EDITORIALS Diet as a Therapy for Irritable Bowel Syndrome: Progress at Last See “A diet low in FODMAPs reduces symptoms of irritable bowel syndrome,” by Halmos EP, Power VA, Shepherd SJ, et al, on page 67.
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ostprandial worsening of symptoms, as well as adverse reactions to one or more foods are common in patients with irritable bowel syndrome (IBS),1 and selfreported food intolerance in IBS is associated with a high symptom burden and reduced quality of life.2 In line with this, approximately two thirds of IBS patients exclude food items from their diet to improve symptoms.3 Despite this, there is no evidence suggesting inadequate nutrient intake in the majority of patients with IBS.4 For patients, identifying the food item/s they do not tolerate is often central when consulting for their symptoms, and in general guidelines for management of IBS, dietary advice is proposed to be of major importance.5 However, there are currently no available evidence-based guidelines for dietetic practice in IBS, as very few randomized, controlled trials exist on dietary treatment of IBS patients. Instead, the current recommendations are primarily based on studies assessing physiologic function in relation to dietary components, and to a lesser degree on research based on randomized, controlled trials examining the role of dietary components in the therapeutic management of IBS patients.6 Therefore, the article by Halmos et al7 published in this issue of Gastroenterology is a welcome addition to the existing literature. In a randomized, controlled trial, they demonstrate that reducing the intake of poorly absorbed short-chain carbohydrates, or fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), substantially improves the severity of the key symptoms of IBS.7 The hypothesis that reducing intake of FODMAPs can improve gastrointestinal (GI) symptoms stems from the clinical observation that a proportion of patients with IBS tolerate intake of certain short-chain carbohydrates poorly.8 Moreover, these carbohydrates can be incompletely absorbed in the small intestine due to absent hydrolyzation (eg, lactose maldigestion, and nondigestible oligosaccharides), dependence on simultaneous intake of glucose for adequate absorption (fructose), or passive diffusion (certain monosaccharides and polyols).9 Therefore, the absorption of short-chain carbohydrates in the small intestine varies depending on different factors such as presence/absence of enzymes to digest disaccharides (eg, lactase), small intestinal transit time, dose of the carbohydrate, meal composition, and also on the presence of mucosal disease.9 If a proportion of the FODMAPs pass unabsorbed through the small intestine, this increases intestinal luminal water content through osmosis, and increases gas production via fermentation by gut bacteria, leading to intestinal distension, which may cause symptoms in susceptible individuals. Moreover,
Gastroenterology 2014;146:10–26
fermentation products such as short-chain fatty acids may also be involved in symptom generation.10 However, incomplete absorption of carbohydrates in the small intestine is not enough to cause symptoms, because not all subjects with, for example, lactose maldigestion and fructose malabsorption report symptoms.11,12 Therefore, other factors implicated in the pathophysiology of IBS such as alterations in gut microbiota composition,13 visceral hypersensitivity,14 GI barrier defects, and abnormal immune function,15 may serve as cofactors in symptom generation after intake of an excess of FODMAPs in the diet. Further, symptom experience after intake of short-chain carbohydrates is also likely to be affected by central nervous system factors, and therefore directly or indirectly influenced by anxiety, depression, and stress, but potentially also by classical conditioning and expectations16 (Figure 1). An important research task is to address the ability of these factors to predict the response to dietary interventions in general, and low-FODMAP diet in particular, as few predictors for a positive symptomatic response to this diet exist.9 The scientific evidence supporting a clinically relevant positive effect of reducing FODMAPs in IBS has so far been relatively limited, but gradually accumulating over the last couple of years, and has, besides observational reports, mainly been based on a randomized single-blinded FODMAP challenge study,17 a nonrandomized, comparative study,18 and a randomized, controlled trial comparing a low FODMAP diet with the habitual diet in IBS.19 Moreover, a recent study also demonstrated that a general reduction of FODMAPs in the diet was effective in patients with suspected nonceliac gluten sensitivity, and no gluten-specific effect beyond that of the effect of the general FODMAP reduction could be demonstrated.20 Because few clinical trials in this area exist, the current study by Halmos et al7 is very important, because it provides high-quality evidence supporting the