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Rajindrajith S, Hathagoda W, Devanarayana NM. Functional Diarrhea in Children. Indian J Pediatr 2024; 91:584-589. [PMID: 37507618 DOI: 10.1007/s12098-023-04730-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 06/09/2023] [Indexed: 07/30/2023]
Abstract
Functional diarrhea in children is a disease that has been focused on by both general pediatricians as well as pediatric gastroenterologists across the world. Although it is seen across the pediatric age group from late infancy to adolescence, most still believe that functional diarrhea only occurs in younger children. Recent epidemiological studies have shown that functional diarrhea is prevalent in all subcontinents. The classic clinical features include chronic loose stools with undigested food particles without growth faltering. Although known for long years, pathophysiological mechanisms and therapeutic options are not well explored, and the existing literature is outdated. In this article, authors review the available literature on functional diarrhea, with a reminder that a fresh look is needed to broaden the horizons of understanding of this disease.
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Affiliation(s)
- Shaman Rajindrajith
- Department of Pediatrics, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo-8, Sri Lanka.
- University Pediatric Unit, Lady Ridgeway Hospital for Children, Dr. Danister de Silva Road, Colombo-8, Sri Lanka.
| | - Wathsala Hathagoda
- Department of Pediatrics, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo-8, Sri Lanka
- University Pediatric Unit, Lady Ridgeway Hospital for Children, Dr. Danister de Silva Road, Colombo-8, Sri Lanka
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DeChristopher LR. 40 years of adding more fructose to high fructose corn syrup than is safe, through the lens of malabsorption and altered gut health-gateways to chronic disease. Nutr J 2024; 23:16. [PMID: 38302919 PMCID: PMC10835987 DOI: 10.1186/s12937-024-00919-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 01/19/2024] [Indexed: 02/03/2024] Open
Abstract
Labels do not disclose the excess-free-fructose/unpaired-fructose content in foods/beverages. Objective was to estimate excess-free-fructose intake using USDA loss-adjusted-food-availability (LAFA) data (1970-2019) for high fructose corn syrup (HFCS) and apple juice, major sources of excess-free-fructose, for comparison with malabsorption dosages (~ 5 g-children/ ~ 10 g-adults). Unlike sucrose and equimolar fructose/glucose, unpaired-fructose triggers fructose malabsorption and its health consequences. Daily intakes were calculated for HFCS that is generally-recognized-as-safe/ (55% fructose/45% glucose), and variants (65/35, 60/40) with higher fructose-to-glucose ratios (1.9:1, 1.5:1), as measured by independent laboratories. Estimations include consumer-level-loss (CLL) allowances used before (20%), and after, subjective, retroactively-applied increases (34%), as recommended by corn-refiners (~ 2012). No contributions from crystalline-fructose or agave syrup were included due to lack of LAFA data. High-excess-free-fructose-fruits (apples/pears/watermelons/mangoes) were not included. Eaten in moderation they are less likely to trigger malabsorption. Another objective was to identify potential parallel trends between excess-free-fructose intake and the "unexplained" US asthma epidemic. The fructose/gut-dysbiosis/lung axis is well documented, case-study evidence and epidemiological research link HFCS/apple juice intake with asthma, and unlike gut-dysbiosis/gut-fructosylation, childhood asthma prevalence data spans > 40 years. Results Excess-free-fructose daily intake for individuals consuming HFCS with an average 1.5:1 fructose-to-glucose ratio, ranged from 0.10 g/d in 1970, to 11.3 g/d in 1999, to 6.5 g/d in 2019, and for those consuming HFCS with an average 1.9:1 ratio, intakes ranged from 0.13 g/d to 16.9 g/d (1999), to 9.7 g/d in 2019, based upon estimates with a 20% CLL allowance. Intake exceeded dosages that trigger malabsorption (~ 5 g) around ~ 1980. By the early 1980's, tripled apple juice intake had added ~ 0.5 g to average-per-capita excess-free-fructose intake. Contributions were higher (~ 3.8 g /4-oz.) for individuals consuming apple juice consistent with a healthy eating pattern (4-oz. children, 8-oz. adults). The "unexplained" childhood asthma epidemic (1980-present) parallels increasing average-per-capita HFCS/apple juice intake trends and reflects epidemiological research findings. Conclusion Displacement of sucrose with HFCS, its ubiquitous presence in the US food-supply, the industry practice of adding more fructose to HFCS than generally-recognized-as-safe, and increased use of apple juice/crystalline fructose/agave syrup in foods/beverages has contributed to unprecedented excess-free-fructose intake levels, fructose malabsorption, gut-dysbiosis and gut-fructosylation (immunogen burden)-gateways to chronic disease.
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Broekaert IJ, Borrelli O, Dolinsek J, Martin-de-Carpi J, Mas E, Miele E, Pienar C, Ribes-Koninckx C, Thomassen R, Thomson M, Tzivinikos C, Benninga M. An ESPGHAN Position Paper on the Use of Breath Testing in Paediatric Gastroenterology. J Pediatr Gastroenterol Nutr 2022; 74:123-137. [PMID: 34292218 DOI: 10.1097/mpg.0000000000003245] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
OBJECTIVES Given a lack of a systematic approach to the use of breath testing in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimise its utility and safety. METHODS Nine clinical questions regarding methodology, interpretation, and specific indications of breath testing and treatment of carbohydrate malabsorption were addressed by members of the Gastroenterology Committee (GIC) of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN).A systematic literature search was performed from 1983 to 2020 using PubMed, the MEDLINE and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes.During a consensus meeting, all recommendations were discussed and finalised. In the absence of evidence from randomised controlled trials, recommendations reflect the expert opinion of the authors. RESULTS A total of 22 recommendations were voted on using the nominal voting technique. At first, recommendations on prerequisites and preparation for as well as on interpretation of breath tests are given. Then, recommendations on the usefulness of H2-lactose breath testing, H2-fructose breath testing as well as of breath tests for other types of carbohydrate malabsorption are provided. Furthermore, breath testing is recommended to diagnose small intestinal bacterial overgrowth (SIBO), to control for success of Helicobacter pylori eradication therapy and to diagnose and monitor therapy of exocrine pancreatic insufficiency, but not to estimate oro-caecal transit time (OCTT) or to diagnose and follow-up on celiac disease. CONCLUSIONS Breath tests are frequently used in paediatric gastroenterology mainly assessing carbohydrate malabsorption, but also in the diagnosis of small intestinal overgrowth, fat malabsorption, H. pylori infection as well as for measuring gastrointestinal transit times. Interpretation of the results can be challenging and in addition, pertinent symptoms should be considered to evaluate clinical tolerance.
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Affiliation(s)
- Ilse Julia Broekaert
- Department of Paediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Osvaldo Borrelli
- Department of Paediatric Gastroenterology, Great Ormond Street Hospital, London, UK
| | - Jernej Dolinsek
- Department of Paediatrics, University Medical Centre Maribor, Maribor, Slovenia
| | - Javier Martin-de-Carpi
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain
| | - Emmanuel Mas
- Unité de Gastroentérologie, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires du Métabolisme, Hôpital des Enfants, CHU de Toulouse, Toulouse, France; IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France
| | - Erasmo Miele
- Department of Translational Medical Science, Section of Paediatrics, University of Naples "Federico", Naples, Italy
| | - Corina Pienar
- Department of Paediatrics, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania
| | - Carmen Ribes-Koninckx
- Department of Paediatric Gastroenterology, Hepatology & Nutrition, La Fe University Hospital, Valencia, Spain
| | - Rut Thomassen
- Department of Paediatric Medicine, Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Norway
| | - Mike Thomson
- Centre for Paediatric Gastroenterology, Sheffield Children's Hospital, Sheffield, UK
| | - Christos Tzivinikos
- Department of Paediatric Gastroenterology, Al Jalila Children's Specialty Hospital, Dubai, UAE
| | - Marc Benninga
- Department of Paediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam University Medical Centres, Amsterdam, The Netherlands
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Kwiecień J, Hajzler W, Kosek K, Balcerowicz S, Grzanka D, Gościniak W, Górowska-Kowolik K. No Correlation between Positive Fructose Hydrogen Breath Test and Clinical Symptoms in Children with Functional Gastrointestinal Disorders: A Retrospective Single-Centre Study. Nutrients 2021; 13:2891. [PMID: 34445050 PMCID: PMC8401680 DOI: 10.3390/nu13082891] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 08/13/2021] [Accepted: 08/19/2021] [Indexed: 12/04/2022] Open
Abstract
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.
