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Pieber TR, Svehlikova E, Mursic I, Esterl T, Wargenau M, Sartorius T, Pauly L, Schwejda-Guettes S, Neumann A, Faerber V, Stover JF, Gaigg B, Kuchinka-Koch A. Blood glucose response after oral lactulose intake in type 2 diabetic individuals. World J Diabetes 2021; 12:893-907. [PMID: 34168736 PMCID: PMC8192256 DOI: 10.4239/wjd.v12.i6.893] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 04/07/2021] [Accepted: 04/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Lactulose is approved for the symptomatic treatment of constipation, a gastrointestinal (GI) complication common in individuals with diabetes. Lactulose products contain carbohydrate impurities (e.g., lactose, fructose, galactose), which occur during the lactulose manufacturing process. These impurities may affect the blood glucose levels of individuals with type 2 diabetes mellitus (T2DM) using lactulose for the treatment of mild constipation. A previous study in healthy subjects revealed no increase in blood glucose levels after oral lactulose intake. However, it is still unclear whether the intake of lactulose increases blood glucose levels in individuals with diabetes.
AIM To evaluate the blood glucose profile after oral lactulose intake in mildly constipated, non-insulin-dependent subjects with T2DM in an outpatient setting.
METHODS This prospective, double-blind, randomized, controlled, single-center trial was conducted at the Clinical Research Center at the Medical University of Graz, Austria, in 24 adult Caucasian mildly constipated, non-insulin-dependent subjects with T2DM. Eligible subjects were randomized and assigned to one of six treatment sequences, each consisting of four treatments stratified by sex using an incomplete block design. Subjects received a single dose of 20 g or 30 g lactulose (crystal and liquid formulation), water as negative control or 30 g glucose as positive control. Capillary blood glucose concentrations were measured over a period of 180 min post dose. The primary endpoint was the baseline-corrected area under the curve of blood glucose concentrations over the complete assessment period [AUCbaseline_c (0-180 min)]. Quantitative comparisons were performed for both lactulose doses and formulations vs water for the equal lactulose dose vs glucose, as well as for liquid lactulose vs crystal lactulose. Safety parameters included GI tolerability, which was assessed at 180 min and 24 h post dose, and adverse events occurring up to 24 h post dose.
RESULTS In 24 randomized and analyzed subjects blood glucose concentration-time curves after intake of 20 g and 30 g lactulose were almost identical to those after water intake for both lactulose formulations despite the different amounts of carbohydrate impurities (≤ 3.0% for crystals and approx. 30% for liquid). The primary endpoint [AUCbaseline_c (0-180 min)] was not significantly different between lactulose and water regardless of lactulose dose and formulation. Also with regard to all secondary endpoints lactulose formulations showed comparable results to water with one exception concerning maximum glucose level. A minor increase in maximum blood glucose was observed after the 30 g dose, liquid lactulose, in comparison to water with a mean treatment difference of 0.63 mmol/L (95% confidence intervals: 0.19, 1.07). Intake of 30 g glucose significantly increased all blood glucose endpoints vs 30 g liquid and crystal lactulose, respectively (all P < 0.0001). No differences in blood glucose response were observed between the different lactulose formulations. As expected, lactulose increased the number of bowel movements and was generally well tolerated. Subjects experienced only mild to moderate GI symptoms due to the laxative action of lactulose.
CONCLUSION Blood glucose AUCbaseline_c (0-180 min) levels in mildly constipated, non-insulin dependent subjects with T2DM are not affected by the carbohydrate impurities contained in 20 g and 30 g crystal or liquid lactulose formulations.
