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Patient Reported Effects of
Treatments for Irritable Bowel Syndrome
A Retrospective Study
Zillan Neiron 307223159
Supervisors:
Mrs Wendy Stuart-Smith, BSc DipEd, MNutDiet, APD
Dr Anne Swain, Dip Nutr Diet, PhD Chief Dietitian, Allergy Unit, RPAH
Dr Robert Loblay, MBBS, FRACP, PhD
Director, Allergy Unit, RPAH
Allergy Unit Department of Clinical Immunology Royal Prince Alfred Hospital, Sydney
Date of Submission: 1st November, 2012
2
Declaration
The candidate, Zillan Neiron hereby declares that none of the work presented in this essay
has been submitted to any other University or Institution for a higher degree and that to
the best of her knowledge contains no material written or published by another person,
except where due reference is made in the text.
Signature ………………………………………………………………………
Date ……………………………………………………………………………….
Candidate: Zillan Neiron
Student Identification Number: 307223159
3
Patient Reported Effects of Treatments for Irritable Bowel Syndrome
Abstract
Aim: The aim of the present study was to investigate the current management practices used for
irritable bowel syndrome (IBS), focusing on patient reported long term efficacies of trialed
therapies.
Methods: An email with a link to an online questionnaire was sent to all patients with
gastrointestinal symptoms who attended the Royal Prince Alfred Hospital (RPAH) Allergy Unit,
between November 2000 and June 2012. Questions focused on therapies trialed by the patients
and long term outcomes of these therapies. Responses were analysed using Excel and Stata.
Results: Data from 249 patients was analysed. Reported efficacy of treatments was varied. Eighty-
five percent of patients reported diet modification, specifically in the form of eliminating specific
chemicals, as the most effective treatment. Medication, especially gastric acid inhibitors, was also
important. Common probiotics were not reported to provide long term benefit. Modified fibre
diets showed mixed results, although data was incomplete. Reported challenges with specific
chemicals caused patients a variety of gastrointestinal and non-gastrointestinal symptoms, of
which salicylates provoked the greatest number of patients’ symptoms.
4
Conclusions: The reported efficacy of different treatments had a consistent theme, that diet
modification provides the greatest gastrointestinal symptomatic relief. The Elimination Diet and
Challenge protocol at RPAH has shown to be the most efficacious reported form of treatment.
Key words: diet, gastrointestinal symptoms, irritable bowel syndrome (IBS), salicylates.
5
Introduction
Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder worldwide affecting
10-20% of the adult population.1, 2 It is characterised by recurring symptoms of abdominal pain or
discomfort, bloating and altered bowel function in the absence of structural, inflammatory, or
biochemical abnormalities.3, 4 The pathophysiology of IBS is still being determined and includes a
complex interaction between altered GI motility, visceral hypersensitivity, altered brain-gut
function, low grade inflammation, psychosocial stress and intestinal microbes.5-7
The majority of patients with IBS perceive their symptoms to be diet related8 with many reporting
exacerbation of their symptoms immediately following food ingestion.9 Reported trigger foods
include milk and milk products, wheat products, caffeine, certain meats, cabbage and other
brassicas, onion, peas, beans, hot spices and fried foods.9 Dietary trials have produced mixed
results, offering minimal guidance to manage IBS symptoms. It has recently been suggested that
removing poorly absorbed, short chain, rapidly fermentable carbohydrate foods will prevent gas
production resulting from fermentation within the gastrointestinal tract and inhibit an osmotic
effect that may cause IBS symptoms.10 These groups of molecules are referred to as FODMAPs,
which stands for Fermentable Oligo-, Di- and Mono-saccharides and Polyols. Fructose, fructans,
lactose, sorbitol and xylitol are some examples of these carbohydrates.
It has also been hypothesised that natural and added food chemicals, including salicylates, amines
and glutamates, preservatives and colourings, some whole foods including wheat, dairy and soy,
the well-described ‘windy foods’ (e.g. brassicas, legumes) may exacerbate symptoms experienced
by patients with IBS. In patients attending the Royal Prince Alfred Hospital (RPAH) Allergy Unit,
6
dietary triggers of IBS are identified using the Elimination Diet and challenge protocol. The
‘elimination’ phase involves the removal/reduction of certain natural foods, food chemicals and
additives (known to elicit adverse reactions) from the patient’s diet for a number of weeks until
symptoms settle to a stable baseline. The patient is then challenged with these foods and food
chemicals, either in the form of food or double blinded placebo controlled capsules to determine
what the patient reacts to. The patient then carefully liberalises their diet to determine their
threshold of reactivity in order to manage symptoms and maintain nutritional adequacy. Thus the
aim is to identify and limit intake of trigger chemicals/foods only as much as required to manage
symptoms.
The aim of this study is to retrospectively investigate the management history of patients
presenting to the RPAH Allergy Unit with IBS symptoms between the years 2000-2012.
7
Methods
Study Design
This is a retrospective study of patients who attended the RPAH Allergy Unit between November
2000 and June 2012 with gastrointestinal symptoms. Many of the patients followed or are
currently following the Elimination Diet and challenge protocol for identification and management
of their dietary triggers. The study protocol was approved by the Sydney Local Health District
(SLHD) RPAH Zone ethics committee. All patients gave online informed consent, including to
patient record access.
Subjects
Patients were selected for inclusion in the study if they had attended the RPAH Allergy Unit
presenting with gastrointestinal symptoms, aged 18 years or over, between the November 2000
and June 2012. One thousand, one hundred and seventy-three subjects were identified and sent
an email outlining the purpose of the study and inviting them to complete an online Survey
Monkey questionnaire. Between 12 September, 2012, and 10 October, 2012, 249 patients
completed the questionnaire.
Questionnaire
The gastrointestinal symptom questionnaire (Appendix III) was constructed for the use of
retrospectively collecting the patients’ symptoms, interventions and trialed therapies before and
after attending the RPAH Allergy Unit. The questionnaire was updated from a previous paper-
based questionnaire, in a similar study conducted by the RPAH Allergy Unit (Stuart-Smith W, 2000,
unpublished data), to reflect current therapies. The questionnaire for this study was implemented
8
using an online survey software tool known as Survey Monkey consisting of 56 questions.
Questions required a mixture of closed and open responses.
Data Processing and Analysis
Patient data and text results from the online Survey Monkey questionnaire were entered into a
Microsoft Office Excel 2007 spreadsheet by the investigator. Analysis of the data and text was
performed using the Excel spreadsheet. When recording text responses to treatments, only a
definite indication of improvement was taken as a ‘yes’. Blanks were treated as a ‘no’ response.
Graphs were generated from the spreadsheet data. Mean, median and age range of patients were
calculated using the RPAH Allergy Unit database and Stata version 12 statistical analysis program.
Patients’ symptom severity, symptom frequency and reactions to challenges were analysed using
Stata.
9
Results
Response Rate
Of 1156 questionnaires sent via an email invitation with a link, 249 (21.5%) were completed.
Participants only filled out relevant sections of each question; hence data for each question differs
in the total number for analysis.
Demographics
The sample comprised 56 (22.5%) males and 193 (77.5%) females. The mean population age was
41.5 years (45 years for males, 39 years for females; range 18-90 years). The median population
age was 39 years (47.5 years for males, 37 years for females).
Symptoms
The symptom severity and frequency decreased for all symptoms over the study period (Figure 1).
Only patients who recorded severity and frequency before and after were included. The majority
of patients had their initial visit in 2011 (Appendix IV). The most severe symptom reported was
fatigue. The most frequently reported symptom was abdominal discomfort. The symptoms that
improved most in severity were abdominal pain, bloating, abdominal discomfort and stomach
cramps. The symptom improving most in frequency was bloating, followed by abdominal
discomfort, stomach cramps and stomach pain. Sixty-two percent (n=149) of patients’ symptoms
of stomach pain, cramps and discomfort were relieved upon defecation.
10
Figure 1. Mean Symptom Severity and Frequency of Patients with Gastrointestinal Symptoms.
Mean severity and frequency axis refers to the participants rating of their experienced symptom severity and frequency within a range. Symptom severity ranges from 0-3 where 0 = none 1 = mild (aware of symptoms, but easily tolerated) 2 = moderate (bad enough to cause interference with daily life or usual activity) 3 = severe (incapacitating, with inability to work/take part in usual activities). Symptom frequency ranges from 0-4 where 0 = never, 1= less than 1 month, 2 = monthly, 3 = weekly and 4 = daily.
0
1
2
3
Mea
n Se
verit
y /
Freq
uenc
y
Symptom Severity Symptom Frequency
11
Medical tests
Prior to presentation at the RPAH Allergy Unit the majority of patients (68.2%) had undergone
some form of medical testing to rule out any other organic disease, including colonoscopy/biopsy
(63.5%), endoscopy (62.9%), thyroid function test (49.4%), ultra-sound (41.8%), stool examination
(40.6%), CT-scan of abdomen (31.1%), small bowel biopsy (21.2%), dissacharidase assay (lactase)
(12.9%) and 3-day fecal fat collection (9.4%). On average, patients had undergone 1.7 medical
tests.
12
Therapies
Table 1. Efficacy of therapies trialed by patients for gastrointestinal symptoms. Therapy Type Trialed
n= (%n) Still Effective
n= (%n) Medications
(n=127) Gastric Acid Inhibitor 40 (31.5) 31 (77.5)
Anti-inflammatory 14 (11.0) 8 (57.1)
Laxative 11 (8.7) 7 (63.6)
Antibiotic 8 (6.3) 3 (37.5)
Anti-depressant 7 (5.5) 3 (42.8)
Anti-spasmodic 7 (5.5) 5 (71.4)
Anti-diarrhoeal 5 (4.0) 3 (60.0)
Relaxation (n=55)
Golf/Other Exercise 24 (43.6) 13 (54.2)
Meditation 21 (38.2) 11 (52.4)
Decreasing workload 18 (32.7) 14 (77.8)
Taking time by self 18 (32.7) 12 (66.7)
Positive thinking 15 (27.3) 10 (66.7)
Deep breathing 15 (27.3) 10 (66.7)
Natural (n=83)
Herbal tea 38 (45.8) 16 (42.1)
Herbal remedies 38 (45.8) 11 (28.9)
Massage 25 (30.1) 14 (56.0)
Meditation 16 (19.3) 7 (43.8)
Antibiotic therapy 14 (16.9) 6 (42.9)
Colonic irrigation 7 (8.4) 1 (14.3)
Aromatherapy 7 (8.4) 2 (28.6)
Exercise (n=60)
Walking 34 (56.7) 21 (61.8)
Yoga 12 (20.0) 7 (58.3)
Running 10 (16.7) 8 (80.0)
Swimming 10 (16.7) 3 (30.0)
Sport 8 (13.3) 7 (87.5)
Pilates 7 (11.7) 5 (71.4)
Probiotics/Prebiotics/
Fermented Foods (n=160)
Probiotics 91(56.9) -
Prebiotics 6 (3.8) -
Fermented Foods 63 (39.4) -
13
Medications
Forty-two percent of 164 patients had been prescribed medication to assist their gastrointestinal
symptoms, stress or anxiety.
