Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome; its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from ...overnutrition and a sedentary lifestyle, recent evidence suggests that diets high in sugar (from sucrose and/or high-fructose corn syrup HFCS) not only increase the risk of NAFLD, but also non-alcoholic steatohepatitis (NASH). Herein, we review the experimental and clinical evidence that fructose precipitates fat accumulation in the liver, due to both increased lipogenesis and impaired fat oxidation. Recent evidence suggests that the predisposition to fatty liver is linked to the metabolism of fructose by fructokinase C, which results in ATP consumption, nucleotide turnover and uric acid generation that mediate fat accumulation. Alterations to gut permeability, the microbiome, and associated endotoxemia contribute to the risk of NAFLD and NASH. Early clinical studies suggest that reducing sugary beverages and total fructose intake, especially from added sugars, may have a significant benefit on reducing hepatic fat accumulation. We suggest larger, more definitive trials to determine if lowering sugar/HFCS intake, and/or blocking uric acid generation, may help reduce NAFLD and its downstream complications of cirrhosis and chronic liver disease.
Excessive sugar intake is now recognized as a key risk factor for obesity, type 2 diabetes, and cardiovascular diseases. In contrast, evidence on the sugar–cancer link is less consistent. ...Experimental data suggest that sugars could play a role in cancer etiology through obesity but also through inflammatory and oxidative mechanisms and insulin resistance, even in the absence of weight gain.
The objective was to study the associations between total and added sugar intake and cancer risk (overall, breast, and prostate), taking into account sugar types and sources.
In total, 101,279 participants aged >18 y (median age, 40.8 y) from the French NutriNet-Santé prospective cohort study (2009–2019) were included (median follow-up time, 5.9 y). Sugar intake was assessed using repeated and validated 24-h dietary records, designed to register participants’ usual consumption for >3500 food and beverage items. Associations between sugar intake and cancer risk were assessed by Cox proportional hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors).
Total sugar intake was associated with higher overall cancer risk (n = 2503 cases; HR for quartile 4 compared with quartile 1: 1.17; 95% CI: 1.00, 1.37; Ptrend = 0.02). Breast cancer risks were increased (n = 783 cases; HRQ4vs.Q1 = 1.51; 95% CI: 1.14, 2.00; Ptrend = 0.0007). Results remained significant when weight gain during follow-up was adjusted for. In addition, significant associations with cancer risk were also observed for added sugars, free sugars, sucrose, sugars from milk-based desserts, dairy products, and sugary drinks (Ptrend ≤ 0.01).
These results suggest that sugars may represent a modifiable risk factor for cancer prevention (breast in particular), contributing to the current debate on the implementation of sugar taxation, marketing regulation, and other sugar-related policies. This trial was registered at clinicaltrials.gov as NCT03335644.
Designing better sugary drink taxes Grummon, Anna H; Lockwood, Benjamin B; Taubinsky, Dmitry ...
Science (American Association for the Advancement of Science),
09/2019, Volume:
365, Issue:
6457
Journal Article
Peer reviewed
Open access
Tax the sugar, not the liquid
Taxes on sugar-sweetened beverages (SSBs), such as soda and bottled iced tea, are an increasingly popular approach to reducing obesity, diabetes, and other health harms ...(
1
). As of mid-2019, 42 countries and seven U.S. cities have implemented SSB taxes (
2
). A basic economic principle is that such corrective taxes should be proportional to the harm caused. The harm from sugary drinks comes from the sugar, and SSBs vary substantially in sugar per unit volume. Yet SSB taxes typically set constant rates per unit volume; only three SSB taxes worldwide are proportional to sugar content. For example, the seven U.S. cities that tax SSBs use volumetric taxes of 34 to 68 cents per liter of liquid (1 to 2 cents per ounce) instead of, say, 0.5 cents per gram of sugar. These volumetric SSB taxes are poorly targeted to the actual health harms from SSBs. We estimate that a simple design change—taxing the amount of sugar in a drink, not the volume of liquid that accompanies the sugar—could boost a SSB tax's health benefits and overall economic gains by roughly 30%.