effectiveness of a low-FODMAP diet in IBS. By using a randomized, cross-over design, the authors were able to demonstrate a convincing reduction of the reported severity of all the key symptoms of IBS—abdominal pain, bloating, and bowel habit dissatisfaction—when the patients were on a low-FODMAP diet compared with when they received a standard Australian diet. Both diets had a similar nutritional composition, except for a difference in the FODMAP content. Moreover, the low FODMAP diet was welltolerated and the nutritional composition met current nutritional recommendations. The dietary intake was also strictly controlled as almost all food was provided to the subjects during the study, which further strengthens the reliability of the findings, but also begs for future studies to evaluate how this diet works in clinical practice when the patient is given dietary advice in an outpatient clinic setting, without receiving all food from a study center. The clinical experience is that a substantial proportion of patients find it difficult to follow strict diets for other than short periods of
EDITORIALS
Figure 1. Proposed mechanisms involved in the generation of gastrointestinal (GI) symptoms after intake of FODMAPs. Several factors affect the absorption of these shortchain carbohydrates in the small intestine. Incomplete absorption of FODMAPs leads to increased water retention through their osmotic activity and to gas production due to fermentation by gas bacteria. This leads to intestinal distension, which together with peripheral and central predisposing factors can generate GI symptoms.
time, and as can be expected adherence to the low-FODMAP diet has been found to be an important predictor for the outcome.21 The authors also assessed the effect on stool parameters objectively, by collection of feces, and here the effect of the diet was modest, despite the fact that the effect on bowel habit dissatisfaction was striking, further highlighting the complex nature of symptom reporting in IBS patients. As the authors rightfully acknowledge in their discussion, there were of course some limitations with the present study. Due to the logistic complexity of the study a relatively limited number of patients (n ¼ 30) was included, which limits the possibility of finding predictors for a favorable response, which is a clinically important question, as not all patients respond favorably to this treatment alternative. Further, a relatively short treatment period (3 weeks) was used and currently no scientific guidance exists on how this diet works in the long run or if gradual reintroduction of excluded food items can be done without worsening of symptoms. Moreover, the use of a cross-over design carries a risk of carry-over effects, but the authors used a relatively long wash-out period to reduce this risk, and also performed several additional analyses to secure the absence of a relevant carry-over effect. In the present study, no further mechanistic insight into the mechanism behind symptom improvement was provided, as for instance the results from breath testing or stool parameters did not predict symptom response. However, based on the current convincing data, clearly demonstrating an excellent short-term response of low-FODMAP diet in a substantial proportion of IBS
patients,7 future studies can address the remaining research questions, such as how to identify the right patients for this therapy and also to determine how strict the diet needs to be to yield a sufficiently favorable long-term response. Moreover, so far no study has demonstrated that this diet therapy is superior to the dietetic practice that has been used for patients with IBS before a low-FODMAP diet was suggested as a treatment alternative for IBS, that is, to encourage a regular meal pattern and a “healthy eating,” to avoid large meals, reduce intake of fat, discourage excessive fiber intake (especially soluble fibers), reduce caffeine, and avoid gas-producing foods, such as beans, cabbage, and onions.6 To conclude, with the study from Halmos et al,7 we now have solid scientific data supporting that a low-FODMAP diet is efficient in reducing GI symptoms in IBS, at least in the short term. Long-term studies are now needed, as well as investigations finding clinically useful predictors that can help clinicians in selecting patients who are likely to respond to this relatively cumbersome form of therapy, for which access to expert dieticians are needed. Moreover, high-quality, head-to-head comparisons with other dietary strategies used in the management of patients with IBS will be helpful for practicing dieticians and gastroenterologists, as well as evaluation of ways to facilitate dissemination of dietary information to large groups of patients, such as group education and web-based tools. For the benefit of our patients, some progress has been made finally regarding diet as a therapy for IBS, but as always, a nice study always raises further questions that need to be addressed in future studies!
