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Dale HF, Hagen M, Bekkelund M, Deb C, Valeur J. Disaccharidase deficiencies and gastrointestinal symptoms in patients referred to gastroscopic examination: a single center study from Norway. Scand J Gastroenterol 2024; 59:1166-1171. [PMID: 39230142 DOI: 10.1080/00365521.2024.2395848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 08/12/2024] [Accepted: 08/19/2024] [Indexed: 09/05/2024]
Abstract
OBJECTIVE Gastrointestinal illnesses have been reported in relation to low disaccharidase activity, yet both the prevalence of disaccharidase deficiency and its association with gastrointestinal symptoms and irritable bowel syndrome (IBS) are largely unknown. We aimed to determine the association between low activity of disaccharidase enzymes on gastrointestinal symptoms and presence of IBS. METHODS Patients referred for gastroscopic examination due to gastrointestinal complaints were consecutively included. A pinch biopsy was taken from the distal part of duodenum, and disaccharidase activity was measured using the Dahlqvist method. Gastrointestinal symptom severity was measured using IBS-Symptom Severity Score (IBS-SSS). RESULTS A total of 40 patients were included. Disaccharidase deficiency was detected in 24 patients (60%). Half of the patients (n = 21) had IBS according to Rome IV criteria. A majority (75%) of all patients reported moderate to severe gastrointestinal symptoms. Moderate to severe gastrointestinal symptoms were reported by 16 patients (67%) with disaccharidase deficiency and in 14 patients (88%) with normal disaccharidase activity. Lactase deficiency was detected in 22 patients (55%), maltase deficiency in 11 patients (28%), sucrase deficiency in 9 patients (23%), isomaltase deficiency in 13 patients (33%) and glucoamylase deficiency in 12 patients (30%). The activity of all enzymes was reduced in 8 patients (20%). Degree of disaccharidase deficiency was not associated with either the severity of gastrointestinal symptoms or the diagnosis of IBS. Enzymes levels were not associated with gastrointestinal symptom scores. CONCLUSION Our findings did not reveal any association between biochemically measured disaccharidase deficiency and gastrointestinal symptoms or the presence of IBS.
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Affiliation(s)
- Hanna Fjeldheim Dale
- Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway
- Department of Clinical Support, Lovisenberg Diaconal Hospital, Oslo, Norway
| | - Milada Hagen
- Faculty of Health Science, Oslo Metropolitan University, Oslo, Norway
- Department of Research, Lovisenberg Diaconal Hospital, Oslo, Norway
| | - Mattis Bekkelund
- Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway
| | - Chirajyoti Deb
- Gastroenterology Translational Research Division, Arnold Palmer Hospital Specialty Diagnostic Laboratory, Orlando, Florida, USA
| | - Jørgen Valeur
- Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Van Wyk H, Lee GO, Schillinger RJ, Edwards CA, Morrison DJ, Brouwer AF. Performance of empirical and model-based classifiers for detecting sucrase-isomaltase inhibition using the 13C-sucrose breath test. J Breath Res 2024; 18:041003. [PMID: 39197471 PMCID: PMC11385691 DOI: 10.1088/1752-7163/ad748d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 08/21/2024] [Accepted: 08/28/2024] [Indexed: 09/01/2024]
Abstract
The13C-sucrose breath test (13C-SBT) has been proposed to estimate sucrase-isomaltase (SIM) activity and is a promising test for SIM deficiency, which can cause gastrointestinal symptoms, and for intestinal mucosal damage caused by gut dysfunction or chemotherapy. We previously showed how various summary measures of the13C-SBT breath curve reflect SIM inhibition. However, it is uncertain how the performance of these classifiers is affected by test duration. We leveraged13C-SBT data from a cross-over study in 16 adults who received 0, 100, and 750 mg of Reducose, an SIM inhibitor. We evaluated the performance of a pharmacokinetic-model-based classifier,ρ, and three empirical classifiers (cumulative percent dose recovered at 90 min (cPDR90), time to 50% dose recovered, and time to peak dose recovery rate), as a function of test duration using receiver operating characteristic (ROC) curves. We also assessed the sensitivity, specificity, and accuracy of consensus classifiers. Test durations of less than 2 h generally failed to accurately predict later breath curve dynamics. The cPDR90 classifier had the highest ROC area-under-the-curve and, by design, was robust to shorter test durations. For detecting mild SIM inhibition,ρhad a higher sensitivity. We recommend13C-SBT tests run for at least a 2 h duration. Although cPDR90 was the classifier with highest accuracy and robustness to test duration in this application, concerns remain about its sensitivity to misspecification of the CO2production rate. More research is needed to assess these classifiers in target populations.
