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Research question Is there an influence of maternal lifestyle factors on the incidence of oocyte dimorphisms and the outcomes of intracytoplasmic sperm injection (ICSI) cycles? Design A total of 752 female patients undergoing ICSI cycle, in a private university-affiliated in vitro fertilization center, from January/2015 to December/2019, were included in this historical cohort study. Prior to start of controlled ovarian stimulation (COS), participants answered a questionnaire regarding cigarette smoking habit, consumption of items such as alcoholic beverages, refined sugar, artificial sweetener, soft drinks, fruits, legumes and vegetables, milk and dairy, and meats, and exercise frequency over the past 6 months. Oocyte morphology was evaluated before ICSI. The influence of maternal lifestyle factors on the incidence of oocyte dimorphisms and ICSI outcomes was evaluated by multivariate general linear models and generalized linear models, adjusted for potential confounders. The main outcome measures were the incidence of oocyte dimorphisms per cycle and clinical outcomes. Results Lifestyle factors and nutritional habits such as cigarette smoking, and the consumptions of alcohol, refined sugar, and artificial sweetener were positively associated with incidence of several oocyte dimorphisms and negatively associated with the response to COS and embryo development. Negative relationships were also observed between those habits and pregnancy outcomes, apart from miscarriage rate, in which positive relationships were observed. Significant negative dose-dependent relationships between those habits and implantation rate were noted. The intake of alcoholic beverages also showed inverse dose-dependent relationships with pregnancy and live-birth rates. Live-birth rate was also negatively associated with cigarette smoking, in a dose-dependent manner. Conclusions Bad maternal habits were associated with reduced oocyte quality and ICSI outcomes. Many of those associations were shown to be dose-dependent.

BACKGROUND: Both the incidence of diabetes mellitus and consumption of sugar-sweetened beverages are high in the Hispanic/Latino population in the United States. The associations between consumption of sugar-sweetened beverages, artificially sweetened beverages, and 100% fruit juice with prediabetes and glucose metabolism markers in the diverse Hispanic/Latino population in the United States are unknown. OBJECTIVES: The objective of this study was to examine the cross-sectional associations between consumption of sugar-sweetened beverages, artificially sweetened beverages, and 100% fruit juice with prediabetes and glucose metabolism markers such as fasting glucose and insulin, 2-h oral-glucose-tolerance test, HOMA-IR, HOMA index for β-cell function (HOMA-B), and glycated hemoglobin (HbA1c) among US Hispanic/Latino adults. METHODS: Using baseline data from the Hispanic Community Health Study/Study of Latinos (2008–2011), beverage consumption was ascertained using two 24-h dietary recalls and a food propensity questionnaire. Diabetes/prediabetes status was defined by self-report, antihyperglycemic medication use, and American Diabetes Association laboratory criteria. Among 9965 individuals without diabetes (5194 normoglycemia, 4771 prediabetes) aged 18–74 y, the associations of beverage consumption with prediabetes and glucose metabolism markers were analyzed using logistic and linear regressions, respectively, accounting for complex survey design. RESULTS: Compared with individuals who consumed 2 servings/d (>480 mL/d) had 1.3 times greater odds of having prediabetes (95% CI: 1.06, 1.61) and higher glucose metabolism markers including fasting glucose, fasting insulin, HOMA-IR, and HbA1c. Consumption of artificially sweetened beverages showed an inverse association with β-cell function (HOMA-B). Intake of 100% fruit juice was not significantly associated with prediabetes nor with glucose metabolism markers. CONCLUSIONS: Among US Hispanic/Latino adults, higher sugar-sweetened beverage consumption was associated with increased odds of prediabetes and higher glucose metabolism markers. Public health initiatives to decrease sugar-sweetened beverage consumption could potentially reduce the burden of diabetes among Hispanics/Latinos in the United States.

Plant cell and tissue culture makes provision of a sustainable and nature-friendly strategy for the production of secondary metabolites, and modern progress in gene editing and genome engineering provides novel possibilities to improve both the qualitative and quantitative aspects of such phytochemicals. The ever-expanding quest for plant-based medicine to treat diabetes facilitates large-scale cultivation of Stevia rebaudiana to enhance the yield of its much-coveted low-calorie sweetener glycosides. The potential to process stevia as a "natural" product should enhance the acceptance of steviosides as a natural calorie-free sweetener especially suitable for use in diabetic and weight control drinks and foods. Besides sweetener agents, S. rebaudiana is a potent source of many antioxidant compounds and is used to cure immunodeficiencies, neurologic disorders, inflammation, diabetes mellitus, Parkinson's disease, and Alzheimer's disease. This comprehensive review presents the research outcomes of the many biotechnological interventions implicated to upscale the yield of steviol glycosides and its derivatives in in vitro cell, callus, tissue, and organ cultures with notes on the use of bioreactor and genetic engineering in relation to the production of these valuable compounds in S. rebaudiana. KEY POINTS: • Critical and updated assessment on sustainable production of steviol glycosides from Stevia rebaudiana. • In vitro propagation of S. rebaudiana and elicitation of steviol glycosides production. • Genetic fidelity and diversity assessment of S. rebaudiana using molecular markers.

Objective: The aim of this study is to examine the effect of diet drinks on dental erosion among a representative sample of US adults. Methods: Adult dietary and dental data were analyzed from the 2003–2004 cycle of the National Health and Nutrition Examination Survey. Erosion was measured with a modified tooth wear index and was analyzed as a dichotomous variable. Cluster analysis was performed, and the cluster number was based on having a separate diet drink cluster and the R2 values. Survey procedure and sample weights were used. Results: Most of the population (80%) had some form of dental erosive lesions. When compared with the total sample, people with erosion were more likely to be male (52.5%) and older. People with no erosive lesions were younger (42.3%) and non-Hispanic Black (21.2%). Cluster analysis resulted in 4 distinct clusters: high water, high diet drinks, high coffee/tea, and high soda. The respective percentage of individuals in each cluster who had erosion was 78.9%, 85%, 83.9%, and 76.2%, where the “high diet drinks” cluster showed the highest erosion ( P = 0.28). Logistic regression modeling showed that the “high diet drinks” cluster had increased odds of erosion (odds ratio = 1.27; 95% CI = 0.58 to 2.77) when compared with the “high water” cluster, but the relationship was not statistically significant. Conclusion: High diet drinks consumption slightly increased the odds of dental erosion among US adults, although this relationship was not statistically significant. It is thus not yet clear that dentists should recommend diet drinks, as they might be linked to systemic diseases. Further research is needed to explore more about risk factors of erosion. Knowledge Transfer Statement: The findings of this study are suggestive, though not significantly, that diet drinks may increase risk for dental erosion. While further research is needed, it is not clear that dentists should recommend these drinks as healthy substitutes for sugary drinks.

BACKGROUND/OBJECTIVE The evidence that maternal non-nutritive sweetener (NNS) intake during pregnancy increases childhood obesity risk is conflicting. A potential reason for this is that all prior studies examined childhood body mass index (BMI) at only one timepoint and at different ages. We examined the extent to which NNS intake during pregnancy is associated with offspring BMI z-score and body fat longitudinally from birth to 18 years. SUBJECTS A total of 1683 children from Project Viva, a prospective pre-birth cohort, were recruited from 1999 to 2002 in Massachusetts. METHODS We assessed maternal NNS intake in the first and second trimesters of pregnancy using a semiquantitative food frequency questionnaire. Our outcomes were offspring BMI z-score, (at birth, infancy (median 6.3 months), early childhood (3.2 years), mid-childhood (7.7 years), and early adolescence (12.9 years)), sum of skinfolds (SS), fat mass index (FMI) measured by dual x-ray absorptiometry, and BMI z-score trajectory from birth to 18 years. We adjusted models for maternal pre-pregnancy BMI, age, race/ethnicity, education, parity, pre-pregnancy physical activity, smoking, and paternal BMI and education. RESULTS A total of 70% of mothers were white and pre-pregnancy BMI was 24.6 ± 5.2 kg/m2. The highest quartile of NNS intake (Q4: 0.98 ± 0.91 servings/day) was associated with higher BMI z-score in infancy (β 0.20 units; 95% CI 0.02, 0.38), early childhood (0.21; 0.05, 0.37), mid-childhood (0.21; 0.02, 0.40), and early adolescence (0.14; -0.07, 0.35) compared with Q1 intake (Q1: 0.00 ± 0.00 servings/day). Q4 was also associated with higher SS in early childhood (1.17 mm; 0.47, 1.88), mid-childhood (2.33 mm; 0.80, 3.87), and early adolescence (2.27 mm; -0.06, 4.60) and higher FMI in mid-childhood (0.26 kg/m2; -0.07, 0.59). Associations of maternal NNS intake with offspring BMI z-score became stronger with increasing age from 3 to 18 years (Pinteraction