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Affiliation(s)
- Jarosław Kwiecień
- Department of Paediatrics, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-800 Zabrze, Poland;
| | - Weronika Hajzler
- Faculty of Medical Sciences in Zabrze, Doctoral School, Medical University of Silesia, 41-800 Zabrze, Poland;
| | - Klaudia Kosek
- Faculty of Medical Sciences in Zabrze, Students’ Scientific Association of the Medical University in Silesia, 41-800 Zabrze, Poland; (K.K.); (D.G.); (W.G.)
| | - Sylwia Balcerowicz
- Clinical Hospital No 1 in Zabrze, Medical University of Silesia, 41-800 Zabrze, Poland;
| | - Dominika Grzanka
- Faculty of Medical Sciences in Zabrze, Students’ Scientific Association of the Medical University in Silesia, 41-800 Zabrze, Poland; (K.K.); (D.G.); (W.G.)
| | - Weronika Gościniak
- Faculty of Medical Sciences in Zabrze, Students’ Scientific Association of the Medical University in Silesia, 41-800 Zabrze, Poland; (K.K.); (D.G.); (W.G.)
| | - Katarzyna Górowska-Kowolik
- Department of Paediatrics, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 41-800 Zabrze, Poland;
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DeChristopher LR, Auerbach BJ, Tucker KL. High fructose corn syrup, excess-free-fructose, and risk of coronary heart disease among African Americans- the Jackson Heart Study. BMC Nutr 2020; 6:70. [PMID: 33292663 PMCID: PMC7722296 DOI: 10.1186/s40795-020-00396-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Accepted: 10/31/2020] [Indexed: 02/07/2023] Open
Abstract
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.
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Affiliation(s)
- Luanne R. DeChristopher
- Independent Researcher, M.Sc. Biochemistry, Molecular Biology, P.O. Box 5542, Eugene, OR 97405 USA
| | | | - Katherine L. Tucker
- Department of Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, MA USA
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Martínez-Azcona O, Moreno-Álvarez A, Seoane-Pillado T, Niño-Grueiro I, Ramiro-Comesaña A, Menéndez-Riera M, Pérez-Domínguez M, Solar-Boga A, Leis-Trabazo R. Fructose malabsorption in asymptomatic children and in patients with functional chronic abdominal pain: a prospective comparative study. Eur J Pediatr 2019; 178:1395-1403. [PMID: 31325029 DOI: 10.1007/s00431-019-03418-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Revised: 06/18/2019] [Accepted: 06/19/2019] [Indexed: 12/17/2022]
Abstract
The objective of this prospective cohort study was to compare fructose malabsorption in patients with functional chronic abdominal pain and in healthy children. The sample was divided into two groups: asymptomatic children and pain-predominant functional gastrointestinal disorders according to the Rome IV criteria. All children were tested for fructose malabsorption by a standardized breath hydrogen test. Hydrogen and methane were measured and the test was presumed positive when it exceeded 20 ppm above baseline. If positive, patients were given a low-fructose diet and the response was evaluated. One hundred five children were included (34 healthy children, 71 with functional chronic abdominal pain), with similar demographic characteristics in both groups (35.2% male, age 9.5 ± 2.8 years). Hydrogen levels in breath were tested through a hydrogen test for fructose demonstrating malabsorption in 58.8% of healthy children (95%CI 40.8%-76.8%) and in 40.8% of children with chronic abdominal pain (95%CI 28.7%-53.0%), removing those who had bacterial overgrowth. Twenty-one of 31 patients with symptoms and a positive test (72.4%) reported an improvement on a low-fructose diet.Conclusion: Fructose malabsorption is more common in asymptomatic children than in patients with chronic abdominal pain. Better standardized test conditions are necessary to improve accuracy of diagnosis before using this test in clinical practice. What is Known: • Although fructose malabsorption is believed to be related with chronic abdominal pain, high-quality evidence is lacking. • Concerns have raised regarding the use of breath hydrogen test for fructose malabsorption in children with chronic abdominal pain. What is New: • Fructose malabsorption is not more common in children with pain-predominant functional gastrointestinal disorders than in asymptomatic children. • Improvement in symptoms with low-fructose diet may indicate that, although patients with pain-predominant functional gastrointestinal disorders did not have a higher percentage of malabsorption, they had greater fructose intolerance.
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Affiliation(s)
- Oihana Martínez-Azcona
- Department of Pediatrics, Complexo Hospitalario Universitario A Coruña, A Coruña, Spain.
| | - Ana Moreno-Álvarez
- Pediatric Gastroenterology, Hepatology and Nutrition Unit, Department of Pediatrics, Complexo Hospitalario Universitario A Coruña, A Coruña, Spain
| | - Teresa Seoane-Pillado
- Clinical Epidemiology and Biostatistics Unit, Complexo Hospitalario Universitario A Coruña, A Coruña, Spain
| | | | | | | | | | - Alfonso Solar-Boga
- Pediatric Gastroenterology, Hepatology and Nutrition Unit, Department of Pediatrics, Complexo Hospitalario Universitario A Coruña, A Coruña, Spain
| | - Rosaura Leis-Trabazo
- Pediatric Gastroenterology, Hepatology and Nutrition Unit, Department of Pediatrics, Complexo Hospitalario Universitario Santiago de Compostela, Santiago de Compostela, Spain
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Hammer V, Hammer K, Memaran N, Huber WD, Hammer K, Hammer J. Relationship Between Abdominal Symptoms and Fructose Ingestion in Children with Chronic Abdominal Pain. Dig Dis Sci 2018; 63:1270-1279. [PMID: 29511898 PMCID: PMC5895692 DOI: 10.1007/s10620-018-4997-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 02/22/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND Limited valid data are available regarding the association of fructose-induced symptoms, fructose malabsorption, and clinical symptoms. AIM To develop a questionnaire for valid symptom assessment before and during a carbohydrate breath test and to correlate symptoms with fructose breath test results in children/adolescents with functional abdominal pain. METHODS A Likert-type questionnaire assessing symptoms considered relevant for hydrogen breath test in children was developed and underwent initial validation. Fructose malabsorption was determined by increased breath hydrogen in 82 pediatric patients with functional abdominal pain disorders; fructose-induced symptoms were quantified by symptom score ≥2 and relevant symptom increase over baseline. The results were correlated with clinical symptoms. The time course of symptoms during the breath test was assessed. RESULTS The questionnaire exhibited good psychometric properties in a standardized assessment of the severity of carbohydrate-related symptoms. A total of 40 % (n = 33) had malabsorption; symptoms were induced in 38 % (n = 31), but only 46 % (n = 15) with malabsorption were symptomatic. There was no significant correlation between fructose malabsorption and fructose-induced symptoms. Clinical symptoms correlated with symptoms evoked during the breath test (p < 0.001, r2 = 0.21) but not with malabsorption (NS). Malabsorbers did not differ from non-malabsorbers in terms of symptoms during breath test. Symptomatic patients had significantly higher pain and flatulence scores over the 9-h observation period (p < 0.01) than did nonsymptomatic patients; the meteorism score was higher after 90 min. CONCLUSIONS Fructose-induced symptoms but not fructose malabsorption are related to increased abdominal symptoms and have distinct timing patterns.
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Affiliation(s)
- Veronika Hammer
- Abteilung für Gastroenterologie und Hepatologie, Universitätsklinik für Innere Medizin 3, Medical University of Vienna, Währinger Gürtel 18 - 20, 1090, Vienna, Austria
| | - Katharina Hammer
- Abteilung für Gastroenterologie und Hepatologie, Universitätsklinik für Innere Medizin 3, Medical University of Vienna, Währinger Gürtel 18 - 20, 1090, Vienna, Austria
| | - Nima Memaran
- Klinische Abteilung für Pädiatrische Nephrologie und Gastroenterologie, Universitätsklinik für Kinder- und Jugendheilkunde, Medical University of Vienna, Vienna, Austria
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Children's Hospital, Hannover Medical School, Hanover, Germany
| | - Wolf-Dietrich Huber
- Klinische Abteilung für Pädiatrische Nephrologie und Gastroenterologie, Universitätsklinik für Kinder- und Jugendheilkunde, Medical University of Vienna, Vienna, Austria
| | - Karin Hammer
- St. Anna Kinderspital, Medical University of Vienna, Vienna, Austria
| | - Johann Hammer
- Abteilung für Gastroenterologie und Hepatologie, Universitätsklinik für Innere Medizin 3, Medical University of Vienna, Währinger Gürtel 18 - 20, 1090, Vienna, Austria.