Relaxation Therapy
Thirty-two percent (n=171) of patients were advised to decrease the stress in their life. Exercise
was the commonest therapy (Appendix V).
Natural Therapy
Just over half (50.9%) of 163 patients had used natural therapies to relieve symptoms. Herbal teas
and herbal remedies were the most trialed therapies (Table 1). Massage and meditation were
reported to relieve symptoms of muscle pain, sleeplessness, fatigue, headaches, stress and
improved their ability to relax.
Exercise
Forty-nine (37%) of 160 patients had used exercise to relieve symptoms. Walking was the most
common type trialed (Appendix VII). Exercise was found to assist with bloating (40.8%),
constipation (28.6%), stress (16.3%), bowel movements, gas and pain (14.3%) and general
wellbeing (12.2%).
Probiotics and Prebiotics
Of 158 patients, 67.1% had trialed probiotics and 19.3% of 140 had trialed prebiotics. The
commonly trialed probiotics were Inner Health Plus (56%), Yakult (32%) and IBS Support (27%)
14
(Appendix VI). Efficacy of this therapy was low with less than half of those trialing them finding
probiotics beneficial. Specific preparations of Lactobacillus (n=14) and Bifidobacteria (n=8) were
reportedly the most effective with 42.9% and 62.5% respectively finding them beneficial but
numbers in these groups are very small. Ten percent experienced adverse effects from probiotics
such as diarrhoea, nausea, cramping, headache and itching.
Fermented Foods
Thirty-two percent of patients (n=157) trialed fermented foods to relieve symptoms. Yoghurt was
most commonly trialed (n=48), although 20.8% found it effective (Appendix VI).
Fibre
Forty-eight percent of 155 patients were advised to increase the fibre content of their diet, while
21% of 142 were advised to decreased dietary fibre. However baseline fibre intake levels were not
quantified in the survey. Fruit was the most commonly trialed form of fibre, with at least 30%
reporting improved symptoms and ongoing benefit (Table 2). One patient reported exacerbation
of symptoms, while 4 patients felt no change. Pulses and lentils were the least modified form of
fibre. Constipation and bloating were the symptoms most improved by altering dietary fibre. Six
patients reported symptom improvements due to reduction in intake of salicylate-containing
forms of fibre. Removal of gluten/wheat and fibre in the form of ‘wind producing vegetables’
(namely cabbage, leek and onion) were also reported to alleviate symptoms.
15
Table 2. Fibre Intake of Patients with Gastrointestinal Symptoms. Fibre Type Trialed Increased Intake Decreased Intake Still Benefitting
Fruit (total amount)
45 29 16 24
Pears 36 28 8 17 Apples 34 16 18 18 Banana 24 12 12 13 Avocado 21 8 13 10 Grapes 19 5 14 9 Kiwifruit 20 9 11 12 Vegetables (total) 21 4 17 10 Broccoli 34 28 6 18 Cabbage 27 15 12 15 Brussels sprouts 23 8 15 9 Onion 21 8 13 9 Leek 27 7 20 10 Garlic 21 12 9 9 Peas 29 14 15 16 Green beans 21 7 14 11 Bok choy 23 15 8 11 Beetroot 12 6 6 8 Grains† 15 6 9 8 Pulses and lentils (total)
30 14 16 16
Lentils 25 15 10 12 Chickpeas 22 12 10 10 Kidney beans 15 6 9 9 Baked beans 16 7 9 11 Bran 19 6 13 11 Bulking agents‡ 20 10 10 11
†Includes breads, pasta and rice. ‡Includes Metamucil and psyllium husks.
Diet Modifications
Almost 70% of 151 patients had trialed dietary modifications with benefit in 34% prior to
presentation at the RPAH Allergy Unit. The most common trialed diets were milk-free, gluten-free
and wheat-free, with around half of patients still continuing these diets and finding them
beneficial (Table 3). Fifteen patients specified avoidance of cabbage, broccoli, legumes, cauliflower,
nuts, beans, dried fruit, onions, garlic and Brussels sprouts of the ‘windy foods’. Seven patients
who reported avoidance of rich foods specified fatty foods, cream, oil and chocolate to be
16
beneficial. Water consumption was reportedly increased to 1-3 litres per day. Advice regarding
dietary modifications came from Doctors (39%), Dietitians (48%), Naturopaths (15%) and other
sources.
Table 3. Diets and Diet Modifications Trialed by Patients with Gastrointestinal Symptoms.
Diet Type Trialed Still Continuing Still Benefitting
Yeast-free 36 16 8 Sugar-free 30 10 7 Hypoglycaemia 5 2 1 Wheat-free 61 29 23 Gluten-free 64 33 25 Milk-free 70 34 30 Soy-free 21 13 9 Egg-free 7 4 1 Nut-free 13 4 3 ‘acid-food’ avoidance 27 16 12 ‘rich-food’ avoidance 24 14 10 ‘windy-food’ avoidance 31 17 12 FODMAPs 14 8 6 Increase water consumption 46 24 20 Vitamin/mineral supplementation
33 18 12
Yakult/acidophilus yoghurt 29 8 5 Food combining 8 1 1 Raw food 5 4 4 Organic 17 7 2 Food timing 3 4 1 Liver-cleansing 11 1 0 Diet from Naturopath 10 1 0
17
Elimination Diet
Of 149 patients, 78% changed their diet after attending the RPAH Allergy Unit. Seventy-five
percent of those who started the RPAH Elimination Diet improved. Eighty-three participants
completed challenges: 53% food, 6% capsule and 41% both food and capsule challenges. On
challenge milk/dairy (55%), salicylates (52.5%), amines (50%), preservatives (47.5%),
glutamates/MSG (45%), additives (45%), gluten (40%) and wheat (38.8%) were the commonest
triggers (Figure 2). Salicylates provoked the greatest number of patients’ symptoms (Appendix VIII).
The most common symptoms reported on challenge were: wind/bloating, stomach pain/cramp
and diarrhoea/constipation (Appendix IX).
18
Figure 2. Elimination Diet Challenge Effects on Gastrointestinal and Non-Gastrointestinal Symptoms.
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Additives
Preservatives
Benzoates
Nitrates
Propionates
Sorbates
Sulfites
Antioxidants
Milk
Artificial Colours
Colour 160b
Lactose
Wheat
Gluten
Salicylates
Amines
Glutamate/MSG
Percent of Patients
Nausea/Vomiting Indigestion/Reflux Wind/Bloating Stomach Pain/Cramp
Diarrhoea/Constipation Mouth Ulcers Hives/Swelling Eczema
Headache/Migraine Fatigue Muscle/Joint Ache Sinus Problems
Bladder/Vaginal Other
n=36
n=40
n=42
n=32
n=10
n=22
n=31
n=8
n=44
n=25
n=28
n=38
n=36
n=9
n=10
n=18
n=10
19
Ranking Treatments
One hundred and twenty-three patients ranked the effectiveness of the treatments they had
trialed (Appendix X). Eighty-five percent found dietary modification was the most effective
treatment. The most frequently cited ‘most effective’ treatment was the RPAH Elimination Diet
(47.2%), gluten-free diet (7.3%), medications (6.5%), FODMAPs diet (4.9%) and lactose-free diet
(4.1%) being the most cited. A high fibre diet, exercise, dairy-free diet, probiotics and surgery were
the least effective.
20
Discussion
General Discussion
In this present study on IBS, patients reported an overall reduction in symptom severity and
frequency over time after attending the RPAH Allergy Unit (the Unit) for management of their
symptoms. These improvements are similar to those of a previous retrospective study conducted
at the Unit, where patients reported a 30% reduction in symptom severity and frequency for all
symptoms (Stuart-Smith W, 2000, unpublished data).
It is estimated that 10% of people with IBS seek medical advice and are mostly managed by
primary care.11 Those who consult secondary care report more severe gastrointestinal symptoms
and increased levels of psychological disturbance compared to those who do not.12 Patients who
have attended the Unit, a tertiary care institution, have already seen either a Gastroenterologist or
General Practitioner. Results show that two-thirds of these patients have undergone some kind of
medical testing in relation to their gastrointestinal symptoms before referral to the Unit. As part of
the assessment process, patients seen at the Unit are screened by the physicians to rule out other
organic diseases.
The reported prescribed medications for patients’ symptoms were similar to that reported in the
literature. Interestingly 77.5% of these patients were prescribed gastric acid inhibitors, of which
80.6% found them effective for reflux. However, reflux is not cited as a symptom of IBS in the
Rome III criteria. In addition there is no indication for the use of gastric acid inhibitors as a
treatment for IBS symptoms, but for gastro-oesophageal reflux disease (GORD). It is unknown
whether these patients have reflux and IBS, or whether gastric acid inhibitors are prescribed to
21
assist with symptom complaints. It is possible reflux regularly occurs concurrently with IBS and
practitioners may need to consider the whole gastrointestinal tract as irritable as opposed to just
the bowels. This would benefit from further research.
Exercise was found to be the most effective relaxation therapy. This is in line with the fact that
physical activity improves IBS symptoms,13 increases gastrointestinal motility,14 gas transit and
decreases bloating.15 Relaxation therapy was found to be effective in a high proportion of patients.
Interestingly, diet was listed as a form of relaxation therapy, although diet was not an option
provided within the question on relaxation. Given patients with IBS find exacerbation of symptoms
upon ingestion of offending food,16 that when restricted reduce symptoms,17 it is understandable
these patients find diet a form of relaxation. Modification of diet may help alleviate their
symptoms, in turn reducing patient distress and helping them to relax. This finding is consistent
with the previous study conducted at the Unit (Stuart-Smith W, 2000, unpublished data).