BackgroundNeonatal hypoglycemia is a common disorder especially in at-risk infants and it can be associated with poor long-term neurological outcomes. Several therapeutic interventions are suggested, from the implementation of breastfeeding to the glucose intravenous administration. Oral dextrose gel massaged into the infant’s inner cheek is a recent treatment option of asymptomatic hypoglycemia, after which oral feeding is encouraged. This approach seems to reduce the admission of infants to neonatal intensive care unit (NICU) so favouring maternal bonding and breastfeeding success at discharge.MethodsIn our ward, we prospectively compared a group of near-term neonates, (Gr2,n = 308) at risk for hypoglycemia, treated with an innovative protocol based on the addition of 40% oral dextrose gel (Destrogel, Orsana®,Italy) administered by massaging gums and cheek with historical matching newborns (Gr1,n = 389) treated with a formerly used protocol, as control group. The primary outcome was occurrence of NICU admission and the requirement of intravenous glucose administration; while discharge with full breastfeeding was the secondary outcome.ResultsIn Gr1, 39/389 (10%) infants presented with asymptomatic hypoglycemia, 19/39 were transferred to the NICU, and 14/39 required intravenous glucose treatment. In Gr2, among the 30/308 infants with asymptomatic hypoglycemia managed according to the new protocol, 3/30 were transferred to the NICU and received intravenous glucose infusion. The mean duration of hospitalization respectively was 6.43 (± 6.36) and 3.73 ± 1.53 days (p p = 0.02). Considering Gr1 vs Gr2, the number of patients that were transferred to NICU was 19 (48.7%) vs 3 (10%) (p = 0.001) and the number of infants that needed intravenous glucose infusion was 14 (35.9%) vs 3 (10%) (p = 0.01), respectively.ConclusionsIn our population of near term infants, the introduction of 40% oral dextrose gel to the protocol, helped in the safe management of asymptomatic hypoglycemia and, at the same time, implemented breastfeeding.

High blood glucose has long been established as a risk factor for tumor metastasis, yet the molecular mechanisms underlying this association have not been elucidated. Here we describe that hyperglycemia promotes tumor metastasis via increased platelet activity. Administration of glucose, but not fructose, reprogrammed the metabolism of megakaryocytes to indirectly prime platelets into a prometastatic phenotype with increased adherence to tumor cells. In megakaryocytes, a glucose metabolism-related gene array identified the mitochondrial molecular chaperone glucose-regulated protein 75 (GRP75) as a trigger for platelet activation and aggregation by stimulating the Ca2+-PKCα pathway. Genetic depletion of Glut1 in megakaryocytes blocked MYC-induced GRP75 expression. Pharmacologic blockade of platelet GRP75 compromised tumor-induced platelet activation and reduced metastasis. Moreover, in a pilot clinical study, drinking a 5% glucose solution elevated platelet GRP75 expression and activated platelets in healthy volunteers. Platelets from these volunteers promoted tumor metastasis in a platelet-adoptive transfer mouse model. Together, under hyperglycemic conditions, MYC-induced upregulation of GRP75 in megakaryocytes increases platelet activation via the Ca2+-PKCα pathway to promote cancer metastasis, providing a potential new therapeutic target for preventing metastasis. Significance: This study provides mechanistic insights into a glucose–megakaryocyte–platelet axis that promotes metastasis and proposes an antimetastatic therapeutic approach by targeting the mitochondrial protein GRP75.

The association between artificial sweetener (AS) consumption and the risk of organ-specific cancers has been debated for decades. We hypothesized that AS consumption is associated with reduced risk of gastrointestinal (GI) cancers. We aimed to test this hypothesis by conducting a systematic review and meta-analysis of the association between AS and GI cancers. We searched 4 databases for comparative studies of AS consumption (exposed) versus no consumption (nonexposed) and the odds or risk of GI luminal or non-luminal cancer (primary outcome). Estimates were pooled using a random-effects model. Studies were evaluated for quality, bias, and heterogeneity. We analyzed 8 (4 prospective, 4 case-control) studies comprising data on 1,043,496 individuals, among whom 3271 pancreatic, 395 gastric, 304 esophageal, 3008 colorectal, and 598 oropharyngeal cancers occurred. While there was no significant association between AS consumption and odds of GI cancer overall, AS consumption was associated with 19% reduced likelihood of luminal GI cancer (OR 0.81, 95% CI:0.68-0.97). There was no association between AS consumption and non-luminal GI cancer. Meta-regression demonstrated no difference in effect estimates based on study type. Based on this first meta-analysis of AS and GI cancer, we demonstrated that AS consumption is associated with a significantly lower likelihood of luminal, but not non-luminal, GI cancer.

BACKGROUND AND AIM The artificial sweetener acesulfame potassium (ACK) is officially approved as safe for intake and has been used in processed foods. However, ACKs have been reported to induce metabolic syndrome, along with alteration of the gut microbiota in mice. In recent years, studies have suggested that this artificial sweetener promotes myeloperoxidase reactivity in Crohn's disease-like ileitis. We aimed to investigate the effect of ACK on the intestinal mucosa and gut microbiota of normal mice. METHODS Acesulfame potassium was administered to C57BL/6J mice (8 weeks old) via free drinking. Intestinal damage was evaluated histologically, and messenger RNA (mRNA) levels of TNF-α, IFN-γ, IL1-β, MAdCAM-1, GLP1R, and GLP2R were determined with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Immunohistochemistry was performed to examine the expression of MAdCAM-1 in the small intestine. The composition of gut microbiota was assessed using high-throughput sequencing. We performed intravital microscopic observation to examine if ACK altered lymphocyte migration to the intestinal microvessels. RESULTS Acesulfame potassium increased the expression of proinflammatory cytokines, decreased the expression of GLP-1R and GLP-2R, and induced small intestinal injury with an increase in intestinal permeability, and ACK treatment induced microbial changes, but the transfer of feces alone from ACK mice did not reproduce intestinal damage in recipient mice. ACK treatment significantly increased the migration of lymphocytes to intestinal microvessels. CONCLUSION Acesulfame potassium induces dysbiosis and intestinal injury with enhanced lymphocyte migration to intestinal mucosa. Massive use of non-caloric artificial sweeteners may not be as safe as we think.

BACKGROUND The brief-access taste aversion (BATA) model has been used as an alternative taste assessment tool to human taste panels and became an important element of pharmaceutical drug development, especially regarding pediatric patient's compliance. This model has been validated, demonstrating a concentration-dependent sensitivity to drug aversiveness, as well as the capacity to evaluate the taste-masking effects of cyclodextrins. In the BATA model, samples are presented randomly to rodents in numerous sipper tubes and a lickometer is used for the electronic record of licks in a sophisticated approach. OBJECTIVES The aim of this study was to test possible drug taste-masking strategies. Additionally, we have used an alternative approach to measure the animal lick number in the presence of different compounds, non-simultaneously. RESULTS In the present work we show for the first time the licking profile of different compounds during the time course of the experiment, with each animal being exposed to only one bottle of testing product. To validate the experiments, quinine hydrochloride dihydrate (QHD) was used as a bitter reference compound. CONCLUSION The results obtained using this simple approach showed that aversiveness is dependent on the assay duration, and that it is possible to predict the aversiveness just by measuring the mass of the tested substance consumption. Moreover, some taste-masking strategies, such as those used in pediatric formulations and corresponding to the addition of sweeteners or flavors, cannot be predicted from rodents BATA model.