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Affiliation(s)
- Thomas R Pieber
- Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz 8036, Austria
| | - Eva Svehlikova
- Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz 8036, Austria
| | - Ines Mursic
- Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz 8036, Austria
| | - Tamara Esterl
- Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz 8036, Austria
| | - Manfred Wargenau
- Department of Statistic, M.A.R.C.O. GmbH & Co. KG, Institute for Clinical Research and Statistics, Düsseldorf 40211, Germany
| | - Tina Sartorius
- Department of Nutritional CRO, BioTeSys GmbH, Esslingen 73728, Germany
| | - Lioba Pauly
- Department of Medical & Clinical Affairs, Market Access & Education Business Unit Enteral Nutrition, Bad Homburg 61352, Germany
| | - Susann Schwejda-Guettes
- Department of Medical & Clinical Affairs, Market Access & Education Business Unit Enteral Nutrition, Bad Homburg 61352, Germany
| | - Annalena Neumann
- Department of Medical, Clinical & Regulatory Affairs, Business Unit Parenteral Nutrition, Keto-Analogues and Standard I.V. Fluids, Fresenius Kabi Deutschland GmbH, Bad Homburg 61352, Germany
| | - Valentin Faerber
- Department of Medical, Clinical & Regulatory Affairs, Business Unit Parenteral Nutrition, Keto-Analogues and Standard I.V. Fluids, Fresenius Kabi Deutschland GmbH, Bad Homburg 61352, Germany
| | | | - Barbara Gaigg
- Market Unit Lactulose, Fresenius Kabi Austria GmbH, Linz 4020, Austria
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Chey WD, Keefer L, Whelan K, Gibson PR. Behavioral and Diet Therapies in Integrated Care for Patients With Irritable Bowel Syndrome. Gastroenterology 2021; 160:47-62. [PMID: 33091411 DOI: 10.1053/j.gastro.2020.06.099] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 05/08/2020] [Accepted: 06/06/2020] [Indexed: 02/06/2023]
Abstract
Irritable bowel syndrome (IBS) is a common, symptom-based condition that has negative effects on quality of life and costs health care systems billions of dollars each year. Until recently, management of IBS has focused on over-the-counter and prescription medications that reduce symptoms in fewer than one-half of patients. Patients have increasingly sought natural solutions for their IBS symptoms. However, behavioral techniques and dietary modifications can be effective in treatment of IBS. Behavioral interventions include gastrointestinal-focused cognitive behavioral therapy and gut-directed hypnotherapy to modify interactions between the gut and the brain. In this pathway, benign sensations from the gut induce maladaptive cognitive or affective processes that amplify symptom perception. Symptoms occur in response to cognitive and affective factors that trigger fear of symptoms or lack of acceptance of disease, or from stressors in the external environment. Among the many dietary interventions used to treat patients with IBS, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols is the most commonly recommended by health care providers and has the most evidence for efficacy. Patient with IBS who choose to follow a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols should be aware of its 3 phases: restriction, reintroduction, and personalization. Management of IBS should include an integrated care model in which behavioral interventions, dietary modification, and medications are considered as equal partners. This approach offers the greatest likelihood for success in management of patients with IBS.
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Affiliation(s)
- William D Chey
- Division of Gastroenterology, Michigan Medicine, Ann Arbor, Michigan.
| | | | - Kevin Whelan
- Department of Nutritional Sciences, King's College London, London, United Kingdom
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Milan AM, Shrestha A, Karlström HJ, Martinsson JA, Nilsson NJ, Perry JK, Day L, Barnett MPG, Cameron-Smith D. Comparison of the impact of bovine milk β-casein variants on digestive comfort in females self-reporting dairy intolerance: a randomized controlled trial. Am J Clin Nutr 2020; 111:149-160. [PMID: 31773165 DOI: 10.1093/ajcn/nqz279] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 10/16/2019] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Lactose malabsorption (LM) is a major cause of digestive discomfort from dairy products. Recently, a role for bovine β-casein A1 has been proposed. OBJECTIVES We examined whether there are distinct symptoms of digestive discomfort due to either lactose or differing bovine β-casein types. METHODS Women (n = 40; age: 25.2 ± 0.5 y) with self-reported varying dairy tolerance underwent a 50-g lactose challenge. Based on postchallenge LM and digestive discomfort, participants were classified as either lactose intolerant (LI; n = 10, self-reported intolerant, diagnosed lactose intolerant), nonlactose dairy intolerant (NLDI; n = 20, self-reported intolerant, diagnosed lactose tolerant), or dairy tolerant (DT; n = 10, self-reported tolerant, diagnosed lactose tolerant). In a double-blinded randomized sequence, participants consumed 750 mL conventional milk (CON; containing A1 and A2 β-casein and lactose), a2 Milk (A2M; exclusively containing A2 β-casein with lactose), or lactose-free conventional milk (LF-CON; containing A1 and A2 β-casein without lactose). Subjective digestive symptoms and breath hydrogen (measuring LM) were recorded regularly over 3 h, and further ad hoc digestive symptoms over 12 h. RESULTS LI subjects experienced prolonged digestive discomfort with CON milk. A2M reduced (P < 0.05) some symptoms (nausea: A2M 8 ± 3 mm compared with CON 15 ± 3mm; fecal urgency: A2M 4 ± 1 compared with CON 10 ± 3 mm), and attenuated the rise in breath hydrogen over 3 h, relative to CON milk (A2M 59 ± 23 compared with CON 98 ± 25 ppm at 150 min; P < 0.01). In contrast, NLDI subjects experienced rapid-onset, transient symptoms (abdominal distension, bloating, and flatulence) without increased breath hydrogen, irrespective of milk type. CONCLUSIONS In LI individuals, LM and digestive comfort with lactose-containing milks was improved with milk containing exclusively A2 β-casein. Furthermore, self-reported dairy intolerance without LM (NLDI) is characterized by early-onset digestive discomfort following milk ingestion, irrespective of lactose content or β-casein type. This trial was registered at www.anzctr.org.au as ACTRN12616001694404.
