Xylitol

Generic name: Pentahydroxypentane, Xylo-1,2,3,4,5-pentol
Brand names: Birch Sugar, Xylitol

Usage of Xylitol

Acute otitis media

The mechanism of action for xylitol in acute otitis media may involve altering the adherence surface by potentially blocking bacterial lectins.(Kontiokari 1998, Mäkinen 2000a) Another mechanism may involve metabolism to xylitol-5-phosphate, which may be toxic to bacteria.(Tapiainen 2001) Although there is some evidence from randomized trials to suggest that xylitol may be beneficial, additional information is necessary before it can be routinely recommended.

Animal and in vitro data

In vitro, a 5% concentration of xylitol inhibited the growth of Streptococcus pneumoniae. The xylitol-induced inhibition of S. pneumoniae is mediated through a fructose phosphotransferase system.(Tapiainen 2001) Xylitol also reduces the level of adherence of S. pneumoniae and Haemophilus influenzae to nasopharyngeal epithelial cells. In addition, xylitol affects the expression of the polysaccharide capsule and cell wall of pneumococci. However, xylitol does not affect nasopharyngeal colonization of pneumococci.(Kontiokari 1995, Kontiokari 1998, Tapiainen 2004)

In an experimental study, dietary xylitol possibly improved oxidative killing in neutrophilic leukocytes and prolonged the survival of rats with sepsis caused by S. pneumoniae.(Renko 2008) In another study in rats with intestinal sepsis, parenteral xylitol had a nitrogen-sparing effect and improved survival.(Ardawi 1992)

Clinical data

In a study evaluating tolerability of xylitol in young children and the implications for otitis media prophylaxis, xylitol oral solution was well tolerated at dosages of 5 g orally 3 times a day and 7.5 g orally once a day.(Vernacchio 2007) Inhalation of aerosolized iso-osmotic xylitol was well tolerated in human volunteers and did not induce any changes in electrolytes and osmolarity.(Durairaj 2004) Airway deposition and retention time of aerosolized xylitol was roughly 3 hours.(Durairaj 2006)

According to results of 2 randomized, double-blind trials, the occurrence of acute otitis media was reduced by 40% in children given xylitol chewing gum. The daily xylitol dose varied from 8.4 g in chewing gum to 10 g in syrup. Compared with control, xylitol formulations reduced the need for administration of antibiotics.(Uhari 1996, Uhari 1998) An updated Cochrane systematic review and meta-analysis evaluating xylitol use for prevention of acute otitis media in children up to 12 years of age identified 5 randomized clinical trials and quasi-randomized clinical trials (N=3,405) that met inclusion criteria. Moderate-quality evidence supported a risk reduction in acute otitis media of 22% to 30% with prophylactic use of any form of xylitol in healthy children attending daycare (dosage, 8 to 10 g/day). However, this benefit appeared to be lost in children who had an existing respiratory infection or who were prone to acute otitis media (moderate-quality and low-quality evidence, respectively), even at dosages of up to 15 g/day.(Azarpazhooh 2016)

The updated Italian Society of Pediatrics guideline (2019) on the management of acute otitis media in children does not recommend use of xylitol in any formulation (ie, chewing gum, syrup) as a preventative measure (weak negative recommendation).(Marchisio 2019)

Antibacterial effects

Clinical data

In a prospective, randomized controlled study, 35 hematopoietic stem cell transplant (HSCT) recipients 2 to 29 years of age were randomized to conventional oral care alone (3 daily oral rinses with chlorhexidine gluconate and nystatin) or oral xylitol (wipes containing 0.7 g of xylitol used to wipe patient teeth and gums once daily) as an adjunct to conventional oral care; treatments were administered for 30 days post-HSCT. The xylitol group showed a significant reduction in bloodstream infections due to oral microorganisms (0% vs 25%; P=0.04) compared with conventional oral care alone. Streptococcus mitis/oralis (n=3) and a Fusobacterium species (n=1) were the infectious agents isolated as early as 2 days posttransplant. The xylitol group also had a significantly lower abundance of potential pathogenic organisms in the oral microbiome (ie, Staphylococcus aureus, Klebsiella pneumoniae) compared with patients who received conventional oral care alone (P=0.036 and P=0.022, respectively).(Badia 2020)

Bowel motility restoration

Clinical data

In a randomized controlled trial, 109 patients requiring laparoscopic surgery for benign or malignant gynecologic disease received usual postoperative care plus either mint-flavored sugarless xylitol chewing gum 3 times daily (to be chewed for 30 minutes at each session starting 6 hours after surgery until first flatus) or no gum. First flatus and first bowel sounds were observed significantly earlier in the treatment group (P<0.001 for each); however, when postoperative GI complications were compared, no significant difference was seen between groups in incidence of mild/severe intestinal obstruction.(Gong 2015)

