Assessment of dietary interventions including low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet as management for fructose intolerance.

OBJECTIVES: Abdominal pain remains one of the most common referral reasons to pediatric gastroenterology. Dietary intolerances are often considered but due to various factors are hardly pursued. We observed that diet review in large number of children with abdominal pain was high in sugary foods which led to food intolerance investigation and dietary intervention. METHODS: A retrospective review was conducted of patients presenting with abdominal pain, diarrhea, or vomiting and negative GI evaluation, who underwent fructose breath testing. Patients younger than 20 years old who were seen between June 1, 2018 and March 1, 2021 were included. Statistical analysis was performed in R. RESULTS: There were 110 pediatric patients during the study period who underwent fructose breath testing, with 31% male and 69% female. The average age was 12.14 ± 4.01 years, and the average BMI was 21.21 ± 6.12. Abdominal pain was the most common presenting symptom (74.5%) followed by diarrhea and vomiting. Seventy-seven patients (70%) had a positive fructose breath test and were diagnosed with dietary intolerance to fructose. The 56 (67.5%) of those patients experienced symptoms during the breath test. Forty-three patients improved with dietary intervention. Twenty-seven on low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet and 16 on other diets. CONCLUSIONS: Based on analysis of our cohort of children with abdominal pain and high incidence of fructose intolerance as well as improvement in symptoms, following dietary changes, this condition should be considered and treated. Further investigation is needed to improve diagnostic testing but also into understanding mechanisms behind symptom presentation in this population.

Reply letter to the editor concerning the article 'Safety of Sars-Cov-2 vaccines administration for adult patients with hereditary fructose intolerance'.

According to the current European medicines legislation, on the labeling is mandatory a warning contraindicating for hereditary fructose intolerance (HFI) patients medicines with oral or parenteral fructose and sorbitol, and oral sucrose, invert sugar, isomaltitol, lactitol and maltitol, but parenteral sucrose is not mentioned. Intravenous administration of sucrose does not increase blood glucose concentrations, because sucrose is poorly oxidized to CO2 and mainly excreted in the urine as a disaccharide; absence of enzimatic activity outside the gut explains why there is not a warning for parenteral sucrose presentations. For this reason, parenteral drugs with sucrose are allowed in HFI patients. Nevertheless, due to interindividual variability and the fact that not all parenterally administered sucrose is recovered in urine, HFI patients need to be closely monitored after parenteral administration of sucrose-containing drugs, especially when the amount exceeds the maximum permissible thresholds.

Fructose intolerance is not associated with malabsorption in patients with functional gastrointestinal disorders.

BACKGROUND: Symptoms following fructose ingestion, or fructose intolerance, are common in patients with functional gastrointestinal disorders (FGID) and are generally attributed to intestinal malabsorption. The relationships between absorption, symptoms, and intestinal gas production following fructose ingestion were studied in patients with FGID. METHODS: Thirty FGID patients ingested a single dose of fructose 35 g or water in a randomized, double-blind, crossover study. Blood and breath gas samples were collected, and gastrointestinal symptoms rated. Plasma fructose metabolites and short-chain fatty acids were quantified by targeted liquid chromatography-tandem mass spectrometry. Patients were classified as fructose intolerant or tolerant based on symptoms following fructose ingestion. KEY RESULTS: The median (IQR) areas under the curve of fructose plasma concentrations within the first 2 h (AUC0-2 h ) after fructose ingestion were similar for patients with and without fructose intolerance (578 (70) µM·h vs. 564 (240) µM·h, respectively, p = 0.39), as well as for the main fructose metabolites. There were no statistically significant correlations between the AUC0-2 h of fructose or its metabolites concentrations and the AUCs of symptoms, breath hydrogen, and breath methane. However, the AUCs of symptoms correlated significantly and positively with the AUC0-2 h of hydrogen and methane breath concentrations (r = 0.73, r = 0.62, respectively), and the AUCs of hydrogen and methane concentrations were greater in the fructose-intolerant than in the fructose-tolerant patients after fructose ingestion (p ≤ 0.02). CONCLUSIONS & INFERENCES: Fructose intolerance in FGID is not related to post-ingestion plasma concentrations of fructose and its metabolites. Factors other than malabsorption, such as altered gut microbiota or sensory function, may be important mechanisms.

