scientific basis and clinical implementation of the low...

SCIENTIFIC BASIS AND CLINICAL IMPLEMENTATION

OF THE LOW FODMAP DIET IN PATIENTS WITH FUNCTIONAL

DIGESTIVE DISORDERS Dr Sue Shepherd

B.App.Sci. (Health Promotion), M. Nut & Diet., PhD.

Advanced Accredited Practising Dietitian

REPRESENTATIONS AND AFFILIATIONS

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DISCLOSURE • Author of Cookbooks for Coeliac Disease and IBS.

– “Irresistibles for the Irritable”, “Two Irresistible for the Irritable”, “Gluten Free Cooking”, “The Gluten Free Kitchen”, “Allergy Free Cooking”, “Food Intolerance Management Plan”, “Gluten and Wheat Free Diabetes” and “Low FODMAP Recipes”.

• Co-author of “Gastrointestinal Nutrition”. – Resource manual for dietetic management of gastrointestinal conditions

• Consultant to Gluten Free Food Show in Melbourne, Sydney, Brisbane, Launceston. – For coeliac disease, low FODMAP diet.

• Consultant dietitian to food companies for development of specialty food products.

• Co-ownership of FODMAP Friendly certification trademark • Co-director of company producing FODMAP Friendly food

products.

FODMAPS

Poorly absorbed short-chain carbohydrates

F O D M A P

ermentable ligosaccharides isaccharide onosaccharide nd olyols

THE SPECTRUM OF FODMAPS

F O D M A P

ermentable – meaning they can be broken down by bacteria in the bowel.

ligosaccharides - e.g. fructans and GOS.

ermentable F O D M A P


ligosaccharides - e.g. fructans and GOS.

saccharide’ means ‘sugar’

‘oligo means ‘many’

ermentable F O DM A P


ermentable

isaccharide – e.g. Lactose.

F O DM A P


ermentable

onosaccharide e.g. Fructose (in excess of glucose)

F O DM A P


ermentable

nd

F O D M A P


ermentable

olyols – e.g. Sorbitol, mannitol

F O D M A P


HOW WAS THE LOW FODMAP DIET DEVELOPED?

1) I was frustrated by why it was that so many people (without coeliac disease) experienced functional gut symptoms when eating wheat. If it wasn’t gluten, what else was in wheat that could be a trigger? Search of the literature: FRUCTANS?

2) I received a referral for a patient with IBS symptoms and +ve fructose breath test. Referral note: “Please teach the fructose malabsorption diet”. However, there were no dietary guidelines! 1)Search of the literature: fructose was well absorbed in the presence of glucose (sugar solutions) – extrapolated to food… EXCESS FRUCTOSE?

Shepherd Works 1999

As a dietitian working in the field of GI nutrition, I was already aware of lactose intolerance, so LACTOSE was a potential symptom trigger. Also knew too many baked beans, etc., were symptom triggers (GOS). And was well aware of the role of POLYOLS – after all there is a warning statement on packaged food…..

• I hypothesised the mechanism of action and put together an “experimental diet”. It was the first time that fructans, excess fructose, lactose, polyols and GOS were pieced together as a dietary intervention for the management of functional gut symptoms.

• I implemented the diet after developing lists of foods to avoid and foods to include. The diet worked!

• I taught it for four years in my private practice (Shepherd Works) and then went on to confirm the efficacy in my PhD (Monash University) by undertaking a well designed clinical trial. This generated the first of a growing list of supportive evidence.

• The low FODMAP diet is now evidence based.

HOW WAS THE LOW FODMAP DIET DEVELOPED?

SO WHY THE LOW FODMAP DIET FOR IBS?

• FODMAPs induce symptoms of IBS. (Shepherd & Gibson 2008)

• The mechanism of how FODMAPs cause symptoms is clear and well understood. (Barrett, et al 2009, Ong et al 2010)

• The Low FODMAP Diet provides symptom relief in ~75% of IBS patients. (Shepherd & Gibson 2006)

• The Low FODMAP Diet is sustainable – patients have continued to follow the diet since it was developed.