The reported efficacy of some natural therapies was similar to results present in the literature. The
majority of patients trialing herbal tea specified peppermint tea. The antispasmodic effect of
peppermint18 may be the reason for 42% of patients in this study finding it effective. Types of
herbal remedies trialed were not specified by patients and therefore it is difficult to draw
conclusions, however data suggests that herbal medicine may be effective in improving IBS
symptoms.19 Seven patients reported symptom exacerbation with either herbal tea or remedies,
of which 3 reported ‘allergic’ reactions. Exacerbation of symptoms reported by patients are likely
to be a result of very high sources of salicylates or other bioactive compounds in the patient
specified peppermint or chamomile teas and Chinese herbs. Meditation was reportedly beneficial
22
in approximately 50% of patients, consistent with other studies. Meditation has been shown to
improve symptoms and sustain effects for up to 1 year. 20, 21 Hypnotherapy has been found to
provide positive long-term results with reduction in IBS symptoms,22 with a high percentage of
patients finding it worthwhile even if they had not responded to it.23 However in contrast to the
literature it was not reported by any patients as a form of treatment. This could be resultant of
possible expense of hypnotherapy and/or lack of knowledge of its therapeutic effects.
Inner Health Plus, Yakult and IBS Support were the most common probiotics trialed. Although
numbers are small, it is interesting that a higher proportion found single strain Lactobacillus and
Bifidobacteria more beneficial than the commonly trialed probiotic mixes. The literature has
indicated that not all probiotics are equivalent (right down to ‘strain’ level) and provide the same
benefits,24-26 which is seen in this study. Whilst a higher proportion of patients are still using
probiotics, on average 16.2% of them are still finding them beneficial. Current research regarding
probiotics is still identifying the most effective organisms for a given patient, if at all, bearing in
mind that different types appear to improve different symptoms.27-31 It is suggested that probiotics
should be used as a supplement to standard therapy and not a therapy on its own.25, 32 Fermented
foods are a growing area of interest, particularly in naturopathy, for treatment of various ailments.
A number of patients trialed yoghurt for its management of symptoms, even though fermented
foods are not cited as a form of therapy for IBS. This may parallel the ‘newness’ of interest in
fermented foods.
Responses to fibre intake were mixed but overall patients found altering their dietary fibre was
beneficial. However due to the questionnaire design it was difficult to determine whether an
23
increased or decreased intake provided benefit. Studies have concluded that fibre has no/limited
benefits for patients who have IBS with constipation.33 Therefore the inconclusive results are
consistent with the literature. It would be interesting for future research to determine the
predominant symptoms (constipation or diarrhoea) of patients benefitting from fibre. Some
patients found professional advice regarding amounts of fibre to consume ‘confusing’ and
‘contradictory’. One patient had been advised to ‘eat some higher-fibre products, but reduce fruit
in the evening’. General avoidance of fibre or avoidance of specific types, such as the ‘windy foods’
were reported by patients as a result of their personal experience. Some patients reported no
change or exacerbation of symptoms from fibre intake, a possible effect of insoluble fibre.34
Reasons for avoidance of fibre went beyond the fibre per se, and included the presence in fibre-
containing foods of gluten (in breads and cereals) and salicylates, which caused symptom
exacerbation. Fruits, vegetables, cereals and grains (and their products) may contain salicylates,
amines or glutamates, or indeed other added chemicals such as colours, flavours or additives.35
Increasing fibre-rich foods will result in an increased intake of these chemical compounds,
potentially beyond threshold in sensitive patients, exacerbating symptoms.35
There is a significant amount of information on the FODMAPs diet in the literature and it is often
the standard dietary intervention used by dietitians with this group (after ensuring basic healthy
eating principles).36-39 In contrast to the literature, avoidance of windy foods was found to be
beneficial in 12 patients, while 6 patients reported a benefit from the FODMAPs diet. Given that
the FODMAPs diet excludes windy foods, gluten, fructose and artificial sweeteners, this is an
interesting result. In those attending the Unit, 42.9% found the FODMAPs diet effective. It is
possible that other patients with IBS trialing the FODMAPs diet found it beneficial and as a result
24
did not attend the Unit. It is possible that those who trialed the FODMAPs diet and found it
beneficial, but subsequently attended the Unit, sought further relief for their symptoms.
The results show a lactose-free diet was cited as an effective treatment by 4.1% of patients. This is
not surprising as following the ingestion of lactose symptoms such as bloating, flatulence,
abdominal discomfort, nausea and loose stools can be experienced, due to lactase insufficiency.33
Although lactose may exist in healthy individuals and patients with IBS,40 it is important to
determine if lactose intolerance is present in every patient. A milk-free diet was shown to have a
beneficial effect on 42.9% of patients. In addition a reaction to milk/dairy challenges was reported
most frequently. Milk contains numerous proteins and chemicals that patients with IBS may be
intolerant to.40 Milk also contains casein which coagulates in the stomach and is hard to digest,
which may cause symptoms.41 Therefore the results are consistent with the literature where milk
and milk products have been reported as offending foods.16
Interestingly, the number of patients reporting continuation of variously modified diets exceeds
the number of patients reporting a benefit. This could be due to patients feeling if they continue
the modified diets they will eventually receive a benefit.
The results show that the Elimination Diet can be effective in improving symptoms, a result
consistent with the previous study (Stuart-Smith W, 2000, unpublished data). Salicylates provoked
the greatest variety of symptoms: indigestion/reflux, mouth ulcers, hives/swelling, fatigue,
muscle/joint ache and bladder/vaginal problems. Wheat and gluten were most frequently
implicated in wind/bloating, stomach pain/cramps and diarrhoea/constipation. Amines,
25
glutamates and gluten caused the greatest number of patients to report nausea/vomiting, while
milk was generally the most commonly cited problem food and the most common cause of
eczema and sinus problems. Additives, preservatives and amines were the most likely to provoke
headaches/migraines. On average patients reacted to 5.5 chemicals, to varying degrees.
Interestingly challenges to food chemicals affected a wide range of non-gastrointestinal symptoms
in addition to their non-gastrointestinal symptoms. This is consistent with the IBS literature where
patients with IBS often have concomitant central nervous system and skin symptoms.42
Food is a complex chemical mixture where one food item contains numerous chemicals and one
food chemical can be found in a variety of foods. The Elimination Diet and challenge protocol
allows identification of a patient’s specific triggers. Therefore, targeted and systematic challenge
of food chemicals is vital for appropriate identification of potential food triggers. For example
bread contains gluten and other wheat components, but also may contain milk (including lactose),
soy, salicylates, amines and glutamates and potentially thousand of other chemicals. However, if a
patient believes symptom exacerbation occurs after the ingestion of gluten, they might exclude all
foods containing gluten (e.g. bread, pizza, cake, biscuits and cereal). If symptoms are relieved with
this dietary change, it cannot be concluded with any certainty which chemical caused the
symptoms without specific challenges. This kind of ad hoc change is common advice, particularly
from naturopaths, but it rarely accompanied challenges. From a dietetic perspective this is of great
concern as it is not only very limiting to the patient, but is potentially not providing a balanced
adequate diet, sometimes entirely removing core food groups.
26
It is possible that patients may trial numerous therapies at one time. The result is that it is not
possible to determine what is responsible for any change in symptom severity or frequency. In
those patients who utilise capsule challenges, these challenges are to single chemicals, double-
blinded and controlled, providing circumstances for the patient are unchanged (e.g. illness or
breaking the diet), the responses will be reproducible. Some patients noted that they had avoided
certain chemicals they had reactions to altogether, while a low or limited intake of chemicals
causing symptoms was reported by 19 patients. The idea of the Elimination Diet is to identify
thresholds and liberalise accordingly. It is possible that some patients are too early in the
Elimination Diet process to commence liberalising their diet, or are too afraid to experience
symptoms and are content with avoiding certain chemicals.
IBS is not a syndrome. It has multiple etiologies. For patients with food intolerance the reactions to
food and food chemicals are different for each patient; every patient reacts differently; the level of
sensitivity is different for each patient; the severity and frequency of symptoms are different;
personal dietary preferences and lifestyle are different. Therefore not one diet is therapeutic for
all patients with IBS. Each patient needs to be treated individually for their trigger(s) to be
determined and to develop an individual plan. This may be a long process of trial and error as well
as combining a number of therapies. Besides the poor quality of a number of studies, a lack of
reproduction of many studies, short duration and small patient numbers, one of the main reasons
for conflicting data is probably that different people respond differently.
27
Limitations of the study
For natural, relaxation, probiotics, fermented foods and fibre therapies exact dose and duration of
therapy were not reported by all patients. Details provided by patients of therapies trialed were
also vague. Some patients reported throughout the questionnaire that their therapy was initially
effective however not effective anymore. Duration of therapy impacts efficacy and further
research needs to be conducted to look into the period of time patients are trialing therapies.
The questionnaire was not filled out completely by all patients. There was no requirement for all
parts of a question to be completed before the patient moved on. Therefore many questions were
left blank and although medical records may have assisted in this, they were not accessed at the
time. Recall bias plays an important part in this study in that some therapies were trialed over a
decade ago and patient memory may have been impacted, which may explain the incompletion of
the questionnaire.
The study utilises a selective sample population of patients attending the Unit in the past 12 years
for management of gastrointestinal symptoms and whose details were retrieved from the Unit’s
database. Most would live within or near the Central Sydney Local Health District. It is quite
possible that the cohort is not representative (e.g. socioeconomic demographics, disease severity,
etc) of the greater IBS population, and this needs to be taken into account.
Due to limited experience with the platform (Survey Monkey), the questionnaire was not designed
optimally meaning that results were more difficult to interpret and analyse. This is well illustrated
by the fibre question where both increased intake and decreased intake were part of the same
28
question. This resulted in unclear answers as to what patients found beneficial and were still using.
Survey Monkey can incorporate logistics within the questionnaire to prevent incompletion of
questions.
The study results demonstrate the significant role of food intolerance in a cohort of patients
presenting to a specialist clinic with gastrointestinal symptoms. It also demonstrates that of all
therapies the Elimination Diet is the most effective form of treatment for IBS in this cohort, an
effect which outlasts what may be expected from the placebo effect. Once patients have identified
chemicals that cause their symptoms they can modify their diets accordingly to suit their lifestyles.
The study also shows that reflux amongst other upper gastrointestinal symptoms may be common
in IBS patients and suggests that practitioners need to recognise that IBS may be a condition of the
whole gastrointestinal tract in some patients and not just a combination of bowel symptoms.
29
Acknowledgments
The authors wish to acknowledge all the patients with IBS and who were involved in the study.