Effects of isocaloric (sweetness differences but constant calories) preloads and isosweet (caloric differences but constant sweetness) preloads, as well as preloads that were neither isosweet nor isocaloric (sweetness and caloric differences) on subsequent ad libitum meal and total (preload + ad libitum) energy intakes were investigated. Thirty-five crossover studies were eligible for inclusion, representing 116 comparisons (41, isocaloric; 41, isosweet; and 34, neither isosweet nor isocaloric). References of existing reviews and literature from 4 databases were searched. The calculated raw mean differences in ad libitum and total energy intakes were pooled in meta-analyses using a random-effects model and the inverse of the variance as the weighting factor. Energy intakes at an ad libitum meal were significantly lower for low-/no-calorie sweetener (LNCS)–sweetened compared with unsweetened preloads in the isocaloric comparison (−55.5 kcal; 95% CI: −82.9, −28.0 kcal; P

Food additives refer to all kinds of trace substances used in food or food processing to preserve flavor or enhance food taste, appearance, or other qualities. At present, artificial synthetic food additives have gradually replaced the natural food additives and many problems related to food additives, involving the abuse of food additives, excessive additives or even toxic additives. Obviously, food additives can bring people great sensory enjoyment and commercial convenience, but they may also cause potential risks to human health. So, it is of high significance to conduct quantitative analysis on the content of food additives. According to their functions and the regulatory requirements of food additives, this review starts from the classification and structures of various food additives involving colorants, preservatives, antioxidants, sweeteners, emulsifiers, stabilizers, thickeners, gelling agents. It then summarizes and discusses analytical methods for quantification of food additives including modern immunoassays and other biotechnological methods. The proposed review aspires to fill in the knowledge gap of food additives between academia and industry by covering all kinds of analytical methods for quantifying food additives.

Background The activation of insulin pathways is hypothesized to promote tumor growth and worsen breast cancer survival. Sugar-sweetened beverages (SSBs) can lead to a higher risk of insulin resistance and may affect survival. The authors prospectively evaluated the relation of postdiagnostic SSB and artificially sweetened beverage (ASB) consumption with mortality among women with breast cancer. Methods In total, 8863 women with stage I through III breast cancer were identified during follow-up of the Nurses' Health Study (NHS; 1980-2010) and Nurses' Health Study II (NHSII; 1991-2011). Women completed a validated food frequency questionnaire every 4 years after diagnosis and were followed until death or the end of follow-up (2014 for the NHS and 2015 for the NHSII). Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer-specific and all-cause mortality after adjusting for measures of adiposity and other potential predictors of cancer survival. Results With a median follow-up of 11.5 years, 2482 deaths were prospectively documented, including 1050 deaths from breast cancer. Compared with women who had no consumption, women who had SSB consumption after diagnosis had higher breast cancer-specific mortality (>1 to 3 servings per week: HR, 1.31 [95% CI, 1.09-1.58]; >3 servings per week: HR, 1.35 [95% CI, 1.12-1.62]; Ptrend = .001) and all-cause mortality (>1 to 3 servings per week: HR, 1.21 [95% CI, 1.07-1.37]; >3 servings per week: HR, 1.28 [95% CI, 1.13-1.45]; Ptrend = .0001). In contrast, ASB consumption was not associated with higher breast cancer-specific or all-cause mortality. Furthermore, replacing 1 serving per day of SSB consumption with 1 serving per day of ASB consumption was not associated with a lower risk of mortality. Conclusions Higher postdiagnostic SSB consumption among breast cancer survivors was associated with higher breast cancer-specific mortality and death from all causes.

Type 2 diabetes mellitus (T2DM) leads to monocyte dysfunction associated with atherogenesis and defective arteriogenesis. Transforming growth factor (TGF)‐β1, placenta growth factor (PlGF)‐1 and vascular endothelial growth factor (VEGF)A play important roles in atherogenesis and arteriogenesis. VEGF‐receptor (VEGFR)‐mediated monocyte migration is inhibited in T2DM (VEGFA resistance), while TGF‐β1‐induced monocyte migration is fully functional. Therefore, we hypothesize that TGF‐β antagonises the VEGFA responses in human monocytes. We demonstrate that monocytes from T2DM patients have an increased migratory response towards low concentrations of TGF‐β1, while PlGF‐1/VEGFA responses are mitigated. Mechanistically, this is due to increased expression of type II TGF‐β receptor in monocytes under high‐glucose conditions and increased expression of soluble (s)VEGFR1, which is known to interfere with VEGFA signalling. VEGFA resistance in monocytes from T2DM patients can be rescued by either experimental down‐regulation of TGF‐β receptor expression in vitro or by functional blocking of TGF‐β signalling using either a TGF‐β receptor kinase inhibitor or a TGF‐β neutralizing antibody. Our data demonstrate that both T2DM and high‐glucose potentiate the TGF‐β pathway. TGF‐β signalling impairs VEGFR‐mediated responses in T2DM monocytes and in this way contributes to mononuclear cell dysfunction, provide novel insights into T2DM vascular dysfunction.

Abstract Steviol glycosides (SvGls) are plant secondary metabolites belonging to a class of chemical compounds known as diterpenes. SvGls have been discovered only in a few plant species, including in the leaves of Stevia rebaudiana Bertoni. Over the last few decades, SvGls have been extensively researched for their extraordinary sweetness. As a result, the nutritional and pharmacological benefits of these secondary metabolites have grown increasingly apparent. In the near future, SvGls may become a basic, low-calorie, and potent sweetener in the growing natural foods market, and a natural anti-diabetic remedy, a highly competitive alternative to commercially available synthetic drugs. Commercial cultivation of stevia plants and the technologies of SvGls extraction and purification from plant material have already been introduced in many countries. However, new conventional and biotechnological solutions are still being sought to increase the level of SvGls in plants. Since many aspects related to the biochemistry and metabolism of SvGls in vivo, as well as their relationship to the overall physiology of S. rebaudiana are not yet understood, there is also a great need for in-depth scientific research on this topic. Such research may have positive impact on optimization of the profile and SvGls concentration in plants and thus lead to obtaining desired yield. This research summarizes the latest approaches and developments in SvGls production. Key points • Steviol glycosides (SvGls) are found in nature in S. rebaudiana plants. • They exhibit nutraceutical properties. • This review provides an insight on different approaches to produce SvGls. • The areas of research that still need to be explored have been identified.

Metabolic syndrome is a multifactorial disorder originating from central obesity through a high caloric intake and a sedentary lifestyle. Metabolic syndrome increases the risk of type 2 diabetes (T2D) disease, converting it to one of the costliest chronic diseases, which reduces life quality. A strategy proposed by the food industry to reduce this problem is the generation of low-caloric products using sweeteners, which are compounds that can substitute sucrose, given their sweet taste. For many years, it was assumed that sweeteners did not have a relevant interaction in metabolism. However, recent studies have demonstrated that sweeteners interact either with metabolism or with gut microbiota, in which sweet-taste receptors play an essential role. This review presents an overview of the industrial application of most commonly consumed sweeteners. In addition, the interaction of sweeteners within the body, including their absorption, distribution, metabolism, gut microbiota metabolism, and excretion is also reviewed. Furthermore, the complex relationship between metabolic syndrome and sweeteners is also discussed, presenting results from in vivo and clinical trials. Findings from this review indicate that, in order to formulate sugar-free or noncaloric food products for the metabolic syndrome market, several factors need to be considered, including the dose, proportions, human metabolism, and interaction of sweeteners with gut microbiota and sweet-taste receptors. More clinical studies, including the metabolic syndrome, are needed to better understand the interaction of sweeteners with the human body, as well as their possible effect on the generation of dysbiosis.

Background Conclusions remain controversial between the consumption of sugar and artificially sweetened beverages (SSBs and ASBs) and mortality. Methods We systematically searched the PubMed, Embase, Cochrane Library and Web of Science databases from their inception date to 1st January 2020, prospective cohort studies researching the mortality risk and SSBs or ASBs consumption were included. Random effects meta-analyses and dose–response analyses were performed to measure the association. Subgroup analyses and sensitivity analyses were further performed to explore the source of heterogeneity. Publication bias was assessed by Funnel plots and Egger’s regression test. Results Across all 15 cohorts, 1211 470 participants were included. High SSB consumption was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.06–1.19, P Conclusions High consumption of both ASBs and SSBs showed significant associations with a higher risk of CVD mortality and all-cause mortality. This information may provide ideas for decreasing the global burden of diseases by reducing sweetened beverage intake.

Objective:There remain inconclusive findings from previous observational epidemiological studies on whether consumption of artificially sweetened soft drinks (ASSD) increases the risk of gastrointestinal (GI) cancer. We investigated the associations between the consumption of ASSD and the risk of GI cancer using a meta-analysis.Design:Systematic review and meta-analysis.Setting:PubMed and EMBASE were searched using keywords until May 2020 to identify observational epidemiological studies on the association between the consumption of ASSD and the risk of GI cancer.Subjects:Twenty-one case–control studies and seventeen cohort studies with 12 397 cancer cases and 2 474 452 controls.Results:In the random-effects meta-analysis of all the studies, consumption of ASSD was not significantly associated with the risk of overall GI cancer (OR/relative risk (RR), 1·02; 95 % CI, 0·92, 1·14). There was no significant association between the consumption of ASSD and the risk of overall GI cancer in the subgroup meta-analyses by study design (case–control studies: OR, 0·95; 95 % CI, 0·82, 1·11; cohort studies: RR, 1·14; 95 % CI, 0·97, 1·33). In the subgroup meta-analysis by type of cancer, consumption of ASSD was significantly associated with the increased risk of liver cancer (OR/RR, 1·28; 95 % CI, 1·03, 1·58).Conclusions:The current meta-analysis of observational epidemiological studies suggests that overall, there is no significant association between the consumption of ASSD and the risk of GI cancer.

Sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) intakes have been reported to be associated with mortality; however, conclusions have been inconsistent. This review synthesized the evidence on the associations of SSB and ASB intakes with mortality from all causes, cardiovascular disease (CVD), and cancer among all populations (including general, diseased, or occupational populations, etc.). PubMed, EMBASE, Web of Science, Cochrane Library, ProQuest, ClinicalTrials.gov, and the International Clinical Trials Registry Platform were searched up to March 2020. Fifteen studies including 17 cohorts were included in meta-analyses. Each serving (12 fluid ounces or 355 mL) increase in daily SSB consumption was associated with higher risks of all-cause (HR: 1.08; 95% CI: 1.04, 1.12; 11 cohorts with 965,851 participants) and CVD (HR: 1.08; 95% CI: 1.04, 1.12; 13 cohorts with 898,005 participants) mortality. The associations of ASB intakes with all-cause and CVD mortality were J-shaped, and HRs (95% CI) across different doses (0, 1, 1.5, 2, and 2.5 servings/d) were 1.00, 1.01 (0.99, 1.03), 1.04 (1.02, 1.07), 1.08 (1.05, 1.11), and 1.13 (1.09, 1.18) for all-cause mortality and 1.00, 1.01 (0.96, 1.07), 1.07 (1.01, 1.13), 1.15 (1.08, 1.23), and 1.25 (1.14, 1.37) for CVD mortality. No significant association was found for cancer mortality. According to the NutriGrade scoring system, the quality of evidence on the associations of SSB intakes with all-cause and CVD mortality was high, and the quality of evidence on other associations was low to moderate. In summary, higher SSB and ASB intakes were associated with higher risks of all-cause mortality and CVD mortality. Given the limited evidence, future studies should further investigate the association between ASB intakes and cause-specific mortality.

The consumption of non-nutritive sweeteners has increased in the last decades. However, there are doubts about its consumption and its impact on body mass and metabolic alterations. For this reason, this study investigates the effects of the consumption of nutritive and non-nutritive sweeteners on body mass in different life stages of male and female Wistar rats: Childhood, adolescence, young adult, adulthood, and aged. For this purpose, 8 groups of male and female rats were used (10 per group/gender): sucrose 10%, glucose 14%, fructose 7%, acesulfame K 0.05%, aspartame:acesulfame mixture 1.55%, sucralose 0.017%, saccharin 0.033%, and a control group. Only in aged male rats (504 days) there were significant differences in body mass. In both genders, there were differences in food, drink, and energy intake along all life stage. It is concluded that non-nutritive sweeteners when consumed together with a balanced diet did not cause a greater body mass gain.

Stevia rebaudiana Bertoni is commonly called stevia and mostly found in the north east regions of South America. It is an herbaceous and shrubby plant belonging to the Asteraceae family. Stevia is considered as a natural sweetener and a commercially important plant worldwide. The leaves of S. rebaudiana contain steviol glycosides (SGs) which are highly potent and non-caloric sweeteners. The sweetening property of S. rebaudiana is contributed to the presence of these high potency, calorie free steviol glycosides. SGs are considerably suitable for replacing sucrose and other artificial sweetening agents which are used in different industries and pharmaceuticals. SGs amount in the plant mostly varies from 8% to 10%, and the enhancement of SGs is always in demand. These glycosides have the potential to become healthier alternatives to other table sugars for having desirable taste and zero calories. SGs are almost 300 times sweeter than sucrose. Being used as alternative sugar intensifier the commercial value of this plant in biopharmaceutical, food and beverages industries and in international market is increasing day by day. SGs have made stevia an important part of the medicinal world as well as the food and beverage industry, but the limited production of plant material is not fulfilling the higher global market demand. Therefore, researchers are working worldwide to increase the production of important SGs through the intercession of different biotechnological approaches in S. rebaudiana. This review aims to describe the emerging biotechnological strategies and approaches to understand, stimulate and enhance biosynthesis of secondary metabolites in stevia. Conventional and biotechnological methods for the production of steviol glycosides have been briefly reviewed and discussed.

Consumption of sugar or artificially-sweetened beverages (SASBs) has been linked to albuminuria, decline in kidney function, and risk of chronic kidney disease (CKD). However, the results are controversial. We therefore aim to evaluate the effects of sugar or artificially-sweetened beverage consumption on CKD risk. Original observational studies reporting relative risks (RRs) with 95% confidence intervals (CIs) for the association between sugar or artificially-sweetened beverage consumption and impaired renal function or CKD risk in adults were identified using a systematic search of PubMed and EMBASE from inception to 20 February, 2019. Random effects model was applied to derive summary RRs and 95% CIs. Linear and non-linear dose–response relationships were estimated using data from sugar or artificially-sweetened beverage consumption categories in each study. The summary RR of CKD for high versus low sugar-sweetened beverage consumption was 1.30 (95% CI 0.88–1.94) according to six included studies with a total of 25,455 participants, while the pooled RR of CKD for high versus low artificially sweetened beverage consumption was 1.40 (95% CI 0.65–3.02) according to three studies with a total of 19,995 participants. For dose–response analysis, a significant, increased risk of CKD was observed with the sugar or artificially-sweetened beverage consumption above seven servings per week (P

Objective:To examine the influence of prenatal artificial sweetener (AS) consumption on birth outcomes.Design:Systematic review and meta-analysis.Setting:Online databases (Medline, CINAHL, Embase, Cochrane Library, Scopus, Web of Science, FSTA – the food resource database, and ClinicalTrials.gov) were searched up to 9 April 2020. Studies of all designs (except case studies and reviews) were eligible, which contained information on the relevant population (pregnant women), intervention/exposure (any AS consumption), comparator (no AS consumption) and birth outcomes (preterm delivery, gestational age, birth weight).Results:From 677 citations, ten cohort studies and one randomised controlled trial (n 138 007 women) were included. ‘Low’ to ‘very low’ certainty evidence revealed that daily consumption of AS was associated with an increased risk of preterm delivery (three studies, n 129 009; risk ratio = 1·18, 95 % CI 1·09, 1·28, I2 = 9 %), a 24 g increase in birth weight (three studies, n 64 417; mean difference (MD): 23·74 g, 95 % CI 0·89, 45·58, I2 = 0 %) and a 0·11 week decrease in gestational age (three studies, n 64 417; MD: –0·11 weeks, 95 % CI –0·19, –0·03, I2 = 0 %).Conclusions:‘Low’ to ‘very low’ certainty evidence suggests daily AS consumption during pregnancy is associated with an increased risk of preterm delivery, increased birth weight and decreased gestational age. Additional ‘high’-quality research is urgently needed to further assess these relationships.PROSPERO registration number: CRD42019136728.

Background: In the last few years there has been emerging interest in substituting added sugars from juices with other sweeteners to make them healthier. But their long-term effects have been poorly evaluated. The aim of this study is to evaluate the effect of the addition of stevia, sucralose and sucrose (control) to maqui-citrus beverages on antioxidant and inflammatory status. Methods: a 3-arm parallel, randomized and triple blind clinical trial was performed in overweight subjects (n = 138), who consumed the test beverage (330 mL day-1) for 60 days. The following markers were determined: antioxidant status (ORAC, homocysteine, and oxidized LDL), safety parameters (ALP, AST, ALT, and total bilirubin), lipid profile (total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides) and inflammatory biomarkers (IL-6, TNF-a, and IL-10). Results: The homocysteine levels significantly increased after consumption of sucralose (27%, p = 0.001) and sucrose (40%, p = 0.006). A significant increase in the IL-10 concentration after consumption of the stevia sweetened beverage, and in ORAC values (21%) in subjects with lower basal antioxidant status were observed. The HDL and total cholesterol levels significantly increased after consumption of sucralose (p = 0.039) and sucrose (p = 0.001), respectively. No changes in triglycerides, LDL or oxidized LDL were observed. Conclusions: Oxidative stress and an inflammatory response were observed after consumption of these sweetened beverages, with the exception of stevia, which produced an anti-inflammatory response. The possible antioxidative effects of this polyphenol-rich beverage may only benefit those individuals with poorer antioxidant status. Many randomized controlled trials at normal levels of consumption using commonly consumed sweeteners are necessary to clarify their roles in health., The authors acknowledge the financial support from Comisión Interministerial de Ciencia y Tecnología (CICYT)

Sucralose is a widely consumed non-nutritive sweetener (NNS). Studies have shown that some NNS can favor weight gain by altering the intestinal microbiota, satiety hormone production, or aspects related to glucose homeostasis. In this study, we investigated the effects of ad libitum sucralose consumption in mice fed with normal or high-fat diet (HFD) for an extended period (16 weeks). Weight gain, final body composition, energy expenditure, intestinal and pancreatic hormone production, and endotoxemia during a voracity test, as well as liver and skeletal muscles were evaluated after 16 weeks. We observed that sucralose supplementation reduced weight gain in HFD-fed mice but did not change weight gain in mice fed with normal diet. The evaluation of HFD mice showed that sucralose supplementation resulted in improvements in glycemic homeostasis, hepatic steatosis, and increased energy expenditure. Our results suggest that sucralose consumption promotes different outcomes in relation to weight gain when combined with different diets, which may explain the controversial data in previous studies, and can be considered in future clinical research aimed at clarifying the impact of NNS consumption on human health.

