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Journal of Hepatology Jul 2021Excessive fructose intake is associated with increased de novo lipogenesis, blood triglycerides, and hepatic insulin resistance. We aimed to determine whether fructose... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Excessive fructose intake is associated with increased de novo lipogenesis, blood triglycerides, and hepatic insulin resistance. We aimed to determine whether fructose elicits specific effects on lipid metabolism independently of excessive caloric intake.
METHODS
A total of 94 healthy men were studied in this double-blind, randomized trial. They were assigned to daily consumption of sugar-sweetened beverages (SSBs) containing moderate amounts of fructose, sucrose (fructose-glucose disaccharide) or glucose (80 g/day) in addition to their usual diet or SSB abstinence (control group) for 7 weeks. De novo fatty acid (FA) and triglyceride synthesis, lipolysis and plasma free FA (FFA) oxidation were assessed by tracer methodology.
RESULTS
Daily intake of beverages sweetened with free fructose and fructose combined with glucose (sucrose) led to a 2-fold increase in basal hepatic fractional secretion rates (FSR) compared to control (median FSR %/day: sucrose 20.8 (p = 0.0015); fructose 19.7 (p = 0.013); control 9.1). Conversely, the same amounts of glucose did not change FSR (median of FSR %/day 11.0 (n.s.)). Fructose intake did not change basal secretion of newly synthesized VLDL-triglyceride, nor did it alter rates of peripheral lipolysis, nor total FA and plasma FFA oxidation. Total energy intake was similar across groups.
CONCLUSIONS
Regular consumption of both fructose- and sucrose-sweetened beverages in moderate doses - associated with stable caloric intake - increases hepatic FA synthesis even in a basal state; this effect is not observed after glucose consumption. These findings provide evidence of an adaptative response to regular fructose exposure in the liver.
LAY SUMMARY
This study investigated the metabolic effects of daily sugar-sweetened beverage consumption for several weeks in healthy lean men. It revealed that beverages sweetened with the sugars fructose and sucrose (glucose and fructose combined), but not glucose, increase the ability of the liver to produce lipids. This change may pave the way for further unfavorable effects on metabolic health.
CLINICAL TRIAL REGISTRATION NUMBER
NCT01733563.
Topics: Adult; Double-Blind Method; Energy Intake; Fatty Acids; Fructose; Glucose; Healthy Volunteers; Humans; Lipid Metabolism; Lipogenesis; Lipoproteins, VLDL; Liver; Male; Sucrose; Sugar-Sweetened Beverages; Sweetening Agents; Triglycerides
PubMed: 33684506
DOI: 10.1016/j.jhep.2021.02.027 -
Nutrients May 2023Irritable bowel syndrome is a typical gastrointestinal disease that causes bloating, flatulence, abdominal pain, diarrhoea, constipation, or alteration of the last two... (Review)
Review
Irritable bowel syndrome is a typical gastrointestinal disease that causes bloating, flatulence, abdominal pain, diarrhoea, constipation, or alteration of the last two in adults and children. A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) is one of the potential treatment strategies to reduce abdominal symptoms and increase the quality of life. The present narrative review aims to present a general overview of current studies that have evaluated the efficacy of a low-FODMAP diet against other diets in gastrointestinal symptoms, nutrient intake in adults and children, and lifestyle quality. The research was performed using seven searchable databases, which included the Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Excerpta Medica Database (EMBASE), Medline, PubMed, Scopus, and Web of Science, up to March 2023. In conclusion, there is significant evidence that the follow-up of a low-FODMAP diet might be a feasible first-line therapeutic strategy to reduce stomach discomfort, pain, bloating, and quality of life for patients with irritable bowel syndrome.
Topics: Humans; Adult; Child; Disaccharides; Irritable Bowel Syndrome; Monosaccharides; Quality of Life; FODMAP Diet; Systematic Reviews as Topic; Oligosaccharides; Diet; Gastrointestinal Diseases; Flatulence; Abdominal Pain; Fermentation; Diet, Carbohydrate-Restricted
PubMed: 37242178
DOI: 10.3390/nu15102295 -
Clinical Gastroenterology and... Oct 2022A gluten-free diet usually leads to mucosal remission in celiac disease, but persistent symptoms are common. A low fermentable oligo-, di-, monosaccharides and polyols... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
A gluten-free diet usually leads to mucosal remission in celiac disease, but persistent symptoms are common. A low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet is an established treatment for irritable bowel syndrome (IBS). We have assessed the efficacy of a moderately low FODMAP diet on persistent symptoms in treated celiac patients.
