Naturally-occurring dietary salicylates in the genesis of functional gastrointestinal symptoms in patients with irritable bowel syndrome: Pilot study.

BACKGROUND AND AIM: An elimination-rechallenge dietary approach targeting naturally-occurring bioactive chemicals has been proposed to alleviate functional gastrointestinal symptoms. A major focus of this approach is salicylates. This study aimed to address the potential role of dietary salicylates in the induction of symptoms in patients with irritable bowel syndrome (IBS). METHODS: A pilot, double-blind, randomized, cross-over trial of 2-week low- versus high-salicylate diets (6.6 and 27.9 g/day salicylate, respectively) was undertaken. All foods were provided containing minimal quantities of other potential food triggers. Gastrointestinal and extraintestinal symptoms were measured daily using a 100-mm visual-analogue-scale. RESULTS: Ten participants with IBS completed the study, including one with known aspirin-sensitivity. Overall, no differences in symptoms were observed (P = 0.625; Friedman test). However, clear symptom provocation was seen in the aspirin-sensitive participant, with all abdominal symptoms and tiredness worsening during the high-salicylate diet. A similar trend was seen in another participant, where abdominal symptoms gradually worsened during the high-salicylate diet. CONCLUSIONS: These results provide some evidence that food-related salicylates may influence the genesis of symptoms in a subset of patients with IBS. A larger cohort is needed to determine the incidence of salicylate-sensitivity and further evaluate the diet as a potential therapeutic target.The protocol was registered at www.anzctr.org.au (ACTRN12620001250921).

High Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAP) Consumption Among Endurance Athletes and Relationship to Gastrointestinal Symptoms.

Endurance athletes commonly experience lower gastrointestinal (GI) symptoms similar to those of irritable bowel syndrome (IBS). Previous research on the restriction of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP), a diet-based mitigation strategy initially developed for IBS, has shown promise for application in athlete populations. Athlete's dietary strategies surrounding exercise have not been formally assessed in relation to FODMAP content of foods or sports nutrition products. Additionally, the FODMAP content of athlete's habitual diets has not been examined in larger sample sizes. This research aims to investigate the FODMAP content of endurance athlete diets by examining these three areas, in conjunction with GI symptoms. Dietary habits surrounding exercise and GI symptoms were examined in 430 endurance athletes using a previously validated Endurance Athlete Questionnaire. A subset of athletes (n = 73) completed a FODMAP-specific food frequency questionnaire for habitual intake. The most commonly reported sports nutrition products were analyzed for FODMAP content using standardized analytical methods. Mean habitual intakes were compared to previous FODMAP studies and medians were compared between those with and without lower GI symptoms. Athletes commonly consumed high FODMAP foods during pre-race dinners and breakfasts, with over 60% reporting specific high FODMAP foods. More frequent nutrition product use, particularly solid, gel/gummy, and homemade products, was often related to increased frequency of GI symptoms. Of the sixteen commonly used sports nutrition products tested, seven were high FODMAP in one serving. All but one of the remaining products became high FODMAP when consumed in multiple servings, as is likely the case during endurance exercise. Average habitual FODMAP intake was 26.1 g (±15.9 g), similar to intakes classified as high FODMAP in previous research on FODMAPs and IBS or GI symptoms. Only 15.1% of athletes consumed a diet that would be considered low in FODMAP. Exploratory analyses showed higher intake of some FODMAP types among athletes exhibiting various lower GI symptoms. Overall, this study demonstrated that FODMAP intake by endurance athletes is high both surrounding exercise and habitually, and may be contributing to GI symptoms experienced during exercise. This information can be utilized when analyzing athlete diets and selecting foods to decrease GI symptoms.