Dental caries

Xylitol inhibits the cariogenicity, adhesivity, and acidogenic potential of plaque.(Mäkinen 2000a) Enamel demineralization is prevented, and plaque-building bacteria do not proliferate because xylitol is not fermented by the bacteria.(Burt 2006) Remineralization is enhanced because xylitol does not decrease pH and thus helps to reduce plaque accumulation on the tooth surface. Reduction in dental caries results from the buffering effect on plaque from saliva stimulation throughout the chewing process.(Burt 2006, Mickenautsch 2007) Also, cariogenic microorganisms cannot metabolize polyols into acids because sucrose is replaced with xylitol.(Ly 2008, Mickenautsch 2007)

Clinical data

Though guidelines for effective use of xylitol in the professional dental community in the United States have not been clarified, benefit has been suggested. Xylitol chewing gum divided into at least 3 consumption periods per day, for a total daily dose of 5 to 10 g, has been suggested for reducing dental caries.(Milgrom 2006) A literature review of randomized controlled trials and observational studies involving nearly 12,000 patients supports the use of polyol-containing chewing gums for reducing dental caries.(Deshpande 2008) A Cochrane review of xylitol-containing products for preventing dental caries in children and adults identified 10 randomized controlled trials (N=5,903), most of which had a high risk of bias. Low-quality evidence suggested that 2.5 to 3 years' use of fluoride toothpaste containing xylitol 10% may reduce caries in permanent teeth by 13% compared with fluoride-only toothpaste. Remaining data were of insufficient quality to make any determinations regarding other monitored parameters.(Riley 2015)

A small, nonblinded pilot study of 41 adolescents and young adults undergoing fixed-appliance orthodontic treatment evaluated the long-term effect of xylitol supplementation on caries risk. Compared with the control group, supplementation with xylitol 6 g/day (as gum or mint) for 3 months did not provide benefit regarding ecology of dental plaque or saliva over the 12-month follow-up period.(Masoud 2015) Similarly in a study in Kuwait, short-term chewing of xylitol gum (daily dose of approximately 6 g/day) for 5 weeks did not significantly change salivary microbial composition.(Söderling 2015)

In a small (N=35) randomized controlled study in children and young adults (2 to 29 years of age) undergoing HSCT, lingual but not dental plaque was significantly reduced at day 7 (P=0.045) and day 14 (P=0.0023) posttransplant with adjunctive use of xylitol oral wipes (containing 0.7 g of xylitol) plus conventional oral care (chlorhexidine gluconate and nystatin) compared with conventional oral care alone. Oral ulcers larger than 10 mm also occurred at significantly lower rates with xylitol (P=0.049).(Badia 2020)

Diabetes

Xylitol is a low-calorie sweetening alternative that is absorbed more slowly than sucrose and contains 40% fewer calories. Xylitol does not increase blood sugar levels because it is metabolized independently of insulin.(Chandramohan 2008, Juśkiewicz 2006, Ly 2006, Mäkinen 2000a)

Energy intake

Clinical data

A systematic review and meta-analysis of controlled intervention studies assessed the effect of sweetened and unsweetened preloads on subsequent energy intake. It was concluded that low-/no-calorie sweetened (LNCS) preloads, such as with xylitol, were at least equivalent to unsweetened preloads on acute energy intake on an isocaloric comparison. In contrast, in isosweet comparisons, significantly greater ad libitum energy intakes were observed following LNCS compared with caloric sweeteners (ie, glucose, fructose).(Lee 2021)

Gingivitis

In vitro data

Xylitol has shown inhibitory effects on growth of the major periodontopathogen Porphyromonas gingivalis, which is responsible for the initiation and progression of periodontitis by reducing inflammatory cytokine expression.(Han 2005)

Clinical data

In a small (N=35), randomized controlled study conducted in HSCT recipients 2 to 29 years of age, gingivitis occurred at a significantly lower rate at 7, 14, and 28 days posttransplant in patients who used xylitol oral wipes (containing 0.7 g of xylitol) as an adjunct to conventional oral care (chlorhexidine gluconate and nystatin) (P=0.031, 0.0039, and 0.0005, respectively) compared with patients who used conventional oral care alone.(Badia 2020)

Myoadenylate deaminase deficiency

Clinical data

Because xylitol can be metabolically converted to D-ribose, it was successfully used to treat a patient with muscle pain and stiffness caused by myoadenylate deaminase deficiency.(Mäkinen 2000a, Zöllner 1986)

