Xylitol is prothrombotic and associated with cardiovascular risk.

BACKGROUND AND AIMS: The pathways and metabolites that contribute to residual cardiovascular disease risks are unclear. Low-calorie sweeteners are widely used sugar substitutes in processed foods with presumed health benefits. Many low-calorie sweeteners are sugar alcohols that also are produced endogenously, albeit at levels over 1000-fold lower than observed following consumption as a sugar substitute. METHODS: Untargeted metabolomics studies were performed on overnight fasting plasma samples in a discovery cohort (n = 1157) of sequential stable subjects undergoing elective diagnostic cardiac evaluations; subsequent stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses were performed on an independent, non-overlapping validation cohort (n = 2149). Complementary isolated human platelet, platelet-rich plasma, whole blood, and animal model studies examined the effect of xylitol on platelet responsiveness and thrombus formation in vivo. Finally, an intervention study was performed to assess the effects of xylitol consumption on platelet function in healthy volunteers (n = 10). RESULTS: In initial untargeted metabolomics studies (discovery cohort), circulating levels of a polyol tentatively assigned as xylitol were associated with incident (3-year) major adverse cardiovascular event (MACE) risk. Subsequent stable isotope dilution LC-MS/MS analyses (validation cohort) specific for xylitol (and not its structural isomers) confirmed its association with incident MACE risk [third vs. first tertile adjusted hazard ratio (95% confidence interval), 1.57 (1.12-2.21), P < .01]. Complementary mechanistic studies showed xylitol-enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma. In interventional studies, consumption of a xylitol-sweetened drink markedly raised plasma levels and enhanced multiple functional measures of platelet responsiveness in all subjects. CONCLUSIONS: Xylitol is associated with incident MACE risk. Moreover, xylitol both enhanced platelet reactivity and thrombosis potential in vivo. Further studies examining the cardiovascular safety of xylitol are warranted.

Secondary oxalosis induced by xylitol concurrent with lithium-induced nephrogenic diabetes insipidus: a case report.

BACKGROUND: Xylitol is an approved food additive that is widely used as a sweetener in many manufactured products. It is also used in pharmaceuticals. Secondary oxalosis resulting from high dietary oxalate has been reported. However, reported cases of oxalosis following xylitol infusion are rare. CASE PRESENTATION: A 39-year-old man with a 16-year history of organic psychiatric disorder was hospitalized for a laparoscopic cholecystectomy because of cholecystolithiasis. He had been treated with several antipsychotics and mood stabilizers, including lithium. The patient had polyuria (> 4000 mL/day) and his serum sodium levels ranged from 150 to 160 mmol/L. Urine osmolality was 141 mOsm/L, while serum arginine vasopressin level was 6.4 pg/mL. The patient was diagnosed with nephrogenic diabetes insipidus (NDI), and lithium was gradually discontinued. Postoperative urine volumes increased further to a maximum of 10,000 mL/day, and up to 10,000 mL/day of 5% xylitol was administered. The patient's consciousness level declined and serum creatinine increased to 4.74 mg/dL. This was followed by coma and metabolic acidosis. After continuous venous hemodiafiltration, serum sodium improved to the upper 140 mmol/L range and serum creatinine decreased to 1.25 mg/dL at discharge. However, polyuria and polydipsia of approximately 4000 mL/day persisted. Renal biopsy showed oxalate crystals and decreased expression of aquaporin-2 (AQP2) in the renal tubules. Urinary AQP2 was undetected. The patient was discharged on day 82 after admission. CONCLUSIONS: Our patient was diagnosed with lithium-induced NDI and secondary oxalosis induced by excess xylitol infusion. NDI became apparent perioperatively because of fasting, and an overdose of xylitol infusion led to cerebrorenal oxalosis. Our patient received a maximum xylitol dose of 500 g/day and a total dose of 2925 g. Patients receiving lithium therapy must be closely monitored during the perioperative period, and rehydration therapy using xylitol infusion should be avoided in such cases.

Xylitol for preventing acute otitis media in children up to 12 years of age.