The long-term associations between the consumption of sugar-sweetened beverages (SSBs) and low-calorie sweetened beverages (LCSBs) with cardiovascular diseases (CVDs) remains inconsistent. To synthesize the evidence, we conducted a meta-analysis of prospective cohort studies published up to 1 December, 2019 on the associations between SSB and LCSB intake and the risk of CVD incidence and mortality. Out of 5301 articles retrieved from our literature search, 11 articles evaluating the consumption of SSBs (16,915 incident CVD cases, 18,042 CVD deaths) and 8 articles evaluating the consumption of LCSBs (18,077 incident CVD cases, 14,114 CVD deaths) were included in the meta-analysis. A 1 serving/d increment of SSBs was associated with an 8% (RR: 1.08; 95% CI: 1.02, 1.14, I2 = 43.0%) and 8% (RR: 1.08; 95% CI: 1.04, 1.13, I2 = 40.6%) higher risk of CVD incidence and CVD mortality, respectively. A 1 serving/d increment of LCSBs was associated with a 7% (RR: 1.07; 95% CI: 1.05, 1.10, I2 = 0.0%) higher risk of CVD incidence. The association between LCSBs and CVD mortality appeared to be nonlinear (P = 0.003 for nonlinearity) with significant associations observed at high intake levels (>2 servings/d). Under an assumption of causality, the consumption of SSBs may be linked to 9.3% (95% CI: 6.6%, 11.9%) of predicted CVD incidence in the USA from 2015 to 2025, among men and nonpregnant women, who were aged 40–79 y in 2015–2016. The habitual consumption of SSBs was associated with a higher risk of CVD morbidity and mortality in a dose-response manner. LCSBs were also associated with a higher risk of these outcomes, however, the interpretation of these findings may be complicated by reverse causation and residual confounding., Habitual consumption of SSBs/LCSBs were associated with higher risk of CVD morbidity and mortality. However, potential reverse causation and residual confounding complicate interpretation of findings related to LCSBs.

Sucralose is one of the most widely used artificial sweeteners, free of nutrients and calories. Its approval and uses correlate with many of the worldwide epidemiological changes in inflammatory bowel disease (IBD). Multiple animal studies by us and others showed that sucralose exacerbated ileitis in SAMP1/YitFc mice and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. In this study, we further investigated the effect of sucralose on dextran sulfate sodium (DSS)-induced colitis in mice and the associated mechanisms. Male C57BL/6 mice received 1.5 mg ml-1 sucralose in drinking water for 6 weeks. Then, 2.5% DSS was added to drinking water for 7 days to induce ulcerative colitis (UC). The results showed that, compared with the DSS group, administration of sucralose exacerbated the severity of colitis as indicated by the further decrease in body weight, increase in disease activity index (DAI) and the expression of pro-inflammatory cytokines, as well as the activation of the TLR5-MyD88-NF-κB signaling pathway, and the disturbances of intestinal barrier function, along with changes in the intestinal microbiota. Our findings indicate that sucralose may increase the susceptibility to DSS-induced colitis through causing dysbiosis of intestinal microbiota and damage to the intestinal barrier.

ObjectiveTo determine the effect of prophylactic dextrose gel for prevention of neonatal hypoglycaemia on neurodevelopment and executive function at 2 years’ corrected age.DesignProspective follow-up of a randomised trial.SettingNew Zealand.PatientsParticipants from the pre-hypoglycaemia Prevention with Oral Dextrose (pre-hPOD) trial randomised to one of four dose regimes of buccal 40% dextrose gel or equivolume placebo.Main outcome measuresCoprimary outcomes were neurosensory impairment and executive function. Secondary outcomes were components of the primary outcomes, neurology, anthropometry and health measures.ResultsWe assessed 360 of 401 eligible children (90%) at 2 years’ corrected age. There were no differences between dextrose gel dose groups, single or multiple dose groups, or any dextrose and any placebo groups in the risk of neurosensory impairment or low executive function (any dextrose vs any placebo neurosensory impairment: relative risk (RR) 0.77, 95% CI 0.50 to 1.19, p=0.23; low executive function: RR 0.50, 95% CI 0.24 to 1.06, p=0.07). There were also no differences between groups in any secondary outcomes. There was no difference between children who did or did not develop neonatal hypoglycaemia in the risk of neurosensory impairment (RR 1.05, 95% CI 0.68 to 1.64, p=0.81) or low executive function (RR 0.73, 95% CI 0.34 to 1.59, p=0.43).ConclusionProphylactic dextrose gel did not alter neurodevelopment or executive function and had no adverse effects to 2 years’ corrected age, but this study was underpowered to detect potentially clinically important effects on neurosensory outcomes.

Aims/Introduction Gut dysbiosis is generally associated with type 2 diabetes mellitus. However, the effect of habitual dietary intake on gut dysbiosis in Japanese patients with type 2 diabetes mellitus has not yet been explicated. This study investigated whether alteration of the gut microbiota was influenced by dietary intake of sucrose in Japanese patients with type 2 diabetes mellitus. Materials and Methods In this cross‐sectional study, 97 patients with type 2 diabetes mellitus and 97 healthy individuals were matched by age and sex, and then, fecal samples were obtained. Next‐generation sequencing of the 16S ribosomal ribonucleic acid gene was carried out, and functional profiles for the gut microbiota were analyzed. We selected the top 30 gut microbial genera and top 20 functional profiles for the gut microbiota specified by the weighted average difference method. The association between gut microbial genera or functional profiles and habitual dietary intake was investigated by Spearman’s rank correlation coefficient, and then, clustering analysis was carried out to clarify the impact of habitual dietary intake. Results The Actinobacteria phylum was highly abundant in patients with type 2 diabetes mellitus, whereas the Bacteroidetes phylum was less abundant. Diabetic‐type gut microbes, specifically Bacteroides and Bifidobacterium, were altered by sucrose intake at the genus level. Furthermore, sucrose intake was associated with glycolysis/gluconeogenesis in the diabetic‐type functional profiles of the gut microbiota. Conclusions The gut microbiota and functional profiles for the gut microbiota in patients with type 2 diabetes mellitus were significantly different from those in healthy individuals. Furthermore, we showed that sucrose intake was closely associated with these differences., Gut dysbiosis and change of functional profiles of the gut microbiota exist in Japanese patients with type 2 diabetes mellitus. Diet habit, especially sucrose intake, has a close association with these changes.

This article examines, using an organ-systems based approach, rapid diagnosis, resuscitation, and critical care management of the crashing poisoned patient in the emergency department. The topics discussed in this article include seizures and status epilepticus, respiratory failure, cardiovascular collapse and mechanical circulatory support, antidotes and drug-specific therapies, acute liver failure, and extracorporeal toxin removal.