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Affiliation(s)
- Amber M Milan
- The Liggins Institute, The University of Auckland, Auckland, New Zealand
| | - Aahana Shrestha
- The Liggins Institute, The University of Auckland, Auckland, New Zealand
| | | | | | | | - Jo K Perry
- The Liggins Institute, The University of Auckland, Auckland, New Zealand
| | - Li Day
- AgResearch Limited, Grasslands Research Centre, Palmerston North, New Zealand
| | - Matthew P G Barnett
- AgResearch Limited, Grasslands Research Centre, Palmerston North, New Zealand
- Riddet Institute, Palmerston North, New Zealand
- The High-Value Nutrition National Science Challenge, Auckland, New Zealand
| | - David Cameron-Smith
- The Liggins Institute, The University of Auckland, Auckland, New Zealand
- AgResearch Limited, Grasslands Research Centre, Palmerston North, New Zealand
- Riddet Institute, Palmerston North, New Zealand
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Steudle J, Schön C, Wargenau M, Pauly L, Schwejda-Güttes S, Gaigg B, Kuchinka-Koch A, Stover JF. Blood glucose response after oral intake of lactulose in healthy volunteers: A randomized, controlled, cross-over study. World J Gastrointest Pharmacol Ther 2018; 9:22-30. [PMID: 30090645 PMCID: PMC6081387 DOI: 10.4292/wjgpt.v9.i3.22] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Revised: 07/03/2018] [Accepted: 07/16/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate possible changes of blood glucose levels after oral intake of lactulose in healthy subjects.
METHODS The study was performed as prospective, randomized, two-part study with 4-way cross-over design with n = 12 in each study arm. Capillary blood glucose levels were determined over a time period of 180 min after intake of a single dose of 10 g or 20 g lactulose provided as crystal or liquid formulation. During the manufacturing process of lactulose, impurities with sugars (e.g., lactose, fructose, galactose) occur. Water and 20 g glucose were used as control and reference. Because lactulose is used as a functional food ingredient, it may also be consumed by people with impaired glucose tolerance, including diabetics. Therefore, it is of interest to determine whether the described carbohydrate impurities may increase blood glucose levels after ingestion.
RESULTS The blood glucose concentration-time curves after intake of 10 g lactulose, 20 g lactulose, and water were almost identical. None of the three applications showed any changes in blood glucose levels. After intake of 20 g glucose, blood glucose concentration increased by approximately 3 mmol/L (mean Cmax = 8.3 mmol/L), reaching maximum levels after approximately 30 min and returning to baseline within approximately 90 min, which was significantly different to the corresponding 20 g lactulose formulations (P < 0.0001). Comparing the two lactulose formulations, crystals and liquid, in the dosage of 10 g and 20 g, there was no difference in the blood glucose profile and calculated pharmacokinetic parameters despite the different amounts of carbohydrate impurities (1.5% for crystals and 26.45% for liquid). Anyhow, the absolute amount of single sugars was low with 0.3 g in crystals and 5.29 g in liquid formulation in the 20 g dosages. Lactulose was well tolerated by most volunteers, and only some reported mild to moderate mainly gastrointestinal side effects.
CONCLUSION The unchanged blood glucose levels after lactulose intake in healthy subjects suggest its safe use in subjects with impaired glucose tolerance.
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Affiliation(s)
| | | | - Manfred Wargenau
- M.A.R.C.O. GmbH and Co. KG, Institute for Clinical Research and Statistics, Düsseldorf 40211, Germany
| | - Lioba Pauly
- Fresenius Kabi Deutschland GmbH, Oberursel 61440, Germany
| | | | | | | | - John F Stover
- Fresenius Kabi Deutschland GmbH, Oberursel 61440, Germany
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Abstract
It has long been known that many short-chain carbohydrates can induce abdominal symptoms that are similar to those in patients with irritable bowel syndrome (IBS). It was hypothesized that restricting the intake of all short-chain carbohydrates that are either slowly absorbed or not digested in the small intestine should be considered together because they all have similar effects on the intestine by distending the lumen. These groups of carbohydrates were called, Fermentable, Oligosaccharides, Disaccharides and Monosaccharides and Polyols (FODMAPs), because of the lack of a known collective term. By reducing their dietary intake, it was also hypothesized that abdominal symptoms in patients with IBS would be alleviated in patients with visceral sensitivity and a low FODMAP diet was subsequently designed. Over the last 12 years, the mechanisms of action, food content of FODMAPs and efficacy of the diet, among other aspects have been intensively studied. In many parts of the world, the low FODMAP diet is now considered a front-line therapy for IBS.
