Caroline J Tuck

Fermentable oligosaccharides, disaccharides, monosaccharides and polyols: role in irritable bowel syndrome

Irritable bowel syndrome (IBS) was previously left poorly treated despite its high prevalence and cost. Over the past decade, significant research has been conducted providing new dietary strategies for IBS management. The ‘low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet’ has shown symptom improvement in 68–76% of patients. Randomized, controlled trials have now proven its efficacy. The diet, low in poorly absorbed and fermentable carbohydrates, uses dietary restriction and re-challenge to determine individual tolerance to various short-chain carbohydrates. However there may be potential detrimental effects of the diet in the long term, due to potential changes to the gastrointestinal microbiota. Appropriate dietary education and management of the diet is imperative. Future research should focus on the relevance of changes to the microbiota and ways to liberalize the dietary restrictions.

Poor reproducibility of breath hydrogen testing: Implications for its application in functional bowel disorders

Background Limited data are available regarding the reproducibility of lactulose and fructose breath testing for clinical application in functional bowel disorders. Objectives The purpose of this study was to investigate the reproducibility of lactulose and fructose breath hydrogen testing and assess symptom response to fructose testing. Methods Results were analysed from 21 patients with functional bowel disorder with lactulose breath tests and 30 with fructose breath tests who completed another test >2 weeks later. Oro-caecal transit time, hydrogen responses, both qualitatively (positive/negative) and quantitatively (area under the curve (AUC) for hydrogen), were compared between tests. In another 36 patients, data scores for overall abdominal symptoms, abdominal pain, bloating, wind, nausea and fatigue were collected during the fructose test and compared to hydrogen responses. Results No correlations were found for lactulose AUC (linear regression, p = 0.58) or transit time (Spearmans p = 0.54) between tests. A significant proportion (30%) lost the presence of fructose malabsorption (p < 0.01). Hydrogen AUC for fructose did not correlate between tests, (r = 0.28, p = 0.17) independent of time between testing (p = 0.82). Whilst patients with fructose malabsorption were more likely to report symptoms than those without (56% vs 17%; p = 0.04), changes in symptom severity were not different (p > 0.05). Conclusions Routine use of lactulose and fructose breath tests in functional bowel disorder patients is not supported due to its poor reproducibility and low predictive value for symptom responses.

Re-challenging FODMAPs: the low FODMAP diet phase two

The low fermentable, oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet has good evidence for use in the treatment of patients with irritable bowel syndrome. Importantly, patients are encouraged not to remain on a strict low FODMAP diet long‐term, and many patients maintain symptom improvement with a relaxed, moderate FODMAP restriction. The re‐challenge phase is crucial to assist patients in identifying specific dietary triggers, reduce the level of dietary restriction required, and increase prebiotic intake. Limited evidence is available to guide best practice, but, in practice, beneficial outcomes can be seen through strategic food reintroductions. Here, we set out some practical recommendations based on clinical experience. Dietitians should tailor the challenge process to the individual patient and their needs. Food challenges should aim to improve dietary variety and nutritional adequacy while considering specific food preferences and usual dietary habits. Identifying FODMAP subgroups that are well tolerated is helpful, allowing the reintroduction of some moderate to high FODMAP foods back into the diet without symptom induction. FODMAP subtypes that are less well tolerated may also be reintroduced, but dosage and frequency of consumption need to be individualized.

Adding glucose to food and solutions to enhance fructose absorption is not effective in preventing fructose-induced functional gastrointestinal symptoms: randomised controlled trials in patients with fructose malabsorption

BACKGROUND In healthy individuals, the absorption of fructose in excess of glucose in solution is enhanced by the addition of glucose. The present study aimed to assess the effects of glucose addition to fructose or fructans on absorption patterns and genesis of gastrointestinal symptoms in patients with functional bowel disorders. METHODS Randomised, blinded, cross-over studies were performed in healthy subjects and functional bowel disorder patients with fructose malabsorption. The area-under-the-curve (AUC) was determined for breath hydrogen and symptom responses to: (i) six sugar solutions (fructose in solution) (glucose; sucrose; fructose; fructose + glucose; fructan; fructan + glucose) and (ii) whole foods (fructose in foods) containing fructose in excess of glucose given with and without additional glucose. Intake of fermentable short chain carbohydrates (FODMAPs; fermentable, oligo-, di-, monosaccharides and polyols) was controlled. RESULTS For the fructose in solution study, in 26 patients with functional bowel disorders, breath hydrogen was reduced after glucose was added to fructose compared to fructose alone [mean (SD) AUC 92 (107) versus 859 (980) ppm 4 h-1 , respectively; P = 0.034). Glucose had no effect on breath hydrogen response to fructans (P = 1.000). The six healthy controls showed breath hydrogen patterns similar to those with functional bowel disorders. No differences in symptoms were experienced with the addition of glucose, except more nausea when glucose was added to fructose (P = 0.049). In the fructose in foods study, glucose addition to whole foods containing fructose in excess of glucose in nine patients with functional bowel disorders and nine healthy controls had no significant effect on breath hydrogen production or symptom response. CONCLUSIONS The absence of a favourable response on symptoms does not support the concomitant intake of glucose with foods high in either fructose or fructans in patients with functional bowel disorders.

