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ABSTRACT: BACKGROUND: & Aims: Patients with non-celiac gluten sensitivity (NCGS) do not have celiac disease but their symptoms improve when they are placed on gluten-free diets. We investigated the specific effects of gluten following dietary reduction of low-fermentable, poorly-absorbed, short-chain carbohydrates (FODMAPs) in subjects believed to have NCGS. METHODS: We performed a double-blind crossover trial of 37 subjects (24-61 y, 6 men) with NCGS and irritable bowel syndrome (based on Rome III criteria), but not celiac disease. Participants were randomly assigned to groups given a 2-week diet of reduced FODMAPs, and were then placed on high-gluten (16 g gluten/day), low-gluten (2 g gluten/day and 14 g whey protein/day), or control (16 g whey protein/day) diets for 1 week, followed by a washout period of at least 2 weeks. We assessed serum and fecal markers of intestinal inflammation/injury and immune activation, and indices of fatigue. Twenty-two participants then crossed-over to groups given gluten (16 g/day), whey (16 g/day), or control (no additional protein) diets for 3 days. Symptoms were evaluated by visual analogue scales. RESULTS: In all participants, gastrointestinal symptoms consistently and significantly improved during reduced FODMAP intake, but significantly worsened to a similar degree when their diets included gluten or whey protein. Gluten-specific effects were observed in only 8% of participants. There were no diet-specific changes in any biomarker. During the 3-day re-challenge, participants' symptoms increased by similar levels among groups. Gluten-specific gastrointestinal effects were not reproduced. An order effect was observed. CONCLUSION: In a placebo-controlled, crossover re-challenge study, we found no evidence of specific or dose-dependent effects of gluten in patients with NCGS placed diets low in FODMAPs.
Gastroenterology 05/2013; · 11.68 Impact Factor
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ABSTRACT: 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.
Journal of Nutrition 06/2012; 142(8):1510-8. · 3.92 Impact Factor
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ABSTRACT: 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.
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.
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.
"Non-celiac gluten intolerance" may exist, but no clues to the mechanism were elucidated.
The American Journal of Gastroenterology 01/2011; 106(3):508-14; quiz 515. · 7.28 Impact Factor
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ABSTRACT: Reduction of short-chain poorly absorbed carbohydrates (FODMAPs) in the diet reduces symptoms of irritable bowel syndrome (IBS). In the present study, we aimed to compare the patterns of breath hydrogen and methane and symptoms produced in response to diets that differed only in FODMAP content.
Fifteen healthy subjects and 15 with IBS (Rome III criteria) undertook a single-blind, crossover intervention trial involving consuming provided diets that were either low (9 g/day) or high (50 g/day) in FODMAPs for 2 days. Food and gastrointestinal symptom diaries were kept and breath samples collected hourly over 14 h on day 2 of each diet.
Higher levels of breath hydrogen were produced over the entire day with the high FODMAP diet for healthy volunteers (181 +/- 77 ppm.14 h vs 43 +/- 18; mean +/- SD P < 0.0001) and patients with IBS (242 +/- 79 vs 62 +/- 23; P < 0.0001), who had higher levels during each dietary period than the controls (P < 0.05). Breath methane, produced by 10 subjects within each group, was reduced with the high FODMAP intake in healthy subjects (47 +/- 29 vs 109 +/- 77; P = 0.043), but was not different in patients with IBS (126 +/- 153 vs 86 +/- 72). Gastrointestinal symptoms and lethargy were significantly induced by the high FODMAP diet in patients with IBS, while only increased flatus production was reported by healthy volunteers.
Dietary FODMAPs induce prolonged hydrogen production in the intestine that is greater in IBS, influence the amount of methane produced, and induce gastrointestinal and systemic symptoms experienced by patients with IBS. The results offer mechanisms underlying the efficacy of the low FODMAP diet in IBS.
Journal of Gastroenterology and Hepatology 08/2010; 25(8):1366-73. · 2.87 Impact Factor
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ABSTRACT: Fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) are short-chain carbohydrates that can be poorly absorbed by the small intestine and may have a wide range of effects on gastrointestinal processes. FODMAPs include lactose, fructose in excess of glucose, fructans and fructooligosaccharides (FOS, nystose, kestose), galactooligosaccharides (GOS, raffinose, stachyose), and sugar polyols (sorbitol, mannitol). This paper describes an analytical approach based on HPLC with ELSD that quantifies the major FODMAPs in 45 vegetables and 41 fruits. Sorbitol and/or mannitol were measured in 18 vegetables (range = 0.09-2.96 g/100 g of fw), raffinose and/or stachyose in 7 vegetables (0.08-0.68 g/100 g of fw), and nystose and/or kestose in 19 vegetables (0.02-0.71 g/100 g of fw). Apple, pear, mango, clingstone peach, and watermelon all contained fructose in excess of glucose. Sorbitol was measured in 15 fruits (0.53-5.99 g/100 g of fw), mannitol was found in 2 fruits, and nystose or kestose was measured in 8 fruits. Understanding the importance of dietary FODMAPs will be greatly assisted by comprehensive food composition data.
