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Oral health benefits of chewing gumWessel, Stefan

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Chewing gum:

From candy to nutraceutical

-

Advantages in oral biofilm control

Stefan W. Wessel, Henny C. van der Mei, Amarnath Maitra,

Michael W.J. Dodds and Henk J. Busscher

Submitted to Clinical Oral Investigations

Chapter 2

CHAPTER 2

6

2

Abstract

Objectives

Over the years, chewing gum has developed from a candy towards an oral-health

promoting nutraceutical. This review summarizes evidence for oral-health benefits of

chewing gum, with emphasis on identification of active ingredients in gum that facilitate

prevention and removal of oral biofilm.

Results

Chewing of sugar-free gum yields oral-health benefits that include clearance of interdental

debris, reduction in oral dryness and amount of occlusal oral biofilm. These basic effects of

the chewing of gum are attributed to increased mastication and salivation. Active

ingredients incorporated in chewing gums aim to expand these effects to inhibition of

extrinsic tooth stain and calculus formation, stimulation of enamel remineralization,

reduction of the numbers of bacteria in saliva and amount of oral biofilm, neutralization of

biofilm pH, and reduction of volatile sulfur compounds. However, clinical benefits of

incorporating active ingredients are often hard to prove, since they are frequently

overshadowed by the effects of increased mastication and salivation and require daily

chewing of gum for prolonged periods of time.

Conclusion

Evidence for oral-health benefits of chewing gum additives is hard to obtain viz a viz

additives in advanced toothpaste formulations or mouthrinses due to their relatively low

concentrations and rapid wash-out. Clinical effects of gum additives are overshadowed by

effects of increased mastication and salivation due to the chewing of gum.

Clinical relevance

Chewing of sugar-free gum can contribute to oral health provided used on a daily basis,

but clinical benefits of incorporating active ingredients into chewing gum are hard to

demonstrate over the beneficial effects of increased mastication and salivation.

CHEWING GUM: FROM CANDY TO NUTRACEUTICAL

7

2

Introduction

Many oral diseases, most notably caries, gingivitis and periodontitis are caused by oral

biofilms. The development of a pathogenic biofilm depends to a major part on the amount

and composition of the biofilm. The formation of oral biofilm constitutes the transition of

bacteria from their freely suspended or planktonic state in saliva to an adhering or sessile

state on oral hard and soft tissues. In the oral cavity, due to the abundant presence of

salivary proteins, bacteria never adhere to bare surfaces but always to an adsorbed

salivary conditioning film (1). Small differences in the forces by which bacteria are attracted

to these salivary conditioning films play a determining role in the composition of oral biofilm

on intra-oral surfaces (2). Upon further growth of the biofilm, more strains and species

become incorporated in a biofilm through co-adhesion with other colonizers, governed by

an interplay between specific ligand-receptor binding and non-specific bacterial interactions

(3,4). Oral diseases develop when cariogenic strains in a biofilm produce an excess of

acids through the fermentation of environmental sugars causing enamel demineralization

or when periodontopathogens residing mostly in gingival pockets, cause gingivitis or in

more advanced state, periodontitis (5).

Although much has been achieved with respect to the prevention of oral diseases

like caries, gingivitis and periodontitis (6,7), maintenance of effective oral hygiene by

toothbrushing, using advanced toothpaste formulations and mouthrinses remains beyond

reach for many people. Therefore a variety of other mechanical aids such as toothpicks,

floss wire and chewing gum has been promoted for the removal of oral biofilm (8). In this

review we evaluate possible oral health benefits of chewing gum, with special emphasis on

the identification of active ingredients incorporated in gum that facilitate prevention and

removal of oral biofilm.

History and development of chewing gum

Throughout history, various materials have been used by people to chew upon in order to

refresh their breath or relieve oral dryness. Early types of chewing gum are based on tree

resins. It was not until 1870 that Thomas Adams was able to successfully market chewing

gum on a mass scale (9,10). Since its first introduction, chewing gum has developed into a

multi-billion dollar industry (9,11) aided by the invention of rubbers in the 1930s and 1940s

(12). In the 1970s, chewing gum developed more and more from a candy towards a

functional food aiming for niche markets, like non-stick gum for denture wearers, gums with

tooth-whitening properties or preventing halitosis (13,14). The current portfolio of chewing

CHAPTER 2

8

2

gums meets the specific demands of various types of consumers and follows the need to

differentiate in a competitive world (15). Following compliance with different consumer

requirements, chewing gum has become recognized for its role in maintenance and

improvement of oral health (9).

