IBS and the Low FODMAP DietNajwa El-Nachef, MDNCSGNA ConferenceSeptember 20, 2014

Irritable Bowel Syndrome Affects up to 20% of adults in US Common symptoms include abdominal

pain, bloating, constipation and/or diarrhea More frequent among females Associated with significant decrease in

quality of life Major economic burden on patients,

healthcare systems and community Remains poorly understood

Horwitz et al. N Engl J Med 2001;344:1846-50

Mechanism of IBS Motility Visceral Hypersensitivity Central Processing Genetic Factors Psychological factors Inflammation Gut Microflora Dietary Factors

Lea et al. Gastroenterol Clin North Am 2005;34:247-55

Treatment for IBS Focus on reduction of symptoms Pharmaceuticals Psychological therapy Fiber Probiotics/Antibiotics Dietary and Lifestyle Interventions

Diet and IBS Relationship between diet and

abdominal symptoms is well recognized From the patient’s perspective, the most

frequently perceived cause for symptoms is food intolerance

Up to 50% of patient’s with IBS symptoms worsen after a meal

60% of patients with IBS believe they have a food allergy

Lea et al. Gastroenterol Clin North Am 2005;34:247-55

Diet and IBS Dairy Free Low fat High Fiber No coffee/alcohol Food diary, self-eliminate Gluten free diet

Fermentable Carbohydrates Dietary carbohydrates can be classified into

sugars, oligosaccharides and polysaccharides based on their degree of polymerisation.

“Fermentable” owing to their availability for fermentation in the colon, which is either due to the absence or reduced concentration of suitable hydrolase enzymes for digestion or in the case of monosaccharides because of incomplete absorption in the small intestine.

Low FODMAP DietIngested FODMAPs are poorly absorbed in

the small bowelSmall, osmotically active molecules which

draw water into the large intestineFODMAPs are also fermented by colonic

microflora, producing hydrogen and/or methane gas

The increase in fluid and gas leads to diarrhea, bloating, flatulence, abdominal pain, and distension

Low FODMAP DietF: FermentableO: Oligo- saccharidesD: Di-saccharidesM: Mono-saccharidesA: and P: Polyols

Fructose Simple monosaccharide Found naturally in many fruits. Also a constituent of

sucrose and fructans. Normally absorbed in small intestine by two

mechanisms: GLUT-5 transporter- present throughout small intesine. GLUT-2 transporter- requires equal amounts of glucose

for more effective absorption. Failure to completely absorb free fructose leads to its

delivery in the colon. Colonic bacteria rapidly ferment free fructose to

hydrogen, carbon dioxide and short-chain fatty acids.

Fructans Major source of fermentable carbohydrates Minimal digestion due to absence of

enzymes in the human GI tract to digest the fructosyl-fructose glycosidic bonds

Wheat and onion are major sources Commercial fructans dervied from sucrose

or chicory root are increasingly added to prepared foods due to their textural and sensory properties

Galacto-oligosaccharides Humans lack a-galactosidase enzymes,

leading to the availability of GOD for colonic fermentation

Milk, legumes and some grains, nuts and seeds

Polyols Sugar Alcohol Absorbed in small intestine by passive

diffusion Present in fruits and vegetables Commonly used in artificial sweeteners

(sorbitol, mannitol, xylitol) Large amounts can cause osmotic

diarrhea

Foods to eliminate Fructans and galactans: wheat and rye in

large amounts, onions, garlic, inulin, legumes, lentils, artichoke, soy milk and almond milk

Lactose: milk, yogurt, ice cream, soft cheese Excess fructose: high fructose corn syrup,

honey, agave, and various fruits (such as apple, pear and watermelon)

Polyols: stones fruits (peach, plum, cherry), mushroom, cauliflower and sorbitol/mannitol

Permissible Foods Grains: rice, oats, gluten free pasta, some gluten free

breads and cereals Fruits: berries (except blackberries), citrus, banana,

grapes, honeydew or cantaloupe melon, kiwifruit Vegetables: Carrots, corn, eggplant, zucchini, peppers,

green beans, lettuce, cucumber, potato, and tomato are a few.

