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Anti-Inflammatory Effects of a Vegan Diet Versus the American Heart Association-Recommended Diet in Coronary Artery Disease Trial.
Shah, B, Newman, JD, Woolf, K, Ganguzza, L, Guo, Y, Allen, N, Zhong, J, Fisher, EA, Slater, J
Journal of the American Heart Association. 2018;7(23):e011367
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Inflammation plays a central role in the progression of atherosclerosis and is associated with adverse cardiovascular events. The aim of this study was to determine the effects of a vegan versus American Heart Association (AHA)-recommended diet on high-sensitivity C-reactive protein (hsCRP) [a type of protein found in blood plasma], as well as other markers of inflammation, glucometabolic markers, and lipid profiles in patients with established coronary artery disease (CAD) on guideline-directed medical therapy. This study is a prospective, randomized, open-label, blinded end point study design. The active study duration was 8 weeks, with an interim visit at 4 weeks and a final visit at 8 weeks. Results show: - a significantly greater reduction in hsCRP with a vegan versus AHA-recommended diet in patients with established CAD on guideline-directed medical therapy. - that the degree of weight loss, as measured by both body mass index and waist circumference, did not significantly differ between the 2 diet groups. - that markers of glycaemic control and lipid profiles, overall, also did not significantly differ in the vegan diet group when compared with the AHA-recommended diet group. Authors conclude that in patients with CAD and an elevated hsCRP, despite guideline-directed medical therapy, a vegan diet may be considered to further lower the parameters of inflammation.
Abstract
Background Dietary interventions may play a role in secondary cardiovascular prevention. hsCRP (High-sensitivity C-reactive protein) is a marker of risk for major adverse cardiovascular outcomes in coronary artery disease. Methods and Results The open-label, blinded end-point, EVADE CAD (Effects of a Vegan Versus the American Heart Association-Recommended Diet in Coronary Artery Disease) trial randomized participants (n=100) with coronary artery disease to 8 weeks of a vegan or American Heart Association-recommended diet with provision of groceries, tools to measure dietary intake, and dietary counseling. The primary end point was high-sensitivity C-reactive protein. A linear regression model compared end points after 8 weeks of a vegan versus American Heart Association diet and adjusted for baseline concentration of the end point. Significance levels for the primary and secondary end points were set at 0.05 and 0.0015, respectively. A vegan diet resulted in a significant 32% lower high-sensitivity C-reactive protein (β, 0.68, 95% confidence interval [0.49-0.94]; P=0.02) when compared with the American Heart Association diet. Results were consistent after adjustment for age, race, baseline waist circumference, diabetes mellitus, and prior myocardial infarction (adjusted β, 0.67 [0.47-0.94], P=0.02). The degree of reduction in body mass index and waist circumference did not significantly differ between the 2 diet groups (adjusted β, 0.99 [0.97-1.00], P=0.10; and adjusted β, 1.00 [0.98-1.01], P=0.66, respectively). There were also no significant differences in markers of glycemic control between the 2 diet groups. There was a nonsignificant 13% reduction in low-density lipoprotein cholesterol with the vegan diet when compared with the American Heart Association diet (adjusted β, 0.87 [0.78-0.97], P=0.01). There were no significant differences in other lipid parameters. Conclusions In patients with coronary artery disease on guideline-directed medical therapy, a vegan diet may be considered to lower high-sensitivity C-reactive protein as a risk marker of adverse outcomes. Clinical Trial Registration URL http://www.clinicaltrials.gov . Unique identifier: NCT 02135939.
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Effect of tai chi versus aerobic exercise for fibromyalgia: comparative effectiveness randomized controlled trial.
Wang, C, Schmid, CH, Fielding, RA, Harvey, WF, Reid, KF, Price, LL, Driban, JB, Kalish, R, Rones, R, McAlindon, T
BMJ (Clinical research ed.). 2018;360:k851
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Fibromyalgia is a complex disorder, characterised by chronic widespread musculoskeletal pain, fatigue, sleep problems and depression. Conventional treatment is multidisciplinary, including medication, exercise and CBT. This randomised, single-blinded trial aimed to determine the effectiveness of regular Tai Chi practice when compared to the standard recommended exercise, aerobic training. 226 adults diagnosed with fibromyalgia were randomly assigned to either 24 weeks of supervised aerobic exercise or 12 or 24 weeks of Tai Chi classes. A standard fibromyalgia impact questionnaire was used to assess changes in pain and quality of life measures, along with patient perception of various aspects of their condition. The study found that Fibromyalgia Impact Questionnaire scores improved across all treatment groups, however the 24-week Tai Chi group saw a statistically significant greater improvement than the aerobic group. In addition, those patients on the 24-week Tai Chi programme experienced greater improvement than those on the 12-week Tai Chi programme. There was also higher attendance and fewer drop-outs in the Tai Chi groups in comparison to the aerobic exercise group. Tai Chi could therefore be considered as an alternative to aerobic exercise in a multi-disciplinary approach to fibromyalgia treatment.