Current chewing gums consist of a few basic ingredients. The gum base provides

elasticity to a gum and should not dissolve during chewing. Moreover, it should allow a

gum to be chewed for relatively long periods of time without major changes in structure.

Generally, gum base consists of a mixture of elastomers, like polyvinylacetate or

polyisobutylene, that are complemented with softeners, texturizers and other ingredients as

emulsifiers and plasticizers. Hydrophilicity of the base system is an important determinant

for the ability of gums to take up water or saliva, which influences chewing gum texture.

Molecular weight of the polymer ingredients, together with the interaction with the other

ingredients, determine gum viscosity. Tendency to absorb saliva is mainly determined by

emulsifiers, which create a stable mixture of normally immiscible ingredients. Formulation

of the latter ingredients is adjusted based on desired functionality.

Approximately 70 % of all gums marketed do not contain conventional

sweeteners, like sucrose, but have sugar substitutes like xylitol, sorbitol, mannitol and/or

maltitol and are considered to be sugar-free gums (16). Aspartame, acesulfame-K and

glycerine add an extra degree of sweetness and also provide longer lasting flavor duration

(15,17,18). Polyols are widely used instead of conventional sugars and the main

advantage is that they are not or hardly fermented by bacteria, classifying them as non-

acidogenic (19) and cariostatic (20). The replacement of conventional sugars to create

sugar-free gums, was the most important development advancing chewing gum from a

candy to a nutraceutical with specific oral health benefits.

Benefits of chewing gum on oral health

Chewing of gum stimulates the salivary glands, causing approximately a tenfold increase in

salivary flow over unstimulated salivation during the first five minutes of chewing (21).

Increased salivation together with the mechanical action of mastication provides the basis

for many effects of chewing gum on oral health (See Fig. 1 and Table 1 for an overview).

Furthermore, chewing gum is an excellent vehicle for administering active ingredients to

the oral cavity. Possible oral health benefits of the chewing of gum are summarized in the

different circle segments in Fig. 1, together with the active ingredients assumed

responsible for these benefits.

CHEWING GUM: FROM CANDY TO NUTRACEUTICAL

9

2

A gradual release profile of active ingredients from chewing gum can readily be

achieved, potentially making their prolonged presence and substantive action in the oral

cavity possible (18). However, at the same time, increased salivation stimulates rapid

wash-out of active ingredients from the oral cavity making their clinical efficacy hard to

demonstrate over the basic effects of increased salivation and mastication.

Figure 1 Basic effects of the chewing of regular sugar-free gum on oral health are displayed in the inner ring,

and are predominantly due to increased mastication and salivation. Potential effects of active

ingredients used in chewing gum on oral health are displayed in the outer ring.

CHAPTER 2

10

2

Reduction of oral dryness Individuals suffering from xerostomia or the subjective feeling of dry mouth, can relief their

symptoms by the use of regular sugar-free chewing gum (Fig. 1), which is generally

preferred by dry mouth patients over the use of artificial saliva (22). Symptom relief is

related to mastication and increased salivation and not to any specific additive incorporated

in chewing gums (23). Importantly, the claim that the chewing of gum reduces dry mouth

perception (23,24), is supported by the European Food Safety Authority (EFSA).

Clearance of interdental debris The chewing of gum can stimulate removal of interdental debris left after food

consumption, as illustrated in Fig. 2. Removal is partly due to direct attachment of debris to

the gum but also due to increased mastication and salivation which aids to wash away

debris (25,26). Since debris left after food consumption often contains fermentable sugars,

its removal prevents oral bacteria from producing acids that desorb calcium (Ca2+) and

phosphates (PO43-) from the enamel (21,27–30), which constitutes a clear oral health

benefit (Fig. 1).

Inhibition of calculus formation

Calculus formation involves the formation of calcium phosphate mineral salts, that calcify

and harden oral biofilm. Among many other factors, biofilm pH and salivary calcium

phosphate saturation play an important role in the rate of calculus formation (31,32).