• Efficacy as primary therapy for IBS has been shown in settings outside Australia. (Staudacher et al 2011)

DIETARY TRIGGERS OF

ABDOMINAL SYMPTOMS IN PATIENTS WITH IRRITABLE BOWEL

SYNDROME: RANDOMISED PLACEBO-CONTROLLED EVIDENCE

Sue J Shepherd, Francis C Parker, Jane G Muir, Peter R Gibson

Clinical Gastroenterology and Hepatology 2008; 6: 765-771

METHOD • Randomised double-blinded, quadruple

arm, cross-over, placebo-controlled rechallenge trial.

• Test substances: – Fructose (14g tds), or – Fructans (7g tds), or – Fructose and fructans (14g + 7g tds), or – Glucose (placebo) (7g tds)

Doses chosen on basis of average Australian dietary intake.

Shepherd, SJ 2008, Shepherd, SJ et al, Clin Gast Hep 2008 Jul;6(7):765-71

METHOD - PATIENTS • n = 25. • Ages 23-60 years, 16% male. • IBS (Rome III). • FM +ve breath test. • Previously responded to FODMAP diet –

de-challenged. • Provided with every meal and snack for 22

weeks (max) FODMAP diet – re-challenge • Symptom diaries.


LOW F O D M A P D I E T (supplied to patient)

>2 week run-in

Patients asymptomatic before starting each test period.

Shepherd, SJ et al, Clin Gast Hep 2008 Jul;6(7):765-71

STUDY DESIGN

>2 w >2 w >2 w 2 w


2 w 2 w 2 w

• Fructan 7g tds

• Fructose 14g tds

• Fructose + fructan 14 + 7g tds

• Glucose (placebo) 7g tds

50ml x 3/day

100ml x 3/day

170ml x 3/day

STUDY DESIGN


>2 week run-in

>2 w >2 w >2 w 2 w 2 w 2 w 2 w

• Fructan 7g tds




STUDY DESIGN


>2 week run-in


Random allocation of drink Drinks taken with meals Volume increased every 3 days – 3 steps Daily food diary (tick box) for compliance

Global symptom question (1o)

S y m p t o m d i a r y (VAS) (2o)

>2 w >2 w >2 w 2 w 2 w 2 w 2 w

• Fructan 7g tds




STUDY DESIGN


>2 week run-in

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Fructan Fructose Fructose andFructans

Glucose

P < 0.001

SYMPTOMS NOT ADEQUATELY CONTROLLED %

OF

PATI

ENTS

Shepherd, SJ 2008

(1O END-POINT)

MEDIAN SYMPTOM SCORES

p<0.001, Fisher’s exact

0

10

20

30

40

50

60

70

80

Fructan Fructose Fructose & Fructans Glucose

Overall

Pain

Bloating

Wind

p<0.001 vs glucose Wilcoxon

*Med

ian

scor

es o

n VA

S p<0.05

Shepherd, SJ 2008

(2O END-POINT)

MEDIAN OVERALL SYMPTOM SCORE IN RELATION TO VOLUME – EFFECT OF DOSE

p<0.001, Fisher’s exact

0

10

20

30

40

50

60

70

Fructan Fructose Fructose &Fructans

Glucose

50ml100ml170ml

Fisher’s exact

*Med

ian

scor

es o

n VA

S

p<0.001, cf glucose

p<0.001, across groups

Shepherd, SJ 2008

CONCLUSION • Rechallenge experiments support the efficacy of the

low FODMAP diet in IBS as: – Not due to placebo – But due to fructans, fructose or both – Not due to low chemical or other food components

• Symptom induction with fructose &/or fructans: – All test drinks induced symptoms greater than placebo

(p<0.001) – Dose-dependent – Effect of fructose and fructans additive

MANIPULATION OF DIETARY SHORT CHAIN CARBOHYDRATES

ALTERS THE PATTERN OF GAS PRODUCTION AND GENESIS OF SYMPTOMS IN IRRITABLE

BOWEL SYNDROME

Derrick K Ong, Shaylyn B Mitchell, Jacqueline S Barrett, Sue J Shepherd, Peter M Irving, Jessica R Biesiekierski, Stuart Smith, Peter R

Gibson and Jane G Muir.