BACKGROUND: Acute otitis media (AOM) is the most common bacterial infection among young children in the United States. There are limitations and concerns over its treatment with antibiotics and surgery and so effective preventative measures are attractive. A potential preventative measure is xylitol, a natural sugar substitute that reduces the risk of dental decay. Xylitol can reduce the adherence of Streptococcus pneumoniae (S pneumoniae) and Haemophilus influenzae (H influenzae) to nasopharyngeal cells in vitro. This is an update of a review first published in 2011. OBJECTIVES: To assess the efficacy and safety of xylitol to prevent AOM in children aged up to 12 years. SEARCH METHODS: We searched CENTRAL (to Issue 12, 2015), MEDLINE (1950 to January 2016), Embase (1974 to January 2016), CINAHL (1981 to January 2016), LILACS (1982 to January 2016), Web of Science (2011 to January 2016) and International Pharmaceutical Abstracts (2000 to January 2016). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs of children aged 12 years or younger where xylitol supplementation was compared with placebo or no treatment to prevent AOM. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials from search results, assessed and rated study quality and extracted relevant data for inclusion in the review. We contacted trial authors to request missing data. We noted data on any adverse events of xylitol. We extracted data on relevant outcomes and estimated the effect size by calculating risk ratio (RR), risk difference (RD) and associated 95% confidence intervals (CI). MAIN RESULTS: We identified five clinical trials that involved 3405 children for inclusion. For this 2016 update, we identified one new trial for inclusion. This trial was systematically reviewed but due to several sources of heterogeneity, was not included in the meta-analysis. The remaining four trials were of adequate methodological quality. In three RCTs that involved a total of 1826 healthy Finnish children attending daycare, there is moderate quality evidence that xylitol (in any form) can reduce the risk of AOM from 30% to around 22% compared with the control group (RR 0.75, 95% CI 0.65 to 0.88). Among the reasons for dropouts, there were no significant differences in abdominal discomfort and rash between the xylitol and the control groups. Xylitol was not effective in reducing AOM among healthy children during a respiratory infection (RR 1.13, 95% CI 0.83 to 1.53; moderate quality evidence) or among otitis-prone healthy children (RR 0.90, 95% CI 0.67 to 1.21; low-quality evidence). AUTHORS' CONCLUSIONS: There is moderate quality evidence showing that the prophylactic administration of xylitol among healthy children attending daycare centres can reduce the occurrence of AOM. There is inconclusive evidence with regard to the efficacy of xylitol in preventing AOM among children with respiratory infection, or among otitis-prone children. The meta-analysis was limited because data came from a small number of studies, and most were from the same research group.

Xylitol: a review on bioproduction, application, health benefits, and related safety issues.

Xylitol is a pentahydroxy sugar-alcohol which exists in a very low quantity in fruits and vegetables (plums, strawberries, cauliflower, and pumpkin). On commercial scale, xylitol can be produced by chemical and biotechnological processes. Chemical production is costly and extensive in purification steps. However, biotechnological method utilizes agricultural and forestry wastes which offer the possibilities of economic production of xylitol by reducing required energy. The precursor xylose is produced from agricultural biomass by chemical and enzymatic hydrolysis and can be converted to xylitol primarily by yeast strain. Hydrolysis under acidic condition is the more commonly used practice influenced by various process parameters. Various fermentation process inhibitors are produced during chemical hydrolysis that reduce xylitol production, a detoxification step is, therefore, necessary. Biotechnological xylitol production is an integral process of microbial species belonging to Candida genus which is influenced by various process parameters such as pH, temperature, time, nitrogen source, and yeast extract level. Xylitol has application and potential for food and pharmaceutical industries. It is a functional sweetener as it has prebiotic effects which can reduce blood glucose, triglyceride, and cholesterol level. This review describes recent research developments related to bioproduction of xylitol from agricultural wastes, application, health, and safety issues.

Biochemical perspectives of xylitol extracted from indigenous agricultural by-product mung bean (Vigna radiata) hulls in a rat model.

