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Background/Objective: To determine gastrointestinal (GI) responses and maximum tolerated dose of erythritol in young children given as a single oral dose in a 250-ml non-carbonated fruit-flavoured beverage in between meals. This is a multicentre double-blind study with sequential design for multiple dose groups and randomised crossover for comparators of placebo vs dose. Subjects/Methods: A total of 185 healthy young children aged 4–6 years were recruited at three clinical investigation centres after informed consent of both parents; 184 children completed the study. Children were included in one of the four dose groups (5, 15, 20 or 25 g erythritol) and exposed randomly to only one single dose vs an isosweet sucrose placebo. After consumption in the clinic and an observation period, GI symptoms and stooling patterns were recorded during the next 48 h. Results: Statistically significantly more episodes of diarrhoea and/or severe GI symptoms were observed in the 20 and 25 g groups compared with placebo, but not in the 5 and 15 g groups. Stool consistency, as measured by Bristol stool scale, was lower in the 15-, 20- and 25 g groups for the first 24 -h period, but not at later time points. Incidences of nausea, vomiting, borborygmi, excess flatus and abdominal pain were not significantly different from the placebo controls at all doses of erythritol. Conclusions: Rapid ingestion of up to and including 15 g (6% w/v) of erythritol in a beverage in between meals by young children aged 4–6 years was well tolerated. The no observed effect level for diarrhoea and/or severe GI symptoms was 15 g (0.73 g/kg body weight (bw)). Children appeared not to be more sensitive to the GI effects of erythritol than published for adults on a g/kg bw basis.

Objectives: To determine and compare the gastrointestinal (GI) responses of young adults following consumption of 45 g sucrose, 20, 35 and 50 g xylitol or erythritol given as a single oral, bolus dose in a liquid. Design: The study was a randomized, double-blind, placebo-controlled study. Subjects: Seventy healthy adult volunteers aged 18–24 years were recruited from the student population of the University of Salford. Sixty-four subjects completed the study. Interventions: Subjects consumed at home without supervision and in random order, either 45 g sucrose or 20, 35 and 50 g erythritol or xylitol in water on individual test days, while maintaining their normal diet. Test days were separated by 7-day washout periods. Subjects reported the prevalence and magnitude of flatulence, borborygmi, bloating, colic, bowel movements and the passage of faeces of an abnormally watery consistency. Results: Compared with 45 g sucrose, consumption of a single oral, bolus dose of 50 g xylitol in water significantly increased the number of subjects reporting nausea ( P <0.01), bloating ( P <0.05), borborygmi ( P <0.005), colic ( P <0.05), watery faeces ( P <0.05) and total bowel movement frequency ( P <0.01). Also 35 g of xylitol increased significantly bowel movement frequency to pass watery faeces ( P <0.05). In contrast, 50 g erythritol only significantly increased the number of subjects reporting nausea ( P <0.01) and borborygmi ( P <0.05). Lower doses of 20 and 35 g erythritol did not provoke a significant increase in GI symptoms. At all levels of intake, xylitol produced significantly more watery faeces than erythritol: resp. 50 g xylitol vs 35 g erythritol ( P <0.001), 50 g xylitol vs 20 g erythritol ( P <0.001) and 35 g xylitol vs 20 g erythritol ( P <0.05). Conclusions: When consumed in water, 35 and 50 g xylitol was associated with significant intestinal symptom scores and watery faeces, compared to the sucrose control, whereas at all levels studied erythritol scored significantly less symptoms. Consumption of 20 and 35 g erythritol by healthy volunteers, in a liquid, is tolerated well, without any symptoms. At the highest level of erythritol intake (50 g), only a significant increase in borborygmi and nausea was observed, whereas xylitol intake at this level induced a significant increase in watery faeces. Sponsorship: Cerestar R&D Center, Vilvoorde, Belgium.

