Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance.

Non-nutritive sweeteners (NNS) are commonly integrated into human diet and presumed to be inert; however, animal studies suggest that they may impact the microbiome and downstream glycemic responses. We causally assessed NNS impacts in humans and their microbiomes in a randomized-controlled trial encompassing 120 healthy adults, administered saccharin, sucralose, aspartame, and stevia sachets for 2 weeks in doses lower than the acceptable daily intake, compared with controls receiving sachet-contained vehicle glucose or no supplement. As groups, each administered NNS distinctly altered stool and oral microbiome and plasma metabolome, whereas saccharin and sucralose significantly impaired glycemic responses. Importantly, gnotobiotic mice conventionalized with microbiomes from multiple top and bottom responders of each of the four NNS-supplemented groups featured glycemic responses largely reflecting those noted in respective human donors, which were preempted by distinct microbial signals, as exemplified by sucralose. Collectively, human NNS consumption may induce person-specific, microbiome-dependent glycemic alterations, necessitating future assessment of clinical implications.

The impact of non-caloric artificial sweetener aspartame on female reproductive system in mice model.

BACKGROUND: Artificial sweeteners, used as sugar substitutes have found their ways into almost all the food items due to the notion that they are non-caloric. Aspartame is used in numerous food products throughout the world. The primary users of aspartame include diabetics and calorie conscious people who intend to limit their calorie intake. METHODS: Female Swiss albino mice were divided into three groups (12 mice each) for the duration of 30 and 60 days consecutively. The treatment groups received 40 mg/kg b. w. aspartame orally. Hormone assays using ELISA and tissue histopathology have been performed along with the fertility assay to access the treatment outcomeon the fertility of treated mice in comparison to controls. RESULTS: Present study reports that female mice treated with aspartame for 30 and 60 days showed significant reduction in body weight, relative organ weight of (liver and kidney) and gonadosomatic index. These changes were more significantly recorded in 60 days treatment group. Aspartame treated animals for 30 and 60 days showed duration-dependent decrease gonandotropins (follicle stimulating hormone and luteinizing hormone), and steroids (estradiol and progesterone). Moreover, severe histopathological changes, reduction in number of growing follicles, degenerative changes in follicular structure, corona radiata and zonagranulosa were also observed. Besides, histomorphological changes were also observed in the uterine structure including atrophic uterine endometrial glands, contracted endometrial lining, disruption of the endometrial structure and the shapes of blood vessels were also altered. CONCLUSION: Non-nutritive artificial sweeteners including aspartame negatively impact the function of ovaries and feedback mechanism of reproductive hormones by affecting the hypothalamic-pituitary-gonadal axis. In light of present findings the aspartame negatively impacted the reproductive system of female mice. More studies are required to identify the molecular mechanism and the pathways involved.

The possible role of the seaweed Sargassum vulgare as a promising functional food ingredient minimizing aspartame-associated toxicity in rats.

Thirty-two male Wistar albino rats were chosen to test the possible protective role of antioxidants of the edible seaweed Sargassum vulgare as a functional food additive to alleviate oxidative stress and toxicity associated with consumption of the artificial sweetener 'aspartame (ASP)'. Biochemical and spleen histopathological analyses of the orally ASP-administrated rats, at a dose of 500 mg/kg for one week daily, showed different apoptotic and inflammatory patterns. Rats treated with ASP and then supplemented orally with the S. vulgare-MeOH extract, at a dose of 150 mg/kg for three consecutive weeks daily, showed significant positive reactions in all investigated assays related to ASP consumption. The protective and immune-stimulant efficacy of S. vulgare-MeOH extract, inferred from combating oxidative stress-induced lipid peroxidation, modulating the low levels of the endogenous antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and of the thyroid hormones T3 and T4, attenuating the elevated levels of apoptotic CASP-3 and inflammatory biomarkers TNF-α and IL-6, as well as heat shock proteins (Hsp70), can be most likely ascribed to the synergistic effect of its potent antioxidant phenolics (mainly gallic, ferulic, salicylic, and chlorogenic, and p-coumaric acids) and flavonoids (rutin, kaempferol, and hesperidin). Mechanism of action of these natural antioxidants was discussed.

Artificial Sweeteners Negatively Regulate Pathogenic Characteristics of Two Model Gut Bacteria, E. coli and E. faecalis.