Non-alcoholic fatty liver in hereditary fructose intolerance.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation affecting >5% of the liver volume that is not explained by alcohol abuse. It is known that fructose gives rise to NAFLD and it has been recently described that the ingestion of fructose in low amounts in aldolase B deficient mice is associated with the development of fatty liver. Therefore, it is reasonable that patients with HFI (Hereditary Fructose Intolerance) present fatty liver at diagnosis, but its prevalence in patients treated and with adequate follow-up is not well documented in the literature. The aim of this study is to analyze the association between HFI and NAFLD in treated patients. METHODS: A cross-sectional observational study was conducted. The population comprised 16 genetically diagnosed HFI patients aged from 3 years to 48 and in dietary treatment of fructose, sorbitol and sacarose exclusion at least for two years. Blood samples were obtained for analytical studies and anthropometric measurements of each patient were performed. RESULTS: Patients presented a Body Mass Index (BMI) of 17.9 ± 2.9 kg/m2. The HOMA index and Quick index were in normal range for our population. The S-adenosyl-methionine (SAM)/S-adenosyl-l-homocysteine (SAH) ratio was increased in the patients in whom this analysis was performed. By imaging techniques it was observed that 9 of the 16 patients presented fatty liver (7 by hepatic MRI). Of these 9 patients, only 3 presented hepatomegaly. 7 of 9 patients affected by the c.448G > C mutation had fatty infiltration, of which three of them presented in addition hepatomegaly. CONCLUSIONS: There is a high prevalence of fatty liver in HFI patients and it is not related to obesity and insulin resistance. The diagnosis of fatty liver in HFI patients and, above all, the identification of new therapeutic approaches, can positively impact the quality of life of these patients.

'Rapid transit' constipation in children: a possible genesis for irritable bowel syndrome.

Children with chronic idiopathic constipation (CIC) often end up at the surgeon when medical treatments have failed. This opinion piece discusses a recently described pattern of CIC called 'Rapid transit constipation (RTC)' first identified in 2011 as part of surgical workup. RTC was identified using a nuclear medicine gastrointestinal transit study (NMGIT or nuclear transit study) to determine the site of slowing within the bowel and to inform surgical treatment. Unexpectedly, we found that RTC occured in 29% of 1000 transit studies in a retrospective audit. Irritable bowel syndrome (IBS) occurs in 7-21% of the population, with a higher prevalence in young children and with constipation type dominating in the young. While 60% improve with time, 40% continue with symptoms. First-line therapy for IBS in adults is a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols which reduces symptoms in > 70% of patients. In children with functional gastrointestinal disorders, fructose intolerance occurs in 35-55%. Reducing fructose produced significant improvement in 77-82% of intolerant patients. In children with RTC and a positive breath test upon fructose challenge, we found that exclusion of fructose significantly improved constipation, abdominal pain, stool consistency and decreased laxative use. We hypothesise that positive breath tests and improvement of pain and bowel frequency with sugar exclusion diets in RTC suggest these children have IBS-C. These observations raise the possibility that many children with CIC could be treated by reducing fructose early in their diet and this might prevent the development of IBS in later life.

Daily Fructose Traces Intake and Liver Injury in Children with Hereditary Fructose Intolerance.

BACKGROUND: Hereditary fructose intolerance (HFI) is a rare genetic disorder of fructose metabolism due to aldolase B enzyme deficiency. Treatment consists of fructose, sorbitol, and sucrose (FSS)-free diet. We explore possible correlations between daily fructose traces intake and liver injury biomarkers on a long-term period, in a cohort of young patients affected by HFI. METHODS: Patients' clinical data and fructose daily intake were retrospectively collected. Correlations among fructose intake, serum alanine aminotransferase (ALT) level, carbohydrate-deficient transferrin (CDT) percentage, liver ultrasonography, genotype were analyzed. RESULTS: We included 48 patients whose mean follow-up was 10.3 ± 5.6 years and fructose intake 169 ± 145.4 mg/day. Eighteen patients had persistently high ALT level, nine had abnormal CDT profile, 45 had signs of liver steatosis. Fructose intake did not correlate with ALT level nor with steatosis severity, whereas it correlated with disialotransferrin percentage (R2 0.7, p < 0.0001) and tetrasialotransferrin/disialotransferrin ratio (R2 0.5, p = 0.0001). p.A150P homozygous patients had lower ALT values at diagnosis than p.A175D variant homozygotes cases (58 ± 55 IU/L vs. 143 ± 90 IU/L, p = 0.01). CONCLUSION: A group of HFI patients on FSS-free diet presented persistent mild hypertransaminasemia which did not correlate with fructose intake. Genotypes may influence serum liver enzyme levels. CDT profile represents a good marker to assess FSS intake.