BACKGROUND: The production of xylitol from lignocellulosic material is of great interest around the world. It can be used as bulk sweetener and its possible lower energy value has increased acceptance for discerning consumers. Xylitol was produced from indigenous agricultural by-product (mung bean hulls) through Candida tropicalis fermentation. Further, xylitol incorporation at different concentrations (0, 100 and 200 g kg⁻¹) was carried out with the purpose of appraising the suitability and claimed health benefits of this dietetic ingredient in food products. Asserted biochemical perspectives of the xylitol intake were evaluated through biological studies for normal and streptozotocin-induced diabetic rats. RESULTS: The addition of xylitol significantly affected feed intake, weight gain, liver and cecum weight in both normal and diabetic rats. The biochemical profile of serum was improved with xylitol incorporation in the diet. Serum glucose, cholesterol and triglycerides levels were decreased depending on xylitol intake level. CONCLUSION: The results of the present study demonstrated that mung bean hulls have high potential as a new feedstock for xylitol production. In addressing the current concerns of obesity and diabetes, xylitol extracted from such agricultural waste should be considered in diet-based therapies for weight loss programmes.

Xylitol nasal spray for prevention of recurrent acute otitis media in children: A prospective two-center cohort study.

OBJECTIVES: The purpose of this study was to assess the effectiveness and safety of xylitol nasal spray as a prophylactic treatment for children with recurrent acute otitis media (AOM). METHODS: This is a prospective pilot study of children aged 1-4 years, diagnosed with recurrent AOM (at least three episodes in the three months before recruitment) between December 1, 2019 and January 31, 2023. Children were treated with nasal xylitol spray 2-3 times daily for 3 months. The number of AOM episodes and treatments administered were compared within 3-month intervals: before recruitment, during xylitol use, and during the three subsequent months. RESULTS: Of 68 children enrolled, 66 (97%) completed the follow-up, until July 2023. Thirty-eight (58%) were males. Sixty-three children (95%) were 12-24-months old. The mean number of AOM episodes during xylitol use, 1.06 (95% confidence interval [CI]: 0.73-1.39), was lower than in the 3-month previous interval, 4.12 (95% CI: 3.89-4.40), p < 0.001; and similar to that in the subsequent 3-month interval, 0.79 (95% CI: 0.49-1.08), p = 0.082. A similar pattern was observed in an analysis of the number of AOM episodes per patient month. The data were similar during spring and summer months as during autumn and winter months. Across the consecutive three-month intervals, decreases were observed in the mean number of AOM episodes treated with systemic antibiotics (3.35, 0.65, and 0.41), p < 0.001; and with topical antibiotics (1.38, 0.55, and 0.32), p < 0.001. No major side effects were recorded. CONCLUSIONS: The findings support the effectiveness and safety of nasal xylitol spray, for preventing recurrent AOM in children aged 1-4 years.

Xylitol for preventing acute otitis media in children up to 12 years of age.