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Excess free fructose, high-fructose corn syrup and adult asthma: the Framingham Offspring Cohort. Br J Nutr 2018; 119:1157-1167. [PMID: 29587887 DOI: 10.1017/s0007114518000417] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
There is growing evidence that intakes of high-fructose corn syrup (HFCS), HFCS-sweetened soda, fruit drinks and apple juice - a high-fructose 100 % juice - are associated with asthma, possibly because of the high fructose:glucose ratios and underlying fructose malabsorption, which may contribute to enteral formation of pro-inflammatory advanced glycation end products, which bind receptors that are mediators of asthma. Cox proportional hazards models were used to assess associations between intakes of these beverages and asthma risk, with data from the Framingham Offspring Cohort. Diet soda and orange juice - a 100 % juice with a 1:1 fructose:glucose ratio - were included for comparison. Increasing intake of any combination of HFCS-sweetened soda, fruit drinks and apple juice was significantly associated with progressively higher asthma risk, plateauing at 5-7 times/week v. never/seldom, independent of potential confounders (hazard ratio 1·91, P<0·001). About once a day consumers of HFCS-sweetened soda had a 49 % higher risk (P<0·011), moderate apple juice consumers (2-4 times/week) had a 61 % higher risk (P<0·007) and moderate fruit drink consumers had a 58 % higher risk (P<0·009), as compared with never/seldom consumers. There were no associations with diet soda/orange juice. These associations are possibly because of the high fructose:glucose ratios, and fructose malabsorption. Recommendations to reduce consumption may be inadequate to address asthma risk, as associations are evident even with moderate intake of these beverages, including apple juice - a 100 % juice. The juice reductions in the US Special Supplemental Nutrition Program for Women, Infants, and Children in 2009, and the plateauing/decreasing asthma prevalence (2010-2013), particularly among non-Hispanic black children, may be related. Further research regarding the consequences of fructose malabsorption is needed.
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DeChristopher LR. Perspective: The Paradox in Dietary Advanced Glycation End Products Research-The Source of the Serum and Urinary Advanced Glycation End Products Is the Intestines, Not the Food. Adv Nutr 2017; 8:679-683. [PMID: 28916568 PMCID: PMC5593110 DOI: 10.3945/an.117.016154] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Inconsistent research results have impeded our understanding of the degree to which dietary advanced glycation end products (dAGEs) contribute to chronic disease. Early research suggested that Western-style fast foods, including grilled and broiled meats and French fries, contain high levels of proinflammatory advanced glycation end products (AGEs). However, recent studies with state-of-the-art ultraperformance LC-tandem mass spectrometry (UPLC-MS) found that there is no evidence that these foods have elevated levels of dAGEs relative to other foods. Paradoxically, observational research found that the intake of fruits (mainly apples), fruit juices (apple juice), vegetables, nuts, seeds, soy, and nonfat milk, which are foods synonymous with healthy eating, as well as the intake of cold breakfast cereals, whole grains (breads), and sweets, which are sources of high-fructose corn syrup (HFCS), were associated with elevated serum and urinary N-ε-carboxymethyl-lysine (CML). Ironically, these are the same foods found to have lower CML levels, as measured by UPLC-MS. One possible explanation for this paradox is that the source of the elevated CML is the intestines, not the food. When considered collectively, dAGE research results are consistent with the "fructositis" hypothesis, which states that intake of foods and beverages with high fructose-to-glucose ratios (HFCS-sweetened foods and beverages, agave syrup, crystalline fructose, apple juice, and apple juice blends) promotes the intestinal in situ formation of readily absorbed, proinflammatory extracellular, newly identified, fructose-associated AGE, an overlooked source of immunogenic AGEs.
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DeChristopher LR, Uribarri J, Tucker KL. Intake of high fructose corn syrup sweetened soft drinks, fruit drinks and apple juice is associated with prevalent coronary heart disease, in U.S. adults, ages 45-59 y. BMC Nutr 2017; 3:51. [PMID: 32153831 PMCID: PMC7050890 DOI: 10.1186/s40795-017-0168-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Accepted: 06/09/2017] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Intake of high excess free fructose (EFF) beverages, including high fructose corn syrup (HFCS), sweetened soft drinks, fruit drinks, and apple juice, may be associated with childhood asthma, adult idiopathic chronic bronchitis/ COPD, and autoimmune arthritis, possibly due to underlying fructose malabsorption. Fructose malabsorption may contribute to the intestinal in situ formation of advanced glycation end-products (enFruAGEs) that travel to other tissues and promote inflammation. Chronic respiratory conditions and arthritis are comorbidities of coronary heart disease (CHD). The objective of this study was to investigate the association between intake of high EFF beverages and CHD. METHODS In this cross sectional study (NHANES 2003-2006) of adults, aged 45-59 y, n = 1230, the exposure variables were non-diet soft drinks, and any combination of high EFF beverages including non-diet soft drinks, fruit drinks, and apple juice. Analyses of diet soft drinks, diet fruit drinks, and orange juice (non/low EFF beverages) were included for comparison. The outcome was self-reported history of coronary heart disease and/or angina (CHD). Rao Scott Ҳ2 was used for prevalence differences and logistic regression for associations, adjusted for age, sex, race-ethnicity, BMI, socio-economic status, health insurance coverage, smoking, physical activity level, hypertension, energy intake, fruit and vegetable intake, glycated hemoglobin, pre-diabetes, and diabetes. RESULTS Intake of any combination of HFCS sweetened soft drinks, fruit drinks, and apple juice (tEFF) was significantly associated with CHD in adults aged 45-59 y. Adults consuming tEFF ≥5 times/wk. were 2.8 times more likely to report CHD than ≤3 times/mo consumers (OR 2.82; 95% CI 1.16-6.84; P = 0.023), independent of all covariates. CONCLUSION HFCS sweetened soft drinks, fruit drinks, and apple juice may contribute to CHD, a common comorbidity of chronic respiratory conditions and autoimmune arthritis, possibly due to the high ratio of fructose to glucose in these beverages. Underlying fructose malabsorption may contribute to the intestinal in situ formation of pro-inflammatory enFruAGEs, that are eventually absorbed and induce inflammation of the coronary arteries. Additional research is needed.
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Affiliation(s)
| | - Jaime Uribarri
- Department of Medicine, the Icahn School of Medicine at Mount Sinai, New York, NY USA
| | - Katherine L. Tucker
- Department of Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, MA USA
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Yuce O, Kalayci AG, Comba A, Eren E, Caltepe G. Lactose and Fructose Intolerance in Turkish Children with Chronic Abdominal Pain. Indian Pediatr 2017; 53:394-7. [PMID: 27254047 DOI: 10.1007/s13312-016-0860-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
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.
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Affiliation(s)
- Ozlem Yuce
- Department of Pediatric Gastroenterology, Ondokuz Mayis University, Samsun, Turkey. Correspondence to: Dr Ozlem Yuce, Ondokuz Mayis University, Faculty of Medicine, Department of Pediatric Gastroenterology, Samsun, Turkey.
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DeChristopher LR, Uribarri J, Tucker KL. The link between soda intake and asthma: science points to the high-fructose corn syrup, not the preservatives: a commentary. Nutr Diabetes 2016; 6:e234. [PMID: 27892935 PMCID: PMC5133361 DOI: 10.1038/nutd.2016.46] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 09/30/2016] [Accepted: 10/05/2016] [Indexed: 12/11/2022] Open
Abstract
Recent research conducted by investigators at the National Center for Chronic Disease Prevention and Health Promotion—a division of the US Centers for Disease Control and Prevention (CDC)—found that 'Regular-Soda Intake, Independent of Weight Status, is Associated with Asthma among US High School Students.' On the basis of their review of prior studies, researchers hypothesized that the association may be due to high intake of sodium benzoate, a commonly used preservative in US soft drinks. But a closer look at these prior research studies suggests that there is no strong scientific evidence that the preservatives in US soft drinks are associated with asthma. Importantly, other recent research suggests that the association may be with the unpaired (excess free) fructose in high fructose corn syrup.