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Affiliation(s)
- Hannah Van Wyk
- Department of Epidemiology, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, United States of America
| | - Gwenyth O Lee
- Rutgers Global Health Institute, 112 Paterson St., New Brunswick, NJ 08901, United States of America
| | - Robert J Schillinger
- Scottish Universities Environmental Research Centre (SUERC), University of Glasgow, Rankine Avenue, East Kilbride G750QF, United Kingdom
- School of Medicine, Dentistry and Nursing, University of Glasgow, New Lister Building, Alexandra Parade, Glasgow G31 2ER, United Kingdom
| | - Christine A Edwards
- School of Medicine, Dentistry and Nursing, University of Glasgow, New Lister Building, Alexandra Parade, Glasgow G31 2ER, United Kingdom
| | - Douglas J Morrison
- Scottish Universities Environmental Research Centre (SUERC), University of Glasgow, Rankine Avenue, East Kilbride G750QF, United Kingdom
| | - Andrew F Brouwer
- Department of Epidemiology, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, United States of America
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3
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Dale HF, Hagen M, Deb C, Skar V, Valeur J. Diagnosing sucrase-isomaltase deficiency: a comparison of a 13C-sucrose breath test and a duodenal enzyme assay. Scand J Clin Lab Invest 2024; 84:268-272. [PMID: 38984772 DOI: 10.1080/00365513.2024.2377960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 06/03/2024] [Accepted: 07/05/2024] [Indexed: 07/11/2024]
Abstract
BACKGROUND Reduced activity of the sucrase-isomaltase (SI) enzyme can cause gastrointestinal symptoms. Biochemical measurement of SI activity in small intestinal biopsies is presently considered the gold standard for the diagnosis of SI deficiency, but this invasive test is not suitable as a routine diagnostic tool. AIM To evaluate a 13C-sucrose-breath test (13CSBT) as a diagnostic tool for SI deficiency in an adult population. METHODS 13CSBT results were compared to sucrase activity measured in duodenal biopsies. RESULTS Forty patients with gastrointestinal symptoms were included in the study, 4 of whom had celiac disease and the rest (n = 36) had normal histological findings. Nine patients (22.5%) had low sucrase activity measured using duodenal biopsies. No correlation was observed between enzymatic sucrase activity and the 13CSBT results. The 13CSBT-curves for the celiac patients versus patients with normal duodenal histology demonstrated that the patients with celiac disease were within the lower range of the distribution. CONCLUSION We observed a mismatch between the 13CSBT results and the biochemically measured sucrase activity, suggesting that SI activity is not uniformly distributed throughout the small intestines. This methodological discrepancy should be acknowledged when diagnosing SI deficiency.