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Affiliation(s)
- Peter R Gibson
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Australia
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6
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Paajanen L, Tuure T, Korpela R. Impaired tolerance of indigestible carbohydrates in adults with subjective milk intolerance. ACTA ACUST UNITED AC 2016. [DOI: 10.1080/11026480410000463] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Affiliation(s)
- L. Paajanen
- Foundation for Nutrition Research, Helsinki
- Department of Allergy, Helsinki University Central Hospital, Helsinki
| | - T. Tuure
- Valio Ltd, Research and Development, Helsinki
| | - R. Korpela
- Foundation for Nutrition Research, Helsinki
- Valio Ltd, Research and Development, Helsinki
- Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland
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7
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Scientific Opinion on the substantiation of a health claim related to non digestible carbohydrates and a reduction of post prandial glycaemic responses pursuant to Article 13(5) of Regulation (EC) No 1924/2006. EFSA J 2014. [DOI: 10.2903/j.efsa.2014.3513] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
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Abstract
Carbohydrates occur across a range of foods regularly consumed including grains such as wheat and rye, vegetables, fruits, and legumes. Short-chain carbohydrates with chains of up to 10 sugars vary in their digestibility and subsequent absorption. Those that are poorly absorbed exert osmotic effects in the intestinal lumen increasing its water volume, and are rapidly fermented by bacteria with consequent gas production. These two effects alone may underlie most of the induction of gastrointestinal symptoms after they are ingested in moderate amounts via luminal distension in patients with visceral hypersensitivity. This has been the basis of the use of lactose-free diets in those with lactose malabsorption and of fructose-reduced diets for fructose malabsorption. However, application of such dietary approaches in patients with functional bowel disorders has been restricted to observational studies with uncertain efficacy. As all dietary poorly absorbed short-chain carbohydrates have similar and additive effects in the intestine, a concept has been developed to regard them collectively as FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) and to evaluate a dietary approach that restricts them all. In patients with irritable bowel syndrome, there is now an accumulating body of evidence, based on observational and comparative studies, and on randomized-controlled trials that supports the notion that FODMAPs trigger gastrointestinal symptoms in patients with functional bowel disorders, and that a diet low in FODMAPs offers considerable symptom relief in the majority of patients who use it.
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Gibson PR, Shepherd SJ. Evidence-based dietary management of functional gastrointestinal symptoms: The FODMAP approach. J Gastroenterol Hepatol 2010; 25:252-8. [PMID: 20136989 DOI: 10.1111/j.1440-1746.2009.06149.x] [Citation(s) in RCA: 392] [Impact Index Per Article: 26.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIM Functional gastrointestinal symptoms are common and their management is often a difficult clinical problem. The link between food intake and symptom induction is recognized. This review aims to describe the evidence base for restricting rapidly fermentable, short-chain carbohydrates (FODMAPs) in controlling such symptoms. METHODS The nature of FODMAPs, their mode of action in symptom induction, results of clinical trials and the implementation of the diet are described. RESULTS FODMAPs are widespread in the diet and comprise a monosaccharide (fructose), a disaccharide (lactose), oligosaccharides (fructans and galactans), and polyols. Their ingestion increases delivery of readily fermentable substrate and water to the distal small intestine and proximal colon, which are likely to induce luminal distension and induction of functional gut symptoms. The restriction of their intake globally (as opposed to individually) reduces functional gut symptoms, an effect that is durable and can be reversed by their reintroduction into the diet (as shown by a randomized placebo-controlled trial). The diet has a high compliance rate. However it requires expert delivery by a dietitian trained in the diet. Breath hydrogen tests are useful to identify individuals who can completely absorb a load of fructose and lactose so that dietary restriction can be less stringent. CONCLUSIONS The low FODMAP diet provides an effective approach to the management of patients with functional gut symptoms. The evidence base is now sufficiently strong to recommend its widespread application.
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Affiliation(s)
- Peter R Gibson
- Monash University Department of Medicine, Box Hill Hospital, Box Hill, Victoria, Australia.
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10
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Lejeune JT, Rajala-Schultz PJ. Food safety: unpasteurized milk: a continued public health threat. Clin Infect Dis 2009; 48:93-100. [PMID: 19053805 DOI: 10.1086/595007] [Citation(s) in RCA: 135] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Although milk and dairy products are important components of a healthy diet, if consumed unpasteurized, they also can present a health hazard due to possible contamination with pathogenic bacteria. These bacteria can originate even from clinically healthy animals from which milk is derived or from environmental contamination occurring during collection and storage of milk. The decreased frequency of bovine carriage of certain zoonotic pathogens and improved milking hygiene have contributed considerably to decreased contamination of milk but have not, and cannot, fully eliminate the risk of milkborne disease. Pasteurization is the most effective method of enhancing the microbiological safety of milk. The consumption of milk that is not pasteurized increases the risk of contracting disease from a foodstuff that is otherwise very nutritious and healthy. Despite concerns to the contrary, pasteurization does not change the nutritional value of milk. Understanding the science behind this controversial and highly debated topic will provide public health care workers the information needed to discern fact from fiction and will provide a tool to enhance communication with clients in an effort to reduce the incidence of infections associated with the consumption of unpasteurized milk and dairy products.
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Affiliation(s)
- Jeffrey T Lejeune
- Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, Ohio 44691, USA.