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Affiliation(s)
| | - J Uribarri
- Department of Medicine, the Icahn School of Medicine at Mount Sinai, New York, USA
| | - K L Tucker
- Department of Clinical Laboratory and Nutritional Sciences, University of Massachusetts, Lowell, MA, USA
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13
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DeChristopher LR, Uribarri J, Tucker KL. Intake of high-fructose corn syrup sweetened soft drinks, fruit drinks and apple juice is associated with prevalent arthritis in US adults, aged 20-30 years. Nutr Diabetes 2016; 6:e199. [PMID: 26950480 PMCID: PMC4817078 DOI: 10.1038/nutd.2016.7] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2015] [Revised: 11/28/2015] [Accepted: 01/23/2016] [Indexed: 01/04/2023] Open
Abstract
OBJECTIVE There is a link between joint and gut inflammation of unknown etiology in arthritis. Existing research indicates that regular consumption of high-fructose corn syrup sweetened (HFCS) soft drinks, but not diet soft drinks, may be associated with increased risk of seropositive rheumatoid arthritis (RA) in women, independent of other dietary and lifestyle factors. One unexplored hypothesis for this association is that fructose malabsorption, due to regular consumption of excess free fructose (EFF) and HFCS, contributes to fructose reactivity in the gastrointestinal tract and intestinal in situ formation of enFruAGEs, which once absorbed, travel beyond the intestinal boundaries to other tissues and promote inflammation. In separate studies, the accumulation of advanced glycation end-products has been associated with joint inflammation in RA. Objective of this study was to assess the association between EFF beverages intake and non-age, non-wear and tear-associated arthritis in US young adults. METHODS In this cross sectional study of 1209 adults aged 20-30y, (Nutrition and Health Examination Surveys 2003-2006) exposure variables were high EFF beverages, including HFCS sweetened soft drinks, and any combination of HFCS sweetened soft drinks, fruit drinks (FD) and apple juice, referred to as tEFF. Analyses of diet soda and diet FD were included for comparison. The outcome was self-reported arthritis. Rao Scott Ҳ(2) was used for prevalence differences and logistic regression for associations, adjusted for confounders. RESULTS Young adults consuming any combination of high EFF beverages (tEFF) ⩾5 times/week (but not diet soda) were three times as likely to have arthritis as non/low consumers (odds ratios=3.01; p⩽0.021; 95% confidence intervals=1.20-7.59), independent of all covariates, including physical activity, other dietary factors, blood glucose and smoking. CONCLUSION EFF beverage intake is significantly associated with arthritis in US adults aged 20-30 years, possibly due to the intestinal in situ formation of enFruAGEs.
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Affiliation(s)
| | - J Uribarri
- Department of Medicine, Icahn School of Medicine, New York, NY, USA
| | - K L Tucker
- Department of Clinical Laboratory and Nutritional Sciences, University of Massachusetts, Lowell, MA, USA
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Abstract
Incomplete intestinal absorption of fructose might lead to abdominal complaints such as pain, flatulence and diarrhoea. Whether defect fructose transporters such as GLUT5 or GLUT2 are involved in the pathogenesis of fructose malabsorption is a matter of debate. The hydrogen production by colonic bacteria is used for diagnosis with the hydrogen breath test. However, the appropriate fructose test dose for correct diagnosis is unclear. Subjects with fructose malabsorption show increased breath hydrogen levels and abdominal symptoms after fructose administration but do not report any symptoms when fructose is given together with glucose. This beneficial effect of glucose, however, cannot be explained yet but might be used for clinical care of these subjects.
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Affiliation(s)
- Karolin Ebert
- Pädiatrische Ernährungsmedizin, Klinikum rechts der Isar (MRI), Technische Universität München (TUM), Gregor-MendelStr. 2, 85354, Freising, Germany. .,Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), Technische Universität München (TUM), Gregor-MendelStr. 2, 85354, Freising, Germany. .,Zentralinstitut für Ernährungs- und Lebensmittelforschung (ZIEL), Technische Universität München (TUM), Gregor-MendelStr. 2, 85354, Freising, Germany.
| | - Heiko Witt
- Pädiatrische Ernährungsmedizin, Klinikum rechts der Isar (MRI), Technische Universität München (TUM), Gregor-MendelStr. 2, 85354, Freising, Germany. .,Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), Technische Universität München (TUM), Gregor-MendelStr. 2, 85354, Freising, Germany. .,Zentralinstitut für Ernährungs- und Lebensmittelforschung (ZIEL), Technische Universität München (TUM), Gregor-MendelStr. 2, 85354, Freising, Germany.
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15
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DeChristopher LR, Uribarri J, Tucker KL. Intake of high fructose corn syrup sweetened soft drinks is associated with prevalent chronic bronchitis in U.S. Adults, ages 20-55 y. Nutr J 2015; 14:107. [PMID: 26474970 PMCID: PMC4609055 DOI: 10.1186/s12937-015-0097-x] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 10/07/2015] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND High fructose corn syrup (HFCS) sweetened soft drink intake has been linked with asthma in US high-schoolers. Intake of beverages with excess free fructose (EFF), including apple juice, and HFCS sweetened fruit drinks and soft drinks, has been associated with asthma in children. One hypothesis for this association is that underlying fructose malabsorption and fructose reactivity in the GI may contribute to in situ formation of enFruAGEs. EnFruAGEs may be an overlooked source of advanced glycation end-products (AGE) that contribute to lung disease. AGE/ RAGEs are elevated in COPD lungs. EFF intake has increased in recent decades, and intakes may exceed dosages associated with adult fructose malabsorption in subsets of the population. Intestinal dysfunction has been shown to be elevated in COPD patients. The objective of this study was to investigate the association between HFCS sweetened soft drink intake and chronic bronchitis (CB), a common manifestation of COPD, in adults. METHODS DESIGN In this cross sectional analysis, the outcome variable was self-reported existing chronic bronchitis or history of CB. Exposure variable was non-diet soda. Rao Scott Ҳ(2) was used for prevalence differences and logistic regression for associations, adjusted for age, sex, race-ethnicity, BMI, smoking, exposure to in-home smoking, pre-diabetes, diabetes, SES, total energy and total fruits and beverages consumption. SETTING Data are from the National Health and Nutrition Examination Survey 2003-2006. SUBJECTS 2801 adults aged 20-55 y. RESULTS There was a statistically significant correlation between intake of non-diet soft drinks and greater prevalence and odds of chronic bronchitis (p < 0.05). Independent of all covariates, intake of non-diet soda ≥5 times a week (vs. non/low non-diet soda) was associated with nearly twice the likelihood of having chronic bronchitis (OR = 1.80; p = 0.047; 95% CI 1.01-3.20). CONCLUSIONS HFCS sweetened soft drink intake is correlated with chronic bronchitis in US adults aged 20-55 y, after adjusting for covariates, including smoking. Results support the hypothesis that underlying fructose malabsorption and fructose reactivity in the GI may contribute to chronic bronchitis, perhaps through in situ formation of enFruAGEs, which may contribute to lung disease. Longitudinal and biochemical research is needed to confirm and clarify the mechanisms involved.
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Affiliation(s)
- Luanne Robalo DeChristopher
- Biochemistry, Molecular Biology, NY Medical College, Valhalla, NY, USA.
- , P.O. Box 5542, Eugene, OR, 97405, USA.
| | - Jaime Uribarri
- Department of Medicine, the Icahn School of Medicine, New York, NY, USA
| | - Katherine L Tucker
- Department of Clinical Laboratory and Nutritional Sciences, University of Massachusetts, Lowell, MA, USA
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17
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Biesiekierski JR. Fructose-induced symptoms beyond malabsorption in FGID. United European Gastroenterol J 2014; 2:10-3. [PMID: 24918003 DOI: 10.1177/2050640613510905] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Accepted: 10/04/2013] [Indexed: 12/11/2022] Open
Abstract
The dietary carbohydrate fructose can be incompletely absorbed in the small intestine and is sometimes associated with gastrointestinal symptoms that include motility disturbances and abdominal pain. Fructose malabsorption has been well documented in variable but similar proportions of healthy and populations with functional gastrointestinal disorders. Recent work into the expression of the main intestinal fructose transporter proteins highlight that our understanding of the mechanistic basis for fructose malabsorption and how it differentiates in gastrointestinal patients is incomplete. Until we have further mechanistic insight, restricting dietary fructose intake and other poorly absorbed short-chain carbohydrates and polyols remains an efficacious approach for managing functional gastrointestinal symptoms.
