The role of diet in irritable bowel syndrome (IBS) has been debated for decades, so far without any consensus as to whether dietary components may be the cause, trigger, or merely an exacerbating factor in an existing condition in the gastrointestinal (GI) tract.  It is likely that any, or a combination of factors, could be the offending mechanism in different individuals.

      There is a  lack of evidence that food allergy is involved in most cases of TBS as numerous studies have failed to show the presence of immunological markers, such as food-specific antibodies and the inflammatory mediators indicative of an allergic response. (l)

      Food intolerances, which do not involve the immune system, have been considered a  possible cause of IBS, but definitive evidence is lacking due to the enormous difficulty in diagnosing intolerance reactions and triggers in suspected adverse responses to food.
Frequently an adverse reaction occurs after a significant delay from when the food responsible had been consumed, making the gold standard of placebo-controlled food challenge unusable. (2)

      In most cases a mixture of foods has been eaten in a meal suspected to include the offending ingredient, again making identification of the specific culprit next to impossible.

      In the majority of cases it is suspected that food is not the cause of the symptoms of IBS (which typically include abdominal pain, bloating, flatus and altered bowel habit), but that food constituents “irritate” an already inflamed GI tract.  Conditions within the irritated system may in turn result in an altered microflora in the bowel and even the establishment of microorganisms higher up in the small intestine (small intestinal bowel overgrowth (SIBO), leading to exacerbation of the inflammation and increased symptom intensity.

      Although the mediators usually associated with inflammation are not normally detectable in IBS, several studies have reported the presence of prostaglandin E2 (PGE2) in the faeces of lBS patients. PCE2 is one of the secondary mediators produced when mast cells are degranulated (release of the granules that store inflammatory mediators within the mast cell) as a result of activation by allergens and a variety of other agents. Mast cells are present in abundance throughout the digestive tract and interact closely with nerves in the area. (3)

      As a result of degranulation, an enzyme called phospholipase A2 is released, which acts on the cell membrane to release one of its constituents, called arachidonic acid (AA), a 20-carbon chain omega-6 fatty acid. Prostag land ins, prostacyclins and thromboxane (collectively called eicosanoids) are produced when arachidonic acid is acted upon by enzymes of the cyclo­-oxygenase pathway (COX enzymes) (4). PCE2 is one of the most active prostaglandins. It dilates blood vessels; can make tissues more sensitive to pain; contributes to swelling by making blood vessels more permeable, allowing seepage of fluid; and invokes an increase in heat in inflamed tissues. (5)

      Aspirin and non-steroid al anti­ inflammatory drugs (NSAID) reduce pain by blocking COX enzymes, particularly COX-2, and thus the production of prostaglandins, including PCE2.

      Research from the University of Michigan published in 2017(6) is helping to elucidate the role of PCE2 and other mediators in diarrhoea-predominant IBS (IBS-D) patients. The authors analysed biopsy material from 17 IBS-D patients and 18 controls without IBS. The IBS-D material showed a 3-times higher level of  PGE2 compared to the normal controls. In addition, there was a 3- fold increase in COX-2 in the IBS-D subjects. As confirmation of the role of mast cells, the authors of the study further demonstrated that the mast cell stabilizer, cromolyn sodium, which inhibits mast cell degranulation, reduced the production of PGE2, and hence decreased the pain and symptoms associated with it.

      Further evidence of the role of mast cells in IBS-D was the observation that there was a 2-3-fold increase in tryptase and histamine in the IBS-D biopsy material compared to the normal controls. The presence of tryptase and histamine is evidence that mast cell degranulation is involved in the generation of these mediators.  Serum tryptase is sometimes used as an indicator of mast cell activation in the diagnosis of mast cell activation disorders (MCAD). (7)  Histamine is produced and stored within mast cells and is one of the first mediators released as a result of mast cell degranulation.  Therefore, this research demonstrates that mast cells are important factors in IBS-D. However, this is not the whole story. The results indicate that the histamine and tryptase from mast cells in turn stimulate the COX-2 enzyme and as a result increase the production of PGE2, and the symptoms associated with it.

