Scientific Name(s): pentahydroxypentane or xylo-1,2,3,4,5-pentol
Common Name(s): xylitol , birch sugar
Uses of Xylitol
Medical literature documents the use of xylitol in medical conditions and applications, including acute otitis media, dental caries, intravenous (IV) nutrition, and osteoporosis, although limited clinical trials exist.
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.
Avoid use if allergic to xylitol. Hypersensitivity reactions are documented.
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.
None well documented.
Xylitol 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.
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.
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
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
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
Xylitol 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. 12In-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. 16Clinical 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. 21Dental caries
Xylitol inhibits the cariogenicity, adhesivity, and acidogenic potential of plaque. 1Clinical 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 , 10Intravenous nutrition
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: Xylitol reduces insulin secretion and hepatic lipogenesis when compared with D-glucose; the flow of amino acids from peripheral tissues to visceral organs remains undisturbed; xylitol enters the pentose phosphate cycle directly, without insulin.Osteoporosis
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 resorption, 33 decreased trabecular bone volume, and the early phase of collagen type II–induced arthritis. 34Other pharmacological uses
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 , 36Gingivitis
Xylitol inhibited the major periodontopathogen Porphyromonas gingivalis , which is responsible for the initiation and progression of periodontitis by reducing inflammatory cytokine expression. 37Myoadenylate deaminase deficiency
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.
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
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
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
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
Bibliography1. Mäkinen KK. Can the pentitol-hexitol theory explain the clinical observations made with xylitol? Med Hypotheses . 2000;54(4):603-613.
2. Huber J. Xylitol: Magic in the making. CDHA Journal . 20(1):29-34.
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.
5. Ly KA, Milgrom P, Rothen M. Xylitol, sweeteners, and dental caries. Pediatr Dent . 2006;28(2):154-63; discussion 192-198.
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.
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.
8. Ly KA, Riedy CA, Milgrom P, Rothen M, Roberts MC, Zhou L. Xylitol gummy bear snacks: a school-based randomized clinical trial. BMC Oral Health . 2008;8:20.
9. Milgrom P, Rothen M, Milgrom L. Developing Public Health Interventions with Xylitol for the US and US-Associated Territories and States. Suom Hammaslaakarilehti . 2006;13(10-11):2-11.
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.
11. Kontiokari T, Uhari M, Koskela M. Antiadhesive effects of xylitol on otopathogenic bacteria. J Antimicrob Chemother . 1998;41(5):563-565.
12. Tapiainen T, Kontiokari T, Sammalkivi L, Ikäheimo I, Koskela M, Uhari M. Effect of xylitol on growth of Streptococcus pneumoniae in the presence of fructose and sorbitol. Antimicrob Agents Chemother . 2001;45(1):166-169.
13. Kontiokari T, Uhari M, Koskela M. Effect of xylitol on growth of nasopharyngeal bacteria in vitro. Antimicrob Agents Chemother . 1995;39(8):1820-1823.
14. Tapiainen T, Sormunen R, Kaijalainen T, Kontiokari T, Ikäheimo I, Uhari M. Ultrastructure of Streptococcus pneumoniae after exposure to xylitol. J Antimicrob Chemother . 2004;54(1):225-228.
15. Renko M, Valkonen P, Tapiainen T, et al. Xylitol-supplemented nutrition enhances bacterial killing and prolongs survival of rats in experimental pneumococcal sepsis. BMC Microbiol . 2008;8:45.
16. Ardawi MS. Effects of xylitol- and/or glutamine-supplemented parenteral nutrition on septic rats. Clin Sci (Lond) . 1992;82(4):419-427.
17. Uhari M, Kontiokari T, Koskela M, Niemelä M. Xylitol chewing gum in prevention of acute otitis media: double blind randomised trial. BMJ . 1996;313(7066):1180-1184.
18. Uhari M, Kontiokari T, Niemelä M. A novel use of xylitol sugar in preventing acute otitis media. Pediatrics . 1998;102(4, pt 1):879-884.
19. Vernacchio L, Vezina RM, Mitchell AA. Tolerability of oral xylitol solution in young children: implications for otitis media prophylaxis. Int J Pediatr Otorhinolaryngol . 2007;71(1):89-94.
20. Durairaj L, Launspach J, Watt JL, et al. Safety assessment of inhaled xylitol in mice and healthy volunteers. Respir Res . 2004;5:13.
21. Durairaj L, Neelakantan S, Launspach J, et al. Bronchoscopic assessment of airway retention time of aerosolized xylitol. Respir Res . 2006;7:27.
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.
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.
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.
25. Georgieff M, Pscheidi E, Götz H, et al. The mechanism of the reduction of protein catabolism following trauma and during sepsis using xylitol [in German]. Anaesthesist . 1991;40(2):85-91.
26. Schricker T, Gross G, von der Emde J, Georgieff M. Effect of intravenous glucose versus glucose-xylose (1:1) administration on carbohydrate and lipid metabolism after trauma and during infection [in German]. Infusionsther Transfusionsmed . 1994;21(1):7-13.
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.
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.
29. Mattila PT, Knuuttila ML, Svanberg MJ. Dietary xylitol supplementation prevents osteoporotic changes in streptozotocin-diabetic rats. Metabolism . 1998;47(5):578-583.
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.
31. Mattila PT, Svanberg MJ, Jämsä T, Knuuttila ML. Improved bone biomechanical properties in xylitol-fed aged rats. Metabolism . 2002;51(1):92-96.
32. Knuuttila ML, Kuoksa TH, Svanberg MJ, Mattila PT, Karjalainen KM, Kolehmainen E. Effects of dietary xylitol on collagen content and glycosylation in healthy and diabetic rats. Life Sci . 2000;67(3):283-290.
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.
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.
35. Chandramohan G, Ignacimuthu S, Pugalendi KV. A novel compound from Casearia esculenta (Roxb.) root and its effect on carbohydrate metabolism in streptozotocin-diabetic rats. Eur J Pharmacol . 2008;590(1-3):437-443.
36. Juśkiewicz J, Klewicki R, Zduńczyk Z. Consumption of galactosyl derivatives of polyols beneficially affects cecal fermentation and serum parameters in rats. Nutr Res . 2006;26(10):531-536.
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.
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.
39. Silk H, Douglass AB, Douglass JM, Silk L. Oral health during pregnancy. Am Fam Physician . 2008;77(8):1139-1144.
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.
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.
42. Sreenath K, Venkatesh YP. Reductively aminated D-xylose-albumin conjugate as the immunogen for generation of IgG and IgE antibodies specific to D-xylitol, a haptenic allergen. Bioconjug Chem . 2007;18(6):1995-2003.
43. Storey D, Lee A, Bornet F, Brouns F. Gastrointestinal tolerance of erythritol and xylitol ingested in a liquid. Eur J Clin Nutr . 2007;61(3):349-354.
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.
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.
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