Chewing of regular sugar-free gum did not have a pronounced effect on inhibiting

calculus formation and it has even been suggested that calculus formation is promoted by

chewing sugar-free gum, due to higher biofilm pH and salivary calcium phosphate

saturation (33–35). Therefore, active ingredients have been incorporated in chewing gums

aiming to maintain calcium phosphate deposits in an amorphous state, preventing

hardening and facilitating removal. When chewing vitamin C supplemented chewing gum

at least five times per day for three months, a reduction in supra-gingival calculus formation

was found compared to not chewing gum (35). Similar results were obtained for pyro/tri-

phosphates supplemented chewing gum after six weeks use (36). Nevertheless, since

reductions in calculus formation were only demonstrated for supra-gingival surfaces, and

not for gingival margins and interproximal spaces that matter most in oral health, a

negative verdict was released by the EFSA on oral health claims regarding a reduction in

calculus formation by pyro/tri- phosphates in sugar-free gums (37) (Table 1).

CHEWING GUM: FROM CANDY TO NUTRACEUTICAL

11

2

Figure 2 Removal of food debris (Cookie) from occlusal surfaces after 2 min chewing of regular sugar-free gum

(top panel) or without the chewing of gum (bottom panel). No specific instructions were given to the

volunteer.

Inhibition of extrinsic tooth stain

Aesthetics, including the appearance of white teeth, is more and more considered as an

important component of oral health. Extrinsic tooth stain is caused by chromogens from

food, drinks or smoking that absorb in superficial enamel layers (or calculus). Extrinsic

tooth stain is more susceptible to whitening regimens than intrinsic tooth stain, but still

usually requires professional removal, depending on the causative chromogen. Chewing of

regular sugar-free gum multiple times per day for four weeks or longer has been shown to

prevent and remove extrinsic tooth stain caused by chromogens (13,38,39), likely again as

a result of increased salivation (Fig. 1).

To enhance extrinsic stain prevention and removal (13), sugar-free chewing gum

has been supplemented with polyphosphates (40,41). Sodium hexametaphosphate (Table

1) in a sugar-free gum, reduced stain formation better than a control gum in short-term, two

day studies during which volunteers chewed eight times two tablets of gum throughout the

day (41–43). When chewing three times two tablets per day for six weeks or longer, tooth

stain prevention has been shown for hexametaphoshate, pyrophosphate and

tripolyphosphate supplemented sugar-free gums (44,45). Stain prevention by

polyphosphates has been attributed to adsorption of these highly negatively charged and

hydrophilic molecules to salivary conditioning films which makes incorporation of

Before

Removal of food debris without chewing of gum

Removal of food debris after chewing of gum

CHAPTER 2

12

2

chromogens in superficial enamel layers more difficult. Administration of sodium

hexametaphosphate through the chewing of gum produced a more hydrophilic tooth

surface in vivo than a control gum (46), while sodium hexametaphosphate caused

desorption of proteins from adsorbed salivary conditioning films and created a more open

film structure in vitro (47,48).

Reduction of volatile sulfur compounds

Oral malodor, or halitosis, results from the production of volatile sulfur compounds (VSCs),

such as hydrogen sulfide and methyl-mercaptan by anaerobic Gram-negative bacteria

adhering to the tongue or associated with periodontitis (49). Regular sugar-free chewing

gum has been shown to successfully reduce VSCs and thereby freshen breath (14) (Fig.

1). Besides the reduction of VSCs by the regular chewing of sugar-free gum, active

ingredients incorporated in a gum have aimed to further reduce halitosis either by directly

interacting with VSCs or by targeting bacteria responsible for oral malodor (Table 1). Zinc

has high affinity for sulfur compounds (50) and, especially in combination with allyl

isothiocyanate (51), results in reduced VSC levels directly after chewing compared to a

control gum (52), although this could not be confirmed in another study (14). Furthermore

magnolia bark extract and eucalyptus both target the viability of VSC producing bacteria

and were shown to be effective against oral malodor in a chewing gum (53,54), especially

when magnolia bark extract was combined with zinc (55) (Table 1).

