gluten vs fodma ps 2014 handout
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GLUTEN VS FODMAPs
Peter Gibson
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Gluten-free epidemic across the Western world
USA Market research survey of 2000 households 24%
had a member currently eating gluten-free (Mintel, 2013)
New Zealand 5% children avoid gluten (coeliac prevalence = 1%)
Tanpowpong et al Arch Dis Child 2012
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Symptoms 8%
No symptoms
2%
Coeliac disease
0.8%
Non wheat avoiders
89%
CSIRO Food & Health Survey Dec 2010-Feb 2011 n = 1184 ≥ 18 years old
Golley et al, Pub Health Nutr 2014
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Australian wheat-avoiders = 11% adults
Coeliac disease
8%
Symptom relief 80%
No symptoms
12%
Bloating, abdo pain, fatigue Mostly female who • like the alternative • but are not neurotic,
illogical or hypochondriacal
40% are strictly gluten-free
Golley et al, Pub Health Nutr 2014
CSIRO Food & Health Survey Dec 2010-Feb 2011
n = 1184 ≥ 18 years old
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Why are people going gluten-free not for symptoms?
USA surveys (NB: data of uncertain quality)
35-65% ‘to be healthier’
~25% ‘for weight loss’
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Issues facing the consumer
Confusion re Wheat intolerance vs gluten intolerance
effect of gluten-containing foods = effect of gluten
Wheat-free = gluten-free
Heavy use of pseudoscience Gluten sticks to the lining of the colon ……….
Opioid peptides associated with wheat/gluten are responsible for ‘addiction to wheat’
…………..
Many of strong believers have conflicts of interest
Commercial gain – e.g., books, products …………….
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Misconceptions in modern medicine The gluten conspiracy
If wheat causes symptoms, it must be the gluten
If gluten-free diet improves symptoms, it must be due to the withdrawal of gluten
But
Nearly all challenges are performed with wheat – e.g., slices of bread or wheat flour in capsules
Wheat contains gluten AND non-gluten proteins AND FODMAPs
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Non-starch polysaccharides • arabinoxylans • cellulose • b-glucans
Metabolic proteins (incl ATI)
Minerals, vitamins Triglycerides
Starch - a-glucans
Storage proteins - gluten
Fructans Phospholipids, glycolipids Minerals, vitamins
Metabolic proteins (incl. WGA)
Minerals, vitamins Non-starch polysaccharides Triglycerides
15%
82%
3%
Wheat kernel
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Wheat proteins
80% gluten = storage proteins
Glutenins
Prolamins – gliadin (wheat), secalin (rye), hordein (barley)
20% albumins/globulins = metabolic proteins
Enzymes
Enzyme inhibitors (e.g., amylase-trypsin inhibitor - ATI)
Lectins (e.g., wheat germ aglutinin - WGA)
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Wheat proteins associated with illness
Uvackova et al, J Proteome Res 2013
??Wheat germ
agglutinin
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Normal Coeliac disease
Coeliac-specific antibodies in the blood e.g., tissue transglutaminase (tTG) antibodies
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What about non-coeliac gluten sensitivity (NCGS)?
Gut symptoms that respond to a gluten-free diet where coeliac disease is excluded
Does it exist?
Confocal laser endomicrosocopy (CLE) following food challenge
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Confocal laser endomicrosocopy (CLE) following food challenge
22/36 IBS +ve CLE
Wheat 13
Milk 9
Yeast 6
Soy 4
Fritscher-Ravens et al, Gastroenterology 2014 on-line
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Wheat protein
Can cause mild reactions in small intestine in those without coeliac disease
non-coeliac wheat protein sensitivity does exist
But, which wheat protein?
No information at all!
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Bioactive peptides
Peptides released during gluten digestion
Opioid actions (‘exorphins’)
Linked to
Autism, schizophrenia, depression …..(?)
‘Wheat addiction’!