Abstract
OBJECTIVES To determine the effectiveness of tai chi interventions compared with aerobic exercise, a current core standard treatment in patients with fibromyalgia, and to test whether the effectiveness of tai chi depends on its dosage or duration. DESIGN Prospective, randomized, 52 week, single blind comparative effectiveness trial. SETTING Urban tertiary care academic hospital in the United States between March 2012 and September 2016. PARTICIPANTS 226 adults with fibromyalgia (as defined by the American College of Rheumatology 1990 and 2010 criteria) were included in the intention to treat analyses: 151 were assigned to one of four tai chi groups and 75 to an aerobic exercise group. INTERVENTIONS Participants were randomly assigned to either supervised aerobic exercise (24 weeks, twice weekly) or one of four classic Yang style supervised tai chi interventions (12 or 24 weeks, once or twice weekly). Participants were followed for 52 weeks. Adherence was rigorously encouraged in person and by telephone. MAIN OUTCOME MEASURES The primary outcome was change in the revised fibromyalgia impact questionnaire (FIQR) scores at 24 weeks compared with baseline. Secondary outcomes included changes of scores in patient's global assessment, anxiety, depression, self efficacy, coping strategies, physical functional performance, functional limitation, sleep, and health related quality of life. RESULTS FIQR scores improved in all five treatment groups, but the combined tai chi groups improved statistically significantly more than the aerobic exercise group in FIQR scores at 24 weeks (difference between groups=5.5 points, 95% confidence interval 0.6 to 10.4, P=0.03) and several secondary outcomes (patient's global assessment=0.9 points, 0.3 to 1.4, P=0.005; anxiety=1.2 points, 0.3 to 2.1, P=0.006; self efficacy=1.0 points, 0.5 to 1.6, P=0.0004; and coping strategies, 2.6 points, 0.8 to 4.3, P=0.005). Tai chi treatment compared with aerobic exercise administered with the same intensity and duration (24 weeks, twice weekly) had greater benefit (between group difference in FIQR scores=16.2 points, 8.7 to 23.6, P<0.001). The groups who received tai chi for 24 weeks showed greater improvements than those who received it for 12 weeks (difference in FIQR scores=9.6 points, 2.6 to 16.6, P=0.007). There was no significant increase in benefit for groups who received tai chi twice weekly compared with once weekly. Participants attended the tai chi training sessions more often than participants attended aerobic exercise. The effects of tai chi were consistent across all instructors. No serious adverse events related to the interventions were reported. CONCLUSION Tai chi mind-body treatment results in similar or greater improvement in symptoms than aerobic exercise, the current most commonly prescribed non-drug treatment, for a variety of outcomes for patients with fibromyalgia. Longer duration of tai chi showed greater improvement. This mind-body approach may be considered a therapeutic option in the multidisciplinary management of fibromyalgia. TRIAL REGISTRATION ClinicalTrials.gov NCT01420640.
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Effect of Lactobacillus rhamnosus HN001 on carriage of Staphylococcus aureus: results of the impact of probiotics for reducing infections in veterans (IMPROVE) study.