FODMAP project: Development, validation and reproducibility of a short food frequency questionnaire to estimate consumption of fermentable carbohydrates.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a functional disorder that is characterized by gastrointestinal symptoms and that has a major impact on quality of life, resulting in direct and indirect health care costs. The majority of patients with IBS suffer from food intolerances, most commonly related to the consumption of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs). This study aimed to develop and verify the validity and reproducibility of a short food frequency questionnaire (FFQ) to assess typical FODMAP consumption in adults with IBS. METHODS: The primary FFQ list consisted of source foods of FODMAPs that contributed at least 10% to the frequency of consumption among 855 adults from a population-based study in the municipality of Campinas in 2014/2015. In addition, source foods of FODMAPs (according to the Monash University Low FODMAP Diet application) and foods commonly consumed by the Brazilian population (according to the FFQ for adults validated in the city of São Paulo) were included. One hundred and five (n = 105) healthy subjects were recruited to respond to the FFQ twice and to respond the 24-h dietary recall (24HR) three times during a 3-month period. The relative validity of the proposed instrument was compared with the average of the three 24HRs, and the reproducibility of the instrument was assessed by comparing both FFQ applications. The following statistical analyses were used for validation and reproducibility: Wilcoxon's test, Spearman's correlation analysis, weighted kappa, Bland Altman's plot and index, and interclass correlation coefficient. RESULTS: The final list of items for the short FFQ included 54 different foods. The foods were organized by FODMAP groups: free fructose, lactose, total oligosaccharides and total polyols, with variations of categories of responses for consumption frequency between 0 and 10 times and the unit of time in days, weeks or months. In the validity analyses, the correlation coefficients ranged from 0.209 (polyols) to 0.652 (lactose) (p < 0.05). There was no correlation between the methods in the fructose and oligosaccharide groups. The lactose group presented good agreement, and the remaining groups had a lack of agreement, with a mean of 15.7%. The Bland-Altman index values were 4.7% (fructose), 3.8% (lactose), 5.7% (oligosaccharides) and 6.6% (polyols). Regarding reproducibility, the interclass and Spearman's correlation coefficients varied from ICC = 0.781 and r = 0.725 (oligosaccharides) to ICC = 0.913 and r = 0.807 (lactose) (p < 0.05), showing strongly reproducible results for lactose and polyols and good results for fructose and oligosaccharides. Accurate agreement between FFQ applications had a mean of 67.3%, and 3.0% showed disagreement between FFQ1 and FFQ2. The weighted kappa coefficient ranged from 0.576 (polyols) to 0.645 (lactose). CONCLUSION: The semi-quantitative short FFQ was developed to evaluate the consumption of FODMAPs in adults in São Paulo. The instrument presents good reproducibility for all groups of FODMAPs, good validity for lactose and weaker validity for fructose, polyols and oligosaccharides. As the short FFQ was carefully designed for the study population, its estimates are relatively reliable at the population group level. A future reanalysis of this questionnaire would be useful when the chemical composition data of FODMAPs are available.

Effects of fiber intake on intestinal pH, transit, and predicted oral mesalamine delivery in patients with ulcerative colitis.

BACKGROUND AND AIM: Limited data are available on the effects of fermentable fiber in altering intestinal pH and transit to predict efficacy-based delivery profiles of pH-dependent mesalamine coatings in ulcerative colitis (UC). This study aimed to examine regional pH and transit after acute changes in fermentable fiber intake in quiescent UC patients and their effects on drug release systems. METHODS: In a randomized, double-blind study, 18 patients with quiescent UC and 10 healthy controls were supplied meals high (13 g) or low (≤ 2 g) in fermentable fiber and subsequently ingested a wireless pH-motility capsule. After a ≥ 3-day washout, they crossed over to the other diet. Measurements of intestinal pH and transit were used to predict drug release for the various pH-dependent coatings. RESULTS: Increasing fermentable fiber intake lowered overall (median 6.2 [6.1-6.7] vs low: 6.9 [range or interquartile range: 6.4-7.4]; P = 0.01) and distal pH (7.8 [7.3-8.1] vs 8.2 [8.0-8.5]; P = 0.04) in controls. In UC patients, only cecal pH was decreased (high: 5.1 [4.8-5.5] vs low: 5.5 [5.3-5.7]; P < 0.01). Colonic transit in the UC cohort varied widely after a low-fiber intake but tended to normalize after the high fermentable fiber intake. Hypothetical coating dissolution profiles were heterogeneous in UC patients, with a multi-matrix delayed release system having the highest likelihood of patients (20-40%) with incomplete dissolution, and predominant small intestinal dissolution predicted for Eudragit L (94% patients) and S (44-69%). CONCLUSIONS: Patients with quiescent UC have abnormalities in intestinal pH and transit in response to acute changes in fermentable fiber intake. These have potentially detrimental effects on predicted luminal release patterns of pH-dependent 5-aminosalicylic acid release systems.