Increasing Symptoms in Irritable Bowel Symptoms With Ingestion of Galacto-Oligosaccharides Are Mitigated by α-Galactosidase Treatment

Objectives:Galacto-oligosaccharides (GOS) are dietary FODMAPs (fermentable carbohydrates) associated with triggering gastrointestinal symptoms in patients with irritable bowel syndrome (IBS). This randomized, double-blind, placebo-controlled, cross-over trial aimed to assess whether oral α-galactosidase co-ingestion with foods high in GOS and low in other FODMAPs would reduce symptoms.Methods:Patients meeting the Rome III criteria for IBS who were hydrogen-producers on breath testing were recruited. Participants were treated with full-dose (300 GALU (galactosidic units) α-galactosidase) and half-dose enzyme (150 GALU α-galactosidase), and placebo (glucose) in a random order with ≤14 days washout between arms. Following a 3-day low FODMAP run-in period, participants consumed provided diets high in GOS for a further 3-days. Gastrointestinal symptoms were measured daily using a 100 mm visual-analogue-scale, and breath samples taken hourly on the second last day with hydrogen content analysed as area-under-the-curve.Results:Thirty-one patients with IBS (20 IBS-D, 4 IBS-C, 7 IBS-M) completed the study. The addition of high GOS foods resulted in a significant increase in overall symptoms with 21 patients exhibiting GOS-sensitivity (>10 mm increase for overall symptoms). Of those, full-dose enzyme reduced overall symptoms (median 24. 5(IQR 17.5–35.8) vs. 5.5(1.5–15.0) mm; P=0.006) and bloating (20.5(9.5–42.0) vs. 6.5(2.0–15.8); P=0.017). Breath hydrogen production was minimal with no differences seen between placebo and full-dose (P=0.597).Conclusions:Oral α-galactosidase taken with high GOS foods provides a clinically significant reduction in symptoms in GOS-sensitive individuals with IBS. This strategy can be translated into practice to improve tolerance to high GOS foods as an adjunct therapy to the low FODMAP diet.

The clinical value of breath hydrogen testing

Breath hydrogen testing for assessing the presence of carbohydrate malabsorption is frequently applied to refine dietary restrictions on a low fermentable carbohydrate (FODMAP) diet. Its application has also been extended for the detection of small intestinal bacterial overgrowth. Recently, several caveats of its methodology and interpretation have emerged. A review of the evidence surrounding its application in the management of patients with a functional bowel disorder was performed. Studies were examined to assess limitations of testing methodology, interpretation of results, reproducibility, and how this relates to clinical symptoms. A wide heterogeneity in testing parameters, definition of positive/negative response, and the use of clinically irrelevant doses of test carbohydrate were common methodological limitations. These factors can subsequently impact the sensitivity, specificity, and false positive or negative detection rates. Evidence is also increasing on the poor intra‐individual reproducibility in breath responses with repeated testing for fructose and lactulose. On the basis of these limitations, it is not surprising that the diagnosis of small intestinal bacterial overgrowth based on a lactulose breath test yields a wide prevalence rate and is unreliable. Finally, symptom induction during a breath test has been found to correlate poorly with the presence of carbohydrate malabsorption. The evidence suggests that breath hydrogen tests have limited clinical value in guiding clinical decision for the patient with a functional bowel disorder.

Editorial: rethinking predictors of response to the low FODMAP diet – should we retire fructose and lactose breath-hydrogen testing and concentrate on visceral hypersensitivity?

Identification of predictors of response to the low FODMAP diet has been limited. The report from WilderSmith et al. provides welcome insight. In a longitudinal observational study in a cohort of patients with functional gastrointestinal disorders (FGID) and fructose and/or lactose intolerance (defined as malabsorption on breath hydrogen/methane testing plus symptoms on breath testing), global adequate symptom relief after 6–8 weeks on the diet was 81%. The only independent predictors of response were in the fructose intolerant: chronic diarrhoea and elevated methane during breath testing were positiveand chronic nausea negative-predictors. Two important clinical questions arise. First, what is the role of breath hydrogen testing in patients with FGID? The reported dietary efficacy was impressive and the highest success rate so far published, but was that due to the selection of patients using a breath test? The authors have previously reported that response to the diet does not correlate with the presence of malabsorption itself, but rather is associated with the induction of symptoms in those with malabsorption. This is in line with our reported lack of association of the induction of symptoms with the presence of malabsorption of fructose, sorbitol or mannitol. What is missing is specific study of the dietary response of patients without malabsorption, with or without symptom induction. The poor reproducibility of demonstrating fructose malabsorption by breath testing and the lack of correlation of malabsorption with symptom induction has led our group to recommend cessation of breath testing in clinical practice. We contend that it can only be misleading in providing a false diagnosis and inappropriately steering therapy away from diet. It may be that the key information from a breath test is the symptom induction as contended by Wilder-Smith et al. 2 It is visceral hypersensitivity that defines symptoms induced by FODMAPs. 7 Perhaps, we should abandon breath tests, but just use much simpler symptom-provocation tests to predict response to a low FODMAP diet? However, fructose and lactose are both flawed for this purpose – in many, they are rapidly digested/absorbed. The indigestible disaccharide, lactulose, has the problem of inducing diarrhoea in provocation doses due to its strong osmotic effects. The use of an oligosaccharide (such as fructo-oligosaccharide) would be hypothetically more sensible as it is less osmotic and indigestible in all. This has been used in research studies, 9 but has yet to be extended to clinical practice. Second, how are the predictors of dietary response identified by Wilder-Smith et al. to be utilised in clinical practice? Should the patient without chronic diarrhoea or with a history of nausea, or both, be excluded from the opportunity to try the low FODMAP diet? We suspect not. What the study has done for us, however, is to reinforce the limited value of breath tests for malabsorption itself, but to move the focus from specific sugar malabsorption to simple tests of visceral hypersensitivity. After all, the dietary approach is not directed towards the specific sugar tested, but to restricting all the FODMAP subgroups.