Acute liver failure in neonates with undiagnosed hereditary fructose intolerance due to exposure from widely available infant formulas.

Hereditary fructose intolerance (HFI) is an autosomal recessive disorder caused by aldolase B (ALDOB) deficiency resulting in an inability to metabolize fructose. The toxic accumulation of intermediate fructose-1-phosphate causes multiple metabolic disturbances, including postprandial hypoglycemia, lactic acidosis, electrolyte disturbance, and liver/kidney dysfunction. The clinical presentation varies depending on the age of exposure and the load of fructose. Some common infant formulas contain fructose in various forms, such as sucrose, a disaccharide of fructose and glucose. Exposure to formula containing fructogenic compounds is an important, but often overlooked trigger for severe metabolic disturbances in HFI. Here we report four neonates with undiagnosed HFI, all caused by the common, homozygous mutation c.448G>C (p.A150P) in ALDOB, who developed life-threatening acute liver failure due to fructose-containing formulas. These cases underscore the importance of dietary history and consideration of HFI in cases of neonatal or infantile acute liver failure for prompt diagnosis and treatment of HFI.

Predictors of response to a low-FODMAP diet in patients with functional gastrointestinal disorders and lactose or fructose intolerance.

BACKGROUND: Diets low in fermentable sugars (low-FODMAP diets) are increasingly adopted by patients with functional gastrointestinal disorders (FGID), but outcome predictors are unclear. AIM: To identify factors predictive of an efficacious response to a low-FODMAP diet in FGID patients with fructose or lactose intolerance thereby gaining insights into underlying mechanisms. METHODS: Fructose and lactose breath tests were performed in FGID patients to determine intolerance (positive symptom score) and malabsorption (increased hydrogen or methane concentrations). Patients with fructose or lactose intolerance consumed a low-FODMAP diet and global adequate symptom relief was assessed after 6-8 weeks and correlated with pre-diet clinical symptoms and breath test results. RESULTS: A total of 81% of 584 patients completing the low-FODMAP diet achieved adequate relief, without significant differences between FGID subgroups or types of intolerance. Univariate analysis yielded predictive factors in fructose intolerance (chronic diarrhoea and pruritus, peak methane concentrations and fullness during breath tests) and lactose intolerance (peak hydrogen and methane concentrations and flatulence during breath tests). Using multivariate analysis, symptom relief was independently and positively predicted in fructose intolerance by chronic diarrhoea [odds ratio (95% confidence intervals): 2.62 (1.31-5.27), P = 0.007] and peak breath methane concentrations [1.53 (1.02-2.29), P = 0.042], and negatively predicted by chronic nausea [0.33 (0.16-0.67), P = 0.002]. No independent predictive factors emerged for lactose intolerance. CONCLUSIONS: Adequate global symptom relief was achieved with a low-FODMAP diet in a large majority of functional gastrointestinal disorders patients with fructose or lactose intolerance. Independent predictors of a satisfactory dietary outcome were only seen in fructose intolerant patients, and were indicative of changes in intestinal host or microbiome metabolism.

Lactose and Fructose Intolerance in Turkish Children with Chronic Abdominal Pain.

OBJECTIVE: To investigate the prevalence of lactose and fructose intolerance in children with chronic abdominal pain. METHODS: Hydrogen breath tests were done to detect lactose and fructose malabsorption in 86 children with chronic abdominal pain (44 irritable bowel syndrome, 24 functional abdominal pain and 17 functional abdominal pain syndrome as per Rome III criteria) presenting to a Pediatric Gastroentreology department. RESULTS: 14 (16.3%) of patients were diagnosed with lactose intolerance and 11 (12.8%) with fructose intolerance. CONCLUSION: Lactose and fructose intolerance in children can lead to chronic abdominal pain and symptoms improve with dietary modifications.

Effects of dietary education, followed by a tailored fructose-restricted diet in adults with fructose malabsorption.