Objective:The associations between sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) consumption and the risk of metabolic syndrome (MetS) remain controversial. A quantitative assessment of dose–response associations has not been reported. This study aims to assess the associations between the risk of MetS and SSB, ASB, and total sweetened beverage (TSB, the combination of SSB and ASB) consumption by reviewing population-based epidemiological studies.Design:Meta-analysis.Setting:We searched PubMed, Embase and Web of Science databases prior to 4 November 2019, for relevant studies investigating the SSB–MetS and ASB–MetS associations. A random effects model was used to estimate pooled relative risks (RR) and 95 % CI. Dose–response association was assessed using a restricted cubic splines model.Participants:We identified seventeen articles (twenty-four studies, including 93 095 participants and 20 749 MetS patients).Results:The pooled RR for the risk of MetS were 1·51 (95 % CI 1·34, 1·69), 1·56 (1·32, 1·83) and 1·44 (1·19, 1·75) in high consumption group of TSB, SSB and ASB, respectively; and 1·20 (1·13, 1·28), 1·19 (1·11, 1·28) and 1·31 (1·05, 1·65) per 250 ml/d increase in TSB, SSB and ASB consumption, respectively. Additionally, we found evidence of non-linear, TSB–MetS and SSB–MetS dose–response associations and a linear ASB–MetS dose–response association.Conclusions:TSB, SSB and ASB consumption was associated with the risk of MetS. The present findings provide evidence that supports reducing intake of these beverages to lower the TSB-, SSB- and ASB-related risk of MetS.

Sweet taste perception is a key factor in the establishment of the food pattern with nonstatic thresholds. Indeed, taste sensitivity can be influenced by physiological factors (age and sex), pathologies (obesity and type 2 diabetes mellitus), and acquired habits (tobacco and alcohol consumption). In order to elucidate how these variables influence the sucrose detection threshold (DT) and recognition threshold (RT), a systematic review and meta-analysis of the relevant literature were performed. After a comprehensive search in the PubMed and Scopus databases, a total of 48 studies were qualitatively considered, and 44 were meta-analyzed. The factors of aging (standard mean difference [SMD]: -0.46; 95% confidence interval (CI), -0.74 to -0.19; I2 : 73%; Tau2 : 0.18) and type 2 diabetes mellitus (SMD: 0.30; 95% CI, 0.06 to 0.55; I2 : 0%; Tau2 : 0.00) were found to significantly increase the sucrose RT, whereas the DT only increased in subjects with a higher body mass index (SMD: 0.58; 95% CI, 0.35 to 0.82; I2 : 0%; Tau2 : 0.00). No effects of sex and tobacco smoking were found, and associations with alcohol consumption could not be assessed, as it was included as a variable in only one study. Feasible mechanisms underlying changes in sucrose thresholds include the modulation of hormones involved in energy and body weight homeostasis, taste bud abundance, taste brain signaling, and the gut-brain axis. The present work provides insights into the variables that should be considered when assessing sweet taste sensitivity, discusses the mechanisms underlying differences in sweet taste, and highlights the need for further research in the field of personalized nutrition.

Objective: This study focused on describing local trends in sugar‐sweetened beverage (SSB) consumption, including variations between subgroups, to inform equitable health policy to curb soft drink consumption. Methods: Weighted data were obtained from the South Australian Monitoring and Surveillance System, a state‐based population health survey that monitors trends in health risk factors and chronic disease via computer‐assisted telephone interviewing. From 2008 onwards, participants provided an estimate of the average amount of soft drink they consumed per day. Results: From 2008–2017, there were significant decreases in the proportion of adults who consumed any SSBs, but the mean consumption per consumer increased. High‐risk dietary and lifestyle behaviours are the strongest predictors for consumption of soft drink, but there is also a significant association with socioeconomic status. Conclusions: Population trends mask increasing inequity. There is a societal trend away from the consumption of SSBs across all subgroups, but at‐risk groups who engage in clusters of unhealthy behaviours remain high consumers. Implications for public health: The identification of at‐risk populations allows research to focus more precisely on the structural barriers, beliefs, attitudes and facilitators of ongoing consumption of SSB in order to inform future health promotion efforts.

Background: It has been suggested that low-energy sweeteners (LES) may be associated with an increased risk of metabolic diseases, possibly due to stimulation of glucose-responsive mechanisms.Objective: We conducted a systematic review and meta-analysis of human intervention studies examining the acute effect of LES intake on postprandial glucose (PPG) and postprandial insulin (PPI) responses, in order to comprehensively and objectively quantify these relations.Methods: We systematically searched the Medline, OVID FSTA, and SCOPUS databases until January 2020. Randomized controlled trials comparing acute postprandial effects on PPG and/or PPI after exposure to LES, either alone, with a meal, or with other nutrient-containing preloads to the same intervention without LES were eligible for inclusion. PPG and PPI responses were calculated as mean incremental area under the curve divided by time. Meta-analyses were performed using random effects models with inverse variance weighing.Results: Twenty-six papers (34 PPG trials and 29 PPI trials) were included. There were no reports of statistically significant differences in the effects of LES on PPG and PPI responses compared with control interventions. Pooled effects of LES intake on the mean change difference in PPG and PPI were -0.02 mmol/L (95% CI: -0.09, 0.05) and -2.39 pmol/L (95% CI: -11.83, 7.05), respectively. The results did not appreciably differ by the type or dose of LES consumed, cointervention type, or fasting glucose and insulin levels. Among patients with type 2 diabetes, the mean change difference indicated a smaller PPG response after exposure to LES compared with the control (-0.3 mmol/L; 95% CI: -0.53, -0.07).Conclusions: Ingestion of LES, administered alone or in combination with a nutrient-containing preload, has no acute effects on the mean change in postprandial glycemic or insulinemic responses compared with a control intervention. Apart from a small beneficial effect on PPG (-0.3 mmol/L) in studies enrolling patients with type 2 diabetes, the effects did not differ by type or dose of LES, or fasting glucose or insulin levels. This review and meta-analysis was registered at PROSPERO as CRD42018099608.

BACKGROUND: Male Kunming mice were divided into the normal diet group (control group) and the high-fat diet group (HF group, 185 g·kg-1 protein, 600 g·kg-1 fat and 205 g·kg-1 carbohydrate). After eight weeks' feeding, the behavioral and biochemical indicators in serum were determined. The double bottle preference experiment was used to study the preference of mice for five sweeteners. The contents of monoamine neurotransmitters and genes expression related to dopamine (DA) and opioid receptor were also determined. RESULTS: The body weight of the mice in HF group increased significantly (p < 0.05) after 36 days compared with the control group. While the feed intake of HF group increased sharply in the first 12 days, and then it became basically unchanged. The preference of the HF group for all the five sweeteners was very significantly lower (p < 0.01) than that of the control group. The depression-related behavior was observed in the HF group mice. The contents of TG, TC and LDLC in the HF group were extremely higher (p < 0.01) than that of the control group. The genes expression related to DA and opioid receptor in the HF group was significantly lower than that of the control group, except for the preproenkephalin (PENK). CONCLUSIONS: In summary, this study suggested that a long-term high-fat diet could result in the decrease of the preference for sweeteners on mice due to the long-term consumption of high-fat diet could result in a state of reward hypofunction on mice. This article is protected by copyright. All rights reserved.

Many older adults suffer from difficulty swallowing thin beverages like water or coffee. To improve swallowing safety, beverages are typically thickened. This creates a new problem: the thickened beverages can be disgusting. New research suggests chemesthesis, particularly spiciness, carbonation, or intense sourness, could improve swallowing without the need for thickeners. Yet, whether such beverages would be liked by older adults is unknown. We thus conducted this experiment to establish older adults' sensory perception and liking/disliking of commercially available chemesthetic beverages. We recruited participants to rate sweetness, sourness, fizziness, stinging, and liking/disliking of unsweetened carbonated waters (1 plain, 5 flavored), sour orange juice, spicy ginger beer, and colas (sugar or aspartame-sweetened). Initial tests (N = 30 older adults) indicated sour orange juice, spicy ginger beer, and two of the flavored waters were not well-liked, so other beverages were selected for a second test (N = 94, 30 younger adults, 64 older adults). Sweetened, carbonated colas were the best-liked of the beverages. The unsweetened, flavored carbonated waters were in general not liked. Regarding comparisons of sensory ratings between older and younger adults, only sweetness differed between age groups. In particular, intensity ratings for the chemesthetic aspects of the beverages (stinging/burning/spiciness, fizziness) and the sour taste did not differ by age. As the chemesthetic properties are the most likely reason the beverages could aid in swallowing safety, observing no suppression of these sensations in older adults is encouraging for the potential of these products as a treatment option.