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Seppo L, Tuure T, Korpela R, Järvelä I, Rasinperä H, Sahi T. Can primary hypolactasia manifest itself after the age of 20 years? A two-decade follow-up study. Scand J Gastroenterol 2008; 43:1082-7. [PMID: 18609167 DOI: 10.1080/00365520802095485] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The age at manifestation of primary hypolactasia varies between ethnic groups. Many people report experiencing the first symptoms of lactose intolerance at adult age. The purpose of this study was to investigate whether primary hypolactasia can appear after the age of 20 among the Finnish population and to investigate the outcome of different diagnostic methods of lactose maldigestion. MATERIAL AND METHODS Lactose digestion status was assessed by the lactose tolerance test with ethanol (LTTE) in 42 subjects (38-71 years) who reported having gastrointestinal symptoms after the ingestion of 20 g or less of lactose and who were diagnosed as lactose digesters in earlier studies. Thirteen of the study subjects underwent upper gastrointestinal endoscopy, and 35 gave a blood sample for DNA analysis. RESULTS Only one of the 42 subjects studied had the genotype C/C(-13910) indicating hypolactasia. Lactase activity was higher in those with the genotype T/T (69.2 U/g protein) than in those with the heterozygous genotype C/T (36.3 U/g protein) (p=0.017). CONCLUSIONS Although primary hypolactasia normally appears before the age of 20 years, the decline in lactase activity may on rare occasions continue after that age. Genotyping of the C/T(-13910) variant was found to be a reliable diagnostic approach in defining the lactase persistence/non-persistence status of the study subjects.
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Gibson PR, Newnham E, Barrett JS, Shepherd SJ, Muir JG. Review article: fructose malabsorption and the bigger picture. Aliment Pharmacol Ther 2007; 25:349-63. [PMID: 17217453 DOI: 10.1111/j.1365-2036.2006.03186.x] [Citation(s) in RCA: 154] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Fructose is found widely in the diet as a free hexose, as the disaccharide, sucrose and in a polymerized form (fructans). Free fructose has limited absorption in the small intestine, with up to one half of the population unable to completely absorb a load of 25 g. Average daily intake of fructose varies from 11 to 54 g around the world. Fructans are not hydrolysed or absorbed in the small intestine. The physiological consequences of their malabsorption include increasing osmotic load, providing substrate for rapid bacterial fermentation, changing gastrointestinal motility, promoting mucosal biofilm and altering the profile of bacteria. These effects are additive with other short-chain poorly absorbed carbohydrates such as sorbitol. The clinical significance of these events depends upon the response of the bowel to such changes; they have a higher chance of inducing symptoms in patients with functional gut disorders than asymptomatic subjects. Restricting dietary intake of free fructose and/or fructans may have durable symptomatic benefits in a high proportion of patients with functional gut disorders, but high quality evidence is lacking. It is proposed that confusion over the clinical relevance of fructose malabsorption may be reduced by regarding it not as an abnormality but as a physiological process offering an opportunity to improve functional gastrointestinal symptoms by dietary change.
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Affiliation(s)
- P R Gibson
- Department of Gastroenterology and Monash University Department of Medicine, Box Hill Hospital, Victoria, Australia.
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13
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Fructose malabsorption and symptoms of irritable bowel syndrome: guidelines for effective dietary management. ACTA ACUST UNITED AC 2006; 106:1631-9. [PMID: 17000196 DOI: 10.1016/j.jada.2006.07.010] [Citation(s) in RCA: 255] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2004] [Indexed: 02/07/2023]
Abstract
Dietary fructose induces abdominal symptoms in patients with fructose malabsorption, but there are no published guidelines on its dietary management. The objective was to retrospectively evaluate a potentially successful diet therapy in patients with irritable bowel syndrome and fructose malabsorption. Tables detailing the content of fructose and fructans in foods were constructed. A dietary strategy comprising avoidance of foods containing substantial free fructose and short-chain fructans, limitation of the total dietary fructose load, encouragement of foods in which glucose was balanced with fructose, and co-ingestion of free glucose to balance excess free fructose was devised. Sixty-two consecutively referred patients with irritable bowel syndrome and fructose malabsorption on breath hydrogen testing underwent dietary instruction. Dietary adherence and effect on abdominal symptoms were evaluated via telephone interview 2 to 40 months (median 14 months) later. Response to the diet was defined as improvement of all symptoms by at least 5 points on a -10- to 10-point scale. Forty-eight patients (77%) adhered to the diet always or frequently. Forty-six (74%) of all patients responded positively in all abdominal symptoms. Positive response overall was significantly better in those adherent than nonadherent (85% vs 36%; P<0.01), as was improvement in individual symptoms (P<0.01 for all symptoms). This comprehensive fructose malabsorption dietary therapy achieves a high level of sustained adherence and good symptomatic response.