Journal of Gastroenterology and Hepatology, 2010; 25: 1366–1373

AIM

• To compare breath H2 production and induction of gastrointestinal symptoms in individuals with IBS and healthy controls after high FODMAP and low FODMAP diet consumption.

Ong, et al 2010

STUDY DESIGN • Randomised, single blinded, crossover

intervention study. • Participants:

– 15 IBS (Rome III) – 15 Healthy volunteers (no GI symptoms)

Ong, et al 2010

Daily symptom questionnaire: Abdominal pain/discomfort, abdominal bloating/ distension, wind, nausea, heartburn and lethargy (Likert scale 0-3, 0=none, 1=mild, 2=moderate, 3=severe)

STUDY PROTOCOL 2-day

High FODMAP 2 day

Low FODMAP 7-day

baseline

7-day washout

Breath samples collected every hour for 14 hours (Day 2 of diet)

Ong, et al 2010

FOODS PROVIDED

Ong, et al 2010

PROFILES OF BREATH HYDROGEN OVER 14 HOURS OF LOW AND HIGH FODMAP

INTAKE IN IBS AND HEALTHY CONTROLS High FODMAP - Healthy Low FODMAP - Healthy

Low FODMAP - IBS High FODMAP - IBS

Ong, et al 2010

COMPOSITE SCORE ON DIETARY REGIMENS IN IBS PATIENTS

0

5

10

15

20

25

30

35

40

Abdo Pain Abdo Bloating ExcessiveFlatus

Nausea Heartburn Tired/Lethargy

LFDHFD

Tota

l Com

posi

te S

ympt

om S

core

**

**

**

* *

*

* = p<0.05, ** = p<0.001

Ong, et al 2010

SUMMARY AND CONCLUSION

• FODMAPs are fermented by intestinal microflora resulting in rapid gas production across the day.

CONCLUSION • This data, in conjunction with study in

ileostomates,1 we now have a physiological explanation as to how FODMAPs trigger symptoms in patients with IBS and why a low FODMAP diet improves functional gut symptoms.

1. Barrett, 2009 Aliment Pharm Ther. Ong, et al 2010

HOW DO FODMAPS TRIGGER SYMPTOMS OF IBS?

Luminal distension and altered bowel

motility

Abdo pain, distension, excess wind, diarrhoea +/- constipation

Adapted from Barrett, et al 2009

HOW DO FODMAPS TRIGGER SYMPTOMS OF IBS?

A LOW FODMAP DIET REDUCES SYMPTOMS IN PATIENTS WITH IRRITABLE BOWEL SYNDROME

Emma Halmos, Claus Christophersen, Anthony Bird, Victoria Power, Susan Shepherd, Jane Muir, Peter Gibson.

Gastroenterology 2014; 146: 67-75

STUDY DESIGN

A randomised controlled trial of efficacy for the low FODMAP diet in unselected IBS and healthy subjects during a low FODMAP diet and a diet representing a typical dietary intake and where all food is provided to control for confounding dietary factors (e.g., fibre).

Halmos, et al 2014

HYPOTHESES

• IBS symptoms are reduced by the low FODMAP diet compared to typical Australian intake of FODMAPs in unselected IBS patients.

• Differences in FODMAP intake have no effect on GI symptoms in healthy subjects.

Halmos, et al 2014

STUDY DESIGN

• Randomised, single-blinded, cross-over controlled trial where all food is provided.

• Primary endpoint. – Overall GI symptoms on low vs typical

Australian diet.

Halmos, et al 2014

Daily food record and visual analogue scale: Overall symptoms, abdominal pain, bloating, passage of wind & dissatisfaction of stool consistency