Eggers, S, Barker, AK, Valentine, S, Hess, T, Duster, M, Safdar, N
BMC infectious diseases. 2018;18(1):129
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The bacteria Staphylococcus aureus (S. aureus) is found in the digestive tract, nostrils, mouth and armpits. Methicillin-resistant S. aureus (MRSA) is responsible for several difficult-to-treat infections in humans. Probiotics are emerging as an alternative to antibiotics in preventing or treating bacterial infections. This randomised controlled trial aimed to determine the ability of Lactobacillus rhamnosus (L. rhamnosus) HN001 to reduce S. aureus at several different body sites. Participants in the study were mostly male, with an average age of 64 years, and all carriers of S. aureus in one or more body sites. Participants were organised into groups depending on whether S. aureus was found within the gastrointestinal tract (GI) or in other body sites (extra-GI), and given either L. rhamnosus HN001 probiotic, or a placebo for four weeks. Subjects given the probiotic had 15% lower levels of S. aureus in their stool samples than those given the placebo at the end of the trial. They also had 73% reduced odds of methicillin-susceptible S. aureus (MSSA) presence, and 83% reduced odds of any S. aureus presence in the stool sample compared to the placebo group. No other sampling sites showed a significant difference in colonisation between the two groups. The authors concluded that use of daily oral L. rhamnosus HN001 reduced odds of carriage of S. aureus in the GI tract, however it did not eradicate S. aureus from other body sites. The results of the study support the use of this probiotic strain for reducing the population of S. aureus in the gut. Further studies are needed to assess the effectiveness of different probiotic strains and to compare probiotics with antibiotics in reducing S. aureus in other body sites.
Abstract
BACKGROUND Infection by Staphylococcus aureus (S. aureus) is a major cause of morbidity and mortality. Colonization by S. aureus increases the risk of infection. Little is known about decolonization strategies for S. aureus beyond antibiotics, however probiotics represent a promising alternative. A randomized controlled trial was conducted to determine the efficacy of Lactobacillus rhamnosus (L. rhamnosus) HN001 in reducing carriage of S. aureus at multiple body sites. METHODS One hundred thirteen subjects, positive for S. aureus carriage, were recruited from the William S. Middleton Memorial Medical Center, Madison, WI, USA, and randomized by initial site of colonization, either gastrointestinal (GI) or extra-GI, to 4-weeks of oral L. rhamnosus HN001 probiotic, or placebo. Nasal, oropharyngeal, and axillary/groin swabs were obtained, and serial blood and fecal samples were collected. Differences in prevalence of S. aureus carriage at the end of the 4-weeks of treatment were assessed. RESULTS The probiotic and placebo groups were similar in age, gender, and health history at baseline. S. aureus colonization within the stool samples of the extra-GI group was 15% lower in the probiotic than placebo group at the endpoint of the trial. Those in the probiotic group compared to the placebo group had 73% reduced odds (OR 0.27, 95% CI 0.07-0.98) of methicillin-susceptible S. aureus presence, and 83% reduced odds (OR 0.17, 95% CI 0.04-0.73) of any S. aureus presence in the stool sample at endpoint. CONCLUSION Use of daily oral L. rhamnosus HN001 reduced odds of carriage of S. aureus in the GI tract, however it did not eradicate S. aureus from other body sites. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01321606 . Registered March 21, 2011.
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Maternal diet during pregnancy is related with the infant stool microbiome in a delivery mode-dependent manner.
Lundgren, SN, Madan, JC, Emond, JA, Morrison, HG, Christensen, BC, Karagas, MR, Hoen, AG
Microbiome. 2018;6(1):109
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The mechanism by which the maternal diet may influence the gut microbiota of an infant remains unknown. This study aimed to examine the association of maternal diet during pregnancy and mode of delivery on the gut microbiome 6 weeks post-delivery. 976 subjects were enrolled aged of 18 and 45 years old, between 24 and 28 weeks of gestation and their maternal diet during pregnancy was assessed with a validated food frequency questionnaire. Effects of maternal dairy intake on infant gut microbiota showed decreased colonization of milk-digesting bacteria in infants delivered by caesarean section, when compared to those who were born vaginally. The authors concluded that future studies examining the relationship between maternal diet and components of breast milk including microbial and nutritional profiles, may help to offer insight into the mechanism by which maternal diet influences the gut microbiome of an infant.