Low-FODMAP Diet Is Associated With Improved Quality of Life in IBS Patients-A Prospective Observational Study.

BACKGROUND: The low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet is effectively manages irritable bowel syndrome (IBS) symptoms. Long-term low-FODMAP studies rarely report quality of life (QoL). We aimed to determine the effect of low-FODMAP diet on long-term QoL, gastrointestinal (GI) and non-GI symptoms in IBS patients. METHODS: A prospective observational study of IBS patients referred for low-FODMAP dietary advice was performed. The primary outcome of QoL and secondary outcomes of GI symptoms, anxiety/depression, fatigue, sleep quality, and happiness were obtained at baseline, 6 weeks (T6), and 6 months (T26). RESULTS: 111 patients were recruited. 91.0%, 71.6%, and 50.5% of participants completed baseline, T6, and T26 assessments, respectively. There were significant improvements in QoL from baseline at T6 and T26 (both P < 0.001). Significant reductions were seen in GI symptoms at T6 and T26 (both P < 0.001), fatigue at T6 and T26 (both P < 0.003), and anxiety at T6 and T26 (both P < 0.007), compared with baseline. A significant reduction was seen for depression (P < 0.010) from baseline at T26, and a significant increase was seen for both happiness and vitality (both P < 0.04) from baseline at T26. There was a significant correlation between GI symptom response and change in QoL, anxiety, depression, and fatigue (all P < 0.034). CONCLUSION: Low-FODMAP diet was associated with improved long-term QoL and GI symptoms, reduced fatigue and anxiety/depression, and increased happiness and vitality. These data support a wider range of benefits for IBS patients consuming a low-FODMAP diet.

Randomised clinical trial: reducing the intake of dietary FODMAPs of breastfeeding mothers is associated with a greater improvement of the symptoms of infantile colic than for a typical diet.

BACKGROUND: Therapeutic diets for infantile colic lack evidence. In breastfed infants, avoiding "windy" foods by the breastfeeding mother is common. AIM: To examine the effects of a maternal low-FODMAP (Fermentable, Oligosaccharides, Disaccharides, Monosaccharides, And Polyols) diet compared to a typical-Australian diet on infant crying-fussing durations of infants with colic in a randomised, double-blind, crossover feeding study. METHODS: Between 2014 and 2016 exclusively breastfed infants aged ≤9 weeks meeting Wessel criteria for colic were recruited. Mothers were provided a 10-day low-FODMAP or typical-Australian diet, then alternated without washout. Infants without colic (controls) were observed prospectively and mothers remained on habitual diet. Infant crying-fussing durations were captured using a Barr Diary. Measures of maternal psychological status and samples of breast milk and infant faeces were collected. RESULTS: Mean crying-fussing durations were 91 min/d in seven controls compared with 269 min/d in 13 colicky infants (P < 0.0001), which fell by median 32% during the low-FODMAP diet compared with 20% during the typical-Australian diet (P = 0.03), confirmed by a two-way mixed-model analyses-of-variance (ƞp 2  = 0.719; P = 0.049) with no order effect. In breast milk, lactose concentrations remained stable and other known dietary FODMAPs were not detected. Changes in infant faecal calprotectin were similar between diets and groups, and faecal pH did not change. Median maternal anxiety and stress fell with the typical-Australian diet (P < 0.01), but remained stable on the low-FODMAP diet. CONCLUSIONS: Maternal low-FODMAP diet was associated with enhanced reduction in crying-fussing durations of infants with colic. This was not related to changes in maternal psychological status, gross changes in breast milk or infant faeces. Mechanisms require elucidation. Trial Registration Australian New Zealand Clinical Trials Registry (ANZCTR): 12616000512426 - anzctr.org.au.

How to institute the low-FODMAP diet.