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Affiliation(s)
- Hanna Fjeldheim Dale
- Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway
- Department of Clinical Support, Lovisenberg Diaconal Hospital, Oslo, Norway
| | - Milada Hagen
- Faculty of Health Science, Oslo Metropolitan University, Oslo, Norway
- Department of Research, Lovisenberg Diaconal Hospital, Oslo, Norway
| | - Chirajyoti Deb
- Gastroenterology Translational Research Division, Arnold Palmer Hospital, Specialty Diagnostic Laboratory, Orlando, USA
| | - Viggo Skar
- Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway
| | - Jørgen Valeur
- Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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4
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Danialifar TF, Chumpitazi BP, Mehta DI, Di Lorenzo C. Genetic and acquired sucrase-isomaltase deficiency: A clinical review. J Pediatr Gastroenterol Nutr 2024; 78:774-782. [PMID: 38327254 DOI: 10.1002/jpn3.12151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 01/05/2024] [Accepted: 01/19/2024] [Indexed: 02/09/2024]
Abstract
Genetic sucrase-isomaltase deficiency (GSID) is an inherited deficiency in the ability to digest sucrose and potentially starch due to mutations in the sucrase-isomaltase (SI) gene. Congenital sucrase-isomaltase deficiency is historically considered to be a rare condition affecting infants with chronic diarrhea as exposure to dietary sucrose begins. Growing evidence suggests that individuals with SI variants may present later in life, with symptoms overlapping with those of irritable bowel syndrome. The presence of SI genetic variants may, either alone or in combination, affect enzyme activity and lead to symptoms of different severity. As such, a more appropriate term for this inherited condition is GSID, with a recognition of a spectrum of severity and onset of presentation. Currently, disaccharidase assay on duodenal mucosal tissue homogenates is the gold standard in diagnosing SI deficiency. A deficiency in the SI enzyme can be present at birth (genetic) or acquired later, often in association with damage to the enteric brush-border membrane. Other noninvasive diagnostic alternatives such as sucrose breath tests may be useful but require further validation. Management of GSID is based on sucrose and potentially starch restriction tailored to the individual patients' tolerance and symptoms. As this approach may be challenging, additional treatment with commercially available sacrosidase is available. However, some patients may require continued starch restriction. Further research is needed to clarify the true prevalence of SI deficiency, the pathobiology of single SI heterozygous mutations, and to define optimal diagnostic and treatment algorithms in the pediatric population.
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Affiliation(s)
- Tanaz Farzan Danialifar
- Children's Hospital Los Angeles, Los Angeles, California, USA
- Keck School of Medicine of USC, Los Angeles, California, USA
| | - Bruno P Chumpitazi
- Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA
- Duke Clinical Research Institute, Durham, North Carolina, USA
| | - Devendra I Mehta
- Center for Digestive Health and Nutrition, Arnold Palmer Hospital for Children, Orlando, Florida, USA
| | - Carlo Di Lorenzo
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus, Ohio, USA
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Dbar S, Akhmadullina O, Sabelnikova E, Belostotskiy N, Parfenov A, Bykova S, Bakharev S, Baulo E, Babanova A, Indeykina L, Kuzmina T, Kosacheva T, Spasenov A, Makarova A. Patients with functional bowel disorder have disaccharidase deficiency: A single-center study from Russia. World J Clin Cases 2021; 9:4178-4187. [PMID: 34141780 PMCID: PMC8173401 DOI: 10.12998/wjcc.v9.i17.4178] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 02/12/2021] [Accepted: 04/22/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Functional bowel disorder (FBD) may be caused by a decrease in disaccharidase activity. Thus, the timely diagnosis of disaccharidase deficiency could lead to a better prognosis in patients with this condition.
AIM To determine the potential value of intestinal disaccharidases glucoamylase, maltase, sucrase, and lactase in understanding the etiology and pathogenesis of FBD.
METHODS A total of 82 FBD patients were examined. According to the Rome IV criteria (2016), 23 patients had diarrhea-predominant irritable bowel syndrome (IBS), 33 had functional diarrhea, 10 had constipation-predominant IBS, 4 had functional constipation, and 12 had mixed IBS. The Dahlqvist method was used to measure disaccharidase activity in the brush-border membrane of mature enterocytes of the small intestine, in duodenal biopsies obtained during esophagogastroduodenoscopy.
RESULTS Lactase deficiency was detected in 86.5% of patients, maltase deficiency in 48.7%, sucrase deficiency in 50%, and glucoamylase deficiency in 84.1%. The activities of all enzymes were reduced in 31.7% of patients, and carbohydrase deficiency was detected in 63.5% of patients. The low activity of enzymes involved in membrane digestion in the small intestine was found in 95.2% of patients.
CONCLUSION In 78 of the 82 patients with FBD, gastrointestinal symptoms were associated with disaccharidase deficiency.