METHODS
A randomized controlled trial was performed from 2018 to 2019 in 70 adults with biopsy-proven celiac disease. Inclusion criteria were as follows: persistent gastrointestinal symptoms defined by a Gastrointestinal Symptom Rating Scale (GSRS)-IBS version score of 30 or higher, gluten-free diet adherence for 12 months or longer, and serologic and mucosal remission. Participants were randomized to a low FODMAP-gluten-free diet (intervention) or usual gluten-free diet (control). The GSRS-IBS score was recorded at baseline and at weeks 1 to 4, and the Celiac Symptom Index at baseline and at week 4. Statistics included marginal models for repeated data and analyses of covariance.
RESULTS
We included 34 participants in the intervention group and 36 in the control group. Time development of GSRS-IBS total scores differed significantly between the groups (P < .001), evident after 1 week (mean difference in intervention vs control, -8.2; 95% CI, -11.5 to -5.0) and persisting through week 4 (mean difference in intervention vs control, -10.8; 95% CI, -14.8 to -6.8). Moreover, significantly lower scores were found for the dimensions of pain, bloating, diarrhea, and satiety (P ≤ .04), but not constipation (P = .43). FODMAP intake during the intervention was moderately low (mean, 8.1 g/d; 95% CI, 6.7-9.3 g/d). The Celiac Symptom Index was significantly lower in the intervention group at week 4 (mean difference, -5.8; 95% CI, -9.6 to -2.0).
CONCLUSIONS
A short-term moderately low FODMAP diet significantly reduced gastrointestinal symptoms and increased celiac disease-specific health, and should be considered for the management of persistent symptoms in celiac disease.
CLINICALTRIALS
gov: NCT03678935.
Topics: Adult; Celiac Disease; Diet; Diet, Gluten-Free; Disaccharides; Fermentation; Humans; Irritable Bowel Syndrome; Monosaccharides
PubMed: 35051648
DOI: 10.1016/j.cgh.2022.01.011 -
Theranostics 2022Autophagy is a catabolic process that degrades cytoplasmic constituents and organelles in the lysosome, thus serving an important role in cellular homeostasis and...
Autophagy is a catabolic process that degrades cytoplasmic constituents and organelles in the lysosome, thus serving an important role in cellular homeostasis and protection against insults. We previously reported that defects in autophagy contribute to neuronal cell damage in traumatic spinal cord injury (SCI). Recent data from other inflammatory models implicate autophagy in regulation of immune and inflammatory responses, with low levels of autophagic flux associated with pro-inflammatory phenotypes. In the present study, we examined the effects of genetically or pharmacologically manipulating autophagy on posttraumatic neuroinflammation and motor function after SCI in mice. Young adult male C57BL/6, CX3CR1-GFP, autophagy hypomorph mice, and their wildtype (WT) littermates were subjected to moderate thoracic spinal cord contusion. Neuroinflammation and autophagic flux in the injured spinal cord were assessed using flow cytometry, immunohistochemistry, and NanoString gene expression analysis. Motor function was evaluated with the Basso Mouse Scale and horizontal ladder test. Lesion volume and spared white matter were evaluated by unbiased stereology. To stimulate autophagy, disaccharide trehalose, or sucrose control, was administered in the drinking water immediately after injury and for up to 6 weeks after SCI. Flow cytometry demonstrated dysregulation of autophagic function in both microglia and infiltrating myeloid cells from the injured spinal cord at 3 days post-injury. Transgenic CX3CR1-GFP mice revealed increased autophagosome formation and inhibition of autophagic flux specifically in activated microglia/macrophages. NanoString analysis using the neuroinflammation panel demonstrated increased expression of proinflammatory genes and decreased expression of genes related to neuroprotection in mice as compared to WT controls at 3 days post-SCI. These findings were further validated by qPCR, wherein we observed significantly higher expression of proinflammatory cytokines. Western blot analysis confirmed higher protein expression of the microglia/macrophage marker IBA-1, inflammasome marker, NLRP3, and innate immune response markers cGAS and STING in mice at 3 day after SCI. Flow cytometry demonstrated that autophagy deficit did not affect either microglial or myeloid counts at 3 days post-injury, instead resulting in increased microglial production of proinflammatory cytokines. Finally, locomotor function showed significantly worse impairments in mice up to 6 weeks after SCI, which was accompanied by worsening tissue damage. Conversely, treatment with a naturally occurring autophagy inducer trehalose, reduced protein levels of p62, an adaptor protein targeting cargo to autophagosomes as well as the NLRP3, STING, and IBA-1 at 3 days post-injury. Six weeks of trehalose treatment after SCI led to improved motor function recovery as compared to control group, which was accompanied by reduced tissue damage. Our data indicate that inhibition of autophagy after SCI potentiates pro-inflammatory activation in microglia and is associated with worse functional outcomes. Conversely, increasing autophagy with trehalose, decreased inflammation and improved outcomes. These findings highlight the importance of autophagy in spinal cord microglia and its role in secondary injury after SCI.