Artificial sweeteners (AS) are synthetic sugar substitutes that are commonly consumed in the diet. Recent studies have indicated considerable health risks which links the consumption of AS with metabolic derangements and gut microbiota perturbations. Despite these studies, there is still limited data on how AS impacts the commensal microbiota to cause pathogenicity. The present study sought to investigate the role of commonly consumed AS on gut bacterial pathogenicity and gut epithelium-microbiota interactions, using models of microbiota (Escherichia coli NCTC10418 and Enterococcus faecalis ATCC19433) and the intestinal epithelium (Caco-2 cells). Model gut bacteria were exposed to different concentrations of the AS saccharin, sucralose, and aspartame, and their pathogenicity and changes in interactions with Caco-2 cells were measured using in vitro studies. Findings show that sweeteners differentially increase the ability of bacteria to form a biofilm. Co-culture with human intestinal epithelial cells shows an increase in the ability of model gut bacteria to adhere to, invade and kill the host epithelium. The pan-sweet taste inhibitor, zinc sulphate, effectively blocked these negative impacts. Since AS consumption in the diet continues to increase, understanding how this food additive affects gut microbiota and how these damaging effects can be ameliorated is vital.

Maternal low-dose aspartame and stevia consumption with an obesogenic diet alters metabolism, gut microbiota and mesolimbic reward system in rat dams and their offspring.

OBJECTIVE: We examined the impact of maternal low-dose aspartame and stevia consumption on adiposity, glucose tolerance, gut microbiota and mesolimbic pathway in obese dams and their offspring. DESIGN: Following obesity induction, female Sprague-Dawley rats were allocated during pregnancy and lactation to: (1) high fat/sucrose diet (HFS) +water (obese-WTR); (2) HFS +aspartame (obese-APM; 5-7 mg/kg/day); (3) HFS +stevia (obese-STV; 2-3 mg/kg/day). Offspring were weaned onto control diet and water and followed until 18 weeks. Gut microbiota and metabolic outcomes were measured in dams and offspring. Cecal matter from offspring at weaning was used for faecal microbiota transplant (FMT) into germ-free (GF) mice. RESULTS: Maternal APM and STV intake with a HFS diet increased body fat in offspring at weaning and body weight long-term with APM. Maternal APM/HFS consumption impaired glucose tolerance in male offspring at age 8 weeks and both APM and STV altered faecal microbiota in dams and offspring. Maternal obesity/HFS diet affected offspring adiposity and glucose tolerance more so than maternal LCS consumption at age 12 and 18 weeks. APM and STV altered expression of genes in the mesolimbic reward system that may promote consumption of a palatable diet. GF mice receiving an FMT from obese-APM and obese-STV offspring had greater weight gain and body fat and impaired glucose tolerance compared with obese-WTR. CONCLUSION: Maternal low-calorie sweetener consumption alongside HFS may disrupt weight regulation, glucose control and gut microbiota in dams and their offspring most notably in early life despite no direct low-calorie sweetener consumption by offspring.

Recent evidence for the effects of nonnutritive sweeteners on glycaemic control.

PURPOSE OF REVIEW: By replacing sugar, nonnutritive sweeteners (NNSs) are thought to aid in weight management and decrease insulin resistance. We reviewed the latest randomized clinical trials (RCTs) investigating the effects NNSs on glycaemic control. RECENT FINDINGS: Six RCTs addressed this topic between 2017 and 2018; the majority tested artificial NNS (sucralose or aspartame), with only one testing natural NNS (stevia and monk fruit extract). Most found no effect of NNS on blood glucose, insulin, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) levels; however, two trials showed an effect of sucralose on the acute insulin response. SUMMARY: We are still incapable of reaching a definite judgement on which types of NNS, if any, impact glycaemic control. There is a need for more research to overcome the limitations of recent RCTs, related to sample size, intervention duration, dose, form of NNSs used, and inclusion of males or female participants only. Future studies should also compare different NNS types with each other, and include the increasingly popular 'natural' NNS.

Behavioral and electrophysiological brain effects of aspartame on well-nourished and malnourished rats.