Background The orbitofrontal cortex (OFC) encodes internal representations of outcomes and subjective value to facilitate flexible reward seeking. OFC activation is associated with drug seeking in both human subjects and animal models. OFC plays a role in alcohol use, but studies in animal models have produced conflicting results with some showing decreased seeking after OFC inactivation but others showing increased seeking or no changes. In part, this may be due to the different measures of alcohol seeking used (e.g., homecage drinking vs. operant seeking). Methods We characterized the impact of transient inactivation of OFC (primarily lateral and, to a lesser extent, ventral subregions) using inhibitory hM4Di designer receptors exclusively activated by designer drugs (DREADDs). OFC neurons were transiently inhibited during 10% and 20% alcohol (ethanol, EtOH) and sucrose homecage consumption, fixed ratio (FR1) operant self-administration, and cue-induced reinstatement of either 10% EtOH or sucrose in male and female rats. Results OFC inactivation did not affect sucrose or EtOH consumption in the homecage, nor did it influence seeking or consumption under FR1 operant conditions. In contrast, OFC inactivation suppressed cued-induced reinstatement for both EtOH and sucrose in both male and female rats. Conclusions Our results are aligned with previous work indicating a selective suppressive effect of OFC inactivation on reinstatement for alcohol and other drugs of abuse. They extend these findings to demonstrate no effect on homecage consumption or FR1 seeking as well as showing an impact of sucrose reinstatement. These data indicate that OFC plays a uniquely important role when reward seeking is driven by associations between external stimuli and internal representations of reward value, both for natural and drug rewards. They further implicate the OFC as a key structure driving relapse-associated seeking and potentially contributing to alcohol use disorder and other diseases of compulsive reward seeking.

Neonatal hypoglycemia is a common diagnosis for which management strategies vary. Our goal was to implement hypoglycemia algorithms (HGA) to streamline management of neonatal hypoglycemia within our hospital system and improve outcomes related to promoting the mother-infant dyad and decreasing hospital costs.A retrospective cohort study analyzed data on 4,666 asymptomatic infants at risk for hypoglycemia and born at two, large, community hospitals between 2010 and 2016. The first algorithm (HGA1) was created in 2012 and subsequently updated (HGA2) in 2014 to include the use of dextrose gel. Infants were separated into three groups by epoch: pre-HGA (2010-2011), HGA1 (2012-2013), and HGA2 (2014-2016). Outcomes between groups were then analyzed. Cost savings were calculated using linear regression.Compared with the pre-HGA group, the HGA1 group had decreased intravenous dextrose use (3.9 vs. 2.5%,By implementing HGA1 and providing resources to unify care for asymptomatic infants at risk for hypoglycemia, short-term outcomes in our hospital system improved. By updating HGA2 to include the use of dextrose gel, the advantages gained by HGA1 were maintained and further enhanced. Overall cost of care was reduced.

Although consumption of sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) has increasingly been linked with obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality, evidence remains conflicted and dose–response meta-analyses of the associations are lacking. We conducted an updated meta-analysis to synthesize the knowledge about their associations and to explore their dose–response relations. We comprehensively searched PubMed, EMBASE, Web of Science, and Open Grey up to September 2019 for prospective cohort studies investigating the associations in adults. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated for the dose–response association. Restricted cubic splines were used to evaluate linear/non-linear relations. We included 39 articles in the meta-analysis. For each 250-mL/d increase in SSB and ASB intake, the risk increased by 12% (RR = 1.12, 95% CI 1.05–1.19, I2 = 67.7%) and 21% (RR = 1.21, 95% CI 1.09–1.35, I2 = 47.2%) for obesity, 19% (RR = 1.19, 95% CI 1.13–1.25, I2 = 82.4%) and 15% (RR = 1.15, 95% CI 1.05–1.26, I2 = 92.6%) for T2DM, 10% (RR = 1.10, 95% CI 1.06–1.14, I2 = 58.4%) and 8% (RR = 1.08, 95% CI 1.06–1.10, I2 = 24.3%) for hypertension, and 4% (RR = 1.04, 95% CI 1.01–1.07, I2 = 58.0%) and 6% (RR = 1.06, 95% CI 1.02–1.10, I2 = 80.8%) for all-cause mortality. For SSBs, restricted cubic splines showed linear associations with risk of obesity (Pnon-linearity = 0.359), T2DM (Pnon-linearity = 0.706), hypertension (Pnon-linearity = 0.510) and all-cause mortality (Pnon-linearity = 0.259). For ASBs, we found linear associations with risk of obesity (Pnon-linearity = 0.299) and T2DM (Pnon-linearity = 0.847) and non-linear associations with hypertension (Pnon-linearity = 0.019) and all-cause mortality (Pnon-linearity = 0.048). Increased consumption of SSBs and ASBs is associated with risk of obesity, T2DM, hypertension, and all-cause mortality. However, the results should be interpreted cautiously because the present analyses were based on only cohort but not intervention studies.

Naturally occurring tumor in animals receiving high minerals from deep oceans (DOM: hardness 600 mg/L) from 6 months of age until natural death was firstly assessed in 200 Sprague Dawley rats, randomized into four groups: Control (C), DOM (D), Fructose (F), and Fructose + DOM (FD). Fructose drink contained 11% fructose. Tumor incidence (necropsy at death) in the D group was ~40% lower than that in the C group (P, Tumor incidence increases with advancing aging. Lifelong supplementation of deep ocean minerals significantly suppresses age‐associated tumorigenesis. This tumor‐suppressive action is associated with preventing weight gain and increasing spontaneous physical activity during the first two‐thirds period of life.

This study aimed to determine the effect of pure forms of sucralose and aspartame, in doses reflective of common consumption, on glucose metabolism. Healthy participants consumed pure forms of a non-nutritive sweetener (NNS) that were mixed with water and standardized to doses of 14% (0.425 g) of the acceptable daily intake (ADI) for aspartame and 20% (0.136 g) of the ADI for sucralose every day for 2 weeks. Blood samples were collected and analyzed for glucose, insulin, active glucagon-like peptide-1 (GLP-1), and leptin. Seventeen participants (10 females and 7 males; age, 24 ± 6.8 years; body mass index, 22.9 ± 2.5 kg/m2) participated in the study. The total area under the curve values of glucose, insulin, active GLP-1 and leptin were similar for the aspartame and sucralose treatment groups compared with the baseline values in healthy participants. There was no change in insulin sensitivity after NNS treatment compared with the baseline values. These findings suggest that daily repeated consumption of pure sucralose or aspartame for 2 weeks had no effect on glucose metabolism among normoglycaemic adults. However, these results need to be tested in studies with longer durations. Novelty Daily consumption of pure aspartame or sucralose for 2 weeks had no effect on glucose metabolism. Daily consumption of pure aspartame or sucralose for 2 weeks had no effect on insulin sensitivity among healthy adults.

Widely differing views exist among experts, policy makers, and the general public with regard to the potential risks and benefits of reduced- or low-energy sweeteners (LES) in the diet. These views are informed and influenced by different types of research in LES, with differing hypotheses, designs, interpretation, and communication. Given the high level of interest in LES, and the public health relevance of the research evidence base, it is important that all aspects of the research process are framed and reported in an appropriate and balanced manner. In this Perspective, we identify and give examples of a number of issues relating to research and reviews on LES, which may contribute toward apparent inconsistencies in the content and understanding of the totality of evidence. We conclude with a set of recommendations for authors, reviewers and journal editors, as general guidance to improve and better standardize the quality of LES research design, interpretation, and reporting. These focus on clarity of underlying hypotheses, characterization of exposures, and the placement and weighting of new research within the wider context of related prior work.

Diabetes is a globally prevalent chronic metabolic disease characterized by blood glucose levels higher than the normal levels. Sugar, a common constituent of diet, is also a major factor often responsible for elevating the glucose level in diabetic patients. However, diabetic patients are more prone to eat sweets amongst the human population. Therefore, we find a popular consumption of zero or low-calorie sweeteners, both natural and artificial. But, the uses of these sweeteners have proved to be controversial. Thus, the purpose of this review was to critically analyze and highlight the considerations needed for the development of sugar-free or low-calorie products for diabetic patients. For this purpose, various measures are taken such as avoiding sugary foods, using natural nectar, artificial sweeteners, etc. It cannot be ignored that many health hazards are associated with the overconsumption of artificial sweeteners only. These sweeteners are high-risk compounds and a properly balanced consideration needs to be given while making a diet plan for diabetic patients.

Dietary habits that include an excess of added sugars have been strongly associated with an increased risk of obesity, heart disease, diabetes, and tooth decay. With this association in view, modern food systems aim to replace added sugars with low calorie sweeteners, such as polyols. Polyols are generally not carcinogenic and do not trigger a glycemic response. Furthermore, owing to the absence of the carbonyl group, they are more stable compared to monosaccharides and do not participate in Maillard reactions. As such, since polyols are stable at high temperatures, and they do not brown or caramelize when heated. Therefore, polyols are widely used in the diets of hypocaloric and diabetic patients, as well as other specific cases where controlled caloric intake is required. In recent years, erythritol and mannitol have gained increased importance, especially in the food and pharmaceutical industries. In these areas, research efforts have been made to improve the productivity and yield of the two polyols, relying on biotechnological manufacturing methods. The present review highlights the recent advances in the biotechnological production of erythritol and mannitol and summarizes the benefits of using the two polyols in the food and pharmaceutical industries.