Journal of Agricultural and Food Chemistry 02/2009; 57(2):554-65. · 2.82 Impact Factor
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ABSTRACT: Observational studies suggest dietary fructose restriction might lead to sustained symptomatic response in patients with irritable bowel syndrome (IBS) and fructose malabsorption. The aims of this study were first to determine whether the efficacy of this dietary change is due to dietary fructose restriction and second to define whether symptom relief was specific to free fructose or to poorly absorbed short-chain carbohydrates in general.
The double-blinded, randomized, quadruple arm, placebo-controlled rechallenge trial took place in the general community. The 25 patients who had responded to dietary change were provided all food, low in free fructose and fructans, for the duration of the study. Patients were randomly challenged by graded dose introduction of fructose, fructans, alone or in combination, or glucose taken as drinks with meals for maximum test period of 2 weeks, with at least 10-day washout period between. For the main outcome measures, symptoms were monitored by daily diary entries and responses to a global symptom question.
Seventy percent of patients receiving fructose, 77% receiving fructans, and 79% receiving a mixture reported symptoms were not adequately controlled, compared with 14% receiving glucose (P < or = 0.002, McNemar test). Similarly, the severity of overall and individual symptoms was significantly and markedly less for glucose than other substances. Symptoms were induced in a dose-dependent manner and mimicked previous IBS symptoms.
In patients with IBS and fructose malabsorption, dietary restriction of fructose and/or fructans is likely to be responsible for symptomatic improvement, suggesting efficacy is due to restriction of poorly absorbed short-chain carbohydrates in general.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 07/2008; 6(7):765-71. · 5.64 Impact Factor
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ABSTRACT: Poorly absorbed short-chain carbohydrates (FODMAPs) in the diet should, by virtue of their osmotic effects, increase fecal output following colectomy and ileal pouch formation or ileorectal anastomosis (IRA). The aim was to perform a proof-of-concept evaluation of this hypothesis.
Fifteen patients (13 pouch, 2 IRA) had dietary and symptomatic evaluation before and during a low FODMAP diet. Carbohydrate malabsorption was evaluated by breath tests. Pouchitis was assessed clinically/endoscopically or by fecal lactoferrin.
Of 8 patients with a breath hydrogen response to lactulose, 7 had fructose malabsorption, 3 with lactose malabsorption, and 1 had lactose malabsorption alone. Five of 7 studied retrospectively improved stool frequency (from median 8 to 4 per day; P = 0.02), this being sustained over 0.5-3 years of follow-up. Five of 8 patients completed a prospective arm of the study. One patient had sustained improvement in stool frequency and 1 had reduced wind production. Overall, none of 8 patients who had pouchitis improved. In contrast, median daily stool frequency fell from 8 to 4 (P = 0.001) in the 7 without pouchitis. The degree of change in FODMAP intake also predicted response. There was a tendency for pouchitis to be associated with low baseline FODMAP intake.
There is a high prevalence of carbohydrate malabsorption in these patients. Reduction of the intake of FODMAPs may be efficacious in reducing stool frequency in patients without pouchitis, depending on dietary adherence and baseline diet.
Inflammatory Bowel Diseases 01/2008; 13(12):1522-8. · 4.86 Impact Factor
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ABSTRACT: Fructans are not digested in the small intestines of humans. While many health benefits have been attributed to these carbohydrates, they can cause gastrointestinal symptoms in some individuals. We measured the total fructans in 60 vegetables and 43 fruits using the Megazyme fructan assay. Vegetables with the highest quantity of fructans included garlic, artichoke, shallots, leek bulb, and onions (range, 1.2-17.4 g/100 g fw). Fruits with low, but detectable, fructans included longon, white peach, persimmon, and melon (range, 0.21-0.46 g/100 g fw). The fructan assay was modified to provide an estimate of the average chain length (degree of polymerization) for high fructan vegetables. d-Fructose can also be malabsorbed in the small intestine of humans, so the d-fructose content in some foods was measured to supplement the current food tables. Research in this area will be facilitated through the availability of more comprehensive food composition data.