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Savaiano DA, Boushey CJ, McCabe GP. Lactose intolerance symptoms assessed by meta-analysis: a grain of truth that leads to exaggeration. J Nutr 2006; 136:1107-13. [PMID: 16549489 DOI: 10.1093/jn/136.4.1107] [Citation(s) in RCA: 76] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
A meta-analysis was conducted to compare the lactose intolerance symptoms of lactose maldigesters after consuming lactose (as milk, lactose dissolved in water, milk products, or commercial product) with responses after a placebo under masked conditions. An English language MEDLINE search was conducted using the medical subject heading of "lactose intolerance" from 1966 to January 2002. From an initial 1,553 citations, 2 independent reviewers selected 21 studies based on study design (randomized, crossover, blind) and use of an amount of lactose likely to be found in a meal (7-25 g) and a placebo among subjects free of gastrointestinal problems and >4 years old. Mean severity of symptom responses were analyzed as standardized differences, and the presence or absence of a symptom was estimated as pooled incidence differences (ID). For severity of flatulence, the standardized difference was 0.18 (95% confidence interval [CI] -0.16 to +0.52). The CIs for abdominal bloating and pain, degree of diarrhea, frequency of bowel movements per day, and frequency of diarrhea per day also included 0. For abdominal bloating, the ID was 5.9 more people per 100 with symptoms after lactose than placebo (CI -0.07 to +0.19). This same nonsignificant relationship was found for abdominal pain. The ID for diarrhea or loose stools was 0.15 (CI 0.03 to 0.28). Although the incidence of diarrhea was significantly higher, the size of the effect was very small. The results indicate that lactose is not a major cause of symptoms for lactose maldigesters following usual intakes of dairy foods, that is, 1 cup.
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Affiliation(s)
- Dennis A Savaiano
- Department of Foods and Nutrition, Purdue University, West Lafayette, Indiana, USA.
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Fernández-Bañares F, Rosinach M, Esteve M, Forné M, Espinós JC, Maria Viver J. Sugar malabsorption in functional abdominal bloating: a pilot study on the long-term effect of dietary treatment. Clin Nutr 2006; 25:824-31. [PMID: 16410032 DOI: 10.1016/j.clnu.2005.11.010] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2005] [Accepted: 11/17/2005] [Indexed: 02/07/2023]
Abstract
BACKGROUND Functional abdominal bloating is a functional bowel disorder dominated by a feeling of abdominal fullness without sufficient criteria for another functional gastrointestinal disorder. Gas-related complaints (i.e., passage of flatus), which are present in a subgroup of these patients, might be associated with carbohydrate malabsorption. AIM To evaluate the presence of lactose and/or fructose plus sorbitol malabsorption, and the long-term efficacy of malabsorbed sugar-free diets, in patients with Rome II criteria of functional abdominal bloating and gas-related symptoms. METHODS Thirty-six consecutive patients (age, 51+/-3.1 years; sex, 12 M, 24 W) with Rome II criteria of functional abdominal bloating and gas-related symptoms were included in a pilot study. In all cases, the presence of malabsorption of both lactose (20 g) and fructose plus sorbitol (20+3.5 g) was assessed by means of hydrogen breath test. Patients with sugar malabsorption were put on a malabsorbed sugar-free diet. Follow-up visits were scheduled at both 1 and 12 months after starting the diet. Global rating scales of change as compared to the beginning of the study were used to assess symptom changes. RESULTS Twenty-six of 36 patients (72.2%) presented sugar malabsorption (six lactose, 12 fructose plus sorbitol, and eight both). Seventeen of the 26 (65%) patients with malabsorption had symptoms of sugar intolerance during the 3-h breath testing period. All 26 were put on malabsorbed sugar-free diets. Eighty-one per cent of patients referred clinical improvement at 1-month visit, which was maintained at 12 months in 67% of them (complete improvement in 50% and partial improvement in 16.7%). CONCLUSIONS Sugar malabsorption and intolerance seem to be frequent in patients with functional abdominal bloating and gas-related complaints. A malabsorbed sugar-free diet might be a long-term effective therapy in a high percentage of patients. Further controlled clinical trials are warranted.
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Affiliation(s)
- Fernando Fernández-Bañares
- Department of Gastroenterology, Hospital Universitari Mutua Terrassa, Plaza Dr Robert 5, 08221 Terrassa, Barcelona, Spain.
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Marteau A, Marteau P. Entre intolérance au lactose et maldigestion. CAHIERS DE NUTRITION ET DE DIETETIQUE 2005. [DOI: 10.1016/s0007-9960(05)80203-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Abstract
The clinical efficacy of probiotics and prebiotics has been proved in several clinical settings. The authors review their proved or potential side effects. Probiotics as living microorganisms may theoretically be responsible for 4 types of side effects in susceptible individuals: infections, deleterious metabolic activities, excessive immune stimulation, and gene transfer. Very few cases of infection have been observed. These occurred mainly in very sick patients who received probiotic drugs because of severe medical conditions. Prebiotics exert an osmotic effect in the intestinal lumen and are fermented in the colon. They may induce gaseousness and bloating. Abdominal pain and diarrhea only occur with large doses. An increase in gastroesophageal reflux has recently been associated with large daily doses. Tolerance depends on the dose and individual sensitivity factors (probably the presence of irritable bowel syndrome or gastroesophageal reflux), and may be an adaptation to chronic consumption.