BACKGROUND: Acute otitis media (AOM) is the most common bacterial infection among young children in the United States with limitations and concerns over its treatment with antibiotics and surgery. Therefore, effective preventative measures are attractive. A potential preventative measure is xylitol, a natural sugar substitute that reduces the risk for dental decay. Xylitol can reduce the adherence of Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae (H. influenzae) to nasopharyngeal cells in vitro. OBJECTIVES: To assess the efficacy and safety of xylitol to prevent AOM in children up to 12 years old. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to August Week 1, 2011), EMBASE (1974 to August 2011), CINAHL (1982 to August 2011), Health and Psychosocial Instruments (1985 to August 2011), Healthstar (OVID) (1966 to August 2011) and International Pharmaceutical Abstracts (2000 to August 2011). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs of children aged 12 years or younger where xylitol supplementation was compared to placebo or no treatment to prevent AOM. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials from search results, assessed and rated study quality and extracted relevant data for inclusion in the review. We contacted trial authors to request missing data. We noted data on any adverse events of xylitol. We extracted data on relevant outcomes and estimated the effect size by calculating risk ratio (RR), risk difference (RD) and associated 95% confidence intervals (CI). MAIN RESULTS: We identified four studies of adequate methodological quality that met our eligibility criteria. In three RCTs with a total of 1826 healthy Finnish children attending day care, there was a reduced risk of occurrence of AOM in the xylitol group (in any form) compared to the control group (RR 0.75; 95% CI 0.65 to 0.88). The fourth RCT included 1277 Finnish day care children with a respiratory infection and found no effect of xylitol on reducing the occurrence of AOM (RR 1.13; 95% CI 0.83 to 1.53). Xylitol chewing gum was superior to xylitol syrup in preventing AOM among healthy children (RR 0.59; 95% CI 0.39 to 0.89) but not during respiratory infection (RR 0.68; 95% CI 0.43 to 1.07). There was no difference between xylitol lozenges and xylitol syrups in preventing AOM among healthy children (RR 0.77; 95% CI 0.53 to 1.11) or among children during respiratory infection (RR 0.74; 95% CI 0.47 to 1.14). Similarly, no difference was noted between xylitol chewing gum and xylitol lozenges in preventing AOM among healthy children (RR 0.73; 95% CI 0.47 to 1.13) or among children during respiratory infection (RR 0.92; 95% CI 0.59 to 1.46). Among the reasons for drop-outs, there were no significant differences in abdominal discomfort and rash between the xylitol and the control groups. AUTHORS' CONCLUSIONS: There is fair evidence that the prophylactic administration of xylitol among healthy children attending day care centres reduces the occurrence of AOM by 25%. This meta-analysis is limited since the data arise from a small number of studies, mainly from the same research group.

Effect of xylitol gum on the level of oral mutans streptococci of preschoolers: block-randomised trial.

OBJECTIVES: To assess the influence of xylitol chewing gum consumption on mutans streptococci level of 3-4 years old Japanese preschoolers. METHODS: 248 participants were examined regarding caries-related factors at baseline and were followed up at 6, 9, and 12 months after the baseline: assessors were blinded, subjects were open labelled and blocked parallel randomised; 142 were selected to use xylitol gum for 3 months (from months 6 to 9) and 106 were controls. RESULTS: 161 participants were analysed (xylitol n = 76, control n = 85). Nineteen caries-related variables, including xylitol gum consumption, were analysed for any association with the main outcome, plaque mutans streptococci scores development within the intervention period, by logistic regression. Six showed statistically significant associations by univariate analysis (P < 0.05). However, only xylitol gum consumption remained a significant negative association (P < 0.05) by multiple analyses. Interestingly, over 10% xylitol group children experienced diarrhoea, which was larger than previous investigations. CONCLUSION: Xylitol gum is effective in avoiding increased plaque mutans streptococci in young children.

Study protocol for a randomized clinical trial to evaluate the effect of the use of Xylitol gum in the prevention of caries lesions in children living in Ladakh-the Caries Prevention Xylitol in Children (CaPreXCh) trial.

BACKGROUND: Xylitol use is reported to be able to reduce dental plaque amount and cariogenic bacteria and, as a consequence, the caries increment. Only few data on the oral health of Ladakh's population are available. The aim of the present protocol will be to record the caries prevalence of primary and permanent molars of schoolchildren living in Ladakh and to implement a school-based Xylitol programme, named the Caries Prevention Xylitol in Children (CaPreXCh) trial, using chewing gums. METHODS: The protocol is designed as a triple-blind randomized, controlled, parallel-group clinical trial in children aged 5-14 years. The study should have been carried out from August 2021 to August 2024 in Zanskar Valley (Ladakh), but the COVID-19 pandemic does not allow today to make predictions on the exact start. Participants will be randomly allocated into two groups: subjects who will receive a chewing gum with Xylitol (70% w/v) as only sweetener, and those who will receive a sugared chewing gum containing Maltitol (23% w/v). The subjects will be instructed to chew a total of 6 pellets for 5 min divided into 3 intakes a day (2 in the morning, 2 after the midday meal and 2 in the afternoon) for one school year. Clinical examination will comprise an oral examination in which caries index (ICDAS scores), bleeding on probing and plaque pH evaluation after sucrose challenge will be recorded at baseline (t0); the clinical examination will be repeated after 12 months since the beginning of the chewing gum administration period (t1), after another 12-month period (t2) and finally after further 12 months (t3) (24 months from the end of the chewing gum use). The primary outcome will be the caries increment measured both at enamel and dentinal levels on primary and permanent molars. Data analysis will be conducted through Kaplan-Meyer graphs to evaluate caries increment. A comparison of the methods will be carried out with Cox regression with shared frailty. The net caries increment for initial, moderate and severe caries levels, using ICDAS (Δ-initial, Δ-moderate and Δ-severe), will be calculated. DISCUSSION: This trial will be the first trial conducted in India assessing the efficacy of a school-based caries preventive programme through the use of chewing gum containing only Xylitol as a sweetener. The findings could help strengthen the evidence for the efficacy of Xylitol use in community-based caries prevention programmes in children. TRIAL REGISTRATION: Clinical trials.gov NCT04420780 . Registered on June 9, 2020.