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18
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Lozinsky AC, Boé C, Palmero R, Fagundes-Neto U. Fructose malabsorption in children with functional digestive disorders. ARQUIVOS DE GASTROENTEROLOGIA 2014; 50:226-30. [PMID: 24322196 DOI: 10.1590/s0004-28032013000200040] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2013] [Accepted: 06/26/2013] [Indexed: 12/18/2022]
Abstract
CONTEXT Fructose is a monosaccharide frequently present in natural and artificial juice fruits. When the concentration of fructose in certain food is present in excess of glucose concentration some individuals may develop fructose malabsorption. OBJECTIVES To report the frequency of fructose malabsorption utilizing the hydrogen breath test in children with gastrointestinal and/or nutritional disorders. METHODS Between July 2011 and July 2012, 43 patients with gastrointestinal and/or nutritional disorders, from both sexes, were consecutively studied, utilizing the hydrogen breath test with loads of the following carbohydrates: lactose, glucose, fructose and lactulose. Fructose was offered in a 10% aqueous solution in the dose of 1 g/kg body weight. Samples were collected fasting and at every 15 minutes after the intake of the aqueous solution for a 2 hour period. Malabsorption was considered when there was an increase of >20 ppm of hydrogen over the fasting level, and intolerance was diagnosed if gastrointestinal symptoms would appear. RESULTS The age of the patients varied from 3 months to 16 years, 24 were boys. The following diagnosis were established: irritable bowel syndrome with diarrhea in 16, functional abdominal pain in 8, short stature in 10, lactose intolerance in 3, celiac disease in 1, food allergy in 1 and giardiasis in 1 patient. Fructose malabsorption was characterized in 13 (30.2%) patients, and intolerance in 1 (2.3%) patient. The most frequent fructose malabsorption was characterized in 7 (16.3%) patients with irritable bowel syndrome and in 4 (9.3%) patients with functional abdominal pain. CONCLUSIONS Patients with irritable bowel syndrome and functional abdominal pain were the main cause of fructose malabsorption.
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Affiliation(s)
- Adriana Chebar Lozinsky
- Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Pediatria, SP, Brasil
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19
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Jones HF, Butler RN, Moore DJ, Brooks DA. Developmental changes and fructose absorption in children: effect on malabsorption testing and dietary management. Nutr Rev 2013; 71:300-9. [DOI: 10.1111/nure.12020] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Affiliation(s)
| | | | - David J Moore
- Gastroenterology Unit; Women's & Children's Hospital; Adelaide; South Australia; Australia
| | - Doug A Brooks
- Mechanisms in Cell Biology and Diseases Research Group; School of Pharmacy and Medical Sciences; Sansom Institute for Health Research; University of South Australia; Adelaide; South Australia; Australia
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20
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Kim Y, Park SC, Wolf BW, Hertzler SR. Combination of erythritol and fructose increases gastrointestinal symptoms in healthy adults. Nutr Res 2011; 31:836-41. [DOI: 10.1016/j.nutres.2011.09.025] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2011] [Revised: 09/25/2011] [Accepted: 09/29/2011] [Indexed: 12/27/2022]
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Effect of age on fructose malabsorption in children presenting with gastrointestinal symptoms. J Pediatr Gastroenterol Nutr 2011; 52:581-4. [PMID: 21502829 DOI: 10.1097/mpg.0b013e3181fd1315] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES Fructose malabsorption can produce symptoms such as chronic diarrhoea and abdominal pain. Here, we retrospectively review breath hydrogen test (BHT) results to determine whether age has an effect on the clinical application of the fructose BHT and compare this with the lactose BHT. PATIENTS AND METHODS Patients were referred to a gastroenterology breath-testing clinic (2003-2008) to investigate carbohydrate malabsorption as a cause of gastrointestinal symptoms. Patients received either 0.5 g/kg body weight of fructose (maximum of 10 g) or 2 g/kg of lactose (maximum of 20 g), in water, and were tested for 2.5 hours. RESULTS Patient age showed a significant effect on the fructose BHT results (P < 0.001, 0.1-79 years old, n = 1093). The odds of testing positive for fructose malabsorption in paediatric patients (15 years old or younger, n = 760) decreased by a factor of 0.82/year (95% confidence interval 0.79-0.86, P < 0.001). There were 88.2% positive in younger than 1-year-olds, 66.6% in 1- to 5-year-olds, 40.4% in 6- to 10-year-olds, and 27.1% in 10- to 15-year-olds. In contrast, 39.3% of lactose BHTs were positive, with no significant relation between patient age and test result (P = 0.115, 0.1-89 years old, n = 3073). CONCLUSIONS The majority of infants with gastrointestinal symptoms exhibited fructose malabsorption, but the capacity to absorb fructose increased with patient age up to 10 years old. The low threshold for fructose absorption in younger children has significant implications for the performance and interpretation of the fructose BHT and for the dietary consumption of fructose in infants with gastrointestinal symptoms.
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22
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Born P. The clinical impact of carbohydrate malabsorption. Arab J Gastroenterol 2011; 12:1-4. [DOI: 10.1016/j.ajg.2011.01.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2010] [Accepted: 11/30/2010] [Indexed: 01/28/2023]
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Jones HF, Butler RN, Brooks DA. Intestinal fructose transport and malabsorption in humans. Am J Physiol Gastrointest Liver Physiol 2011; 300:G202-6. [PMID: 21148401 DOI: 10.1152/ajpgi.00457.2010] [Citation(s) in RCA: 109] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Fructose is a hexose sugar that is being increasingly consumed in its monosaccharide form. Patients who exhibit fructose malabsorption can present with gastrointestinal symptoms that include chronic diarrhea and abdominal pain. However, with no clearly established gastrointestinal mechanism for fructose malabsorption, patient analysis by the proxy of a breath hydrogen test (BHT) is controversial. The major transporter for fructose in intestinal epithelial cells is thought to be the facilitative transporter GLUT5. Consistent with a facilitative transport system, we show here by analysis of past studies on healthy adults that there is a significant relationship between fructose malabsorption and fructose dose (r = 0.86, P < 0.001). Thus there is a dose-dependent and limited absorption capacity even in healthy individuals. Changes in fructose malabsorption with age have been observed in human infants, and this may parallel the developmental regulation of GLUT5 expression. Moreover, a GLUT5 knockout mouse has displayed the hallmarks associated with profound fructose malabsorption. Fructose malabsorption appears to be partially modulated by the amount of glucose ingested. Although solvent drag and passive diffusion have been proposed to explain the effect of glucose on fructose malabsorption, this could possibly be a result of the facilitative transporter GLUT2. GLUT5 and GLUT2 mRNA have been shown to be rapidly upregulated by the presence of fructose and GLUT2 mRNA is also upregulated by glucose, but in humans the distribution and role of GLUT2 in the brush border membrane are yet to be definitively decided. Understanding the relative roles of these transporters in humans will be crucial for establishing a mechanistic basis for fructose malabsorption in gastrointestinal patients.
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Affiliation(s)
- Hilary F Jones
- Mechanisms in Cell Biology and Disease Research Group, Sansom Institute for Health Research, Univ. of South Australia, South Australia 5001, Australia
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24
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Benefits of breath hydrogen testing after lactulose administration in analysing carbohydrate malabsorption. Eur J Gastroenterol Hepatol 2010; 22:318-26. [PMID: 19636251 DOI: 10.1097/meg.0b013e32832b20e8] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND AND AIMS Breath hydrogen testing after lactulose administration may yield findings of clinical value, but whether it should be a routine part of breath testing has not been evaluated. We examined the contribution of breath testing after lactulose administration to the conduct and interpretation of breath hydrogen responses after fructose and lactose administration. METHODS Two hundred consecutive patients were given lactulose, fructose or lactose on separate days (at least 2 days apart); breath hydrogen was monitored every 15 min after the administration of each sugar. RESULTS Peak breath hydrogen levels after lactulose administration correlated with those after fructose (r = 0.26; P = 0.03) and lactose (r = 0.44; P = 0.004). Of the patients with a reduced response to lactulose, 51% had definite or borderline evidence of fructose malabsorption (FM); similarly, 23% of patients had definite or borderline lactose malabsorption. After lactulose administration, an increase in breath hydrogen levels occurred after the same amount of time or longer than after the administration of fructose or lactose (>120 min). The earlier the first rise in breath hydrogen levels after lactulose administration, the more frequently FM occurred, indicating an association between FM and rapid transit and/or small intestinal bacterial overgrowth. CONCLUSION Routine breath hydrogen testing with lactulose administration before other sugars cannot be used to define non-hydrogen producers, but might, by indicating the vigour of hydrogen production in the individual, allow more rational interpretation of results after testing with other sugars. It permits the duration of testing to be judged and provides information on possible mechanisms of FM.
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25
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Drozdowski LA, Clandinin T, Thomson ABR. Ontogeny, growth and development of the small intestine: Understanding pediatric gastroenterology. World J Gastroenterol 2010; 16:787-99. [PMID: 20143457 PMCID: PMC2825325 DOI: 10.3748/wjg.v16.i7.787] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Throughout our lifetime, the intestine changes. Some alterations in its form and function may be genetically determined, and some are the result of adaptation to diet, temperature, or stress. The critical period programming of the intestine can be modified, such as from subtle differences in the types and ratios of n3:m6 fatty acids in the diet of the pregnant mother, or in the diet of the weanlings. This early forced adaptation may persist in later life, such as the unwanted increased intestinal absorption of sugars, fatty acids and cholesterol. Thus, the ontogeny, early growth and development of the intestine is important for the adult gastroenterologist to appreciate, because of the potential for these early life events to affect the responsiveness of the intestine to physiological or pathological challenges in later life.
