Carbohydrate Maldigestion Research Articles

S1817 Symptoms of Bloating Are Poor Predictors of Carbohydrate Maldigestion

S1817 Symptoms of Bloating Are Poor Predictors of Carbohydrate Maldigestion

Nonallergic Diseases Associated With Foods

Clinicians are faced with evaluating real and alleged reactions to foods that may be allergic or nonallergic. Pathogenesis, diagnosis, and treatment of various non-IgE-mediated diseases are discussed in this review. These food-related conditions range from mild to severe. Referral for an allergy workup may be pursued despite the lack of IgE-mediated symptoms. Diagnostic testing is available for defined non-IgE-mediated food diseases that are either immunologic or nonimmunologic. These include celiac disease and related disorders, carbohydrate maldigestion, pancreatic insufficiency, and histamine intolerance. In contrast, there is a paucity of definitive studies to prove food intolerance diseases. There are no definitive diagnostic criteria or testing for nonceliac gluten sensitivity. Functional gastrointestinal disorders, such as irritable bowel syndrome, are better stratified diagnostically but still lack reliable testing. Both nonceliac gluten sensitivity and irritable bowel syndrome are linked to dietary triggers including fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. Therefore, dietary alteration alone may be diagnostic and therapeutic when all other conditions are ruled out. These conditions are important considerations when evaluating a patient with history of a food reaction. There is little evidence that foods are causative in other ailments such as acne, migraines, and nasal congestion and hypersecretion.

Carbohydrate Maldigestion and Intolerance.

This review summarizes dietary carbohydrate intolerance conditions and recent advances on the possible role of carbohydrate maldigestion and dietary outcomes in patients with functional bowel disease. When malabsorbed carbohydrates reach the colon, they are fermented by colonic bacteria, with the production of short-chain fatty acids and gas lowering colonic pH. The appearance of diarrhoea or symptoms of flatulence depends in part on the balance between the production and elimination of these fermentation products. Different studies have shown that there are no differences in the frequency of sugar malabsorption between patients with irritable bowel disease (IBS) and healthy controls; however, the severity of symptoms after a sugar challenge is higher in patients than in controls. A diet low in ‘Fermentable, Oligo-Di- and Monosaccharides and Polyols’ (FODMAPs) is an effective treatment for global symptoms and abdominal pain in IBS, but its implementation should be supervised by a trained dietitian. A ‘bottom-up’ approach to the low-FODMAP diet has been suggested to avoid an alteration of gut microbiota and nutritional status. Two approaches have been suggested in this regard: starting with only certain subgroups of the low-FODMAP diet based on dietary history or with a gluten-free diet.

Routine disaccharidase testing: are we there yet?

Disaccharidase testing, as applied to the evaluation of gastrointestinal disturbances is available but it is not routinely considered in the diagnostic work-up. The purpose of this review was to determine if disaccharidase testing is clinically useful and to consider how the results could alter patient management. Indicate that carbohydrate maldigestion could contribute functional bowel disorders and negatively impact the fecal microbiome. Diagnostic techniques include enzyme activity assays performed on random endoscopically obtained small intestinal biopsies, immunohistochemistry, stable isotope tracer and nonenriched substrate load breath testing, and genetic testing for mutations. More than 40 sucrase--isomaltase gene variants coding for defective or reduced enzymatic activity have been reported and deficiency conditions are more common than previously thought. The rationale for disaccharidase activity testing relates to a need to fully assess unexplained recurrent abdominal discomfort and associated symptoms. All disaccharidases share the same basic mechanism of mucosal expression and deficiency has far reaching consequences. Testing for disaccharidase expression appears to have an important role in symptom evaluation, but there are accuracy and logistical issues that should be considered. It is likely that specific recommendations for patient management, dietary modification, and enzyme supplementation would come from better testing methods.

Heterozygotes Are a Potential New Entity among Homozygotes and Compound Heterozygotes in Congenital Sucrase-Isomaltase Deficiency.

Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive disorder of carbohydrate maldigestion and malabsorption caused by mutations in the sucrase-isomaltase (SI) gene. SI, together with maltase-glucoamylase (MGAM), belongs to the enzyme family of disaccharidases required for breakdown of α-glycosidic linkages in the small intestine. The effects of homozygote and compound heterozygote inheritance trait of SI mutations in CSID patients have been well described in former studies. Here we propose the inclusion of heterozygote mutation carriers as a new entity in CSID, possibly presenting with milder symptoms. The hypothesis is supported by recent observations of heterozygote mutation carriers among patients suffering from CSID or patients diagnosed with functional gastrointestinal disorders. Recent studies implicate significant phenotypic heterogeneity depending on the character of the mutation and call for more research regarding the correlation of genetics, function at the cellular and molecular level and clinical presentation. The increased importance of SI gene variants in irritable bowel syndrome (IBS) or other functional gastrointestinal disorders FGIDs and their available symptom relief diets like fermentable oligo-, di-, mono-saccharides and polyols FODMAPs suggest that the heterozygote mutants may affect the disease development and treatment.

Posttranslational Processing and Function of Mucosal Maltases.

The final step of carbohydrate digestion in the intestine is performed by 2 major α-glucosidases of the intestinal mucosa, sucrase-isomaltase (SI) and maltase-glucoamylase. Both of these enzymes are type II membrane glycoproteins, which share a significant level of homology in gene and protein structures and yet have differences in the posttranslational processing, substrate specificity and functional capacity. Insufficient activity of these disaccharidases particularly SI as a result of genetic mutations or secondary intestinal pathologies is associated with carbohydrate maldigestion and gastrointestinal intolerances. This review will discuss the maturation profiles of SI and maltase-glucoamylase relative to their functional capacities and deficiencies.

Carbohydrate Maldigestion and Malabsorption

Carbohydrate Maldigestion and Malabsorption

Low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet improves symptoms in adults suffering from irritable bowel syndrome (IBS) compared to standard IBS diet: A meta-analysis of clinical studies.

BackgroundIrritable bowel syndrome (IBS) and functional digestive tract disorders, e.g. functional bloating, carbohydrate maldigestion and intolerances, are very common disorders frequently causing significant symptoms that challenge health care systems. A low Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols (FODMAP) diet is one of the possible therapeutic approaches for decreasing abdominal symptoms and improving quality of life.ObjectivesWe aimed to meta-analyze data on the therapeutic effect of a low-FODMAP diet on symptoms of IBS and quality of life and compare its effectiveness to a regular, standard IBS diet with high FODMAP content, using a common scoring system, the IBS Symptom Severity Score (IBS-SSS).MethodsA systematic literature search was conducted in PubMed, EMBASE and the Cochrane Library as well as in the references in a recent meta-analysis. Adult patients diagnosed with IBS according to the Rome II, Rome III, Rome IV or NICE criteria were included in the analysis.Statistical methodsMean differences with 95% confidence intervals were calculated from studies that contained means, standard deviation (SD) or mean differences and SD of differences and p-values. A random effect model was used because of the heterogeneity (Q test (χ2) and I2 indicator). A p-value of less than 0.05 was chosen to indicate a significant difference.ResultsThe literature search yielded 902 publications, but only 10 were eligible for our meta-analysis. Both regular and low-FODMAP diets proved to be effective in IBS, but post-diet IBS-SSS values were significantly lower (p = 0.002) in the low-FODMAP group. The low-FODMAP diet showed a correlation with the improvement of general symptoms (by IBS-SSS) in patients with IBS.ConclusionsThis meta-analysis provides high-grade evidence of an improved general symptom score among patients with irritable bowel syndrome who have maintained a low-FODMAP diet compared to those on a traditional IBS diet, therefore showing its superiority to regular IBS dietary therapy. These data suggest that a low-FODMAP diet with dietitian control can be a candidate for first-line therapeutic modality in IBS. Because of a lack of data, well-planned randomized controlled studies are needed to ascertain the correlation between improvement of separate key IBS symptoms and the effect of a low-FODMAP diet.