Abstract
BACKGROUND The gut microbiome has an important role in infant health and immune development and may be affected by early-life exposures. Maternal diet may influence the infant gut microbiome through vertical transfer of maternal microbes to infants during vaginal delivery and breastfeeding. We aimed to examine the association of maternal diet during pregnancy with the infant gut microbiome 6 weeks post-delivery in mother-infant dyads enrolled in the New Hampshire Birth Cohort Study. Infant stool samples were collected from 145 infants, and maternal prenatal diet was assessed using a food frequency questionnaire. We used targeted sequencing of the 16S rRNA V4-V5 hypervariable region to characterize infant gut microbiota. To account for differences in baseline and trajectories of infant gut microbial profiles, we stratified analyses by delivery mode. RESULTS We identified three infant gut microbiome clusters, characterized by increased abundance of Bifidobacterium, Streptococcus and Clostridium, and Bacteroides, respectively, overall and in the vaginally delivered infant stratum. In the analyses stratified to infants born vaginally and adjusted for other potential confounders, maternal fruit intake was associated with infant gut microbial community structure (PERMANOVA, p < 0.05). In multinomial logistic regression analyses, increased fruit intake was associated with an increased odds of belonging to the high Streptococcus/Clostridium group among infants born vaginally (OR (95% CI) = 2.73 (1.36, 5.46)). In infants delivered by Cesarean section, we identified three clusters that differed slightly from vaginally delivered infants, which were characterized by a high abundance of Bifidobacterium, high Clostridium and low Streptococcus and Ruminococcus genera, and high abundance of the family Enterobacteriaceae. Maternal dairy intake was associated with an increased odds of infants belonging to the high Clostridium cluster in infants born by Cesarean section (OR (95% CI) = 2.36 (1.05, 5.30)). Linear models suggested additional associations between maternal diet and infant intestinal microbes in both delivery mode strata. CONCLUSIONS Our data indicate that maternal diet influences the infant gut microbiome and that these effects differ by delivery mode.
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Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics.
Krumbeck, JA, Rasmussen, HE, Hutkins, RW, Clarke, J, Shawron, K, Keshavarzian, A, Walter, J
Microbiome. 2018;6(1):121
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Numerous studies have established that the gut microbiota contributes to gastrointestinal health and this can also be achieved through dietary consumption of probiotics and prebiotics. Gut microbiota have also been associated in impacting the markers of metabolic diseases but not many studies are available. Henceforth on this basis this study, looked into the synergistic effects of administering prebiotic together with a select probiotic Bifidobacterium strain. The main objective of this study was to establish the synergistic effect of probiotics and prebiotics and compare their effects on microbiota composition. This study was a randomised, double-blinded, placebo-controlled, clinical trial conducted on a total of 151 volunteers assigned to six treatments groups. The authors concluded that the synergistic combinations tested in this study did not demonstrate functional synergism, and neither any significant effects on metabolic disease outcomes were observed within the six treatment groups. Although, the findings from this study clearly demonstrated that the pro and prebiotic components improved markers of colonic permeability, henceforth providing a rational for their use in gut microbiota health.
Abstract
BACKGROUND One way to improve both the ecological performance and functionality of probiotic bacteria is by combining them with a prebiotic in the form of a synbiotic. However, the degree to which such synbiotic formulations improve probiotic strain functionality in humans has not been tested systematically. Our goal was to use a randomized, double-blind, placebo-controlled, parallel-arm clinical trial in obese humans to compare the ecological and physiological impact of the prebiotic galactooligosaccharides (GOS) and the probiotic strains Bifidobacterium adolescentis IVS-1 (autochthonous and selected via in vivo selection) and Bifidobacterium lactis BB-12 (commercial probiotic allochthonous to the human gut) when used on their own or as synbiotic combinations. After 3 weeks of consumption, strain-specific quantitative real-time PCR and 16S rRNA gene sequencing were performed on fecal samples to assess changes in the microbiota. Intestinal permeability was determined by measuring sugar recovery in urine by GC after consumption of a sugar mixture. Serum-based endotoxin exposure was also assessed. RESULTS IVS-1 reached significantly higher cell numbers in fecal samples than BB-12 (P < 0.01) and, remarkably, its administration induced an increase in total bifidobacteria that was comparable to that of GOS. Although GOS showed a clear bifidogenic effect on the resident gut microbiota, both probiotic strains showed only a non-significant trend of higher fecal cell numbers when administered with GOS. Post-aspirin sucralose:lactulose ratios were reduced in groups IVS-1 (P = 0.050), IVS-1 + GOS (P = 0.022), and GOS (P = 0.010), while sucralose excretion was reduced with BB-12 (P = 0.002) and GOS (P = 0.020), indicating improvements in colonic permeability but no synergistic effects. No changes in markers of endotoxemia were observed. CONCLUSION This study demonstrated that "autochthony" of the probiotic strain has a larger effect on ecological performance than the provision of a prebiotic substrate, likely due to competitive interactions with members of the resident microbiota. Although the synbiotic combinations tested in this study did not demonstrate functional synergism, our findings clearly showed that the pro- and prebiotic components by themselves improved markers of colonic permeability, providing a rational for their use in pathologies with an underlying leakiness of the gut.