Recent preclinical research strongly suggests that dietary sugars can enhance colorectal tumorigenesis by direct action, particularly in the proximal colon that unabsorbed fructose reaches.
We aimed ...to examine long-term consumption of sugar-sweetened beverages (SSBs) and total fructose in relation to incidence and mortality of colorectal cancer (CRC) by anatomic subsite.
We followed 121,111 participants from 2 prospective US cohort studies, the Nurses’ Health Study (1984–2014) and Health Professionals Follow-Up Study (1986–2014), for incident CRC and related death. Cox proportional hazards regression was used to compute HRs and 95% CIs.
During follow-up, we documented 2733 incident cases of CRC with a known anatomic location, of whom 901 died from CRC. Positive associations of SSB and total fructose intakes with cancer incidence and mortality were observed in the proximal colon but not in the distal colon or rectum (Pheterogeneity ≤ 0.03). SSB consumption was associated with a statistically significant increase in the incidence of proximal colon cancer (HR per 1-serving/d increment: 1.18; 95% CI: 1.03, 1.34; Ptrend = 0.02) and a more pronounced elevation in the mortality of proximal colon cancer (HR: 1.39; 95% CI: 1.13, 1.72; Ptrend = 0.002). Similarly, total fructose intake was associated with increased incidence and mortality of proximal colon cancer (HRs per 25-g/d increment: 1.18; 95% CI: 1.03, 1.35; and 1.42; 95% CI: 1.12, 1.79, respectively). Moreover, SSB and total fructose intakes during the most recent 10 y, rather than those from a more distant period, were associated with increased incidence of proximal colon cancer.
SSB and total fructose consumption were associated with increased incidence and mortality of proximal colon cancer, particularly during later stages of tumorigenesis.
Rare sugars have recently attracted much attention because of their potential applications in the food, nutraceutical, and pharmaceutical industries. A systematic strategy for enzymatic production of ...rare sugars, named Izumoring, was developed >10years ago. The strategy consists of aldose-ketose isomerization, ketose C-3 epimerization, and monosaccharide oxidation-reduction. Recent development of the Izumoring strategy is reviewed herein, especially the genetic approaches to the improvement of rare sugar-producing enzymes and the applications of target-oriented bioconversion. In addition, novel non-Izumoring enzymatic approaches are also summarized, including enzymatic condensation, phosphorylation-dephosphorylation cascade reaction, aldose epimerization, ulosonic acid decarboxylation, and biosynthesis of rare disaccharides.
Nucleotide sugar (NS) dehydratases play a central role in the biosynthesis of deoxy and amino sugars, which are involved in a variety of biological functions in all domains of life. Bacteria are true ...masters of deoxy sugar biosynthesis as they can produce a wide range of highly specialized monosaccharides. Indeed, deoxy and amino sugars play important roles in the virulence of gram-positive and gram-negative pathogenic species and are additionally involved in the biosynthesis of diverse macrolide antibiotics. The biosynthesis of deoxy sugars relies on the activity of NS dehydratases, which can be subdivided into three groups based on their structure and reaction mechanism. The best-characterized NS dehydratases are the 4,6-dehydratases that, together with the 5,6-dehydratases, belong to the NS-short-chain dehydrogenase/reductase superfamily. The other two groups are the less abundant 2,3-dehydratases that belong to the Nudix hydrolase superfamily and 3-dehydratases, which are related to aspartame aminotransferases. 4,6-Dehydratases catalyze the first step in all deoxy sugar biosynthesis pathways, converting nucleoside diphosphate hexoses to nucleoside diphosphate-4-keto-6-deoxy hexoses, which in turn are further deoxygenated by the 2,3- and 3-dehydratases to form dideoxy and trideoxy sugars. In this review, we give an overview of the NS dehydratases focusing on the comparison of their structure and reaction mechanisms, thereby highlighting common features, and investigating differences between closely related members of the same superfamilies.
