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Xylitol

Scientific Name(s): Pentahydroxypentane, Xylo-1,2,3,4,5-pentol
Common Name(s): Birch sugar, Xylitol

Clinical Overview

Use

Medical literature documents the use of xylitol in medical conditions and applications, including acute otitis media, dental caries, intravenous (IV) nutrition, restoration of bowel motility after surgery, and osteoporosis, although limited clinical trials exist.

Dosing

Dosage regimens vary. In one study to prevent ear infections in children, the daily dose varied from 8.4 g in chewing gum to 10 g in syrup. Xylitol oral solution at dosages of 5 g orally 3 times a day and 7.5 g orally once a day was well tolerated in young children. Xylitol chewing gum was effective in reducing dental caries when divided into at least 3 consumption periods per day for a total dose of 6 to 10 g. For adults 21 years and older at high risk of caries, consideration may be given for daily use of five 1 gram xylitol lozenges.

Contraindications

Avoid use if allergic to xylitol. Hypersensitivity reactions are documented.

Pregnancy/Lactation

Pregnancy: Category B. Xylitol is considered safe in pregnancy and during breast-feeding, according to the US Food and Drug Administration (FDA). The use of xylitol chewing gum in mothers lowered maternal oral bacterial load and reduced transmission of mutans streptococci to infants late in pregnancy and during the postpartum period.

Interactions

None well documented.

Adverse Reactions

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 the intestine), colic, diarrhea, and increased total bowel movement frequency.

Toxicology

Xylitol is generally nontoxic based on various clinical studies and its historical use in foods, pharmaceuticals, and nutraceuticals. Animal studies also confirm its overall safety profile. Renocerebral oxalosis with renal failure is documented with large doses of IV administered xylitol.

Source

Xylitol is a 5-carbon sugar alcohol naturally found in the fibers of many fruits and vegetables, including raspberries, strawberries, yellow plum, lettuce, cauliflower, corn, and corn husks.1, 2, 3, 4 It is a natural product that may be extracted from the bark of birch trees and other hardwood species containing xylan.2, 5 The commercial chemical process for producing xylitol was developed in the 1970s in Finland.6, 7

History

Xylitol was first discovered in 1891 by a German chemist, Emil Fischer.2 This natural sweetener was used in the sugar shortages of World War II in the 1930s in Finland. During the 1960s, the product was marketed in Germany, Switzerland, the Soviet Union, Japan, Italy, and China.2 It was approved by the FDA in 1963 as a food additive.8, 9 It is currently approved for use in foods, pharmaceuticals, oral health products, and nutraceuticals in more than 35 countries.5, 10 Some commercially available xylitol-containing products include gums, mints, energy bars and foods, oral hygiene products, and vitamins.5

In Europe, Korea, Japan, Thailand, and China, chewing gum and lozenges containing xylitol are widely available and used by consumers. Finland implemented a national campaign and was the first country to promote xylitol to reduce tooth decay in children. Other European and Asian countries, including Japan and Korea, implemented similar programs, in which xylitol chewing gum has captured nearly 50% of the commercial chewing gum market. Even the US Army implemented an initiative to promote xylitol to improve oral health among deployed troops. Xylitol chewing gum and hard candy products are considered choking hazards in young children; therefore, initiatives addressing tooth decay in young children have not been adopted until the creation of an acceptable xylitol delivery vehicle.8

Chemistry

Xylitol is a natural carbohydrate and is classified as a polyhydric alcohol or sugar alcohol. All 5 carbon atoms bind to a hydroxide group; thus, the molecule has no reducing groups. A review article documents the chemical profile and clinical structural importance (ie, the pentitol-hexitol theory) of xylitol.1

Xylitol is a normal intermediate of human metabolism and the human body produces nearly 5 to 15 g daily, with nearly 80% metabolized by the liver.1, 3 Xylitol is almost identical in sweetness and bulk to sucrose, has 40% fewer calories, and an energy value of 2.4 versus 4 calories per gram of sucrose. One teaspoonful of xylitol contains approximately 10 calories, while 1 teaspoonful of sucrose contains 15 calories.

Industrially, xylitol is produced by chemical hydrogenation of D-xylose into xylitol by the presence of a nickel catalyst.2, 3, 7 Direct extraction from the birch tree bark leads to the most pure and desirable product, but the process is expensive and uneconomical.3 The xylitol yield ranges from 50% to 60% from the total xylan content of the wood hemicellulose, and annual production is estimated at 20,000 to 40,000 tons per year.7

Alternative forms of industrial production of xylitol, such as the use of metabolically engineered yeasts, have been studied.7

Uses and Pharmacology

Medical literature documents the use of xylitol in medical conditions and applications, including acute otitis media, dental caries, IV nutrition, and osteoporosis.