The non-caloric sweetener aspartame can be potentially harmful to the developing brain, as some studies suggest an association between aspartame intake and adverse neural effects. This study aimed to evaluate the possible effects of aspartame, with or without associated early nutritional deficiency, on behavioral parameters suggestive of anxiety and electrophysiological features of the excitability-related phenomenon known as cortical spreading depression (CSD). Newborn Wistar rats (n = 80) were suckled under favorable (L9; n = 40) or unfavorable lactation conditions (L15; n = 40), consisting of litters with 9 or 15 pups, respectively. In each lactation condition, animals were divided into 4 groups that received per gavage, from postnatal day 8 to 28, 75 mg/kg/d or 125 mg/kg/d aspartame (groups ASP75 and ASP125), or water (vehicle group), or no treatment (naive group). Behavioral tests (elevated plus-maze [EPM]) were performed at postnatal days 86-95 and CSD was recorded between postnatal days 96-115. Compared to the control groups, aspartame dose-dependently reduced body weight, suggesting a negative impact on animal development; aspartame also caused behavioral changes suggestive of anxiety (shorter stay in the open arms in the EPM) and decelerated CSD (lower propagation speed). Some of these parameters were more affected in L15 animals, suggesting an interaction among aspartame and lactation condition. We concluded that early consumption of aspartame adversely affects development of the organism (weight loss), with actions on behavioral (anxiety-like) and cerebral electrophysiological (CSD) parameters. The data suggest caution in aspartame consumption by lactating mothers and their infants.

The acute effects of the non-nutritive sweeteners aspartame and acesulfame-K in UK diet cola on glycaemic response.

Substituting sugar-sweetened for artificially sweetened beverages may reduce energy intakes. This study aims to ascertain the acute glycaemic effects of the NNS aspartame and acesulfame-K in UK diet-cola (DC). Ten healthy participants attended the laboratory fasted on three occasions. Individuals drank (1) 25 g glucose in 125 mL water + 236 mL water, (2) 25 g glucose in 125 mL water with 236 mL DC and (3) 236 mL sucrose-sweetened cola with 125 mL water. Blood (glucose) was measured pre-test and every 15 minutes over a 120-minute period using portable glucometers. The glucose-control and glucose + DC elicited similar blood glucose rises above pre-prandial levels. Sucrose-sweetened cola showed a non-significant lower rise in postprandial glycaemia, exhibiting the lowest glycaemic index (GI) (77.0 ± 9.1). GI of glucose (100.0 ± 15.2) and glucose + DC (104.3 ± 8.5) was similar and a one-way repeated-measures ANOVA showed no significant differences in glycaemic response between test drinks (F(2,29) = 1.68, p > .05). Results demonstrate the glycaemic inactivity of non-nutritive sweeteners.

Synergistic Effects of The Enhancements to Mitochondrial ROS, p53 Activation and Apoptosis Generated by Aspartame and Potassium Sorbate in HepG2 Cells.

The safety of food additives has been widely concerned. Using single additives in the provisions of scope is safe, but the combination of additives, may induce additive, synergy, antagonism and other joint effects. This study investigated the cytotoxicity of aspartame (AT) together with potassium sorbate (PS). Thiazolyl Blue Tetrazolium Bromide (MTT) assay indicated that AT and PS had IC50 values of 0.48 g/L and 1.25 g/L at 24 h, respectively. High content analysis (HCA) showed that both AT and PS had a negative effect on mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and DNA damage while the joint group behaved more obviously. The biochemical assays revealed typical cell morphological changes and the activation of cytochrome c and caspase-3 verified apoptosis induced by AT together with PS. With dissipation of MMP and increase of cell membrane permeability (CMP), it indicated AT together with PS-induced apoptosis was mediated by mitochondrial pathway. Meanwhile, p53 were involved in DNA damage, and the ratio of Bax/Bcl-2 was increased. Moreover, excessive ROS induced by AT together with PS is a key initiating factor for apoptosis. All these results proved that p53 was involved in apoptosis via mitochondria-mediated pathway and the process was regulated by ROS.

Aspartame supplementation in starter accelerates small intestinal epithelial cell cycle and stimulates secretion of glucagon-like peptide-2 in pre-weaned lambs.

