Prof Peter 145 main thursday - Living FODMAP Free · Core concept intensity stimuli intensity ......
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Transcript of Prof Peter 145 main thursday - Living FODMAP Free · Core concept intensity stimuli intensity ......
FODMAPs Fermentable Oligo- Di- & Mono-
saccharides And Polyols
Theory: Act by distending the intestinal
lumen via being:
� Osmotically active� Osmotically active
� Small molecules
� Trapped in the lumen ���� ↑ luminal water volume
� Osmotic effect related to molecular size
� fructose = ~0.5 lactose (lactulose) = ~0.25 FOS
� Rapidly fermented
� ���� gas ����↑ luminal volume
Enteric
nervous
system
Controller of most GI
functions - secretion,
motility, blood flow,
mucosal growth
“Normal”
low
“Abnormal”
high
Food
Luminal
distension
Core concept
low
intensity
stimuli
high
intensity
stimuli
• Little effect on motility
• Few conscious messages
• Alter motility
• Pain, discomfort, awareness
750
1000
To
tal o
utp
ut
(g)
p=0.01
• 4-day randomised cross-over dietary study
• Diets differed in FODMAP content by ~10 g/day
• Daytime ileostomy output measured
0
250
500
To
tal o
utp
ut
(g)
High FODMAP Low FODMAP
22%
Wilcoxon signed rank testBarrett et al APT 2010
FODMAP recovery
High FODMAP
Low FODMAP
Gra
ms
(g)
10
*
* p<0.05 Wilcoxon signed rank test
0
Gra
ms
(g)
5
*
Barrett et al APT 2010
Correlation of water and FODMAP recovery
600
800
Wate
r co
nte
nt
dayti
me o
utp
ut
(ml)
r = 0.7223
p=0.018
0 5 10 15 20 25
0
200
400
FODMAPs recovered
Wate
r co
nte
nt
dayti
me o
utp
ut
(ml)
Spearman's correlationBarrett et al APT 2010
↑ colonic water: Dose-dependence of effect on faecal volume in response to lactulose/FOS
���� lactulose���� FOS
Volume with lactulose = 2 x volume with FOS
2 sugars 4 sugars
Clausen et al DDS 1998
2 sugars 4 sugars
Luminal
FODMAPs in terminal ileumFODMAPs in terminal ileum
Increased water Increased water
delivery delivery (osmotic)(osmotic)
Bacterial Bacterial
fermentation fermentation ColonColon
Bloating Luminal
distension
Propulsive motor
activity
Luminal retention
of Na & H2O
Bloating
Pain/discomfort
FODMAPs are rapidly fermentable
� In vitro - fecal slurries:� Rapid fermentation of FODMAPs
� Lactulose = fructose = lactose = FOS >sorbitol > GOS
Clausen et al Dig Dis Sci 1998
� Fermentability of carbohydrates dependent � Fermentability of carbohydrates dependent upon chain length� e.g., in vivo - breath hydrogen production:
� 4.7 ppm/h………Resistant starch
� 19.1 ppm/h………Inulin
� 26.6 ppm/h………Lactulose
Brighenti et al Ital J Gastro 1995
20
25
30
35
Hy
dro
ge
n P
rod
uc
tio
n / p
pm
Diet A Low
FODMAP
Diet B High
FODMAP
Typical effect of FODMAP intake on
hydrogen production during the day
0
5
10
15
20
1 2 3 4 5 6 7 8 9 10 11 12 13 14
Time / hours
Hy
dro
ge
n P
rod
uc
tio
n / p
pm
Ong et al J Gastro Hepatol In press
AUC breath gas production over 12 h in
15 healthy volunteers
400.00
200.00
Hy
dro
gen
AU
C
p<0.001* H2 CH4
High FODMAP DietLow FODMAP diet
200.00
0.00
Hy
dro
gen
AU
C
FODMAP content of diet
Low High
AUC breath gas production over 12 h in
15 healthy volunteers
400.00
200.00
Hy
dro
gen
AU
C
350.00
300.00
250.00
200.00
Me
tha
ne
AU
C
p<0.001* p=0.025*H2 CH4
High FODMAP DietLow FODMAP diet
200.00
0.00
Hy
dro
gen
AU
C
High FODMAP DietLow FODMAP Diet
150.00
100.00
50.00
0.00M
eth
an
e A
UC
FODMAP content of diet
Low High HighLow
Gas
(H2, CO2, CH4)
Short-chain fatty
acids
Luminal
FODMAPs in terminal ileumFODMAPs in terminal ileum
Increased water Increased water
delivery delivery (osmotic)(osmotic)
Bacterial Bacterial
fermentation fermentation ColonColon
Bloating
Promote Na &
H2O absorption
Luminal
distension
Propulsive motor
activity
Luminal retention
of Na & H2O
Bloating
Pain/discomfort
Dose-dependence of effect on fecal volume in
response to lactulose/FOS
���� lactulose���� FOS
Clausen et al DDS 1998
Luminal retention
of Na & H2O
Promote Na &
H2O absorption
Opposing forces of FODMAP
disposal in colon
Diarrhea Desiccation
� Dose of FODMAPs� Efficiency of fructose & lactose absorption
� Efficiency of fermentation� Motility responses to distension/butyrate
� Epithelial function/dysfunction
Wide individual variation of fecal volume in
response to lactulose/FOS
���� lactulose���� FOS
Clausen et al DDS 1998
Small intestine
FODMAPs
Large intestineMode of action of FODMAPs
gas production
water deliveryLuminal distension
Altered motility
Pain, bloating, distension, constipation &/or diarrhoea
2 days’ (blinded) high FODMAP