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Affiliation(s)
- Philippe Marteau
- Gastroenterology Department, European Hospital Georges Pompidou, Assistance Publique des Hôpitaux de Paris and Paris V University, France.
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Oku T, Nakamura S. Comparison of digestibility and breath hydrogen gas excretion of fructo-oligosaccharide, galactosyl-sucrose, and isomalto-oligosaccharide in healthy human subjects. Eur J Clin Nutr 2003; 57:1150-6. [PMID: 12947435 DOI: 10.1038/sj.ejcn.1601666] [Citation(s) in RCA: 59] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
OBJECTIVES To clarify the difference of digestibility in the small intestine among fructo-oligosaccharide (FOS), galactosyl-sucrose (GS), and isomalto-oligosaccharide (IMO) using breath hydrogen test. DESIGN The first step: screening test of breath hydrogen excretion and FOS tolerance test to select the subjects. The second step: breath hydrogen test of three kinds of oligosaccharides, carried out using precautionary regulations. The ingestion order was 10 g of FOS, GS, and IMO, with increases, at 1-week interval, up to 20 g, respectively. Breath gas was collected before, at 20 min intervals from 40 to 120 min after, and at 30 min intervals from 120 min to 7 h after ingestion of test substance. SETTING Laboratory of Public Health Nutrition, Department of Nutrition and Health Sciences, Siebold University of Nagasaki, Nagasaki, Japan. SUBJECTS A total of nine males (average: age 25.7+/-3.5 y, weight 61.9+/-8.8 kg, height 170.0+/-6.0 cm) and 29 females (average: 23.1+/-7.2 y, 52.9+/-5.3 kg, 157.5+/-5.1 cm) from the University of Tokyo and Siebold University of Nagasaki. MAIN OUTCOME MEASURES Breath hydrogen excretion from end-expiratory gas. RESULT : Breath hydrogen of FOS was more remarkably excreted than that of GS; that of IMO was slight; and that of AUC (10 g) was significantly different. FOS was 9768+/-3253 ppm, GS was 3662+/-2632 ppm, and IMO was 831+/-1154 ppm. A dose dependence was observed at doses between 10 and 20 g of FOS and GS, and the initial time of 20 g was earlier than that of 10 g. CONCLUSIONS FOS was not hydrolyzed, GS was slightly hydrolyzed, and IMO was readily hydrolyzed by small intestinal enzymes. H(2) gas reflected fermentability in the large intestine. SPONSORSHIP Siebold University of Nagasaki.
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Affiliation(s)
- T Oku
- Department of Nutrition and Health Sciences, Siebold University of Nagasaki, Nagasaki, Japan.
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Abstract
Lactose maldigestion, which affects a large majority of the world's population, has been mostly linked with uncomfortable symptoms. In addition, dairy consumption is variably blamed or recommended for a number of ill effects. There is, however, emerging evidence that certain lactic acid-producing bacteria, which selectively consume prebiotics, may be beneficial against some lower intestinal diseases. Lactose maldigestion and lactose should perhaps be re-evaluated as a potential provider of such a prebiotic. This historical and observational review discusses lactose and argues the opinion that it has prebiotic potential. Moreover, in maldigesters, natural ingestion or lack thereof may be relevant in the pathogenesis of diseases such as colorectal cancer and inflammatory bowel diseases.
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Affiliation(s)
- A Szilagyi
- McGill University, School of Medicine, Division of Gastroenterology, Department of Medcine, The Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada.
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Boeckner LS, Schnepf MI, Tungland BC. Inulin: a review of nutritional and health implications. ADVANCES IN FOOD AND NUTRITION RESEARCH 2001; 43:1-63. [PMID: 11285681 DOI: 10.1016/s1043-4526(01)43002-6] [Citation(s) in RCA: 45] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- L S Boeckner
- Panhandle Research and Extension Center, University of Nebraska, Scottsbluff, NE 69361, USA
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21
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Marteau P, Flourié B. Tolerance to low-digestible carbohydrates: symptomatology and methods. Br J Nutr 2001; 85 Suppl 1:S17-21. [PMID: 11321024 DOI: 10.1079/bjn2000258] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Low-digestible carbohydrates (LDCs) are incompletely or not absorbed in the small bowel and fermented in the colon. They are usually well tolerated but may also have some dose-related undesirable effects due to their natural osmotic potential and/or excessive fermentation: borborygmi, excessive flatus, bloating, abdominal cramps and eventually diarrhoea. There is an important intersubject variability in the tolerance to LDCs because of differences in absorption capacity, motility pattern, colonic response and intestinal sensitivity. There is also a great intrasubject variability, depending on the type of LDC, dosage and type of consumption. Absorption of LDC in the small intestine can be assessed using hydrogen breath test or intubation techniques or analysis of ileostomy effluents. Double-blind, placebo-controlled studies are required to assess the subjective symptoms of intolerance, and the experimental conditions may influence the results.
