No Correlation between Positive Fructose Hydrogen Breath Test and Clinical Symptoms in Children with Functional Gastrointestinal Disorders: A Retrospective Single-Centre Study

Fructose malabsorption is regarded as one of the most common types of sugar intolerance. However, the correlation between gastrointestinal symptoms and positive results in fructose hydrogen breath tests (HBTs) remains unclear. The aim of this study was to assess the clinical importance of positive fructose HBT by correlating the HBT results with clinical features in children with various gastrointestinal symptoms. Clinical features and fructose HBT results were obtained from 323 consecutive children (2–18 years old, mean 10.7 ± 4.3 years) that were referred to the Tertiary Paediatric Gastroenterology Centre and diagnosed as having functional gastrointestinal disorders. A total of 114 out of 323 children (35.3%) had positive HBT results, of which 61 patients were females (53.5%) and 53 were males (46.5%). Children with positive HBT were significantly younger than children with negative HBT (9.0 vs. 11.6 years old; p < 0.001). The most frequent symptom among children with fructose malabsorption was recurrent abdominal pain (89.5%). Other important symptoms were diarrhoea, nausea, vomiting, and flatulence. However, no correlation between positive fructose HBT results and any of the reported symptoms or general clinical features was found. In conclusion, positive fructose HBT in children with functional gastrointestinal disorders can be attributed to their younger age but not to some peculiar clinical feature of the disease.

Systematic Review and Meta-Analysis: What is the Prevalence of Non-Malignant, Organic Gastrointestinal Disorders Misdiagnosed as Lrritable Bowel Syndrome?

IntroductionTreatable gastrointestinal disorders in patients with symptoms typical for irritable bowel syndrome (IBS) may be overlooked. The prevalence of five gastrointestinal conditions - bile acid diarrhoea (BAD), carbohydrate malabsorption (CM), microscopic colitis (MC), pancreatic exocrine insufficiency (PEI) and small intestinal bacterial overgrowth (SIBO) was systematically assessed from studies including consecutive patients meeting diagnostic criteria for IBS. Methods4 databases were searched from 1978-2020. Studies were included if they evaluated the prevalence of these conditions in secondary healthcare setting. Estimated pooled rates were calculated and statistical heterogeneity between studies was evaluated using Q and I2 statistics.ResultsSeven studies (n=597) estimated the pooled prevalence for BAD as 41% (95% CI 29-54). 17 studies (n=5,068) estimated that of MC as 3% (95% CI 2-4%). Two studies (n=478) suggested a rate of 4·6% (range: 1·8-6·1%) for PEI. Using breath testing, 26 studies (n=6,700) and 13 studies (n=3,415) estimated the prevalence of lactose and fructose malabsorption as 54% (95% CI 44-64%) and 43% (95% CI 23-62%); 36 studies (n=4,630) and 22 studies (n=2,149) estimated that of SIBO as 49% (95% CI 40-57%) with lactulose and 19% (95% CI 13-27%) with glucose. Rates of all conditions were significantly higher than in healthy controls.ConclusionA significant proportion of patients presenting to secondary care with IBS have an organic condition which may account for their symptoms. Failure to exclude such conditions will deny patients effective treatment.

Expression of the fructose transporter GLUT5 in patients with fructose malabsorption

Background Patients with abdominal symptoms are frequently diagnosed with fructose malabsorption (FM). Fructose is absorbed by monosaccharide transporters located in the brush border of the human small intestine. The aim of this study was to investigate the histoanatomical distribution of the main fructose transporter GLUT5. Materials and methods We studied 223 patients diagnosed with FM by a hydrogen breath test and grouped according to their response to a fructose-free diet. The control group were 42 healthy individuals and 29 patients with celiac disease (CD). The fructose breath test was done with 50 g fructose. The expression of Glut5 in duodenal biopsy specimens was studied by immunohistochemistry. The Kruskal-Wallis-test and Mann-Whitney U-test were used to carry out the statistical analysis. Results The histoanatomical expression pattern of GLUT5 did not differ significantly between those patients with FM who responded completely to a fructose-free diet (n = 183) and healthy individuals (n = 42); nor did it correlate to H2 production measured in fructose breath testing. In patients with FM, the GLUT5 expression pattern did not differ between those individuals responding to a fructose-free diet and those who did not. However, GLUT5 expression pattern was significantly different in patients with CD (n = 29) compared to patients with FM and to healthy individuals (p = 0.009). Conclusion GLUT5 expression patterns are not be related to adult patients with FM. However, in secondary malabsorption, a decreased GLUT5 expression was found. Further investigation is needed to understand the essential factors in FM and the influence on functional gastrointestinal disorders.