Neutralization of biofilm pH The pH buffering ability of saliva counteracts acids produced in oral biofilm and is therefore of importance to maintain the intra-oral balance between enamel re- and demineralization. Bicarbonate (HCO3

-) provides the main buffering system of saliva and neutralizes oral

biofilm pH (56,57). Neutralization of biofilm pH is also achieved via a different mechanism

involving carbamide ((NH2)2CO) or urea. Oral bacteria that produce urease hydrolyze and

convert carbamide into ammonia and create a more alkaline environment. Chewing of

regular sugar-free gum has been shown to increase biofilm pH, as also recognized by the

EFSA (58). Furthermore it increases the resting pH of oral biofilm and resistance of the

enamel surface to acid challenges (59) as a result of increased salivation. This effect was

enhanced by the addition of xylitol to chewing gum (Table 1) (60).

Addition of other actives such as bicarbonate to chewing gum also caused an

increase in the buffering capacity of saliva (61). Accordingly, interproximal biofilm pH, after

a sucrose challenge, was elevated more rapidly and maintained at a higher level compared

to a gum without bicarbonate (62). Furthermore chewing of carbamide supplemented gum

CHEWING GUM: FROM CANDY TO NUTRACEUTICAL

13

2

yielded a concentration dependent rise in biofilm pH (63,64). The EFSA has concluded that

the claim that chewing gum containing carbamide stimulates biofilm pH neutralization

directly after chewing is justified when the gum contained at least 20 mg of carbamide and

was chewed for 20 min after food intake (65). However, when effects of the chewing of

carbamide supplemented gum were evaluated for four weeks or longer, no change in acid

production by oral biofilm was observed (64), neither were caries preventive effects

observed after three years of use in terms of a reduced number of decayed, missing or

filled surfaces (66). This shows that short term results cannot be readily extrapolated to

long term effects, most likely because short term studies do not include enamel

demineralization due to food and drink consumption, effects that are apparently only

influential in long-term studies.

Enamel remineralization

Saliva is rich in calcium and phosphates, facilitating enamel remineralization and

preventing demineralization (9). Chewing of regular sugar-free gum can enhance calcium

and phosphate levels in the oral cavity through increased salivation. Long-term clinical

studies showed that chewing of regular sugar-free gum multiple times per day, especially

after a meal in addition to normal oral hygiene, can results in lower caries incidence

(66,67). The latter was acknowledged by the EFSA (24,68) (Fig. 1).

In order to increase the effects of the chewing of gum on remineralization, calcium

has been added to chewing gums either in the form of ionic calcium or casein-calcium

conjugates (CPP-ACP) (Table 1). In situ studies with demineralized enamel slabs placed in

the oral cavity using specific intra oral appliances and removed after the chewing of gum

supplemented with calcium phosphates, demonstrated increased remineralization

compared to chewing of regular sugar-free gum (69,70). Unfortunately, in these studies the

intra oral appliances were worn only for approximately forty minutes after the chewing of

gum or were removed during food intake. Therewith demineralization is largely left out of

consideration (71). A review on calcium phosphate supplemented chewing gum concluded

that these additives to chewing gum did not yield increased caries prevention (72). In

accordance with the latter study, the EFSA does not support a health claim on increased

remineralization of chewing gum containing calcium phosphates as compared to regular,

sugar-free gums (73).

CPP-ACP has been suggested to deposit a calcium and phosphate reservoir on the tooth

surface and the surface of oral biofilm, inhibiting enamel demineralization and promoting

remineralization (74). Similar to calcium phosphates, significant, dose-dependent, enamel

remineralization and increased resistance against demineralization were reported in situ

CHAPTER 2

14

2

after use of CPP-ACP containing gum compared to a control gum (75–77). However,

contrary to calcium phosphates, the caries preventive effect of CPP-ACP could be

demonstrated in a long-term, two year study involving 2720 volunteers, showing that when

CPP-ACP gum was chewed three times per day, there was 18% less chance of a tooth

surface progressing to caries compared to a control gum (78). Nonetheless there is no

unanimous positive judgment on the remineralization potential of CPP-ACP in chewing

gum and while most studies on CPP-ACP were done by the same research group, studies

by others did not confirm beneficial effects of chewing CPP-ACP supplemented gums on

remineralization (79,80).