Exorphins also released from b-casomorphin (A1 milk), rubisco (spinach), others
Controversial as to whether they cause illness
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Non-starch polysaccharides • arabinoxylans • cellulose • b-glucans
Metabolic proteins (incl ATI)
Minerals, vitamins Triglycerides
Starch - a-glucans
Storage proteins - gluten
Fructans Phospholipids, glycolipids Minerals, vitamins
Metabolic proteins (incl. WGA)
Minerals, vitamins Non-starch polysaccharides Triglycerides
15%
82%
3%
Wheat kernel
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Wheat carbohydrates of interest = indigestible
Fibre
important for laxation
Fructans – mostly fructose oligosaccharides with glucose terminal sugar = FODMAP
trigger gastrointestinal symptoms
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FODMAPs
18
Fructose in excess of glucose
Lactose
Oligo-saccharides
Polyols
Fructans (FOS) Galacto-oligosaccahrides (GOS)
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Supporting up-to-date information
http://www.med.monash.edu/cecs/gastro/fodmap/
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Major mechanisms of action of FODMAPs
in symptom generation
Polyol
Fructose
Fructose
Polyol H2
CH4
CO2
Oligosaccharide Lactose
gas production
water delivery Luminal distension
when visceral hypersensitivity
Diarrhoea and/or constipation,
pain, bloating, wind
Barrett et al APT 2010
Ong et al JGH 2010
Marciani et al GE 2010
Murray et al AJG 2014
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Evidence-base for efficacy of low FODMAP diet in IBS
• Challenge with individual FODMAPs
• Observational cohort studies (retro- & prospective)
• Randomised controlled trials
• Cross-over – rechallenge
• Cross-over – all food supplied
• high vs low FODMAP diets
• typical Aussie intake vs low FODMAP
• Cross-over – dietitian-taught
• low FODMAP vs habitual diet
• Non-randomised comparative study
Australia UK NZ
USA Denmark
et al
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Comparison of low FODMAP with standard diet (UK) – non-randomised
Standard advice (39)
Low FODMAP (43)0
10
20
30
40
50
60
70
80
90
Overallsatisfaction
Improvedbloating Improved
abdo pain
P<0.05 for all
%
Staudacher et al, J Hum Nutr Diet 2011
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The BIG FODMAP study
To compare the effects of low FODMAP diet with those of a typical Australian FODMAP diet on gut symptoms
In:
Unselected, FODMAP-naïve patients with IBS (Rome III –any bowel habit type) (n=30)
Healthy controls (n=8)
Halmos et al Gastroenterology 2014
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Daily food record and visual analogue scale: Overall symptoms, abdominal pain, bloating, passage of wind &
dissatisfaction of stool consistency
Study protocol 21-day typical Aust. FODMAP
21-day low FODMAP
7-day baseline
≥ 21-day washout
0
100 None at all Worst ever
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Overall symptoms – IBS (n=30)
Mean 22.8mm 95%CI [16.7-28.8] 45.7mm 95%CI [37.2-54.3]
P<0.001; repeated measures ANOVA
Halmos et al Gastroenterology 2014
P<0.001
70% had overall symptoms >20 mm
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P<0.001 Repeated measures ANOVA
P<0.001 Repeated measures ANOVA
P<0.001 Repeated measures ANOVA
P<0.001 Repeated measures ANOVA
Effect on specific symptoms in IBS (n=30)
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Summary
The low FODMAP diet
halves gastrointestinal symptoms in IBS patients compared to a typical Australian diet
Clinically relevant symptoms in 70%
Gastrointestinal symptoms unaffected by FODMAP content in the healthy population
Halmos et al Gastroenterology 2014
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Wheat protein (gluten) vs FODMAPs
Mechanism of symptom reduction of a wheat-free (gluten-free) diet in those without coeliac disease (‘NCGS’) ??
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FODMAP content of cereal products per serve
Biesiekierski et al, J Human Nutr Dietetics 2011
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FODMAP content of cereal products per serve
Biesiekierski et al, J Human Nutr Dietetics 2011
Low FODMAP
grains suitable
for people with
IBS
Gluten-free products
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Pilot study: Can gluten induce gut symptoms in non-coeliacs?
34 patients with IBS Coeliac disease excluded All had improved markedly on a gluten-free diet No immune reaction to gluten
= all had ‘non-coeliac gluten sensitivity’ (NCGS)
Continued on gluten-free diet & challenged for up to 6 weeks with gluten-free muffins/bread spiked with 16 g/d FODMAP-free gluten in 19 not spiked (i.e., placebo) in 15
Measured bowel symptoms
Biesiekierski et al , Am J Gastroenterol 2011
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Change in overall symptoms
VAS score: 100=worst
0=none
*p=0.047; Independent
Samples t-test
Bas
elin
e
Wee
k 1*
Wee
k 2
Wee
k 3
Wee
k 4
Wee
k 5
Wee
k 6
0
10
20
30
40
50Gluten
Placebo
VA
S (
0-1
00m
m)
Gluten rechallenge in non-coeliacs with gluten-free diet-responsive IBS
*p=0.047
Independent Samples
t-test
worst
none
(19)
(15)
Biesiekiesrki, et al Am J Gastroenterol 2011
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Conclusions
Gluten may induce more severe gut symptoms in patients with IBS (NCGS) than placebo
NCGS may indeed exist !
