rebaudioside-a and Obesity

The goal of this review is to discuss the data on natural alternative sweeteners and their effects on glucose homeostasis and other metabolic parameters within the past five years. We sought to answer whether common natural alternative sweeteners have a positive or negative effect on glucose control in both human and animal models, and whether the data supports their widespread use as a tool to help reduce the prevalence of diabetes and associated comorbid conditions.. Recent studies suggest that natural alternative sweeteners may reduce hyperglycemia, improve lipid metabolism, and have antioxidant effects particularly in those that have baseline diabetes. Diabetes and metabolic syndrome have become a global healthcare crisis and the sugar overconsumption plays a major role. The use of artificial sweeteners has become more prevalent to improve insulin resistance in those with diabetes, obesity, and metabolic syndrome, although the evidence does not support this result. There are however some promising data to suggest that natural alternative sweeteners may be a better alternative to sugar and artificial sweeteners.

Topics: Animals; Diabetes Mellitus; Glucose; Homeostasis; Humans; Insulin Resistance; Obesity; Plant Preparations; Stevia; Sugar Alcohols; Sugars; Sweetening Agents

Noncaloric sweeteners (NCS) are food additives used to provide sweetness without adding calories. Their consumption has become more widespread around the world in all age groups, including children. The aim of this study is to show the state of the art about the intake of noncaloric sweeteners in children, as well as their benefits and consumption risk. Scientific searchers were used (PUBMED, Scopus, and Scielo) to analyze articles that included keywords (noncaloric sweeteners/saccharin/cyclamate/acesulfame potassium/aspartame/sucralose/stevia/children) in English, Spanish, and Portuguese. Authors conclude that it is imperative that health professionals judiciously and individually evaluate the overall benefits and risks of NCS use in consumers before recommending their use. Different subgroups of the population incorporate products containing NCS in their diet with different objectives, which should be considered when recommending a diet plan for the consumer. In childhood, in earlier age groups, this type of additives should be used as a dietary alternative when other forms of prevention in obesity are not sufficient.

Topics: Aspartame; Child; Cyclamates; Energy Intake; Food Additives; Humans; Obesity; Risk Assessment; Saccharin; Stevia; Sucrose; Sweetening Agents; Thiazines

The current review summarizes and discusses current knowledge on sweeteners and sweetness enhancers.. The perception of sweet taste is mediated by the type 1 taste receptor 2 (T1R2)/type 1 taste receptor 3 (T1R3) receptor, which is expressed in the oral cavity, where it provides input on the caloric and macronutrient contents of ingested food. This receptor recognizes all the compounds (natural or artificial) perceived as sweet by people. Sweeteners are highly chemically diverse including natural sugars, sugar alcohols, natural and synthetic sweeteners, and sweet-tasting proteins. This single receptor is also the target for developing novel sweet enhancers. Importantly, the expression of a functional T1R2/T1R3 receptor is described in numerous extraoral tissues. In this review, the physiological impact of sweeteners is discussed.. Sweeteners and sweetness enhancers are perceived through the T1R2/T1R3 taste receptor present both in mouth and numerous extraoral tissues. The accumulated knowledge on sugar substitutes raises the issue of potential health effects.

Topics: Animals; Dietary Carbohydrates; Humans; Obesity; Receptors, G-Protein-Coupled; Stevia; Sugar Alcohols; Sweetening Agents; Taste; Taste Perception

Stevia rebaudiana Bertoni is a sweet and nutrient-rich plant belonging to the Asteraceae family. Stevia leaves contain steviol glycosides including stevioside, rebaudioside (A to F), steviolbioside, and isosteviol, which are responsible for the plant's sweet taste, and have commercial value all over the world as a sugar substitute in foods, beverages and medicines. Among the various steviol glycosides, stevioside, rebaudioside A and rebaudioside C are the major metabolites and these compounds are on average 250-300 times sweeter than sucrose. Steviol is the final product of Stevia metabolism. The metabolized components essentially leave the body and there is no accumulation. Beyond their value as sweeteners, Stevia and its glycosdies possess therapeutic effects against several diseases such as cancer, diabetes mellitus, hypertension, inflammation, cystic fibrosis, obesity and tooth decay. Studies have shown that steviol glycosides found in Stevia are not teratogenic, mutagenic or carcinogenic and cause no acute and subacute toxicity. The present review provides a summary on the biological and pharmacological properties of steviol glycosides that might be relevant for the treatment of human diseases.

