The role of FODMAPs in irritable bowel syndrome

Transcription

1 REVIEW C URRENT OPINION The role of FODMAPs in irritable bowel syndrome Susan J. Shepherd a,b, Emma Halmos b, and Simon Glance c Purpose of review Irritable bowel syndrome (IBS) is a condition affecting approximately 10 15% of Western populations. The Rome III criteria are applied to many studies to validate the diagnosis of IBS. The low fermentable oligo, di, monosaccharides and polyol (FODMAP) diet has been the subject of many robust clinical trials and is now used as the primary dietary therapy internationally. This review examines the current evidence for the role of the low FODMAP diet in IBS. Recent findings Detailed commentary on original research involving FODMAPs and IBS symptoms from 2013 to 2014 is provided. Summary The low FODMAP diet has been shown to be an efficacious therapy for reduction of functional gastrointestinal symptoms seen in IBS. Recent publications provide randomized controlled trial and prospective observational evidence in support of the diet for symptom management. The low FODMAP diet appears to be superior to a gluten-free diet in people with self-reported nonceliac gluten sensitivity. Although the low FODMAP diet has not been shown to reduce the prebiotic effect in the colon, total colonic bacterial load was reduced. Further research investigating the potential health implications of both this and the nutritional adequacy of the liberalized low FODMAP diet is required. Keywords diet, fermentable oligo, di, monosaccharides and polyol, functional gut, irritable bowel syndrome INTRODUCTION Irritable bowel syndrome is the most common functional gastrointestinal disorder and is estimated to affect approximately 15% of the population [1]. The condition is characterized by recurrent episodes of functional gastrointestinal symptoms, including abdominal pain, changes in bowel habits (diarrhoea and/or constipation), abdominal bloating, distension and excessive passage of wind. The main approaches to control symptoms have centred on pharmacological and dietary therapies. Pharmacological agents have historically targeted only one symptom, for example, hypomotility agents for diarrhoea, but have little effect on the array of symptoms seen in irritable bowel syndrome (IBS). The most commonly prescribed medications are selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), with some evidence of efficacy [2]. Alternatively, dietary therapies are becoming increasingly more popular and are often very appealing to IBS sufferers. Fibre supplementation has received much attention although the majority of studies have shown no clear difference over placebo [3]. Elimination-type diets to remove suspected dietary triggers have had anecdotal success, but few have had proper scientific rigor and validated outcome measures. The first diet to show promise in effectively reducing the range of symptoms in IBS is the low fermentable oligo, di, monosaccharides and polyol (FODMAP) diet. FODMAPs are a collection of poorly absorbed, short-chain carbohydrates that naturally occur in many foods. Mechanism studies have shown that FODMAPs cause luminal distension through their fermentation by colonic bacteria and subsequent gas production, and through their osmotic activity [4 & ]. The acronym FODMAP describes: the oligosaccharides fructans and galacto-oligosaccharides present in wheat, rye, onions, garlic and legumes; a Department of Dietetics and Human Nutrition, La Trobe University, Bundoora, b Shepherd Works P/L, Box Hill North and c Department of Gastroenterology, Northern Hospital, Epping, Victoria, Australia Correspondence to Susan J. Shepherd, Department of Dietetics and Human Nutrition, La Trobe University, cnr Plenty Road and Kingsbury Drive, Bundoora, VIC 3083,. Australia. Tel: ; fax: ; sue@shepherdworks.com.au, s.shepherd@latrobe. edu.au Curr Opin Clin Nutr Metab Care 2014, 17: DOI: /MCO ß 2014 Wolters Kluwer Health Lippincott Williams & Wilkins

2 Functional foods and dietary supplements KEY POINTS The low FODMAP diet provides effective symptom relief in 68 76% in people with IBS. Symptoms from luminal distension may originate from both the small and the large bowel. The low FODMAP diet has been seen to be superior to the gluten-free diet in people with self-reported NCGS. The low FODMAP diet is associated with a reduction in total bacterial abundance, but not specific antiprebiotic effects. Implications of a reduced total bacterial load and potential nutritional inadequacies of a low FODMAP diet require further investigation. Analysis of long-term applications of the low FODMAP diet, including dietary liberalization commonly achieved in many IBS patients, is indicated. the disaccharide lactose present in milk and yoghurt; the monosaccharide fructose (when consumed in excess of glucose) present in honey, apples, pears and high fructose corn syrup; and polyols including sorbitol and mannitol