Gluten Ingestion
Coeliac Disease
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<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
The term gluten free defines a quantity of gluten that is thought to do no harm
While the details of the standards differ4
Gluten Free Internationally
10mg(aim for <20ppm)
2mg 30mg 50mgPotential small bowel damage
0mg
Mg gluten/day
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Gluten Free Diets before the year 2000 5,6,7,8,9
▪ daily gluten intake between 5-150mg
▪ Wheat starch
Coeliac Disease Recovery
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10mg(aim for <20ppm)
2mg 30mg 50mgPotential small bowel damage
0mg
Mg gluten/day
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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
Coeliac Disease Recovery
10mg(aim for <20ppm)
2mg 30mg 50mgPotential small bowel damage
0mg
Mg gluten/day
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Symptoms0.15mg gluten
per day10
Biopsy≤7mg gluten
per day10
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
Coeliac Disease Recovery
There is a high variability of sensitivity among those with
coeliac disease
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50
~400-500 mg
Gluten Quantities
~50mg gluten = 1/50 of a slice of wheat bread
Using the figure of ~2.5g gluten in a slice of wheat bread
(=2,500mg gluten)
Several crumbs ≡
6 -10 mg gluten
Gluten Quantities
10
~ 2.5 g gluten in a slice of wheat bread
Average gluten intake on 20 ppm GFD
is 66 – 108 mg gluten/day
~ 10 mg gluten = 1/250 slice of bread
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Stats vary from paper to paper
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
Recovery of Coeliac Disease
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
Adherence to the GFD varies from 36-96%23
▪ Demographic
▪ Psychosocial
▪ Clinical factors
Adherence has 2 main components
▪ Deliberate choice to eat a gluten product
▪ Inadvertent ingestion of gluten
▪ Trace backwards and find the gluten
▪ Background contamination
New tests: detect Gluten Immunogenic Peptides in faeces and urine
Made the theory of background gluten a reality
GIP
Adherence to a GFD
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▪ GIP’s can be detected in urine▪ 4-6 hours after ingesting gluten▪ Remain detectable for 1-2 days
50% of the study group▪ Had positive urine GIPs
Patients with no villi damage:▪ 89% had negative urine GIPs
Patients with villous damage▪ All had detectable urine GIP’s
Morenos’ 2017 study reports11GIP Detection Kits
GIP: Gluten Immunogenic peptides▪ Make it through the intestine unabsorbed▪ Excreted in stool and urine
Developing tests to measure this suggest….▪ Stool:
▪ Detects gluten intakes greater than 40mg/day▪ Could be positive ~2-7 days after ingestion▪ Detects a more chronic exposure
▪ Urine:▪ Detect from about 40-500mg of gluten /day▪ Detects a more accurate exposure
More research is needed to define ▪ Cut off points▪ Conversion factors to gluten consumed▪ Potential gut microbiota influences on GIPs▪ Best uses
Syage 2018 study reports 24
▪ Background gluten ingestion on a GFD was▪ Between 200-400mg gluten/day ▪ Moderate symptoms :- significantly more than
200mg/day
GIP Detection Kits
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Useful in refractory CD if obvious gluten has been excluded ▪ measure if background gluten could be a contributing factor
Research clinical trials▪ Measure compliance
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
Typical Western Diet
10-20g gluten/day25
(ie 10 000- 20 000 mg)
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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
May be a reason for symptoms and villi damage
Accidental & Inadvertent Gluten Ingestion
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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▪ Shared pop-up toasters OK
▪ Be wary of GF pasta and GF cut cakes
▪ Restaurants
▪ School fetes
Contamination Summary27
OVERALL Cross contamination when cooking is not a huge risk for most people
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%
USA Sharma 2015 31 275 265 96%
Australia Not R5-Eliza
Forbes & Dods2016 32
169 imported GF foods
169 100%
Italy Verma 2017 33 93 91 98% 2 2%
10 with detectable gluten
Gluten Free in Australia
Gluten Free Internationally
Not Gluten Free
Food labelled Gluten Free
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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%
Gluten Free in Australia
Gluten Free Internationally
Not Gluten Free
Gluten free by ingredientbut not labelled Gluten Free
▪ Foods labelled gluten free are quite safe
▪ Foods not labelled gluten free, but are gluten free by ingredient, are concerning
Conclusions
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91% were gluten free
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
Restaurant MealsMelbourne21:
▪ 158 meals sold as gluten free
▪ Meals tested in a laboratory
USA22:
▪ 5624 meals sold as gluten free
▪ Meals tested by NIMA
Unknowingly, gluten can creep into the background of your diet over a day
Personal symptomtolerance level
Personal villi damagetolerance level
The gluten threshold for inflammation, symptoms and villi damage ▪ varies between people and ▪ may vary over time.
