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Objectives: Peri-implant mucositis is a biofilm-related, reversible inflammatory disease that can evolve into peri-implantitis if not adequately treated. The aim of the present randomized controlled clinical trial was to evaluate the efficacy of air-abrasive powder as compared to chlorhexidine (CHX) for the treatment of peri-implant mucositis, in terms of clinical and patient-reported outcomes (PROMs) and occurrence of peri-implantitis 12 months after treatment., Methods: In the control group, full-mouth calculus and plaque removal was performed with ultrasound and manual devices, and a 1.0% CHX gel was applied; in the test group, supra- and subgingival biofilm removal was performed using erythritol powder with a dedicated nozzle and calculus removal was performed with ultrasonic instruments if needed. Bleeding and plaque indexes, peri-implant probing depth and tissue level were measured at 1 week, and 1, 3, 6 and 12 months after treatment, while PROMs were evaluated up to 7 days after treatment., Results: Among 80 included implants, 70 were analysed at 12 months follow-up (30 in the test group, 40 in the control group, and 20 subjects). Success rates (implant-level) in terms of bleeding index were significantly different between the test (96.7%) and control group (92.5%); as for PROMs, only taste sensation was significantly better in the test group. The test group was significantly correlated to the smallest changes in peri-implant probing depth between baseline and 3 months., Conclusions: The study showed that both treatment strategies are effective. This suggests that the use of air-abrasive powders could be used as an alternative biofilm removal method instead of adjunctive treatments with antiseptics., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Although artificial and non-nutritive sweeteners are widely used and generally recognized as safe by the US and European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term cardiovascular disease-relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly used sweetener, are clinically associated with heightened incident cardiovascular disease risks and enhance thrombosis potential in vitro and in animal models. Effects of dietary erythritol on thrombosis phenotypes in humans have not been examined., Methods: Using a prospective interventional study design, we tested the impact of erythritol or glucose consumption on multiple indices of stimulus-dependent platelet responsiveness in healthy volunteers (n=10 per group). Erythritol plasma levels were quantified with liquid chromatography tandem mass spectrometry. Platelet function at baseline and following erythritol or glucose ingestion was assessed via both aggregometry and analysis of granule markers released., Results: Dietary erythritol (30 g), but not glucose (30 g), lead to a >1000-fold increase in erythritol plasma concentration (6480 [5930-7300] versus 3.75 [3.35-3.87] μmol/L; P <0.0001) and exhibited acute enhancement of stimulus-dependent aggregation responses in all subjects, agonists, and doses examined. Erythritol ingestion also enhanced stimulus-dependent release of the platelet dense granule marker serotonin ( P <0.0001 for TRAP6 [thrombin activator peptide 6] and P =0.004 for ADP) and the platelet α-granule marker CXCL4 (C-X-C motif ligand-4; P <0.0001 for TRAP6 and P =0.06 for ADP). In contrast, glucose ingestion triggered no significant increases in stimulus-dependent release of either serotonin or CXCL4., Conclusions: Ingestion of a typical quantity of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity in healthy volunteers, raising concerns that erythritol consumption may enhance thrombosis potential. Combined with recent large-scale clinical observational studies and mechanistic cell-based and animal model studies, the present findings suggest that discussion of whether erythritol should be reevaluated as a food additive with the Generally Recognized as Safe designation is warranted., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04731363., Competing Interests: S.L. Hazen and Z. Wang report being named as coinventors on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics, all unrelated to the subject and contents of this article. S.L. Hazen and Z. Wang also report having received royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Procter & Gamble and Cleveland HeartLab, Inc, a fully owned subsidiary of Quest Diagnostics. S.L. Hazen is a paid consultant at Zehna Therapeutics, has received research funds from Zehna Therapeutics, and is eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics and therapeutics from Zehna Therapeutics. W.H.W. Tang reports being a consult at Sequana Medical A.G., Cardiol Therapeutics, Zehna Therapeutics, Genomics plc, Boston Scientific, WhiteSwell, Bristol Myers Squibb, Intellia Therapeutics, Alexion Pharmaceuticals, Alleviant Medical, CardiaTec Biosciences, Salubris Biotherapeutics, BioCardia, and has received honoraria from American Board of Internal Medicine, Belvoir Media Group, and Springer Nature. The other authors report no conflicts.

Introduction: High sugar intake is associated with many chronic diseases. However, non-caloric sweeteners (NCSs) might fail to successfully replace sucrose due to the mismatch between their rewarding sweet taste and lack of caloric content. The natural NCS erythritol has been proposed as a sugar substitute due to its satiating properties despite being non-caloric. We aimed to compare brain responses to erythritol vs. sucrose and the artificial NCS sucralose in a priori taste, homeostatic, and reward brain regions of interest (ROIs)., Methods: We performed a within-subject, single-blind, counterbalanced fMRI study in 30 healthy men (mean ± SEM age:24.3 ± 0.8 years, BMI:22.3 ± 0.3 kg/m2). Before scanning, we individually matched the concentrations of both NCSs to the perceived sweetness intensity of a 10% sucrose solution. During scanning, participants received 1 mL sips of the individually titrated equisweet solutions of sucrose, erythritol, and sucralose, as well as water. After each sip, they rated subjective sweetness liking., Results: Liking ratings were significantly higher for sucrose and sucralose vs. erythritol (both pHolm = 0.0037); water ratings were neutral. General Linear Model (GLM) analyses of brain blood oxygen level-depended (BOLD) responses at qFDR<0.05 showed no differences between any of the sweeteners in a priori ROIs, but distinct differences were found between the individual sweeteners and water. These results were confirmed by Bayesian GLM and machine learning-based models. However, several brain response patterns mediating the differences in liking ratings between the sweeteners were found in whole-brain multivariate mediation analyses. Both subjective and neural responses showed large inter-subject variability., Conclusion: We found lower liking ratings in response to oral administration of erythritol vs. sucrose and sucralose, but no differences in neural responses between any of the sweeteners in a priori ROIs. However, differences in liking ratings between erythritol vs. sucrose or sucralose are mediated by multiple whole-brain response patterns., Competing Interests: Declaration of competing interest All authors certify no conflict of interest. This research has been funded by the Research Foundation - Flanders (FWO) [grant number G0D2420N, 2020]., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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.