OBJECTIVE: Fructose is absorbed by GLUT transporters in the small intestine. If this process is inadequate, abdominal symptoms because of fructose intolerance may arise. The effect of a tailored fructose-restricted diet on gastrointestinal complaints was assessed in patients with fructose intolerance. MATERIALS AND METHODS: Following an abnormal fructose breath test (50 g), 107 patients (64 also with lactose intolerance) entered three study periods: weeks 0-32 (free diet), weeks 32-36 (progressive increasing amount of fructose up to quantity inducing symptoms, 'trigger dose'), and weeks 36-48 (tailored fructose-restricted diet according to the 'trigger dose'). A subgroup of 15 patients underwent additional fructose breath tests (35, 25 g) to compare three different doses. RESULTS: At baseline, the most frequent symptoms were bloating and abdominal pain, and were more severe with combined fructose and lactose intolerance. During the free diet, patients reported eliminating (48%) or reducing (52%) fructose-containing foods, with a significant improvement in symptoms (abdominal pain from 79.7 ± 1.3 to 19.3 ± 1.8 mm; bloating from 83.1 ± 1.3 to 19.4 ± 1.8 mm; number of evacuations/day from 3.9 ± 0.16 to 1.1 ± 0.04; Bristol score from 5.1 ± 0.14 to 3.8 ± 0.1, P < 0.00001). During the tailored fructose-restricted diet, the consistent improvement in symptoms persisted and was similar to the improvement on free diet (abdominal pain 23.6 ± 1.9 mm; bloating 19.4 ± 1.8 mm; number of evacuations/day 1.7 ± 0.07; Bristol score 3.5 ± 0.06, P<0.00001 vs. baseline). A dose-dependent effect of fructose was observed on symptoms during the fructose breath test. CONCLUSION: In our setting, individuals with fructose intolerance show an inappropriate dietary self-management. By contrast, a tailored fructose-restricted diet improves gastrointestinal symptoms without senseless food deprivation.

Fructose intolerance/malabsorption and recurrent abdominal pain in children.

OBJECTIVES: The purpose of the present study was to ascertain whether pediatric patients with chronic abdominal pain had concurrent fructose intolerance as determined by a standardized dose breath hydrogen test (BHT), and whether symptoms would improve with a low-fructose diet. METHODS: The fructose BHT test was administered to patients evaluated in clinic with unexplained chronic abdominal pain alone or associated with constipation, gas or bloating, and/or diarrhea. The patients were given a standard dose of 1 g/kg fructose to maximum of 25 g. Hydrogen and methane were measured at 8 time points. The test was presumed positive if breath hydrogen exceeded 20 ppm above baseline. If positive, patients were given a dietitian-prescribed low-fructose diet. RESULTS: A total of 222 patients were part of the study. Ages ranged from 2 to 19 years with a mean of 10.5. BHT for fructose was performed in all of the patients and it was positive for fructose intolerance in 121 of 222 patients (54.5%). A total of 101 of 222 (45.5%) patients had negative BHT for fructose intolerance. All BHT-positive patients had a nutrition consult with a registered dietitian and were placed on a low-fructose diet. Using a standard pain scale for children, 93 of 121 patients (76.9%) reported resolution of symptoms on a low-fructose diet (P < 0.0001). Furthermore, 55 of 101 patients (54.4%) with negative BHT for fructose reported resolution of symptoms without a low-fructose diet (P = 0.37). CONCLUSIONS: Fructose intolerance/malabsorption is common in children with recurrent/functional abdominal pain and a low-fructose diet is an effective treatment.

Dietary fructose intolerance, fructan intolerance and FODMAPs.

Dietary intolerances to fructose, fructans and FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) are common, yet poorly recognized and managed. Over the last decade, they have come to the forefront because of new knowledge on the mechanisms and treatment of these conditions. Patients with these problems often present with unexplained bloating, belching, distension, gas, abdominal pain, or diarrhea. Here, we have examined the most up-to-date research on these food-related intolerances, discussed controversies, and have provided some guidelines for the dietary management of these conditions. Breath testing for carbohydrate intolerance appears to be standardized and essential for the diagnosis and management of these conditions, especially in the Western population. While current research shows that the FODMAP diet may be effective in treating some patients with irritable bowel syndrome, additional research is needed to identify more foods items that are high in FODMAPs, and to assess the long-term efficacy and safety of dietary interventions.

The low FODMAP diet improves gastrointestinal symptoms in patients with irritable bowel syndrome: a prospective study.