10mg
Contamination build up
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QUALITY OF LIFE: QoL
Strict Gluten Free Diet Adherence
▪ Motivation
▪ Symptom or villi damage…. presence/absence
▪ Long-term medical outcomes
▪ Economic
▪ GF food availability and cost
QoL is a major reason for non-compliance 23, 24
▪ Psychological and emotional needs▪Hypervigilance and anxiety 4, 24
▪Less socializing▪More self-isolation
▪ Social ▪Cultural/Religious ▪Spontaneity▪Travel
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NCGS and CD struggle with social gatherings
Socialising
▪ Hypervigilance
▪ More self-isolation and home cooking
▪ Less restaurants and social food gatherings
▪ Also impacts loved onesRef: 24, 25, 26,27
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 non-
coeliac gluten sensitivity
Quality of Life on a
Gluten Free DietQoL is a balance between
▪ Adherence to a GFD and
▪ Social and emotional well-being
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QoL is a balance between
▪ Adherence to a GFD and
▪ Social and emotional well-being
▪ To assist a gluten free diet
▪ Help to improve quality of life
▪ More socialization
▪ Less symptoms
Non Dietary Therapies 28
Enzyme Therapy 30,31,32
Quality of Life on a
Gluten Free Diet
Current enzymes in research overseas31,32,33
▪ ALV003▪ AN-PEP▪ Kumamax
Enzyme Therapies Under Development
Enzymes can be ▪ engineered or ▪ made from recombinant technologies
or sourced from▪ Fungi▪ Plants; eg
▪ Barley▪ Papaya
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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
Bloodstream
Inside the lining of the small intestine
Enterocytes
Small intestine – Digested food
Bloodstream
Inside the lining of the small intestine
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Enterocytes
Small intestine – Digested food
Bloodstream
Inside the lining of the small intestine
Proposed protection against background gluten contamination
on a gluten-free diet
▪ Symptom and well-being scores were collected throughout
▪ Intestinal biopsies and blood TTG antibodies collected before and after
Clinical Trials: GluteGuard in Coeliac Disease
2014 & 2016: Trials using GluteGuard
▪ Assessed GluteGuard in Dermatitis Herpetiformis35
▪ Assessed GluteGuard use in Coeliac Disease36
People with Coeliac Disease
▪ 1 gram gluten (1000 mg)
▪ daily for 42 days (6 weeks)
➢ Group 2 received GluteGuard daily
➢ Group 1 received placebo/dummy tablet daily
https://glutagen.com
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No adverse effects of GluteGuard were recorded during the trial
Dummy/Placebo tablet daily
4 of 6 (67%) STOPPED after 14 days due to symptoms
GluteGuard tablet daily
12 of 14 (93%) FINISHED the 42 days
Clinical Trials: GluteGuard in Coeliac Disease
Significantly less symptoms in the group receiving GluteGuard
https://glutagen.com
Study Conclusions
No harmful effects of GluteGuard were recorded during the trial
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45. Ido H et al. Combination of Gluten-Digesting Enzymes Improved Symptoms of Non-Celiac Gluten Sensitivity: A
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