Macronutrient malabsorption in acute diarrhea: Prevalence and affecting factors

Introduction Diarrhea remains a major problem for communityhealth in Indonesia. More than 25% of children with severe diar-rhea suffer from malabsorption syndrome.Objectives This study aimed to determine the age range of chil-dren with acute diarrhea, the prevalence of macronutrient malab-sorption, and the relationship between age and bacterial infec-tion in macronutrient malabsorption.Methods This was a cross-sectional study, subjects were chil-dren aged 0-59 months with acute diarrhea whose stools wereobtained and examined in the laboratory of GastrohepatologyDivision, Department of Child Health, Cipto Mangunkusumo Hospi-tal, Jakarta from January 2002 to December 2003.Results Children with acute diarrhea were mostly in the agerange of 0-11 months (61%). The prevalence of lactose malab-sorption was 11%, carbohydrate malabsorption was 19%, andfat malabsorption was 51%. Moreover, the age group of 0-11months had a 1.5 times greater possibility of lactose and fatmalabsorption compared to that of 12-59 months. The 12-59 monthsage group had a greater possibility of suffering carbohydratemaldigestion (70%). The group of children who did not sufferfrom bacterial infection had a higher prevalence of lactose mal-absorption (54%), carbohydrate maldigestion (65%), and fatmalabsorption (58%).Conclusions Acute diarrhea occurred more frequently in theage of 0-11 months. There was a significant correlation betweenthe age groups of 0-11 months and 12-59 months in experiencingmacronutrient malabsorption. Lactose malabsorption, carbohy-drate maldigestion, and fat malabsorption were encountered morefrequently in the group that did not have bacterial infection

Long term differential consequences of miglustat therapy on intestinal disaccharidases.

Miglustat is an oral medication for treatment of lysosomal storage diseases such as Gaucher disease type I and Niemann Pick disease type C. In many cases application of Miglustat is associated with symptoms similar to those observed in intestinal carbohydrate malabsorption. Previously, we have demonstrated that intestinal disaccharidases are inhibited immediately by Miglustat in the intestinal lumen. Nevertheless, the multiple functions of Miglustat hypothesize long term effects of Miglustat on intracellular mechanisms, including glycosylation, maturation and trafficking of the intestinal disaccharidases. Our data show that a major long term effect of Miglustat is its interference with N-glycosylation of the proteins in the ER leading to a delay in the trafficking of sucrase-isomaltase. Also association with lipid rafts and plausibly apical targeting of this protein is partly affected in the presence of Miglustat. More drastic is the effect of Miglustat on lactase-phlorizin hydrolase which is partially blocked intracellularly. The de novo synthesized SI and LPH in the presence of Miglustat show reduced functional efficiencies according to altered posttranslational processing of these proteins. However, at physiological concentrations of Miglustat (≤50μM) a major part of the activity of these disaccharidases is found to be still preserved, which puts the charge of the observed carbohydrate maldigestion mostly on the direct inhibition of disaccharidases in the intestinal lumen by Miglustat as the immediate side effect.

Vinegar ingestion at mealtime reduced fasting blood glucose concentrations in healthy adults at risk for type 2 diabetes

This 12-week pilot study examined effects of vinegar on markers of type 2 diabetes in at-risk adults. Participants (n=14) ingested 750mg acetic acid as a vinegar drink or a control pill (40mg acetic acid) twice daily at mealtime. Blood glucose (fasting and 2-h postprandial) was recorded daily. Fasting blood collected at weeks 0 and 12 was analyzed for insulin and glycated hemoglobin. Average change in fasting glucose was reduced in the vinegar group versus control group (−0.91±0.27 versus −0.26±0.17mmol/l) (p=0.05). Average change in 2-h postprandial glucose, insulin and glycated hemoglobin did not vary between groups. Fasting breath hydrogen at week 12 was elevated 19% in the vinegar group versus control group suggesting an increase in colonic fermentation in the vinegar group. These data indicate that vinegar, a simple addition to meals, has antiglycaemic effects in adults at-risk for type 2 diabetes, possibly related to carbohydrate maldigestion.

