NUTRITION IN IBS - Rhode Island Hospital

3/21/2014
Irritable Bowel Syndrome (IBS)
NUTRITION IN IBS
Judy Nee, MD
November 2013
Brown University
• 20% of the North American population
• 2:1 Female to Male predominance
• The burden of disease is high such that the
annual cost of IBS treatment in the United States
is estimated to be nearly $10 billion in direct
costs and $20 billion in indirect costs
– To compare, in 2003, estimated costs of HTN and
CHF were $50 billion and $30 billion respectively
Simren et al. Food-related gastrointestinal symptoms in the irritable bowel syndrome. Digestion 2001
IBS: Why Should We Still Search
• Direct costs – “over”utilitization of health care
– IBS may also be the reason for the largest percentage of
referrals to GEs (30% to 50%).
– Total costs were 51% higher in IBS patients, who also had higher
costs for outpatient visits, drugs, and radiology and laboratory
tests (p < 0.05).
Irritable Bowel Syndrome:
Pathophysiology
Visceral hypersensitivity
• Indirect costs – loss of productivity (30% report missing
work/school due to symptoms)
• Why are we spending so much on IBS?
Altered motility
– Length of time to diagnosis
– Comorbidities: An estimated 48% of patients with chronic pain
syndromes
– History of abdominal surgeries
Altered gut-brain axis
• Misinterpretation of IBS symptoms as indicators of abdominal or
gynecological conditions that can be remediated by surgery
Altered flora
Hulisz D et al. J Manag Care Pharm. 2004 Jul-Aug;10(4):299-309
Longstreth GF et al. Am J Gastroenterol. 2003 Mar;98(3):600-7.
Diet in IBS
IBS and Fiber
• What we say: Increased consumption of
soluble fibers like psyllium or oats
Two-thirds of IBS patients report food triggers
and subsequently report food restrictions
– ACG: Bulking agents that contain psyllium
(ispaghula husk) — for example, Metamucil,
Fiberall, Hydrocil, and Konsyl — improve overall
symptoms, but neither wheat bran nor corn bran
is better than a placebo in managing IBS (grade
2C).
Vernia et al. Self-reported milk intolerance in irritable bowel syndrome: what should we believe? Clin Nutrition 2004 Oct 23 (5); 996-1000
Carrocio et al. Non-celiac gluten sensitiviity diagnosed by DBPC trial. AJG July 2012
Biesiekierski JR. Am J Gastro 2011. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled
trial.
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IBS and Lactose
• Definitions
– Lactose malabsorption does not universally lead
to symptoms in persons with lactase deficiency
– Lactose intolerance: when individuals with lactose
malabsorption develop GI symptoms, such as
abdominal cramping, bloating, flatulence, and
diarrhea
Based on studies with variable quality (low-> moderate) and high drop out rates
Gupta et al. Gastro Hepatol 2007;22:2261-2265
Farup et al. Scan J Gastroenterol 2004; 39:645-649
Zhu et al. Am J Gastro 2013; 108: 1516-1525
Alexander Ford et al. BMJ. 2008
Breath Testing
Lactose in IBS
• Breath testing in IBS patients
– Prevalence lactose malabsorption is the same in IBS vs. controls (as
high as 70-75% LHT positive)
– However, some studies show that IBS pts are 3xs more likely to
complain of sxs compared to healthy controls (Bloating and
borborygmi more frequent without objective evidence of distension)
• Self reported milk intolerance in IBS patients does not help in
identifying lactose malabsorbers
• Inconsistent improvement in IBS patients who restrict lactose:
29-75%
Simren et al. Gut. 2006 March; 55(3): 297–303.
Pimentel M et al. Am J Gastroenterol. 2003 Dec;98(12):2700-4.
Vesa Thet a;. Am J Clin Nutr. 1998 Apr;67(4):710-5
Zhu Y et al. Am J Gastroenterol. 2013 Sep;108(9):1516-25.