Topics: Cystic Fibrosis; Dental Caries; Diabetes Mellitus; Diterpenes, Kaurane; Glycosides; Humans; Hypertension; Inflammation; Neoplasms; Obesity; Plant Extracts; Stevia

Low-calorie sweeteners (LCSs) provide sweetness with little or no energy. However, each LCS's unique chemical structure has potential to elicit different sensory, physiological, and behavioral responses that affect body weight.. The purpose of this trial was to compare the effects of consumption of 4 LCSs and sucrose on body weight, ingestive behaviors, and glucose tolerance over a 12-wk intervention in adults (18-60 y old) with overweight or obesity (body mass index 25-40 kg/m2).. In a parallel-arm design, 154 participants were randomly assigned to consume 1.25-1.75 L of beverage sweetened with sucrose (n = 39), aspartame (n = 30), saccharin (n = 29), sucralose (n = 28), or rebaudioside A (rebA) (n = 28) daily for 12 wk. The beverages contained 400-560 kcal/d (sucrose treatments) or <5 kcal/d (LCS treatments). Anthropometric indexes, energy intake, energy expenditure, appetite, and glucose tolerance were measured at baseline. Body weight was measured every 2 wk with energy intake, expenditure, and appetite assessed every 4 wk. Twenty-four-hour urine collections were completed every 4 wk to determine study compliance via para-aminobenzoic acid excretion.. Of the participants enrolled in the trial, 123 completed the 12-wk intervention. Sucrose and saccharin consumption led to increased body weight across the 12-wk intervention (Δweight = +1.85 ± 0.36 kg and +1.18 ± 0.36 kg, respectively; P ≤ 0.02) and did not differ from each other. There was no significant change in body weight with consumption of the other LCS treatments compared with baseline, but change in body weight for sucralose was negative and significantly lower compared with all other LCSs at week 12 (weight difference ≥ 1.37 ± 0.52 kg, P ≤ 0.008). Energy intake decreased with sucralose consumption (P = 0.02) and ingestive frequency was lower for sucralose than for saccharin (P = 0.045). Glucose tolerance was not significantly affected by any of the sweetener treatments.. Sucrose and saccharin consumption significantly increase body weight compared with aspartame, rebA, and sucralose, whereas weight change was directionally negative and lower for sucralose compared with saccharin, aspartame, and rebA consumption. LCSs should be categorized as distinct entities because of their differing effects on body weight. This trial was registered at clinicaltrials.gov as NCT02928653.

Topics: Adult; Aspartame; Beverages; Body Mass Index; Body Weight; Diet; Dietary Sucrose; Diterpenes, Kaurane; Energy Intake; Feeding Behavior; Female; Humans; Male; Non-Nutritive Sweeteners; Obesity; Overweight; Saccharin; Stevia; Sucrose; Sweetening Agents; Weight Gain; Young Adult

Obesity is a public health problem characterized by increased body weight due to abnormal adipose tissue expansion. Bioactive compound consumption from the diet or intake of dietary supplements is one of the possible ways to control obesity. Natural products with adipogenesis-regulating potential act as obesity treatments. We evaluated the synergistic antiangiogenesis, antiadipogenic and antilipogenic efficacy of standardized rebaudioside A, sativoside, and theasaponin E1 formulations (RASE1)

