Fructose malabsorption and dysfunctional gastrointestinal manifestations]

BACKGROUND: Individuals with impaired intestinal absorption of fructose may exhibit recurrent abdominal discomfort after the ingestion of fructose-containing foods. We report on patients with this disorder in whom the diagnosis was made by the fructose hydrogen breath test. METHODS: We investigated 293 patients with recurrent abdominal pain, meteorism or diarrhea in connection with the ingestion of fruits, apple juice or soft drinks. Mixed expired air was collected before and at 30 minute intervals after a fructose load and analysed thereafter by a hydrogen sensitive electrochemical cell. Incomplete absorption of fructose was defined as a peak rise in breath hydrogen of > 20 ppm. RESULTS: 108 out of 293 patients showed an abnormal peak rise after fructose (mean 71.8 ppm, SD 31.4). This malabsorption of fructose was associated with clinical symptoms in 79 of them. Sensitivity and specificity of the fructose hydrogen breath test were 98 or 86 per cent respectively. 19 patients with an abnormal breath test and symptoms following fructose were reexamined after a load with equimolar concentrations of glucose and fructose. Hydrogen breath test was normal in all of them, none developed abdominal discomfort. CONCLUSION: A considerable number of individuals suffer from dysfunctional gastrointestinal problems due to fructose malabsorption. The fructose hydrogen breath test is a simple, sensitive and noninvasive method for the diagnosis for this disorder. Possible means of treatment are dietary fructose restriction or a modification of the diet in which fructose-containing foods are exchanged for those with equal concentrations of glucose and fructose.     

Fructose breath hydrogen tests.

Fructose absorption was studied by the breath hydrogen test in 114 healthy children aged 0.1-6 years, given either 2 g/kg or 1 g/kg of fructose. All 57 children given 2 g/kg had peak breath hydrogen excretions > or = 20 ppm. At 1 g/kg only 25/57 (44%) showed incomplete absorption and the percentage incompletely absorbing fructose and the peak breath hydrogen value were significantly higher in children aged 1-3 years. Interestingly, this age distribution correlates with that of toddler diarrhoea.     

Fructose breath hydrogen tests

Fructose absorption was studied by the breath hydrogen test in 114 healthy children aged 0.1-6 years, given either 2 g/kg or 1 g/kg of fructose. All 57 children given 2 g/kg had peak breath hydrogen excretions > or = 20 ppm. At 1 g/kg only 25/57 (44%) showed incomplete absorption and the percentage incompletely absorbing fructose and the peak breath hydrogen value were significantly higher in children aged 1-3 years. Interestingly, this age distribution correlates with that of toddler diarrhoea.     

Apple juice,fructose, and chronic nonspecific diarrhoea

Apple juice contains fructose and sorbitol, substances that have been shown to be incompletely absorbed by most people. As this might have clinical consequences, especially in young children, we investigated the absorption of the carbohydrate content of apple juice in apple juice consuming toddlers with chronic nonspecific diarrhoea as compared to controls, using the breath hydrogen (H₂) test. Incomplete absorption of the carbohydrates from 250 ml of apple juice, as indicated by a maximum breath H₂ increase of 20 parts per million (ppm), was found in all nine patients (mean ±SEM 57±8 ppm), and in five out of eight controls (22±7 ppm) (P<0.01). Six patients were retested with apple juice enriched with glucose, which is known to improve fructose absorption. The maximum breath H₂ increase as well as the area under the breath H₂ curve decreased significantly. It was thus estimated that fructose accounted for 80% of the incomplete absorption and sorbitol for 20%. Elimination of apple juice from the diets of the nine patients resulted in normalisation of both the frequency and the consistency of the stools. Incomplete absorption of the carbohydrates, particularly fructose, from apple juice seems to be quite common, and may contribute to chronic diarrhoea in young children.Abbreviations H₂ hydrogen - ppm parts per million     