A diet low in poorly absorbed, fermentable, short chain carbohydrates (FODMAPs) is an effective strategy to manage symptoms of irritable bowel syndrome (IBS). The diet has gained traction since its original description in Australia 10 years ago and is now an internationally accepted dietary management strategy for IBS. Randomized controlled trials have raised the profile of the low-FODMAP diet to become a viable first-line therapy for IBS, when implemented under a dietitian's guidance. Importantly, the diagnosis of IBS should be confirmed before commencement of the dietary approach. The skill set of the dietitian is then paramount to the success of the diet. Experience in gastrointestinal disorder management, consideration of symptom types, severity, baseline FODMAP intake, and overall nutritional content and meal pattern are vital in the assessment of the patient. If a strict low-FODMAP diet is deemed necessary, it should only be for an initial period of 4 to 6 weeks. Research suggests that a strict long-term, low-FODMAP diet may negatively impact intestinal microbiome. After the initial strict period, follow up with the dietitian should be conducted to achieve the overall goal-a relaxed FODMAP restriction that enables inclusion of prebiotic FODMAPs while still maintaining symptom relief. The diet will be effective in the vast majority of patients. For those in which it fails, FODMAPs should be reintroduced to the diet, and other dietary (or non-dietary) approaches should be considered.

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 (Spearman's 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.

Poor predictive value of breath hydrogen response for probiotic effects in IBS.

BACKGROUND AND AIMS: Previous observations suggested that an early rise in breath hydrogen after lactulose (ERBHAL) may identify patients with irritable bowel syndrome (IBS) likely to respond to probiotics. Therefore, we aimed to (i) investigate whether treatment with a probiotic changes breath hydrogen response in patients with ERBHAL and (ii) whether these changes identify patients who may benefit symptomatically from probiotics. METHODS: In a randomized, double-blind, placebo-controlled trial, patients with IBS (Rome III) were randomized to either 65 mL/day fermented milk product containing probiotic (FMPP) or placebo for 6 weeks, followed by 6 weeks' open-label treatment and 6 weeks' withdrawal. Breath hydrogen responses to lactulose (15 g) and liquid-gastric emptying time were evaluated before and at the end of each treatment period. Symptoms were measured using a 100-mm visual analog scale. RESULTS: Loss of ERBHAL occurred in 36% of 23 patients receiving FMPP and 41% of 22 receiving placebo (P = 1.00). Amongst 40 patients who completed open-label FMPP treatment, ERBHAL was lost in a further 38%, continued in 25%, and regained in 10%. Similar variability occurred in the withdrawal phase. Variability was unrelated to changes in gastric emptying. No differences in symptom response were seen between treatment groups nor in relation to the loss or retention of ERBHAL. CONCLUSIONS: Breath hydrogen patterns after lactulose are poorly reproducible. No FMPP-specific effects on fermentation patterns or symptoms were observed. The presence of ERBHAL is not useful to predict symptomatic response to probiotic therapy in patients with IBS.

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.

Management Strategies for Abdominal Bloating and Distension.

Bloating and distension are among the most common gastrointestinal complaints reported by patients with functional gut disorders and by the general population. These 2 complaints are also among the most prevalent of the severe symptoms reported by patients with irritable bowel syndrome. Nonetheless, only a limited number of published studies have specifically addressed bloating; it is infrequently studied as a primary endpoint, and what little systematic information exists has often been garnered from the assessment of secondary endpoints or the dissection of composite endpoints. This lack of data, and our consequent limited understanding of the pathophysiology of bloating, had hampered the quest for effective and targeted therapies until recently. Advances in the knowledge of underlying mechanisms, particularly with regard to the roles of diet, poorly absorbed fermentable carbohydrates, dysbiosis of the gut bacteria, alterations in visceral hypersensitivity, and abnormal viscerosomatic reflexes, have enabled the development of improved treatment options. The most significant recent advance has been a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, which significantly reduces patients' symptoms and improves quality of life. Given the prevalence of bloating and its perceived severity, it is clear that further studies regarding the pathogenesis and treatment of this problem are needed.

Extending our knowledge of fermentable, short-chain carbohydrates for managing gastrointestinal symptoms.