Fluoride (Table 1) hardens the enamel as it is incorporated in the hydroxyapatite

lattice network of the crystallites, creating less soluble fluorohydroxyapatite (81). Its

incorporation in a chewing gum was shown in four week in situ studies to enhance

remineralization of enamel compared to a control gum (82), likely to be more effective on

the side of the dentition which is used mostly for chewing (83). The EFSA considers that

the general health claims with respect to the use of fluoride also apply to fluoridated

chewing gum (84). However, the chewing of fluoridated gum did not yield additional

benefits when used in combinations with a regular oral hygiene with fluoridated products

(85).

Reduction of oral biofilm formation and impact on biofilm composition

Oral bacteria adhere to salivary conditioning films in order to avoid being washed away by

salivary flow, and adhesion is governed by the forces by which specific planktonic bacteria

are attracted to the salivary conditioning film (2). Only the so-called initial colonizers adhere

directly to the conditioning film and later colonizers co-adhere with initial colonizers to yield

a multispecies biofilm (4). Disease usually develops when the composition of oral biofilm

shifts towards a predominance of specific pathogens. Active ingredients in chewing gums

(Table 1) can affect oral biofilm formation at various stages either by reducing the number

of specific planktonic bacteria, preventing their adhesion or reducing growth of adhering

bacteria to yield less biofilm or biofilm with a different microbial composition.

Effects on planktonic bacteria in saliva

Planktonic bacteria suspended in saliva constitute the source of bacteria for initial adhesion

and biofilm formation on oral surfaces. Therefore the effects of active ingredients in

chewing gum on the amount of salivary pathogens such as cariogenic Streptococcus

mutans or Streptococcus sobrinus, commonly referred to as mutans streptococci, are often

used as an indicator of potential oral health benefits. Chewing of regular, sugar-free gum

CHEWING GUM: FROM CANDY TO NUTRACEUTICAL

15

2

was shown to be able to non-specifically trap oral bacteria within a piece of gum and

thereby remove bacteria from the oral cavity, although it could not be firmly established

whether the bacteria trapped in chewed gum originated from saliva or the biofilm formed on

the dentition (86). Chewing of gum had no specific effect on salivary mutans streptococcal

concentrations (87,88). However, some artificial polyol sweeteners, particularly xylitol when

used exclusively, were reported to reduce salivary mutans streptococcal numbers (89). A

minimum of 6 g of xylitol per day during five weeks was necessary to reach a significant

reduction in mutans streptococcal numbers (90–93). Xylitol should be preferred over other

sweeteners such as sorbitol which are reported to be low cariogenic, which again should

highly be preferred over conventional sugars (94,95). Other ingredients incorporated in

chewing gum such as chlorhexidine, chitosan, magnolia bark extract and mastic were also

shown to lower the number of planktonic bacteria in saliva compared to a control gum

(88,96–98).

Effects on bacterial adhesion to oral surfaces

Adhesion of planktonic bacteria to oral surfaces is the first step in the formation of oral

biofilm and is mediated by attractive forces between oral surfaces and adhering bacteria.

Accordingly, the properties of the oral surfaces play a major role in the development of

these adhesion forces and changing the forces may impact the amount and composition of

oral biofilm formed (2,99). Chewing a gum containing polyphosphates made adsorbed

salivary conditioning films more hydrophilic and more negatively charged as compared with

other gums. Since most oral bacterial strains are negatively charged (46,48), this implies

weaker adhesion of oral bacteria and polyphosphates may even promote detachment of

bacteria from salivary conditioning films on enamel surfaces (100).

Effects on biofilm formation, composition and removal

Chewing of regular sugar-free gum dislodges loosely bound bacteria from the oral mucosa

(101) and inhibits regrowth and maturation of oral biofilm on occlusal surfaces (102) (Fig.

1). Nonetheless, biofilm regrowth was not inhibited on smooth lingual and buccal surfaces

and a relation between complete biofilm removal directly after a single gum chew has not

been established (103,104), not even when abrasive agents were included in the gum

(105). Therefore the EFSA concluded that the claim that the chewing of regular sugar-free

gum “reduces plaque formation” is unsubstantiated (103) so direct and clinically relevant

biofilm reduction is not a supportable claim for chewing gum without active ingredients,

although it is possible that gum chewing could modify the biofilm composition to a less

cariogenic state.