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Angiogenesis Inhibitors; Animals; Biological Products; Disease Models, Animal; Diterpenes, Kaurane; Drug Compounding; Drug Synergism; Female; Glucosides; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Lipid Metabolism; Lipogenesis; Lipolysis; Mice; Mice, Inbred ICR; Obesity; Oleanolic Acid; Phytotherapy; RNA, Messenger; Saponins; Signal Transduction; Stevia; Tea

Sugar-sweetened beverage consumption is a known independent risk factor for nonalcoholic steatohepatitis (NASH). Non-caloric sweeteners (NCS) are food additives providing sweetness without calories and are considered safe and/or not metabolized by the liver. The potential role of newer NCS in the regulation of NASH, however, remain unknown. Our study aimed to determine the impact of newer NCS including Rebaudioside A and sucralose on NASH using high fat diet induced obesity mouse model by substituting fructose and sucrose with NCS in the drinking water. We characterized the phenotype of NCS- treated obesity and investigated the alterations of hepatic function and underlying mechanisms. We found that NCS have no impact on weight gain and energy balance in high fat diet induced obesity. However, in comparison to fructose and sucrose, Rebaudioside A significantly improved liver enzymes, hepatic steatosis and hepatic fibrosis. Additionally, Rebaudioside A improved endoplasmic reticulum (ER) stress related gene expressions, fasting glucose levels, insulin sensitivity and restored pancreatic islet cell mass, neuronal innervation and microbiome composition. We concluded that Rebaudioside A significantly ameliorated murine NASH, while the underlying mechanisms requires further investigation.

Topics: Adiposity; Animals; Diet, High-Fat; Diterpenes, Kaurane; Endoplasmic Reticulum Stress; Energy Metabolism; Fructose; Glucose; Homeostasis; Insulin Resistance; Insulin-Secreting Cells; Liver; Mice; Microbiota; Non-alcoholic Fatty Liver Disease; Obesity; Protective Agents; Sugar-Sweetened Beverages; Weight Gain

Artificial sweeteners have been shown to induce glucose intolerance by altering the gut microbiota; however, little is known about the effect of stevia. Here, we investigate whether stevia supplementation induces glucose intolerance by altering the gut microbiota in mice, hypothesizing that stevia would correct high fat diet-induced glucose intolerance and alter the gut microbiota. Mice were split into four treatment groups: low fat, high fat, high fat + saccharin and high fat + stevia. After 10 weeks of treatment, mice consuming a high fat diet (60% kcal from fat) developed glucose intolerance and gained more weight than mice consuming a low fat diet. Stevia supplementation did not impact body weight or glucose intolerance. Differences in species richness and relative abundances of several phyla were observed in low fat groups compared to high fat, stevia and saccharin. We identified two operational taxonomic groups that contributed to differences in beta-diversity between the stevia and saccharin groups: Lactococcus and Akkermansia in females and Lactococcus in males. Our results demonstrate that stevia does not rescue high fat diet-induced changes in glucose tolerance or the microbiota, and that stevia results in similar alterations to the gut microbiota as saccharin when administered in concordance with a high fat diet.

Topics: Animals; Disease Models, Animal; Female; Gastrointestinal Microbiome; Glucose; Male; Mice; Mice, Inbred C57BL; Obesity; Stevia

It is difficult to know if the cause for obesity is the type of sweetener, high fat (HF) content, or the combination of sweetener and fat. The purpose of the present work was to study different types of sweeteners; in particular, steviol glycosides (SG), glucose, fructose, sucrose, brown sugar, honey, SG + sucrose (SV), and sucralose on the functionality of the adipocyte. Male Wistar rats were fed for four months with different sweeteners or sweetener with HF added. Taste receptors T1R2 and T1R3 were differentially expressed in the tongue and intestine by sweeteners and HF. The combination of fat and sweetener showed an additive effect on circulating levels of GIP and GLP-1 except for honey, SG, and brown sugar. In adipose tissue, sucrose and sucralose stimulated TLR4, and c-Jun N-terminal (JNK). The combination of HF with sweeteners increased NFκB, with the exception of SG and honey. Honey kept the insulin signaling pathway active and the smallest adipocytes in white (WAT) and brown (BAT) adipose tissue and the highest expression of adiponectin, PPARγ, and UCP-1 in BAT. The addition of HF reduced mitochondrial branched-chain amino transferase (BCAT2) branched-chain keto acid dehydrogenase E1 (BCKDH) and increased branched chain amino acids (BCAA) levels by sucrose and sucralose. Our data suggests that the consumption of particular honey maintained functional adipocytes despite the consumption of a HF diet.