The objective of this study was to test the hypothesis that aspartame supplementation in starter diet accelerates small intestinal cell cycle by stimulating secretion and expression of glucagon-like peptide -2 (GLP-2) in pre-weaned lambs using animal and cell culture experiments. In vivo, twelve 14-day-old lambs were selected and allocated randomly to two groups; one was treated with plain starter diet (Con, n = 6) and the other was treated with starter supplemented with 200 mg of aspartame/kg starter (APM, n = 6). Results showed that the lambs received APM treatment for 35 d had higher (p < .05) GLP-2 concentration in the plasma and greater jejunum weight/live body weight (BW) and jejunal crypt depth. Furthermore, APM treatment significantly upregulated (p < .05) the mRNA expression of cyclin D1 in duodenum; and cyclin A2, cyclin D1, cyclin-dependent kinases 6 (CDK6) in jejunum; and cyclin A2, cyclin D1, CDK4 in ileum. Moreover, APM treatment increased (p < .05) the mRNA expression of glucagon (GCG), insulin-like growth factor 1 (IGF-1) in the jejunum and ileum and mRNA expression of GLP-2 receptor (GLP-2R) in the jejunum. In vitro, when jejunal cells were treated with GLP-2 for 2 hr, the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) OD, IGF-1 concentration, and the mRNA expression of IGF-1, cyclin D1 and CDK6 were increased (p < .05). Furthermore, IGF-1 receptor (IGF-1R) inhibitor decreased (p < .05) the mRNA expression of IGF-1, cyclin A2, cyclin D1 and CDK6 in GLP-2 treatment jejunal cells. These results suggest that aspartame supplementation in starter accelerates small intestinal cell cycle that may, in part, be related to stimulate secretion and expression of GLP-2 in pre-weaning lambs. Furthermore, GLP-2 can indirectly promote the proliferation of jejunal cells mainly through the IGF-1 pathway. These findings provide new insights into nutritional interventions that promote the development of small intestines in young ruminants.

Plasma fatty acid ethanolamides are associated with postprandial triglycerides, ApoCIII, and ApoE in humans consuming a high-fructose corn syrup-sweetened beverage.

Epidemiological and clinical research studies have provided ample evidence demonstrating that consumption of sugar-sweetened beverages increases risk factors involved in the development of obesity, Type 2 diabetes, and cardiovascular disease (CVD). Our previous study demonstrated that when compared with aspartame (Asp), 2 wk of high-fructose corn syrup (HFCS)-sweetened beverages provided at 25% of daily energy requirement was associated with increased body weight, postprandial (pp) triglycerides (TG), and fasting and pp CVD risk factors in young adults. The fatty acid ethanolamide, anandamide (AEA), and the monoacylglycerol, 2-arachidonoyl- sn-glycerol (2-AG), are two primary endocannabinoids (ECs) that play a role in regulating food intake, increasing adipose storage, and regulating lipid metabolism. Therefore, we measured plasma concentrations of ECs and their analogs, oleoylethanolamide (OEA), docosahexaenoyl ethanolamide (DHEA), and docosahexaenoyl glycerol (DHG), in participants from our previous study who consumed HFCS- or Asp-sweetened beverages to determine associations with weight gain and CVD risk factors. Two-week exposure to either HFCS- or Asp-sweetened beverages resulted in significant differences in the changes in fasting levels of OEA and DHEA between groups after the testing period. Subjects who consumed Asp, but not HFCS, displayed a reduction in AEA, OEA, and DHEA after the testing period. In contrast, there were significant positive relationships between AEA, OEA, and DHEA vs. ppTG, ppApoCIII, and ppApoE in those consuming HFCS, but not in those consuming Asp. Our findings reveal previously unknown associations between circulating ECs and EC-related molecules with markers of lipid metabolism and CVD risk after HFCS consumption.

Consumption of a Carbonated Beverage with High-Intensity Sweeteners Has No Effect on Insulin Sensitivity and Secretion in Nondiabetic Adults.