11
EDITORIALS MAGNUS SIMRÉN Department of Internal Medicine and Clinical Nutrition Institute of Medicine and University of Gothenburg Centre for Person-Centred Care Sahlgrenska Academy University of Gothenburg Gothenburg, Sweden
References 1. Simrén M, Månsson A, Langkilde AM, et al. Food-related gastrointestinal symptoms in the irritable bowel syndrome. Digestion 2001;63:108–115. 2. Böhn L, Storsrud S, Tornblom H, et al. Self-reported food-related gastrointestinal symptoms in IBS are common and associated with more severe symptoms and reduced quality of life. Am J Gastroenterol 2013; 108:634–641. 3. Monsbakken KW, Vandvik PO, Farup PG. Perceived food intolerance in subjects with irritable bowel syndrome: etiology, prevalence and consequences. Eur J Clin Nutr 2006;60:667–672. 4. Böhn L, Storsrud S, Simren M. Nutrient intake in patients with irritable bowel syndrome compared with the general population. Neurogastroenterol Motil 2013; 25:23–30. 5. Wilkins T, Pepitone C, Alex B, et al. Diagnosis and management of IBS in adults. Am Fam Physician 2012; 86:419–426. 6. Heizer WD, Southern S, McGovern S. The role of diet in symptoms of irritable bowel syndrome in adults: a narrative review. J Am Diet Assoc 2009; 109:1204–1214. 7. Halmos EP, Power VA, Shepherd SJ, et al. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology 2014;146:67–75. 8. Gibson PR, Shepherd SJ. Evidence-based dietary management of functional gastrointestinal symptoms: the FODMAP approach. J Gastroenterol Hepatol 2010; 25:252–258. 9. Shepherd SJ, Lomer MC, Gibson PR. Short-chain carbohydrates and functional gastrointestinal disorders. Am J Gastroenterol 2013;108:707–717. 10. Tana C, Umesaki Y, Imaoka A, et al. Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol Motil 2010;22:512–519. 11. Farup PG, Monsbakken KW, Vandvik PO. Lactose malabsorption in a population with irritable bowel syndrome: prevalence and symptoms. A case-control study. Scand J Gastroenterol 2004;39:645–649.
12
12. Gibson PR, Newnham E, Barrett JS, et al. Review article: fructose malabsorption and the bigger picture. Aliment Pharmacol Ther 2007;25:349–363. 13. Simren M, Barbara G, Flint HJ, et al. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut 2013;62:159–176. 14. Posserud I, Syrous A, Lindstrom L, et al. Altered rectal perception in irritable bowel syndrome is associated with symptom severity. Gastroenterology 2007;133:1113–1123. 15. Öhman L, Simren M. Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nat Rev Gastroenterol Hepatol 2010;7:163–173. 16. Elsenbruch S. Abdominal pain in irritable bowel syndrome: a review of putative psychological, neural and neuro-immune mechanisms. Brain Behav Immun 2011;25:386–394. 17. Shepherd SJ, Parker FC, Muir JG, et al. Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence. Clin Gastroenterol Hepatol 2008;6:765–771. 18. Staudacher HM, Whelan K, Irving PM, et al. Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) versus standard dietary advice in patients with irritable bowel syndrome. J Hum Nutr Diet 2011;24:487–495. 19. Staudacher HM, Lomer MC, Anderson JL, et al. Fermentable carbohydrate restriction reduces luminal bifidobacteria and gastrointestinal symptoms in patients with irritable bowel syndrome. J Nutr 2012;142:1510–1518. 20. Biesiekierski JR, Peters SL, Newnham ED, et al. No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterology 2013;145:320–328. 21. Shepherd SJ, Gibson PR. Fructose malabsorption and symptoms of irritable bowel syndrome: guidelines for effective dietary management. J Am Diet Assoc 2006; 106:1631–1639.
Reprint requests Address requests for reprints to: Professor Magnus Simrén, Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden. e-mail: [email protected].