STUDY PROTOCOL 21-day

Low FODMAP 21-day

Typical Aust. 7-day

baseline ≥ 21-day washout

0 100 None at all Worst ever

bloatinistenc

Halmos, et al 2014

STUDY DIETS

Typical Aust. FODMAP diet

Low FODMAP diet

Breakfast Weet-bix & lactose-free milk, wheat bread with spread

Corn flakes & lactose-free milk, spelt bread with spread

Morning tea Pear Orange

Lunch High FODMAP frittata apple juice

Low FODMAP frittata cordial

Afternoon tea Ryvita with cheese Rice cakes with cheese

Dinner Salmon with vegetable couscous

Salmon with vegetable quinoa

Supper Apple crumble Berry crumble

Corn flakes & lactose

spelt bread with spread

Rice cakes with cheese

Salmon with vegetable quinoa

Weet-bix & lactosemilk,wheat bread with spread

Salmon with vegetable couscous

Ryvita with cheese

Orange

Berry crumble

cordial

Apple crumble

Pear

apple juiceLow FODMAP frittataHigh FODMAP frittata

Halmos, et al 2014

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 2014

IMPROVEMENT IN GI SYMPTOMS IN IBS

• Effect on overall symptoms independent of Rome III sub-type: – IBS-D (n=10): 46% improvement; p=0.016 – IBS-C (n=13): 61% improvement; p=0.003 – IBS-M (n=5): 24% improvement; p=0.078 – IBS-U (n=2): 49% improvement

Halmos, et al 2014

OVERALL SYMPTOMS HEALTHY CONTROLS (N=8)

Mean 8.4mm 95%CI [4.3-12.4] 10.7mm 95%CI [3.9-17.4]

P=0.153; repeated measures ANOVA

Halmos, et al 2014

P<0.001 Repeated measures ANOVA




EFFECT ON SPECIFIC SYMPTOMS IN IBS (N=30)

Halmos, et al 2014

ADHERENCE TO THE DIET

Definition: ≥17 of 21 days adherent.

• Typical Australian diet – 100% adherent. • Low FODMAP diet: 80% of IBS. 100% of healthy subjects.

Halmos, et al 2014

POTENTIAL BIASES • Blinding of diet successful:

– 71% of healthy controls did not correctly identify ‘diet for IBS management’

• No order effect for overall GI symptoms: – Ratio low: Australian diet

• 1st diet low FODMAP: 0.73 [0.41-1.04]* • 2nd diet low FODMAP: 0.74 [0.46-1.01]*

*Mean [95%CI]

Halmos, et al 2014

SUMMARY AND CONCLUSION • The low FODMAP diet halves gastrointestinal

symptoms in IBS patients compared to a typical Australian diet.

• Gastrointestinal symptoms are unaffected by FODMAP content in the healthy population.

CONCLUSION • Efficacy of low FODMAP diet now has high

quality evidence for unselected patients with IBS. Halmos, et al 2014

• In Australia and • Overseas

and

A large number of scientific studies, from 2003-today, have consistently proven that the Low FODMAP Diet relieves symptoms of irritable

bowel syndrome.

The first was my PhD research, involving a double-blinded, randomised, quadruple arm, placebo-

controlled, cross-over rechallenge trial.

This proved that 3 out of 4 people who try the diet have symptom relief, and it was not due to any

other dietary factor – it was FODMAPs.

Overseastttttttttttttttttfrom 2003 today have consistently proven that thettttttttttthefrom 2003-today have consistently proven that the

In a study performed in Guys Thomas Hospital in London (Staudacher et al 2013), researchers taught two groups of 40 IBS patients different diets, and measured the symptoms before

and 6 weeks after.

The first group were taught the UK’s GI experts’ diet (the NICE guidelines). 53% of patients improved.

The second group were taught the Low FODMAP Diet.

78% of patients improved.

This is important as it shows it is not just an Australian phenomenon. It also shows the Low FODMAP Diet is superior

to any dietary advice ever previously offered.

THE LOW FODMAP DIET IS SUPPORTED BY SCIENTIFIC RESEARCH

Now used around the world

THE LOW FODMAP DIET IS SUPPORTED BY SCIENTIFIC RESEARCH

Danish cookbook

International online media

International print media

GLOBAL UPTAKE OF THE LOW FODMAP DIET

IMPLEMENTING THE LOW FODMAP DIET

• Two phases: – Elimination phase – Reintroduction/liberalisation phase

THE ELIMINATION PHASE

• Identify which FODMAPs are likely or known culprits – use breath test results if available.

• Avoid all foods known to be high in each problem FODMAP.

• Restrict for 6-8 weeks. • Improvement should be seen in two weeks, with

ongoing improvement. • Review appointment with nutritionist with view to

reintroducing some FODMAP-containing foods.