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Affiliation(s)
- P Marteau
- Gastroenterology Department, European Hospital Georges Pompidou, Paris, France.
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Olesen M, Gudmand-Hoyer E. Efficacy, safety, and tolerability of fructooligosaccharides in the treatment of irritable bowel syndrome. Am J Clin Nutr 2000; 72:1570-5. [PMID: 11101487 DOI: 10.1093/ajcn/72.6.1570] [Citation(s) in RCA: 84] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Interest in fructooligosaccharides as a health-promoting food component is increasing. Fructooligosaccharides are mainly indigestible and large amounts in the colon may provoke gastrointestinal symptoms. OBJECTIVE The symptoms of irritable bowel syndrome (IBS) may be provoked by large quantities of carbohydrates in the colon. The objective of this study was to determine whether regular consumption of fructooligosaccharides worsens gastrointestinal symptoms in patients with IBS. DESIGN A multicenter, prospective, randomized, double-blind, placebo-controlled parallel group comparison was conducted at 24 sites. The study consisted of a 2-wk, single-blind run-in phase and a 12-wk, double-blind comparative phase. Subjects were randomly assigned to receive 20 g fructooligosaccharides powder/d (n = 52) or a placebo (n = 46). Efficacy was based on the patients' overall response to treatment at completion of the study and on the severity and duration of individual symptoms (abdominal distension, abdominal rumbling, abnormal flatulence, and abdominal pain). RESULTS Data from 96 patients (16 men and 80 women) were analyzed. After 4-6 wk of treatment, IBS symptoms improved more in the placebo group than in the fructooligosaccharide group. After completion of the study, there were no significant differences between the 2 groups: symptoms improved in 58% of the fructooligosaccharide group and in 65% of the placebo group and symptoms worsened in 8% of the fructooligosaccharide group and in 13% of the placebo group. CONCLUSION Although symptoms worsened in patients with IBS at the onset of treatment with 20 g fructooligosaccharides/d, continuous treatment for 12 wk resulted in no worsening of symptoms.
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Affiliation(s)
- M Olesen
- Department of Medical Gastroenterology F, Copenhagen County Hospital, Hellerup, Denmark.
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Abstract
Lactose maldigestion has been under intensive research since its discovery in the 1960's. We know the prevalence of lactose maldigestion in a great number of countries and ethnic groups. However, there is often no provision made for the secondary type of maldigestion, and the study populations have sometimes been selected rather than picked at random. New methods for the measurement of lactose digestion have been developed, and its genetic mechanisms have received a great deal of attention during the last few years. However, in many studies the measurement and/or reporting of symptoms has quite often been overlooked. In this review, various topics related to lactose intolerance are discussed with a special emphasis on its symptoms.
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Affiliation(s)
- T H Vesa
- Foundation for Nutrition Research, Helsinki, Finland
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Peuhkuri K, Vapaatalo H, Korpela R, Teuri U. Lactose intolerance-a confusing clinical diagnosis. Am J Clin Nutr 2000; 71:600-2. [PMID: 10648279 DOI: 10.1093/ajcn/71.2.600] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
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Peuhkuri K, Nevala R, Vapaatalo H, Moilanen E, Korpela R. Ibuprofen augments gastrointestinal symptoms in lactose maldigesters during a lactose tolerance test. Aliment Pharmacol Ther 1999; 13:1227-33. [PMID: 10468706 DOI: 10.1046/j.1365-2036.1999.00608.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Clinical symptoms during lactose tolerance test mimic those seen after therapeutic administration of prostaglandins, and resemble inflammatory processes. AIM To investigate the possibility that lactose-induced gastrointestinal symptoms are associated with prostaglandins and/or nitric oxide. METHODS After an overnight fast, nine maldigesters ingested lactose or sucrose with or without an inhibitor of prostaglandin synthesis (ibuprofen), in a randomised double-blind crossover trial. Gastrointestinal symptoms, concentrations of PGE2-M in blood and urine, and urinary 6-keto PGF1alpha (as indicators of prostaglandin synthesis), and urinary nitrate and nitrite as well as cyclic GMP excretions (as indicators of nitric oxide formation), were measured. RESULTS Ibuprofen increased the first 3-h symptom scores (flatulence + borborygmi + abdominal bloating + pain) caused by lactose (P=0.008) but not sucrose. The concentrations of PGE2-M in the plasma and in the urine were unaffected. Lactose increased the urinary excretion of 6-keto PGF1alpha by about 30% (P=0.17), which was inhibited by ibuprofen (P=0.02). The production of nitric oxide was unaffected by lactose or ibuprofen. CONCLUSION The inhibition of prostaglandin synthesis intensified gastrointestinal symptoms in lactose maldigesters, suggesting a negligible role for prostanoids in lactose-induced symptoms.
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Affiliation(s)
- K Peuhkuri
- Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki, Finland
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