•No effect of caloric labels on liking or neural responses to erythritol vs. sucrose.•Erythritol elicited lower liking ratings than sucrose.•No neural differences between sweeteners.•Brain activity differed between sucrose and water, less so for erythritol vs. water.•Sucrose triggers a stronger craving signature response than erythritol. The beneficial effects of substituting sugar with non-caloric sweeteners (NCSs) remain uncertain due to the mismatch between their rewarding sweet taste and lack of energy content. Functional magnetic resonance imaging (fMRI) studies indicate an influence of cognitive processes (e.g., beliefs, expectations) on reward system responses to NCSs, thereby changing their rewarding properties. We measured the impact of cognitive influences about the caloric content on brain responses and liking ratings to erythritol, a natural NCS with satiating properties, versus sugar (i.e., sucrose). We performed a within-subject, single-blind, counterbalanced fMRI study in 30 healthy males (mean ± SD: age 23 ± 0.6 years, BMI 22.5 ± 0.3 kg/m²). Concentrations of erythritol were individually titrated to match the perceived sweetness intensity of a 16 % sucrose solution. During the scan, sucrose and equisweet erythritol solutions were delivered as 1 mL sips with either correct or purposefully incorrect \"low-calorie\" or \"high-calorie\" labels. After each sip, participants rated sweetness liking. Water with a \"water\" label was used as the control condition. A 2 × 2 ANOVA revealed lower liking ratings for erythritol than sucrose (p < 0.0001), but no main effect of the label, nor label-by-sweetener interaction. General Linear Model (GLM) analysis of brain responses at FDR q < 0.05 showed no main effect of sweetener nor label, nor a label-by-sweetener interaction. However, several patterns of brain activity mediated the differences in subjective liking ratings between the sweeteners. Moreover, different neural responses were found for sucrose vs. water in parcel-wise, SVM, and ROI-based analyses, whereas for erythritol vs. water, only the latter two showed differences. Lastly, sucrose induced a stronger craving signature response compared to erythritol, driven by the pattern specific to drug craving. Liking ratings were lower for erythritol than sucrose, and they were unaffected by the caloric label. There were no differences in neural responses between the sweeteners and labels, except in comparisons with water.

Background: Erythritol, a sugar alcohol, is widely used as a substitute for sugar in diets for patients with diabetes or obesity. Methods: In this study, we aimed to investigate the effects of erythritol on metabolic disorders induced by a high-fat diet in C57BL/6J mice, while focusing on changes in innate immunity. Results: Mice that were fed a high-fat diet and administered water containing 5% erythritol (Ery group) had markedly lower body weight, improved glucose tolerance, and markedly higher energy expenditure than the control mice (Ctrl group) (n = 6). Furthermore, compared with the Ctrl group, the Ery group had lesser fat deposition in the liver, smaller adipocytes, and significantly better inflammatory findings in the small intestine. The concentrations of short-chain fatty acids (SCFAs), such as acetic acid, propanoic acid, and butanoic acid, in the serum, feces, and white adipose tissue of the Ery group were markedly higher than those in the Ctrl group. In flow cytometry experiments, group 3 innate lymphoid cell (ILC3) counts in the lamina propria of the small intestine and ILC2 counts in the white adipose tissue of the Ery group were markedly higher than those in the Ctrl group. Quantitative real-time reverse transcription polymerase chain reaction analyses showed that the Il-22 expression in the small intestine of the Ery group was markedly higher than that in the Ctrl group. Conclusions: Erythritol markedly decreased metabolic disorders such as diet-induced obesity, glucose intolerance, dyslipidemia, and fat accumulation in the mouse liver by increasing SCFAs and modulating innate immunity.

