The rapid increase in the worldwide prevalence of obesity and certain non-communicable diseases (NCDs), such as: cardiovascular diseases, cancers, chronic respiratory diseases, and diabetes, has been mainly attributed to an excess of sugar consumption. Although the potential benefits of the synergetic use of sweeteners have been known for many years, recent development based on synthesis strategies to produce sucrose-like taste profiles is emerging where biocatalyst approaches may be preferred to produce and supply specific sweetener compounds. From a nutritional standpoint, high-intensity sweeteners have fewer calories than sugars while providing a major sweet potency, placing them in the spotlight as valuable alternatives to sugar. Due to the modern world awareness and incidence of metabolic diseases, both food research and growing markets have focused on two generally regarded as safe (GRAS) groups of compounds: the sweet diterpenoid glycosides present on the leaves of Stevia rebaudiana and, more recently, on the cucurbitane triterpene glycosides present on the fruits of Siraitia grosvenorii. In spite of their flavor advantages, biological benefits, including: antidiabetic, anticancer, and cardiovascular properties, have been elucidated. The present bibliographical review dips into the state-of-the-art of sweeteners and their role in human health as sugar replacements, as well as the biotransformation methods for steviol gylcosides and mogrosides apropos of enzymatic technology to update and locate the discoveries to date in the scientific literature to help boost the continuity of research efforts of the ongoing sweeteners.

High sugar consumption is associated with cardiovascular diseases and diabetes. Current sugar substitutes may cause taste sensations and gastrointestinal symptoms. ENSO 16 is a combination of 16 different sugar substitutes and plant fibers and has been designed as a sugar alternative. The impact on plasma glucose metabolism as well as on gastrointestinal tolerance has not been investigated yet. 17 healthy participants were enrolled in this randomized, double-blind trial. Participants received a single oral dose of 30 g glucose or 30 g ENSO 16 and crossed over to the alternate treatment after a 7 day wash out period. The study endpoint was the effect on plasma glucose, insulin, C-peptide concentrations and gastrointestinal disorders. A questionnaire regarding gastrointestinal symptoms was used for individual subjective scoring. The mean baseline adjusted plasma glucose AUC0-180 min was significantly greater after glucose administration compared to ENSO 16 (n = 15, p = 0.0128, paired t-test). Maximum plasma glucose elevation over baseline was 117 mg*dl-1 and 20 mg*dl-1 after oral glucose or ENSO 16, respectively. Insulin and C-peptide AUC0-180 min were significantly greater after glucose compared to ENSO 16 intake (p < 0.01, Wilcoxon rank sum test). The mean maximal concentrations of plasma glucose, insulin and C-peptide after glucose intake were 1.5, 4.6 and 2.7-fold greater after glucose intake compared to ENSO 16 intake, respectively. Adverse reactions were mostly mild and not different between treatments. Conclusion. ENSO 16 has only a small impact on plasma glucose metabolism. This may be of interest in a dietary context and may help to reduce calory intake.Trail registration NCT05457400. First registration: 14/07/2022. https://clinicaltrials.gov/study/NCT05457400 .

Natural sweeteners generally refer to a sweet chemical component directly extracted from nature or obtained through appropriate modifications, mainly secondary metabolites of plants. Compared to the first-generation sweeteners represented by sucrose and the second-generation sweeteners represented by sodium cyclamate, natural sweeteners usually have high sweetness, low-calorie content, good solubility, high stability, and rarely toxic side effects. Historically, researchers mainly focus on the function of natural sweeteners as substitutes for sugars in the food industry. This paper reviews the bioactivities of several typical natural sweeteners, including anti-cancer, anti-inflammatory, antioxidant, anti-bacterial, and anti-hyperglycemic activities. In addition, we have summarized the extraction, physicochemical properties, and application of natural sweeteners. The article aimed to comprehensively collate vital information about natural sweeteners and review the potentiality of tapping bioactive compounds from natural products. Hopefully, this review provides insights into the further development of natural sweeteners as therapeutic agents and functional foods.