Yang J et al. Clin Gastroenterol Hepatol. 2013 Mar;11(3):262-268
Gluten Free: Popular for a Reason?
“People returned several months later
and did indeed show lower blood sugar,
often sufficient for pre-diabetics to be
non-prediabetics. But it was the other
results they described that took me by
surprise: weight loss of 25 to 30 lbs over
several months, marked improvement or
total relief from arthritis, improvement
in asthma sufficient to chuck 2 or 3
inhalers, complete relief from acid reflux
and irritable bowel syndrome symptoms,
disappearance of leg swelling and
numbness. Most reported increased
mental clarity, deeper sleep, and more
stable moods and emotions.”
Wheat Belly, August 2011
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IBS and gluten
• Non-celiac gluten sensitivity (NCGS or
GS) was originally described in the
1980s but has been “rediscovered”
recently
• Sapone et al described 13 CD vs. 13 GS
vs. controls
• Not a new entity, reported in 19801
• Prevalence unknown, probably greater than
celiac disease but no data
– GS: Marsh 0-1
– CD subjects compared to GS had
increased:
– Varies from 0.548% to 30% of US!!
– Studies reporting prevalence reflect referral bias
• IL-17 expression
• Intestinal permeability measured by
urinary lactulose/mannitol ratio
• Adaptive immunity markers IL-6 and IL21
– GS subjects compared to CD had
increased:
• Expression of the innate immunity
marker TLR-2 was increased in NCGS
but not in celiac disease
NCGS
First time evidence of
differential intestinal mucosal
immune responses to gluten
between CD and GS.
• Currently no specific criteria or validated tests
for diagnosing NCGS
• Reported in association with allergic diseases
Massari, S, et al, Ine Arch Allergy Immunol, 155;389, 2011
Sapone et al. Int Arch Allergy Immunol. 2010 April; 152(1): 75–80
Sapone A, et al. BMC Med. 2011 Mar 9;9:23
Gluten causes symptoms in IBS
patients without celiac disease
Fructose
Double-blind, randomized, placebocontrolled rechallenge trial in IBS pts
excluded for celiac disease
34 subjects with IBS
• 13/19 patients (68%) in the gluten
group vs. 6 of 15 (40%) on placebo
(P=0.0001) with inadequately
controlled symptoms
• VAS: patients were significantly worse
with gluten within 1 week for overall
symptoms, pain, bloating, satisfaction
with stool consistency, and tiredness
(p <0.05)
Biesiekierski JR et al. Am J Gastroenterol. 2011 Mar;106(3):508-14
IBS and Fructose
• Previous studies observed incomplete
absorption after 50 g of fructose in 37.5%
- 80% of healthy subjects and IBS
• Fructose breath testing is fraught with
problems
– GI symptoms associated with fructose
malabsorption are generally magnified
– Perception that fructose does not play a
major role in patients with IBS often leads to a
lack of treatment
According to the U.S. Agriculture Fact Book, HFCS
consumption increased from 16% to 42% of total sweetener
consumption between the years 1978 and 1999
Barrett JS etl al. Prevalence of fructose and lactose malabsorption in patients with gastrointestinal disorders. Aliment Pharmacol Therapeut 30: 165-174
Choi YK, Kraft N, Zimmerman B, et al. Fructose intolerance in IBS and utility of fructose-restricted diet. J Clin Gastroenterol. 2008;42:233–238.
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Fructose
Food Allergy vs. Food Intolerance
• Three separate studies have shown an
identification and counseling re fructose
consumption lead to improvement in IBS
symptoms
• Choi et al
– 31 of 80 IBS patients with positive hydrogen breath tests
received verbal and written instructions on fructose
restriction or exclusion, and then were followed up to 1 year
later
– 14 of the subjects were compliant  experienced a
statistically significant reduction in abdominal pain, belching,
bloating, fullness, indigestion, and diarrhea symptom scores
compared to baseline 1 year prior
Choi YK, Kraft N, Zimmerman B, et al. Fructose intolerance in IBS and utility of fructose-restricted diet. J Clin
Gastroenterol. 2008;42:233–238.