CHAPTER 2

16

2

Chlorhexidine is the most effective antimicrobial for the chemical control of oral

biofilm (106). Its antimicrobial properties are based on disturbing the bacterial cell-

membrane and its binding to intra-oral surfaces ensures substantive action (106).

Chlorhexidine tastes bitter, alters long term taste perception (106) and causes (reversible)

tooth stain (107). Antimicrobially effective chlorhexidine containing chewing gums with

acceptable taste can be made (108), but consumer hesitance remains to exist and in

certain countries chlorhexidine containing chewing gums are likely to only be available on

prescription (59,109). Application of chlorhexidine in chewing gum reduces planktonic

levels of mutans streptococci directly after chewing (96), but also reduces oral biofilm

formation. Incorporation of chlorhexidine in chewing gum inhibited oral biofilm growth in a

four day study when only two pieces of gum were chewed per day in absence of other oral

hygiene measures (109). When used for one year, chlorhexidine containing chewing gum

showed a stronger reduction in gingival index and amount of oral biofilm formed than a

xylitol containing gum (110,111), but concerns remain about long-term consumption of

potent antimicrobial agents.

Similar to chlorhexidine, xylitol also resulted in reduction of salivary mutans

streptococcal numbers when used for five weeks, but this was too short to result in a

change in composition of oral biofilm (89,112). Also, in combination with regular brushing,

no effects of xylitol containing gum on biofilm and gingivitis scores were observed

compared to chewing gum base only (113). Six months chewing of xylitol containing gum

caused a decrease in the acidogenicity of oral biofilm (60), indicative of a change in biofilm

composition. In general, oral health care benefits of xylitol on oral biofilm are still subject to

debate and it is not clear whether effects of xylitol containing gum are solely due to

increased salivation or to the addition of xylitol as well (87,114,115).

Of the other ingredients mentioned above to lower planktonic levels of bacteria,

only mastic and eucalyptus containing chewing gum were hinted to successfully reduce

oral biofilm formation better than a control gum under the artificial condition of refraining

from other oral hygiene measures (116–118).

CHEWING GUM: FROM CANDY TO NUTRACEUTICAL

17

2

CHAPTER 2

18

2

Table 1 – Overview of active ingredients used in different chewing gums and oral health benefits

reported in the literature.

Activ

e in

gred

ient

Ef

fect

R

emar

ks

EFSA

su

ppor

t R

efer

ence

s

Non

e (b

asic

effe

cts

of

regu

lar s

ugar

-free

gu

m)

Red

uctio

n of

ora

l dry

ness

Che

win

g of

gum

can

relie

f dry

mou

th s

ympt

oms

durin

g ch

ewin

g Ye

s (2

3,24

)

C

lear

ance

of i

nter

dent

al

debr

is

Che

win

g gu

m in

crea

ses

rate

of c

lear

ance

of f

ood

debr

is, i

t rem

oves

sou

rces

of f

erm

enta

ble

suga

rs

-

(25,

26)

In

hibi

tion

of e

xtrin

sic

toot

h st

ain

Che

win

g at

leas

t 4 ti

mes

15

min

per

day

for 4

wee

ks o

r lon

ger r

educ

es e

xtrin

sic

toot

h st

ain

- (1

3,39

)

R

educ

tion

of V

SCs

Che

win

g gu

m te

mpo

raril

y fre

shen

s br

eath

by

redu

cing

VSC

s af

ter c

hew

ing

- (1

4)

N

eutra

lizat

ion

of b

iofil

m p

H

Incr

ease

d sa

livat

ion

neut

raliz

es b

iofil

m p

H

Yes

(24,

56–5

8)

R

emin

eral

izat

ion

of e

nam

el

Stim

ulat

ed s

aliv

a is

sat

urat

ed w

ith m

iner

als

incr

easi

ng re

min

eral

izat

ion

Yes

(9,2

4,68

)

R

educ

tion

of o

ral b

iofil

m

Prev

entin

g bi

ofilm

regr

owth

at o

cclu

sal s

urfa

ces

whe

n re

frain

ing

from

ora

l hyg

iene

for 4

day

s. N

o bi

ofilm

re

duct

ion

at o

ther

toot

h su

rface

s N

o (1

02,1

03,1

05)