Natural rare sugars are an alternative category of sweeteners with positive physiologic and metabolic effects both in in vitro and animal models. D-allulose is a D-fructose epimer that combines 70% sucrose sweetness with the advantage of an extremely low energy content. However, there are no data about the effect of D-allulose against adipose dysfunction; thus, it remains to be confirmed whether D-allulose is useful in the prevention and in treatment of adipose tissue alterations. With this aim, we evaluated D-allulose\'s preventive effects on lipid accumulation in 3T3-L1 murine adipocytes exposed to palmitic acid (PA), a trigger for hypertrophic adipocytes. D-allulose in place of glucose prevented adipocyte hypertrophy and the activation of adipogenic markers C/EBP-β and PPARγ induced by high PA concentrations. Additionally, D-allulose pretreatment inhibited the NF-κB pathway and endoplasmic reticulum stress caused by PA, through activation of the Nrf2 pathway. Interestingly, these effects were also observed as D-allulose post PA treatment. Although our data need to be confirmed through in vivo models, our findings suggest that incorporating D-allulose as a glucose substitute in the diet might have a protective role in adipocyte function and support a unique mechanism of action in this sugar as a preventive or therapeutic compound against PA lipotoxicity through the modulation of pathways connected to lipid transport and metabolism.

The food industry is looking for substitutes for sucrose in food items due to the excessive consumption of products with added sugar and the demand for healthier products. Alternative natural sweeteners can help achieve this goal. Different types of low-fat yoghurts (1% fat), with low-protein and high-protein levels (3% and 4.5-6.5% protein, respectively), were produced using alternative natural sweeteners. The low-protein yoghurts were made with stevia (0.03% w/w) or agave syrup (4.5% w/w). The high-protein yoghurts were made with stevia (0.04% w/w), xylitol (6% w/w) or honey (6% w/w). Sucrose (6% w/w) was used as a control in both trials. pH and titratable acidity, CIEL*a*b* color parameters, syneresis index, rheology and the texture profile of the low-fat yoghurts were evaluated over refrigerated storage. All products underwent sensory evaluation by an untrained panel. The high-protein yoghurts were found to be more acidic (>1% as lactic acid), had a lower syneresis index (between 2.1 and 16.2%) and a better consistency (stronger gel structure) than the low-protein yoghurts. In terms of rheological parameters, stevia-sweetened yoghurts scored higher than the other sweetened yoghurts, showing a better gel structure. The different sweeteners tested did not significantly affect the sensory properties of the yoghurts, although the high-protein yoghurts scored higher for most of the attributes evaluated. Overall, consumers preferred stevia-sweetened yoghurts to yoghurts sweetened with sucrose or agave for the low-protein yoghurts. Of the tested formulations, those containing high protein with the alternative natural sweetener xylitol received higher scores in all attributes. These results reveal the potential of the tested natural sweeteners as sucrose substitutes, while contributing to improving the nutritional value of yoghurts.

This article presents the results of a comprehensive toxicity assessment of brazzein and monellin, yeast-produced recombinant sweet-tasting proteins. Excessive sugar consumption is one of the leading dietary and nutritional problems in the world, resulting in health complications such as obesity, high blood pressure, and cardiovascular disease. Although artificial small-molecule sweeteners widely replace sugar in food, their safety and long-term health effects remain debatable. Many sweet-tasting proteins, including thaumatin, miraculin, pentadin, curculin, mabinlin, brazzein, and monellin have been found in tropical plants. These proteins, such as brazzein and monellin, are thousands-fold sweeter than sucrose. Multiple reports have presented preparations of recombinant sweet-tasting proteins. A thorough and comprehensive assessment of their toxicity and safety is necessary to introduce and apply sweet-tasting proteins in the food industry. We experimentally assessed acute, subchronic, and chronic toxicity effects, as well as allergenic and mutagenic properties of recombinant brazzein and monellin. Our study was performed on three mammalian species (mice, rats, and guinea pigs). Assessment of animals\' physiological, biochemical, hematological, morphological, and behavioral indices allows us to assert that monellin and brazzein are safe and nontoxic for the mammalian organism, which opens vast opportunities for their application in the food industry as sugar alternatives.