A New Peritoneal Dialysis Solution Containing L-Carnitine and Xylitol for Patients on Continuous Ambulatory Peritoneal Dialysis: First Clinical Experience.

Peritoneal dialysis (PD) is a feasible and effective renal replacement therapy (RRT) thanks to the dialytic properties of the peritoneal membrane (PM). Preservation of PM integrity and transport function is the key to the success of PD therapy, particularly in the long term, since the prolonged exposure to unphysiological hypertonic glucose-based PD solutions in current use is detrimental to the PM, with progressive loss of peritoneal ultrafiltration capacity causing technique failure. Moreover, absorbing too much glucose intraperitoneally from the dialysate may give rise to a number of systemic metabolic effects. Here we report the preliminary results of the first clinical experience based on the use in continuous ambulatory PD (CAPD) patients of novel PD solutions obtained through partly replacing the glucose load with other osmotically active metabolites, such as L-carnitine and xylitol. Ten CAPD patients were treated for four weeks with the new solutions. There was good tolerance to the experimental PD solutions, and no adverse safety signals were observed. Parameters of dialysis efficiency including creatinine clearance and urea Kt/V proved to be stable as well as fluid status, diuresis, and total peritoneal ultrafiltration. The promising tolerance and local/systemic advantages of using L-carnitine and xylitol in the PD solution merit further research.

Too much of too little: xylitol, an unusual trigger of a chronic metabolic hyperchloremic acidosis.

Homeopathic globules are frequently used in children as a first-line treatment. Most of these globules are coated with sugar substitutes like xylitol; these substitutes are known for their laxative effect. Our patient shows that consumption of globules coated with xylitol does not have only laxative effects. It may cause indeed considerable weight loss and life-threatening enteral bicarbonate loss by diarrhea when overdosed in an infant.

Xylitol as a prophylaxis for acute otitis media: systematic review.

A systematic review was conducted to evaluate evidence regarding xylitol, a sugar alcohol, as a prophylaxis for acute otitis media (AOM) in children. The authors searched PubMed and other databases to identify evidence. Criteria for included studies were: appear in English-language, peer-reviewed journals; at least quasi-experimental designs; use xylitol; and present outcome data. The authors completed evaluation forms for the included studies at all phases of the review. The authors reviewed 1479 titles and excluded 1435. Abstracts and full texts were reviewed for the remaining 44; four randomized controlled trials met inclusion criteria. Xylitol was a generally well accepted prophylaxis for AOM with few side effects when administered via chewing gum or syrup at 10 g/day given five times daily. Meta-analysis revealed significant treatment effects (Risk ratio = 0.68; 95% confidence interval = 0.57 to 0.83). Xylitol can be a prophylaxis for AOM, but warrants further study, especially of vehicles other than chewing gum for young children, and information is needed regarding cost, duration of administration required, and expected long-term effects.