Background: The effects of the regular intake of beverages containing high-intensity sweeteners on insulin sensitivity in healthy individuals remain controversial. Objective: This trial compared the effects of the consumption of a carbonated beverage containing aspartame and acesulfame K (high-intensity sweeteners beverage-HISB) with those of an unsweetened, no-calorie carbonated beverage (UB) on insulin sensitivity and secretion in nondiabetic adults. Methods: SEDULC was a randomized, double-blind, crossover study. Nondiabetic adults [mean age 31 y, 44% men, body mass index (BMI; kg/m²) 19-29] who did not consume high-intensity sweeteners were randomized 1:1 to drink 1 of the 2 carbonated beverages, 2 cans (330 mL each)/d, for 12 wk. After a 4-wk washout period, participants were switched to the opposite beverage for 12 wk. The primary outcome tested was the change in insulin sensitivity as assessed by the Matsuda Insulin Sensitivity Index (MISI) after an oral glucose load. Secondary outcomes were indexes of insulin secretion. Results: Sixty individuals were enrolled and 50 completed the study (28 nonoverweight and 22 overweight participants). The change in MISI from baseline did not significantly differ between beverages and noninferiority was demonstrated (difference = -0.23; 95% CI: -1.31, 0.85; P < 0.0001). The change in insulinogenic (means ± SEMs: 0.23 ± 0.14 for HISB compared with 0.08 ± 0.1 for UB) and disposition indexes (2.70 ± 0.99 for HISB compared with 1.62 ± 0.90 for UB) did not differ, and no differences in insulin secretion estimates were confirmed by the Stumvoll indexes. Consuming the high-intensity sweeteners did not affect body weight, self-reported dietary consumption, or self-reported physical activity. Conclusions: These findings suggest that the daily consumption of 2 cans of a beverage containing aspartame and acesulfame K over 12 wk has no significant effect on insulin sensitivity and secretion in nondiabetic adults. This trial was registered at clinicaltrials.gov as NCT02031497.

Aspartame Consumption for 12 Weeks Does Not Affect Glycemia, Appetite, or Body Weight of Healthy, Lean Adults in a Randomized Controlled Trial.

Background: Low-calorie sweeteners are often used to moderate energy intake and postprandial glycemia, but some evidence indicates that they may exacerbate these aims. Objective: The trial's primary aim was to assess the effect of daily aspartame ingestion for 12 wk on glycemia. Effects on appetite and body weight were secondary aims. Methods: One hundred lean [body mass index (kg/m2): 18-25] adults aged 18-60 y were randomly assigned to consume 0, 350, or 1050 mg aspartame/d (ASP groups) in a beverage for 12 wk in a parallel-arm design. At baseline, body weight and composition were determined, a 240-min oral-glucose-tolerance test (OGTT) was administered, and measurements were made of appetite and selected hormones. Participants also collected a 24-h urine sample. During the intervention, the 0-mg/d ASP group consumed capsules containing 680 mg dextrose and 80 mg para-amino benzoic acid. For the 350-mg/d ASP group, the beverage contained 350 mg aspartame and the 1050-mg/d ASP group consumed the same beverage plus capsules containing 680 mg dextrose and 700 mg aspartame. Body weight, blood pressure, heart rate, and waist circumference were measured weekly. At weeks 4, 8, and 12, participants collected 24-h urine samples and kept appetite logs. Baseline measurements were repeated at week 12. Results: With the exception of the baseline OGTT glucose concentration at 60 min (and resulting area under the curve value), there were no group differences for glucose, insulin, resting leptin, glucagon-like peptide 1, or gastric inhibitory peptide at baseline or week 12. There also were no effects of aspartame ingestion on appetite, body weight, or body composition. Compliance with the beverage intervention was ∼95%. Conclusions: Aspartame ingested at 2 doses for 12 wk had no effect on glycemia, appetite, or body weight among healthy, lean adults. These data do not support the view that aspartame is problematic for the management of glycemia, appetite, or body weight. This trial was registered at www.clinicaltrials.gov as NCT02999321.

Metabolic effects of aspartame in adulthood: A systematic review and meta-analysis of randomized clinical trials.