      To further complicate the picture, the  researchers  suggest  that  the level of PGE2 may be increased  by an additional process involving interactions  between  the  immune and nervous systems, mediated by a neuropeptide called substance P. Substance P (SP) is secreted by nerves and immune  system  cells such as macrophages, eosinophils, lymphocytes, and dendritic cells. SP has inflammatory effects in immune and epithelial cells and participates in inflammatory diseases of the respiratory, gastrointestinal, and musculoskeletal systems.   Many substances including allergens, histamine, prostaglandins, and leukotrienes induce SP release from sensory nerves in these organs. SP released from sensory nerves in the GI tract (8), can increase the quantity of arachidonic acid (AA) released from the mast cell membrane.  As mentioned above, AA is the substrate on which the COX-2 enzyme acts to produce PGE2. The increased amount of AA-induced by SP, together with the increased activity induced by histamine and tryptase, results in increased amounts of  PGE2, thus resulting in an elevated intensity of the symptoms associated with it.

To summarize:

  • Prostaglandin PGE2 is largely responsible for the pain as well as other symptoms in IBS-D
  • PGE2 is an inflammatory mediator generated from activated mast cells
  • PGE2 is produced by the action of the COX-2 enzyme on the arachidonic acid of the mast cell membrane
  • Histamine and tryptase are also released from activated mast cells
  • Histamine and tryptase increase the activity of the COX-2 enzyme and consequently increase the amount of PGE2 generated from arachidonic acid (AA)
  • Substance P (SP) is released from sensory nerve cells in an inflamed or irritated GI tract
  • The mediators released in the inflammatory response, including h1stamme, prostaglandins, leukotrienes and allergens, can increase the amount of SP released from sensory nerves in the GI tract
  • SP increases the amount of AA released from activated mast cells
  • The increased amount of AA together with enhanced COX-2 activity increases the amount of PGE
  • Increased PGE2 results in an elevated level of pain and other symptoms
  • This demonstrates that histamine is both a product and an inducer of the inflammatory response in IBS.

      Based on the research discussed above, it is now becoming clear that increased histamine from various sources will exacerbate, or even trigger, the inflammatory response that results in the symptoms of IBS. It would be logical to assume that one of these sources would be histamine­ containing food. Therefore, any diet designed to manage or reduce the severity of symptom s in IBS should also restrict the amount of histamine arising from the diet. This would be especially important in people who have evidence of deficiency in histamine-degrading enzymes, particularly diamine oxidase (DAO), or have a mast cell activation disorder (MCAD).

      While this research explains a great deal about the immunological mechanisms involved in the inflammatory response in IBS, it does not reveal the underlying causes of the inflammation that
initiates the process. These causes are diverse, and probably unique to each individual, involving both genetic factors, such as enzyme deficiencies; lifestyle issues such as stress; and the intake of reactive chemicals including ingredients in many foods. Effective management of IBS should address any lifestyle issues as well as removal of the predominant dietary triggers and exacerbating factors, based on an elimination and challenge approach. However, it is likely that an entirely satisfactory outcome will not be achieved without addressing the extremely important contribution of histamine in the process.

Diet and IBS
As the head of the Allergy nutrition Clinic at Vancouver Hospital, Canada from 1990 to 2003 I spent a great deal of time in developing a diet that excludes all the known triggers and exacerbating factors in IBS in an effort to help the more than a thousand patients referred to me for dietary control of their symptoms. In 2004 my dietary approach and the scientific basis for all the directives was published by Rutgers University Press. (9).

      The book contains information about the rationale for the diet, specific details about the foods allowed and those restricted, extensive recipes and meal plans, and instructions on how to reintroduce foods in order to determine their role in an individual’s response. A chart audit of the outcome of this dietary approach revealed that more than 80% of my patients obtained either total or partial relief of their symptoms while adhering to the diet.

      Unfortunately, because the book included a great deal of referenced scientific data the publisher concluded that the work would be more appropriately classified as a textbook rather than a book for general readership. Although several institutions did adopt the book as a course text, the information was not widely recognized within the population who would benefit the most- IBS sufferers. Happily, the book is now available to be downloaded from the internet (9) and is readily accessible to everyone.

      At the time of writing and researching the book, little was known about the involvement of histamine in IBS. Since I was researching histamine throughout my tenure at VGH I was able to observe that a significant number of my IBS patients were also histamine intolerant. They responded amazingly well to my combined IBS and histamine restricted diet. (To obtain a copy of this diet contact the AAA office.)

Results of this approach were elevated from a “Somewhat improved” on the IBS diet alone to “Greatly improved”, and even up to “Amazing results!” on an informal outcome assessment questionnaire.

The FODMAP diet is becoming increasingly known as a dietary management strategy for irritable bowel syndrome (IBS). The acronym refers to fermentable oligo- di- and mono-saccharides and polyols. It originated at Monash University in Melbourne, Australia (10), (11). As with all good research, the information on the diet and its effects in various clinical applications is frequently being updated as new reliable information becomes available. (12) As a result, there is no single standardised, peer­ reviewed version of the diet available.