Randomized controlled study of aerosolized hypertonic xylitol versus hypertonic saline in hospitalized patients with pulmonary exacerbation of cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and recurrent pulmonary exacerbations. Xylitol is a 5-carbon sugar that can lower the airway surface salt concentration and augment innate immunity. We examined the safety and efficacy of aerosolized xylitol use for 2 weeks in subjects hospitalized with a pulmonary exacerbation of CF. METHODS: In a 2-week study, 60 subjects with cystic fibrosis and FEV1 > 30% predicted were enrolled to receive aerosolized 7% hypertonic saline (4 ml) or 15% xylitol (5 ml) twice a day for 14 days. Outcomes assessed included change from baseline in FEV1% predicted, change in sputum microbial density, revised CF quality of life questionnaire including the respiratory symptom score, time to next hospitalization for a pulmonary exacerbation, and frequency of adverse events. RESULTS: 59 subjects completed the study (one subject in the saline group withdrew before any study product administration). No significant differences were noted between the 2 arms in mean changes in lung function, sputum microbial density for Pseudomonas aeruginosa and Staphylococcus aureus, body weight, quality of life, and frequency of adverse events. CONCLUSIONS: Aerosolized hypertonic xylitol was well-tolerated among subjects hospitalized for CF pulmonary exacerbation. Future studies examining efficacy for long term use in patients with CF lung disease would be worthwhile. The clinical trial registration number for this study is NCT00928135.

Calciuria, oxaluria and phosphaturia after ingestion of glucose, xylitol and sorbitol in two population groups with different stone-risk profiles.

The effects of glucose, sorbitol and xylitol ingestion on calciuria, oxaluria and phosphaturia in healthy black and white males on a standardized diet were investigated. After ingestion, they collected urine hourly for 3 h. Glucose decreased phosphaturia in blacks. Sorbitol decreased phosphaturia in both groups and increased oxaluria in whites. Xylitol increased oxaluria in blacks. Decreases in phosphaturia are attributed to penetration by phosphate into cells leading to decreases in phosphatemia and the renal filtered load. We suggest that this mechanism is more sensitive in blacks. We speculate that the increase in oxaluria after sorbitol ingestion occurs via its conversion to glyoxylate and that this pathway may be blocked in blacks. For the increase in oxaluria after xylitol ingestion, it is hypothesized that ketohexokinase and aldolase may be more active in blacks. Our results demonstrate, for the first time, a urinary effect due to sorbitol ingestion and an ethnic dependency of these and other effects.

In vitro reproduction of noncarious cervical lesions.

STATEMENT OF PROBLEM: A review of the dental literature indicates that noncarious cervical lesions (NCCLs) are formed by erosion, abrasion, and/or abfraction of tooth structure, but their etiology remains scientifically unsubstantiated. PURPOSE: The purpose of this study was to reproduce noncarious cervical lesions in vitro. This study was not designed to statistically quantify the amount of lost tooth structure via abrasion, but rather to attempt to create NCCLs in the various shapes and sizes that are clinically observed. MATERIAL AND METHODS: Three pairs of toothbrush types (generic and name-brand) with soft, medium, or firm bristles were tested with 3 different toothpastes of varying abrasive potentials (low, medium, and high) or with water only, on mounted human teeth with and without simulated gingival tissues (6 toothbrushes x 4 brushing solutions (L, M, H, dentifrices, or water only) x 2 gingival mask conditions = 48 test/control groups of 4 teeth each = 192). RESULTS: The control sets, brushed in water only, demonstrated no visible loss of tooth structure. Each set brushed with toothpaste, regardless of the degree of abrasiveness or toothbrush bristle firmness, demonstrated visible wear at the level of the CEJ. CONCLUSIONS: Significant noncarious cervical lesions were created via horizontal brushing with common commercial toothpaste, while brushing with water only did not create these cervical lesions.

Safety assessment of inhaled xylitol in subjects with cystic fibrosis.