Conflicts of interest The author discloses the following: Magnus Simrén has received unrestricted research grants from Danone and AstraZeneca, served as a Consultant/ Advisory Board member for Danone, Novartis, Almirall, Albireo, and Shire, and been on the Speaker’s bureau for Almirall, Danone, Shire, Menarini, Abbvie, MSD, Tillotts and Vifor Pharma. © 2014 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2013.11.027
P
ostprandial worsening of symptoms, as well as adverse reactions to one or more foods are common in patients with irritable bowel syndrome (IBS),1 and selfreported food intolerance in IBS is associated with a high symptom burden and reduced quality of life.2 In line with this, approximately two thirds of IBS patients exclude food items from their diet to improve symptoms.3 Despite this, there is no evidence suggesting inadequate nutrient intake in the majority of patients with IBS.4 For patients, identifying the food item/s they do not tolerate is often central when consulting for their symptoms, and in general guidelines for management of IBS, dietary advice is proposed to be of major importance.5 However, there are currently no available evidence-based guidelines for dietetic practice in IBS, as very few randomized, controlled trials exist on dietary treatment of IBS patients. Instead, the current recommendations are primarily based on studies assessing physiologic function in relation to dietary components, and to a lesser degree on research based on randomized, controlled trials examining the role of dietary components in the therapeutic management of IBS patients.6 Therefore, the article by Halmos et al7 published in this issue of Gastroenterology is a welcome addition to the existing literature. In a randomized, controlled trial, they demonstrate that reducing the intake of poorly absorbed short-chain carbohydrates, or fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), substantially improves the severity of the key symptoms of IBS.7 The hypothesis that reducing intake of FODMAPs can improve gastrointestinal (GI) symptoms stems from the clinical observation that a proportion of patients with IBS tolerate intake of certain short-chain carbohydrates poorly.8 Moreover, these carbohydrates can be incompletely absorbed in the small intestine due to absent hydrolyzation (eg, lactose maldigestion, and nondigestible oligosaccharides), dependence on simultaneous intake of glucose for adequate absorption (fructose), or passive diffusion (certain monosaccharides and polyols).9 Therefore, the absorption of short-chain carbohydrates in the small intestine varies depending on different factors such as presence/absence of enzymes to digest disaccharides (eg, lactase), small intestinal transit time, dose of the carbohydrate, meal composition, and also on the presence of mucosal disease.9 If a proportion of the FODMAPs pass unabsorbed through the small intestine, this increases intestinal luminal water content through osmosis, and increases gas production via fermentation by gut bacteria, leading to intestinal distension, which may cause symptoms in susceptible individuals. Moreover,
Gastroenterology 2014;146:10–26
fermentation products such as short-chain fatty acids may also be involved in symptom generation.10 However, incomplete absorption of carbohydrates in the small intestine is not enough to cause symptoms, because not all subjects with, for example, lactose maldigestion and fructose malabsorption report symptoms.11,12 Therefore, other factors implicated in the pathophysiology of IBS such as alterations in gut microbiota composition,13 visceral hypersensitivity,14 GI barrier defects, and abnormal immune function,15 may serve as cofactors in symptom generation after intake of an excess of FODMAPs in the diet. Further, symptom experience after intake of short-chain carbohydrates is also likely to be affected by central nervous system factors, and therefore directly or indirectly influenced by anxiety, depression, and stress, but potentially also by classical conditioning and expectations16 (Figure 1). An important research task is to address the ability of these factors to predict the response to dietary interventions in general, and low-FODMAP diet in particular, as few predictors for a positive symptomatic response to this diet exist.9 The scientific evidence supporting a clinically relevant positive effect of reducing FODMAPs in IBS has so far been relatively limited, but gradually accumulating over the last couple of years, and has, besides observational reports, mainly been based on a randomized single-blinded FODMAP challenge study,17 a nonrandomized, comparative study,18 and a randomized, controlled trial comparing a low FODMAP diet with the habitual diet in IBS.19 Moreover, a recent study also demonstrated that a general reduction of FODMAPs in the diet was effective in patients with suspected nonceliac gluten sensitivity, and no gluten-specific effect beyond that of the effect of the general FODMAP reduction could be demonstrated.20 Because few clinical trials in this area exist, the current study by Halmos et al7 is very important, because it provides high-quality evidence supporting the effectiveness of a low-FODMAP diet in IBS. By using a randomized, cross-over design, the authors were able to demonstrate a convincing reduction of the reported severity of all the key symptoms of IBS—abdominal pain, bloating, and bowel habit dissatisfaction—when the patients were on a low-FODMAP diet compared with when they received a standard Australian diet. Both diets had a similar nutritional composition, except for a difference in the FODMAP content. Moreover, the low FODMAP diet was welltolerated and the nutritional composition met current nutritional recommendations. The dietary intake was also strictly controlled as almost all food was provided to the subjects during the study, which further strengthens the reliability of the findings, but also begs for future studies to evaluate how this diet works in clinical practice when the patient is given dietary advice in an outpatient clinic setting, without receiving all food from a study center. The clinical experience is that a substantial proportion of patients find it difficult to follow strict diets for other than short periods of
EDITORIALS
Figure 1. Proposed mechanisms involved in the generation of gastrointestinal (GI) symptoms after intake of FODMAPs. Several factors affect the absorption of these shortchain carbohydrates in the small intestine. Incomplete absorption of FODMAPs leads to increased water retention through their osmotic activity and to gas production due to fermentation by gas bacteria. This leads to intestinal distension, which together with peripheral and central predisposing factors can generate GI symptoms.