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Affiliation(s)
- Saria Dbar
- Non-inflammatory Bowel Diseases, Moscow Health Department, Moscow Clinical Scientific Center n.a. A.S. Loginov, Moscow 111123, Russia
| | - Olga Akhmadullina
- Non-inflammatory Bowel Diseases, Moscow Health Department, Moscow Clinical Scientific Center n.a. A.S. Loginov, Moscow 111123, Russia
| | - Elena Sabelnikova
- Moscow Health Department, Moscow Clinical Scientific Center n.a. A.S. Loginov, Moscow 111123, Russia
| | - Nikolai Belostotskiy
- Pre-Clinical Research Laboratory, Moscow Clinical Scientific Center Named after A.S. Loginov MHD, Moscow 111123, Russia
| | - Asfold Parfenov
- Department of Bowel Pathology, Moscow Health Department, Moscow Clinical Scientific Center n.a. A.S. Loginov, Moscow 111123, Russia
| | - Svetlana Bykova
- Non-inflammatory Bowel Diseases, Moscow Health Department, Moscow Clinical Scientific Center n.a. A.S. Loginov, Moscow 111123, Russia
| | - Sergey Bakharev
- Non-inflammatory Bowel Diseases, Moscow Health Department, Moscow Clinical Scientific Center n.a. A.S. Loginov, Moscow 111123, Russia
| | - Elena Baulo
- Non-inflammatory Bowel Diseases, Moscow Health Department, Moscow Clinical Scientific Center n.a. A.S. Loginov, Moscow 111123, Russia
| | - Alexandra Babanova
- Non-inflammatory Bowel Diseases, Moscow Health Department, Moscow Clinical Scientific Center n.a. A.S. Loginov, Moscow 111123, Russia
| | - Lilia Indeykina
- Laboratory of Functional Diagnostics of Intestinal Diseases, Moscow Health Department, Moscow Clinical Scientific Center n.a. A.S. Loginov, Moscow 111123, Russia
| | - Tatyana Kuzmina
- Nutraceuticals Laboratory, Moscow Health Department, Moscow Clinical Scientific Center n.a. A.S. Loginov, Moscow 111123, Russia
| | - Tatiana Kosacheva
- Non-inflammatory Bowel Diseases, Moscow Health Department, Moscow Clinical Scientific Center n.a. A.S. Loginov, Moscow 111123, Russia
| | - Aleksey Spasenov
- Department of Medical Statistics, Moscow Health Department, Moscow Clinical Scientific Center n.a. A.S. Loginov, Moscow 111123, Russia
| | - Alina Makarova
- Laboratory of Functional Diagnostics of Intestinal Diseases, Moscow Health Department, Moscow Clinical Scientific Center n.a. A.S. Loginov, Moscow 111123, Russia
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Intermittent fasting from dawn to sunset for four consecutive weeks induces anticancer serum proteome response and improves metabolic syndrome. Sci Rep 2020; 10:18341. [PMID: 33110154 PMCID: PMC7592042 DOI: 10.1038/s41598-020-73767-w] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Accepted: 09/18/2020] [Indexed: 12/11/2022] Open
Abstract
Metabolic syndrome is characterized by central obesity, insulin resistance, elevated blood pressure, and dyslipidemia. Metabolic syndrome is a significant risk factor for several common cancers (e.g., liver, colorectal, breast, pancreas). Pharmacologic treatments used for the components of the metabolic syndrome appear to be insufficient to control cancer development in subjects with metabolic syndrome. Murine models showed that cancer has the slowest progression when there is no food consumption during the daily activity phase. Intermittent fasting from dawn to sunset is a form of fasting practiced during human activity hours. To test the anticancer effect of intermittent fasting from dawn to sunset in metabolic syndrome, we conducted a pilot study in 14 subjects with metabolic syndrome who fasted (no eating or drinking) from dawn to sunset for more than 14 h daily for four consecutive weeks. We collected serum samples before 4-week intermittent fasting, at the end of 4th week during 4-week intermittent fasting and 1 week after 4-week intermittent fasting. We performed serum proteomic analysis using nano ultra-high performance liquid chromatography-tandem