The World Health Organization guideline to use less sugar may be an opportunity and support for dentistry in its goal to get the message of using less sugar across to the public. Two ways (with all ...the combinations of these) to achieve a reduction of sugar consumption are the reduction of the amount of sugar in products or the reduction of the frequency of consumption of sugar-containing products. Which sugar-reducing strategy is best for caries prevention? To answer this question, this manuscript discusses the shape of the dose-response association between sugar intake and caries, the influence of fluoridated toothpaste on the association of sugar intake and caries and the relative contribution of frequency and amount of sugar intake to caries levels. The results suggest that when fluoride is appropriately used, the relation between sugar consumption and caries is very low or absent. The high correlation between amount and frequency hampers the decision related to which of both is of more importance, but frequency (and stickiness) fits better in our understanding of the caries process. Reducing the amount without reducing the frequency does not seem to be an effective caries preventive approach in contrast to the reciprocity. Goals set in terms of frequency may also be more tangible for patients to follow than goals set in amount. Yet, in sessions of dietary counselling to prevent dental caries, the counsellor should not forget the importance of quality tooth brushing with fluoride toothpaste.
Consumption of fructose has risen markedly in recent decades owing to the use of sucrose and high-fructose corn syrup in beverages and processed foods
, and this has contributed to increasing rates ...of obesity and non-alcoholic fatty liver disease
. Fructose intake triggers de novo lipogenesis in the liver
, in which carbon precursors of acetyl-CoA are converted into fatty acids. The ATP citrate lyase (ACLY) enzyme cleaves cytosolic citrate to generate acetyl-CoA, and is upregulated after consumption of carbohydrates
. Clinical trials are currently pursuing the inhibition of ACLY as a treatment for metabolic diseases
. However, the route from dietary fructose to hepatic acetyl-CoA and lipids remains unknown. Here, using in vivo isotope tracing, we show that liver-specific deletion of Acly in mice is unable to suppress fructose-induced lipogenesis. Dietary fructose is converted to acetate by the gut microbiota
, and this supplies lipogenic acetyl-CoA independently of ACLY
. Depletion of the microbiota or silencing of hepatic ACSS2, which generates acetyl-CoA from acetate, potently suppresses the conversion of bolus fructose into hepatic acetyl-CoA and fatty acids. When fructose is consumed more gradually to facilitate its absorption in the small intestine, both citrate cleavage in hepatocytes and microorganism-derived acetate contribute to lipogenesis. By contrast, the lipogenic transcriptional program is activated in response to fructose in a manner that is independent of acetyl-CoA metabolism. These data reveal a two-pronged mechanism that regulates hepatic lipogenesis, in which fructolysis within hepatocytes provides a signal to promote the expression of lipogenic genes, and the generation of microbial acetate feeds lipogenic pools of acetyl-CoA.
Deoxy-sugars often play a critical role in modulating the potency of many bioactive natural products. Accordingly, there has been sustained interest in methods for their synthesis over the past ...several decades. The focus of much of this work has been on developing new glycosylation reactions that permit the mild and selective construction of deoxyglycosides. This Review covers classical approaches to deoxyglycoside synthesis, as well as more recently developed chemistry that aims to control the selectivity of the reaction through rational design of the promoter. Where relevant, the application of this chemistry to natural product synthesis will also be described.
This study aims to estimate the free sugars intake, identify the primary food sources of free sugars, and explore the relationship between free sugars intake and dental caries among Chinese ...adolescents. This cross-sectional study included 1517 middle-school students aged 12-14 years in Changsha city, China. Adolescents completed a 12-item Food Frequency Questionnaire (FFQ) and oral health assessment. The students' dental caries experience was available as DMFT score (number of decayed, missing, and filled permanent teeth). Statistical analyses included the Mann-Whitney test, Kruskal-Wallis test, Chi-square test, and binary logistic regression model. The average intake of free sugars was 53.1 g/d in adolescents, and 43.2% of the students consumed more than 50 g of free sugars daily. The primary contributor to free sugars was sugar-sweetened beverages (SSBs). Age, boarders, and high family income were risk factors for excessive free sugars intake (
< 0.05), and increased free sugars intake was a risk factor for dental caries (odds ratio, OR = 1.446, 95% confidence interval: 1.138-1.839). Both the free sugars intake and dental caries prevalence in Chinese adolescents were high. Targeted interventions are urgently needed to address the excessive consumption of free sugars and improve Chinese adolescents' oral health.
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