      However, because the diet has become so widely recommended both in popular literature and in the medical profession, especially among gastroenterologists, numerous versions of the diet are available in print and on the internet. Unfortunately, many of these differ, sometimes quite significantly, from the versions in published reports from the original researchers at Monash University.

      Although gluten is not one of the components of the FODMAP diet, [gluten is a protein, called an alpha-gliadin, and therefore would not logically be excluded on a diet designed to eliminate sugar molecules], because so many patients report non-celiac gluten intolerance, later versions of the diet exclude gluten. Presumably, many practitioners exclude gluten as a possible factor in GI tract disorders such as IBS as a precaution rather than as a diagnosed causative agent as in celiac disease.

      In order to help that people who are following a FODMAP diet, I have modified the lists of allowed foods to exclude histamine-containing foods in addition to those excluded on the FODMAP diet. This should be of assistance to those IBS sufferers who have achieved less than their expected improvement on the FODMAP diet alone. (To obtain a copy of these lists contact the AAA office.)

 In Summary:

      Dietary components are suspected to h·igger or exacerbate IBS, regardless of the underlying cause of the condition. Recent research is indicating that histamine is playing an important role in diarrhoea-predominant IBS.
      Although many different diets have been designed to remove food ingredients that have been demonstrated or suspected to cause distress in IBS patients, none of the published diets take into account the potentially significant contribution that dietary histamine may be playing in the condition. To address this omission, two dietary approaches to IBS with modifications to include histamine restrictions are presented here for the first time. People who are achieving less than satisfactory outcomes on their current lBS diet are encouraged to try this approach, to determine to what extent histamine may be an important contributor to their symptoms.

References :

  1. Jones VA,  Mclaughlan  P, Shorthouse M,  Workman  E, Hunter JO. Food intolerances: a major factor in the pathogenesis of irritable bowel syndrome. 1982 Nov 20;2(8308):1115-1117.
  2. Shepherd SJ, Parker FC, Muir JG, Gibson PR. Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence. Clin Gastroenterol Hepato l. 2008 J ul;6 (7):765-77 1.
  3. De Winter BY, van den Wijngaard RM, de Jonge WJ. Intestinal mast cells in gut inflammation and motility disturbances. Biochim Biophys Acta . 2012 Jan;l 822(1):66-73.
  4. Joneja Vickerstaff J. The Health Professional’s Guide to Food Allergies and Intolerance. Academy of Nutrition and Dietetics. October 2012 ISBN 978-0-88091-453-6 Chapter 1: Food allergy: the Science 3-21.
  5. Joneja Vickerstaff J, Bielory B. Understanding Allergy. Sensitivity, and Immunity:  A comprehensive guide Rutgers University Press, New Brunswick and London 1990.
  6. Grabauskas G, Wu X, Turgeon DK, Chung 0. PGE2 produced by mast cells is critical to induce visceral hypersensitivity in IBS. Gastroenterology April 2017;152(5):Suppll :S213.
  7. Ravi A, Butter field J, Weiler CR. Mast cell activation syndrome: improved identification by combined determinations of serum tryptase and 24-hour urine 11a-prostaglandin2a J Allergy  Clin  Immunol  Pract.  2014 Nov -Dec;2(6):775-778.
  8. O’Connor TM, O’Connell J,O ‘ Brien DI, Goode T, Bredin CP, Shanahan F. The role of substance P in inflammatory disease. J Cell Physiol. 2004 Nov;201(2):167-180.
  9. Joneja JM Vickerstaff Digestion. Diet and Disease: Irritable Bowel Syndrome and Gastrointestinal Function. Rutgers University Press, Piscataway, New Jersey. August 2004 ISBN 0-8135-3387-2.
  10. Gibson PR, Shepherd SJ. Personal view: food for thought  –  western lifestyle and susceptibility to Crohn’s disease. The FODMAP hypothesis. Aliment Pharmacol Ther 2005; 21: 1399-1409.
  11. Shepherd SJ, Gibson PR.  Fructose malabsorption and symptoms of irritable bowel syndrome: guidelines for effective dietary management. J Am Diet Assoc 2006; 106: 1631- 1639.
  12. Barrett JS, Gibson Fermentable oligosaccharides. disaccharides. monosaccharides and polyols (FODMAPs) and nonallergic food intolerance: FODMAPs or food chemicals? Therap Adv Gastroenterol. 2012 Jul; 5(4):261-268.

This article was first published in Allergy Newsletter No. 123 Summer 2018