Diabetes mellitus (DM) is a serious metabolic disorder, where impaired postprandial blood glucose regulation often leads to severe health complications. The natural chemical erythritol is a C4 polyol approved by the U.S. Food and Drug Administration for use as a sweetener. Here, we examined a potential role for erythritol in the control of postprandial blood glucose levels in DM. An anti-postprandial hyperglycemia effect upon erythritol administration (500 mg kg -1 ) was demonstrated in alloxan-induced DM model mice by monitoring changes in blood glucose after intragastric administration of drugs and starch. We also found that erythritol most likely exerts its anti-postprandial hyperglycemic activities by inhibiting α-glucosidase in a competitive manner. This was supported by enzyme activity assays and molecular modeling experiments. In the latter experiments, it was possible to successfully dock erythritol into the catalytic pocket of α-glucosidase, with the resultant interaction likely driven by electrostatic interactions involving Asp215, Asp69, and Arg446 residues. This study suggests that erythritol may not only serve as a glucose substitute but also be a useful agent in the treatment of DM to help manage postprandial blood glucose levels.

Background: Peri-implantitis is a frequent disease that may lead to implant loss. The aim of this case series was to evaluate the clinical results of a new non-surgical treatment protocol., Methods: Fifteen patients with dental implants affected by peri-implantitis were treated with a multiple anti-infective non-surgical treatment (MAINST) which included two steps: 1) supra-gingival decontamination of the lesion and sub-gingival treatment with a controlled-release topical doxycycline; 2) after one week, a session of supra and sub gingival air polishing with Erythritol powder and ultrasonic debridement (where calculus was present) of the whole oral cavity was performed along with a second application of topical doxycycline around the infected implant. Primary outcome measures were: implant failure; complications and adverse events; recurrence of peri-implantitis; secondary outcome measure were presence of Plaque (PI), Bleeding on Probing (BOP), Probing Pocket Depth (PPD). Recession (REC), Relative Attachment level (RAL)., Results: Neither implant failure nor complications nor adverse events were reported. Statistically (P<0.01) and clinically significant reductions between baseline and 1 year of PI (100% vs. 13.9%, 95% CI: 72.4% to 93.7%); BOP (98.5% vs. 4.5%, 95% CI: 85.4% to 98.5%) and PPD (7.89 vs. 3.16 mm, 95% CI: -5.67 to -3.77), were detected. At baseline, all 15 patients had a PPD>5 mm at the affected implant(s), whereas only 3.7% at 3-month follow-up a PPD>5 mm, and none at 6 and 12 months., Conclusions: Within the limits of this study, the MAINST protocol showed improvement of clinical parameters for the treatment of peri-implantitis, which were maintained for up to 12 months.

Background: The purpose of this in vitro study was to evaluate the antibiofilm activity of a novel air-polishing powder consisting of erythritol and chlorhexidine, assessing its ability to reduce previously grown microbial biofilm and to prevent biofilm formation on titanium surfaces., Methods: Clinical strains of Staphylococcus aureus, Pseudomonas aeruginosa, Bacteroides fragilis and Candida albicans isolated from peri-implantitis lesions were used. Biofilm was grown on sandblasted titanium discs and treated with erythritol/chlorhexidine. The antimicrobial activity was evaluated by determining the minimum inhibitory concentration and the minimum microbicidal concentration. The antibiofilm activity was assessed by semiquantitative spectrophotometric assay and by confocal laser scanning microscopy., Results: Erythritol/chlorhexidine displayed an inhibitory and a microbicidal activity against all the tested strains. The spectrophotometric analysis showed that the treatment was effective in both reducing the previously developed biofilm and decreasing biofilm formation on titanium surfaces. Confocal laser scanning microscopy analysis showed a significant reduction of the total biofilm volume, with an increase of the percentage of dead cells of all the microorganisms tested., Conclusions: Erythritol/chlorhexidine displayed significant antimicrobial and antibiofilm activity against microorganisms isolated from peri-implantitis lesions. Due to its properties, it might represent a promising approach for the prevention and treatment of peri-implant diseases associated to microbial biofilm infections., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Polyols, also known as sugar alcohols, are widely used in the formulation of tooth-friendly and reduced-calorie foods. Considering the significant health benefits of polyols in products formulated for human use, there is increased interest in evaluating potential uses in companion animal applications. Erythritol and xylitol are two polyols which are currently widely used in products ranging from reduced-sugar foods to personal care and cosmetics. Published studies have shown that both of these compounds are well-tolerated in rodents. Their toxicity profiles differ when comparing canine safety data. Doses of xylitol as low as 0.15 g/kg-BW in dogs can result in life-threatening hypoglycemia and acute liver failure, whereas erythritol is well-tolerated in dogs with reported No Adverse Effect Levels upwards of 5 g/kg-BW/day in repeat-dose studies. While pivotal studies substantiating the safe use of erythritol in humans have been published, there are limited published studies to support the safe use of erythritol in dogs. Here we present the results of an acute oral and a sub-chronic oral toxicity study in Beagle dogs. Given the potential health benefits of oral products formulated with erythritol and the data presented herein substantiating the safe use in dogs, erythritol can be safely used in products for canines., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