diet induces abdominal pain
Healthy controls IBS
*
* p<0.05 Mann-Whitney U
& Wilcoxon signed ranks testsOng et al JGH 2010
Healthy controls IBS
*
2 days’ (blinded) high FODMAP
diet induces bloating
*
* p<0.05 Mann-Whitney U &
Wilcoxon signed ranks testsOng et al JGH 2010
0
50
100
150
200
250
300
350
400
450
0 5 10 15 20
Total bowel symptom score
Bre
ath
hy
dro
ge
n (
AU
C) Breath hydrogen vs
total symptom score
r=0.467
p=0.012
-50
0
50
100
150
200
250
300
350
0 5 10 15 20
Total bowel symptom score
Bre
ath
me
tha
ne
(A
UC
)
Breath methane vs
total symptom score
r=-0.434
p=0.021
Ong et al JGH 2010
Ch
an
ge
s in
VA
S s
core
(m
m)
35
40
45
50
100
Effect of 10 g sorbitol or mannitol on symptoms4 h changes in overall abdo symptoms in IBS (n=20)
p=0.03
p=0.05, Wilcoxon sign-rank test
Malabsorption (BH2T) 60% 20% 0%C
ha
ng
es
in V
AS s
core
(m
m)
0
5
10
15
20
25
30
Sorbitol GlucoseMannitol
Yao et al AGW 2011
Is benefit of low FODMAP diet only a
placebo effect? – ‘rechallenge’Randomised placebo-controlled 4-arm cross-over
trial of reintroduction of fructose/fructans
25 patients with IBS (12 IBS-D)
� 23-60 y; 4 men� 23-60 y; 4 men
� Fructose malabsorption (breath test)
� Durable response to low FODMAP diet
(at least 3 months)
� Well controlled symptomsShepherd et al, Clin Gast Hep 2008
11oo endend--pointpoint
% % symptoms not adequately controlledsymptoms not adequately controlled
P < 0.001
Shepherd et al Clin Gastro Hepatol 2008
Median overall symptom score Median overall symptom score
in relation to dosein relation to dose
Median scores onVAS
p<0.001, cf glucose
p<0.001, across groups
p<0.001, Fisher’s exact
Fisher’s exact
*Median scores onVAS
p<0.001, cf glucose
Shepherd et al, Clin Gast Hep 2008
Rechallenge RCT
� Improvement with low FODMAP diet was
not a placebo effect
� Involved not just fructose but fructans� Involved not just fructose but fructans
� Fructose & fructans have additive effects
= supporting the FODMAP concept
FODMAP content of food
� By combination of enzymatic and HPLC
techniques, content of wide variety of
Australian foods now known
Muir et al JAFC 2007 & 2009; Biesierkierski et al JHND 2011Muir et al JAFC 2007 & 2009; Biesierkierski et al JHND 2011
� Tables of ‘safe’ and ‘unsafe’ foods
continuing to be updated → beware old lists on the internet!
Oligosaccharide content
7.1g*
3.0g
1.3g
1.2g
33.0g
10.6g
7.1g*
* Barrett FFQ, data unpublished, upper range of daily oligosaccharide intake
9.6g‡
Oligosaccharide content
7.1g*
3.0g
1.3g
1.2g
33.0g
10.6g
7.1g*
* Barrett FFQ, data unpublished, upper range of daily oligosaccharide intake‡ Barrett et al. Aliment Pharmacol Ther 2010
9.6g‡
Oligosaccharide content
7.1g*
3.0g
1.3g
1.2g
33.0g
10.6g
7.1g*
* Barrett FFQ, data unpublished, upper range of daily oligosaccharide intake‡ Barrett et al. Aliment Pharmacol Ther 2010
9.6g‡
Oligosaccharide content
7.1g*
3.0g
1.3g
1.2g
33.0g
10.6g
7.1g*
* Barrett FFQ, data unpublished, upper range of daily oligosaccharide intake‡ Barrett et al. Aliment Pharmacol Ther 2010
9.6g‡
Do IBS patients consume more
FODMAPs than non-IBS?
� Not known, but now have a validated Food
Frequency Questionnaire (‘Monash CNAQ’)
Barrett & Gibson JADA 2011Barrett & Gibson JADA 2011
� Fructose & lactose malabsorption occurs at
similar frequency in IBS as for healthy
population Barrett et al APT 2010
Unanswered questions
� Long-term safety� Nutritional adequacy of the diet
� Effect on microbiota (reduction of natural prebiotics)
� Effect on colorectal carcinogenesis
� Effect on physiology of the bowel� e.g., does it change visceral hypersensitivity?
� Mechanism of action in � Induction of fatigue Ong et al JGH 2010
� Increasing gastro-oesophageal reflux Piche et al GE 2003
The science behind FODMAPs
� FODMAPs distend the intestinal lumen
� Retain water via osmotic effects
� Induce increased gas production → favours higher volume H2 vs methanehigher volume H2 vs methane
� FODMAPs induce symptoms when present in
food most likely via luminal distension with
water and gas
� Many questions still to be answered
� Senior Dietitians
� Sue Shepherd
� Jane Muir
� Jaci Barrett
� Dietitians/PhD students
� Emma Halmos
� Jessica Biesierkierski
� Gastroenterology Fellows
� Richard Gearry
� Peter Irving
� Sally James
� Debbie Nathan
� Melissa Haines
� Evan Newnham� Jessica Biesierkierski
� CK Yao
� Scientists
� Nia Rosella
� Rosemary Rose
� Kelly Liels
� Evan Newnham
� Catherine Croagh
� Daniel van Langenberg
� Honours students
� Derrick Ong
� Shayleen Mitchell