Thank you to the Royal Prince Alfred Hospital Allergy Unit, the staff and in particular Mrs Wendy
Stuart-Smith (APD), Dr Anne Swain (Chief Dietitian) and Dr Robert Loblay (Director) for their
guidance and assistance. Thank you to Tim Watkins for assistance with statistical data analysis.
Contributions to the study
Zillan Neiron: contributed to the study design, data collection and analysis, to writing and
reviewing the manuscript and applying or ethics approval.
Wendy Stuart Smith: contributed to study design, writing and reviewing the manuscript and
applying for ethics approval.
Anne Swain: contributed to study design, writing and reviewing the manuscript and applying for
ethics approval.
Robert Loblay: contributed to applying for ethics.
Tim Watkins: contributed to analysis of the data.
30
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28. Kim HJ, Camilleri M, McKinzie S, Lempke MB, Burton DD, Thomforde GM, et al. A
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35
Appendices
Appendix I Irritable Bowel Syndrome Literature Review
(2000-2012)
Appendix II Rome Criteria III
Appendix III Questionnaire
Appendix IV Time Frame of RPAH Patient Visits
Appendix V Ranked Relaxation Therapies
Appendix VI Probiotics, Prebiotics and Fermented Foods
Appendix VII Exercise Efficacy Ranking
Appendix VIII RPAH Elimination Diet Challenge Reactions (Compound Effects on Symptoms)
Appendix IX RPAH Elimination Diet Challenge Reactions (Symptoms Affected by Compounds)
Appendix X Patient Efficacy Ranking
36
Appendix I: Irritable Bowel Syndrome Literature Review (2000-2012) Introduction
Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder worldwide. It is
characterised by recurring symptoms of abdominal pain or discomfort, bloating and altered bowel
function (constipation, diarrhoea, or both) in the absence of structural, inflammatory, or biochemical
abnormalities.1, 2 IBS affects 10-20% of the adult population3, 4 and the numerous gastrointestinal
symptoms cause significant morbidity, quality of life impairment, disruption to daily activities resulting
in significant healthcare costs.5-7 Prevalence of IBS is higher in women and relatively stable according to
geography and criteria used to define its presence.8
The etiology is poorly understood and many factors are involved, including gut hypersensitivity, low
grade mucosal inflammation, disturbed colonic motility and previous gastrointestinal infection.9 Due to
lack of reliable biological markers or complete understanding of the pathophysiology, IBS is currently
defined by clinical criteria and by exclusion of ‘organic’ disease.6, 10
Symptoms
IBS is characterised by symptomatic flare ups and a high rate of transition to other functional
gastrointestinal disease over the long term.11 The most bothering symptom of IBS is abdominal pain,
followed by bloating, abdominal distension and gas.12 The abdominal pain of IBS is visceral in nature,
typically episodic and unpredictable. Periods of pain recur over a range of 2-8 days, mixed with a few
pain-free days.13 However in some cases painful periods may be prolonged. The abdominal pain of IBS is
associated with a disturbed bowel habit, where the frequency and consistency of bowel movements
37
change.14 These symptoms are often associated with a reduced quality of life and are therefore a
frequent reason to seek medical care.12, 15
Diagnosis and Subtypes of IBS
The lack of sensitivity and specificity of symptoms to diagnose IBS led to the development of several sets
of diagnostic criteria.16 The first attempt, the Manning criteria, published in 1978 lasted over 30 years.16
The Rome criteria, with three versions (Rome I, II and III) were developed as studies found the sensitivity
and specificity of the Manning criteria low.16 Currently the definition and sub-classification of IBS is given
by the Rome III criteria, which was introduced in 20066(Appendix II). This criterion defines a number of
symptoms including abdominal pain, change in stool frequency, stool consistency or relief of pain upon
defecation, bloating, flatulence, passage of mucus, straining, urgency or incomplete evacuation,
allowing for diagnosis. However despite the criteria, it is often difficult to compare research studies as
different forms of the criteria are used.
The Rome III criteria groups patients into different subtypes based on the predominant stool consistency
which is recognized as a marker of intestinal transit time.17-19 Hence different subtypes are thought to
reflect different pathophysiological mechanisms. Four subtypes are defined: IBS with constipation (IBS-
C), IBS with diarrhoea (IBS-D), IBS with mixed type (IBS-M) and IBS unsubtyped (IBS-U).20 IBS-D is the
most frequent subtype, followed by IBS-U, IBS-C and IBS-M.21 Alternating IBS (IBS-A) is defined as a
subgroup of patients experiencing both periods of diarrhoea and constipation over time.20 The Rome III
committee6 recommends prospective subtyping by self reporting of the patient’s stool pattern using the
Bristol Stool Scale (BSS).22 However, no recommendations exist on the optimal length of self reporting
and no specification of time period required to define IBS-A 20.
38
Subtyping is required to appropriately select and describe study populations in research. However it is
also used in clinical settings to help recommend diagnostic tests and treatment based on the
predominant stool pattern.1, 6, 14, 23-25 A study evaluating the stability of IBS subtypes found that changes
may occur over time mainly between IBS-C or IBS-D and IBS-U.20 Although a predominant IBS subtype
still existed.20
The severity of IBS is determined by symptom reports and behaviours of the patient, rather than by
blood test or histopathological markers in the bowel.26 IBS must be understood from the patient’s
personal experience and perceived illness severity.26 It is the severity levels that determine clinical
diagnostic and treatment decisions. However if clinicians rely exclusively on patient reports of severity,
unnecessary intensive investigations or treatments may occur.26 Severity should not primarily be based
on individual symptoms such as abdominal pain, but on a broader multi-component construct, including
health-related quality of life, psychosocial factors, health care utilisation behaviours, and burden of
illness associated with IBS.26, 27 Therefore severity needs to reflect more on the IBS generally as opposed
to the intensity of symptoms.
Quality of Life and Health Care Burden
IBS is a chronic condition that has been associated with psychiatric co-morbidity, reduced quality of life,
work absenteeism, and impaired social functioning.26 The impact of IBS symptoms on daily functioning
and quality of life can be considerable and comparable to chronic diseases such as congestive heart
failure, hepatic cirrhosis, renal insufficiency and diabetes.28 Significant impairment in health-related
quality of life is most pronounced in energy/fatigue, role limitations caused by physical health problems,
bodily pain and health perceptions.5
39
In a European survey (2003) annually patients with IBS spent 3.9 days in bed (corresponding figure for
those without IBS, 2.7), 5.5 days on sick leave from work (3.1 days), 8.4 days visiting a doctor or nurse
(5.2 days) and 10.2 days when work activities had to be cut short (4.8 days).29 In 2000, a study in the US
found that compared with subjects who did not have IBS, patients with IBS had significantly more
outpatient visits (medical, surgery and emergency), were hospitalised more often and had more
outpatient prescriptions.30 Total annual costs (direct and indirect) of IBS in the United States in 2000
were estimated to be approximately $30 billion excluding prescription and over-the-counter drugs
costs.31 The cost associated with IBS and its impact on patients’ lives is partly due to the inability to
effectively manage symptoms which vary greatly among patients.32
Patients with IBS have reported the integration of IBS into their lives to the extent that it becomes part
of their identity.33 They utilise strategies to manage their symptoms daily and events which threaten the
routine coping strategies have caused stress and exacerbation of symptoms.33 Patients create
individualised strategies that incorporate advice from their doctor.33 A study looking at the benefit-risk
trade off found that women subjects were willing to accept higher risks of serious adverse events in
return for treatments offering better symptom control.34 This indicates the desperation patients with IBS
have for symptomatic relief to improve quality of life.