With the increasing prevalence of obesity and a possible association with increasing sucrose consumption, nonnutritive sweeteners are gaining popularity. Given that some studies indicate that artificial sweeteners might have adverse effects, alternative solutions are sought. Xylitol and erythritol have been known for a long time and their beneficial effects on caries prevention and potential health benefits in diabetic patients have been demonstrated in several studies. Glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) are released from the gut in response to food intake, promote satiation, reduce gastric emptying (GE), and modulate glucose homeostasis. Although glucose ingestion stimulates sweet taste receptors in the gut and leads to incretin and gastrointestinal hormone release, the effects of xylitol and erythritol have not been well studied. Ten lean and 10 obese volunteers were given 75 g of glucose, 50 g of xylitol, or 75 g of erythritol in 300 ml of water or placebo (water) by a nasogastric tube. We examined plasma glucose, insulin, active GLP-1, CCK, and GE with a [(13)C]sodium acetate breath test and assessed subjective feelings of satiation. Xylitol and erythritol led to a marked increase in CCK and GLP-1, whereas insulin and plasma glucose were not (erythritol) or only slightly (xylitol) affected. Both xylitol and erythritol induced a significant retardation in GE. Subjective feelings of appetite were not significantly different after carbohydrate intake compared with placebo. In conclusion, acute ingestion of erythritol and xylitol stimulates gut hormone release and slows down gastric emptying, whereas there is no or only little effect on insulin release., (Copyright © 2016 the American Physiological Society.)

Objective: To assess the effect of daily consumption of erythritol, xylitol, and sorbitol candies on caries development in mixed dentition during a 3-year intervention and 3 years after the intervention., Methods: 485 Estonian first- and second-grade primary school children participated. Children were randomly allocated to an erythritol, xylitol, or sorbitol (control) group. Polyol-containing candies were administered on school days with a daily polyol consumption of 3 × 2.5 g. Yearly, caries development was assessed by calibrated dentists using the ICDAS criteria. Six years after initiation of the study and 3 years after cessation of daily polyol consumption, 420 participants were re-examined to identify potential long-term effects of polyol consumption. Survival curves were generated at the end of the intervention period and 3 years after intervention. The model included age of the subjects, schools, tooth surface ages and years of surface exposure to intervention. ICDAS scoring system-based events included enamel/dentin caries development, dentin caries development, increase in caries score, and dentist intervention., Results: At the end of the intervention, time to enamel/dentin caries development, dentin caries development, increase in caries score, and dentist intervention were significantly longer in the erythritol group as compared to the sorbitol group. Except for increase in caries score, all effects persisted 3 years after cessation of daily polyol consumption., Conclusions: A caries-preventive effect of 3-year erythritol consumption as compared to sorbitol was established in children with mixed dentition. The effect persisted up to 3 years after the end of the intervention., (© 2016 S. Karger AG, Basel.)

Owing to the special characteristics and abilities polymeric networks have received special interest for a range of biomedical applications especially for drug delivery systems. This study was devoted to preparation of new polymeric compounds based on maleic anhydride and 3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5) undecane copolymer (poly maleic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5) undecane) (PMAU) patterned as a network for bioconjugation and tested as drug carrier systems. The PMAU copolymer was improved in its functionality by opening the maleic anhydride ring with different amounts of erythritol, which is free of side effects in regular use and a multifunctional compound, and also confers antioxidant character for the new compounds. The new polymeric matrices were loaded with acetaminophen, codeine and their fixed dose combinations. The investigation demonstrated the capability of the new structures to be used as polymer networks for linking bioactive compounds and to perform controlled delivery. The physico-chemical investigations--Fourier transform infrared spectroscopy (FTIR) spectra, contact angle, zeta potential (ZP - z, PMAU and its derivatives samples loaded with medicines present decreased values of zeta potential attesting the bioconjugate formation and as well their stability), and hydrodynamic radius, near infrared chemical imaging evaluation (new specific bands being registered for bio-conjugate with acetaminophen around of 1150-1200 nm and 1700 nm, and also between 1150 and 1200 nm in case of the codeine bio-conjugate), scanning electron microscopy (SEM) studies, X-ray diffraction analysis--evidenced the formation of the bioconjugates in relation to the chemical composition of the polymer matrices, while in vitro release study and in vivo tests confirm the capacity for drug delivery of the prepared bioactive systems., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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 characterize the physical characteristics of a new low abrasive erythritol powder (EPAP) and to evaluate its influence on the clinical and microbiologic parameters over a period of 6 months in patients undergoing supportive periodontal therapy (SPT)., Method and Materials: Prior to the clinical application, the particle size and abrasion level of EPAP were compared to glycine air-polishing powder (GPAP) ex vivo. Subsequently, 40 chronic periodontitis patients previously enrolled in SPT were randomly assigned into two groups for the treatment with subgingival EPAP or repeated scaling and root planing (SRP). At baseline (BL), bleeding on probing positive (BOP+) sites with probing pocket depth (PPD) of ≥ 4 mm but no detectable calculus were defined as study sites. During SPT, these sites were either treated by EPAP or SRP at BL, 3, and 6 months (3M, 6M). When indicated, additional SRP was provided. Plaque Index, BOP, PPD, clinical attachment level (CAL), and subgingival plaque were evaluated at BL and 6M., Results: EPAP yielded lower abrasiveness and smaller particle sizes when compared to GPAP. In 38 patients completing the study, EPAP and SRP resulted in significant reductions of BOP% (EPAP, 40.45%; SRP, 42.53%), PPD (EPAP, -0.67; SRP, -0.68), and increase of CAL (EPAP, 0.48; SRP, 0.61) while at 6M no statistically significant between-group differences were observed (P > .05). Microbiologic evaluation revealed minor shifts in the composition of the subgingival biofilm without influence on periodontopathogenic bacteria., Conclusion: The subgingival use of EPAP by means of an air-polishing device may be considered safe and may lead to comparable clinical and microbiologic outcomes to those obtained with SRP., Clinical Relevance: The subgingival use of EPAP appears to represent a promising modality for the removal of subgingival biofilm during SPT.