Data about harms or benefits associated with the consumption of aspartame, a nonnutritive sweetener worldwide consumed, are still controversial. This systematic review and meta-analysis of randomized controlled clinical trials aimed to assess the effect of aspartame consumption on metabolic parameters related to diabetes and obesity. The search was performed on Cochrane, LILACS, PubMed, SCOPUS, Web of Science databases, and on a gray literature using Open Grey, Google Scholar, and ProQuest Dissertations & Theses Global. Searches across all databases were conducted from the earliest available date up to April 13, 2016, without date and language restrictions. Pooled mean differences were calculated using a random or fixed-effects model for heterogeneous and homogenous studies, respectively. Twenty-nine articles were included in qualitative synthesis and twelve, presenting numeric results, were used in meta-analysis. Fasting blood glucose (mmol/L), insulin levels (µU/mL), total cholesterol (mmol/L), triglycerides concentrations (mmol/L), high-density lipoprotein cholesterol (mmol/L), body weight (kg), and energy intake (MJ) were considered as the main outcomes in subjects that consumed aspartame, and results were presented as mean difference; % confidence interval, range. Aspartame consumption was not associated with alterations on blood glucose levels compared to control (-0.03 mmol/L; 95% CI, -0.21 to 0.14) or to sucrose (0.31 mmol/L; 95% CI, -0.05 to 0.67) and on insulin levels compared to control (0.13 µU/mL; 95% CI, -0.69 to 0.95) or to sucrose (2.54 µU/mL; 95% CI, -6.29 to 11.37). Total cholesterol was not affected by aspartame consumption compared to control (-0.02 mmol/L; 95% CI, -0.31 to 0.27) or to sucrose (-0.24 mmol/L; 95% CI, -0.89 to 0.42). Triglycerides concentrations were not affected by aspartame consumption compared to control (0.00 mmol/L; 95% CI, -0.04 to 0.05) or to sucrose (0.00 mmol/L; 95% CI, -0.09 to 0.09). High-density lipoprotein cholesterol serum levels were higher on aspartame compared to control (-0.03 mmol/L; 95% CI, -0.06 to -0.01) and lower on aspartame compared to sucrose (0.05 mmol/L; 95% CI, 0.02 to 0.09). Body weight did not change after aspartame consumption compared to control (5.00 kg; 95% CI, -1.56 to 11.56) or to sucrose (3.78 kg; 95% CI, -2.18 to 9.74). Energy intake was not altered by aspartame consumption compared to control (-0.49 MJ; 95% CI, -1.21 to 0.22) or to sucrose (-0.17 MJ; 95% CI, -2.03 to 1.69). Data concerning effects of aspartame on main metabolic variables associated to diabetes and obesity do not support a beneficial related to its consumption.

Beverages containing low energy sweeteners do not differ from water in their effects on appetite, energy intake and food choices in healthy, non-obese French adults.

The usefulness of replacement of caloric sugars by low-calorie sweeteners (LCS) for weight management has been questioned on the grounds that the uncoupling of LCS sweet taste and dietary energy may confuse physiological mechanisms, leading potentially to higher energy and sugar intake. The aim of the present study was to determine whether LCS beverages compared to water, when consumed with meals, differ in their effects on energy and food intake in acute trials and after long-term habituation. Ad libitum food intake of 166 (80 women; 86 men) healthy non-obese adults (BMI between 19 and 28 kg/m2), infrequent consumers of LCS was measured in four 2-consecutive-day testing sessions (Day 1 in the laboratory, Day 2 free-living). During the first 3 sessions, held one-week apart, participants were required to drink either water or commercial non-carbonated LCS lemonade (330 ml) with their main meals (randomised cross-over design). On Day 1, motivational ratings were obtained using visual analogue scales and ad libitum food intakes (amounts and types of foods selected) were measured using the plate waste method. On Day 2, participants reported their ad libitum intakes using a food diary. After Session 3, participants were randomly assigned to the LCS habituation group or to the water control group. The habituation (660 ml LCS lemonade daily vs 660 ml water) lasted 5 weeks. The fourth and final test session measured food intakes and motivational ratings after habituation. Water and LCS beverage did not differ in their effects on total energy intake, macronutrient intakes or the selection of sweet foods and on motivational ratings. Similar results were obtained in both LCS-naïve and LCS-habituated individuals.

Effects of aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages on postprandial glucose, insulin and energy intake.