Boettcher E, Crowe SE. Dietary proteins and functional gastrointestinal disorders. Am J Gastroenterol. 2013 May;108(5):72836. doi: 10.1038/ajg.2013.97.
AGA Guidelines in IBS 2002
Dietary modification:
• Although many patients may attribute their symptoms
to specific food substances, the type of food does not
generally contribute to symptoms. Patients are more
likely to experience symptoms as a generalized effect
of eating, and at times may even become conditioned
to reduce eating to avoid postprandial discomfort.
However, certain dietary substances may aggravate
symptoms in some individuals. This might include fatty
foods, beans, and gas-producing foods, alcohol,
caffeine, lactose in lactose-deficient individuals, and, in
some cases, excess fiber. Care should be taken to avoid
an unnecessarily restrictive diet.
• Determine the effect of a diet low in fermentable
carbohydrates (FODMAPs) on symptom severity
and global improvement in diarrhea predominant
irritable bowel syndrome (IBS)
• Evaluate the changes in bacterial stool
composition following a low FODMAP diet with
high-throughput metagenomic DNA sequencing of
short hypervariable regions of 16S rDNA genes
Does a diet low in fermentable
carbohydrates (FODMAPs) change
symptoms and gut microbiota in irritable
bowel syndrome?
Low FODMAP
Diet avoids:
Fermentable
Oligosaccharides
Disaccharides,
Monosaccharides
And
Polyols
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The low FODMAP diet: Pearls
• This is a learning diet
• Hallmarks: Lactose-free, wheat/gluten free,
and low disproportionate fructose
• Gluten free ≠ FODMAP friendly
• Fiber is important … keep fiber up with oats,
oat bran, rice bran, green beans, potato skins
• Read labels
Mechanisms
Low FODMAPs … how does it work?
Poorly absorbed, rapidly fermented by GI bacteria,
leading to increased water and gas in the GI tract
• Poorly absorbed in the small intestine
– Poor absorption occurs by virtue of slow, low-capacity transport mechanisms
across the epithelium (fructose)
– Reduced activity of brush border hydrolases (lactose)
– Lack of hydrolases (fructans, galactans)
– Molecules being too large for simple diffusion (polyols)
• Osmotically-active molecules
• Rapidly fermented by bacteria
– The rapidity of fermentation by bacteria is dictated by the chain length of the
carbohydrate (oligosaccharides and sugars are very rapidly fermented
compared with polysaccharides such as soluble dietary fiber)
Inulin/Fructan Consumption
Murray K et al. AJG 2013 Nov 19
Gibson et al. Clinical ramifications of malabsorption of fructose and other short-cahin carbohydrates. Practical Gastro 2007
Mechanisms
? Alteration in the microbiota
• Barrett et al 2010: Ileostomy model  high
FODMAPs increased water content
• Ong et al. 2010: breath tests  Ingestion of a
low-FODMAP diet significantly reduced breath
hydrogen production in healthy volunteers
and patients with IBS with consequential
reduction in gastrointestinal symptom scores
in the IBS population
Barrett et al. Aliment Pharmacol Ther 2010;31:874-882
Ong et al. J Gastroenterol Hepatol 2010; 25: 1366–1373
Staudacher et al. J Nutr. 142: 1510–1518, 2012
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FODMAPs: A History
Primary endpoint: “Were your symptoms adequately controlled in this phase?