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Shelley H, Brennan M, Heuschkel R. Hydrogen breath testing in children: What is it and why is it performed? ACTA ACUST UNITED AC 2009. [DOI: 10.12968/gasn.2009.7.5.42906] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Affiliation(s)
| | | | - Robert Heuschkel
- Children′s Services, Addenbrooke′s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge
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27
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Abstract
Insulin resistance is associated with type 2 diabetes, hypertension and cardiovascular disease and the dietary factors involved in these metabolic disorders are still misunderstood. In animal studies, sugars, particularly sucrose and fructose, have been shown to decrease insulin sensitivity, with potential association with an induced hypertriglyceridemia. But in humans, the effects of sugars on insulin sensitivity are still debated. The present work first gives an overview of the metabolic pathways that could be implicated in the development of insulin resistance by sugars. Then, a review of the studies (intervention, prospective and cross-sectional) on the relationship between sugars, insulin resistance and diabetes is made in order to determine the level of proof concerning the association of sugars consumption and diabetes. All these studies failed to demonstrate an obvious relationship between the intake of total simple carbohydrates and glycaemic control or risk to develop a type 2 diabetes and particularly specific evidence is missing in terms of sucrose effect on diabetes. Concerning fructose, there are still discrepancies between studies' conclusions about the long-term deleterious effect on diabetes development. But its effect on lipogenesis and triglyceridemia has to be taken into account, considering the growing use of fructose in food industry and sugar-sweetened drinks.
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Affiliation(s)
- M Laville
- Centre de Recherche en Nutrition Humaine Rhône-Alpes, Univ de lyon, Lyon, France.
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28
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Abstract
Non-specific abdominal complaints are a considerable problem worldwide. Many patients are affected and many differential diagnoses have to be considered. Among these, carbohydrate malabsorption seems to play an important role. However, so far, only incomplete absorption of lactose is broadly accepted, while the malabsorption of fructose and sorbitol is still underestimated, although in many parts of the world it is much more frequent. Despite the success of dietary interventions in many patients, there are still a lot of unanswered questions that make further investigations necessary.
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Gibson PR, Newnham E, Barrett JS, Shepherd SJ, Muir JG. Review article: fructose malabsorption and the bigger picture. Aliment Pharmacol Ther 2007; 25:349-63. [PMID: 17217453 DOI: 10.1111/j.1365-2036.2006.03186.x] [Citation(s) in RCA: 154] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Fructose is found widely in the diet as a free hexose, as the disaccharide, sucrose and in a polymerized form (fructans). Free fructose has limited absorption in the small intestine, with up to one half of the population unable to completely absorb a load of 25 g. Average daily intake of fructose varies from 11 to 54 g around the world. Fructans are not hydrolysed or absorbed in the small intestine. The physiological consequences of their malabsorption include increasing osmotic load, providing substrate for rapid bacterial fermentation, changing gastrointestinal motility, promoting mucosal biofilm and altering the profile of bacteria. These effects are additive with other short-chain poorly absorbed carbohydrates such as sorbitol. The clinical significance of these events depends upon the response of the bowel to such changes; they have a higher chance of inducing symptoms in patients with functional gut disorders than asymptomatic subjects. Restricting dietary intake of free fructose and/or fructans may have durable symptomatic benefits in a high proportion of patients with functional gut disorders, but high quality evidence is lacking. It is proposed that confusion over the clinical relevance of fructose malabsorption may be reduced by regarding it not as an abnormality but as a physiological process offering an opportunity to improve functional gastrointestinal symptoms by dietary change.
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Affiliation(s)
- P R Gibson
- Department of Gastroenterology and Monash University Department of Medicine, Box Hill Hospital, Victoria, Australia.
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31
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Opinion of the Scientific Panel on Dietetic products, nutrition and allergies [NDA] related to the evaluation of fructose for labelling purposes. EFSA J 2005. [DOI: 10.2903/j.efsa.2005.279] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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Romagnuolo J, Schiller D, Bailey RJ. Using breath tests wisely in a gastroenterology practice: an evidence-based review of indications and pitfalls in interpretation. Am J Gastroenterol 2002; 97:1113-26. [PMID: 12014715 DOI: 10.1111/j.1572-0241.2002.05664.x] [Citation(s) in RCA: 163] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Breath tests are a simple and safe alternative to more invasive investigation strategies for many gastroenterological conditions. Both the hydrogen breath tests and the new 13C stable radioisotope breath tests are nonradioactive and safe in children and pregnancy. The range of diseases that can be identified include Helicobacter pylori infection, lactose and fructose intolerance, bacterial overgrowth, bile salt wastage, pancreatic insufficiency, liver dysfunction, and abnormal small bowel transit. In this review, the physiology supporting these tests and the principles of normal gas dynamics in the gut are briefly reviewed and then related to the test preparation and interpretation in two parts: 1) detection of H. pylori and 2) small bowel, pancreatic, and hepatobiliary disorders. A MEDLINE search reviewing all English language abstracts from 1966 to March, 2001 was performed, with an additional review of abstracts from major national meetings from 1997 to 2001. Using the information from this review, the performance characteristics of the various tests were detailed, and an attempt is made to provide some literature-based guidance regarding their indications and limitations. The interpretation of "flat" breath tests and the selective use of methane collection and colonic alkalinization are discussed. Breath tests are valuable tools that are, in general, underutilized in evaluating dyspepsia and functional bloating and diarrhea, as well as suspected malabsorption, including lactose intolerance.
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Abstract
The Na(+)-dependent glucose transporter SGLT1 and the facilitated fructose transporter GLUT5 absorb sugars from the intestinal lumen across the brush-border membrane into the cells. The activity of these transport systems is known to be regulated primarily by diet and development. The cloning of these transporters has led to a surge of studies on cellular mechanisms regulating intestinal sugar transport. However, the small intestine can be a difficult organ to study, because its cells are continuously differentiating along the villus, and because the function of absorptive cells depends on both their state of maturity and their location along the villus axis. In this review, I describe the typical patterns of regulation of transport activity by dietary carbohydrate, Na(+) and fibre, how these patterns are influenced by circadian rhythms, and how they vary in different species and during development. I then describe the molecular mechanisms underlying these regulatory patterns. The expression of these transporters is tightly linked to the villus architecture; hence, I also review the regulatory processes occurring along the crypt-villus axis. Regulation of glucose transport by diet may involve increased transcription of SGLT1 mainly in crypt cells. As cells migrate to the villus, the mRNA is degraded, and transporter proteins are then inserted into the membrane, leading to increases in glucose transport about a day after an increase in carbohydrate levels. In the SGLT1 model, transport activity in villus cells cannot be modulated by diet. In contrast, GLUT5 regulation by the diet seems to involve de novo synthesis of GLUT5 mRNA synthesis and protein in cells lining the villus, leading to increases in fructose transport a few hours after consumption of diets containing fructose. In the GLUT5 model, transport activity can be reprogrammed in mature enterocytes lining the villus column. Innovative experimental approaches are needed to increase our understanding of sugar transport regulation in the small intestine. I close by suggesting specific areas of research that may yield important information about this interesting, but difficult, topic.
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Abstract
The Na(+)-dependent glucose transporter SGLT1 and the facilitated fructose transporter GLUT5 absorb sugars from the intestinal lumen across the brush-border membrane into the cells. The activity of these transport systems is known to be regulated primarily by diet and development. The cloning of these transporters has led to a surge of studies on cellular mechanisms regulating intestinal sugar transport. However, the small intestine can be a difficult organ to study, because its cells are continuously differentiating along the villus, and because the function of absorptive cells depends on both their state of maturity and their location along the villus axis. In this review, I describe the typical patterns of regulation of transport activity by dietary carbohydrate, Na(+) and fibre, how these patterns are influenced by circadian rhythms, and how they vary in different species and during development. I then describe the molecular mechanisms underlying these regulatory patterns. The expression of these transporters is tightly linked to the villus architecture; hence, I also review the regulatory processes occurring along the crypt-villus axis. Regulation of glucose transport by diet may involve increased transcription of SGLT1 mainly in crypt cells. As cells migrate to the villus, the mRNA is degraded, and transporter proteins are then inserted into the membrane, leading to increases in glucose transport about a day after an increase in carbohydrate levels. In the SGLT1 model, transport activity in villus cells cannot be modulated by diet. In contrast, GLUT5 regulation by the diet seems to involve de novo synthesis of GLUT5 mRNA synthesis and protein in cells lining the villus, leading to increases in fructose transport a few hours after consumption of diets containing fructose. In the GLUT5 model, transport activity can be reprogrammed in mature enterocytes lining the villus column. Innovative experimental approaches are needed to increase our understanding of sugar transport regulation in the small intestine. I close by suggesting specific areas of research that may yield important information about this interesting, but difficult, topic.
