The Journal of Laryngology & Otology (2014), 128, 580–585.

REVIEW ARTICLE
© JLO (1984) Limited, 2014
doi:10.1017/S0022215114001340

Xylitol and its usage in ENT practice

Ö SAKALLIOĞLU1, I ADADAN GÜVENÇ2, C CİNGİ3

1
Department of Otorhinolaryngology and Head and Neck Surgery, Elazığ Research and Training Hospital,
2
Department of Otorhinolaryngology and Head and Neck Surgery, Başkent University, Zübeyde Hanım Research
and Training Hospital, İzmir, and 3Department of Otorhinolaryngology and Head and Neck Surgery, University of
Osmangazi, Eskişehir, Turkey

Abstract
Background: Xylitol is a five-carbon sugar alcohol. Natural sources of xylitol include plums, strawberries and
raspberries. Xylitol is commercially available in chewing gums, lozenges, syrups, nasal sprays, toothpastes,
mouthwashes and other products in some countries. It has gained relative prominence in the past decade as a
naturally occurring antibacterial agent.
Objective: A review of contemporary literature was conducted to evaluate the efficacy of xylitol usage in ENT practice.
Method: The English-language literature was searched using the following terms: xylitol, otitis media, nasal,
sinusitis, dental caries and preventive therapy. The articles identified were included in this review.
Results: Xylitol has no antibacterial properties of its own; rather, it appears to enhance the body’s own
innate immunity. Xylitol has anti-adhesive effects on micro-organisms like Streptococcus pneumoniae and
Streptococcus mutans, inhibiting their growth. Xylitol has already been used for preventing otitis media,
rhinosinusitis and dental caries. The worldwide spread of drug-resistant strains of pneumococci substantiates the
need for new approaches to prevent ENT-related infectious diseases.
Conclusion: Xylitol may be a promising agent for this purpose in ENT practice, but further experimental and
clinical studies are required.

Key words: Xylitol; Otitis Media; Rhinitis; Sinusitis; Dental Caries; Preventive Therapy

Introduction innate immune system, and thereby decrease or

Xylitol is a five-carbon sugar alcohol that is widely dis- prevent airway infections.9 Xylitol also reduces the
tributed in plants; it is found in significant concentra- adhesiveness of mutans streptococci to tooth biofilms
tions in plums, strawberries and raspberries.1 It is and inhibits the growth of Streptococcus mutans,
used as a bulking agent in foods, and as a low-caloric which is the most important bacterium in the develop-
sweetener in medications, dental care products, ment of dental caries.10 Xylitol exerts selective antibac-
chewing gums and candies.2 Xylitol may also be con- terial-like actions against mutans streptococci by
sumed by diabetics, as an insulin-independent dietary disrupting glucose cell-wall transport and intracellular
sweetener, having about one-third less calories than glycolysis, thus inhibiting growth.11
sugar.3 In humans, xylitol is metabolised in the liver This review of contemporary literature aimed to
to glucose, glycogen and lactic acid. It affects blood evaluate the efficacy of xylitol usage in ENT practice.
glucose levels less than glucose does.4 It has also For this purpose, the English literature was searched
been used as a component in parenteral nutrition.5 using the following terms: xylitol, otitis media, nasal,
Xylitol is an unsuitable source of energy for many sinusitis, dental caries and preventive therapy. The arti-
micro-organisms, and it inhibits the growth of cles identified were included in this review.
Streptococcus pneumoniae in the presence of glucose.6
It has anti-adhesive effects on both S pneumoniae and Xylitol for acute otitis media
Haemophilus influenzae.7 In addition, xylitol decreases Acute otitis media is a common disease and is the main
the salt concentration of human airway surface liquid reason for antimicrobial treatment in children.
that contains many antimicrobial substances, including Streptococcus pneumoniae is the most common bacter-
lysozyme, lactoferrin, human β defensins and cathelici- ium causing middle-ear infections or sinusitis, and
din LL-37.8 Lowering the human airway surface liquid nasopharyngeal carriage of this bacterium has been
salt concentration can increase the efficacy of the shown to be a predisposing factor.12 In their in vitro