• Initially described in a 2006 retrospective study examining IBS
patients with proven fructose intolerance
– Fructose restriction lead to 75% symptom improvement of common
IBS symptoms of abdominal pain, gas, bloating, diarrhea, and
constipation, nausea
– In those who adhered to the diet 86% vs non-adherent 36%
• A randomized control trial in 2008, again in Australia, showed that
IBS patients with fructose malabsorption not only improved with a
low fructose diet, but also developed symptoms with a
carbohydrate undetectable by breath testing named fructans
(garlic, onion, wheat)
– Upon rechallenge, these IBS patients reports significant worsening of
symptoms
• 70% receiving fructose, 77% receiving fructans, 79% receiving fructans and
fructose were not adequately controlled vs. 14% receiving glucose only
• Dose dependent response
Shepherd et al. Fructose Malabsorption and Symptoms of IBS. Journal of the American Dietetic Association. 2006
Shepherd et al. Dietary Triggers of Abdominal Symptoms in Pts with IBS: Randomized Placebo Controlled Evidence. Clin Gastro and hepatol 2008
FODMAPs: A History
• Finally, in 2011, the diet was expanded to
include many other malabsorbed
carbohydrates including lactose, fructose,
and fructans compared to a the UK NICE
diet
IBS symptoms evaluated were significantly greater with ingestion of
fructose, fructans, and fructose-fructan mix than with glucose. In
contrast, nausea and tiredness did not significantly differ across
treatment groups.
– Low FODMAP with 75% satisfaction in
symptom improvement in global
symptoms compared to standard group
(50%)
– Trend for more patients in the low
FODMAP group to report improvement in
diarrhea vs. control, but not statistically
significant 82% vs. 62%
– Magnitude of diarrhea symptoms
improved: moderately or substantially
improved
– No difference in constipation
– Self reported compliance 50-64% of time
Staudacher et al 2011. Comparison of Symptom Response Following Advice for a diet low in fermentable carbohydrates. Jour of Human Nutrition and Dietetics. 2011
FODMAPs
• 2013 Gastroenterology
• First blinded, randomized control trial: 30 IBS, 8
healthy controls on 21 days of low FODMAP (each
<0.5grams/meal) vs. normal Australian diet
– 10 had IBS-D, 13 had IBS-C, 5 had IBS-M, and 2 had
IBS-U
– Wash-out 21 days
– Cross-over to alternate diet
• All food was provided (if need more, advised
regarding appropriate additions)
Hamos et al. Gastroenterology 2013
Hamos et al. Gastroenterology 2013
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FODMAPs vs. Gluten
Mean satisfaction with stool
consistency improved despite no
change in stool frequency/volume
Hamos et al. Gastroenterology 2013
FODMAPs vs. Gluten only
Currently Unanswered Questions
•
•
•
•
Do you need breath testing?
Can this be applied to the US?
Can ppl be adherent to the diet?
How do we counsel pts about the FODMAP
diet? Physician, nutritionist?
Biesiekirski et al. Gastroenterology. 2013;145:320–328
Does a diet low in fermentable carbohydrates
(FODMAPs) change symptoms and gut microbiota in
IBS?
Low FODMAP
20 patients
“Habitual” diet
Recruitment
IBS-diarrhea
Randomization
8 weeks
20 patients
Low FODMAP
diet
Food diary
IBS-SSS, GIS
Stool sample
4 week phone call
Food diary
IBS-SSS, GIS
8 week in-person visit
Food diary
IBS-SSS, GIS
Stool sample
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Low FODMAP Booklet
Fecal Microbiome
• The fecal microbiome has been
implicated in the etiology of IBS
• At baseline, compared to healthy
controls, the intestinal microbiota of
patients with IBS have been shown to
have increased numbers of Clostridium,
and a decrease in the number of
Bacterioides, Bifidobacterium and
Faecalibacterium species
– Reduction in diversity of species
• Particular organisms are associated with
higher IBS symptom scores
Malinen et al. Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR. Am Journ Gastro 2005
Kassenin et al. Fecal Microbiota of IBS patients differs significantly from that of healthy subjects. Gastro 2007
Rajilid-Stojanovid Global and deep molecular analysis of microbiota signatures from patients with IBS. Gastro 2011
Conclusions
• IBS therapies are not satisfactory
• Food may exacerbate symptoms of IBS
– Fiber, lactose, gluten, fructose
• Low FODMAP diet may be effective for
symptoms of IBS but it has yet to be applied to
the US
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