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Affiliation(s)
- R P Ferraris
- Department of Pharmacology and Physiology, UMDNJ-New Jersey Medical School, 185 S. Orange Avenue, Newark, NJ 07103-2714, USA.
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Ledochowski M, Murr C, Lass-Flörl C, Fuchs D. Increased serum amylase and lipase in fructose malabsorbers. Clin Chim Acta 2001; 311:119-23. [PMID: 11566171 DOI: 10.1016/s0009-8981(01)00580-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
BACKGROUND Fructose malabsorption is frequently seen in the general population and is characterised by the inability to absorb fructose efficiently. Due to fructose malabsorption, fructose reaches the colon where it is broken down by bacteria to short fatty acids, CO(2) and H(2). Bloating, cramps, osmotic diarrhea and other symptoms of irritable bowel syndrome are the consequence. We recently found that fructose malabsorption is associated with low plasma folic acid concentrations and low serum tryptophan and zinc. Because fructose malabsorption apparently is associated not only with malabsorption of other nutrients, but also with abdominal discomfort, it was of interest to examine whether mild pancreatitis may be involved. METHODS We retrospectively examined our data in 159 otherwise healthy adults (110 females, 49 males) aged 14-84 years (mean 45.6+/-14.4 S.D.) with gastrointestinal complaints for serum amylase and serum lipase concentrations. The patients have been tested earlier for fructose malabsorption and lactose maldigestion by measuring breath H(2) concentrations after an oral dose of 25 g fructose and 50 g lactose, respectively, 1 week apart. RESULTS Fructose malabsorption (H(2) concentrations > or =20 ppm over baseline values) was detected in 107 of 159 individuals (67.3%). These subjects with fructose malabsorption presented with significantly higher serum amylase concentrations (73.1 U/l+/-25.7 S.D.) compared to individuals with normal fructose absorption (59.6 U/l+17.9 S.D; p=0.0009). Fructose malabsorbers also presented with higher serum lipase concentrations (122.0 U/l+/-100.3 S.D.) compared to normals (89.5 U/l+/-46.5 S.D.; p<0.05). To determine whether this finding is a consequence of any sort of malabsorption syndrome or whether it is specific for fructose malabsorption, all subjects were screened for lactose maldigestion. Lactose maldigestion (H(2) concentrations>20 ppm over baseline after lactose loading) was found in 50 of 159 individuals (31.4%). There were no significant differences in either amylase or lipase concentrations in lactose maldigestors. CONCLUSION Serum amylase and lipase concentrations are higher in subjects with fructose malabsorption compared to normals. Therefore, fructose malabsorption should be considered as a differential diagnosis in moderately elevated serum amylase.
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Affiliation(s)
- M Ledochowski
- Department of Clinical Nutrition, University of Innsbruck, Abteilung für Ernährungsmedizin, Anichstrasse 35, A-6020 Innsbruck, Austria.
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Affiliation(s)
| | - Bernhard Widner
- Institute of Medical Chemistry and Biochemistry, University of Innsbruck, A-6020 Innsbruck, Austria
| | - Christian Murr
- Institute of Medical Chemistry and Biochemistry, University of Innsbruck, A-6020 Innsbruck, Austria
| | - Dietmar Fuchs
- Institute of Medical Chemistry and Biochemistry, University of Innsbruck, A-6020 Innsbruck, Austria
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Ledochowski M, Widner B, Bair H, Probst T, Fuchs D. Fructose- and sorbitol-reduced diet improves mood and gastrointestinal disturbances in fructose malabsorbers. Scand J Gastroenterol 2000; 35:1048-52. [PMID: 11099057 DOI: 10.1080/003655200451162] [Citation(s) in RCA: 80] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Fructose malabsorption is characterized by the inability to absorb fructose efficiently. As a consequence fructose reaches the colon where it is broken down by bacteria to short fatty acids, CO2 and H2. Bloating, cramps, osmotic diarrhea and other symptoms of irritable bowel syndrome are the consequences and can be seen in about 50% of fructose malabsorbers. We have previously shown that fructose malabsorption is associated with early signs of mental depression and low serum tryptophan concentrations. It was therefore of interest whether a fructose-reduced diet could not only improve gastrointestinal complaints but also depressive signs seen in fructose malabsorbers. METHODS Fifty-three adults (12 males, 41 females), who were identified as fructose malabsorbers according to their breath-H2 concentrations, filled out a Beck's depression inventory-questionnaire, and a questionnaire with arbitrary scales for measurement of meteorism, stool frequency and quality of life for a 4-week period before dietary intervention and 4 weeks after dietary change as for fructose- and sorbitol-reduced diet. RESULTS Depression scores were reduced by 65.2% after 4 weeks of diet (P < 0.0001), and there was a significant reduction of meteorism (P < 0.0001) and stool frequency (P < 0.01). Improvement of signs of depression and of meteorism was more pronounced in females than in males. CONCLUSION Fructose- and sorbitol-reduced diet in subjects with fructose malabsorption does not only reduce gastrointestinal symptoms but also improves mood and early signs of depression.
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Affiliation(s)
- M Ledochowski
- Dept. of Clinical Nutrition, Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Austria
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Ledochowski M, Überall F, Propst T, Fuchs D. Fructose Malabsorption Is Associated with Lower Plasma Folic Acid Concentrations in Middle-Aged Subjects. Clin Chem 1999. [DOI: 10.1093/clinchem/45.11.2013] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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39
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Affiliation(s)
- C P Corpe
- Department of Medicine, University of Chicago, Illinois, USA
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40
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Affiliation(s)
- R J Vonk
- Department of Paediatrics, University Hospital Groningen, The Netherlands
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41
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Affiliation(s)
- J H Hoekstra
- Department of Paediatrics, Bosch Medicentrum, ME's-Hertogenbosch, Netherlands
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42
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Nobigrot T, Chasalow FI, Lifshitz F. Carbohydrate absorption from one serving of fruit juice in young children: age and carbohydrate composition effects. J Am Coll Nutr 1997; 16:152-8. [PMID: 9100216 DOI: 10.1080/07315724.1997.10718666] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES To test the hypotheses that: the efficiency of carbohydrate absorption in childhood increases with age, and decreased carbohydrate absorption occurs more frequently with juices containing more fructose than glucose and/or sorbitol than with juices which contain equal amounts of fructose and glucose and are sorbitol-free. METHODS One hundred and four healthy children were recruited from the Ambulatory Center at Maimonides Children's Center. They were assigned to one of three age groups: approximately 1, 3 and 5 years of age. Each child received one age-specific dose (by randomization) of one of four juices: a) pear juice which contains fructose in excess to glucose and a large amount of sorbitol; b) apple juice which is similar to pear juice in its fructose to glucose ratio but contains four times less sorbitol than pear juice; c) white grape juice or d) purple grape juice both of which contain equal amounts of fructose and glucose and are sorbitol-free. Breath hydrogen excretion (BH2) was utilized as the index of carbohydrate absorption. It was measured in fasting children and at 30-minute intervals for 3 hours after drinking the single serving of juice. Multiple breath hydrogen related parameters were quantified and results were expressed as: BH2 peak, area under the curve, and degree of carbohydrate malabsorption. After the test, parents completed a questionnaire and recorded signs and symptoms of intestinal malabsorption for 24 hours. RESULTS Pear juice related BH2 levels were significantly higher among children 1 and 3 years of age as compared to the levels achieved after the other juices. Apple juice related BH2 levels were significantly higher only among the youngest age group of children. There was no significant difference in carbohydrate absorption among the 5 year old children regardless of the juice consumed. Incomplete carbohydrate absorption (BH2 peak above 20 ppm) occurred more frequently after pear juice consumption (84%) than after apple juice (41%) or grape juice (white 20%, purple 24%) [p < 0.05]. Further outcome measures of BH2 excretion did not elicit differences beyond those detected by the above-mentioned parameters. Parents reported diarrhea in six children after pear juice, two after apple juice and two after purple grape juice and these children had the highest BH2 levels in their respective groups. No other symptoms were reported. CONCLUSIONS The data show that the efficiency of carbohydrate absorption of one age-specific serving of juice increases with advancing age of children. Decreased carbohydrate absorption occurs more often after ingestion of juices that contain more sorbitol, a nonabsorbable sugar and higher concentrations of fructose over glucose than after ingestion of juices which lack sorbitol and contain equal amounts of fructose and glucose.