Erythritol, a non-nutritive polyol, is the main component of the artificial sweetener Truvia®. Recent research has indicated that erythritol may have potential as an organic insecticide, given its harmful effects on several insects but apparent safety for mammals. However, for erythritol to have practical use as an insecticide in agricultural settings, it must have neutral to positive effects on crop plants and other non-target organisms. We examined the dose-dependent effects of erythritol (0, 5, 50, 500, 1000, and 2000 mM) on corn (Zea mays) and tomato (Solanum lycopersicum) seedling growth and seed germination. Erythritol caused significant reductions in both belowground (root) and aboveground (shoot) dry weight at and above the typical minimum insecticidal dose (500 mM erythritol) in tomato plants, but not in corn plants. Both corn and tomato seed germination was inhibited by erythritol but the tomato seeds appeared to be more sensitive, responding at concentrations as low as 50 mM erythritol (in contrast to a minimum damaging dose of 1000 mM erythritol for corn seeds). Our results suggest erythritol may have damaging non-target effects on certain plant crops when used daily at the typical doses needed to kill insect pests. Furthermore, if erythritol's damaging effects extend to certain weed species, it also may have potential as an organic herbicide.

The effect of 2–month usage of saliva–stimulating pastils containing either erythritol or xylitol was studied in a cohort of 30 subjects assigned to the respective polyol groups (n = 15). The daily consumption level of both polyols was 5.2 g, used in 5 daily chewing episodes. The mean weight of total plaque mass (collectable during a standard period of 3 min from all available tooth surfaces) was reduced significantly in the xylitol–group, while no such effect was observed in the erythritol–group. This reduction in plaque mass was accompanied by a significant reduction in the turbidity readings (A 660 ) of aqueous plaque suspensions; no such effect was observed in the erythritol–group. However, plaque protein levels did not differ between baseline and endpoint in either polyol group. The plaque and salivary levels of Streptococcus mutans and plaque levels of total streptococci were reduced significantly in the xylitol–group, while no such effect was detected in the erythritol–group. However, either polyol regimen had no effect on plaque levels of S. sobrinus. The results suggest that systematic use of xylitol–containing saliva stimulants may be more effective in controlling some oral–hygiene–related and caries–associated parameters than similar use of erythritol–containing products. The results also speak for a special relationship between xylitol and S. mutans. However, owing to the great potential of erythritol as a caries–reducing agent – based on the tetritol nature of erythritol – the present laboratory results should be considered preliminary and subject to verifying clinical studies.

Sugar substitutes are important in the dietary management of diabetes mellitus. Erythritol is a non-caloric dietary bulk sweetener that reverses endothelial dysfunction in diabetic rats. We completed a pilot study to examine the effects of erythritol on vascular function in patients with type 2 diabetes mellitus. Participants ( n  = 24) consumed erythritol 36 g/day as an orange-flavored beverage for 4 weeks and a single dose of 24 g during the baseline and final visits. We assessed vascular function before and after acute (2 h) and chronic (4 weeks) erythritol consumption. Acute erythritol improved endothelial function measured by fingertip peripheral arterial tonometry (0.52 ± 0.48 to 0.87 ± 0.29 au, P  = 0.005). Chronic erythritol decreased central pulse pressure (47 ± 13 to 41 ± 9 mmHg, P  = 0.02) and tended to decrease carotid-femoral pulse wave velocity ( P  = 0.06). Thus, erythritol consumption acutely improved small vessel endothelial function, and chronic treatment reduced central aortic stiffness. Erythritol may be a preferred sugar substitute for patients with diabetes mellitus.