time, and as can be expected adherence to the low-FODMAP diet has been found to be an important predictor for the outcome.21 The authors also assessed the effect on stool parameters objectively, by collection of feces, and here the effect of the diet was modest, despite the fact that the effect on bowel habit dissatisfaction was striking, further highlighting the complex nature of symptom reporting in IBS patients. As the authors rightfully acknowledge in their discussion, there were of course some limitations with the present study. Due to the logistic complexity of the study a relatively limited number of patients (n ¼ 30) was included, which limits the possibility of finding predictors for a favorable response, which is a clinically important question, as not all patients respond favorably to this treatment alternative. Further, a relatively short treatment period (3 weeks) was used and currently no scientific guidance exists on how this diet works in the long run or if gradual reintroduction of excluded food items can be done without worsening of symptoms. Moreover, the use of a cross-over design carries a risk of carry-over effects, but the authors used a relatively long wash-out period to reduce this risk, and also performed several additional analyses to secure the absence of a relevant carry-over effect. In the present study, no further mechanistic insight into the mechanism behind symptom improvement was provided, as for instance the results from breath testing or stool parameters did not predict symptom response. However, based on the current convincing data, clearly demonstrating an excellent short-term response of low-FODMAP diet in a substantial proportion of IBS
patients,7 future studies can address the remaining research questions, such as how to identify the right patients for this therapy and also to determine how strict the diet needs to be to yield a sufficiently favorable long-term response. Moreover, so far no study has demonstrated that this diet therapy is superior to the dietetic practice that has been used for patients with IBS before a low-FODMAP diet was suggested as a treatment alternative for IBS, that is, to encourage a regular meal pattern and a “healthy eating,” to avoid large meals, reduce intake of fat, discourage excessive fiber intake (especially soluble fibers), reduce caffeine, and avoid gas-producing foods, such as beans, cabbage, and onions.6 To conclude, with the study from Halmos et al,7 we now have solid scientific data supporting that a low-FODMAP diet is efficient in reducing GI symptoms in IBS, at least in the short term. Long-term studies are now needed, as well as investigations finding clinically useful predictors that can help clinicians in selecting patients who are likely to respond to this relatively cumbersome form of therapy, for which access to expert dieticians are needed. Moreover, high-quality, head-to-head comparisons with other dietary strategies used in the management of patients with IBS will be helpful for practicing dieticians and gastroenterologists, as well as evaluation of ways to facilitate dissemination of dietary information to large groups of patients, such as group education and web-based tools. For the benefit of our patients, some progress has been made finally regarding diet as a therapy for IBS, but as always, a nice study always raises further questions that need to be addressed in future studies!