Miglustat‐induced intestinal carbohydrate malabsorption is due to the inhibition of α‐glucosidases, but not β‐galactosidases

Miglustat is an oral medication that has approved indication for type I Gaucher disease and Niemann pick disease type C. Usually treatment with Miglustat is associated with occurrence of gastrointestinal side effects similar to carbohydrate maldigestion symptoms. Here, we studied the direct influence of Miglustat on the enzymatic function of the major disaccharidases of the intestinal epithelium. Our findings show that an immediate effect of Miglustat is its interference with carbohydrate digestion in the intestinal lumen via reversible inhibition of disaccharidases that cleave α-glycosidically linked carbohydrates. Higher non physiological concentrations of Miglustat can partly affect lactase activity. We further show that the inhibition of the disaccharidases function by Miglustat is mainly competitive and does not occur via alteration of the enzyme folding.

Diagnostic Yield of Testing in Diarrhea Predominant-Irritable Bowel Syndrome

Purpose: The diagnosis of irritable bowel syndrome (IBS) is based on clinical criteria and diagnostic testing is advised only for certain “red flag” alarm or warning signs. Recently, more extensive testing has been advocated for patients with diarrhea predominant-irritable bowel syndrome (D-IBS). This investigation was designed to examine the yield of testing in D-IBS for carbohydrate maldigestion, bacterial overgrowth, celiac sprue, endocrinopathy, and inflammatory bowel disease. Methods: Consecutive patients who were prospectively evaluated and met ROME III criteria for IBS were reviewed for D-IBS, testing, and findings. Results: There were 200 patients who met IBS criteria; 105 had D-IBS. The D-IBS subjects were 15 men and 90 women. Conclusion: 1) Additional testing for D-IBS is not routinely performed. 2) The yield for testing done in D-IBS is low, other than lactose maldigestion which has previously been shown not to alter the course of IBS or its symptoms.Table: Diagnostic yield of testing in diarrhea predominant-irritable bowel syndrome

Functional dyspepsia, H. pylori and post infectious FD

Functional dyspepsia has been defined by Rome III as the presence of one or more chronic dyspepsia symptoms in the absence of any organic, systemic, or metabolic disease that is likely to explain the symptoms. Delayed gastric emptying, antral hypomotility and altered intestinal motility, decreased gastric accommodation, H.pylori infection, enhanced visceral sensitivity, abnormal duodenal sensitivity to acid, carbohydrate maldigestion and psychological factors have all been identified in subgroups of patients with functional dyspepsia. RELATIONSHIP BETWEEN H.PYLORI, FD AND POST INFECTIOUS FD: The relationship between H. pylori infection and functional dyspepsia is controversial. H.pylori infection is present in a minority of patients with FD. Symptoms and abnormalities of function such as gastric emptying have not been consistently shown to be related to H.pylori infection. However, meta-analysis has shown that H.pylori eradication therapy in FD results in a small but statistically significant effect in H.pylori positive FD (relative risk reduction 10%). Guidelines for Helicobacter pylori infection have therefore strongly recommended H.pylori eradication therapy in H.pylori positive FD patients. Post-infectious dyspepsia has been described as a distinct clinical entity, based on a large retrospective study that showed a subset of dyspeptic patients who had a history suggestive of post-infectious dyspepsia. In a prospective study, investigators in Spain have found that development of dyspepsia was increased fivefold at 1 year after acute Salmonella gastroenteritis. In post-infectious FD patients, early satiety, weight loss, nausea, and vomiting are frequently reported together with a higher prevalence of impaired gastric accommodation. More recently, infectious FD has been found to be associated with persisting focal T-cell aggregates, decreased CD4+ cells and increased macrophage counts in the duodenum for several moths after acute infection. This suggests impaired ability of the immune system to terminate the inflammatory response after acute insult. In conclusion, H. pylori infections, as well as other gut infections, have been associated with a subset of FD patients. Treatment of underlying infections can potentially lead to improvement in this group of patients.

Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs

Necrotizing enterocolitis (NEC) remains the most severe gastrointestinal disorder in preterm infants. It is associated with the initiation of enteral nutrition and may be related to immature carbohydrate digestive capacity. We tested the hypothesis that a formula containing maltodextrin vs. a formula containing lactose as the principal source of carbohydrate would predispose preterm pigs to a higher NEC incidence. Cesarean-derived preterm pigs were given total parenteral nutrition for 48 h followed by total enteral nutrition with a lactose-based (n = 11) or maltodextrin-based (n = 11) formula for 36 h. A higher incidence (91% vs. 27%) and severity (score of 3.3 vs. 1.8) of NEC were observed in the maltodextrin than in the lactose group. This higher incidence of NEC in the maltodextrin group was associated with significantly lower activities of lactase, maltase, and aminopeptidase; reduced villus height; transiently reduced in vivo aldohexose uptake; and reduced ex vivo aldohexose uptake capacity in the middle region of the small intestine. Bacterial diversity was low for both diets, but alterations in bacterial composition and luminal concentrations of short-chain fatty acids were observed in the maltodextrin group. In a second study, we quantified net portal absorption of aldohexoses (glucose and galactose) during acute jejunal infusion of a maltodextrin- or a lactose-based formula (n = 8) into preterm pigs. We found lower net portal aldohexose absorption (4% vs. 42%) and greater intestinal recovery of undigested carbohydrate (68% vs. 27%) in pigs acutely perfused with the maltodextrin-based formula than those perfused with the lactose-based formula. The higher digestibility of the lactose than the maltodextrin in the formulas can be attributed to a 5- to 20-fold higher hydrolytic activity of tissue-specific lactase than maltases. We conclude that carbohydrate maldigestion is sufficient to increase the incidence and severity of NEC in preterm pigs.

Clinical Impact of Identifying Lactose Maldigestion or Fructose Malabsorption in Irritable Bowel Syndrome or Other Conditions

The role of carbohydrate maldigestion or malabsorption remains unclear in patients with irritable bowel syndrome (IBS). The purpose of this study was to examine the impact of identifying lactose maldigestion (LM) and fructose malabsorption (FM) on patients with and without IBS. Patients who received lactose and fructose challenge testing formed the study group. Carbohydrate challenge testing was performed with 50 g lactose and 25 g fructose. Breath samples were collected and analyzed for hydrogen, methane, and CO2 (for correction) using a MicroLyzer Model SC (QuinTron Instrument Company, Milwaukee, WI). Questionnaires were used to assess Rome III IBS criteria, compliance with carbohydrate dietary modifications, and changes in symptoms. One hundred and twenty-one of the 181 (67%) study subjects were able to be contacted 8 months to 4 years after carbohydrate testing. LM (21) and FM (2) were seen in 33% of the 66 IBS subjects. LM (12) and FM (9) were seen in 33% of the 55 subjects without IBS. Seventy-seven percent of IBS and 72% of those without IBS reported compliance with dietary advice. Of the subjects who reported compliance, 47% of IBS and 77% of those without IBS reported that, after identifying LM or FM, their symptoms resolved or improved. Carbohydrate maldigestion has a similar incidence in patients with and without IBS and both populations have similar compliance with therapeutic diets. However, patients without IBS are more likely to have improvement in symptoms when dietary changes are instituted when compared to IBS patients.

Hydrogen Breath Testing in Adults

A hydrogen breath test is a safe, easy-to-perform, 2-to 3-hour outpatient procedure used to identify the presence of small intestine bacterial overgrowth, evaluate carbohydrate maldigestion or malabsorption, and measure intestinal transit time. Breath sample analysis can reveal bacterial overgrowth in the small intestine by the characteristic early rise in breath hydrogen concentration (i.e., an earlier-than-expected rise at approximately 90 minutes when the substrate reaches the colon). Patients with irritable bowel syndrome are often referred for a hydrogen breath test because of symptoms of abdominal bloating, cramping, and diarrhea that are also characteristic of bacterial overgrowth. The elderly are at greater risk for nutritional compromise from untreated small intestine bacterial overgrowth than are younger patients. Treatment often consists of one or more courses of antibiotics. Most patients experience a reduction in symptoms with treatment.