Background: Biofilm removal plays a central role in the prevention of periodontal and peri-implant diseases associated with microbial infections. Plaque debridement may be accomplished by air polishing using abrasive powders. In this study, a new formulation consisting of erythritol and chlorhexidine is compared with the standard glycine powder used in air-polishing devices. Their in vitro antimicrobial and antibiofilm effects on Staphylococcus aureus, Bacteroides fragilis, and Candida albicans are investigated., Methods: Biofilm was allowed to grow on sandblasted titanium disks and air polished with glycine or erythritol-chlorhexidine powders. A semiquantitative analysis of biofilm by spectrophotometric assay was performed. A qualitative analysis was also carried out by confocal laser scanning microscopy. Minimum inhibitory concentrations and minimum microbicidal concentrations were evaluated, together with the microbial recovery from the residual biofilm after air-polishing treatment., Results: The combination of erythritol and chlorhexidine displayed stronger antimicrobial and antibiofilm activity than glycine against all microbial strains tested., Conclusion: Air polishing with erythritol-chlorhexidine seems to be a viable alternative to the traditional glycine treatment for biofilm removal.

Objectives: To evaluate repeated subgingival air-polishing in residual pockets with a new erythritol powder containing 0.3% chlorhexidine., Material and Methods: Single-centre, examiner masked, randomized clinical trial of 12 months with a two-arm, within-subject parallel design. Fifty patients in periodontal maintenance were monitored in 3-month intervals. At months 0, 3, 6 and 9, all sites presenting with a probing depth (PD) >4 mm were subject to subgingival air-polishing (test side) or ultrasonic debridement (control side). The primary endpoint was presence/absence of PD >4 mm after 12 months., Results: Totally 6918 sites were monitored at baseline, 457 of them had a PD >4 mm (range 5-9 mm). The number of pockets >4 mm per subject, PD and bleeding on probing were significantly lower at month 12. Differences between test and control were not significant. There was a significant difference in favour of air-polishing for the perception of pain/discomfort. Differences of frequencies at >1000 and >100,000 cells/ml of six microorganisms between baseline and month 12 were not significant. At month 12, test sites were less frequently positive for Aggregatibacter actinomycetemcomitans at >1000 cells/ml than controls, and counts never exceeded 100,000 cells/ml., Conclusions: Repeated subgingival air-polishing reduced the number of pockets >4 mm similar to ultrasonic debridement. It was safe and induced less pain., (© 2014 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.)

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.

Objective: The objective of the present paper is to report results from oral biologic studies carried out in connection with a caries study., Methods: Samples of whole-mouth saliva and dental plaque were collected from initially 7- to 8-year-old subjects who participated in a 3-year school-based programme investigating the effect of the consumption of polyol-containing candies on caries rates. The subjects were randomized in three cohorts, consumed erythritol, xylitol, or sorbitol candies. The daily polyol consumption from the candies was approximately 7.5 g., Results: A significant reduction in dental plaque weight from baseline (p<0.05) occurred in the erythritol group during almost all intervention years while no changes were found in xylitol and sorbitol groups. Usage of polyol candies had no significant or consistent effect on the levels of plaque protein, glucose, glycerol, or calcium, determined yearly in connection with caries examinations. After three years, the plaque of erythritol-receiving subjects contained significantly (p<0.05) lower levels of acetic acid and propionic acid than that of subjects receiving xylitol or sorbitol. Lactic acid levels partly followed the same pattern. The consumption of erythritol was generally associated with significantly (p<0.05) lower counts of salivary and plaque mutans streptococci compared with the other groups. There was no change in salivary Lactobacillus levels., Conclusion: Three-year consumption of erythritol-containing candies by initially 7- to 8-year old children was associated with reduced plaque growth, lower levels of plaque acetic acid and propionic acid, and reduced oral counts of mutans streptococci compared with the consumption of xylitol or sorbitol candies., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this prospective, randomized, controlled clinical study was to compare the clinical outcomes of the subgingival treatment with erythritol powder by means of an air-polishing (EPAP) device and of scaling and root planing (SRP) during supportive periodontal therapy (SPT)., Method and Materials: 40 patients enrolled in SPT were randomly assigned to two groups of equal size. Sites had to show signs of inflammation (bleeding on probing [BOP]-positive) and a probing pocket depth (PPD) of ≥ 4 mm, however, without presence of detectable subgingival calculus. During SPT, these sites were treated with EPAP or SRP, respectively. Full mouth and site-specific plaque indices, BOP, PPD, and clinical attachment level (CAL) were recorded at baseline (BL) and at 3 months, whereas the percentage of study sites positive for BOP (BOP+) was considered as primary outcome variable. Additionally, patient comfort using a visual analog scale (VAS) and the time needed to treat per site was evaluated., Results: At 3 months, mean BOP level measured 45.1% at test sites and 50.6% at control sites, respectively, without a statistically significant difference between the groups (P > .05). PPD and CAL slightly improved for both groups with comparable mean values at 3 months. Evaluation of patient tolerance showed statistically significantly better values among patients receiving the test treatment (mean VAS [0-10], 1.51) compared to SRP (mean VAS [0-10], 3.66; P = .0012). The treatment of test sites was set to 5 seconds per site. The treatment of control sites, on the other hand, lasted 85 seconds on average., Conclusion: The new erythritol powder applied with an air-polishing device can be considered a promising modality for repeated instrumentation of residual pockets during SPT., Clinical Relevance: With regard to clinical outcomes during SPT, similar results can be expected irrespective of the two treatment approaches of hand instrumentation or subgingival application of erythritol powder with an air-polishing device in sites where only biofilm removal is required.