present in apples, pears, stone fruit and many artificially sweetened gums and confectionary [4 & ]. CURRENT VIEWS Since observing the benefit of the low FODMAP diet when it was first applied in clinical practice to IBS patients in 1999 [5], a series of studies were completed to show proof-of-concept, and it has gone on to be the subject of much scientific research amongst different research teams around the globe. In 2013 and 2014, many review papers refer to FODMAPs, featuring in exclusive commentary or within recommendations and/or guidelines [4 &,6 12]. Editorials [13,14] and other commentary in peer-reviewed journals have also contributed points of view regarding the low FODMAP diet in IBS. Overwhelmingly, the summation and conclusions of these reviews support the role of the low FODMAP diet as an effective dietary therapy for IBS and functional gastrointestinal symptoms. It is the recommended practice to administer a low FODMAP diet via two phases. The first phase is to assess each individual patient s degree of benefit and ease of application. This is best achieved through an initial phase of strict elimination of foods high in FODMAPs, generally of 6 8-week duration, guided by a specialist dietician. Indeed, individual and group consultations have been shown to be effective [4 &,15]. After completing this initial phase, follow-up consultations with a dietician are indicated to then liberalize the diet in a step-wise fashion to determine the type and amount of FODMAPs that is tolerated in individual patients. This second-phase procedure tailors the low FODMAP diet to each patient to ensure that unnecessary dietary restriction is minimized and maximum variety in the diet is achieved, whilst still maintaining a satisfactory level of symptom control [4 & ]. ORIGINAL RESEARCH This review will now describe the recent (2013/ 2014) original research publications relating to FODMAPs and functional gastrointestinal symptoms. Randomized controlled trial of low fermentable oligo, di, monosaccharides and polyol and typical Australian diet in irritable bowel syndrome patients The study by Halmos et al. [16 ] has provided evidence of the relationship between FODMAPs and gastrointestinal symptoms. This randomized controlled single-blind cross-over trial convincingly demonstrated that compared with a provided typical (Australian) diet, a low FODMAP diet reduced the severity of functional gastrointestinal symptoms in 30 unselected patients with IBS. Participants were subjected to a 21-day treatment period (Australian diet vs. low FODMAP diet), and their gastrointestinal symptoms were assessed using a 100 mm visual analogue scale (VAS) daily, with the VAS scores of the final 14 days of the treatment period being used in analysis. Overall symptoms were halved by the low FODMAP diet. Clinically significant improvement was seen in 70% of IBS participants, and this encompassed IBS with diarrhoea-predominance, constipation-predominance, both diarrhoea and constipation-predominance and those with neither diarrhoea nor constipation. Additionally, the low FODMAP diet showed a reduction of specific symptoms, including abdominal pain, bloating, passage of wind and dissatisfaction with stool consistency (P < for all). Symptoms in a control group of eight healthy participants remained low and unaltered by dietary FODMAPs, showing that the effect was not exaggerated by over-supplementation of FODMAPs in the typical Australian diet. This study used a whole diet approach (rather than pure FODMAP supplementation) in which confounding variables from other dietary components Volume 17 Number 6 November 2014

3 Role of FODMAPs in IBS Shepherd et al. were controlled, enabling a clear confirmation of the effects of FODMAP restriction compared with a typical diet in IBS subjects. Observational study of a dietician-taught low fermentable oligo, di, monosaccharides and polyol diet in irritable bowel syndrome patients A New Zealand prospective observational study by de Roest et al. [1] provided positive reinforcement for existing efficacy data. Researchers examined 90 IBS patients who had undergone sugar malabsorption breath tests for fructose and lactose using lactulose standard and then underwent dietary intervention for a low FODMAP diet. Dietary intervention involved initial appointment with a dietician, well versed in the low FODMAP diet and review 6 weeks later. Study participants completed a symptom questionnaire using the gastrointestinal symptom rating scale before intervention and mean 15.7 months after intervention. Participants were also asked to rate adherence, opinions about the diet and degree of symptom change at the time of the follow-up. The education intervention significantly improved abdominal pain, bloating, constipation, diarrhoea, nausea, passing of gas, loose bowel movements, hard stools, urgent need for bowel movement and abdominal distension (P for all). Despite being a