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1. GLUTEN VS FODMAPs
Peter Gibson

2. 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

3. 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

4. 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

5. 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’

6. 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 …………….

7. 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

8. 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

9. 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)

10. Wheat proteins associated with illness
Uvackova et al, J Proteome Res 2013
??Wheat
germ
agglutinin

11. Normal
Coeliac disease
Coeliac-specific antibodies in the blood
e.g., tissue transglutaminase (tTG) antibodies

12. 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

13. 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

14. 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!

15. 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

16. 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

17. Wheat carbohydrates of interest = indigestible
Fibre
 important for laxation
Fructans – mostly fructose oligosaccharides with glucose terminal sugar = FODMAP
trigger gastrointestinal symptoms

18. FODMAPs
18
Fructose in excess of glucose
Lactose
Oligo- saccharides
Polyols
Fructans (FOS)
Galacto-oligosaccahrides (GOS)

19. Supporting up-to-date information
http://www.med.monash.edu/cecs/gastro/fodmap/

20. 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

21. 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

22. 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
Overall
satisfaction
Improved
bloating
Improved
abdo pain
P<0.05 for all
%
Staudacher et al, J Hum Nutr Diet 2011

23. 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

24. 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

25. 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

26. 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)

27. 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

28. Wheat protein (gluten) vs FODMAPs
Mechanism of symptom reduction of a wheat-free (gluten-free) diet in those without coeliac disease (‘NCGS’) ??

29. FODMAP content of cereal products per serve
Biesiekierski et al, J Human Nutr Dietetics 2011

30. 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

31. 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

32. Change in overall symptoms
VAS score: 100=worst
0=none
*p=0.047; Independent
Samples t-test
Baseline
Week 1*
Week 2
Week 3
Week 4
Week 5
Week 6
0
10
20
30
40
50
Gluten
Placebo
VAS (0-100mm)
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

33. 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

34. 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

35. Baseline Run-in
0
20
40
60
VAS (0-100mm)
Effect of  FODMAPs on overall symptoms
VAS symptom severity
score: 0 = none
100=worst
n = 37
P<0.0001
Biesiekierski et al Gastroenterology 2013 Wilcoxon signed rank test

36. 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

37. Effect on overall gut symptoms
Biesiekierski et al Gastroenterology 2013
Only 3 subjects had a gluten-specific response

38. 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

39. 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

40. 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

41. 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

42. Lessons from the wheat/NCGS controversy
A major question in patients with food intolerance is:
Protein vs FODMAPs

43. 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

44. 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

45. 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

46. 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