Accepted for publication 29 October 2013 First published online 7 July 2014
XYLITOL IN ENT PRACTICE 581

study, Kontiokari et al. showed that xylitol reduced the In a systematic review published in 2010 on acute
growth of S pneumoniae in the nasopharynx, and thus otitis media preventative treatment, Danhauer et al.
could reduce the carriage of bacteria.6 This has clinical stated that the prophylactic effects of xylitol have
significance for preventing attacks of acute otitis media been shown in children with acute otitis media.22
caused by pneumococci. Xylitol is well tolerated in children, with minimal
In 1996, a group from Finland (Uhari and collea- side effects. The best vehicle for administration in chil-
gues) reported their first trial on xylitol chewing gum dren is chewing gum. The act of chewing and swallow-
for the prevention of acute otitis media. In this rando- ing assists with the disposal of earwax and clearing of
mised trial, a total dose of 8.4 g of xylitol was adminis- the middle ear, whilst the presence of xylitol prevents
tered regularly in the form of chewing gum, five times a the growth of bacteria in the eustachian tubes.23 As
day for two months. This was shown to reduce the mentioned above, the Finnish group of researchers
occurrence of acute otitis media by about 40 per cent observed that 10 g of xylitol daily, given as 2 g orally
when compared with a sucrose (control) gum group. five times a day, is well tolerated in children as
However, unexpectedly, there was no decrease in the young as nine months of age for acute otitis media pre-
carriage rate over time in the xylitol group.13 Two vention. Xylitol lozenges, however, seem to be poorly
years later, the researchers published the findings of a tolerated; abdominal discomfort and a dislike of the
second trial. In that trial, xylitol was given in syrup product are more common.13–15
form to those children who were not able to chew Sezen et al. investigated the effect of chewing gum
gum, and in gum or lozenges to those who were old containing xylitol on middle-ear pressure in children
enough to consume them, for three months. The with chronic otitis media with effusion (Table I).17
authors reported a significant reduction in the occur- The patients who received the xylitol chewing gum
rence of acute otitis media when xylitol chewing gum had more improvement in pressure levels for the right
or xylitol syrup was administered five times daily. and left ears than those in the sorbitol group.
There was also a decrease in the occurrence of acute However, there were no statistically significant differ-
otitis media with xylitol lozenges, but the difference ences between the groups in terms of the presence of
was not significant. The use of antimicrobials was sig- glue in the middle ear or the pure tone audiometric
nificantly lower among those receiving xylitol syrup results for right and left ears after the treatment.
and xylitol chewing gum compared with their controls, Danhauer et al. mailed a 48-item questionnaire to a
but not in the lozenge group as compared with the random sample of 506 paediatricians within the USA
control chewing gum group.14 The results of the clinic- to assess their opinions on the prophylactic use of
al trials reviewed in this paper are summarised in xylitol in children with acute otitis media.22 The
Table I.13–20 authors found that most of the paediatricians knew
The practicability of giving xylitol five times per day about the medical uses of xylitol and most were
for preventing acute otitis media was questioned, but aware of its use in chewing gum to prevent acute
the group’s search for more convenient ways of admin- otitis media. However, the majority had not used
istering xylitol was not successful. In Uhari and collea- xylitol in their practice, and were not sure of the effect-
gues’ subsequent study (Tapiainen et al.), they iveness or appropriate dosage.
reported that xylitol administered only during an In a case report, it was stated that nasally adminis-
acute respiratory infection was ineffective in prevent- tered xylitol dramatically reduced acute otitis media
ing acute otitis media (Table I).15 In addition, xylitol episodes in children who previously suffered chronic
seemed to be ineffective when given immediately ear complaints (Table I).18 In the same paper, two
after the placement of tympanostomy tubes.21 Later, other patients with asthma were reported to benefit
Hautalahti et al. reported that xylitol given regularly from nasal saline sprays containing xylitol.
three times a day during acute respiratory infection epi-
sodes for three months also failed to prevent the occur- Xylitol for rhinosinusitis
rence of acute otitis media (Table I).16 The authors Bacteria are thought to play a central role in sinusitis. In
pointed out once more that continuous xylitol prophy- establishing rhinosinusitis, bacteria first need to over-
laxis administered five times a day was able to effect- come the body’s natural defences. In the treatment of
ively prevent acute otitis media attacks. In 2007, rhinosinusitis, especially in refractory cases, attention
Vernacchio et al. demonstrated that oral xylitol solu- on innate immunity has been limited.
tion, at dosages of 5 g three times a day and 7.5 g Respiratory tract secretions contain a variety of anti-
once daily, is reasonably well tolerated by and accept- microbial factors, including lysozymes, lactoferrin, β-
able for children at the highest risk of recurrent acute defensins, secretory phospholipase A2 and cathelici-
otitis media.2 They suggested that clinical trials using dins.24 These antimicrobial factors reside in the thin
these dosages of xylitol could be conducted, given layer of airway surface liquid. Experimentally lowering
the potential for xylitol as a safe, inexpensive option the airway surface liquid salt concentration increases
for acute otitis media prophylaxis. Hence, the search the activity of endogenous antimicrobials. A promising
for the most suitable dosage of xylitol for acute otitis osmolyte for lowering airway surface liquid ionic
media prophylaxis continues. strength is sugar xylitol. Zabner et al. showed that
 582
TABLE I
CLINICAL TRIALS ON XYLITOL USAGE IN ENT PRACTICE
Author (year) Methods Outcome measures Results