Purpose: To evaluate the efficacy of osmoprotectants on prevention and treatment of dry eye in a murine model., Methods: Dry eye was induced in mice by using an intelligently controlled environmental system (ICES). Osmoprotectants betaine, L-carnitine, erythritol, or vehicle (PBS) were topically administered to eyes four times daily following two schedules: schedule 1 (modeling prevention): dosing started at the beginning of housing in ICES and lasted for 21 or 35 days; schedule 2 (modeling treatment): dosing started after ICES-housed mice developed dry eye (day 21), continuing until day 35. Treatment efficacy was evaluated for corneal fluorescein staining; corneal epithelial apoptosis by TUNEL and caspase-3 assays; goblet cell numbers by PAS staining; and expression of inflammatory mediators, TNF-α, IL-17, IL-6, or IL-1β by using RT-PCR on days 0, 14, 21, and/or 35., Results: Compared with vehicle, prophylactic administration of betaine, L-carnitine, or erythritol significantly decreased corneal staining and expression of TNF-α and IL-17 on day 21 (schedule 1). Treatment of mouse dry eye with osmoprotectants significantly reduced corneal staining on day 35 compared with day 21 (schedule 2). Relative to vehicle, L-carnitine treatment of mouse dry eye for 14 days (days 21 to 35) resulted in a significant reduction in corneal staining, number of TUNEL-positive cells, and expression of TNF-α, IL-17, IL-6, or IL-1β, as well as significantly increased the number of goblet cells., Conclusions: Topical application of betaine, L-carnitine, or erythritol systematically limited progression of environmentally induced dry eye. L-carnitine can also reduce the severity of such dry-eye conditions.

Purpose: To compare a treatment containing carboxymethylcellulose (CMC) and the osmoprotective (OsPr) compatible osmolytes erythritol, L-carnitine, and glycerin (OsPr-CMC) with a standard sodium hyaluronate (Na-HY) formulation in patients with dry eye disease., Methods: This was a 3-month, phase III, noninferiority study. Patients were randomized 1:1 to receive OsPr-CMC (OPTIVE®) or Na-HY (VISMED®). The primary efficacy outcome was the mean change from baseline in total ocular staining at day 35, scored using the 15-point Oxford scale. Noninferiority was assessed using the adjusted means. The secondary efficacy outcome was change in ocular surface disease index (OSDI) score from baseline to day 35. Other outcomes included tear osmolarity, Schirmer-I test score, OSDI, ease of use, patient acceptability, tolerability, and safety., Results: A total of 82 patients were randomized. The primary efficacy analysis was per protocol (OsPr-CMC, n=37; Na-HY, n=29). OsPr-CMC was noninferior to Na-HY in terms of adjusted mean change (SE) in ocular staining score at day 35: -2.0 (0.33) with OsPr-CMC vs -1.7 (0.37) with Na-HY. Similar improvements were seen in tear osmolarity, Schirmer-I test score, OSDI, and ocular staining for OsPr-CMC and Na-HY. More patients treated with OsPr-CMC vs Na-HY liked using their eyedrops, reported that their eyes felt comfortable, and found the treatment easy to use. Both treatments were well tolerated, with no serious treatment-related adverse events., Conclusions: Compared with Na-HY, OsPr-CMC was noninferior in terms of efficacy and safety, preferred by patients, and easier to use. Osmoprotection using OsPr-CMC therefore represents a viable option for dry eye disease management.

Objective: Xylitol studies suggest caries reductions in the order of 50%. Based on animal/microbial studies, erythritol potentially has caries-preventive properties. However, clinical studies are required to confirm this. The aim of the study was to investigate the additional caries-preventive effect of xylitol/maltitol and erythritol/maltitol lozenges delivered at school, relative to controls receiving comprehensive prevention, in a low-caries prevalence population., Methods: A 4-year, cluster-randomized, double-blinded clinical trial. Five hundred and seventy-nine 10-year-old consenting subjects from 21 schools were randomly assigned to one of five groups. Four groups used the lozenges on school days, in three teacher-supervised sessions daily, over 1 or 2 years. The daily amount was 4.7 g/4.6 g for xylitol/maltitol and 4.5 g/4.2 g for erythritol/maltitol. The groups received free examinations and care in the public health centre. Four hundred and ninety-six children were analysed. The main outcome measure was dentin caries increment based on a clinical examination at 4 years since the start. The groups were compared in relation to the increment using hierarchical logistic regression to adjust for potential clustering., Results: Use of xylitol/maltitol or erythritol/maltitol lozenges did not result in caries reduction. A strong relationship between baseline caries prevalence and the 4-year increment was observed (OR = 7.38; 95% CI: 3.78-14.41)., Conclusions: The results suggest that in relatively low-caries conditions the school-based use of xylitol/maltitol or erythritol/maltitol lozenges would not have additional caries-preventive effect when compared with comprehensive prevention., (© 2011 The Authors. International Journal of Paediatric Dentistry © 2011 BSPD, IAPD and Blackwell Publishing Ltd.)