Topics: 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); Adiponectin; Adipose Tissue; Animals; Diet, High-Fat; Dietary Fats; Dietary Sugars; Honey; Incretins; Inflammation; Insulin; Male; Membrane Transport Proteins; Mitochondrial Proteins; Monocarboxylic Acid Transporters; NF-kappa B; Obesity; PPAR gamma; Rats, Wistar; Solute Carrier Proteins; Stevia; Sucrose; Sweetening Agents; Taste; Taste Buds; Toll-Like Receptor 4; Transaminases; Uncoupling Protein 1

This study aimed to investigate the interaction between obesity, low-calorie sweeteners, and prebiotic oligofructose on reproductive parameters in rats.. Data were derived from two separate studies of female Sprague-Dawley rats with (1) Lean (n = 24), (2) Obese (n = 27), (3) Obese+Aspartame (n = 14), (4) Obese+Stevia (n = 15), and (5) Obese+Prebiotic (n = 15) groups. Obesity was induced with a high-fat/high-sucrose diet prior to pregnancy. In one study, human-approved doses of aspartame (5-7 mg/kg/d) and stevia (2-3 mg/kg/d) in drinking water were examined, and in the second, 10% prebiotics (oligofructose) in the diet was examined. Reproductive parameters, including fertility, pregnancy, and delivery indexes, were analyzed.. Obesity significantly reduced pregnancy index in Obese dams (60.7% successful pregnancies) compared with lean (100%). Obesity also reduced the number of pups born alive and pup survival percentage compared with those of Lean dams (P < 0.001). Only 53.3% of rats were able to conceive in the Obese+Stevia group, but if rats did become pregnant, they had 100% pregnancy and delivery index. While prebiotic administration rescued the pregnancy index, it could not remediate pup survival percentage (P = 0.025) in Obese dams.. Both obesity status and dietary ingredients affect the ability to conceive. Future rigorously controlled studies designed to examine reproductive outcomes in depth are needed to confirm these findings.

Topics: Animals; Aspartame; Female; Fertility; Food Ingredients; Obesity; Prebiotics; Pregnancy; Rats; Rats, Sprague-Dawley; Reproduction; Stevia

There is a close interaction between Type 2 Diabetes, obesity and liver disease. We have studied the effects of the two most abundant Stevia-derived steviol glycosides, stevioside and rebaudioside A, and their aglycol derivative steviol on liver steatosis and the hepatic effects of lipotoxicity using a mouse model of obesity and insulin resistance. We treated ob/ob and LDLR-double deficient mice with stevioside (10 mg⋅kg(-1)⋅day-1 p.o., n = 8), rebaudioside A (12 mg⋅kg(-1)⋅day-1 p.o., n = 8), or steviol (5 mg⋅kg(-1)⋅day(-1) p.o., n = 8). We determined their effects on liver steatosis and on the metabolic effects of lipotoxicity by histological analysis, and by combined gene-expression and metabolomic analyses. All compounds attenuated hepatic steatosis. This could be explained by improved glucose metabolism, fat catabolism, bile acid metabolism, and lipid storage and transport. We identified PPARs as important regulators and observed differences in effects on insulin resistance, inflammation and oxidative stress between Stevia-derived compounds. We conclude that Stevia-derived compounds reduce hepatic steatosis to a similar extent, despite differences in effects on glucose and lipid metabolism, and inflammation and oxidative stress. Thus our data show that liver toxicity can be reduced through several pathophysiological changes. Further identification of active metabolites and underlying mechanisms are warranted.