Topics: Animals; Autophagy; Cytokines; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia; NLR Family, Pyrin Domain-Containing 3 Protein; Neuroinflammatory Diseases; Spinal Cord Injuries; Trehalose
PubMed: 35910787
DOI: 10.7150/thno.72713 -
British Journal of Clinical Pharmacology May 2021Hypophosphataemia is an increasingly recognized side-effect of ferric carboxymaltose (FCM) and possibly iron isomaltoside/ferric derisomaltose (IIM), which are used to... (Meta-Analysis)
Meta-Analysis Review
AIMS
Hypophosphataemia is an increasingly recognized side-effect of ferric carboxymaltose (FCM) and possibly iron isomaltoside/ferric derisomaltose (IIM), which are used to treat iron deficiency. The aim of this study was to determine frequency, severity, duration and risk factors of incident hypophosphataemia after treatment with FCM and IIM.
METHODS
A systematic literature search for articles indexed in EMBASE, PubMed and Web of Science in years 2005-2020 was carried out using the search terms 'ferric carboxymaltose' OR 'iron isomaltoside'. Prospective clinical trials reporting outcomes on hypophosphataemia rate, mean nadir serum phosphate and/or change in mean serum phosphate from baseline were selected. Hypophosphataemia rate and severity were compared for studies on IIM vs. FCM after stratification for chronic kidney disease. Meta-regression analysis was used to investigate risk factors for hypophosphataemia.
RESULTS
Across the 42 clinical trials included in the meta-analysis, FCM induced a significantly higher incidence of hypophosphataemia than IIM (47%, 95% CI 36-58% vs. 4%, 95% CI 2-5%), and significantly greater mean decreases in serum phosphate (0.40 vs. 0.06 mmol/L). Hypophosphataemia persisted at the end of the study periods (maximum 3 months) in up to 45% of patients treated with FCM. Meta-regression analysis identified low baseline serum ferritin and transferrin saturation, and normal kidney function as significant predictors of hypophosphataemia.
CONCLUSION
FCM is associated with a high risk of hypophosphataemia, which does not resolve for at least 3 months in a large proportion of affected patients. More severe iron deficiency and normal kidney function are risk factors for hypophosphataemia.
Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Disaccharides; Ferric Compounds; Fibroblast Growth Factor-23; Humans; Hypophosphatemia; Maltose; Prospective Studies
PubMed: 33188534
DOI: 10.1111/bcp.14643 -
BMJ Open Gastroenterology Aug 2020A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) is an effective way to reduce gut symptoms in people with irritable bowel... (Randomized Controlled Trial)
Randomized Controlled Trial
Does Fibre-fix provided to people with irritable bowel syndrome who are consuming a low FODMAP diet improve their gut health, gut microbiome, sleep and mental health? A double-blinded, randomised controlled trial.
INTRODUCTION
A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) is an effective way to reduce gut symptoms in people with irritable bowel syndrome (IBS). This diet reduces the intake of fermentable fibres, leading to changes of the gut microbiota and insufficient fermentation in the large bowel, resulting in reduced production of short-chain fatty acids (SCFAs), such as butyrate, which has unfavourable implications for gut health, sleep and mental health. This study will examine the effect of Fibre-fix, a supplement containing a mix of dietary fibres, on the human gut microbiome composition, fermentative capacity, sleep, quality of life (QOL) and mental health of people with IBS who consume a low FODMAP diet (LFD).