Consumption of a large amount of dietary fructose induces gastrointestinal intolerance, and glucose has been known as an enhancer of fructose absorption. Erythritol is a nonglycemic sugar alcohol, and it has been suggested that erythritol is absorbed paracellularly. It was hypothesized that paracellular absorption of erythritol could also enhance paracellular absorption of fructose in healthy adults. This is one of the proposed pathways for how additional glucose enhances the absorption of fructose. Thirty-seven nondiabetic, healthy adults participated in a randomized, double-masked, controlled crossover study. After an overnight fast, participants consumed beverages containing either 50 g fructose and 50 g glucose, 50 g fructose and 33.3 g erythritol (an equimolar concentration of fructose), or 50 g fructose alone. Breath hydrogen response was determined for 8 hours postprandially. Gastrointestinal intolerance symptoms and the number and consistency of bowel movements were recorded for 24 hours postprandially. The breath hydrogen area under the curve (AUC) of the fructose and erythritol beverage was 2 times the AUC of the fructose beverage and 8.75 times the AUC of the fructose and glucose beverage (P < .001, respectively). Compared with fructose and glucose beverage and fructose alone, frequency of watery stools increased (P < .05) and gastrointestinal tolerance worsened (P < .05) when participants consumed fructose and erythritol. These data suggest that coingestion of equimolar concentrations of fructose and erythritol increased carbohydrate malabsorption., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Dental caries is a diet-associated disease which continues to be a serious health problem in most industrialized and developing countries. Strategies to maximize caries prevention should automatically consider the use of sugar substitutes. It is important that public health authorities are made cognizant of the availability of new polyol-type sugar substitutes., Review Summary: Clinical studies have shown that xylitol, a natural, physiologic sugar alcohol of the pentitol type, can be used as a safe and effective caries-limiting sweetener. Habitual use of xylitol-containing food and oral hygiene adjuvants has been shown to reduce the growth of dental plaque, to interfere with the growth of caries-associated bacteria, to decrease the incidence of dental caries, and to be associated with remineralization of caries lesions. Numerous public regulatory bodies have endorsed the use of xylitol as a caries-limiting agent. Other sugar alcohols that have been successfully used as sugar substitutes include D-glucitol (sorbitol), which, however, owing to its hexitol nature, normally has no strong effect on the mass and adhesiveness of bacterial plaque and on the growth of mutans streptococci. A tetritol-type alditol, erythritol, has shown potential as a non-cariogenic sugar substitute. Combinations of xylitol and erythritol may reduce the incidence of caries more effectively than either alditol alone., Conclusions: Partial sugar substitution with polyols is an important dietary tool in the prevention of dental caries that should be used to enhance existing fluoride-based caries prevention programmes. The most effective method of conveying this information to the public is through a proper health claim for these alditols in food labelling. The present review summarizes clinical and biochemical aspects of the above three dietary polyols and emphasizes the role of sugar substitution as a potential health-promoting strategy., (Copyright © 2011 S. Karger AG, Basel.)

In order to evaluate the effect of preparation method on the properties of orally disintegrating (OD) tablets, OD tablets were prepared by compressing a mixture of high melting point sugar alcohol (HMP-SA) and low melting point sugar alcohol (LMP-SA) and subsequent heating. In the direct compression method (DCM) where the LMP-SA was added as a powder, both hardness and disintegration time were increased by decreasing the particle size of the LMP-SA. In the wet granule compression method (WGCM), where the LMP-SA was added as an aqueous binder solution, the tablets became harder with less heating compared to tablets prepared by DCM. Using 1% xylitol as the LMP-SA provided tablets with sufficient hardness when prepared by WGCM, as opposed to DCM where 5% xylitol was necessary to prepare tablets with similar hardness. These results suggest that uniformly distributed LMP-SA on the surface of HMP-SA particles in WGCM might diffuse more easily during the heating process compared to mechanically mixed LMP-SA in DCM, resulting in an increase in tablet hardness even with a short heating time and low content of LMP-SA. In addition, disintegration and hardness stability of the tablets were affected by the LMP-SA content when prepared by WGCM, suggesting that the LMP-SA content should be regulated to assure the stability of OD tablet characteristics.

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.

The ingestion of a sufficiently large amount of non-digestible and/or non-absorbable sugar substitutes causes overt diarrhea. The objective is to estimate the non-effective dosage that does not cause transitory diarrhea for xylitol, lactitol, and erythritol in healthy subjects. Twenty-seven males and 28 females gave informed and written consent to participate, were selected, and participated in the study. The oral dose levels of xylitol were 10, 20, 30, 40 and 50 g, while those of lactitol were 10, 20, 30, and 40 g. Those of erythritol were 20, 30, 40 and 50 g. The test substance was ingested in 150 mL of water 2-3 h after a meal. The ingestion order progressed from the smallest to larger amounts, and stopped at the dose that caused diarrhea, or at the largest dose level to be set up. The non-effective dose level of xylitol was 0.37 g/kg B.W. for males and 0.42 g/kg B.W. for females. That of lactitol was 0.25 g/kg B.W. for males and 0.34 g/kg B.W. for females, and that of erythritol was 0.46 g/kg B.W. for males and 0.68 g/kg B.W. for females. These results appear reasonable, because xylitol is poorly absorbed from the small intestine, and the absorption rate is less than that of erythritol, while lactitol is not hydrolyzed. Non-digestible and/or non-absorbable sugar alcohols and oligosaccharides with beneficial health effects inevitably cause overt diarrhea. The estimation of the non-effective dose level of these sugar substitutes is essential and important to produce processed foods that the consumer can use safely and with confidence.

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., (Copyright (c) 2005 S. Karger AG, Basel.)

Glucagon, a key regulatory element of glycogen metabolism, is known to be effective in the clinical treatment of hypoglycemia and the maintenance of normal circulating glucose levels in patients with total pancreatectomy, however the clinical use of this gut hormone has been restricted to parenteral administration. In this investigation, we prepared dry powder dosage forms of glucagon, which were formulated by mixing micronized glucagon particles and excipients with larger carrier particles. To achieve alveolar deposition for subsequent systemic absorption, a dry powder inhalant (DPI) of glucagon was size-reduced to a mass median diameter between 1 and 6 microm, as measured by laser diffraction analysis. The use of erythritol as both excipient and carrier in DPI of glucagon resulted in high and reproducible flowability and dispersibility of the powder mixtures, and therefore it provided a low dosing of the active substances. Distinct transpulmonary absorption of glucagon was confirmed after intratracheal administration of the glucagon dry powder to anesthetized rats, as evidenced by the increase in the blood glucagon and blood sugar levels. These results suggested the usefulness of an erythritol-based powder form of glucagon for systemic administration.