Epidemiology
The Rome criteria have led to greater uniformity in epidemiological studies of IBS and have facilitated
comparisons among population subgroups. Estimates of the prevalence of IBS among adults are based
on population surveys. Most surveys have been conducted in developed countries and reflect the
prevalence of IBS in those cultures.35 The last comprehensive review of the prevalence and
epidemiology of IBS in North America, in which five population-based prevalence studies were evaluated,
40
was conducted in 2002.36 The prevalence of IBS varies among countries due mainly to the use of
different criteria utilised to define it; the pooled global prevalence has been estimated at 11%.37 The
prevalence ranged from 3-20%, with most studies between 10% and 15%.38 There is a higher proportion
of women who develop IBS compared to men, (2:1), and onset of IBS symptoms occurred mainly in
patients younger than 45 years and also in the elderly.38
Pathophysiology
The pathophysiological mechanisms of IBS are not completely known, however it appears to be linked to
a complex interaction between altered gastrointestinal (GI) motility, visceral hypersensitivity, altered
brain-gut function, low grade inflammation, psychosocial stress and intestinal microbes.39-41
Altered Gastrointestinal Motility
Observations of motility in the stomach, small intestine, colon and rectum in patients with IBS are
generally qualitatively similar to those of healthy controls; 25-75% of patients with IBS show motility
abnormalities.9 In the ileum, colon and rectum, patients with IBS exhibit an exaggerated response to a
variety of provocative stimuli including meals, distention, stress, cholecystokinin, neostigmine and
corticotrophin-releasing hormone (CRH).9 No comparable pattern of hyper-reactivity has been
demonstrated in the proximal small intestine and stomach, where the response to stress changes
(inhibition of contractions) alters from the response to meals (increase in contractions).9
Although accelerated transit appears in diarrhoea and slowed transit appears in constipation, there is no
consensus regarding patterns of motility. In patients with IBS exhibiting diarrhoea and abdominal pain,
there are more significant high-amplitude spreading contractions compared to those seen in healthy
controls.9 These high-amplitude contractions are more likely to be related to a sensation of pain.9
41
Visceral Hypersensitivity
The threshold to report pain is below the normal range in 50%-70% of patients with IBS, as well as their
enhanced perception of visceral events including intestinal contraction and gas.23 Patients with IBS have
an increased sensitivity to stimuli arising from the gut wall and colonic distension compared with healthy
volunteers, known as visceral hypersensitivity.42, 43 Visceral hypersensitivity is an important
pathophysiological mechanism underlying symptom generation in IBS and is present in 33-65% of
patients with IBS and contributes to abdominal pain/discomfort.44
A significant factor involved in the initiation and exacerbation of IBS is stress.45 Animal studies have
demonstrated that stress is an important trigger leading to visceral hypersensitivity, which involves the
release of corticotrophin releasing hormone (CRH)46 and subsequent mast cell activation.47
Seventy-seven percent of patients with IBS showed a significantly increased area of mucosa occupied by
mast cells compared with controls in a study investigating visceral hypersensitivity and microscopic
inflammation.43 Activation of mast cells leads to increased mucosal permeability and increased exposure
of the mucosal immune system to intraluminal antigens.43 Furthermore, mast cell mediators are potent
chemotaxic agents that contribute to increased influx of immune cells. These mediators have been
found to spontaneously be released in patients with IBS43 and sensitise visceral afferent nerves.48 As
these mediators are inflammatory it is proposed that a microscopic inflammation may play a role in
visceral hypersensitivity, with an increased number of mast cells and T cells found in mucosal biopsies
from IBS patients.42 Also mast cells have been shown to be in proximity to visceral afferent nerves in IBS
patients49 which is significantly correlated with severity and frequency of abdominal pain/discomfort.43
42
Altered Brain-Gut Axis
The relationship between neural and immunological networks within the gut and the communication
between the gut and central nervous system, is often known as the brain-gut axis (BGA).50 The gut is
connected to the central nervous system (CNS) through the autonomic nervous system in a bidirectional
way.38 This connection allows for transmission of emotional states from the CNS to the gut and
perception of GI changes (including pain, contractions and bloating) to the CNS.51 In addition to
perception of GI changes, signals from the GI tract influence the brain and can exert changes in motility,
secretion and immune function.52 The axis is therefore a vital communication system for healthy
regulation of food intake, digestion, gut sensations and bowel movement control. Structural and
functional disruptions in the BGA may cause changes in perceptual and reflexive responses of the
nervous system and has been implicated in IBS.53 IBS-D is thought to be associated with increased
motility patterns while IBS-C with decreased motility.9
Independent of connections from the CNS, the gut is able to release the neurotransmitters serotonin
and acetylcholine as part of the enteric nervous system (ENS).54 The role of serotonin in intestinal motor
and secretory function has instigated the hypothesis that altered serotonin signaling can lead to either
constipation or diarrhoea in IBS.55 Serotonin is released from the GI mucosa to stimulate acetycholine
release which initiates GI motility.56 The main serotonin receptors involved in ENS communication are 5-
HT3 and 5-HT4 receptors.57 5-HT3 receptors signal changes in intestinal motility and operate as the main
neurotransmitter connecting to the CNS, whereas 5-HT4 receptors transmit signals to effector
acetycholine neurons. It has been demonstrated that a decrease in serotonin reuptake transporter
(SERT) located within the intestinal mucosa,58 consistently leads to dysfunction of GI motility through
increased serotonin concentrations.59 Increased concentrations of serotonin stimulate 5-HT3 and 5-HT4
43
receptors leading to dysregulated contractions and dilations of the intestinal tract. Weakening of this
signaling cascade has been implemented for the treatment of IBS.38
Low Grade Inflammation
IBS has been viewed as a localised low grade inflammatory disorder with mast cells playing a crucial
role.60 The gut-associated immune system is upregulated in IBS, confirmed by increased inflammatory
cytokines such as interleukins 1, 6 and 1061 and increased activated mast cells, CD3+ve, CD4+ve and
CD8+ve T cells.41 There is a change in the microbial gut colonies in IBS62 and the types of microflora
colonising the gut have a role in regulating immunity.63
Furthermore, upregulated GI associated immune tissue stimulates the release of enterochromaffin cells
and other cells that release serotonin and histamine resulting in GI symptoms.64 Inflammation can result
in opening of tight junctions between enterocytes with the movement of large proteins across the GI
lumen.64 These large proteins act as antigens and lead to antibody production.65 The combination of an
activated immune system, altered gut microbiota and release of serotonin and histamine affecting GI
symptoms in patients with IBS show how a low grade inflammation may be a pathophysiological
mechanism.
Psychosocial Stress
Psychological and social factors (stressful life events or psychological distress) during life may influence
digestive function, symptom perception, illness behaviour and consequently health outcome, daily
function and quality of life.66 Psychological distress and major life events are frequently present in IBS
and are in some part responsible for certain outcomes. On the other hand visceral pain can influence
central pain perception, mood and behaviour.67 Data has shown that environmental factors and
44
psychosocial stressors such as a history of being psychologically abused, less than 6 hours of sleep per
night and an irregular diet, can influence the progression from a healthy individual to a patient with
IBS.68 Also data has shown that anxiety disorders, depression69 and somatisation70 are risk factors for IBS.
Depression is the most common psychiatric diagnosis in patients with IBS with a prevalence of 31.4%
and 17.5% in controls.71 Depressive disorders have been found to be more common in patients with IBS
than patients with similar symptoms, organic GI diseases or healthy controls.71 In addition to depression,
higher levels of neuroticism and anxiety are seen in patients with IBS compared to the general
population.72 In light of the data psychological status, in particular stress, appears to be associated with
IBS.
Microbiota
The human body is inhabited by a complex community of microbes, collectively known as microbiota.73
The majority of these are found in the GI tract. Bacteria may be involved in IBS through the metabolic
capacity of the luminal microbiota and its potential to influence the host-via immune-microbial
interaction.74 A study aimed at evaluating intestinal microbial populations by examining fecal microbiota
found that patients with IBS have a different composition of microbiota compared to healthy controls,75
however there was no explanation how this might be so and how this interacts with IBS symptoms and
health.
IBS may develop post infective gastroenteritis (PI-IBS) which depletes commensal microbiota76 that
normally inhibits pathogen colonisation.77 Onset of new IBS symptoms after infective gastroenteritis is
reported by 6%-17% of patients with IBS.78 Up to 57% of patients continue to have altered bowel
function 6 years after recovery of an acute episode.63 A meta-analysis indicated an increased risk of
developing IBS 1 year after bacterial gastroenteritis, an effect still evident after 36 months.79 Broad
45
spectrum antibiotics are another cause for the depletion of commensal microbiota, with an increased
risk of PI-IBS associated with antibiotic use.80 Exposure to broad spectrum antibiotics, particularly
macrolides or tetracyclines, may be associated with IBS development.81 Studies have therefore shown
that depletion of commensal microbiota via numerous ways may develop IBS despite method of
microbiota depletion.
Genetics
Epidemiological studies of familial aggregation82 and twins83 have suggested a genetic aspect to IBS.
However there are no published genome-wide correlation studies in functional GI or motility disorders
specifically focusing on genetic epidemiology and pharmacogenetics.
The best studied polymorphisms are those related to serotonin signalling in the brain-gut axis, including
serotonin transporter (SERT) and several 5-HT receptors. The 5-HTTLPR polymorphism (for serotonin
transporter-linked polymorphic region) in the promoter region of serotonin transporter gene SLC6A4 is
the most studied polymorphism in IBS. However recent meta-analysis found no clear association
between 5-HTTLPR and the clinical phenotype of IBS.84
Familial aggregation has been reproducibly shown in several clinic-based studies of patients with IBS.82,
85-87 However, clustering of IBS in families does not necessarily indicate a genetic basis, as it could also
result from environmental exposures shared in a household, including diet or lifestyle behaviours
exposure to adverse life events within the family, learned cognitions about disease and illness behaviour,
or shared exposure to microorganisms.82, 88 A study conducted on 6060 twin pairs (117 monozygotic and
164 dizygotic twins) showed that concordance for IBS was significantly greater in monozygotic twins
than in dizygotic twins. Hence having a mother or father with IBS was an independent predictor of IBS
46
status, which was stronger than having a twin with IBS, suggesting that social learning (what an
individual learns from those in his or her environment) may also have an influence on the development
of IBS than genetics.89
Food Allergy
The term ‘food allergy’ refers to an adverse immunologic response to the protein in foods.90 These
responses are based on the development of immunoglobulin E (IgE)-type antibodies to a food
constituent. IgE-mediated food allergies are rare in adults with typically rapid reactions after ingestion of
nuts, shellfish, or fish.90 IgE mediated reactions are generally not responsible for IBS symptoms.91
Treatment and Management
IBS has historically been managed mainly by physicians focusing on normalising bowel habits and
treating pain pharmacologically.92 Medication (antispasmodics, bulking agents, laxatives or
antidepressants), diet and lifestyle alterations have been the main therapeutic options for treatment.93
Management is often based on severity of disease, and the patient and practitioner preferences.
Pharmacological Drugs
Alosetron - Alosetron (5-hydroxytryptamine 3), is a 5-HT3 receptor antagonist used for the treatment of
diarrhoea-predominant irritable bowel syndrome (IBS-D) in women. Clinical trials with alosetron showed
significant efficacy, especially in improving fecal urgency, stool frequency and consistency.94 However
cases of ischemic colitis (IC) and complications of constipation (CoC) associated with its use lead to its
withdrawal in 2000.95 As a result of patient advocacy, it was reintroduced in 2002 with a risk
management plan to limit availability to women with severe IBS-D.95
47
Tegaserod - Tegaserod is a partial agonist of the 5-HT4 receptor that has been shown to provide
improvements in global IBS symptoms and constipation in female patients with IBS-C.9 However reports
of cerebrovascular and cardiac events with Tegaserod usage led to it being removed from the USA
market in 2007.
Prucalopride - Prucalopride is full 5-HT4 agonist with high affinity and selectivity. It has demonstrated
treatment in IBS-C.96 Prucalopride accelerates colonic transit improving bowel function and frequency in
patients with chronic constipation. As a result is has shown to improve satisfaction of bowel movements,
decrease perceived severity of constipation and improve constipation related quality of life.96
Lubiprostone - Lubiprostone is a bicyclic fatty-acid derivative of prostaglandin E1.97 It is a highly specific
luminal activator of Type-2 chloride channels (ClC-2), a transmembrane protein believed to have a role
in IBS-C and constipation. As lubiprostone activates ClC-2, an efflux of chloride ions followed by sodium
ions into the lumen of the GI tract, result in the efflux of water into the lumen.97 Lubiprostone has
shown to improve frequency and consistency of stools, reducing discomfort, straining and severity of
abdominal pain.97 However its adverse effects include nausea, diarrhoea and abdominal pain.97
Crofelemer - Crofelemer belongs to a class of polyphenols that has an antisecretory mechanism of
action. It reduces excess chloride ion secretion via the cystic fibrosis transmembrane conductance-
regulator channel.98 By reducing excess chloride ion secretion, crofelemer decreases excess fluid in the
intestines, and therefore reduce diarrhoea symptoms in IBS-D. In an evaluation study, improvements in
pain and discomfort in females were reported. However no significant change was noticed in
consistency, frequency and urgency to defecate.99 As Crofelemer did not show benefit on bowel
function in this study, further studies are required to assess it as a visceral analgesic effect.