Fruit juice malabsorption: not only fructose

Malabsorption of free fructose, when ingested in excess over glucose, is considered a significant factor in apple juice induced diarrhoea. Absorption of the carbohydrates in fruit juices was investigated by means of the hydrogen breath test in 15 healthy children aged 2.2-6.4 years, consuming 15 ml kg'of each juice with a maximum of 375 ml. Incomplete absorption was found following the ingestion of apple juice (5/5), grape juice (10/10) and bilberry juice (8/10), although the last two contain equivalent concentrations of fructose and glucose. When the same tests were repeated after yeast treatment of the juices, which leads to major reductions in fructose and glucose contents, malabsorption was found to persist. No symptoms were observed following any of the tests. Our results suggest a significant role for other carbohydrates than fructose, possibly those originating from the fruit skin, with respect to fruit juice-induced breath hydrogen excretion.     

Dumping syndrome in children. Diagnosis and effect of glucomannan on glucose tolerance and absorption

Dumping syndrome is rarely seen in children. We studied ten children with symptoms following various types of gastric surgery. All had abnormal blood glucose and breath hydrogen responses after oral glucose challenge, indicating reduction of both glucose tolerance and glucose absorption, as compared to controls. Glucose tolerance was best expressed as the difference between peak and subsequent lowest blood glucose level, the upper limit of normal (mean + 3 SD) being 5.9 mmol/l. In eight children with persisting symptoms we tested the effects of glucomannan, a highly hygroscopic tasteless fibre, on glucose tolerance and glucose absorption. Glucomannan significantly improved glucose tolerance, but did have no overall effect on glucose absorption. Four children tested glucomannan added to the main meals. Breath hydrogen excretion, as established with the daytime breath hydrogen profile, decreased significantly in two, but complaints increased in three children. Glucomannan does not appear to be suitable for the treatment of dumping syndrome in children as the side effects seem to overrule the beneficial effects.     

Dumping Syndrome in Children

ABSTRACT. Dumping syndrome is rarely seen in children. We studied ten children with symptoms following various types of gastric surgery. All had abnormal blood glucose and breath hydrogen responses after oral glucose challenge, indicating reduction of both glucose tolerance and glucose absorption, as compared to controls. Glucose tolerance was best expressed as the difference between peak and subsequent lowest blood glucose level, the upper limit of normal (mean + 3 SD) being 5.9 mmol/l. In eight children with persisting symptoms we tested the effects of glucomannan, a highly hygroscopic tasteless fibre, on glucose tolerance and glucose absorption. Glucomannan significantly improved glucose tolerance, but did have no overall effect on glucose absorption. Four children tested glucomannan added to the main meals. Breath hydrogen excretion, as established with the daytime breath hydrogen profile, decreased significantly in two, but complaints increased in three children. Glucomannan does not appear to be suitable for the treatment of dumping syndrome in children as the side effects seem to overrule the beneficial effects.     

The cut-off criterion for a positive hydrogen breath test in children: a reappraisal

Seventy-three preschool children with adequate nutritional status underwent interval-sampling, 3-hour breath-hydrogen carbohydrate absorption tests after consuming either 240 ml of intact milk (containing 12 g of lactose) or the same volume of milk with 90-95% of its lactose prehydrolyzed in vitro (containing less than 1 g lactose, with the remaining sugar as glucose and galactose). Results were examined in a reappraisal of the cut-off criterion for the rise of breath H2 concentration signifying biologically incomplete absorption. If the greater than or equal to 10-ppm criterion advocated by some investigators is used, 83% of our subjects would have been classified as incomplete lactose digesters and 30% would have their tests with the monosaccharide-rich milk classified as positive. With the greater than or equal to 20 ppm criterion used in our laboratory and others, the prevalence of lactose maldigestion in the sample becomes 60% and only 4% of subjects have apparent monosaccharide absorption, 96% having a rise below the cut-off level with prehydrolyzed milk. At least in Guatemalan preschoolers, the 20-ppm criterion for a positive breath H2 test provides a superior specificity-sensitivity balance and more reasonable diagnostic conclusions.     

Breath hydrogen excretion in infants with colic.

