Gluten vs fodma ps 2014 handout

GLUTEN VS FODMAPs

Peter Gibson

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

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

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

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’

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 …………….

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

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

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)

Wheat proteins associated with illness

Uvackova et al, J Proteome Res 2013

??Wheat germ

agglutinin

Normal Coeliac disease

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

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

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

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!

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

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

Wheat carbohydrates of interest = indigestible

Fibre

important for laxation

Fructans – mostly fructose oligosaccharides with glucose terminal sugar = FODMAP

trigger gastrointestinal symptoms

FODMAPs

18

Fructose in excess of glucose

Lactose

Oligo-saccharides

Polyols

Fructans (FOS) Galacto-oligosaccahrides (GOS)

Supporting up-to-date information

http://www.med.monash.edu/cecs/gastro/fodmap/

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

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

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

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

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

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


P<0.001

70% had overall symptoms >20 mm

P<0.001 Repeated measures ANOVA




Effect on specific symptoms in IBS (n=30)

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


Wheat protein (gluten) vs FODMAPs

Mechanism of symptom reduction of a wheat-free (gluten-free) diet in those without coeliac disease (‘NCGS’) ??

FODMAP content of cereal products per serve

Biesiekierski et al, J Human Nutr Dietetics 2011

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

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

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

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

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

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

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


Effect on overall gut symptoms


Only 3 subjects had a gluten-specific response

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

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

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

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

Lessons from the wheat/NCGS controversy

A major question in patients with food intolerance is:

Protein vs FODMAPs

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

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

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

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

Gluten vs fodma ps 2014 handout

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