Topics: Amino Acids; Animals; Bile Acids and Salts; Disease Models, Animal; Diterpenes, Kaurane; Fatty Liver; Glucose; Glucosides; Glutathione; Insulin Resistance; Lipid Metabolism; Liver; Male; Metabolomics; Mice; Mice, Obese; Obesity; Oxidative Stress; Peroxisome Proliferator-Activated Receptors; Plant Preparations; Stevia; Transcriptome

Consumption of sugar-sweetened beverages may be one of the dietary causes of metabolic disorders, such as obesity. Therefore, substituting sugar with low calorie sweeteners may be an efficacious weight management strategy. We tested the effect of preloads containing stevia, aspartame, or sucrose on food intake, satiety, and postprandial glucose and insulin levels.. 19 healthy lean (BMI=20.0-24.9) and 12 obese (BMI=30.0-39.9) individuals 18-50 years old completed three separate food test days during which they received preloads containing stevia (290kcal), aspartame (290kcal), or sucrose (493kcal) before the lunch and dinner meal. The preload order was balanced, and food intake (kcal) was directly calculated. Hunger and satiety levels were reported before and after meals, and every hour throughout the afternoon. Participants provided blood samples immediately before and 20min after the lunch preload. Despite the caloric difference in preloads (290kcal vs. 493kcal), participants did not compensate by eating more at their lunch and dinner meals when they consumed stevia and aspartame versus sucrose in preloads (mean differences in food intake over entire day between sucrose and stevia=301kcal, p<.01; aspartame=330kcal, p<.01). Self-reported hunger and satiety levels did not differ by condition. Stevia preloads significantly reduced postprandial glucose levels compared to sucrose preloads (p<.01), and postprandial insulin levels compared to both aspartame and sucrose preloads (p<.05). When consuming stevia and aspartame preloads, participants did not compensate by eating more at either their lunch or dinner meal and reported similar levels of satiety compared to when they consumed the higher calorie sucrose preload.

Topics: Adolescent; Adult; Aspartame; Blood Glucose; Body Mass Index; Eating; Female; Food; Humans; Hunger; Insulin; Male; Middle Aged; Obesity; Satiation; Stevia; Sucrose; Sweetening Agents; Taste

Stevia (Stevia rebaudiana Bertoni) is a non-caloric natural-source alternative to artificially produced sugar substitutes. This study investigated the effect of stevia extract on lipid profiles in C57BL/6J mice. Forty mice were divided into four groups: N-C (normal diet and distilled water), H-C (high-fat diet and distilled water), H-SC (high fat diet and sucrose, 1 mL kg(-1) per day), and H-SV (high-fat diet and stevia extract, 1 mL kg(-1) per day).. Body weight gain was significantly higher in the H-SC group than in the H-SV group. Triglyceride concentrations in serum and liver were lower in the H-SV group than in the H-SC group. Serum total cholesterol concentrations were lower in the H-SV and H-C groups compared to the H-SC group. The concentrations of acid-insoluble acylcarnitine (AIAC) in serum were higher in the H-SV group than in the H-C and H-SC groups and the acyl/free carnitine level in liver was significantly higher in the H-SV group than in the N-C group. These results were supported by mRNA expression of enzymes related to lipid metabolism (ACO, PPARalpha, ACS, CPT-I, ACC) assessed by real-time polymerase chain reaction.. These results suggest that the supplementation of stevia extract might have an anti-obesity effect on high-fat diet induced obese mice.

Topics: Animals; Body Weight; Carnitine; Dietary Fats; Dietary Sucrose; Dietary Supplements; Enzymes; Hypercholesterolemia; Lipid Metabolism; Lipids; Mice; Mice, Inbred C57BL; Obesity; Plant Extracts; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stevia; Sucrose; Weight Gain