Breath hydrogen excretion as an index of incomplete lactose absorption was measured in 118 healthy infants who were either breast fed or given a formula feed containing lactose, some of whom had colic. Infants with colic (n = 65) were selected on the basis of the mother''s report of a history of inconsolable crying lasting several hours each day. Infants in the control group (n = 53) were not reported to cry excessively by their mothers. Breath samples were collected using a face mask sampling device preprandially, and 90 and 150 minutes after the start of a feed. Normalised breath hydrogen concentrations were higher in the group with colic than in the control group at each time point. The median maximum breath hydrogen concentration in the colic group was 29 ppm, and in the control group 11 ppm. The percentage of infants with incomplete lactose absorption (breath hydrogen concentration more than 20 ppm) in the colic group was 62% compared with 32% in the control group. The clinical importance of the observed association between increased breath hydrogen excretion and infantile colic remains to be determined. Increased breath hydrogen excretion indicative of incomplete lactose absorption may be either a cause or an effect of colic in infants.     

‘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.     

The Daytime Breath Hydrogen Profile in Children with Abdominal Symptoms and Diarrhoea

ABSTRACT. The daytime breath hydrogen profile (DBHP) enables the study of breath hydrogen (BH) excretion in children under normal dietary and environmental circumstances. We studied the DBHP in 43 children with abdominal pain and (or) diarrhoea in order to evaluate its use in the detection of carbohydrate malabsorption (CHM). The results were compared to those of the lactose BH test. The DBHP was abnormal in 16 patients (37%), 8 of whom also had an abnormal lactose BH test. Five other patients with an abnormal lactose BH test had a normal DBHP. In 7 out of 10 children with an abnormal DBHP, the recorded abdominal symptoms coincided with a sharp increase in BH excretion. Abnormal DBHPs were most frequently found in children with functional abdominal complaints and with giardiasis. Our findings indicate that CHM is more frequently encountered in children with abdominal symptoms than can be detected by the lactose BH test. The DBHP offers new possibilities in the investigation of gastrointestinal conditions by correlating the symptoms directly to the effect induced by CHM.     

The daytime breath hydrogen profile in children with abdominal symptoms and diarrhoea

The daytime breath hydrogen profile (DBHP) enables the study of breath hydrogen (BH) excretion in children under normal dietary and environmental circumstances. We studied the DBHP in 43 children with abdominal pain and (or) diarrhoea in order to evaluate its use in the detection of carbohydrate malabsorption (CHM). The results were compared to those of the lactose BH test. The DBHP was abnormal in 16 patients (37%), 8 of whom also had an abnormal lactose BH test. Five other patients with an abnormal lactose BH test had a normal DBHP. In 7 out of 10 children with an abnormal DBHP, the recorded abdominal symptoms coincided with a sharp increase in BH excretion. Abnormal DBHPs were most frequently found in children with functional abdominal complaints and with giardiasis. Our findings indicate that CHM is more frequently encountered in children with abdominal symptoms than can be detected by the lactose BH test. The DBHP offers new possibilities in the investigation of gastrointestinal conditions by correlating the symptoms directly to the effect induced by CHM.     

Lactose and fructose malabsorption in children with recurrent abdominal pain: results of double-blinded testing

Aim: To investigate malabsorption of lactose and fructose as causes of recurrent abdominal pain (RAP). Methods: In 220 children (128 girls, mean age 8,8 [4.1–16.0] years) with RAP, hydrogen breath tests (H₂BT; abnormal if ΔH₂ > 30 ppm) were performed with lactose and fructose. Disappearance of RAP with elimination, recurrence with provocation and disappearance with re‐elimination, followed by a 6‐month pain‐free follow‐up, were considered indicative of a causal relation with RAP. For definite proof, a double‐blinded placebo‐controlled (DBPC) provocation was performed. Results: Malabsorption of lactose was found in 57 of 210, of fructose in 79 of 121 patients. Pain disappeared upon elimination in 24/38 patients with lactose malabsorption, and in 32/49 with fructose malabsorption. Open provocation with lactose and fructose was positive in 7/23 and 13/31 patients. DBPC provocation in 6/7 and 8/13 patients was negative in all. However, several children continued to report abdominal symptoms upon intake of milk or fructose. Conclusion: Lactose intolerance nor fructose intolerance could be established as causes of RAP, according to preset criteria including elimination, open provocation and DBPC provocation. However, in clinical practice, persistent feeling of intolerance in some patients should be taken seriously and could warrant extended elimination with repeated challenges.     