BACKGROUND: Substituting sweeteners with non-nutritive sweeteners (NNS) may aid in glycaemic control and body weight management. Limited studies have investigated energy compensation, glycaemic and insulinaemic responses to artificial and natural NNS. OBJECTIVES: This study compared the effects of consuming NNS (artificial versus natural) and sucrose (65 g) on energy intake, blood glucose and insulin responses. METHODS: Thirty healthy male subjects took part in this randomised, crossover study with four treatments: aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages. On each test day, participants were asked to consume a standardised breakfast in the morning, and they were provided with test beverage as a preload in mid-morning and ad libitum lunch was provided an hour after test beverage consumption. Blood glucose and insulin concentrations were measured every 15 min within the first hour of preload consumption and every 30 min for the subsequent 2 h. Participants left the study site 3 h after preload consumption and completed a food diary for the rest of the day. RESULTS: Ad libitum lunch intake was significantly higher for the NNS treatments compared with sucrose (P=0.010). The energy 'saved' from replacing sucrose with NNS was fully compensated for at subsequent meals; hence, no difference in total daily energy intake was found between the treatments (P=0.831). The sucrose-sweetened beverage led to large spikes in blood glucose and insulin responses within the first hour, whereas these responses were higher for all three NNS beverages following the test lunch. Thus, there were no differences in total area under the curve (AUC) for glucose (P=0.960) and insulin (P=0.216) over 3 h between the four test beverages. CONCLUSIONS: The consumption of calorie-free beverages sweetened with artificial and natural NNS have minimal influences on total daily energy intake, postprandial glucose and insulin compared with a sucrose-sweetened beverage.

Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach.

The current work was undertaken to settle the debate about the toxicity of artificial sweeteners (AS), particularly aspartame and saccharin. Twenty-five, 7-week-old male Wistar albino rats with an average body weight of 101 ± 4.8 g were divided into a control group and four experimental groups (n = 5 rats). The first and second experimental groups received daily doses equivalent to the acceptable daily intake (ADI) of aspartame (250 mg/Kg BW) and four-fold ADI of aspartame (1000 mg/Kg BW). The third and fourth experimental groups received daily doses equivalent to ADI of saccharin (25 mg/Kg BW) and four-fold ADI of saccharin (100 mg/Kg BW). The experimental groups received the corresponding sweetener dissolved in water by oral route for 8 weeks. The activities of enzymes relevant to liver functions and antioxidants were measured in the blood plasma. Histological studies were used for the evaluation of the changes in the hepatic tissues. The gene expression levels of the key oncogene (h-Ras) and the tumor suppressor gene (P27) were also evaluated. In addition to a significant reduction in the body weight, the AS-treated groups displayed elevated enzymes activities, lowered antioxidants values, and histological changes reflecting the hepatotoxic effect of aspartame and saccharin. Moreover, the overexpression of the key oncogene (h-Ras) and the downregulation of the tumor suppressor gene (P27) in all treated rat groups may indicate a potential risk of liver carcinogenesis, particularly on long-term exposure.

Aspartame-stabilized gold-silver bimetallic biocompatible nanostructures with plasmonic photothermal properties, antibacterial activity, and long-term stability.

Gold-silver core-shell nanoparticles stabilized with a common sweetener, aspartame (AuNP@Ag@Asm), combine the antimicrobial properties of silver with the photoinduced plasmon-mediated photothermal effects of gold. The particles were tested with several bacterial strains, while biocompatibility was verified with human dermal fibroblasts.

Effect of carbonation on brain processing of sweet stimuli in humans.

Little is known about how CO2 affects neural processing of taste. We used functional magnetic resonance imaging to investigate the effects of carbonation on brain processing of sweet stimuli, which has relevance to studies of food selection and satiety. The presence of carbonation produced an overall decrease in the neural processing of sweetness-related signals, especially from sucrose. CO2 reduced the neural processing of sucrose more than that of artificial sweeteners. These findings might be relevant to dietary interventions that include noncaloric beverages, whereas the combination of CO2 and sucrose might increase consumption of sucrose.

The effect of non-caloric sweeteners on cognition, choice, and post-consumption satisfaction.

Consumers often turn to non-caloric sweeteners (NCS) as a means of promoting a healthy body weight. However, several studies have now linked their long-term use to increased weight gain, raising the question of whether these products produce unintended psychological, physiological, or behavioral changes that have implications for weight management goals. In the following, we present the results of three experiments bearing on this issue, testing whether NCS-consumption influences how individuals think about and respond to food. Participants in each of our three experiments were randomly assigned to consume a sugar-sweetened beverage, an unsweetened beverage, or a beverage sweetened with NCS. We then measured their cognition (Experiment 1), product choice (Experiment 2), and subjective responses to a sugar-sweetened food (Experiment 3). Results revealed that consuming NCS-sweetened beverages influences psychological processes in ways that - over time - may increase calorie intake.