nonrandomized observational study, 75% of patients reported being satisfied with symptom relief, which is consistent with other randomized control trials [16,17,18]. Adherence rate to the low FODMAP diet was high; compliance was 76%, and adherence was positively correlated with symptom improvement for bloating, abdominal pain, flatulence and diarrhoea. The unblinded, uncontrolled study design may be criticized for many biases, which is worthy of consideration given the high placebo response commonly seen in IBS populations. However, this observational study reflects real-life practice. In reality, IBS patients are commonly educated on a low FODMAP diet in this fashion; thus, this study is a good indication of the efficacy of a dietician-taught low FODMAP education used in the community. Another finding from this study was that a positive fructose breath test was a predictor of response, although this finding may be misrepresented because of the possible placebo response from the unblinded participants. Mechanism study investigating luminal distension of different fermentable oligo, di, monosaccharides and polyols To date, the concept of FODMAPs inducing symptoms was thought to originate from large intestine, in which luminal distension would result from both colonic gas and the osmotic load from unabsorbed FODMAPs [4 & ]. This concept has been challenged by the 2014 mechanism study by Murray et al. [19 ], showing that osmotic load from FODMAPs also distended the small bowel. Sixteen healthy volunteers were recruited to take part in this single-blinded randomized quadruple arm cross-over study investigating the volume of the small and large bowel after individual FODMAP and glucose challenges using the MRI technique. Following an FODMAP, alcohol and caffeine restricted diet the day prior, participants ingested 40 g of the efficiently absorbed glucose, poorly and slowly absorbed fructose, less osmotically active inulin (a fructan) and 1 : 1 mix of fructose and glucose (in which glucose should aidabsorptionoffructose).mriscansweretaken preingestion and hourly until approximately 5 h after ingestion of the solution and breath hydrogen readings were taken every 30 min (approx) for 5h. The small bowel findings from this study related to an area under the curve (AUC) measurement for changes in small bowel water content (SBWC) (l/min). Glucose triggered the smallest increase in SBWC (mean AUC l/min), with progressively increasing water delivery seen after ingestion of 1 : 1 fructose and glucose mix (55 28) and fructose alone (71 23). Significantly increased SBWC was seen after 40 g fructose was ingested compared with glucose (P < 0.001). Large intestinal gas production recorded via breath hydrogen measures was consistent with early findings [20], showing increased gas production after ingestion of inulin and fructose compared with glucose and fructose present in equimolar concentrations with glucose (P < 0.01). This well designed study showed that longer chain carbohydrates such as inulin have a greater effect on colonic gas production and little effect on SBWC, whereas smaller chain FODMAPs such as fructose are likely to cause luminal distension in both the small and large intestines. Contrary to the observational findings in Roest et al., the results of this study question the importance of breath testing in predicting specific FODMAPs-inducing symptoms. The majority of healthy volunteers in this study tolerated the physiological effects of the challenges, likely due to the absence of visceral hypersensitivity, which is a common feature of IBS [4 &,10]. Understanding the effects of differing lengths of FODMAPs in both healthy and IBS populations could be valuable in further refining the teachings of the low FODMAP diet ß 2014 Wolters Kluwer Health Lippincott Williams & Wilkins 607

4 Functional foods and dietary supplements The role of fermentable oligo, di, monosaccharides and polyols in patients with self-reported noncoeliac gluten sensitivity A role for the low FODMAP diet in minimizing symptoms in people with nonceliac gluten sensitivity (NCGS) was recently suggested in a doubleblinded placebo-controlled cross-over trial in patients with self-reported NCGS by Biesiekierski et al. [21 ]. This study showed that gluten did not induce any specific gastrointestinal symptoms in the 37 participants; however, the provision of a low FODMAP diet reduced symptoms in all 37 participants, leading to greater symptom improvement than following their habitual gluten free diet (P < 0.001). As both gluten AND FODMAPs are present in wheat, rye and barley, the improvement people with self-reported NCGS feel on a gluten-free diet (i.e. wheat-, rye- and barley-free diet) may actually be attributable to reduction of FODMAPs not gluten. NCGS may be a subset of IBS; it is worthwhile considering a low FODMAP diet in those who report symptom induction after consumption of glutencontaining grains, in