Delayed complete functional lactase sufficiency in breast-fed infants

Colonic fermentation of unabsorbed lactose was evaluated by measuring breath hydrogen (BH2) after a regular feeding in 17 white, normal, exclusively breast-fed infants 4-5 weeks of age. Interval breath samples were collected with a specially modified face mask and analyzed by gas chromatography for H2 and CO2 concentrations. Five infants (29%) produced 20 ppm or more of H2, four of whom underwent repeated testing. Three infants stopped producing over 20 ppm of H2 as they grew older. On a repeat evaluation, one of these three infants had levels over 20 ppm when other foods were introduced into his diet. The other continued to have elevated BH2 when weaned. Stools of infants with elevated BH2 levels had no detectable glucose, and pH was over 5.5. Weight-for-age of infants with elevated BH2 was at or above the 75th percentile. BH2 levels, normalized for the amount of breast milk ingested, fell significantly with age. These results show that complete small bowel absorption of lactose from breast milk does not occur in all white, normal, term, appropriate-for-gestational-age infants in the first months of life. The absence of glucose in the stool and the normal stool pH suggest that the unabsorbed lactose that produced H2 can be degraded in the colon.     

Is small-bowel bacterial overgrowth an underdiagnosed disorder in children with gastrointestinal symptoms?

Small-bowel bacterial overgrowth (SBBO) has been implicated in chronic abdominal pain and irritable bowel syndrome in children. This was a retrospective study that aimed to assess the occurrence of SBBO by the lactulose breath hydrogen test in children referred primarily for investigation of carbohydrate malabsorption (n = 287). There were profiles indicative of SBBO in 16% (39/250) of hydrogen-producing children. This indicated that SBBO may be more common in children with gastrointestinal symptoms and apparent carbohydrate malabsorption than previously recognised.     

Beta-galactosidase tablets in the treatment of lactose intolerance in pediatrics

Lactose-intolerant children manifest diminished or nonexistent intestinal lactase activity, resulting in flatulence, abdominal pain, and diarrhea. To assess the hydrolytic capability of lactase-containing tablets taken immediately before oral lactose challenge, we studied 18 children previously identified as being lactose intolerant and having no underlying organic gastrointestinal disease. Subjects had a mean (+/- SEM) age of 11.4 +/- 3.4 years; 72% were male. At time of the study, lactase-containing tablets or placebo tablets were ingested (double-blind) immediately before drinking a solution of lactose. Breath samples were obtained for hydrogen analysis at 30-minute intervals during a 2-hour period, and clinical symptoms were monitored. In lactose-intolerant patients, hydrogen production was significantly greater following placebo (maximum hydrogen excretion, approximately 60 ppm) compared with lactase-containing tablets (maximum hydrogen excretion, 7 ppm). Increased hydrogen production was associated with clinical symptoms including abdominal pain (89% of subjects following placebo ingestion), bloating (83%), diarrhea (61%), and flatulence (44%). These results indicate, therefore, that coingestion of lactose and lactase-containing tablets significantly reduces both breath hydrogen excretion and clinical symptoms associated with lactose intolerance.     

Fructose-induced hyperuricemia: observations in normal children and in patients with hereditary fructose intolerance and galactosemia.