The effect of chewable saliva-stimulants on Streptococcus mutans levels in dental plaque and paraffin-stimulated whole saliva among participants who were mentally disabled was investigated. Over 64-days, 98 participants chewed one of four saliva-stimulating tablets five times/day. The tablets contained one of the following: xylitol (X) or sorbitol (S), or 1:1 mixtures of xylitol and erythritol (XE) or sorbitol and erythritol (SE). Consumption of xylitol and sorbitol in Groups X and S was 5.4 grams/day/ subject, and of each polyol in Groups XE and SE, consumption was 2.7 g/day/subject. Interproximal dental plaque and stimulated whole saliva were sampled at baseline, at Day 36, and Day 64. There was a statistically significant reduction of S. mutans in plaque and saliva counts in Groups X and XE. The percentage of S. mutans in total streptococci increased significantly in dental plaque in Group S but decreased in the other groups. The results suggest that xylitol-containing saliva stimulants may be more effective than sorbitol-containing products in controlling some caries-associated parameters in people who are mentally disabled. Also a relationship may exist between the pentitol-type xylitol and S. mutans, and erythritol may exert a specific biochemical effect on this organism, although further studies are needed.

It was investigated the influence of a diet supplemented with erithritol on dynamic of basal and postprandial glycemia, lipid levels, blood pressure, body weight in 30 patients with type 2 diabetes. The results indicated that supplementation of erithritol (30 g/day) in traditional hypocaloric diet did not decrease the efficacy of dietary therapy in patients with type 2 diabetes. After ingestion 30 g erithritol dissolved in 300 ml of water, blood glucose did not show a marked increase in compared with 30 g isomalt (control).

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.

The aim of the present study was to compare the ability of four dietary polyols to reduce bone resorption. Urinary excretion of 3H radioactivity from [3H]tetracycline-prelabeled rats was used as a marker of bone resorption. After prelabeling, the rats were divided randomly into five groups of 10, and fed for 1 mo a nonpurified diet that was supplemented in four groups with either xylitol, sorbitol, D-mannitol or erythritol, respectively, to give a polyol concentration of 1 mol/kg. Xylitol (42%), sorbitol (44%) and to a lesser degree D-mannitol (23%) decreased the excretion of 3H relative to the basal diet. The erythritol group, however, did not differ from the controls. Sorbitol caused continuous diarrhea, whereas in the other groups, intestinal adaptation took place during the 1st wk of polyol feeding. In conclusion, dietary xylitol, sorbitol and to a lesser degree D-mannitol supplementations in rats retard bone resorption, whereas dietary erythritol has no effect.

Objectives: To investigate the effect of an oral administration of erythritol on serum glucose and insulin levels in healthy subjects and estimate available energy of erythritol in human., Design: Ingestion of erythritol (0.3 g/kg body weight) or the same dose of glucose as a control., Setting: Omiya Research Lab., Nikken Chemicals Co., Japan., Subjects: 5 healthy male volunteers aged 45-58 years., Main Outcome Measures: Serum glucose, insulin and erythritol levels after erythritol ingestion. Urinary erythritol excretion., Results: Erythritol did not increase serum levels of glucose or insulin, while the same dose of glucose increased rapidly glucose and insulin levels within 30 min. Erythritol did not induce any significant effects on serum levels of total cholesterol, triacylglycerol, free fatty acids, Na, K and Cl. Also, urinary Na, K and Cl were not affected by erythritol ingestion. Serum levels of erythritol reached the maximum concentration of 426.5 +/- 113.4 micrograms/ml at 30 min and declined to 13.5 +/- 3.2 micrograms/ml at 24 h. Total urinary excretion of erythritol was 85.8 +/- 4.6% for 24 h and 90.3 +/- 4.5% for 48 h, respectively., Conclusions: Erythritol did not affect serum levels of glucose, insulin or other serum constituents. More than 90% of ingested erythritol was readily absorbed and excreted in urine without degradation. This fact suggests that available energy of erythritol in human is less than 1.7 kJ/g (0.4 kcal/g)., Descriptors: erythritol, glucose, insulin, low energy sweetener.

The metabolism and disposition of erythritol was studied using [14C]erythritol in rats. When [14C]erythritol was administered orally at a dose of 0.1 g/kg body wt to male rats, only 6% of the total radioactivity was excreted as expired 14CO2 and 88% was excreted in the urine within 24 h. The excreted metabolite in the urine consisted of a single component identified as intact [14C]erythritol. The excretion of 14CO2 and the incorporation ratios of radioactivity into tissues increased with the oral dosage. After rats were given an intravenous injection of [14C]erythritol, approximately 1% was excreted as 14CO2 and greater than 94% was excreted in the urine as intact [14C]erythritol. The excretion of 14CO2 within 24 h was increased to approximately 10% when [14C]erythritol was administered to rats that had been adapted to erythritol by feeding a diet containing 10% erythritol for 2 wk. When [14C]erythritol was incubated in vitro with the cecal contents from rats adapted to erythritol, greater than 20% was fermented to 14CO2 and 60% to short-chain fatty acids in 6 h. These results indicate that most orally administered erythritol was excreted in the urine without any degradation and that the remainder was transferred to the lower intestine and fermented by microbes.