11
EDITORIALS MAGNUS SIMRÉN Department of Internal Medicine and Clinical Nutrition Institute of Medicine and University of Gothenburg Centre for Person-Centred Care Sahlgrenska Academy University of Gothenburg Gothenburg, Sweden
References 1. Simrén M, Månsson A, Langkilde AM, et al. Food-related gastrointestinal symptoms in the irritable bowel syndrome. Digestion 2001;63:108–115. 2. Böhn L, Storsrud S, Tornblom H, et al. Self-reported food-related gastrointestinal symptoms in IBS are common and associated with more severe symptoms and reduced quality of life. Am J Gastroenterol 2013; 108:634–641. 3. Monsbakken KW, Vandvik PO, Farup PG. Perceived food intolerance in subjects with irritable bowel syndrome: etiology, prevalence and consequences. Eur J Clin Nutr 2006;60:667–672. 4. Böhn L, Storsrud S, Simren M. Nutrient intake in patients with irritable bowel syndrome compared with the general population. Neurogastroenterol Motil 2013; 25:23–30. 5. Wilkins T, Pepitone C, Alex B, et al. Diagnosis and management of IBS in adults. Am Fam Physician 2012; 86:419–426. 6. Heizer WD, Southern S, McGovern S. The role of diet in symptoms of irritable bowel syndrome in adults: a narrative review. J Am Diet Assoc 2009; 109:1204–1214. 7. Halmos EP, Power VA, Shepherd SJ, et al. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology 2014;146:67–75. 8. Gibson PR, Shepherd SJ. Evidence-based dietary management of functional gastrointestinal symptoms: the FODMAP approach. J Gastroenterol Hepatol 2010; 25:252–258. 9. Shepherd SJ, Lomer MC, Gibson PR. Short-chain carbohydrates and functional gastrointestinal disorders. Am J Gastroenterol 2013;108:707–717. 10. Tana C, Umesaki Y, Imaoka A, et al. Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol Motil 2010;22:512–519. 11. Farup PG, Monsbakken KW, Vandvik PO. Lactose malabsorption in a population with irritable bowel syndrome: prevalence and symptoms. A case-control study. Scand J Gastroenterol 2004;39:645–649.
12
12. Gibson PR, Newnham E, Barrett JS, et al. Review article: fructose malabsorption and the bigger picture. Aliment Pharmacol Ther 2007;25:349–363. 13. Simren M, Barbara G, Flint HJ, et al. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut 2013;62:159–176. 14. Posserud I, Syrous A, Lindstrom L, et al. Altered rectal perception in irritable bowel syndrome is associated with symptom severity. Gastroenterology 2007;133:1113–1123. 15. Öhman L, Simren M. Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nat Rev Gastroenterol Hepatol 2010;7:163–173. 16. Elsenbruch S. Abdominal pain in irritable bowel syndrome: a review of putative psychological, neural and neuro-immune mechanisms. Brain Behav Immun 2011;25:386–394. 17. Shepherd SJ, Parker FC, Muir JG, et al. Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence. Clin Gastroenterol Hepatol 2008;6:765–771. 18. Staudacher HM, Whelan K, Irving PM, et al. Comparison of symptom response following advice for a diet low in fermentable carbohydrates (FODMAPs) versus standard dietary advice in patients with irritable bowel syndrome. J Hum Nutr Diet 2011;24:487–495. 19. Staudacher HM, Lomer MC, Anderson JL, et al. Fermentable carbohydrate restriction reduces luminal bifidobacteria and gastrointestinal symptoms in patients with irritable bowel syndrome. J Nutr 2012;142:1510–1518. 20. Biesiekierski JR, Peters SL, Newnham ED, et al. No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates. Gastroenterology 2013;145:320–328. 21. Shepherd SJ, Gibson PR. Fructose malabsorption and symptoms of irritable bowel syndrome: guidelines for effective dietary management. J Am Diet Assoc 2006; 106:1631–1639.
Reprint requests Address requests for reprints to: Professor Magnus Simrén, Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 41345 Gothenburg, Sweden. e-mail: [email protected].
Conflicts of interest The author discloses the following: Magnus Simrén has received unrestricted research grants from Danone and AstraZeneca, served as a Consultant/ Advisory Board member for Danone, Novartis, Almirall, Albireo, and Shire, and been on the Speaker’s bureau for Almirall, Danone, Shire, Menarini, Abbvie, MSD, Tillotts and Vifor Pharma. © 2014 by the AGA Institute 0016-5085/$36.00 http://dx.doi.org/10.1053/j.gastro.2013.11.027