After the infusion of fructose, 0.25 g/kg body wt, the mean peak plasma uric acid level was 5.4 +/- 0.7 (SEM) mg/100 ml in six normal children and was not significantly increased compared with that of the mean basal value of 4.1 +/- 0.5 mg/100 ml. The mean blood inorganic phosphate (Pi) levels were significantly less than the mean fasting value after fructose. Blood glucose, lactic acid, and fructose levels were significantly increased after fructose, but serum magnesium levels did not change. In two patients with hereditary fructose intolerance (HFI) the peak blood uric acid levels were 12.1 and 7.6 mg/100 ml, respectively, after fructose. In both patients the blood glucose concentrations decreased 69 and 26 mg/100 ml below the fasting levels after fructose. The serum Pi level decreased 2.3 and 1.2 mg/100 ml below fasting values, decrements greater than the mean decrement in serum Pi of 0.8 +/- 0.2 mg/100 ml which occurred in six normal children. The mean uric acid excretion, expressed as milligrams per mg urinary creatinine, was 0.6 +/- 0.1 (SEM) before fructose in the normal children and increased significantly to 1.0 +/- mg/mg creatinine after fructose. In two patients with HFI the uric acid excretion increased four- to fivefold after fructose administration; the increased uric acid excretion in HFI exceeded that of normal children. In three patients with galactosemia, increases in blood uric acid levels after galactose ingestion were similar to those in normal children after fructose, but less than those in patients with HFI after fructose. The serum Pi levels decreased less in galactosemic patients after galactose administration than in patients with HFI after fructose infusion. These studies support the hypothesis that fructose-induced hyperuricemia results from degradation of adenosine monophosphate. This effect appears to be specific for fructose. The lack of hyperruricemia in galactosemia patients after galactose ingestion may be explained by the observation that galactose is phosphorylated more slowly than fructose.     

Intestinal fructose malabsorption is associated with increased lactulose fermentation in the intestinal lumen

Objective

To study fructose malabsorption in children and adolescents with abdominal pain associated with functional gastrointestinal disorders. As an additional objective, the association between intestinal fructose malabsorption and food intake, including the estimated fructose consumption, weight, height, and lactulose fermentability were also studied.

Absorption and oxidation of glucose polymers of different lengths in young infants

Because mucosal glucoamylase is most active against glucose polymers less than 10 glucose units in length, longer chain polymers may not be completely absorbed by young infants. In order to investigate this possibility, the absorption and oxidation of 13C-rich glucose, short-chain (3 to 8 glucose units in length) and long-chain (average length 43 units) glucose polymers (GP) were compared in 12 healthy, 1-month-old infants. Recovery of the GP and glucose in stool was measured by determining the 13C enrichment of stool. The oxidation of the GP was measured by tracing the increase in breath 13CO2 after GP were fed. Carbohydrate malabsorbed in the small bowel was assessed by measurement of breath H2, a gas formed from the fermentation of carbohydrate in the colon. Analysis of the infants' stools revealed that one infant excreted 9.7% of the dose of glucose, another 6.7% of the dose of short-chain GP, and five infants excreted 2.6 to 18.5% (mean 8.4%) of the dose of long-chain GP. The percent of the administered dose recovered in breath was similar among substrates (mean = 28.7% of the dose fed). A rise in breath H2 greater than 20 ppm was found in four of the 12 infants after the feeding of glucose, in five of 12 after the short-chain GP, and in six of 12 after the long-chain GP. None of the infants developed diarrhea. The results suggest that healthy young infants do not absorb long-chain GP as completely as they absorb short-chain GP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fructose breath hydrogen tests in infants with chronic non-specific diarrhoea

Clear fluids high in fructose (e.g., apple juice) have been incriminated for symptoms of chronic non-specific diarrhoea (CNSD), in particular in children 1–4 years of age. H₂ breath tests were performed, after ingestion of fructose (1 g/kg), in 15 patients referred with CNSD and 35 controls. All 15 CNSD children (100%) had breath peak H₂ of 20 ppm versus 49% of the 35 controls (P=0.0005). Median peak H₂ in CNSD (90 ppm, range 31–136) was significantly higher than in controls (20 ppm, range 1–139) (P<0.001). Orocoecal transit time in children with positive tests was similar in both groups. Similary, median H₂ increases during the test period had the same distribution. We demonstrated fructose malabsorption in CNSD, but found a great overlap with the control group. Our results strongly discourage the use of fructose breath H₂ tests in children suspected of CNSD. A positive test has no diagnostic value and a negative test has no clinical implications.Conclusion For clinical practice, we suggest a dietary history and a trial of appropriate measures in infants with chronic nonspecific diarrhoea, instead of performing the fructose H₂ breath test.