Diseases in Chronic Non-infective Diarrhea

Background : Chronic diarrhea is common in Indonesia. The chronic non-infective diarrhea cases seem to be increasing recently. The aim of this study is to reveal the pattern of diseases that can cause chronic non-infective diarrhea. Methods : We examined all patients suffering from chronic non-infective diarrhea over a six years period. The patients underwent physical examination and performed laboratory tests, colon enema X-ray, colonoscopy, ileoscopy, upper gastrointestnal endoscopy and small bowel X-ray. Result : Chronic non-infective diarrhea was observed in 107 (51.7%) cases from 207 chronic diarrhea cases respectively. The frequently found abnormalities that had caused chronic non-infective diarrhea were carbohydrate maldigestion (62.61%), colorectal cancer (14.01%), Crohn’s disease (11.21%), ulcerative colitis (9.34%), irritable bowel syndrome (8.41%), colorectal polyp (8.41%) etc. Conclusion : The most frequent abnormality found in chronic non-infective diarrhea was maldigestion. Keywords : Chronic diarrhea, non-infective

Recurrent abdominal pain.

1. Paul N. Thiessen, MD* 1. *Editorial Board. Clinical Professor of Pediatrics, B.C. Children’s Hospital, Vancouver, B.C., Canada After completing this article, readers should be able to: 1. Characterize the epidemiology and classification of recurrent abdominal pain. 2. List the major clinical conditions that manifest with recurrent abdominal pain. 3. Describe the most important findings in the history and physical examination of the child who has recurrent abdominal pain that suggest an organic medical condition. 4. Outline a targeted approach to ordering investigations that will confirm or disprove suspected organic disease. 5. Delineate the prognosis of recurrent abdominal pain. Recurrent abdominal pain (RAP) is a frequent and troublesome complaint in childhood and adolescence, and the search for a cause and a credible approach to management can be taxing for both family and physician. The term “recurrent abdominal pain” was coined by the British pediatrician John Apley, who first published on the subject in 1958. His definition included at least three attacks of pain occurring over a period of 3 months that were severe enough to affect activities and for which no organic cause was identified. In practice, the definition may include any child or adolescent who has RAP for which the family seeks medical attention and explanation, even if the duration of the pain does not adhere strictly to the Apley definition. The definition explicitly excludes the many causes of acute abdominal pain, which lie outside the scope of this review. There is wide variation in the threshold of severity and frequency that must be crossed before a family will seek medical attention for a child who has RAP. Inevitably, parents want a clear explanation and reassurance that no sinister causes lurk undetected, and the clinician wants to oblige but often lacks the conviction that organic causes have been excluded. The most difficult challenge for the clinician is to determine to what extent diagnostic studies should be employed before the label “recurrent abdominal …

Variations in Colonic H2 and CO2 Production As a Cause of Inadequate Diagnosis of Carbohydrate Maldigestion in Breath Tests

Background: Lactose maldigestion is usually diagnosed by means of the H2 breath test. When 13C-lactose is used as substrate, a 13CO2 breath test can be performed simultaneously. In an earlier publication we described the relation between both the H2 and 13CO2 exhalation in breath and the measured intestinal lactase activity after consumption of 13C-lactose. We found a discrepancy between both breath test results in 36% of the cases. To investigate the possible cause of these incongruous breath test results, we studied gas production from carbohydrate in the colon, using 13C-lactulose as a non-absorbable substrate. Methods: Experiments were performed in 21 subjects, by applying 5 different doses of 13C-lactulose. Repeatability studies were performed in six of these subjects, using 10 g substrate (three tests with 1-week intervals). Results: Both the H2 and the 13CO2 excretion in breath varied strongly interindividually and intraindividually after consumption of 13C-lactulose. In both cases no dose-response relation was observed. A significant positive linear relationship was found between H2 and 13CO2 exhalation (r = 0.45, P < 0.005). Extrapolation of these results to 13C-lactose breath tests indicates that the colonic contribution of 13CO2 production to the total 13CO2 excretion in breath varies but is on the average large enough to cause false-negative 13CO2 breath test results. Conclusions: Excretion in breath of 13CO2 produced in the colon during a 13C-lactulose breath test correlates with the breath H2 excretion. This could explain the occurrence of false-negative 13CO2 lactose breath tests when colonic gas production is high and false-negative lactose H2 breath test results when gas production is low. It can also explain the improved sensitivity of the combined H2/13CO2 lactose breath test compared with both breath tests alone.