Acute otitis media (middle ear infections)

The mechanism of action for xylitol may involve altering the adherence surface by potentially blocking bacterial lectins.1, 11 Another mechanism may involve xylitol being metabolized to xylitol-5-phosphate, which may be toxic to bacteria.12

In-vitro and animal data

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.12 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.11, 13, 14

Dietary xylitol may improve oxidative killing in neutrophilic leukocytes and prolong the survival of rats suffering from sepsis caused by S. pneumoniae.15 Parenteral xylitol has a nitrogen-sparing effect and improves the survival of rats suffering from intestinal sepsis.16

Clinical data

According to the 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 dose varied from 8.4 g in chewing gum to 10 g in syrup and reduced the need for administration of antibiotics.17, 18 Xylitol oral solution at dosages of 5 g orally 3 times a day and 7.5 g orally once a day was well tolerated in young children.19 Inhalation of aerosolized iso-osmotic xylitol was well tolerated in human volunteers and did not induce any changes in electrolytes and osmolarity.20 Airway deposition and retention time of aerosolized xylitol was roughly 3 hours.21 An updated Cochrane review identified 5 randomized clinical trials and quasi-randomized clinical trials (N=3,405) that met inclusion for a systematic review and meta-analysis of xylitol for preventing acute otitis media (AOM) in children up to 12 years of age. Moderate-quality evidence supported a risk reduction in AOM of 22% to 30% with prophylactic use of any form of xylitol in healthy children attending daycare (dose, 8 to 10 g/day). However, this benefit appeared to be lost in children with an existing respiratory infection or who were prone to AOM (moderate-quality and low-quality evidence, respectively) even at doses of up to 15 g/day.50

Bowel motility restoration

Postoperative restoration of bowel motility was found to be significantly improved in patients who were given xylitol gum to chew after surgery. 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, no significant difference was seen in postoperative GI complications between groups.49

Dental caries

Xylitol inhibits the cariogenicity, adhesivity, and acidogenic potential of plaque.1

Clinical data

A literature review of randomized controlled trials and observational studies involving nearly 12,000 patients supports the use of polyol-containing chewing gums in reducing dental caries.22 Enamel demineralization is prevented, and plaque building bacteria do not proliferate because xylitol is not fermented by the bacteria.23 Remineralization is enhanced because xylitol does not decrease pH and, thus, helps reduce plaque accumulation on the tooth surface. Dental caries reduction results from the buffering effect on plaque from saliva stimulation throughout the chewing process.23, 24 Also, cariogenic microorganisms cannot metabolize polyols into acids because sucrose is replaced with xylitol.8, 24 Studies have explored the safety and efficacy of xylitol delivery vehicles, such as gummy bear snacks and syrups in organized caries prevention programs in schools and daycare centers for small children.8, 9, 10 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 10% xylitol may reduce caries in the permanent teeth by 13%, compared to fluoride-only toothpaste. Remaining data was of insufficient quality to make any determinations regarding other monitored parameters.48 A small non-blind pilot study in 41 adolescents and young adults undergoing fixed-appliance orthodontic treatment evaluated the long-term effect of xylitol supplementation on caries risk. Compared to the control group, supplementation with xylitol 6 g/day (as gum or mint) for 3 months was not found to provide any significant difference in the ecology of dental plaque or saliva over the 12-month follow-up period.51 Similarly, short-term chewing of 6 g/day of xylitol gum for 5 weeks did not significantly change the salivary microbial composition in Kuwait children.52

Diabetes

Xylitol is a low-calorie sweetening alternative and is absorbed more slowly than sugar. It contains 40% fewer calories and does not cause increased blood sugar levels, because it is metabolized independently of insulin.1, 5, 35, 36

Gingivitis

Xylitol inhibited the major periodontopathogen Porphyromonas gingivalis, which is responsible for the initiation and progression of periodontitis by reducing inflammatory cytokine expression.37

Intravenous nutrition

Clinical data

In parenteral nutrition, xylitol is often given with amino acids and other carbohydrates. Metabolically, parenterally administered xylitol products reduce gluconeogenesis, promote fatty acid oxidation, and moderate blood glucose and insulin levels.1, 25, 26, 27 Numerous studies document how xylitol was more effective than glucose during total parenteral nutrition after trauma and sepsis. Because high plasma glucose concentrations are avoided, high hepatic glucose production is reduced and the release and oxidative use of free fatty acids is enhanced.25, 26, 27

Three primary metabolic advantages over D-glucose include:

  1. Xylitol reduces insulin secretion and hepatic lipogenesis when compared with D-glucose;

  2. the flow of amino acids from peripheral tissues to visceral organs remains undisturbed;

  3. xylitol enters the pentose phosphate cycle directly, without insulin.