The Monash University low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet is now accepted as an effective strategy for managing symptoms of irritable bowel syndrome (IBS) in Australia, with interest expanding across the world. These poorly absorbed, short-chain carbohydrates have been shown to induce IBS symptoms of diarrhea, bloating, abdominal pain, and flatus due to their poor absorption, osmotic activity, and rapid fermentation. Four clinical trials have been published to date, all with significant symptomatic response to the low FODMAP diet. Up to 86% of patients with IBS have achieved relief of overall gastrointestinal symptoms and, more specifically, bloating, flatus, abdominal pain, and altered bowel habit from the approach. This review provides an overview of the low FODMAP diet and summarizes the research to date, emerging concepts, and limitations. FODMAPs are known to be beneficial to bowel health; the importance of this and how this should be considered in the clinical management of IBS is also discussed. A clinical management flowchart is provided to assist nutrition professionals in the use of this approach.

Semiquantitative assessment of breath hydrogen testing.

BACKGROUND AND AIM: A major use of breath hydrogen testing is to assess absorptive capacity for sugars to assist dietary design for management of gut symptoms. Qualitative reporting takes no account of the vigor of hydrogen response and provides little insight into degrees of malabsorption. This study aimed to describe a semiquantitative reporting method and to compare results with those reported qualitatively. METHODS: In consecutive Caucasian patients with Crohn's disease (n = 87), ulcerative colitis (59), functional gastrointestinal disorders (FGID) (162), and healthy controls (76), area under the curve was calculated for lactulose (15 g). This was compared with that for lactose (50 g) and fructose (35 g). Degree of malabsorption was categorized into arbitrary groups. RESULTS: Semiquantitative results for ≥ 30% (designated "convincing") malabsorption was most similar to those using a qualitative cutoff value of 20 ppm, but in 38% and 21% of patients, the classification of malabsorption (nil or clinically significant) changed for fructose and lactose, respectively. Using a cutoff of 10 ppm, 49% and 5% were classified differently. Crohn's disease had a higher prevalence (42%) of convincing fructose malabsorption than controls (24%) or patients with FGID (33%) (P < 0.02). Highest prevalence of convincing lactose malabsorption (38%) was in ulcerative colitis, greater than controls (18%) and FGID (18%) (P < 0.02). CONCLUSIONS: Semiquantitative assessment provides different results with different clinical implications in more than one third of patients, but disease-related alterations in prevalence are similar to those defined qualitatively. This method may be preferable because it lessens the confounding influence of the vigor of the hydrogen response.

Fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and nonallergic food intolerance: FODMAPs or food chemicals?

Food intolerance in irritable bowel syndrome (IBS) is increasingly being recognized, with patients convinced that diet plays a role in symptom induction. Evidence is building to implicate fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) in the onset of abdominal pain, bloating, wind and altered bowel habit through their fermentation and osmotic effects. Hypersensitivity to normal levels of luminal distension is known to occur in patients with IBS, with consideration of food chemical intolerance likely to answer many questions about this physiological process. This paper summarizes the evidence and application of the most common approaches to managing food intolerance in IBS: the low-FODMAP diet, the elimination diet for food chemical sensitivity and others including possible noncoeliac gluten intolerance.

Fermentable carbohydrate restriction reduces luminal bifidobacteria and gastrointestinal symptoms in patients with irritable bowel syndrome.

Preliminary studies indicate that dietary restriction of fermentable short-chain carbohydrates improves symptoms in irritable bowel syndrome (IBS). Prebiotic fructo-oligosaccharides and galacto-oligosaccharides stimulate colonic bifidobacteria. However, the effect of restricting fermentable short-chain carbohydrates on the gastrointestinal (GI) microbiota has never been examined. This randomized controlled trial aimed to investigate the effects of fermentable carbohydrate restriction on luminal microbiota, SCFA, and GI symptoms in patients with IBS. Patients with IBS were randomized to the intervention diet or habitual diet for 4 wk. The incidence and severity of symptoms and stool output were recorded for 7 d at baseline and follow-up. A stool sample was collected and analyzed for bacterial groups using fluorescent in situ hybridization. Of 41 patients randomized, 6 were withdrawn. At follow-up, there was lower intake of total short-chain fermentable carbohydrates in the intervention group compared with controls (P = 0.001). The total luminal bacteria at follow-up did not differ between groups; however, there were lower concentrations (P < 0.001) and proportions (P < 0.001) of bifidobacteria in the intervention group compared with controls when adjusted for baseline. In the intention-to-treat analysis, more patients in the intervention group reported adequate control of symptoms (13/19, 68%) compared with controls (5/22, 23%; P = 0.005). This randomized controlled trial demonstrated a reduction in concentration and proportion of luminal bifidobacteria after 4 wk of fermentable carbohydrate restriction. Although the intervention was effective in managing IBS symptoms, the implications of its effect on the GI microbiota are still to be determined.