Uhari et al. (1996)13

Design: DBPCRT Occurrence of AOM (examination with Xylitol: 19/157 (12.1%) had ≥1 AOM attack
Subjects: 336 healthy children pneumatic otoscope), prescriptions Placebo: 31/149 (20.8%) had ≥1 AOM attack
Age range: 1–5 years for antibacterials & nasopharyngeal Difference: significant ( p = 0.04)
Dropout: n = 30 carriage of S pneumoniae Overall 40% implied reduction in incidence of AOM in control
Vehicles: xylitol gum, 2 pieces 5 times daily group
(xylitol, 8.4 g/day) for 2 months vs sucrose A clear decrease in AOM occurrence in children who chewed
gum (placebo) xylitol gum 5 times daily
Side effects (e.g. gastrointestinal discomfort) were minimal, &
similar for experimental & control groups
Uhari et al. (1998)14 Design: PCRT – double-blind for syrup & gum Occurrence of ARI & AOM, & For younger children:
groups, but not gum & lozenge groups prescriptions for antibacterials Xylitol syrup: 46/159 (29%) had ≥1 AOM attack
Subjects: 857 healthy children Control syrup: 68/165 (41%) had ≥1 AOM attack
Age range: 6 months–6 years Significant difference, p = 0.04
Dropout: n = 93 Overall 30% implied reduction in incidence of AOM in control
Vehicles: xylitol gum (8.4 g/day), xylitol group
lozenge (10 g/day) or xylitol syrup (10 g/ For older children:
day), vs placebo gum or placebo syrup Xylitol gum: 29/179 (16%) had ≥1 AOM attack
Control gum: 49/178 (28%) had ≥1 AOM attack
Significant difference, p < 0.05
Overall 40% implied reduction in incidence of AOM in control
group
Xylitol lozenge not as effective
Tapiainen et al. (2002)15 Design: PCRT – double-blind for syrup & gum Occurrence of AOM when xylitol For younger children:
groups, but not gum & lozenge groups administered during ARI Xylitol syrup: 34/166 (20.5%) had ≥1 AOM attack
Subjects: 1277 healthy children Placebo: 32/157 (20.4%) had ≥1 AOM attack
Age range:10 months–7 years For older children:
Dropouts: n = 24 Xylitol gum: 24/218 (11.0%) had ≥1 AOM attack
Vehicles: xylitol syrup & lozenge (10 g/day) & Xylitol lozenge: 31/220 (14.1%) had ≥1 AOM attack
xylitol gum (8.4 g/day), vs placebo syrup or Placebo: 34/219 (15.5%) had ≥1 AOM attack
gum (0.5 g/day) 5 times daily Xylitol not effective when administered intermittently during