Loss of intestinal ChREBP impairs absorption of dietary sugars and prevents glycemic excursion curves

Increased sugar consumption is a risk factor for features of the metabolic syndrome including obesity, hypertriglyceridemia, insulin resistance, diabetes, and nonalcoholic fatty liver disease. The gut epithelium, which plays a central role in dietary sugar digestion, absorption and metabolism has emerged a key actor of metabolic disorders. While the transcription factor ChREBP (Carbohydrate response element binding protein) has been established as a key player of the adaptive reprograming of cellular metabolism in various tissues upon glucose or fructose challenge, its specific contribution to the regulation of blood glucose upon dietary sugar intake was not previously addressed. We demonstrate here that ChREBP is abundantly expressed in the proximal gut epithelium, where carbohydrate digestion and absorption primarily occur and in particular L cells, which produce the glucoincretin GLP-1. The inducible deletion of ChREBP specifically in the mouse gut epithelium (ChΔGUT mice) resulted in the reduction of early glycemic excursion upon oral glucose load. Surprisingly, despite being associated with reduced GLP-1 production, loss of gut ChREBP activity significantly dampened glucose transepithelial flux, and thereby delayed glucose distribution to peripheral tissues. Among the underlying mechanisms, we unveil that ChΔGUT mice show an impaired expression of key intestinal hexose (glucose, galactose, fructose) transporters and metabolic enzymes as well as brush border dissacharidases. In agreement, intestinal ChREBP deficiency was accompanied by a precocious intolerance to both high-lactose and high-sucrose diets concomitant with mild galactose and severe fructose malabsorption syndromes. Altogether, our study demonstrates that, by transcriptionally orchestrating local digestion and absorption of dietary sugars, ChREBP activity in the mouse gut epithelium controls glucose appearance rate into systemic circulation and prevents against intolerance to mono- and disaccharides.

Fructose malabsorption: Causes, diagnosis and treatment

This review intends to act as an overview of Fructose Malabsorption (FM) and its role in the aetiology of diseases including, but not limited to, Irritable Bowel Syndrome (IBS) and Infantile colic and the relationship between fructose absorption and the propagation of some cancers. IBS results in a variety of symptoms including stomach pains, cramps and bloating. Patients can be categorised into two groups, depending on whether the patients’ experiences either constipation (IBS-C) or diarrhoea (IBS-D). Fructose Malabsorption has been proposed as a potential cause of IBS-D and other diseases, such as infantile colic. However, our knowledge of FM is limited by our understanding of the biochemistry related to the absorption of fructose in the small intestine and FM’s relationship with Small Intestinal Bacteria Overgrowth (SIBO). It is important to consider the dietary effects on FM and most importantly, the quantity of excess free fructose consumed. The diagnosis of FM is difficult and often requires indirect means that may result in false positives. Current treatments of FM include dietary intervention, such as low fermentable oligo-, di-, mono-saccharides and polyols (FODMAP) diets and enzymatic treatments, such as the use of xylose isomerase. More research is needed to accurate diagnose and effectively treat FM. This review is designed with the goal of providing a detailed outline of the issues regarding the causes, diagnosis and treatment of FM.