mass spectrometry. We found a significant fold increase in the levels of several tumor suppressor and DNA repair gene protein products (GP)s at the end of 4th week during 4-week intermittent fasting (CALU, INTS6, KIT, CROCC, PIGR), and 1 week after 4-week intermittent fasting (CALU, CALR, IGFBP4, SEMA4B) compared with the levels before 4-week intermittent fasting. We also found a significant reduction in the levels of tumor promoter GPs at the end of 4th week during 4-week intermittent fasting (POLK, CD109, CAMP, NIFK, SRGN), and 1 week after 4-week intermittent fasting (CAMP, PLAC1) compared with the levels before 4-week intermittent fasting. Fasting from dawn to sunset for four weeks also induced an anti-diabetes proteome response by upregulating the key regulatory proteins of insulin signaling at the end of 4th week during 4-week intermittent fasting (VPS8, POLRMT, IGFBP-5) and 1 week after 4-week intermittent fasting (PRKCSH), and an anti-aging proteome response by upregulating H2B histone proteins 1 week after 4-week intermittent fasting. Subjects had a significant reduction in body mass index, waist circumference, and improvement in blood pressure that co-occurred with the anticancer, anti-diabetes, and anti-aging serum proteome response. These findings suggest that intermittent fasting from dawn to sunset actively modulates the respective genes and can be an adjunct treatment in metabolic syndrome. Further studies are needed to test the intermittent fasting from dawn to sunset in the prevention and treatment of metabolic syndrome-induced cancers.
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Chumpitazi BP, Lewis J, Cooper D, D’Amato M, Lim J, Gupta S, Miranda A, Terry N, Mehta D, Scheimann A, O’Gorman M, Tipnis N, Davies Y, Friedlander J, Smith H, Punati J, Khlevner J, Setty M, Di Lorenzo C. Hypomorphic SI genetic variants are associated with childhood chronic loose stools. PLoS One 2020; 15:e0231891. [PMID: 32433684 PMCID: PMC7239456 DOI: 10.1371/journal.pone.0231891] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 04/02/2020] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVE The SI gene encodes the sucrase-isomaltase enzyme, a disaccharidase expressed in the intestinal brush border. Hypomorphic SI variants cause recessive congenital sucrase-isomaltase deficiency (CSID) and related gastrointestinal (GI) symptoms. Among children presenting with chronic, idiopathic loose stools, we assessed the prevalence of CSID-associated SI variants relative to the general population and the relative GI symptom burden associated with SI genotype within the study population. METHODS A prospective study conducted at 18 centers enrolled 308 non-Hispanic white children ≤18 years old who were experiencing chronic, idiopathic, loose stools at least once per week for >4 weeks. Data on demographics, GI symptoms, and genotyping for 37 SI hypomorphic variants were collected. Race/ethnicity-matched SI data from the Exome Aggregation Consortium (ExAC) database was used as the general population reference. RESULTS Compared with the general population, the cumulative prevalence of hypomorphic SI variants was significantly higher in the study population (4.5% vs. 1.3%, P < .01; OR = 3.5 [95% CI: 6.1, 2.0]). Within the study population, children with a hypomorphic SI variant had a more severe GI symptom burden than those without, including: more frequent episodes of loose stools (P < .01), higher overall stool frequency (P < .01), looser stool form (P = .01) and increased flatulence (P = .02). CONCLUSION Non-Hispanic white children with chronic idiopathic loose stools have a higher prevalence of CSID-associated hypomorphic SI variants than the general population. The GI symptom burden was greater among the study subjects with a hypomorphic SI variant than those without hypomorphic SI variants.