Ö SAKALLIOĞLU, I ADADAN GÜVENÇ, C CİNGİ

episodes of ARI
Hautalahti et al. (2007)16 Design: DBPCRT Occurrence of first AOM attack Xylitol: 98/331 (30%) had ≥1 AOM attack
Subjects: 663 healthy children Placebo:94/332 (28%) had ≥1 AOM attack
Age range: 7 months–7 years Xylitol administered TID not effective for preventing AOM
Dropouts: n = 27 because of bacterial regeneration & impaired anti-adhesive
Vehicles: xylitol solution or xylitol gum (9.6 g/ effect of xylitol with lengthened intervals between doses
day), vs placebo solution or gum (0.5 g/day)
TID
Sezen et al. (2008)17 Design: single-blind PCRT Tympanometry (middle-ear pressure), Xylitol: difference in R middle-ear pressure (117.71 daPa) was
Subjects: 29 COME patients frequency of glue ear & audiometric highly significant ( p < 0.01); difference in L middle-ear
Age range: 4–10 years evaluation pressure (167.00 daPa) was highly significant ( p < 0.05)
Dropout: n = 0 Sorbitol: difference in R middle-ear pressure (39.21 daPa) was
Vehicles: xylitol gum (8.4 g/day) vs sorbitol significant ( p < 0.05); difference in L middle-ear pressure
gum (placebo) (11.85 daPa) was not significant
No differences in frequency of glue ear & PTA between groups
Continued
XYLITOL IN ENT PRACTICE 583

xylitol can lower the airway surface liquid salt concen-

of irrigation (mean reduction of 2.43) compared with saline

DBPCRT = double-blind, placebo-controlled, randomised trial; AOM = acute otitis media; PCRT = placebo-controlled, randomised trial; ARI = acute respiratory infection; TID = three times a day; COME =
chronic otitis media with effusion; R = right; L = left; PTA = pure tone audiometry; FU = follow up; ASL = airway surface liquid; w/v = weight/volume; SNOT-20 = Sino-Nasal Outcome Test 20; VAS =
Over an average of 11 months FU, AOM incidence decreased

Short-term, xylitol irrigations resulted in greater improvement

concentration & enhancing innate antimicrobial defence at

Significant reduction in SNOT-20 score during xylitol phase

tration in both cystic fibrosis and non-cystic fibrosis

staphylococcus on nasal surface compared with saline

airway epithelia in vitro, and can thus enhance the

phase (mean increase of 3.93), indicating improved

of CRS symptoms compared with saline irrigation

innate immunity. In the nasal mucosa, xylitol spray
Xylitol significantly reduced coagulase-negative
was observed to reduce nasal staphylococcal carriage

Xylitol may be of value in decreasing ASL salt

rates in normal volunteers (Table I).19
In an experimental study, Brown et al. administered
xylitol, saline and Pseudomonas aeruginosa to the

sinonasal symptoms ( p = 0.0437)

rabbit maxillary sinus.25 They observed that the simultan-
Results

from 0.86 to 0.06 per month

eous administration of xylitol and P aeruginosa produced

No difference in VAS scores

a statistically significant increase in bacterial killing after
20 minutes compared with normal saline. They reported
that xylitol reduced experimentally induced sinusitis
airway surface

when administered simultaneously with bacteria, but its

effect in established sinusitis was not clear.
Recently, Weissman et al. evaluated the effect of
nasal irrigation with xylitol in subjects with chronic rhi-
nosinusitis (Table I).20 Twenty subjects with chronic
sinusitis were instructed to complete two sequential
10-day courses of daily xylitol and saline irrigations,
in a randomised fashion. The authors observed a sig-
nificant reduction in Sino-Nasal Outcome Test 20
Coagulase-negative staphylococcus in

scores associated with xylitol irrigation as compared

with saline irrigation, indicating improved sinonasal
Outcome measures

symptoms for xylitol irrigation.