Myoadenylate deaminase deficiency

Xylitol was successfully used to treat a patient with muscle pain and stiffness caused by myoadenylate deaminase deficiency, because it can be metabolically converted to D-ribose.1, 38

Osteoporosis

Animal studies

Dietary xylitol increases the intestinal absorption of calcium and when added to calcium supplements, accelerates bone repair and improves the bioavailability of calcium salts in calcium-deficient rats.28 In streptozotocin diabetic rats, dietary xylitol reduced loss of bone mineral and trabecular bone volume, and improved bone biomechanical properties.29 A 10% (wt/wt) dietary xylitol supplement has been used in most animal studies, corresponding to a daily intake of approximately 2 g of xylitol or 40 g total daily intake in humans.30, 31 The metabolism of xylitol also improves collagen synthesis and glycosylation.32 Xylitol also protects against ethanol-induced bone resorption33 decreased trabecular bone volume, and the early phase of collagen type II–induced arthritis.34

Dosing

Dosage regimens vary in clinical studies. In one study to prevent ear infections in children, the daily dose varied from 8.4 g in chewing gum to 10 g in syrup.17, 18 Xylitol oral solution at dosages of 5 g orally 3 times a day and 7.5 g orally once a day was well tolerated in young children.19 Xylitol chewing gum was effective in reducing dental caries when divided into at least 3 consumption periods per day for a total dose of 6 to 10 g.9 Numerous foods and pharmaceutical and commercial products contain xylitol. Research has shown that xylitol lozenges (1 g xylitol, 5 times daily) reduced the caries increment 10 percent. This reduction, representing less than one-third of a surface per year, was not statistically significant.47

Pregnancy / Lactation

Pregnancy: Category B. Xylitol is considered safe in pregnancy and during breast-feeding, according to the FDA.39 The use of xylitol chewing gum in mothers lowered maternal oral bacterial load and reduced transmission of mutans streptococci to infants late in pregnancy and during the postpartum period.40, 41 The optimal dose of xylitol for prevention is not known.1, 39, 40, 41

Interactions

Patients should be counseled if taking laxative products, because most sugar alcohols may have an additive laxative effect; sugar alcohols are not fully broken down during digestion. Xylitol appears to protect against ethanol-induced bone resorption and trabecular bone mineral density changes.33

Adverse Reactions

Avoid use in individuals allergic to xylitol. Hypersensitivity reactions are documented in the medical literature.42

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.43 Oral erosive eczema from xylitol is also documented.34 No major changes in serum electrolytes were documented with a xylitol infusion, and parenteral xylitol resulted in minimal hyperuricemia without any pathophysiological consequences in human patients.20

Toxicology

Xylitol is generally nontoxic, considering the data from various clinical studies and its historical use in foods, pharmaceuticals, and nutraceuticals. Animal studies also confirm its overall safety profile.44 Renocerebral oxalosis with renal failure is documented with large doses of IV-administered xylitol.20, 45 A dog suffered vomiting, mild hypoglycemia, and fulminant hepatic failure after ingesting half of a loaf of bread containing xylitol.46