Osteoporosis

Animal data

Dietary xylitol increased the intestinal absorption of calcium and, when added to calcium supplements, accelerated bone repair and improved bioavailability of Calcium Salts in calcium-deficient rats.(Hämäläinen 1994) In streptozotocin diabetic rats, dietary xylitol reduced loss of bone mineral content and trabecular bone volume and improved bone biomechanical properties.(Mattila 1998a) A 10% (w/w) dietary xylitol supplement has been used in most animal studies, corresponding to a daily intake of approximately 2 g of xylitol.(Mattila 1998b, Mattila 2002) In a study in rats, metabolism of xylitol improved collagen synthesis and glycosylation.(Knuuttila 2000) Xylitol also protected against ethanol-induced bone resorption,(Mattila 2005) decreased trabecular bone volume, and imbalance of bone metabolism during the early phase of collagen type II–induced arthritis in rats.(Kaivosoja 2008)

Pharyngitis

Clinical data

In a randomized, placebo-controlled trial, xylitol had no effect on the acute symptomatic management of pharyngitis. Primary outcome data were collected on 689 participants. Patients were 3 years or older and had an acute illness, with sore throat as the main symptom and abnormal results on throat examination. All patients received probiotics plus chewing gum with or without xylitol or no gum for 3 months.(Little 2017)

Sinonasal disease

Clinical data

In 100 patients with sinonasal disease who underwent endoscopic sinus surgery and/or septoplasty, postoperative bilateral nasal irrigation with xylitol (4 mg per 240 mL 3 times daily for 14 days) led to significant improvements in SNOT-20 general nasal symptom scores (P=0.022), sneezing (P=0.003), headache (P=0.02), and facial pain (P=0.037) compared with normal saline. These results remained consistent for patients with chronic rhinosinusitis without polyps, but not for those with polyps. Xylitol nasal irrigation also improved rhinorrhea symptoms in patients with allergic sensitization (P=0.024). No difference was observed between groups in the modified Lund-Kennedy score.(Kim 2019)

Xylitol side effects

Avoid use in individuals allergic to xylitol. Hypersensitivity reactions, including anaphylaxis, have been documented in the medical literature.(Okamoto 2019, Sreenath 2007)

The main adverse effects reported from oral xylitol use at a dosage exceeding 40 to 50 g/day included nausea, bloating, borborygmi (rumbling sounds of gas moving through intestine), colic, diarrhea, and increased total bowel movement frequency.(Storey 2007) Oral erosive eczema from xylitol has also been documented.(Kaivosoja 2008) In a study of healthy human volunteers, no major changes in serum electrolytes were documented with a xylitol infusion, and parenteral xylitol resulted in minimal hyperuricemia without any pathophysiological consequences.(Durairaj 2004)

Before taking Xylitol

Pregnancy: Category B. Xylitol is considered safe during pregnancy and breastfeeding, according to the FDA.(Silk 2008) Maternal consumption of xylitol-sweetened chewing gum lowered maternal oral bacterial load and reduced transmission of mutans streptococci to infants late in pregnancy and during the postpartum period.(Söderling 2000, Söderling 2001) The optimal xylitol dose for prevention is not known.(Mäkinen 2000a, Silk 2008, Söderling 2000, Söderling 2001)

How to use Xylitol

Dosing regimens vary in clinical studies. Numerous foods and pharmaceutical and commercial products contain xylitol.

Acute otitis media

In one study evaluating xylitol use for prevention of acute otitis media in children, the daily dose varied from 8.4 g in chewing gum to 10 g in syrup.(Uhari 1996, Uhari 1998) A tolerability study evaluating implications for otitis media prophylaxis showed xylitol oral solution was well tolerated in young children at dosages of 5 g orally 3 times a day and 7.5 g orally once a day.(Vernacchio 2007)

Dental caries

Though guidelines for effective use in the professional dental community in the United States have not been clarified, xylitol chewing gum divided into at least 3 consumption periods per day, for a total daily dose of 5 to 10 g, has been suggested for reducing dental caries.(Milgrom 2006)

Warnings

Xylitol is generally nontoxic based on data from various clinical studies and historical use in foods, pharmaceuticals, and nutraceuticals. Animal studies also confirm its overall safety profile.(Ellwood 1999) Renocerebral oxalosis with renal failure has been documented with large IV doses of xylitol.(Durairaj 2004, Meier 2005) A dog developed vomiting, mild hypoglycemia, and fulminant hepatic failure after ingesting half of a loaf of bread containing xylitol.(Todd 2007)

What other drugs will affect Xylitol

Patients should be counseled if taking laxative products; sugar alcohols are not fully broken down during digestion, and most sugar alcohols may have an additive laxative effect. Xylitol appears to protect against ethanol-induced bone resorption and trabecular bone mineral density changes.(Mattila 2005)

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