48
Antispasmodics
The idea that pain in IBS is a result of colonic spasm has led to the use of antispasmodics.1 Commonly
used antispasmodics include otilonium, hyoscine, cimetropium, pinaverium and peppermint oil due to
their anticholinergic or relaxatory effects on smooth muscle. Systematic reviews have supported the
efficacy and use of antispasmodics for IBS treatment.1 Otilonium, cimetropium, hyoscine and pinaverium
have been shown to significantly reduce the risk of persistent symptoms after treatment, while
trimebutine appears to have no benefit compared to placebo in treating IBS.100 The biological rationale
for the efficacy of antispasmodics is unclear, but research has shown that patients with IBS-D have a
reduced colon diameter as well as accelerated small bowel transit.101 Therefore antispasmodics may act
by reducing colonic contraction and transit time resulting in decreased pain and stool frequency.
Antibiotics
The use of antibiotics was initially based on the assumption that small intestinal bacterial overgrowth
(SIBO) was a common phenomenon in IBS. This led to the investigation of antimicrobials whose
spectrum activity was appropriate for this indication, such as neomycin and rifaximin.102 Although it has
now been established that SIBO is not a major factor in IBS,103 initial trials with neomycin improved
global IBS symptoms by 50% compared to placebo treated patients.104 However neomycin has been
shown to produce clinical resistance quickly.105 Alternatively the poorly absorbed rifaximin has shown
efficacy in at least two randomised controlled clinical trials,102, 106 with a low incidence of resistance and
few side effects.107 Rifaximin has been shown to improve bloating and abdominal pain after 10 weeks of
treatment.108 A short course of antibiotics for IBS symptoms may be useful, but perhaps only in patients
with altered intestinal microbiota.109 Longer term treatment responsiveness, antibiotic resistance and
the efficacy of re-treatment needs to be investigated.110
49
Tricyclic Antidepressants (TCAs) and Selective Serotonin reuptake inhibitors (SSRIs)
TCAs and SSRIs have been utilised for their modulation of hyperalgesia rather than their psychotropic
effects.111, 112 TCAs have shown to be effective in treating neuropathic pain, while SSRIs appear to
improve the effectiveness of endogenous pain inhibition systems.111 Data has shown that both drug
classes were equally effective in improving IBS symptoms, 112 however TCAs have indicated variable
effects on abdominal pain and uncertain tolerability.109
Psychological Treatment
There are a number of psychological therapies employed to treat IBS, of which cognitive behavioural
therapy (CBT), mindfulness, gut directed hypnotherapy and brief psychodynamic therapy have achieved
promising results.113 A study on patients with IBS showed treatment with CBT for 8 weeks in conjunction
with medical treatment increased mental health of patients more so than those receiving medical
treatment alone.114 CBT demonstrated a reduction in IBS symptoms in combination with medical
treatment and as a single form of treatment.114 Recognition and treatment of anxiety and depression in
patients with IBS using psychotropic drugs and CBT, may require special.115 However a major clinical
disadvantage of psychological treatments for IBS is that they are not widely available for patients and
are relatively expensive.116
Hypnotherapy
Gut-directed hypnotherapy has been shown to have positive long-term results with reduction of IBS
symptoms, in turn improving quality of life and work productivity after treatment.117 It is based on
muscular and mental relaxation utilising general hypnotic suggestions to either focus on symptoms or
distract from them.117 Individually adapted suggestions are used to bring forward a deeper feeling of
being able to control symptoms.117 In a randomised controlled trial using gut-directed hypnotherapy,
50
the severity of GI symptoms, sensory symptoms and bowel habits were reduced.118 The symptom
reduction in the gut-directed hypnotherapy group was maintained 1 year post treatment.118
A retrospective study on 208 patients with IBS investigating the long term effects of gut-directed
hypnotherapy had 87% of patients considering the gut-directed hypnotherapy worthwhile.117 A
proportion of patients that did not respond to the treatment still found it worthwhile hence gut-directed
hypnotherapy may positively affect the ability of patients to cope with IBS symptoms.117 This study
found that patients with IBS responding favourably to hypnotherapy reported a reduction in visits to
gastroenterologists and GPs for GI symptoms.117
Probiotics
Probiotics are live microorganisms which when administered in sufficient amounts presents a health
benefit on the host, with lactobacilli and bifidobacteria being the most commonly used.119 Probiotics can
be packaged in many formulations containing either one organism or a mixture. The modes of action of
probiotics are believed to act through increasing barrier function of intestinal epithelium, inhibition of
pathogenic bacteria binding to intestinal epithelial cells, acidification of the colon and suppression of
growth of pathogens, alteration of immunity, inhibition of visceral hypersensitivity, change in mucosal
response to stress and improving bowel dysmotility.120 However, not all probiotics are the same and the
effect of one probiotic strain cannot be extrapolated to another.121-123
A probiotic preparation must contain sufficient quantities of microbes and requires enzyme and acid
resistance with good mucosal adherence being advantageous. It is not apparent which organisms are
most effective as some reduce bloating and flatulence,124-126 others improve bowel frequency,127 and
some have a positive effect on global symptom scores.62, 128-133 The safety of probiotics in IBS is
51
acceptable, however some aggravate symptoms.134 Currently the strongest evidence to support overall
efficacy in IBS comes from Bifidobacterium infantis 35624 at a dose of 1x108 cfu/day taken for at least 4
weeks.132 Two meta-analysis studies both concluded probiotics improve symptoms of IBS and therefore
can be used as a supplement to standard therapy.122, 135
Prebiotics
Prebiotics are defined as non-digestible but fermentable foods that beneficially affect the host by
selectively stimulating the growth and activity of one species, or a limited number of species of bacteria
in the colon, especially Lactobacilli and Bifidobacteria.136 Among the most extensively studied prebiotics
are the inulin-type fructans, which are linked by [beta]-(2-1) bonds which prevent their digestion by
upper intestinal enzymes, and fructo-oligosaccharides. Both are present in considerable amounts in
many edible fruits and vegetables, including wheat, onion, chicory, garlic, leeks, artichokes and bananas.
Due to their chemical structure, prebiotics are not absorbed in the small intestine, but are fermented in
the colon by endogenous bacteria, releasing energy and producing metabolic substrates, with lactic acid
and short-chain carboxylic acids as end products of the fermentation.
One study utilising a specially developed prebiotic, a trans-galactooligosaccharide (t-GOS), produced
from Bifidobacterium bifidum NCIMB 41171 was examined on 60 patients with IBS.137 Following
prebiotics treatment, proportions of Bifidobacterium species in faeces was increased. It was found that
t-GOS performed better than the placebo in relieving flatulence and bloating, and improving subjects’
global assessment scores. This study supports the idea that this specific prebiotic produced beneficial
effects on some individuals with IBS symptoms and promoted the growth of ‘good’ bacteria
(Bifidobacteria).
52
The ideal duration of probiotic and prebiotic therapy is unknown. Most studies have been short term
and those that have shown a benefit have relapsed soon after therapy cessation as the microbiota
reverts to normal.138 Thus, a lifelong therapy with prebiotics or probiotics may be necessary for patients
with IBS who respond to this type of therapy.131, 139
Symbiotic mixtures
Theoretically certain probiotics at the correct dose and in the appropriate formulation can assist to re-
establish an appropriate balance of intestinal microbiota. This can lead to a better digestive and
intestinal function and therefore improve gastrointestinal symptoms.140 A mixture of probiotics and
prebiotics, called symbiotic should apply a synergistic benefit as the prebiotic substrate enhances the
probiotic organisms.141 A randomised double blinded study showed that a symbiotic mixture has a
beneficial effect in reducing the severity of flatulence in IBS patients with a lack of adverse effects.
However it did not provide overall satisfactory respite of abdominal flatulence and bloating.12
Placebo effect
A placebo is usually described as an inactive substance or form of sham therapy which is identical in
appearance and method of administration to the active treatment. Clinical trials of treatment for IBS
present significant challenges due to a high and variable placebo response ranging from 0%-84%, which
is greater than most treatment effects.142 High placebo rates make it difficult to detect therapeutic gain
and are major concerns for both study design and result interpretation.143
Patient-practitioner interaction has been proposed to affect the placebo response.144 This demonstrates
the necessity for patients with IBS to have a positive patient-practitioner relationship in conjunction
with other forms of treatment to help further reduce symptom severity.
53
Complementary and Alternative Therapies
Many patients with IBS have turned to complementary and alternative medicine (CAM),145 such as
herbal supplements/tea, massage therapy, biofeedback, acupuncture, yoga, reflexology and
aromatherapy.146 For most of these, few or no published studies exist and those that do are often poorly
conducted. However acupuncture and herbal medicines have been studied extensively. A Cochrane
systematic review of herbal medicine treatment was conducted evaluating the effectiveness in treating
IBS and concluded that herbal medicines may be effective in improving IBS symptoms; however future
high quality studies are required.147
Acupuncture
A study conducted on patients with IBS using acupuncture or sham acupuncture found a significant
improvement in global quality of life.148 However a similar study found no statistical difference between
groups.149 In general current evidence does not support the use of acupuncture for the treatment of
IBS.148 The apparent effect though is likely due to placebo and may be predicted by high coping capacity
and low sleep quality in individual patients.148
Meditation and Reflexology
Meditation is a mind-body medicine commonly used to treat various psychological and pain disorders
such as headache, fibromyalgia, lower back pain, anxiety, depression and cancer pain. A pilot study
assessed a relaxation response meditation program in 16 patients with IBS who were asked to practice
the taught meditation at home regularly.150 A significant improvement was seen in flatulence, bloating
and diarrhoea, which were sustained with continued meditation at 1-year follow-up.151 These two
studies show that relaxation may play a role in relieving IBS symptoms which can be continued for a long
period of time. Reflexology on the other hand has not been able to demonstrate the same effects as
54
relaxation. A trial using reflexology foot massage and non-reflexology foot massage as a control,
showed no significant difference in bowel symptoms.152 In addition a systematic review found that
reflexology was not effective in treating other diseases, therefore current evidence does not support the
use of this treatment for any medical condition, including IBS.153
Herbal Therapies
A variety of herbal therapies are available for IBS symptoms. However their efficacies vary greatly, and
especially with a high placebo affect within the IBS population some such as Aloe Vera does not show a
significant effect. 154 The Curcuma longa, extracted from turmeric has shown to decrease IBS prevalence
and reduce abdominal pain/discomfort when taken daily for 8 weeks by approximately 22%. However,
there was no placebo control in this study,155 so no conclusions can be drawn.