BACKGROUND AND AIM: Current treatment for irritable bowel syndrome (IBS) is suboptimal. Fermentable oligo-, di-, mono-saccharides and polyols (FODMAPs) may trigger gastrointestinal symptoms in IBS patients. Our aim was to determine whether a low FODMAP diet improves symptoms in IBS patients. METHODS: Irritable bowel syndrome patients, who had performed hydrogen/methane breath testing for fructose and lactose malabsorption and had received dietary advice regarding the low FODMAP diet, were included. The effect of low FODMAP diet was prospectively evaluated using a symptom questionnaire. Furthermore, questions about adherence and satisfaction with symptom improvement, dietary advice and diet were assessed. RESULTS: Ninety patients with a mean follow up of 15.7 months were studied. Most symptoms including abdominal pain, bloating, flatulence and diarrhoea significantly improved (p < 0.001 for all). 75.6%, 37.8% and 13.3% of patients had fructose, lactose malabsorption or small intestinal bacterial overgrowth respectively. Fructose malabsorption was significantly associated with symptom improvement (abdominal pain odds ratio (OR) 7.09 [95% confidence interval (CI) 2.01-25.0], bloating OR 8.71 (95% CI 2.76-27.5), flatulence OR 7.64 (95% CI 2.53-23.0) and diarrhoea OR 3.39 (95% CI 1.17-9.78), p < 0.029 for all). Most patients (75.6%) were adherent to the diet, which was associated with symptom improvement (abdominal pain, bloating, flatulence and diarrhoea all significantly associated with adherence, r > 0.27, p < 0.011). Most patients (72.1%) were satisfied with their symptoms. CONCLUSIONS: The low FODMAP diet shows efficacy for IBS patients. The current strategy of breath testing and dietary advice provides a good basis to understand and adhere to the diet.

Non responsive celiac disease due to coexisting hereditary fructose intolerance.

Celiac disease is associated with several genetic disorders, but its association with hereditary fructose intolerance is rare. Hereditary fructose intolerance is a rare autosomal recessive disease of fructose metabolism presenting as vomiting after intake of fructose. An association between these two distinct genetic gastrointestinal disorders is important as treatment failure of celiac disease calls for careful evaluation for hereditary fructose intolerance. We report a patient with an association of these two disorders.

Toddler diarrhoea: is it a useful diagnostic label?

Toddler diarrhoea is a term coined many years ago to describe a young child who passes several loose stools a day but who is otherwise healthy with excellent growth and normal examination. It could be argued that it is not an appropriate diagnostic term as it potentially stops the clinician from thinking about the possible causes of loose stools in this clinical situation. This article, which follows a debate between the authors on the topic at the 2010 Royal College of Paediatrics and Child Health Annual meeting, discusses the differential diagnoses of a young child presenting with the so-called toddler diarrhoea.

The role of diet in symptoms of irritable bowel syndrome in adults: a narrative review.

This review summarizes what is known about the effect of diet on irritable bowel syndrome (IBS) symptoms emphasizing data from randomized, controlled clinical trials. Studies suggest that IBS symptoms in one quarter of patients may be caused or exacerbated by one or more dietary components. Recent studies indicate that a diet restricted in fermentable, poorly absorbed carbohydrates, including fructose, fructans (present in wheat and onions), sorbitol, and other sugar alcohols is beneficial, but confirmatory studies are needed. Despite a long history of enthusiastic use, fiber is marginally beneficial. Insoluble fiber may worsen symptoms. Some patients with IBS, especially those with constipation, will improve with increased intake of soluble fiber. Prebiotic fibers have not been adequately tested. Daily use of peppermint oil is effective in relieving IBS symptoms. The usefulness of probiotics in the form of foods such as live-culture yogurt and buttermilk for IBS symptoms is not established. In clinical practice, it is very difficult to establish that a patient's symptoms result from an adverse reaction to food. A double blind placebo-controlled food challenge is the most reliable method, but it is not suitable for routine clinical use. A modified exclusion diet and stepwise reintroduction of foods or trials of eliminating classes of food may be useful.

Fructose intolerance in children presenting with abdominal pain.

OBJECTIVES: We determined the occurrence of fructose malabsorption in pediatric patients with previous diagnoses of abdominal pain caused by a functional bowel disorder, whether the restriction of fructose intake changes the reporting of symptoms, the role of fructose dosage, and the severity of resultant symptoms. PATIENTS AND METHODS: We administered a fructose breath test to children presenting with persistent unexplained abdominal pain. Patients randomly received 1, 15, or 45 g fructose, and breath hydrogen was measured for 3 hours after ingestion. Test results were positive when breath hydrogen was 20 ppm greater than baseline and was accompanied by gastrointestinal symptoms. RESULTS: A total of 32 patients was enrolled, and none of the 9 who received 1 g had positive results. Three of 10 who received 15 g and 8 of 13 who received 45 g had positive results. All patients with positive test results restricted their fructose intake. Among the group with positive results, 9 of 11 had rapid improvement of their gastrointestinal symptoms. After 2 months, all 9 patients continued to report improvement. CONCLUSIONS: We concluded that fructose malabsorption may be a significant problem in children and that management of dietary intake can be effective in reducing gastrointestinal symptoms.