Aim The aim of the present study was to characterize the role of Smad3 signalling on high glucose‐induced podocyte injury. Methods Synchronized conditionally immortalized mouse podocyte cell line (MPC5) cells were treated with either D‐glucose alone or D‐glucose plus the Smad3 inhibitor SIS3. The distribution of F‐actin and transgelin in a high glucose‐induced model of podocyte injury were examined by immunofluorescence. Levels of transgelin and Smad3 signalling proteins in MPC5 cells were determined by Western blot. Results A disordered distribution of F‐actin, as well as co‐localization of F‐actin and transgelin, was observed in podocytes exposed to high glucose. Increased levels of transgelin were first observed 10 minutes after treatment with glucose, suggesting that this protein is sensitive to hyperglycaemic injury. Levels of phosphorylated Smad3 and cleaved caspase 3 increased significantly with glucose stimulation. Moreover, expression of the downstream protein c‐Myc, but not JAK1/STAT3, was induced in conditions of high glucose. The Smad3‐specific inhibitor SIS3 prevented the effects of high glucose on Smad3 phosphorylation, expression of transgelin and c‐Myc, caspase 3 cleavage and cytoskeletal organization. Expression of the tumour suppressor protein p15INK4B increased after podocyte injury but was unaffected by Smad3 inhibition, suggesting that Smad3 regulation of high glucose‐induced podocyte injury occurs through a p15INK4B‐independent mechanism. Conclusion Smad3 signalling plays a critical role in the modulation of hyperglycaemic injury. Targeted inhibition of the Smad3 pathway may offer a novel route for treatment of podocyte damage, especially in cases of diabetic nephropathy., SUMMARY AT A GLANCE Podocyte damage is characteristic of diabetic kidney disease. This study showed that inhibition of Smad‐3 signalling using the specific inhibitor SIS3 in vitro, could alleviate podocyte abnormalities induced by high glucose including actin cytoskeletal rearrangement and actviation of cell death pathways.

The effect on cognitive test scores of generating differences in postprandial glycaemia using test foods or beverages has been inconsistent. Methodological issues may account for some of the variable results requiring further investigation using strong study designs into the relationship between glycaemia and cognitive functioning. The objective of this study was to determine the effects of postprandial glycaemia on cognitive function by examining cognition after consumption of foods that differ only by the rate of digestion of available carbohydrate in a population of young adults. In a double-blind, randomised, crossover trial, sixty-five participants received trifle sweetened either with a higher-glycaemic index (GI) sugar (sucrose; GI 65) or a lower-GI sugar (isomaltulose; GI 34). Cognitive tests were completed prior to trifle consumption, and 60 and 120 min after. There was no between-trifle difference at 60 min in performance on free word recall (0·0 (95 % CI –0·6, 0·5)), short delay word recall (0·0 (95 % CI –0·5, 0·5)), long delay word recall (0·0 (95 % CI –0·6, 0·6)), letter–number sequence recall (0·3 (95 % CI − 0·2, 0·7)) and visuo-spatial recall (–0·2 (95 % CI –0·6, 0·2)) tests. At 120 min, no difference was detected in any of these tests. The participants performed 7·7 (95 % CI 0·5,14·9) s faster in Reitan’s trail-making test B 60 min after the higher-GI trifle than the lower-GI trifle (P = 0·037). Our findings of a null effect on memory are generally consistent with other works in which blinding and robust control for confounding have been used.

The use of low and no-calorie sweeteners (LNCS) in food and beverages has become increasingly common in the development and reformulation of products to reduce energy derived from added sugars. Our aim was to identify the presence and consumption of LNCS through food and beverages according to consumption patterns in a representative sample (n = 256) of the Portuguese adult population. The study had a descriptive cross-sectional observational design and was based on the application of a Food Frequency Questionnaire. Overall, it was found that 4.1% of the foods and 16.7% of the beverages consumed by the Portuguese adult population contained LNCS. Food groups mostly contributing to LNCS consumption were non-alcoholic beverages such as soft drinks and juices (34.2%); milk and dairy products (16.5%); appetizers such as chips (8.6%); sugars and sweets such as chocolates, candies, or chewing gums (6.1%); meat and derivative products (2.2%); cereals and derivatives (1.2%) and canned fruits (1.2%). Main LNCS consumed were acesulfame-K, sucralose, and aspartame, single or combined, although their prevalence of use differs greatly among foods, beverages, or tabletop sweeteners. In conclusion, LNCS were found across a wide variety of products available in the Portuguese market and their prevalence of inclusion in the diet of the population evidences the need to develop more studies on the evolution of LNCS intake and its impact on the full dietary model and health. Consequently, these food additives should be included in food composition databases and, periodically, updated to reflect the recurrent reformulation strategies adopted by the food industry in its efforts to reduce the energy contribution of added sugars.

Adult and childhood obesity have reached pandemic level proportions. The idea that caloric excess and insufficient levels of physical activity leads to obesity is a commonly accepted answer for unwanted weight gain. This paradigm offers an inconclusive explanation as the world continually moves towards an unhealthier and heavier existence irrespective of energy balance. Endocrine disrupting chemicals (EDCs) are chemicals that resemble natural hormones and disrupt endocrine function by interfering with the body’s endogenous hormones. A subset of EDCs called obesogens have been found to cause metabolic disruptions such as increased fat storage, in vivo. Obesogens act on the metabolic system through multiple avenues and have been found to affect the homeostasis of a variety of systems such as the gut microbiome and adipose tissue functioning. Obesogenic compounds have been shown to cause metabolic disturbances later in life that can even pass into multiple future generations, post exposure. The rising rates of obesity and related metabolic disease are demanding increasing attention on chemical screening efforts and worldwide preventative strategies to keep the public and future generations safe. This review addresses the most current findings on known obesogens and their effects on the metabolic system, the mechanisms of action through which they act upon, and the screening efforts through which they were identified with. The interplay between obesogens, brown adipose tissue, and the gut microbiome are major topics that will be covered.

Reduced Glycemic Index (GI) of breakfast has been linked to improved cognitive performance in both children and adult populations across the morning. However, few studies have profiled the post-prandial glycemic response (PPGR) in younger children. The aim of this study was to assess PPGR to breakfast interventions differing in GI in healthy children aged 5–7 years. Eleven subjects completed an open-label, randomized, cross-over trial, receiving three equicaloric test beverages (260 kcal) consisting of 125 mL semi-skimmed milk and 50 g sugar (either glucose, sucrose, or isomaltulose). On a fourth occasion, the sucrose beverage was delivered as intermittent supply. PPGR was measured over 180 min using Continuous Glucose Monitoring (CGM). The incremental area under the curve (3h-iAUC) was highest for the glucose beverage, followed by intermittent sucrose (−21%, p = 0.288), sucrose (−27%, p = 0.139), and isomaltulose (−48%, p = 0.018). The isomaltulose beverage induced the smallest Cmax (7.8 mmol/L vs. >9.2 mmol/L for others) and the longest duration with moderate glucose level, between baseline value and 7.8 mmol/L (150 vs.

Background New Nutri-Grade labelling, aimed at reducing Singaporeans’ sugar consumption will be implemented for all pre-packaged non-alcoholic beverages (NABs) sold in retail outlets from end 2021 onwards. It is expected such labelling will have a major impact on sugar content of beverages, as well as the replacement of sugar with non-caloric alternatives. Methods This study used product label data obtained from in-store surveys to investigate sugar and sweetener composition of NABs present on the Singapore market. Using this data we calculated products prospective Nutri-Grade classification in order to compare the current market composition with relation to sugar and/or sweetener use. Results Over half of the NABs on market were sweetened with sugar (59%) and were associated with less healthy Nutri-Grades of ‘C’ and ‘D’. The use of natural sweeteners; Stevia and Monk fruit, remains low (6%). Conclusion With continuous efforts by the government in promoting public health nutrition, it is expected that there will be a greater usage of sugar substitutes among NABs in response to the upcoming implementation of Nutri-Grade and ever-fluctuating consumers’ demands. The data collected in this study provide a point estimate (July–September 2020) on market composition and use of both sugar and artificial sweeteners in beverages prior to integration of the mandatory labelling requirements.