Cynara scolymus (Artichoke leaf extract) has shown a significant fall in symptoms after treatment and an
improvement in quality of life in patients with IBS and dypepsia.156 Cynara scolymus has been reported
to affect intestinal microbiota as it is a source of inulin. It has been found to be a substrate for selective
growth of beneficial gut bacteria such as Bifidobacteria and Lactobacilli.157 Cynara scolymus also has an
antispasmodic activity which could also contribute to its positive effect.158
Hypericum perforatum (St John’s Wort) is a popular herbal medicine for the treatment of depression and
potentially beneficial in managing IBS by altering psychological stress and serotonin.159 A trial evaluating
the efficacy of Hypericum perforatum showed it reduced overall bowel symptom score from baseline,
however resulted in lower efficacy for IBS treatment compared with the placebo.160
55
Mentha x piperita (Peppermint Oil) has effects on smooth muscle, reducing colonic contractility and pain
as a result of its calcium channel blocking activity.161 In a prospective, randomised, double-blind, placebo
controlled clinical study 79% of patients taking an enteric coated oil capsule experienced an alleviation
of the severity of abdominal pain.162 Eighty-three percent reported less abdominal distension, 83%
exhibited a reduction in stool frequency, 73% had fewer borborygmi and 79% had less flatulence.162
Results for the placebo were less than half for the corresponding symptoms.162 Another herbal therapy,
STW 5 (Iberogast), composed of hydroethanolic extracts of nine herbs has demonstrated a reduction in
total abdominal pain and IBS symptom scores more so than the placebo.163 It appears it may directly
acts on the epithelium through enteric neuron activation and has a prosecretory effect.164
These herbal therapies are a few examples of new (and in the case of peppermint oil existing) herbal
therapies that may be used currently by patients with IBS. Peppermint oil and STW 5 have shown
greater effects than their comparative placebos and are hence possibly alternative or adjunct forms of
treatment.
IgG based food elimination diet
The antibody, immunoglobulin G (IgG), has been implicated in food-related responses in IBS, particularly
IgG4 which has been demonstrated to be elevated in patients with IBS.165 Two centres have reported
significant symptomatic responses among some patients with IBS who have undergone diets eliminating
offending foods based on a base-line IgG antibody profile.165-167 However, IgG antibodies to food are
common in the normal population and not exclusive to patients with IBS.166 When foods are removed
based on IgG testing, symptoms may improve. However, as foods are complex chemically, the intake of
many other compounds is significantly reduced, and the improvement may be due to the reduction of
these other compounds. The Australasian Society of Clinical Immunology and Allergy (ASCIA) states that
56
‘there is no credible evidence that measuring IgG antibodies is useful for diagnosing food allergy or
intolerance, nor that IgG antibodies cause symptoms’.
Dietary Modifications
Food Intolerance
Subjective food intolerance is defined as symptoms related to intake of food with or without objective
findings, and is reported by 25-65% of patients with IBS.168 Food intolerance has been linked with
immunological, allergic, toxic and psychiatric mechanisms, however the etiology is poorly understood.167
Many patients with IBS describe the exacerbation of their symptoms immediately following food
ingestion,168 which include the sudden onset of abdominal cramps and urgency to defecate. More than
60% of IBS patients report worsening of symptoms after meals, 28% of these within 15 minutes after
eating and 93% within 3 hours.169 Reported offending foods are milk and milk products, wheat products,
caffeine, certain meats, cabbage, onion, peas, beans, hot spices and fried foods.168 As a result many
patients with IBS restrict their intake of certain foods to control symptoms,170 which instigates concerns
regarding the nutritional adequacy of their diet. However, a 2005 population-based survey comparing
dietary consumption of specific food items and nutrients between individuals with IBS or dyspeptic
symptoms to those without, found no difference in consumption of the suspected offending foods.171
No differences were observed for the intake of calories, fibre, protein, iron, calcium, niacin, and vitamins
C, D, E, niacin, B1, B2, B6 and B12 between groups.171
The use of Elimination diets may help patients with IBS identify foods that trigger their symptoms.
Patients are put on a diet consisting of few foods and beverages believed to be least likely to trigger IBS
symptoms.142 If symptoms stop or diminish significantly on the elimination diet, on food or food group is
added back into the diet gradually.142 If no symptoms return with reintroduction of a food, that food
57
stays in the diet while others continue to be added. Return of symptoms after the addition of a food
leads to it being withheld. Ideally double-blind testing of trigger foods are conducted by providing the
triggering food and placebo, but this is rarely done. Response rates of elimination diets range from 6%-
58% .145 The literature on elimination diets is variable, due to the labourious nature of the diets, the
type or quantity of foods restricted, the level of restriction, the types of testing, and the range of
symptom responses to the suspect foods for each individual. Foods are complex and contain numerous
bioactive substances, and if testing is only done with whole foods, it is not possible to isolate the
particular compound causing a reaction. Of some reported triggers, histamine, a component in cheeses,
has been reported to cause diarrhoea and flatulence,172 and perhaps may be necessary to avoid/limit if
causing symptoms. Coffee may behave as a colonic stimulant causing upset in some patients, so
excluding/limiting coffee or caffeine containing products should be considered.173 Numerous other
foods and components may cause symptoms which is why it is not surprising that 63% of patients are
interested in knowing what food to avoid.174
The discussion of food, smell of food, or even sham feeding has been shown to lead to an increased
colonic motor activity and demonstrates that gut activation can take place prior to food ingestion.175
This is known as the cephalic response. As increased colonic motor activity has been shown to be
strongly related with abdominal pain in patients with IBS, it is crucial to recognise that the process of
eating, despite the component of food may exacerbate IBS symptoms.175 Beside the cephalic response,
interactions between nutrient intake, motility and visceral sensation may lead to IBS symptoms. For
example lipid has been found to increase colonic sensitivity and change the pattern of viscerosomatic
pain referral in IBS.176
58
Bulking agents and Fibre
Fibre supplementation is the most extensively and carefully studied dietary treatment for IBS, although
a heterogeneous patient population and strong placebo effect have been the studies shortcomings.142
Bulking agents increase stool frequency by adding water and bulk to stool. Calcium polycarbophil, fibre,
ispaghula husk, methylcellulose and wheat bran are the most commonly used as first treatment for IBS.
Studies have concluded that fibre either has no efficacy or possibly limited benefits for patients who
have IBS with constipation.142
Ligaarden et al. showed a higher intake of vegetables was associated with an increased severity in IBS-C
and IBS-A, while a higher intake of fruits and berries associated with the severity of symptoms in IBS-
D.134 Brussels sprouts, beans and prunes have been reported to produce gas due to fermentation, which
some patients with IBS report to handle poorly.177 Some fruits may exert a laxative effect due to their
carbohydrate composition, which may suggest a cause for symptoms in IBS-D.178
A systematic review and meta-analysis examining the type of fibre, showed that wheat bran (insoluble
fibre) was no more effective in treating IBS than placebo or a low fibre diet.100 The use of insoluble fibre
is discouraged because of concerns that it may exacerbate symptoms.100, 179 The beneficial effect of fibre
seemed to be limited to ispaghula husk (soluble fibre), which only reached marginal statistical
significance in one study.100 In general the studies show how variable the effects of fibre and particularly
type of fibre can be. What may be beneficial for one individual may not be for another, and may even
exacerbate symptoms. The same type of fibre may have different effects on different patients. Hence it
is recommended that if fibre is going to be added to the diet, it should be started at low doses and
slowly titrated up to 20g to 30g per day as it can exacerbate abdominal pain, bloating and intestinal
gas.180
59
Gluten
Recent attention has been given to ‘gluten sensitivity’, which may present with IBS or dyspepsia-like
symptoms without an enteropathy or positive tissue transglutaminase antibodies, which are the
diagnostic determinants for Coeliac disease.181 GI symptoms in these patients improve once gluten has
been excluded from the diet,181 and it has been shown that patients with IBS exhibit more symptoms
upon gluten re-challenge compared to patients receiving placebo.182 However the gluten challenges
were gluten-free muffins and gluten-free breads.182 Due to the nature of the gluten-challenge, i.e. not
being pure gluten, patients symptoms could have been a result of reactions to other chemicals within
the muffins or breads. Giving a ‘whole food’ to a patient as a challenge does not test for one particular
chemical, but a range, making it impossible to conclude that one chemical was the trigger.
Lactose
Lactose is a disaccharide that cannot be absorbed in the small bowel until it is split by the enzyme
lactase.183 Lactose intolerance is a broad term used for individuals who have difficulty digesting lactose
due to a deficiency of lactase in the intestinal mucosa.142, 183 The amount of enzyme produced is usually
low and many will tolerate a small dose (10-12g) without symptoms developing.183 Hence exceeding this
small dose, equivalent to a 250mL glass of milk, symptoms will develop. The prevalence of lactose
intolerance varies widely across ethnic groups, being more prevalent in Indo-Asian populations and
those groups who traditionally have a non-dairy diet. Individuals with and without IBS may report
increased symptoms such as bloating, flatulence, abdominal discomfort, nausea and loose stools,
following ingestion of lactose-containing foods, such as milk and ice-cream.142 Therefore lactose
intolerance does not appear to be a cause of IBS or more prevalent in this group than the general
population.142 As lactose intolerance can imitate IBS symptoms, or be a coexistent condition, it is
60
important to establish whether it is a factor, especially in patients where symptoms are associated with
dairy products.184
Fat
A consistent finding is that IBS symptoms are exacerbated by the consumption of large and irregular
meals high in fat. This could possibly result from an exaggerated gastro-colonic response and
gastrointestinal sensitivity after a fatty meal.185, 186 However there is no clear evidence that high-fat
meals cause symptom exacerbation, given no prospective, randomised controlled trial of a low-fat diet
for IBS treatment has been conducted.