C

arie

s pr

even

tion

Red

uced

car

ies

inci

denc

e ov

er 2

-3 y

ears

whe

n us

ing

2-3

g of

gum

for 2

0 m

in d

irect

ly a

fter m

eal

Yes

(24,

58,6

6–68

)

Bica

rbon

ate

Neu

traliz

atio

n of

bio

film

pH

Bi

ofilm

pH

ele

vate

d fa

ster

by

chew

ing

bica

rbon

ate

gum

afte

r suc

rose

cha

lleng

e -

(61,

62)

Cal

cium

R

emin

eral

izat

ion

of e

nam

el

In s

itu s

tudi

es s

how

sho

rt te

rm in

crea

sed

rem

iner

aliz

atio

n. N

o ad

ditio

nal c

arie

s pr

even

tive

effe

ct

No

(69,

70,7

3)

Car

bam

ide

Neu

traliz

atio

n of

bio

film

pH

C

once

ntra

tion

depe

nden

t ris

e in

bio

film

pH

. At l

east

20

mg

per p

iece

for 2

0 m

in d

irect

ly a

fter a

mea

l. N

o ad

ditio

nal c

arie

s pr

even

tive

effe

ct

Yes

(63–

65)

C

hito

san

Red

uctio

n of

pla

nkto

nic

bact

eria

in s

aliv

a R

educ

es to

tal n

umbe

r of o

ral b

acte

ria in

sal

iva

dire

ctly

afte

r che

win

g -

(97)

Chl

orhe

xidi

ne

Red

uctio

n of

pla

nkto

nic

bact

eria

in s

aliv

a

Dec

reas

e of

leve

ls o

f sal

ivar

y m

utan

s st

rept

ococ

ci d

irect

ly a

fter c

hew

ing

- (9

6)

R

educ

tion

of o

ral b

iofil

m

Bi

ofilm

gro

wth

was

inhi

bite

d w

hen

refra

inin

g fro

m o

ral h

ygie

ne fo

r 4 d

ays

-

(109

,110

)

In

crea

sed

ging

ival

hea

lth

Si

gnifi

cant

redu

ctio

n in

gin

giva

l ind

ex c

ompa

red

to c

ontro

l gum

afte

r 1 y

ear u

se

- (1

10,1

11)

CHEWING GUM: FROM CANDY TO NUTRACEUTICAL

19

2

CPP

-AC

P R

emin

eral

izat

ion

of e

nam

el

In

situ

stu

dies

sho

w s

hort

term

incr

ease

d re

min

eral

izat

ion

- (7

6,77

)

C

arie

s pr

even

tion

Larg

e sc

ale

2 ye

ar s

tudy

sho

ws

18%

less

cha

nce

of to

oth

surfa

ce p

rogr

essi

ng to

car

ies

whe

n ch

ewin

g C

PP-A

CP

3 tim

es p

er d

ay c

ompa

red

to c

ontro

l gum

-

(78)

Euca

lypt

us

Red

uctio

n of

bac

teria

pr

oduc

ing

VSC

s

Dec

reas

e in

org

anol

eptic

sco

re a

nd V

SCs

afte

r 14

wee

k us

e co

mpa

red

to c

ontro

l gum

-

(54)

R

educ

tion

of o

ral b

iofil

m

Bi

ofilm

form

atio

n w

as s

igni

fican

tly re

duce

d co

mpa

red

to c

ontro

l gum

whe

n re

frain

ing

from

ora

l hyg

iene

for 4

day

s -

(116

)

In

crea

sed

ging

ival

hea

lth

Bene

ficia

l effe

ct o

n pr

obin

g de

pth

and

ging

ival

ble

edin

g af

ter 1

2 w

eeks

use

-

(118

)

Fluo

ride

Rem

iner

aliz

atio

n of

ena

mel

G

ener

al fl

uorid

e cl

aim

s al

so a

pply

on

fluor

idat

ed c

hew

ing

gum

. Effe

ctiv

e in

cas

e ot

her w

ays

of a

dmin

istra

ting

fluor

ide

are

not p

ossi

ble

Yes

(82–

84)