Occurrence of ear infection

SNOT-20 & VAS scores

culture of nasal swabs
Continued

Miscellaneous studies on xylitol in ENT

disorders
An in vitro study by Kontiokari et al. showed that
Table I

xylitol markedly reduced the growth of α-haemolytic

streptococci, including S pneumoniae.6 In addition, it
slightly reduced the growth of β-haemolytic strepto-
cocci, but not that of H influenzae or Moraxella catar-
12 g dissolved in 240 ml water – 5% w/v) vs
Vehicle: xylitol nasal irrigation (10-day course,

rhalis. A later study by the same research group

Vehicle: xylitol nasal spray (xylitol/water 5%
w/v spray for 4 days) vs saline (placebo)

indicated the anti-adhesive effects of xylitol against

Design: DBPCRT cross-over pilot study

both S pneumoniae and H influenzae in a mixture of

oropharyngeal epithelial cells and bacteria.7
Vehicle: xylitol + saline nasal spray

In an experimental study, Renko et al. reported the

Subjects: 20 subjects with CRS
Design: DBPCRT cross-over
Subjects: 21 healthy subjects

saline irrigation (placebo)

beneficial effects of xylitol-supplemented nutrition on

Methods

both the oxidative killing of bacteria in neutrophilic

Age range: 20–52 years

Average age: 44 years

leucocytes and on the survival of rats with experimen-

Design: case report

tally induced sepsis with S pneumoniae.26 Xylitol was

visual analogue scale; CRS = chronic rhinosinusitis
Dropout: n = 5

also shown to be cytoprotective during oxidative

stress.27
In clinical trials, xylitol supplementation has been
shown to decrease the occurrence of acute otitis
media in day-care children; however, the nasopharyn-
geal carriage of the pneumococci was not reduced.13
The capsular cpsB gene is essential for encapsulation
Weissmann et al. (2011)20

and for regulation of the production of capsular poly-

saccharide for streptococci.28 Kurola et al. showed
Zabner et al. (2000)19

that exposure to xylitol significantly lowered cpsB

gene expression levels in S pneumoniae isolates.29
Jones (2001)18
Author (year)

They reported that xylitol changed the ultrastructure

of the pneumococcal capsule, which could explain
the high clinical efficacy of xylitol in preventing
otitis media without reducing nasopharyngeal carriage.
584 Ö SAKALLIOĞLU, I ADADAN GÜVENÇ, C CİNGİ