BACKGROUND: Xylitol is a 5-carbon sugar that can lower the airway surface salt concentration, thus enhancing innate immunity. We tested the safety and tolerability of aerosolized iso-osmotic xylitol in subjects with cystic fibrosis. METHODS: In this pilot study, 6 subjects with cystic fibrosis and an FEV1>60% predicted underwent a baseline spirometry followed by exposures to aerosolized saline (10 ml) and 5% xylitol (10 ml). Serum osmolarity and electrolytes were measured at baseline and after xylitol exposure. Spirometry, oxygen saturation and respiratory symptom questionnaire using visual analog scale were tested at baseline and after each exposure. Sputum for cytokine analysis was collected after saline and xylitol nebulizations. RESULTS: There was no change in FEV1 after xylitol exposure compared with baseline or normal saline exposure (p=0.19). Laboratory values and respiratory symptoms were not affected by xylitol inhalation. The mean IL-8 level in the sputum was similar with saline and xylitol exposures (3.5+/-0.5 vs. 3.5+/-0.6 ng/ml). CONCLUSIONS: A single dose inhalation of aerosolized iso-osmotic xylitol was well tolerated by subjects with cystic fibrosis. Future studies of long term safety are required.

Gastrointestinal tolerance of erythritol and xylitol ingested in a liquid.

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.

Tolerability of oral xylitol solution in young children: implications for otitis media prophylaxis.

OBJECTIVE: Xylitol, given as 2g orally five times-a-day, significantly reduces the incidence of acute otitis media (AOM) in children. A less frequent dosing schedule, if tolerable and efficacious, would promote the more widespread use of this treatment. We sought to determine the tolerability and acceptability in young children of oral xylitol solution at doses of 5g three times-a-day (TID) and 7.5g once daily (QD). METHODS: The study was a 3-month randomized placebo-controlled trial of the tolerability and acceptability of oral xylitol solution in 120 children 6-36 months of age performed in the SCOR Network. RESULTS: Study withdrawals and unscheduled medical visits for gastrointestinal complaints did not differ significantly among the study groups. The proportions of subjects in the xylitol TID group who experienced excessive gas or diarrhea at months 1, 2, and 3 were 22.7%, 10.0%, and 14.3%, respectively, and in the xylitol QD group were 27.3%, 17.4%, and 14.3%, respectively, and these did not differ from the placebo groups. The proportions who accepted the study solution easily or with only minor difficulty at 1, 2, and 3 months in the xylitol TID group were 77.3%, 90.0%, and 90.5% and in the xylitol QD group, 77.3%, 82.6%, and 90.5%, respectively. CONCLUSIONS: Oral xylitol solution at dosages of 5g TID and 7.5g QD is well-tolerated by young children. Given the potential for xylitol as a safe, inexpensive option for AOM prophylaxis, clinical trials using these dosages of xylitol can be conducted.

Threshold for transitory diarrhea induced by ingestion of xylitol and lactitol in young male and female adults.

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.

Acute hepatic failure and coagulopathy associated with xylitol ingestion in eight dogs.

CASE DESCRIPTION: 8 adult dogs were evaluated for treatment of lethargy and vomiting after ingestion of xylitol, a sugar alcohol used as a sweetener in various products. CLINICAL FINDINGS: In addition to vomiting and lethargy, 5 of the dogs had widespread petechial, ecchymotic, or gastrointestinal tract hemorrhages. Common clinicopathologic findings included moderately to severely high serum activities of liver enzymes, hyperbilirubinemia, hypoglycemia, hyperphosphatemia, prolonged clotting times, and thrombocytopenia. Necropsies were performed on 3 dogs and severe hepatic necrosis was found in 2. In the third dog, histologic examination revealed severe hepatocyte loss or atrophy with lobular collapse. TREATMENT AND OUTCOME: Treatments varied among dogs and included IV administration of fluids; plasma transfusions; and, if indicated, administration of dextrose. Three dogs were euthanatized, 2 dogs died, 2 dogs made a complete recovery, and 1 dog was recovering but was lost to follow-up. CLINICAL RELEVANCE: Although xylitol causes hypoglycemia in dogs, hepatic failure after ingestion has not previously been reported. Because an increasing number of consumer products contain xylitol, clinicians should be aware that ingestion of xylitol can have serious, life-threatening effects.