References

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3. Vandeska E, Amartey S, S Kuzmanova, Jeffries TW. Fed-batch culture for xylitol production by Candida boidinii. Process Biochem. 1996;31(3):265-270.
4. Cheng KK, Zhang JA, Ling HZ, et al. Optimization of pH and acetic acid concentration for bioconversion of hemicellulose from corncobs to xylitol by Candida tropicalis. Biochem Eng J. 2009;43(2):203-207.
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6. Granström TB, Izumori K, Leisola M. A rare sugar xylitol. Part I: the biochemistry and biosynthesis of xylitol. Appl Microbiol Biotechnol. 2007;74(2):277-281.17216457
7. Granström TB, Izumori K, Leisola M. A rare sugar xylitol. Part II: biotechnological production and future applications of xylitol. Appl Microbiol Biotechnol. 2007;74(2):273-276.17216458
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10. Riedy CA, Milgrom P, Ly KA, et al. A surrogate method for comparison analysis of salivary concentrations of Xylitol-containing products. BMC Oral Health. 2008;8:5.18267030
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22. Deshpande A, Jadad AR. The impact of polyol-containing chewing gums on dental caries: a systematic review of original randomized controlled trials and observational studies. J Am Dent Assoc. 2008;139(12):1602-1614.19047666
23. Burt BA. The use of sorbitol- and xylitol-sweetened chewing gum in caries control [published correction appears in J Am Dent Assoc. 2006;137(4):447]. J Am Dent Assoc. 2006;137(2):190-196.16521385
24. Mickenautsch S, Leal SC, Yengopal V, Bezerra AC, Cruvinel V. Sugar-free chewing gum and dental caries: a systematic review. J Appl Oral Sci. 2007;15(2):83-88.19089107
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27. Schricker T, Gross G, Wölfel R, Georgieff M. Enhancement of fatty acid mobilization and oxidation by glucose-xylitol compared to glucose alone in posttraumatic and septic patients. Nutr Hosp. 1995;10(1):13-18.7711146
28. Hämäläinen MM. Bone repair in calcium-deficient rats: comparison of xylitol+calcium carbonate with calcium carbonate, calcium lactate and calcium citrate on the repletion of calcium. J Nutr. 1994;124(6):874-881.8207545
29. Mattila PT, Knuuttila ML, Svanberg MJ. Dietary xylitol supplementation prevents osteoporotic changes in streptozotocin-diabetic rats. Metabolism. 1998;47(5):578-583.9591750
30. Mattila PT, Svanberg MJ, Pökkä P, Knuuttila ML. Dietary xylitol protects against weakening of bone biomechanical properties in ovariectomized rats. J Nutr. 1998;128(10):1811-1814.9772154
31. Mattila PT, Svanberg MJ, Jämsä T, Knuuttila ML. Improved bone biomechanical properties in xylitol-fed aged rats. Metabolism. 2002;51(1):92-96.11782878
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33. Mattila PT, Kangasmaa H, Knuuttila ML. The effect of a simultaneous dietary administration of xylitol and ethanol on bone resorption. Metabolism. 2005;54(4):548-551.15798965
34. Kaivosoja SM, Mattila PT, Knuuttila ML. Dietary xylitol protects against the imbalance in bone metabolism during the early phase of collagen type II-induced arthritis in dark agouti rats. Metabolism. 2008;57(8):1052-1055.18640381
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37. Han SJ, Jeong SY, Nam YJ, Yang KH, Lim HS, Chung J. Xylitol inhibits inflammatory cytokine expression induced by lipopolysaccharide from Porphyromonas gingivalis. Clin Diagn Lab Immunol. 2005;12(11):1285-1291.16275942
38. Zöllner N, Reiter S, Gross M, et al. Myoadenylate deaminase deficiency: successful symptomatic therapy by high dose oral administration of ribose. Klin Wochenschr. 1986;64(24):1281-1290.3102830
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40. Söderling E, Isokangas P, Pienihäkkinen K, Tenovuo J. Influence of maternal xylitol consumption on acquisition of mutans streptococci by infants. J Dent Res. 2000;79(3):882-887.10765964
41. Söderling E, Isokangas P, Pienihäkkinen K, Tenovuo J, Alanen P. Influence of maternal xylitol consumption on mother-child transmission of mutans streptococci: 6-year follow-up. Caries Res. 2001;35(3):173-177.11385196
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44. Ellwood KC, Bhathena SJ, Johannessen JN, Bryant MA, O'Donnell MW. Biomarkers used to assess the effect of dietary xylitol or sorbitol in the rat. Nutr Res. 1999;19(11):1637-1648.
45. Meier M, Nitschke M, Perras B, Steinhoff J. Ethylene glycol intoxication and xylitol infusion--metabolic steps of oxalate-induced acute renal failure. Clin Nephrol. 2005;63(3):225-228.15786825
46. Todd JM, Powell LL. Xylitol intoxication associated with fulminant hepatic failure in a dog. J Vet Emerg Crit Care. 2007;17(3):286-289.
47. Bader JD, Vollmer WM, Shugars DA, et al. Results from the xylitol for adult caries trial (X-ACT). JADA. 2013;144(1):21-30.23283923
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49. Gong Y, Zhang Q, Qiao L, et al. Xylitol gum chewing to achieve early postoperative restoration of bowel motility after laparoscopic surgery. Surg Laparosc Endosc Percutan Tech. 2015;25:303-306.26121546
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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

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