Steviol glycosides obtained from Stevia rebaudiana leaves are increasingly used in the food industry as natural low-calorie sweeteners. Among them, the sweetness of major glycosides composed of glucose residues (e.g., stevioside and rebaudioside A) has been widely studied. However, the properties of minor natural products containing rhamnose or xylose residues are poorly investigated. In this study, five unreported steviol glycosides containing rhamnose or xylose were extracted from our developing stevia leaves, and their sweetness was evaluated. The highly glycosylated steviol glycosides were identified, and their structures were examined by fragmentation analysis using mass spectrometry. Chemical synthesis of these glycosides confirmed their structures and allowed sensory evaluation of minor steviol glycosides. Our study revealed that a xylose-containing glycoside, rebaudioside FX1, exhibits a well-balanced sweetness, and thus, it is a promising candidate for natural sweeteners used in the food industry.

Overconsumption of added sugars is associated with higher incidences of obesity, type II diabetes, and cardiovascular disease. Alternative sweeteners have long been relied on as a strategy to reduce consumption of added sugars; however these alternatives differ notably from sucrose in their sensory properties. Recently, consumers have also been looking to reduce consumption of ingredients deemed \"artificial,\" seeking natural alternatives despite poor definitions of these terms on the whole. Wider knowledge of the sensory properties of natural sweeteners would greatly aid in this goal. Descriptive analysis and time-intensity scaling were used to characterize the temporal profile and off-flavors of allulose, erythritol, rebaudioside (Reb) A, Reb D, Reb M, monk fruit, and thaumatin, as compared to sucrose. Further, each was blended to reduce sucrose by 50% and 75% in binary mixtures. Where significant off-flavors were frequently reported with sweeteners, when delivered in binary mixtures for partial sugar reduction, these were much mitigated, while also bringing temporal profiles closer to that of sucrose. This suggests that partial sugar reduction may be an effective way of reducing caloric intake while not compromising sensory experience. PRACTICAL APPLICATION: The use of both descriptive analysis and time-intensity scaling allows for a more complete understanding of the sensory properties of natural alternative sweeteners. Understanding their sensory deficits and ways to improve these sweeteners plays a critical role in creating healthier products that will be accepted by consumers.

Increased added sugar consumption is associated with type II diabetes, metabolic syndrome, and cardiovascular disease. Low and no-calorie alternative sweeteners have long been used as an aid in the reduction of added sugar. Unfortunately, these alternative sweeteners often have notable sensory deficits when compared to sucrose. Furthermore, many alternative sweeteners have synthetic origins, while consumers are increasingly turning to foods from natural origins, and from more sustainable sources. Such sweeteners include the rare sugar allulose, which can be manufactured from common agricultural waste and dairy co-product streams, and is reported to have a sensory profile similar to sucrose. This study aimed to determine the influence of the rare sugar allulose on consumer perception of sweetened vanilla yogurt. Participants were recruited to evaluate 4 vanilla yogurts sweetened with either sucrose, allulose, stevia or sucralose, and to rate their liking of the samples overall, and for flavor, texture, and their purchase intent. Statistical analysis of hedonic data from 100 consumers suggested that allulose performed similarly to sucrose in liking and purchase intent, and superior to other sweeteners tested in this study, with fewer off-flavors. Moreover, when consumers were queried on their purchase intent after learning details on the sweetener for each formulation, allulose scored significantly higher than all other formulations in purchase intent. This study highlights the potential of the rare sugar allulose as a low calorie, zero glycemic index, natural and better tasting sugar replacement in sweetened yogurt.

The natural sweeteners erythritol and xylitol might be helpful to reduce sugar consumption and therefore prevent obesity and diabetes. The aim of the present study was to determine the absorption and metabolization into erythronate of different concentrations of erythritol and xylitol. Seventeen healthy lean participants received intragastric solutions of 10, 25, or 50 g erythritol or 7, 17, or 35 g xylitol on three study days in a randomized order. The study was double blinded with respect to the doses administered. We assessed plasma concentrations of erythritol, xylitol, and erythronate at fixed time intervals after administration with gas chromatography-mass spectrometry. We found: (i) a dose-dependent and saturable absorption of erythritol, (ii) a very low absorption of xylitol, (iii) a dose-dependent metabolization of erythritol into erythronate, and (iv) no metabolization of xylitol into erythronate. The implications of the metabolization of erythritol into erythronate for human health remain to be determined and more research in this area is needed.