METHODS AND ANALYSIS
A randomised, double-blind, placebo-controlled, study design is proposed to examine whether Fibre-fix added to an existing LFD may help modulate gastrointestinal function, improve markers of sleep, mental health and promote QOL in patients with IBS. Participants will provide stool and blood samples, daily bowel symptoms diaries and 3-day diet records. Additionally, they will complete validated questionnaires relating to FODMAP intake, sleep, mental health and QOL before and after a 3-week intervention. Gut health will be assessed via faecal microbiome composition, faecal pH and SCFA levels. Alteration of sleep will be recorded using an actigraphy device worn by all participants over the whole study. Multivariate analysis will be used to examine the gut microbiome and repeated measures Analysis of variance (ANOVA) will be used for dependent variables from questionnaires related to bowel symptoms, stool type, sleep, mental health and QOL to assess the differences between intervention and control groups after adjustment for confounding variables.
ETHICS AND DISSEMINATION
Ethics approval was obtained from the Human Research Ethics Committee of Edith Cowan University (2019-00619-YAN). Results will be disseminated in peer-review journal publications, and conference presentations. Participants will be provided with a summary of findings once the study is completed. If Fibre-fix is shown to result in favourable changes in gut microbial composition, SCFA production, sleep and mental well-being without exacerbating symptoms, this will provide additional dietary management options for those with IBS following an LFD.
TRIAL REGISTRATION NUMBER
ACTRN12620000032954.
Topics: Adult; Aged; Case-Control Studies; Dietary Fiber; Disaccharides; Double-Blind Method; Fatty Acids, Volatile; Feces; Female; Fermentation; Gastrointestinal Diseases; Gastrointestinal Microbiome; Humans; Irritable Bowel Syndrome; Male; Mental Health; Middle Aged; Monosaccharides; Oligosaccharides; Outcome Assessment, Health Care; Polymers; Quality of Life; Sleep; Surveys and Questionnaires
PubMed: 32816830
DOI: 10.1136/bmjgast-2020-000448 -
The American Journal of Gastroenterology Jun 2022Irritable bowel syndrome (IBS) and functional constipation (FC) are among the most common disorders of gut-brain interaction, affecting millions of individuals...
Irritable bowel syndrome (IBS) and functional constipation (FC) are among the most common disorders of gut-brain interaction, affecting millions of individuals worldwide. Most patients with disorders of gut-brain interaction perceive food as a trigger for their gastrointestinal symptoms, and specific dietary manipulations/advice have now been recognized as a cornerstone therapeutic option for IBS and FC. We discuss in detail the 2 most common dietary interventions used for the management of IBS-general dietary advice based on the National Institute for Health and Care Excellence guidelines and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). We summarize the literature around the possible mechanisms of FODMAP-mediated IBS pathophysiology, the current 3-step, top-down approach of administering a low FODMAP diet (LFD) (restriction phase, followed by reintroduction and personalization), the efficacy data of its restriction and personalization phases, and possible biomarkers for response to an LFD. We also summarize the limitations and challenges of an LFD along with the alternative approach to administering an LFD (e.g., bottom-up). Finally, we discuss the available efficacy data for fiber, other dietary interventions (e.g., Mediterranean diet, gluten-free diet, and holistic dietary interventions), and functional foods (e.g., kiwifruit, rhubarb, aloe, and prunes) in the management of IBS and FC.
Topics: Constipation; Diet; Diet, Carbohydrate-Restricted; Disaccharides; Fermentation; Humans; Irritable Bowel Syndrome; Monosaccharides; Oligosaccharides
PubMed: 35435179
DOI: 10.14309/ajg.0000000000001767 -
The American Journal of Clinical... Oct 2022A low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet is increasingly used to manage symptoms in irritable bowel syndrome (IBS).... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet is increasingly used to manage symptoms in irritable bowel syndrome (IBS). Although this approach may alter the colonic microbiome, the nature of these changes has not been comprehensively synthesized.
OBJECTIVES
The aim of this study was to conduct a systematic review with meta-analysis of randomized controlled trials examining the impact of a low FODMAP diet on the composition and function of the microbiome in patients with IBS.
METHODS
A systematic search was conducted for randomized controlled trials evaluating the effects of a low FODMAP diet on the colonic microbiome in patients with IBS in MEDLINE, EMBASE, CENTRAL, and Web of Science from inception to April 2022. Outcomes included diversity of the microbiome, specific bacterial abundances, fecal SCFA concentration, and fecal pH. For fecal SCFA concentrations and pH, meta-analyses were performed via a random-effects model.