which celiac disease has been appropriately excluded. A newly developed patient management flow chart supports this approach [22]. Investigations of biomarkers of colonic health in irritable bowel syndrome patients following a low fermentable oligo, di, monosaccharides and polyol diet FODMAPs (particularly oligosaccharides) are prebiotic when supplemented into a diet, that is, they specifically increase growth of bacteria with reputed health benefits [23 ]. FODMAPs are also precursors for short-chain fatty acid (SCFA) production in the colon, known to be important for colonic health [23 ]. Given the known benefits of FODMAP supplementation, it is reasonable to hypothesize that a low FODMAP diet would counteract the prebiotic actions of FODMAPs and reduce SCFA production. This hypothesis was investigated by Halmos et al. [23 ] in which 27 IBS and six healthy subjects collected a 5-day faecal sample during their habitual diet and after 17 days of a provided low FODMAP diet and a typical Australian diet which was carefully matched in all nutrients, except for FODMAPs in a single-blinded, cross-over study. Faecal samples were analyzed for SCFA concentration and abundance of bacteria thought to be biomarkers of colonic health. Compared with both the typical Australian and habitual diets, the low FODMAP diet did not specifically reduce abundance of any measured bacteria [23 ]. This finding contradicted previous indications that a dietician-taught low FODMAP diet reduced proportion of faecal bifidobacteria (traditionally a marker of prebiotic effect), compared with a parallel group of IBS subjects on their habitual diet [24]. Interestingly, the slightly higher FODMAP intake of the provided typical Australian diet was associated with an increased prebiotic effect. This study indicates that despite a prebiotic effect from FODMAP supplementation, FODMAP reduction is not antiprebiotic. It is important to note, however, that although there was no reduced prebiotic effect by FODMAPs, there was a reduction in total bacterial abundance by an average of 47%. The significance of this finding on colonic health is not known. No alterations in faecal SCFA were seen, which is consistent with previous investigations [23,24]. IMPLICATIONS OF CURRENT RESEARCH The trials published in the period 2013 to 2014 have strengthened the efficacy for the low FODMAP diet and review papers have promoted its use as a firstline dietary approach to manage functional symptoms seen in IBS. The clinical benefit may be superior to that of SSRIs and TCAs, which do not provide such broad symptom relief [2] and is also shown to be better than a gluten-free diet in people with self-reported NCGS [21 ]. The recent randomized controlled trial demonstrated that the benefit in therapy was due to the reduction in FODMAPs rather than confounding factors [16 ], and the observational trial highlights the clinical significance of implementing the low FODMAP diet in a real-life setting [1]. As with any therapy, potential negative consequences must be considered and examined. Indeed, the low FODMAP diet has been shown to change the microbiome [23 ]; however, implications of such changes are still not clearly understood. Another potential consequence is the nutritional implications of a restrictive diet. It is expected that as no food groups are avoided on the low FODMAP diet, that nutritional adequacy may be achieved with specialist guidance [4 & ]. Staudacher et al. [24] reported that the initial strict low FODMAP diet phase had a reduced intake of total carbohydrate, including starch and total sugars; however, total energy, protein, fat and nonstarch polysaccharide levels did not change compared with their habitual diet. Additionally calcium intake was reduced in those following a low FODMAP diet for 4 weeks [24]. To make certain of nutritional adequacy, any person following a low FODMAP diet Volume 17 Number 6 November 2014

5 Role of FODMAPs in IBS Shepherd et al. should consult with a specialist dietician to discuss their dietary needs [1,4 & ]. This will ensure patients find the minimal level of FODMAP restriction required for symptom control to achieve the greatest food variety and FODMAPs in the diet, as tolerated [4 &,9]. CONCLUSION The low FODMAP diet has been concluded in many reviews to be an efficacious therapy for the broad spectrum of symptoms associated with irritable bowel syndrome; indeed, recently published research studies add further evidence supporting this notion. The low FODMAP diet appears to be superior to a gluten-free diet in people with selfreported NCGS. Despite obvious efficacy in symptom benefit, further research is required regarding health implications of the liberalized phase of the low FODMAP diet, given the reduced total bacterial load that was observed during the strict elimination phase of the diet. Additionally, research regarding nutritional adequacy of the liberalized low FODMAP diet