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Glucotypes reveal new patterns of glucose dysregulation.
Hall, H, Perelman, D, Breschi, A, Limcaoco, P, Kellogg, R, McLaughlin, T, Snyder, M
PLoS biology. 2018;16(7):e2005143
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One in 10 individuals is affected by diabetes, a condition involving abnormal regulation of blood glucose. Currently, diabetes is assessed using single-time or average measurements of blood glucose, without consideration for how blood glucose fluctuates over time. This study used continuous glucose monitoring (CGM) technology to evaluate how blood glucose fluctuates in individuals over time. The authors found that many individuals considered nondiabetic by standard measures experienced frequent elevations in blood glucose levels into the pre-diabetic or diabetic range (15% and 2% of the time, respectively). The authors developed a model for determining the “glucotype” (low, moderate or severe variability) of an individual, a more comprehensive measure of glucose patterns than the standard tests currently used. The authors argue that CGM should become an important tool in early identification of those at risk for type 2 diabetes.
Abstract
Diabetes is an increasing problem worldwide; almost 30 million people, nearly 10% of the population, in the United States are diagnosed with diabetes. Another 84 million are prediabetic, and without intervention, up to 70% of these individuals may progress to type 2 diabetes. Current methods for quantifying blood glucose dysregulation in diabetes and prediabetes are limited by reliance on single-time-point measurements or on average measures of overall glycemia and neglect glucose dynamics. We have used continuous glucose monitoring (CGM) to evaluate the frequency with which individuals demonstrate elevations in postprandial glucose, the types of patterns, and how patterns vary between individuals given an identical nutrient challenge. Measurement of insulin resistance and secretion highlights the fact that the physiology underlying dysglycemia is highly variable between individuals. We developed an analytical framework that can group individuals according to specific patterns of glycemic responses called "glucotypes" that reveal heterogeneity, or subphenotypes, within traditional diagnostic categories of glucose regulation. Importantly, we found that even individuals considered normoglycemic by standard measures exhibit high glucose variability using CGM, with glucose levels reaching prediabetic and diabetic ranges 15% and 2% of the time, respectively. We thus show that glucose dysregulation, as characterized by CGM, is more prevalent and heterogeneous than previously thought and can affect individuals considered normoglycemic by standard measures, and specific patterns of glycemic responses reflect variable underlying physiology. The interindividual variability in glycemic responses to standardized meals also highlights the personal nature of glucose regulation. Through extensive phenotyping, we developed a model for identifying potential mechanisms of personal glucose dysregulation and built a webtool for visualizing a user-uploaded CGM profile and classifying individualized glucose patterns into glucotypes.
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Human Gut Microbiota and Gastrointestinal Cancer.
Meng, C, Bai, C, Brown, TD, Hood, LE, Tian, Q
Genomics, proteomics & bioinformatics. 2018;16(1):33-49
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In this article the authors review research on the influence of the human gut microbiota on the development and progression of gastrointestinal cancers, and go into significant detail about the molecular mechanisms involved. Helicobacter pylori is a known risk factor for gastric cancer (GC) but other dysbiotic changes in the gut microbiota are also observed in GC. On the other hand, H. pylori is associated with a decreased risk for oesophageal cancer (OC). An increase in gram-negative bacteria is associated with OC, whilst gram-positive bacteria are dominant in a healthy oesophagus. Dietary factors are associated with the risk for colorectal cancer (CRC) and may be due to their effect on the bacterial composition of the bowel. The authors explore possible mechanisms for these links. Although the liver is considered sterile, carcinogenesis can be influenced by the gut microbiota through pathogens and bacterial metabolites which can disturb metabolic pathways and immune responses in the liver. In pancreatic cancer (PC), the gut microbiota may influence carcinogenesis by promoting inflammation. In addition to various lifestyle factors, H. pylori is a risk factor for PC. The authors also review the use of prebiotics, probiotics, synbiotics (a combination of pre- and pro-biotics) and Traditional Chinese Medicine as an adjunct to conventional cancer treatment to reduce side effects, as well as their potential preventive mechanisms.
Abstract
Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.
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Fructose metabolism and metabolic disease.