Several sugar alcohols (polyols) have been promoted as potential sugar substitutes in caries limitation. However, differences in the effects of simple alditol-type sugar alcohol homologues on dental plaque have not been compared in clinical tests. The effects of 6-month use of erythritol (a sugar alcohol of the tetritol type), xylitol (a pentitol) and D-glucitol (sorbitol, a hexitol) were investigated in a cohort of 136 teenage subjects assigned to the respective polyol groups or to an untreated control group (n = 30-36 per group). The daily use of the polyols was 7.0 g in the form of chewable tablets, supplemented by twice-a-day use of a dentifrice containing those polyols. The use of erythritol and xylitol was associated with a statistically significant reduction (p < 0.001 in most cases) in the plaque and saliva levels of mutans streptococci. The amount of dental plaque was also significantly reduced in subjects receiving erythritol and xylitol. Such effects were not observed in other experimental groups. Chemical analyses showed D-glucitol to be a normal finding in dental plaque while xylitol was less consistently detected. Erythritol was detected in measurable amounts only in the plaque of subjects receiving this polyol. Erythritol and xylitol may exert similar effects on some risk factors of dental caries, although the biochemical mechanism of the effects may differ. These in vivo studies were supported by cultivation experiments in which xylitol, and especially erythritol, inhibited the growth of several strains of mutans streptococci.

Brucellosis is a bacterial zoonosis caused by the genus Brucella , which mainly affects domestic animals. In these natural hosts, brucellae display a tropism towards the reproductive organs, such as the placenta, replicating in high numbers and leading to placentitis and abortion, an ability also exerted by the B. melitensis live-attenuated Rev1 strain, the only vaccine available for ovine brucellosis. It is broadly accepted that this tropism is mediated, at least in part, by the presence of certain preferred nutrients in the placenta, particularly erythritol, a polyol that is ultimately incorporated into the Brucella central carbon metabolism via two reactions dependent on transaldolase (Tal) or fructose-bisphosphate aldolase (Fba). In the light of these remarks, we propose that blocking the incorporation of erythritol into the central carbon metabolism of Rev1 by deleting the genes encoding Tal and Fba may impair the ability of the vaccine to proliferate massively in the placenta. Therefore, a Rev1Δfba Δtal double mutant was generated and confirmed to be unable to use erythritol. This mutant exhibited a reduced intracellular fitness both in BeWo trophoblasts and THP-1 macrophages. In the murine model, Rev1Δfba Δtal provided comparable protection to the Rev1 reference vaccine while inducing fewer adverse reproductive events in pregnant animals. Altogether, these results postulate the Rev1Δfba Δtal mutant as a reproductively safer Rev1-derived vaccine candidate to be studied in the natural host.

PurposeStudies have reported that erythritol, a low or non-glycemic sugar alcohol possesses anti-hyperglycemic and anti-diabetic potentials but the underlying mode of actions is not clear. This study investigated the underlying mode of actions behind the anti-hyperglycemic and anti-diabetic potentials of erythritol using different experimental models (experiment 1, 2 and 3).MethodsExperiment 1 examined the effects of increasing concentrations (2.5–20%) of erythritol on glucose absorption and uptake in isolated rat jejunum and psoas muscle, respectively. Experiments 2 and 3 examined the effects of a single oral dose of erythritol (1 g/kg bw) on intestinal glucose absorption, gastric emptying and postprandial blood glucose increase, glucose tolerance, serum insulin level, muscle/liver hexokinase and liver glucose-6 phosphatase activities, liver and muscle glycogen contents and mRNA and protein expression of muscle Glut-4 and IRS-1 in normal and type 2 diabetic animals.ResultsExperiment 1 revealed that erythritol dose dependently enhanced muscle glucose ex vivo. Experiment 2 demonstrated that erythritol feeding delayed gastric emptying and reduced small intestinal glucose absorption as well as postprandial blood glucose rise, especially in diabetic animals. Experiment 3 showed that erythritol feeding improved glucose tolerance, muscle/liver hexokinase and liver glucose-6 phosphatase activities, glycogen storage and also modulated expression of muscle Glut-4 and IRS-1 in diabetic animals.ConclusionData suggest that erythritol may exert anti-hyperglycemic effects not only via reducing small intestinal glucose absorption, but also by increasing muscle glucose uptake, improving glucose metabolic enzymes activity and modulating muscle Glut-4 and IRS-1 mRNA and protein expression. Hence, erythritol may be a useful dietary supplement for managing hyperglycemia, particularly for T2D.