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Affiliation(s)
- T Nobigrot
- Department of Pediatrics, Maimonides Medical Center, Brooklyn, New York, USA
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Abdelshaheed NN, Goldberg DM. Biochemical tests in diseases of the intestinal tract: their contributions to diagnosis, management, and understanding the pathophysiology of specific disease states. Crit Rev Clin Lab Sci 1997; 34:141-223. [PMID: 9143817 DOI: 10.3109/10408369709049587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Biochemical testing plays a major role in the complete evaluation of patients with suspected or established intestinal disease. We have classified these tests according to the medium in which they are performed: breath tests, including isotopic and nonisotopic tests, fecal tests, urine tests, serum tests, tissue tests, and other tests. The principles of various tests are outlined, and the role of each test in the evaluation of particular gastrointestinal disorders is discussed.
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Affiliation(s)
- N N Abdelshaheed
- Department of Clinical Biochemistry, Faculty of Medicine, University of Toronto, Banting Institute, Ontario, Canada
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44
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Wasserman D, Hoekstra JH, Tolia V, Taylor CJ, Kirschner BS, Takeda J, Bell GI, Taub R, Rand EB. Molecular analysis of the fructose transporter gene (GLUT5) in isolated fructose malabsorption. J Clin Invest 1996; 98:2398-402. [PMID: 8941659 PMCID: PMC507692 DOI: 10.1172/jci119053] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Fructose, a naturally occurring monosaccharide, is increasingly used as an added sweetener in processed foods in the form of high fructose corn syrup. Increased fructose intake combined with the identification of children with clinical evidence of isolated fructose malabsorption (IFM) has stimulated interest in possible disorders of fructose absorption. The intestinal absorption of fructose is carried out by the facilitative hexose transporter, which has been designated as GLUT5. Functional properties and tissue distribution of GLUT5 suggest that IFM might be due to mutations in the GLUT5 gene. To test this hypothesis, we screened the GLUT5 gene for mutations in a group of eight patients with IFM and in one subject with global malabsorption, as compared with 15 healthy parents of subjects and up to 6 unrelated controls. No mutations were found in the protein coding region of this gene in any of the subjects. A single G to A substitution in the 5' untranslated region of exon 1 was identified in the subject with global malabsorption. This subject and her healthy mother were heterozygous for the variant sequence, suggesting that it was unlikely to be clinically significant. In addition, sequence analysis of each of the 12 GLUT5 exons was performed in the index case and confirmed the negative single-strand conformation polymorphism findings. These studies demonstrate that IFM does not result from the expression of mutant GLUT5 protein.
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Affiliation(s)
- D Wasserman
- Children's Hospital of Philadelphia, Division of Gastroenterology & Nutrition, Pennsylvania 19104, USA
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45
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Abstract
As consumption of dietary fructose and sorbitol increases, the association between consumption of these sugars and gastrointestinal symptoms has been recognized. As a result, studies of fructose and sorbitol absorption and malabsorption have emerged with investigations relying largely on the use of breath hydrogen (H2) measurements. Since these sugars are prevalent in fruit juices, a major dietary staple in the first 5 years of life, an understanding of fructose and sorbitol absorption is particularly important to pediatric health care providers. This review examines fructose and sorbitol absorption in humans, reviewing as well the breath H2 method upon which studies of fructose and sorbitol absorption largely depend.
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Affiliation(s)
- J A Perman
- Department of Pediatrics, Johns Hopkins University School of Medicine, USA
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46
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Hoekstra JH, van den Aker JH. Facilitating effect of amino acids on fructose and sorbitol absorption in children. J Pediatr Gastroenterol Nutr 1996; 23:118-24. [PMID: 8856576 DOI: 10.1097/00005176-199608000-00004] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
The facilitating effect of glucose on free fructose absorption has been suggested to be due to a sucrase-related transport mechanism. In contrast, the conditions influencing the absorption of sorbitol have hardly been investigated. As amino acids promote transcellular water flow, we investigated their effects on the absorption of fructose and sorbitol. We studied 15 healthy children using breath hydrogen tests following the ingestion of fructose and sorbitol, alone and in combination with glucose or amino acids. Similarly, the effect of acarbose pretreatment on sucrose and fructose-glucose absorption was investigated. The inhibition of sucrase isomaltase by acarbose impedes the absorption of sucrose but not of the fructose-glucose mixture. Fructose absorption is enhanced by glucose and by the amino acids L-alanine, L-glutamine, L-phenylalanine, and L-proline. Similarly, the absorption of sorbitol is facilitated by glucose and L-alanine. These results are not in concordance with a sucrase-related fructose-transport system and suggest another mechanism for glucose-induced enhancement of fructose (and sorbitol) absorption. We hypothesize that the absorption of fructose and sorbitol may be stimulated by the increased water flux induced by active absorption of glucose as well as amino acids.
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Affiliation(s)
- J H Hoekstra
- Division of Paediatrics, Bosch Medicentrum, 's-Hertogenbosch, The Netherlands
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Abstract
Chronic nonspecific diarrhea, or toddler's diarrhea, is a frequently encountered disorder of defecation in otherwise healthy children. Although the precise pathophysiology remains to be elucidated, evidence suggests that toddler's diarrhea primarily is a gut motility disorder, modulated by dietary factors. Although the role of low-fat diets has since long been established, the liberal consumption of fruit juices and soft drinks is considered an equally important factor. Normalization of the child's diet, especially with regard to fat, fiber, fluids, and fruit juices, usually suffices to attain resolution of the diarrhea.
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Affiliation(s)
- C M Kneepkens
- Department of Pediatrics, Free University Hospital, Amsterdam, The Netherlands
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Hoekstra JH, van den Aker JH, Kneepkens CM, Stellaard F, Geypens B, Ghoos YF. Evaluation of 13CO2 breath tests for the detection of fructose malabsorption. THE JOURNAL OF LABORATORY AND CLINICAL MEDICINE 1996; 127:303-9. [PMID: 9273364 DOI: 10.1016/s0022-2143(96)90099-2] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Breath hydrogen (H2) studies have made clear that small intestinal absorption of fructose is limited, especially in toddlers. Malabsorption of fructose may be a cause of recurrent abdominal pain and chronic nonspecific diarrhea (toddler's diarrhea). Fructose absorption is facilitated by equimolar doses of glucose and, as we have found, amino acids (especially L-alanine); the mechanism underlying this effect remains unclear. To study fructose absorption in a more direct way, we combined breath H2 studies with breath 13CO2 studies. Gastric emptying was studied by using L-glycine-1-13C in 4 children from 12.1 to 16.0 years of age. After 25 gm of fructose and 27.5 gm of glucose, when given together, gastric emptying was significantly (p<0.05) slower than with either sugar alone. In a second series of experiments, 5 children from 12.0 to 15.9 years of age were tested with 25 gm of fructose, alone and with equimolar doses of glucose and L-alanine, and 4 younger children from 3.1 to 6.1 years of age were tested with 2 gm/kg (max 37.5 gm) fructose, alone or with an equimolar dose of L-alanine. All fructose solutions were enriched with 15 mg of D-fructose-13C-6. In all 9 children, fructose was malabsorbed as judged by breath H2 increases > or = 20 ppm, and the addition of glucose or L-alanine resulted in significantly lower breath H2 increases (p < or = 0.005 for glucose, p < or = 0.001 for alanine). In contrast, the addition of alanine or glucose did not change the pattern of breath 13CO2 excretion in the 5 older children, whereas in the 4 younger children (with relatively higher doses), L-alanine addition resulted in significantly lower increases in breath 13CO2. In the latter group, for each time point, breath H2 and 13CO2 concentrations after fructose were compared with those after fructose plus L-alanine; in 20 out of 24 points, both H2 and 13CO2 were higher after fructose. These results suggest that 13CO2 not only originated from the oxidation of absorbed substrate but also, at least in part, from colonic bacterial metabolism. For the detection of [correction of or] fructose malabsorption--as opposed to, for instance, lactose--the 13CO2 breath test seems to be of limited value.
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Affiliation(s)
- J H Hoekstra
- Department of Pediatrics, Bosch Medicentrum, 's-Hertogenbosch, The Netherlands
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49
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Abstract
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-1 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.
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Affiliation(s)
- J H Hoekstra
- Department of Paediatrics, Bosch Medicentrum, 's-Hertogenbosch, Amsterdam, The Netherlands
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