EXAMPLES OF HIGH FODMAP FOODS Excess

Fructose Polyols Lactose Fructans Galacto-

oligosaccharides

Apples, pears, mangoes, nashi fruit, boysenberry, watermelon, cherries, asparagus, Jerusalem artichokes, sugar snap peas, honey, high fructose corn syrup, agave.

Apple, apricot, avocado, blackberry, cherry, nashi fruit, peach, pear, plum, prune, watermelon, cauliflower, mushrooms

Milk, ice cream, custard, yoghurt, ricotta cheese, cream cheese, cottage cheese.

Custard apple, persimmon, nectarine, watermelon, globe artichoke, asparagus, garlic, legumes, lentils, leek, onion, shallot, spring onion (white part), cashew, pistachio, wheat, rye, barley (in large amounts).

Legumes, lentils, chickpeas.

EXAMPLES OF LOW FODMAP FOODS Fruit* Vegetables Cereals and

Grains Milk Products Other foods

Banana, kiwifruit, strawberry, blueberry, orange, mandarin, lemon, lime, honeydew melon, grapes, pineapple, passionfruit. *Limit serving size.

Potato, carrot, spinach, capsicum, eggplant, zucchini, lettuce, tomato, cucumber, turnip, swede, green beans, parsnip, squash

Rice, cornflour, quinoa, millet, sorghum, oats, polenta.

Lactose free milk, lactose free yoghurt, fermented cheeses (block cheese) e.g. parmesan, cheddar, gouda, edam, brie, camembert, fetta, mozarella. Small amounts of cream and soft cheeses.

Sugar, maple syrup, golden syrup. Small handful of nuts and seeds (all except cashews and pistachios), unprocessed meat, fish, chicken, eggs. Garlic-infused olive oil.

THE RE-INTRODUCTION (LIBERALISATION) PHASE

• Goal is to liberalise the diet so that the diet is not unnecessarily restricted. – Eat a greater variety of foods whilst still maintaining symptom

control.

• Important as FODMAPs are pre-biotics. – Restricting all FODMAPs from the diet may have a negative

effect on microbiota. • Decreased diversity and faecal pH but not faecal SCFA

levels (Halmos, 2014). – Including FODMAPs in the diet is encouraged, as tolerated.

• Commence this phase at the review appointment assess symptom response to elimination phase.

• If symptoms well managed, then reintroduce FODMAPs in a controlled re-introduction to determine TYPE and AMOUNT of FODMAPs tolerated. – It is possible that more foods were avoided than an

individual may have needed to achieve symptom relief.

THE RE-INTRODUCTION (LIBERALISATION) PHASE

WHEN TO TREAT? Treat the GI symptomatic patients only

KEYS ASPECTS OF FODMAP RESTRICTION

• Symptoms are due to dose response. • All patients with IBS have different FODMAP

tolerance levels. • Not every person has a problem with every type

of FODMAP. • The liberalisation phase in consultation with a

nutritionist is important and should be encouraged.

WHAT IF THE LOW FODMAP DIET DOES NOT ADEQUATELY RESOLVE SYMPTOMS?

In people in whom the low FODMAP diet is not effective, consider: • Alternative dietary triggers:

– Excessive fat – Alcohol – Caffeine – Food chemicals (e.g. salicylates, amines, etc.)

• Psychological triggers: – Referral to a gut-focused hypnotherapist is often

valuable

PRACTICAL IMPLICATIONS

• The low FODMAP diet is the most efficacious dietary therapy for IBS.

• Specialist nutritionist education required for BOTH phases of implementation (elimination and reintroduction phases).

• Gut-focussed hypnotherapy for patients who do not respond or have insufficient response to dietary intervention.

ACKNOWLEDGEMENTS

Thanks to Ms Emma Halmos for use of her slides regarding the “A low FODMAP diet reduces symptoms in patients with irritable

bowel syndrome” study.

• www.shepherdworks.com.au/shop/category/books

• www.fodmap.com

FURTHER INFORMATION AND FOOD LISTS

http://shepherdworks.com.au/shop/category/books

http://www.fodmap.com/

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