Meats: All meats; avoid processed meats that contain ingredients like high fructose corn syrup, milk solids, or onion/garlic powder

Milk: Lactose free milk, rice milk, lactose free yogurt, hard or ripened cheeses like cheddar and feta

What is the data?

Studies of the mechanisms underlying the effects of fermentable carbohydrates on gastrointestinal symptoms

Delivery of Water/Fermentable Substrate Ileostomy volunteers Two diets tested for 4 days each. One

high in FODMAPs and one low in FODMAPs

All food prepared by investigators At baseline and on day 4, 24 hours

effluent collected 10 patients, ileostomy because of IBD,

no active disease

Barrett et al. Aliment Pharmacol Ther 2010 Apr;31(8):874-82

Main effluent weight significantly less during LFD

Subjects perceived significantly thicker consistency on LFD

Barrett et al. Aliment Pharmacol Ther 2010 Apr;31(8):874-82

MRI Data with and without FODMAPs

Murray et al. Am J Gastroenterol 2014;109:110-9

MRI Data Cont’d

Studies investigating effectiveness on IBS symptoms

Shepherd 2008 Double blinded, randomized placebo-

controlled rechallenge trial 25 patients responded to dietary change Patients were randomly challenged by

graded dose introduction of fructose, fructans or glucose taken as drinks

70-80% developed symptoms when rechallenged

Shepherd. Clin Gastroenterol Hepatol 2008; 6: 765–71.

Positive Global Symptoms

Shepherd Clin Gastroenterol Hepatol 2008;6:765-771

Results for Overall SymptomsOverall Pain Bloatin

gWind Nausea Tiredn

ess

Fructan v. Fructose Mix Gluocse

0.45890.01030.0005

0.19860.09740.0016

0.19070.04050.0005

0.06400.03850.0003

0.84760.57270.2467

0.88380.42170.0148

Fructose v. Mix Glucose

0.00200.0010

0.00780.0176

0.00280.0046

0.00030.0611

0.25390.3065

0.76510.3312

Mix v. Glucose

0.0020 0.0002 0.0003 0.0002 0.1265 0.3328

Low FODMAP Diet v. Standard Dietary Advice

Symptom Group Improved %

P value

Bloating StandardFODMAP

4982

0.002

Abdominal pain

StandardFODMAP

6185

0.023

Flatulence StandardFODMAP

5087

0.001

Nausea StandardFODMAP

2967

0.04

Composite score

Standard FODMAP

4986

<0.001

Staudacher J Hum Nutr Diet 2011;5:487-95

Halmos 2014 Crossover trial, 30 patients with IBS and 8

healthy individuals Randomly assigned to groups that received 21

days either of diet low in FODMAPs or a typical Australian diet

Washout period 21 day before crossing over to the alternate diet.

Almost all food was provided during the interventional diet periods

All stools were collected from days 17-21 and assessed for frequency, weight, water content

Halmos et al. Gastroenterology 2014;146:67–75

“I don’t know what the heck gluten is either but I’m avoiding it- just to be safe.”

Supplementary Figure 1 Recruitment pathway and reasons for screen failure. Recruitment survey was a 23-item questionnaire about symptoms, diet, and investigations for celiac disease described previously.<ce:cross-ref refid="bib20" id="crosref0245"> 20 </c...

Is Gluten the Key Player?

Figure 2 Change in symptom severity from run-in for each dietary treatment over 7-day study period. Data shown represent mean ± SEM. Differences across the treatment arms were compared by Friedman test, in which overall symptoms ( P  = .001), bloating ( P ...

Biesiekiersk Gastroenterology, Volume 145, Issue 2, 2013, 320 - 328.e3i

Is FODMAP Accepted by Patients?

FODMAP Popularity 668,000 results on Google

16,000“Likes” on Facebook

Several Apps available

Many complain too restrictive

Summary FODMAPs do not cause IBS

Delivery of dietary FODMAP to the distal small and proximal large intestine is a normal phenomenon, one that will generate symptoms if the underlying bowel response is exaggerated or abnormal.

Summary Limited data, which are mainly composed of

studies with relatively small sample sizes, support IBS symptom improvement with a low-FODMAP diet.

Beneficial effect of a low FODMAP diet does not appear to be predominantly based on gluten avoidance

No definite biomarkers as of now that are associated with symptom response

Thank you!