Gold standard for food intolerance: Randomised, placebo-controlled, cross-over rechallenge study where all food provided
dose effect to be determined
low FODMAP background
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Protocol: Run-in phase
Education low FODMAP diet 14 days
RUN-IN
7 days
BASELINE
Usual GFD +
Low in FODMAPs
Usual GFD
Biesiekierski et al Gastroenterology 2013
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Baseline Run-in0
20
40
60
VA
S (
0-1
00m
m)
Effect of FODMAPs on overall symptoms
VAS symptom severity
score: 0 = none
100=worst
n = 37
P<0.0001
Wilcoxon signed rank test Biesiekierski et al Gastroenterology 2013
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7 days
LOW GLUTEN
7 days
PLACEBO
7 days
HIGH GLUTEN
>14 day washout >14 day washout
16 g wheat-gluten daily
16 g highly-digestable whey
protein daily
2 g wheat- gluten daily
Low FODMAP, gluten-free diet
+ 14 g highly-
digestable whey protein daily
Protocol: Intervention phase
*All food provided* during the interventions
Biesiekierski et al Gastroenterology 2013
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Effect on overall gut symptoms
Biesiekierski et al Gastroenterology 2013
Only 3 subjects had a gluten-specific response
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Repeated the study in 20 patients bowel symptoms + current mental state following gluten ingestion
Were those who continue gluten avoidance even though gut symptoms are not relieved do so because they feel better (e.g., less depressed, less anxious)??
Biesiekierski et al Gastroenterology 2013 Peters et al Alimentary Pharmacol Ther 2014
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Gut symptoms after 3 days of gluten, whey or placebo (blinded)
Peters et al, Aliment Pharmacol Ther 2014
o/3 subjects with previous gluten-specific response had a gluten-specific response
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Depression scores in after 3 days of gluten, whey or placebo (blinded)
Peters et al, Aliment Pharmacol Ther 2014
P=0.011 Linear mixed model analysis
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Wheat in NCGS when small intestine is normal
FODMAP intake further ed symptoms
FODMAPs rather than ‘gluten’ culprit for gut symptoms
BUT ….. Wheat protein may (?) induce current feelings of depression
Wheat protein has non-intestinal effects
Which component of wheat protein?? Biesiekierski et al Gastroenterology 2013
Peters et al Alimentary Pharmacol Ther 2014
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Lessons from the wheat/NCGS controversy
A major question in patients with food intolerance is:
Protein vs FODMAPs
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Proteins + FODMAPs??
Protein sensitivity in some (how often??)
FODMAP benefit in 70-80%
Why not a combination?
Protein-mediated activation of inflammatory events sensitivity of the bowel
FODMAPs work in the setting of sensitivity of the bowel
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What does all this mean?
Wheat intolerance more likely to be due to its carbohydrate (FODMAP) content than wheat protein
The belief that wheat protein causes symptoms in this patient group may only occur in a minority
Wheat protein’s effects on psychological status need further evaluation both in those who believe they are sensitivity to gluten & in healthy people
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Why is going gluten-free a problem?
Community burden Economic – costs more Psychosocial – paying constant attention to your diet
Interferes with best medical practice Once gluten-free, more difficult to diagnose coeliac disease IBS better treated with a low FODMAP diet
Risk of nutritional inadequacy Wheat is the a major source of fibre in our diets (~30%) Many GF products not nutritionally balanced (sugar +++) Risk of micronutrient deficiencies
Exploitation of ‘gluten-free’ by industry & individuals
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Conclusions Gluten-free epidemic
Grossly overblown
Has health implications to the population
Driven Primarily by pseudoscience & mistaken belief that gluten
is the cause of symptoms and ill health
Secondarily by exploitation of the gluten frenzy by those interested in commercial gain
Needs continuing research to enable identification of those who do have wheat protein sensitivity