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Affiliation(s)
| | - Jeffery Lewis
- Children’s Center for Digestive Health Care, Atlanta, GA, United States of America
| | - Derick Cooper
- QOL Medical, LLC, Vero Beach, FL, United States of America
| | - Mauro D’Amato
- School of Biological Sciences, Monash University, Clayton, VIC, Australia
| | - Joel Lim
- Children's Mercy Hospital, Kansas City, MO, United States of America
| | - Sandeep Gupta
- Sacramento Pediatric Gastroenterology, Sacramento, CA, United States of America
| | - Adrian Miranda
- Children’s Hospital of Wisconsin, Milwaukee, WI, United States of America
| | - Natalie Terry
- Children’s Hospital of Philadelphia, Philadelphia, PA, United States of America
| | - Devendra Mehta
- Arnold Palmer Children's Hospital, Orlando, FL, United States of America
| | - Ann Scheimann
- Johns Hopkins University, Baltimore, MD, United States of America
| | - Molly O’Gorman
- Primary Children's Medical Center, Salt Lake City, UT, United States of America
| | - Neelesh Tipnis
- University of Mississippi Medical Center, Jackson, MS, United States of America
| | - Yinka Davies
- Sacramento Pediatric Gastroenterology, Sacramento, CA, United States of America
| | - Joel Friedlander
- Children’s Hospital Colorado, Digestive Health Institute, University of Colorado School of Medicine, Aurora, CO, United States of America
| | - Heather Smith
- QOL Medical, LLC, Vero Beach, FL, United States of America
| | - Jaya Punati
- Children’s Hospital of Los Angeles, Los Angeles, CA, United States of America
| | - Julie Khlevner
- Columbia University Medical Center, New York, NY, United States of America
| | - Mala Setty
- UCSF Benioff Children’s Hospital Oakland, Oakland, CA, United States of America
| | - Carlo Di Lorenzo
- Department of Pediatrics, The Ohio State University, Columbus, OH, United States of America
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Mindikoglu AL, Abdulsada MM, Jain A, Choi JM, Jalal PK, Devaraj S, Mezzari MP, Petrosino JF, Opekun AR, Jung SY. Intermittent fasting from dawn to sunset for 30 consecutive days is associated with anticancer proteomic signature and upregulates key regulatory proteins of glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system and cognitive function in healthy subjects. J Proteomics 2020; 217:103645. [PMID: 31927066 PMCID: PMC7429999 DOI: 10.1016/j.jprot.2020.103645] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Revised: 12/13/2019] [Accepted: 01/08/2020] [Indexed: 02/06/2023]
Abstract
Murine studies showed that disruption of circadian clock rhythmicity could lead to cancer and metabolic syndrome. Time-restricted feeding can reset the disrupted clock rhythm, protect against cancer and metabolic syndrome. Based on these observations, we hypothesized that intermittent fasting for several consecutive days without calorie restriction in humans would induce an anticarcinogenic proteome and the key regulatory proteins of glucose and lipid metabolism. Fourteen healthy subjects fasted from dawn to sunset for over 14 h daily. Fasting duration was 30 consecutive days. Serum samples were collected before 30-day intermittent fasting, at the end of 4th week during 30-day intermittent fasting, and one week after 30-day intermittent fasting. An untargeted serum proteomic profiling was performed using ultra high-performance liquid chromatography/tandem mass spectrometry. Our results showed that 30-day intermittent fasting was associated with an anticancer serum proteomic signature, upregulated key regulatory proteins of glucose and lipid metabolism, circadian clock, DNA repair, cytoskeleton remodeling, immune system, and cognitive function, and resulted in a serum proteome protective against cancer, metabolic syndrome, inflammation, Alzheimer's disease, and several neuropsychiatric disorders. These findings suggest that fasting from dawn to sunset for 30 consecutive days can be preventive and adjunct therapy in cancer, metabolic syndrome, and several cognitive and neuropsychiatric diseases. SIGNIFICANCE: Our study has important clinical implications. Our results showed that intermittent fasting from dawn to sunset for over 14 h daily for 30 consecutive days was associated with an anticancer serum proteomic signature and upregulated key regulatory proteins of glucose and lipid metabolism, insulin signaling, circadian clock, DNA repair, cytoskeleton remodeling, immune system, and cognitive function, and resulted in a serum proteome protective against cancer, obesity, diabetes, metabolic syndrome, inflammation, Alzheimer's disease, and several neuropsychiatric disorders. Importantly, these findings occurred in the absence of any calorie restriction and significant weight loss. These findings suggest that intermittent fasting from dawn to sunset can be a preventive and adjunct therapy in cancer, metabolic syndrome and Alzheimer's disease and several neuropsychiatric diseases.