Questioning the Utility of Breath Testing in Clinical Practice

To the Editor: We commend Rezaie et al. ( 1 ) for their important eff orts in standardizing hydrogen breath testing (HBT) practices to optimize clinical management of patients with functional gastrointestinal disorders (FGID). However, in light of accumulating evidence suggesting re-evaluation of HBT indications in clinical practice, we express concerns with the reco mmendations suggested by the consensus report. Specifi cally, evidence for poor test reproducibility, high rates of positive HBT in healthy controls, and the disparity between testing dose and dietary intake all question the clinical utility of HBT ( 2 ). Th e foremost limitation with HBT is its poor reproducibility. Wilder-Smith et al. ( 3 ) found that 81% of patients with fructose or lactose intolerance (defi ned as symptoms on HBT irrespective of hydrogen response on HBT) will respond to a low FODMAP (fermentable carbohydrate) diet ( 3 ). In addition, our group has demonstrated poor reproducibility of lactulose and fructose HBT, with 30% losing positive response to fructose at re-test, regardless of the duration of testing ( 2 ). Furthermore, if clinical response is achievable aft er dietary therapy regardless of HBT results ( 3 ), then the negative predictive value should be a consideration, and the risk of denying eff ective therapy imminent. Th e term “diagnostic test” used by Rezaie et al. ( 1 ) to describe HBT is problematic especially in the case of fructose. Fructose “malabsorption” is a normal phenomenon and only of signifi cance in those with visceral hypersensitivity, as seen in FGID. Th at is, physiological distention Specifi c author contributions : C.J.T., C.K.Y., H.L.P. and J.S.B. wrote the paper. C.J.T. had primary responsibility for the fi nal content. All authors read and approved the fi nal manuscript. Financial support : Th e Department of Gastroenterology fi nancially benefi ts from the sales of a digital application and booklets on the low FODMAP diet. Potential competing interests : None.

Fermentable short chain carbohydrate (FODMAP) content of common plant-based foods and processed foods suitable for vegetarian- and vegan-based eating patterns

BACKGROUND The low FODMAP (fermentable, oligo-, di-, mono-saccharides and polyols) diet is an effective strategy to improve symptoms of irritable bowel syndrome. However, combining the low FODMAP diet with another dietary restriction such as vegetarianism/veganism is challenging. Greater knowledge about the FODMAP composition of plant-based foods and food processing practices common to vegetarian/vegan eating patterns would assist in the implementation of the diet in this patient population. The present study aimed to quantify the FODMAP content of plant-based foods common in vegetarian/vegan diets and to investigate whether food processing can impact FODMAP levels. METHODS Total FODMAP content was quantified in 35 foods, including fructose-in-excess-of-glucose, lactose, sorbitol, mannitol, galacto-oligosaccharide and total fructan, using high-performance-liquid-chromatography and enzymatic assays. The effects of cooking, sprouting, pickling, fermentation, activation and canning on FODMAP content were assessed. The Monash University criteria to classify foods as low FODMAP was used. RESULTS Of the 35 foods, 20 were classified as low FODMAP, including canned coconut milk (0.24 g serve-1 ), dulse (0.02 serve-1 ), nutritional yeast (0.01 serve-1 ), soy cheese (0.03 serve-1 ), tempeh (0.26 serve-1 ), wheat gluten (0.13 serve-1 ) and wheat grass (0.05 serve-1 ). No FODMAPs were detected in agar-agar, egg replacer, vegan egg yolk, kelp noodles and spirulina. Food processing techniques that produced the greatest reduction in FODMAP content included pickling and canning. CONCLUSIONS The present study provides a greater FODMAP composition knowledge of plant-based foods that can now be applied to the dietetic management of vegetarians/vegans requiring a low FODMAP diet. Food processing lowered the FODMAP content of foods, thereby increasing options for patients following a low FODMAP diet.