is also required. Acknowledgements None. Conflicts of interest S.J.S. has coauthored a book on the management of food intolerance and authored several cookbooks for food intolerances; codirector and shareholder of FODMAP P/L, which has the trademark, FODMAP FRIENDLY, and codirector and shareholder of the Low FODMAP Food Company P/L; dietetic private practice specializing in FGID. REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest of outstanding interest 1. de Roest RH, Dobbs BR, Chapman BA, et al. The low FODMAP diet improves gastrointestinal symptoms in patients with irritable bowel syndrome: a prospective study. Int J Clin Pract 2013; 67: Brandt LJ, Chey WD, Foxx-Orenstein AE, et al., American College of Gastroenterology Task Force on Irritable Bowel Syndrome. An evidence-based position statement on the management of irritable bowel syndrome. Am J Gastroenterol 2009; 104 (Suppl 1):S1 S Eswaran S, Muir J, Chey WD. Fiber and functional gastrointestinal disorders. Am J Gastroenterol 2013; 108: Shepherd SJ, Lomer MCE, Gibson PR. Short-chain carbohydrates and & functional gastrointestinal disorders. Am J Gastroenterol 2013; 108: Comprehensive review of the role of short chain carbohydrates as functional gut symptom triggers. 5. Food Navigator Asia. cian-claims-world-first-with-fodmap-range-for-ibs-sufferers. [Accessed 20 June 2014] 6. Hunt R, Quigley E, Abbas Z, et al. Coping with common gastrointestinal symptoms in the community: a global perspective on heartburn, constipation, bloating, and abdominal pain/discomfort. J Clin Gastroenterol 2014; 48: Vanuytsel T, Tack JF, Boeckxstaens GE. Treatment of abdominal pain in irritable bowel syndrome. J Gastroenterol 2014; 49: Tuck CJ, Muir JG, Barrett JS, Gibson PR. Fermentable oligosaccharides, disaccharides, monosaccharides and polyols: role in irritable bowel syndrome. Expert Rev Gastroenterol Hepatol 2014; 8: Staudacher HM, Irving PM, Lomer MC, Whelan K. Mechanisms and efficacy of dietary FODMAP restriction in IBS. Gastroenterol Hepatol 2014; 11: Hayes PA, Fraher MH, Quigley EM. Irritable bowel syndrome: the role of food in pathogenesis and management. Gastroenterol Hepatol 2014; 10: Randall CW, Saurez AV, Zaga-Galante J. Current strategies in the management of irritable bowel syndrome. Intern Med 2014; S1: / ; S Fedewa A, Rao SS. Dietary fructose intolerance, fructan intolerance and FODMAPs. Curr Gastroenterol Rep 2014; 16: Sharma A, Ghoshal UC. Low FODMAP diet in the treatment of irritable bowel syndrome: is it the end of the road or the beginning of the journey? Gastroenterol 2014; 146: Lowe AW, Moseley RH. Role of dietary FODMAPs in IBS-related symptoms. Gastroenterol 2014; 146: Joyce T, Staudacher HM, Whelan K, Irving PM. Group education is as effective as one-to-one sessions when administering the low FODMAP diet in functional bowel disorders. Gut 2013; 62:A Halmos EP, Power VA, Shepherd SJ, et al. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterol 2014; 146: State-of-the-art original research article confirming the effects of FODMAP restriction in IBS patients. 17. Staudacher HM, Whelan K, Irving PM, et al. Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) verses standard dietary advice in patients with irritable bowel syndrome. J Human Nutr Diet 2011; 24: Shepherd SJ, Gibson PR. Fructose malabsorption and symptoms of irritable bowel syndrome: guidelines for effective dietary management. J Am Diet Assoc 2006; 106: Murray K, Wilkinson-Smith V, Hoad C, et al. Differential effects of FODMAPs (fermentable oligo, di-, mono-saccharides and polyols) on small and large intestinal contents in healthy subjects shown by MRI. Am J Gastroenterol 2014; 109: State-of-the-art original research article confirming the effects of FODMAP restriction in IBS patients. 20. Nelis GF, Vermeeren MA, Jansen W. Role of fructose-sorbitol malabsorption in the irritable bowel syndrome. Gastroenterol 1990; 99: Biesiekierski JR, Peters SL, Newnham ED, et al. No effects of gluten in patients with self-reported nonceliac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterol 2013; 145: Hiqh-quality original research article implicating role of FODMAPs in functional gastrointestinal symptoms in people with nonceliac gluten intolerance. 22. Biesiekierski JR, Newnham E, Shepherd SJ, et al. Characterization of adults with a self-diagnosis of nonceliac gluten sensitivity. Nutr Clin Pract 2014; 29: Halmos EP, Christopherson CT, Bird AR, et al. Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut [Epub ahead of print]. doi: /gutjnl Excellent original research paper with comprehensive comparison of dietary changes on gut microbiota. 24. Staudacher HM, Lomer MCE, Anderson JL, et al. Fermentable carbohydrate restriction impacts on luminal bifidobacteria and gastrointestinal symptoms in a randomized controlled trial of patients with irritable bowel syndrome. J Nutr 2012; 142: ß 2014 Wolters Kluwer Health Lippincott Williams & Wilkins 609