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Affiliation(s)
- Ayse L Mindikoglu
- Margaret M. and Albert B. Alkek Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, United States of America; Michael E. DeBakey Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, United States of America.
| | - Mustafa M Abdulsada
- Margaret M. and Albert B. Alkek Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, United States of America
| | - Antrix Jain
- Advanced Technology Core, Mass Spectrometry Proteomics Core, Baylor College of Medicine, Houston, TX, United States of America
| | - Jong Min Choi
- Advanced Technology Core, Mass Spectrometry Proteomics Core, Baylor College of Medicine, Houston, TX, United States of America
| | - Prasun K Jalal
- Margaret M. and Albert B. Alkek Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, United States of America; Michael E. DeBakey Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX, United States of America
| | - Sridevi Devaraj
- Clinical Chemistry and Point of Care Technology, Texas Children's Hospital and Health Centers, Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States of America
| | - Melissa P Mezzari
- The Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX, United States of America
| | - Joseph F Petrosino
- The Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX, United States of America
| | - Antone R Opekun
- Margaret M. and Albert B. Alkek Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, United States of America; Department of Pediatrics, Division of Gastroenterology, Nutrition and Hepatology, Baylor College of Medicine, Houston, TX, United States of America
| | - Sung Yun Jung
- Advanced Technology Core, Mass Spectrometry Proteomics Core, Baylor College of Medicine, Houston, TX, United States of America; Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX, United States of America
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Abstract
PURPOSE OF REVIEW Disaccharidase testing, as applied to the evaluation of gastrointestinal disturbances is available but it is not routinely considered in the diagnostic work-up. The purpose of this review was to determine if disaccharidase testing is clinically useful and to consider how the results could alter patient management. RECENT FINDINGS Indicate that carbohydrate maldigestion could contribute functional bowel disorders and negatively impact the fecal microbiome. Diagnostic techniques include enzyme activity assays performed on random endoscopically obtained small intestinal biopsies, immunohistochemistry, stable isotope tracer and nonenriched substrate load breath testing, and genetic testing for mutations. More than 40 sucrase--isomaltase gene variants coding for defective or reduced enzymatic activity have been reported and deficiency conditions are more common than previously thought. SUMMARY The rationale for disaccharidase activity testing relates to a need to fully assess unexplained recurrent abdominal discomfort and associated symptoms. All disaccharidases share the same basic mechanism of mucosal expression and deficiency has far reaching consequences. Testing for disaccharidase expression appears to have an important role in symptom evaluation, but there are accuracy and logistical issues that should be considered. It is likely that specific recommendations for patient management, dietary modification, and enzyme supplementation would come from better testing methods.
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Affiliation(s)
- Antone R. Opekun
- Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, USA
- Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Houston, TX, USA
- Section of Gastroenterology, Hepatology and Nutrition, Texas Children’s Hospital, Houston, TX, USA
| | - Bruno P. Chumpitazi
- Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, USA
- Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Houston, TX, USA
- Section of Gastroenterology, Hepatology and Nutrition, Texas Children’s Hospital, Houston, TX, USA
| | - Mustafa M. Abdulsada
- Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX, USA
| | - Buford L Nichols
- Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Houston, TX, USA
- Director Emeritus, USDA/ARS Children’s Nutrition Research Center, Houston, TX, USA
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10
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Puertolas MV, Fifi AC. The Role of Disaccharidase Deficiencies in Functional Abdominal Pain Disorders-A Narrative Review. Nutrients 2018; 10:E1835. [PMID: 30501067 PMCID: PMC6315563 DOI: 10.3390/nu10121835] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 11/13/2018] [Accepted: 11/21/2018] [Indexed: 12/16/2022] Open
Abstract
Disaccharidase deficiencies are reportedly underdiagnosed in pediatric populations. Though typically thought to cause diarrheal disease, they can also be a cause of abdominal pain and dyspepsia, and patients diagnosed with these functional disorders may actually have associated enzyme deficiencies. While the effects of lactose deficiency have been widely studied, sucrase, maltase, and isomaltase are less frequently considered when approaching a patient with an apparent functional abdominal pain disorder. This review seeks to provide an up-to-date narrative on the current scientific literature on the possible role of sucrase, maltase, and isomaltase deficiency in pediatric functional gastrointestinal disorders.