The cytotoxicity of bleomycin (BLM) toward Chinese Hamster V79 and murine leukemia L1210 was extraordinarily potentiated in the presence of glycerol. The synergistic effect of glycerol emerged in combinations with BLM analogs (peplomycin and libromycin) as well, but not with other cytotoxic drugs such as adriamycin, neocarzinostatin, paraquat, hydrogen peroxide, and N-methyl-N-nitrosourea. The cytotoxicity of BLM and its analogs was potentiated by some polyhydric alcohols as intensely as by glycerol. Polyhydric alcohols containing more than two hydroxyl groups in the molecule were effective in V79 cells, and those containing more than three hydroxyl groups were effective in L1210 cells. The cellular uptake of [3H] peplomycin was not affected by glycerol. For antitumor activity, when 0.5 ml of glycerol (10%) and erythritol (10%) were combined with 2.0 mg/kg/day of BLM, the 5-day treatment of Ehrlich cell-bearing (i.p.) mice prolonged the life span by 244% and 282% (T/C), respectively. When a low dose of BLM (0.2 mg/kg/day) was combined with 0.5 ml of glycerol (20%) and erythritol (30%), the therapeutic gains were 1.82 and 1.88, respectively. These results suggest the possibility that the adjuvant treatment of BLM with polyhydric alcohols might be applied to the clinical treatment of cancerous peritonitis and pleuritis.

Lycurium [1,4-di-(methylsulfonyloxy-ethylamino)-1,4-didesoxy-erythrioldimethylsulfonate; R-74; NSC-122402] undergoes rapid hydrolysis in aqueous solutions. The concentration of the alkylating compound(s), demonstrated by the 4-(4'-nitrobenzyl)pyridine reaction, decreases approximately by 80% in 10 min following the dissolution of the drug in saline. In patients peak plasma concentration of radioactivity after the intracavitary injection of 14C-labelled Lycurim is observed between 4 and 6 h. It is assumed, therefore, that only a negligible amount of pharmacologically active alkylating compounds reaches the circulation after intracavitary application. This conclusion is supported by clinical experience showing that intracavitary administration of the same amount of Lycurim causes much milder systemic side-effects than intravenous injection. A dose escalation study was started to determine the applicability of Lycurim in the form of high volume intraperitoneal instillation ('belly bath') for the treatment of ovarian cancer.

Bile flow, erythritol clearance (measured after administration of 14-C-erythritol) and bile acid excretion were studied in 8 non-icteric patients operated upon for gallstone disease without biliary obstruction in whom a T-tube had been inserted. Bile flow increased from the 2nd (0.27 plus or minus SEM 0.01 ml/min) to the 7th (0.50 plus or minus SEM 0.05 ml/min) postoperative days and remained stable thereafter. Because the values obtained between the 7th and the 15th postoperative days (average: 0.46 plus or minus SEM 0.02 ml/min) were not lower and were of the same order of magnitude as those previously reported in the literature for quantitative bile collections, it was assumed that bile collection had been complete. Bile-to-plasma concentration ratio of erythritol was 0.77 plus or minus SEM 0.04. The regression line between erythritol clearance and bile flow had a slope of 0.99 (indicating that increments in clearance were followed by equivalent increments of flow) and an intercept for a zero-clearance of 0.11, suggesting a ductular/ductal secretion of 0.11 ml/min. The relationship between erythritol clearance and bile acid excretion suggested that canalicular bile was formed both of a bile acid-dependent flow (11 mul of water being excreted per mumol of bile acid secreted) and a bile acid-independent flow of 0.16 ml/min (or 35 percent of the average bile flow). These findings indicate that erythritol clearance provides a valid estimate of canalicular bile flow in man and that the three bile fractions previously postulated in animals (canalicular bile acid-dependent, canalicular bile acid-independent and ductular/ductal) may also be present in man.

Following surgical removal of papillary tumours of the bladder from 60 patients the authors performed short instillations of the bladder with LYCURIM. The histological picture revealed tumours in the stage O-A-B1 and grade I-II-III. In a control group (n = 129) 89 recidive cases were observed in 2 years. Out of the 60 patients of the LYCURIM group 19 (31.7%) were free of tumours for 2 years and 43 (71.7%) for 11/2 years. A transient cystitis which occurred with short application of the medicament was easily cured. Toxic effects on the blood picture were not observed.

An attempt was made to explore the quantitative relationship between the intestinal absorption data obtained from in vivo studies and in situ perfusion studies. The time course of the fraction remaining to be absorbed of L-glucose, erythritol, and urea in the small intestine following the intrajejunal administration to rats was described by a one-compartment model. Thus derived first-order intestinal absorption rate constants (ka) obtained from the in vivo studies in rats were compared with the membrane permeability clearances (CLa,m) estimated in a single-pass perfusion system. Not only were ka and CLa,m in the same increasing order of L-glucose less than erythritol less than urea, but also the operational luminal volumes given as CLa,m/ka were in agreement with the in vivo luminal volume of jejunum estimated by an inulin dilution method. This result suggests that the in vivo intestinal absorption rate (or ka) can be correlated with the intestinal membrane permeability (or CLa,m) by taking the in vivo luminal volume into account.

The authors gave Lycurim to 30 patients with malignant lymphoma (LLC--12 cases, Hodgkin's disease - 15 cases, reticulosarcoma - 2 cases and lymphosarcoma - 1 case). The patients were divided into three groups. Group I received only Lycurim, group II - Lycurim and prednisone, group III - Lycurim and Solcoseryl. Significant improvement was observed in 22 patients, with complete remission in 5 cases and partial in 17 cases. Leucopenia and thrombocytopenia precluding treatment were never observed in cases treated simultaneously with prednisone or Solcoseryl. The authors believe that the proportion of remissions may be increased combining Lycurim with vincristine, procarbazine and glycocorticosteroids (LOP or LOPP).

Mongrel dogs were prepared by cholecystectomy, ligation of the lesser pancreatic duct, and insertion of cannulas into the duodenum and stomach. During experiments on the unanesthetized dogs, bile was collected by cannulating the common bile duct through the duodenal cannula. Canalicular secretion was estimated by the biliary clearance of erythritol. Feeding caused increased bile flow, increased erythritol clearance, decreased bile salt concentration, and unchanged bile salt output. These findings indicate that feeding stimulated the bile salt-independent canalicular secretion.