Fructose and lactose testing.

This article forms part of our 'Tests and results' series for 2012, which aims to provide information about common tests that general practitioners order regularly. It considers areas such as indications, what to tell the patient, what the test can and cannot tell you, and interpretation of results. Functional gut symptoms are a common problem in the community and many patients present to their general practitioner for assessment and guidance.While part of the GP's role is excluding other pathology, helping patients to manage their symptoms is also important.

Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial.

OBJECTIVES: Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism. METHODS: A double-blind, randomized, placebo-controlled rechallenge trial was undertaken in patients with irritable bowel syndrome in whom celiac disease was excluded and who were symptomatically controlled on a gluten-free diet. Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. Symptoms were evaluated using a visual analog scale and markers of intestinal inflammation, injury, and immune activation were monitored. RESULTS: A total of 34 patients (aged 29-59 years, 4 men) completed the study as per protocol. Overall, 56% had human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high. Of 19 patients (68%) in the gluten group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation). On a visual analog scale, patients were significantly worse with gluten within 1 week for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001). Anti-gliadin antibodies were not induced. There were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with or without DQ2/DQ8. CONCLUSIONS: "Non-celiac gluten intolerance" may exist, but no clues to the mechanism were elucidated.

Development and validation of a comprehensive semi-quantitative food frequency questionnaire that includes FODMAP intake and glycemic index.

BACKGROUND: Fermentable, short chain carbohydrates (FODMAPs) have been identified as triggers for functional gastrointestinal symptoms. In addition, excess FODMAP consumption has been implicated in the onset of Crohn's disease, and animal studies suggest that a low glycemic index diet can impair absorption of fructose, a major dietary FODMAP. Such hypotheses cannot be tested without the ability to quantify FODMAP ingestion with a validated dietary assessment tool. OBJECTIVE: To assess the validity and reproducibility of a 297-item comprehensive, semi-quantitative food frequency questionnaire (FFQ) in estimating intake of macro- and micronutrients, FODMAPs, and glycemic index/load. SUBJECTS/SETTING: One hundred healthy participants were recruited to complete the FFQ on two occasions, plus four 1-week food diaries kept during a 12-month period. Participants exhibiting major dietary change during the study period or low energy reporting on the FFQ were excluded. MAIN OUTCOME MEASURES: Validation and reproducibility of the semi-quantitative FFQ by comparison with the mean of four 1-week food diaries. STATISTICAL ANALYSES PERFORMED: Validation was assessed using Wilcoxon signed rank test, Spearman's correlation, Bland-Altman, and weighted κ statistics. Reproducibility was examined using Shrout-Fleiss intraclass correlation coefficient. RESULTS: Seventy-two participants fulfilled inclusion and exclusion criteria. Demographics of the participants were comparable with 2006 Australian Census data. Consistent with other reported FFQs, the FFQ overestimated nutrient intake by a mean 140% (range=95% to 249%). However, based on the other analyses performed, it demonstrated validity for intake of sugars, fiber, alcohol, glycemic index, glucose, FODMAPs, calcium, folate, phosphate, potassium, iron, and magnesium; moderate validation for energy, total fat, saturated fat, carbohydrates, sodium, thiamin, sucrose, and retinol; poor validation for protein, mono/polyunsaturated fat, starch, glycemic load, niacin, and zinc. Riboflavin intake was not validated. Intraclass correlation coefficients for reproducibility ranged from 0.352 to 0.928. CONCLUSIONS: The FFQ was validated for assessment of a wide range of nutrients, including the new class of carbohydrates, FODMAPs, and glycemic index. This provides a useful tool for dietary research, particularly in the area of gastroenterological disorders.