Hannou, SA, Haslam, DE, McKeown, NM, Herman, MA
The Journal of clinical investigation. 2018;128(2):545-555
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Sugar consumption is thought to be a contributing factor in the increase in diabetes and obesity and the associated risk of cardiovascular disease worldwide. Sucrose (table sugar) and high fructose corn syrup contain almost equal amounts of fructose and glucose and are commonly added to processed foods. Whilst long-term studies are lacking, some short-term intervention studies show that fructose can impair lipid metabolism and insulin sensitivity in humans. This article reviews the biochemistry and molecular genetics of fructose metabolism as well as potential mechanisms by which excessive fructose consumption contributes to cardiometabolic disease. Fructose absorption in the human intestine is saturable, and there is a large range in capacity to absorb fructose between individuals, and unabsorbed fructose may contribute to gastrointestinal symptoms including pain and bloating. Fructose concentrations in the blood can increase 10-fold after consumption, but are rapidly cleared, mostly by the liver, where it provides substrate for metabolic processes, but may also be involved in signalling functions. Fructose may enhance glucose uptake by the liver and storage as glycogen and lipids. It may also increase production of uric acid which is implicated with gout. Excessive fructose consumption affects lipid metabolism and may contribute to fat accumulation in the liver and increase circulating triglycerides, a risk factor for heart disease. In animal models it also induces increased insulin levels. Fructose is one of the sweetest sugars which may affect appetite and overeating. It may also induce addiction-like behaviours such as binging and dependence in part by stimulating dopaminergic pathways. It also appears to induce leptin resistance which further increases food intake and obesity.
Abstract
Increased sugar consumption is increasingly considered to be a contributor to the worldwide epidemics of obesity and diabetes and their associated cardiometabolic risks. As a result of its unique metabolic properties, the fructose component of sugar may be particularly harmful. Diets high in fructose can rapidly produce all of the key features of the metabolic syndrome. Here we review the biology of fructose metabolism as well as potential mechanisms by which excessive fructose consumption may contribute to cardiometabolic disease.
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Endotoxin-initiated inflammation reduces testosterone production in men of reproductive age.
Tremellen, K, McPhee, N, Pearce, K, Benson, S, Schedlowski, M, Engler, H
American journal of physiology. Endocrinology and metabolism. 2018;314(3):E206-E213
Abstract
Inflammation, both acute and chronic, is associated with testosterone deficiency, raising the possibility of a direct causal link. One potential trigger for inflammation in obese men is the passage of intestinal bacteria into the circulation due to a breakdown in mucosal barrier integrity. Recently, we hypothesized that this endotoxin exposure may cause androgen deficiency in obese men. To test this hypothesis, we analyzed the relationship between serum levels of lipopolysaccharide-binding protein (LBP), an indirect measure of endotoxin exposure, against male reproductive hormones, inflammatory markers (C-reactive protein, IL-1β, IL-6, TNF-α), and adiposity in 75 men. Adiposity was positively correlated with endotoxin exposure (LBP) and inflammation (C-reactive protein, IL-6) and negatively correlated with testosterone. Furthermore, endotoxemia (LBP) was negatively correlated with serum testosterone but positively correlated with IL-6. Multivariate analysis revealed a significant, negative correlation between serum IL-6 and free testosterone. In a second interventional study, low-dose endotoxin challenge in lean men produced a transient inflammatory response that was followed by a decline in serum testosterone, without changes in LH or FSH, providing further evidence that endotoxin-driven inflammation may result in impaired Leydig cell function.
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Intestinal Absorption of Fructose.
Ferraris, RP, Choe, JY, Patel, CR
Annual review of nutrition. 2018;38:41-67
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Increased understanding of fructose metabolism, which begins with uptake via the intestine, is important because fructose now constitutes a physiologically significant portion of human diets and is associated with increased incidence of certain cancers and metabolic diseases. New insights in our knowledge of intestinal fructose absorption mediated by the facilitative glucose transporter GLUT5 in the apical membrane and by GLUT2 in the basolateral membrane are reviewed. We begin with studies related to structure as well as ligand binding, then revisit the controversial proposition that apical GLUT2 is the main mediator of intestinal fructose absorption. The review then describes how dietary fructose may be sensed by intestinal cells to affect the expression and activity of transporters and fructolytic enzymes, to interact with the transport of certain minerals and electrolytes, and to regulate portal and peripheral fructosemia and glycemia. Finally, it discusses the potential contributions of dietary fructose to gastrointestinal diseases and to the gut microbiome.