Journal of Agricultural and Food Chemistry 09/2007; 55(16):6619-27. · 2.82 Impact Factor
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ABSTRACT: Butyrate, the four-carbon fatty acid, is formed in the human colon by bacterial fermentation of carbohydrates (including dietary fiber), and putatively suppresses colorectal cancer (CRC). Butyrate has diverse and apparently paradoxical effects on cellular proliferation, apoptosis and differentiation that may be either pro-neoplastic or anti-neoplastic, depending upon factors such as the level of exposure, availability of other metabolic substrate and the intracellular milieu. In humans, the relationship between luminal butyrate exposure and CRC has been examined only indirectly in case-control studies, by measuring fecal butyrate concentrations, although this may not accurately reflect effective butyrate exposure during carcinogenesis. Perhaps not surprisingly, results of these investigations have been mutually contradictory. The direct effect of butyrate on tumorigenesis has been assessed in a number of in vivo animal models, which have also yielded conflicting results. In part, this may be explained by methodological differences in the amount and route of butyrate administration, which are likely to significantly influence delivery of butyrate to the distal colon. Nonetheless, there appears to be some evidence that delivery of an adequate amount of butyrate to the appropriate site protects against early tumorigenic events. Future study of the relationship between butyrate and CRC in humans needs to focus on risk stratification and the development of feasible strategies for butyrate delivery.
Journal of Gastroenterology and Hepatology 02/2006; 21(1 Pt 2):209-18. · 2.87 Impact Factor
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ABSTRACT: Wheat bran (WB) increases fecal bulk and hastens colonic transit, whereas resistant starch (RS) has effects on colonic fermentation, including increasing concentrations of butyrate.
We hypothesized that a diet combining WB with RS would produce more favorable changes in fecal variables (eg, fecal bulk, rapid transit time, lower pH, and higher butyrate) than would WB alone.
This was a randomized crossover block-design study for which 20 volunteers with a family history of colorectal cancer were recruited. The study included 3 diets: control, WB (12 g fiber/d), and WBRS (12 g WB fiber/d plus 22 g RS/d), each continued for 3 wk. In each diet, the major source of protein was lean red meat. During 5 consecutive days (days 15-19) of each dietary period, the subjects collected their total fecal output for analysis.
The WB diet resulted in greater fecal output (by 23% and 21% for wet and dry weights, respectively) and a lesser transit time (-11 h) than did the control diet but did not have major effects on fermentation variables. Compared with the control diet, the WBRS diet resulted in greater fecal output (by 56%) and a shorter transit time (-10 h), lower fecal pH (-0.15 units), higher fecal concentration (by 14%) and daily excretion (by 101%) of acetate, higher fecal concentration (by 79%) and daily excretion (by 162%) of butyrate, a higher fecal ratio of butyrate to total short-chain fatty acids (by 45%), and lower concentrations of total phenols (-34%) and ammonia (-27%).
Combining WB with RS had more benefits than did WB alone. This finding may have important implications for the dietary modulation of luminal contents, especially in the distal colon (the most common site of tumor formation).
American Journal of Clinical Nutrition 07/2004; 79(6):1020-8. · 6.67 Impact Factor
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ABSTRACT: Background: Wheat bran (WB) increases fecal bulk and hastens colonic transit, whereas resistant starch (RS) has effects on colonic fermentation, including increasing concentrations of butyrate. Objective: We hypothesized that a diet combining WB with RS would produce more favorable changes in fecal variables (eg, fecal bulk, rapid transit time, lower pH, and higher butyrate) than would WB alone. Design: This was a randomized crossover block-design study for which 20 volunteers with a family history of colorectal cancer were recruited. The study included 3 diets: control, WB (12 g fiber/d), and WBRS (12 g WB fiber/d plus 22 g RS/d), each continued for 3 wk. In each diet, the major source of protein was lean red meat. During 5 consecutive days (days 15-19) of each dietary period, the subjects collected their total fecal output for analysis. Results: The WB diet resulted in greater fecal output (by 23% and 21% for wet and dry weights, respectively) and a lesser transit time (11 h) than did the control diet but did not have major effects on fermentation variables. Compared with the control diet, the WBRS diet resulted in greater fecal output (by 56%) and a shorter transit time (10 h), lower fecal pH (0.15 units), higher fecal concentra- tion (by 14%) and daily excretion (by 101%) of acetate, higher fecal concentration (by 79%) and daily excretion (by 162%) of butyrate, a higher fecal ratio of butyrate to total short-chain fatty acids (by 45%), and lower concentrations of total phenols (34%) and am- monia (27%). Conclusions: Combining WB with RS had more benefits than did WB alone. This finding may have important implications for the dietary modulation of luminal contents, especially in the distal colon (the most common site of tumor formation). Am J Clin Nutr 2004;79:1020 - 8.