RESULTS
Nine trials involving 403 patients were included. There were no clear effects of the low FODMAP diet on diversity of the microbiome. A low FODMAP diet consistently led to lower abundance of Bifidobacteria, but there were no clear effects on diversity of the microbiome or abundances of other specific taxa. There were no differences in total fecal SCFA concentration between the low FODMAP diet and control diets (standardized mean difference: -0.25; 95% CI: -0.63, 0.13; P = 0.20), nor were there differences for fecal concentrations of specific SCFAs or fecal pH.
CONCLUSIONS
In patients with IBS, the effects of a low FODMAP diet on the colonic microbiome appear to be specific to Bifidobacteria with no consistent impacts on other microbiome metrics, including diversity, fecal SCFA concentrations, and fecal pH. Further, adequately powered trials are needed to confirm these findings.This review was registered at https://www.crd.york.ac.uk/prospero/ as CRD42020192243.
Topics: Bifidobacterium; Diet; Diet, Carbohydrate-Restricted; Disaccharides; Fermentation; Humans; Irritable Bowel Syndrome; Microbiota; Monosaccharides; Oligosaccharides
PubMed: 35728042
DOI: 10.1093/ajcn/nqac176 -
American Journal of Hematology Sep 2019Iron deficiency anemia (IDA) is prevalent, and intravenous iron, especially if given in a single dose, may result in better adherence compared with oral iron. The... (Comparative Study)
Comparative Study Randomized Controlled Trial
Iron deficiency anemia (IDA) is prevalent, and intravenous iron, especially if given in a single dose, may result in better adherence compared with oral iron. The present trial (FERWON-IDA) is part of the FERWON program with iron isomaltoside 1000/ferric derisomaltose (IIM), evaluating safety and efficacy of high dose IIM in IDA patients of mixed etiologies. This was a randomized, open-label, comparative, multi-center trial conducted in the USA. The IDA patients were randomized 2:1 to a single dose of 1000 mg IIM, or iron sucrose (IS) administered as 200 mg intravenous injections, up to five times. The co-primary endpoints were adjudicated serious or severe hypersensitivity reactions, and change in hemoglobin from baseline to week eight. A total of 1512 patients were enrolled. The frequency of patients with serious or severe hypersensitivity reactions was 0.3% (95% confidence interval: 0.06;0.88) vs 0.4% (0.05;1.45) in the IIM and IS group, respectively. The co-primary safety objective was met, and no risk difference was observed between groups. The co-primary efficacy endpoint of non-inferiority in hemoglobin change was met, and IIM led to a significantly more rapid hematological response in the first two weeks. The frequency of cardiovascular events was 0.8% and 1.2% in the IIM and IS group, respectively (P = .570). The frequency of hypophosphatemia was low in both groups. Iron isomaltoside administered as 1000 mg resulted in a more rapid and more pronounced hematological response, compared with IS, which required multiple visits. The safety profile was similar with a low frequency of hypersensitivity reactions and cardiovascular events.
Topics: Adult; Anemia, Iron-Deficiency; Disaccharides; Female; Ferric Compounds; Ferric Oxide, Saccharated; Humans; Male; Middle Aged; Prospective Studies
PubMed: 31243803
DOI: 10.1002/ajh.25564 -
Virulence Dec 2020Trehalose is a disaccharide of two D-glucose molecules linked by a glycosidic linkage, which plays both structural and functional roles in bacteria. Trehalose can be... (Review)
Review
Trehalose is a disaccharide of two D-glucose molecules linked by a glycosidic linkage, which plays both structural and functional roles in bacteria. Trehalose can be synthesized and degraded by several pathways, and induction of trehalose biosynthesis is typically associated with exposure to abiotic stress. The ability of trehalose to protect against abiotic stress has been exploited to stabilize a range of bacterial vaccines. More recently, there has been interest in the role of this molecule in microbial virulence. There is now evidence that trehalose or trehalose derivatives play important roles in virulence of a diverse range of Gram-positive and Gram-negative pathogens of animals or plants. Trehalose and/or trehalose derivatives can play important roles in host colonization and growth in the host, and can modulate the interactions with host defense mechanisms. However, the roles are typically pathogen-specific. These findings suggest that trehalose metabolism may be a target for novel pathogen-specific rather than broad spectrum interventions.
Topics: Animals; Bacteria; Bacterial Infections; Host-Pathogen Interactions; Humans; Plants; Stress, Physiological; Trehalose; Virulence
PubMed: 32862781
DOI: 10.1080/21505594.2020.1809326