High fructose corn syrup, excess-free-fructose, and risk of coronary heart disease among African Americans– the Jackson Heart Study

Background Researchers have sought to explain the black-white coronary heart disease (CHD) mortality disparity that increased from near parity to ~ 30% between 1980 and 2010. Contributing factors include cardiovascular disease prevention and treatment disparities attributable to disparities in insurance coverage. Recent research suggests that dietary/environmental factors may be contributors to the disparity. Unabsorbed/luminal fructose alters gut bacterial load, composition and diversity. There is evidence that such microbiome disruptions promote hypertension and atherosclerosis. The heart-gut axis may, in part, explain the black-white CHD disparity, as fructose malabsorption prevalence is higher among African Americans. Between 1980 and 2010, consumption of excess-free-fructose–the fructose type that triggers malabsorption-exceeded dosages associated with fructose malabsorption (~ 5 g–10 g), as extrapolated from food availability data before subjective, retroactively-applied loss adjustments. This occurred due to an industrial preference shift from sucrose to high-fructose-corn-syrup (HFCS) that began ~ 1980. During this period, HFCS became the main sweetener in US soda. Importantly, there has been more fructose in HFCS than thought, as the fructose-to-glucose ratio in popular sodas (1.9-to-1 and 1.5-to-1) has exceeded generally-recognized-as-safe levels (1.2-to-1). Most natural foods contain a ~ 1-to-1 ratio. In one recent study, ≥5 times/wk. consumers of HFCS sweetened soda/fruit drinks/and apple juice-high excess-free-fructose beverages–were more likely to have CHD, than seldom/never consumers. Methods Jackson-Heart-Study data of African Americans was used to test the hypothesis that regular relative to low/infrequent intake of HFCS sweetened soda/fruit drinks increases CHD risk, but not orange juice-a low excess-free-fructose juice. Cox proportional hazards models were used to calculate hazard ratios using prospective data of 3407–3621 participants, aged 21–93 y (mean 55 y). Results African Americans who consumed HFCS sweetend soda 5-6x/wk. or any combination of HFCS sweetened soda and/or fruit drinks ≥3 times/day had ~ 2 (HR 2.08, 95% CI 1.03–4.20, P = 0.041) and 2.5–3 times higher CHD risk (HR 2.98, 95% CI 1.15–7.76; P = 0.025), respectively, than never/seldom consumers, independent of confounders. There were no associations with diet-soda or 100% orange-juice, which has a similar glycemic profile as HFCS sweetened soda, but contains a ~ 1:1 fructose-to-glucose ratio. Conclusion The ubiquitous presence of HFCS in the food supply may pre-dispose African Americans to increased CHD risk.

Increasing Expiratory Hydrogen in Lactose Intolerance Is Associated with Additional Food Intolerance/Malabsorption

Single and/or combined food intolerance/malabsorption may cause nonspecific, functional gastrointestinal (GI) complaints. In lactose-intolerant patients we evaluated the influence of additional food intolerance/malabsorption with hydrogen (H2) breath tests. In a retrospective analysis of charts from 279 lactose-intolerant patients, we found 128 patients with only lactose intolerance (LIT). Then, we identified 106 LIT patients with additional histamine intolerance (HIT). Additionally, 45 LIT and HIT patients also had fructose malabsorption (FM). A hydrogen (H2) breath test was performed to evaluate LIT and FM. A serum diamine oxidase value of <10 U/mL and a response to a histamine-reduced diet was used to identify HIT. Using pairwise comparison with the Kruskal–Wallis test to associate the area under the curve (AUC) of LIT patients and, LIT with HIT, to LIT with HIT and FM it was found, that the exhaled hydrogen values were significantly higher in patients with two-fold and triple combined food intolerance/malabsorption (p < 0.004 and p < 0.001, respectively). Within the pool of 170 LIT patients with >20 ppm increase of expiratory H2 from baseline, there were 74 LIT-only patients, 60 LIT with HIT patients, and 36 LIT patients with additional HIT and FM. With the Kruskal–Wallis test AUCs demonstrated a significant difference between all three groups (p = 0.024). In patients with LIT, the presence of additional food intolerance/malabsorption, significantly increases expiratory H2 values. We demonstrate evidence, which may suggest HIT to embody an own GI disorder as food intolerance/malabsorption.

Reply to Comments on the editor Re: Carsten Posovszky et al. “Roles of Lactose and Fructose Malabsorption and Dietary Outcomes in Children Presenting with Chronic Abdominal Pain.”, Nutrients 2019, 11(12), 3063

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