FODMAPs
Fermentable oligosaccharides, dissacharide, monosaccharide and polyols (FODMAPs) are short-chain
carbohydrates that have common functional properties in that they are poorly absorbed, osmotically
active178 and quickly fermented by bacteria.187 FODMAPs include fructans, raffinose, lactose, polyols and
galactans and have the potential to cause IBS symptoms such as bloating and diarrhoea. Galactans are
present in onions, legumes, cabbage and sprouts, while fructans are found in wheat, onions, spring
onions, shallots, leeks, artichokes and chicory.188, 189 Fermentation of these substrates results in gas
production and increased fluid load.187
It is hypothesised that FODMAPs trigger gastrointestinal symptoms in people with visceral
hypersensitivity or abnormal motility by inducing luminal distension via osmotic effects and gas
production resulting from rapid fermentation by bacteria in the intestine.187 A randomised placebo-
controlled trial showed that patients with IBS respond well symptomatically to restriction of FODMAP
intake.189 Breath hydrogen testing was utilised to identify which specific sugars behave as FODMAPs in
61
the individual.190 However it has been shown that the capacity to absorb fructose (a FODMAP) is
considerably varied.191 If the capacity is exceeded symptoms such as wind, bloating and loose/watery
motions are may be experienced.191 Up to 50% of healthy individuals can exceed their fructose
absorptive capacity and have a positive hydrogen breath test with 25g fructose. This has shown to
increase to 80% of healthy individuals exceeding their fructose absorptive capacity with 50g fructose.191
The fructose absorptive capacity and gas production has shown to be equivalent between health
individuals and patients with IBS.191 Only in those with IBS are there additional symptoms due to altered
muscle tone and motility patterns and visceral hypersensitivity.191 Hence IBS is not a result of FODMAP
intolerance as the restriction of FODMAPs will benefit both healthy individuals and patients with IBS.
Essentially FODMAPs are prebiotics and may promote the growth of beneficial bacteria and similarly
produce improvements in IBS symptoms. However the amount of FODMAPs consumed with prebiotic
intent requires trial and error to not exacerbate symptoms.
Glutamate
A study conducted on 57 patients with fibromyalgia and IBS investigated the effects of monosodium
glutamate (MSG) and aspartame after a 4-week diet excluding these chemicals.192 Of the 37 patients
that completed the diet 84% reported that more than 30% of their symptoms had resolved.192
Challenges resulted in a significant return of symptoms and decreased quality of life in regards to IBS
symptoms. This study shows that the effect of glutamate in the diet is more pronounced than the
placebo effect, indicating it that glutamate can cause IBS symptoms.192 Therefore it might be beneficial
to exclude/limit glutamate from the diet if it can be shown to be a trigger for symptoms in a particular
patient.
62
Physical Activity
It has been proposed that physical activity stimulates and increases gastrointestinal motility,193
enhances gas clearance and reduces bloating in patients with IBS.194 Patients with chronic constipation
have demonstrated decreased colonic transit time and improved defecation patterns when starting
regular physical activity.195 IBS patients with a more sedentary lifestyle report more symptoms than
those who are physically active.196 Overall physical activity improves IBS symptoms.197 However the role
of intensity, type of activity, frequency and duration needs to be explored as in endurance athletes
exercise can have adverse effects such as an urge to defecate, diarrhoea and gastrointestinal cramps.198
Conclusion
The etiology of IBS is complex and most likely involving a range of mechanisms interacting with one
another as opposed to a single mechanism. Current treatments available include drugs, psychotherapy,
herbal therapy, relaxation, diet modification and physical activity, and perhaps a mixture depending on
the patient’s symptom severity/symptom frequency, and their personal preferences. However given all
form of treatment, it is diet that over two-thirds of patients report as triggering onset of GI symptoms.
So essentially should it not be diet that is utilised as a main form of treatment for this population group?
Studies have shown diet to help improve symptoms; however there are fewer studies on diet and IBS
compared to drug treatment. Perhaps not all patients with IBS want to be taking drugs indefinitely for
symptom relief. In conclusion more thorough research into foods that trigger GI symptoms needs to be
conducted and considered a major player in symptom management.
63
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84
Appendix II: Rome Criteria III Rome Foundation
Diagnostic criterion* for Irritable Bowel Syndrome:
Recurrent abdominal pain or discomfort**at least 3 days/month in the last 3 months associated
with two or more of the following:
1. Improvement with defecation
2. Onset associated with a change in stool frequency
3. Onset associated with a change in stool form (appearance)
*Criterion fulfilled for the last 3 months with symptom onset at least 6 months prior to
diagnosis
** ‘Discomfort’ means an uncomfortable sensation not described as pain.
In pathophysiology research and clinical trials, a pain/discomfort frequency of at least 2 days a
week during screening evaluation is recommended for subject eligibility.
Reference: Rome Foundation. Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders; 2006. (Also available from: http://www.romecriteria.org/assets/pdf/19_RomeIII_apA_885-898.pdf), accessed on 25 October 2012
85
Appendix III: Questionnaire
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
Appendix IV: Year of Initial RPAH Allergy Unit Patient Visit
Figure. A1. Time period between initial RPAH visit and current survey of patients with gastrointestinal symptoms.
1 0 2 2
8
2 3 6
16
10
25
67
26
0
10
20
30
40
50
60
70
80
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
No.
of P
atie
nts
Years
110
Appendix V: Ranked Relaxation Therapies
Figure. A2. Ranked relaxation therapies by patients in relation to gastrointestinal symptom improvements.
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Therapy 1 (n= 47)
Therapy 2 (n= 33)
Therapy 3 (n=27)
Perc
ent o
f Pat
ient
s
Ranked Relaxation Therapy
Exercise
Diet
Meditation
Deep Breathing
Positive Thinking
Delegation
Talking to friends
Relaxation
Time Alone
111
Appendix VI: Probiotics, Prebiotics and Fermented Foods Table A1. Common Probiotics, Prebiotics and Fermented Foods utilised by participants for relief of gastrointestinal symptoms and efficacy. Product Trialed Effective Still
Using Still
Benefitting
Prob
iotic
s†
Inner Health Plus 54 14 7 5 IBS Support 26 8 4 2 Symbiotique 0 1 0 0 Lactobacillus 14 6 4 4 Bifidobacteria 8 5 4 4 Vaalia Innergy yoghurt 7 3 2 1 Danone Activia yoghurt 11 5 4 2 SKI Activ yoghurt 12 4 5 2 Yakult 30 6 6 2
Prebiotic†
EcoBloom 6 3 3 2
Ferm
ente
d Fo
ods‡
Yoghurt 48 16 17 10 Kefir 5 0 2 0 Kimchi 5 0 0 0 Kombucha 1 1 0 0 Miso 8 1 2 0 Umeboshi 0 0 0 0 Sauerkraut 3 1 0 0 Tempeh 3 0 0 0 Pickles (including Carrots/Beets)
7 1 0 0
Pickled Ginger 9 2 0 0
For the treatment of gastrointestinal symptoms number of patients responded to the questions on the use of Probiotics† and Prebiotics† is 97 in total. Number of patients responded to questions of Fermented Foods‡ is 63.
112
Appendix VII: Exercise Efficacy Ranking
Figure A3. Ranked exercise types by patients for symptomatic relief of gastrointestinal symptoms.
0
10
20
30
40
50
60
70
Exercise 1 Exercise 2 Exercise 3
Num
ber o
f Pat
ient
s
Exercise Rank
Walking
Other
Yoga
Swimming
Running
Pilates
Gym
113
Appendix VIII: RPAH Elimination Diet Challenge Reactions (Compound Effects on Symptoms)
Figure A4. Symptoms experienced by patients reacting to chemical compounds.
0 5
10 15 20 25 30
No.
of P
atie
nts
Milk
0 5
10 15 20 25
No.
of P
atie
nts
Wheat
0 5
10 15 20 25
No.
of P
atie
nts
Gluten
0 5
10 15 20 25
No.
of P
atie
nts
Salicylates
0 5
10 15 20 25
No.
of P
atie
nts
Amines
0
5
10
15
20
No.
of P
atie
nts
Glutamates/MSG
114
Figure A4. Symptoms experienced by patients reacting to chemical compounds.
0
5
10
15
20
No.
of P
atie
nts
Additives
0
5
10
15
20
No.
of P
atie
nts
Preservatives
0 1 2 3 4 5 6
No.
of P
atie
nts
Benzoates
0 2 4 6 8
10 12
No.
of P
atie
nts
Nitrates
0 1 2 3 4 5 6
No.
of P
atie
nts
Propionates
0 1 2 3 4 5
No.
of P
atie
nts
Sorbates
115
Figure A4. Symptoms experienced by patients reacting to chemical compounds.
0 2 4 6 8
10 12
No.
of P
atie
nts
Sulfites
0 0.5
1 1.5
2 2.5
3 3.5
4 4.5
No.
of P
atie
nts
Antioxidants
0 2 4 6 8
10 12 14
No.
of P
atie
nts
Artificial Colours
0 1 2 3 4 5 6 7
No.
of P
atie
nts
Colour 160b
0
5
10
15
20
No.
of P
atie
nts
Lactose
116
Appendix IX: RPAH Elimination Diet Challenge Reactions (Symptoms Affected by Compounds) Figure A5. RPAH Elimination Diet challenges causing symptoms in patients reacting to chemical compounds.
0 2 4 6 8
10 12 14 16
No.
of P
atie
nts
Nausea/Vomiting
0 2 4 6 8
10 12 14 16
No.
of P
atie
nts
Indigestion/Reflux
0
5
10
15
20
25
No.
of P
atie
nts
Wind/Bloating
0
5
10
15
20
25
No.
of P
atie
nts
Stomach Pain/Cramp
0 5
10 15 20 25 30
No.
of P
atie
nts
Diarrhoea/Constipation
0 1 2 3 4 5 6 7
No.
of P
atie
nts
Mouth Ulcers
117
Figure A5. RPAH Elimination Diet challenges causing symptoms in patients reacting to chemical compounds.
0 2 4 6 8
10 12
No.
of P
atie
nts
Hives/Swelling
0 1 2 3 4 5 6
No.
of P
atie
nts
Eczema
0
5
10
15
20
No.
of P
atie
nts
Headache/Migraine
0
5
10
15
20 N
o. o
f Pat
ient
s
Fatigue
0
5
10
15
No.
of P
atie
nts
Muscle/Joint Ache
0
5
10
15
No.
of P
atie
nts
Sinus Problems
118
Figure A5. RPAH Elimination Diet challenges causing symptoms in patients reacting to chemical compounds.
0 1 2 3 4 5 6 7 8
No.
of P
atie
nts
Bladder/Vaginal
0 2 4 6 8
10 12
No.
of P
atie
nts
Other
119
Appendix X: Patient Efficacy Ranking
Figure. A3. Patient reported efficacy of trialed therapies in relation to gastrointestinal symptoms.
47.2
17.9
7.3 6.5 4.9 4.1
2.4 2.4 1.6 1.6 0.8 0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
40.0
45.0
50.0
Perc
ent o
f Pat
ient
Therapy
Recommended