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Affiliation(s)
- Mora V Puertolas
- Department of Pediatrics, Holtz Children's Hospital, University of Miami Miller School of Medicine/Jackson Memorial Medical Center, 1611 NW 12th Ave, Miami, FL 33136, USA.
| | - Amanda C Fifi
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, University of Miami Miller School of Medicine, 1601 NW 12th Ave, Miami, FL 33137, USA.
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Graham DY, Ketwaroo GA, Money ME, Opekun AR. Enzyme therapy for functional bowel disease-like post-prandial distress. J Dig Dis 2018; 19:650-656. [PMID: 30101562 PMCID: PMC6910206 DOI: 10.1111/1751-2980.12655] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 08/10/2018] [Indexed: 12/11/2022]
Abstract
Post-prandial gastrointestinal symptoms such as diarrhea, abdominal distension, flatulence, bloating and a feeling of fullness are common complaints of often unknown etiology and pathogenesis. There is a long history of trials reporting the successful use of products containing a variety of combinations of digestive enzymes including a number of randomized placebo-controlled trials. We provide a narrative review of studies describing the use of multi-digestive enzymes for symptoms consistent with irritable bowel syndrome. We describe clinical trials reported over the past 60 years including double-blinded randomized, placebo-controlled studies and recent trials that focused on post-prandial diarrhea consistent with diarrhea-predominant irritable bowel syndrome. Disaccharidase deficiencies or deficiencies of other carbohydrate digesting enzymes were excluded. Worldwide studies have generally reported success with multi-enzyme preparations although none used a factorial design to identify subgroups or attempted to link specific symptom responses to specific components of therapy. Although there is a long history of the successful use of multi-enzyme preparations for post-prandial symptoms consistent with irritable bowel syndrome, long-term studies using validated scoring systems and factorial designs are needed to confirm the results for specific symptoms and the components of the combination drugs received.
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Affiliation(s)
- David Y. Graham
- Department of Medicine, Michael E. DeBakey VA Medical Center, Houston, Texas,Baylor College of Medicine, Houston, Texas
| | - Gyanprakash A. Ketwaroo
- Department of Medicine, Michael E. DeBakey VA Medical Center, Houston, Texas,Baylor College of Medicine, Houston, Texas
| | - Mary E. Money
- Department of Internal Medicine, University of Maryland School of Medicine, Baltimore, Maryland,Department of Internal Medicine, Meritus Medical Center, Hagerstown, Maryland
| | - Antone R. Opekun
- Department of Medicine, Michael E. DeBakey VA Medical Center, Houston, Texas,Baylor College of Medicine, Houston, Texas
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Abstract
BACKGROUND AND HYPOTHESES Human starch digestion is a multienzyme process involving 6 different enzymes: salivary and pancreatic α-amylase; sucrase and isomaltase (from sucrose-isomaltase [SI]), and maltase and glucoamylase (from maltase-glucoamylase [MGAM]). Together these enzymes cleave starch to smaller molecules ultimately resulting in the absorbable monosaccharide glucose. Approximately 80% of all mucosal maltase activity is accounted for by SI and the reminder by MGAM. Clinical studies suggest that starch may be poorly digested in those with congenital sucrase-isomaltase deficiency (CSID). Poor starch digestion occurs in individuals with CSID and can be documented using a noninvasive C-breath test (BT). METHODS C-Labled starch was used as a test BT substrate in children with CSID. Sucrase deficiency was previously documented in study subjects by both duodenal biopsy enzyme assays and C-sucrose BT. Breath CO2 was quantitated at intervals before and after serial C-substrate loads (glucose followed 75 minutes later by starch). Variations in metabolism were normalized against C-glucose BT (coefficient of glucose absorption). Control subjects consisted of healthy family members and a group of children with functional abdominal pain with biopsy-proven sucrase sufficiency. RESULTS Children with CSID had a significant reduction of C-starch digestion mirroring that of their duodenal sucrase and maltase activity and C-sucrase BT. CONCLUSIONS In children with CSID, starch digestion may be impaired. In children with CSID, starch digestion correlates well with measures of sucrase activity.
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