Xylitol safety and side effects 7 Kontiokari T, Uhari M, Koskela M. Antiadhesive effects of
xylitol on otopathogenic bacteria. J Antimicrob Chemother
Xylitol is absorbed slowly by the gut wall and may 1998;41:563–5
cause loose stools when ingested in large amounts. 8 Goldman MJ, Anderson GM, Stolzenberg ED, Kari UP, Zasloff
Oral xylitol is well tolerated in adults and children. M, Wilson JM. Human beta-defensin-1 is a salt-sensitive anti-
biotic in lung that is inactivated in cystic fibrosis. Cell 1997;
Whilst adults can tolerate daily doses of up to 200 g 88:553–60
of xylitol without gastrointestinal symptoms, children 9 Durairaj L, Launspach J, Watt JL, Businga TR, Kline JN,
can only tolerate daily xylitol doses of up to 45 g Thorne PS et al. Safety assessment of inhaled xylitol in mice
and healthy volunteers. Respir Res 2004;5:13
without gastrointestinal symptoms.30,31 In addition to 10 Milgrom P, Ly KA, Tut OK, Mancl L, Roberts MC, Briand K
loose stools, large amounts of xylitol may cause et al. Xylitol pediatric topical oral syrup to prevent dental
abdominal discomfort and osmotic diarrhoea.15 These caries: a double blind, randomized clinical trial of efficacy.
Arch Pediatr Adolesc Med 2009;163:601–7
side effects do not appear particularly dependent on 11 Miyasawa-Hori H, Aizawa S, Takahashi N. Difference in the
age or weight. It has been shown that adaptation to xylitol sensitivity of acid production among Streptococcus
xylitol occurs rapidly, such that the laxative effect mutans strains and the biochemical mechanism. Oral Microbiol
Immunol 2006;21:201–5
diminishes within several days of regular use.32 12 Faden H, Waz MJ, Bernstein JM, Brodsky L, Stanievich J, Ogra
Parenteral xylitol can cause minimal hyperuricaemia PL. Nasopharyngeal flora in the first three years of life in normal
without any pathophysiological consequences.5 and otitis-prone children. Ann Otol Rhinol Laryngol 1991;100:
612–5
Though tolerated well in modest doses, large amounts 13 Uhari M, Kontiokari T, Koskela M, Niemela M. Xylitol
of xylitol administered intravenously have been chewing gum in prevention of acute otitis media: double blind
reported to cause reno-cerebral oxalosis with renal randomised trial. BMJ 1996;313:1180–4
14 Uhari M, Kontiokari T, Niemela M. A novel use of xylitol
failure.33 sugar in preventing acute otitis media. Pediatrics 1998;102:
879–84
Conclusion 15 Tapiainen T, Luotonen L, Kontiokari T, Renko M, Uhari M.
Xylitol administered only during respiratory infections failed
Acute otitis media is one of the most prevalent and to prevent acute otitis media. Pediatrics 2002;109:1–5
costly illnesses in children throughout the world. The 16 Hautalahti O, Renko M, Tapiainen T, Kontiokari T, Pokka T,
prophylactic use of antibiotics has the desired effect, Uhari M. Failure of xylitol given three times a day for
preventing acute otitis media. Pediatr Infect Dis 2007;26:
but is liable to lead to the development of antimicro- 423–7
bial-resistant bacteria. Thus, new approaches are 17 Sezen OS, Kaytancı H, Eraslan G, Coşkuner T, Kubilay U,
required to prevent acute otitis media. The efficacy of Aydın S et al. Xylitol containing chewing gums in the manage-
ment of chronic otitis media with effusion. Mediterranean J
xylitol is comparable to that of the best-known prophy- Otol 2008;4:203–10
lactic methods, such as continuous antimicrobial 18 Jones AH. Intranasal xylitol, recurrent otitis media and asthma:
prophylaxis and surgical procedures. Xylitol delivered three case studies. Clinical Practice of Alternative Medicine
2001;2:112–7
to the nasal or sinus mucosa may enhance innate bac- 19 Zabner J, Seiler MP, Launspach JL, Karp PH, Kearney WR,
terial defences by modifying the airway surface liquid Look DC et al. The osmolyte xylitol reduces the salt concentra-
salt concentration. Xylitol can be used to prevent tion of airway surface liquid and may enhance bacterial killing.
Proc Natl Acad Sci USA 2000;97:11614–9
the onset or delay the progress of rhinosinusitis. 20 Weissman JD, Fernandez F, Hwang PH. Xylitol nasal irrigation
Furthermore, in populations with high rates of tooth in the management of chronic rhinosinusitis: a pilot study.
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21 Uhari M, Tapiainen T, Kontiokari T. Xylitol in preventing otitis
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Xylitol may be a promising agent for this purpose in 23 Ear infections and xylitol. In: http://www.drgreene.com/qa/
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Dr I Adadan Guvenc takes responsibility for the integrity
Address for correspondence:
of the content of the paper
Dr I Adadan Guvenc,
Competing interests: None declared
Başkent Üniversitesi,