Mag

nolia

bar

k ex

tract

R

educ

tion

of p

lank

toni

c ba

cter

ia in

sal

iva

Red

uctio

n of

tota

l sal

ivar

y ba

cter

ia a

nd m

utan

s st

rept

ococ

ci d

irect

ly a

fter c

hew

ing

and

afte

r 30

days

of u

se

- (5

3,88

)

R

educ

tion

of b

acte

ria

prod

ucin

g VS

Cs

Red

uctio

n of

VSC

s di

rect

ly a

fter c

hew

ing

and

in v

itro

effe

ctiv

enes

s ag

ains

t bac

teria

resp

onsi

ble

for o

ral m

alod

or

- (5

3,55

)

Mas

tic

Red

uctio

n of

pla

nkto

nic

bact

eria

in s

aliv

a

Red

uctio

n of

tota

l sal

ivar

y ba

cter

ia a

nd s

aliv

ary

mut

ans

stre

ptoc

occi

dire

ctly

afte

r che

win

g co

mpa

red

to c

ontro

l gu

m

- (9

8,11

7)

R

educ

tion

of o

ral b

iofil

m

Inhi

bitio

n of

bio

film

form

atio

n w

hen

refra

inin

g fro

m o

ther

ora

l hyg

iene

for 7

day

s co

mpa

red

to c

ontro

l gum

-

(117

)

Poly

ols -

Xyl

itol

Red

uctio

n of

pla

nkto

nic

bact

eria

in s

aliv

a

Whe

n us

ed fo

r 5 w

eeks

xyl

itol g

um is

mor

e ef

fect

ive

in re

duci

ng s

aliv

ary

mut

ans

stre

ptoc

occi

than

a c

ontro

l gum

. N

o ch

ange

in b

iofil

m c

ompo

sitio

n w

as o

bser

ved

- (8

9,11

4)

N

eutra

lizat

ion

of b

iofil

m p

H

N

eutra

lizat

ion

of b

iofil

m p

H w

as o

bser

ved

afte

r lon

g te

rm u

se (6

mon

ths)

N

o (6

0)

C

arie

s pr

even

tion

Valid

whe

n 10

0% x

ylito

l gum

is u

sed

thre

e tim

es p

er d

ay in

hig

h do

se (≥

6 g

per d

ay)

Yes

(92,

93)

Poly

phos

phat

es

Inhi

bitio

n of

cal

culu

s fo

rmat

ion

Cal

culu

s re

duct

ion

supr

agin

giva

lly, n

ot a

t site

s w

hich

mat

ter m

ost f

or g

ingi

val h

ealth

(gin

giva

l mar

gin,

in

terp

roxi

mal

spa

ces)

N

o (3

6,37

)

In

hibi

tion

extri

nsic

toot

h st

ain

Stai

n in

hibi

tion

with

in tw

o da

ys w

hen

chew

ed 8

tim

es p

er d

ay. W

ith 3

tim

es p

er d

ay s

tain

inhi

bitio

n w

as s

how

n af

ter s

ix w

eeks

- (4

1,42

,45)

Vita

min

C

Inhi

bitio

n of

cal

culu

s fo

rmat

ion

Red

uctio

n of

sup

ragi

ngiv

al c

alcu

lus

form

atio

n co

mpa

red

to n

o ch

ewin

g w

hen

used

5 ti

mes

per

day

for t

hree

m

onth

s -

(35)

Zinc

R

educ

tion

of V

SCs

Red

uctio

n of

VSC

s di

rect

ly a

fter c

hew

ing

com

para

ble

to z

inc

mou

thrin

se

- (5

2)

CHAPTER 2

20

2

Future outlook: improving the performance of chewing gum as an oral health promoting nutraceutical

Over the last decades chewing gum developed from a candy towards an oral health

promoting nutraceutical to be used as an adjunct to regular oral hygiene. The basic

beneficial effects of the chewing of gum on oral health have been well documented and are

mostly officially approved by the EFSA (see Fig. 1 and Table 1). The same cannot be said

about many active ingredients that are incorporated in chewing gum to enhance the oral

health benefits perceived, mainly because most effects aimed for by chewing gum

additives are overshadowed by effects of increased salivation and mastication as readily

achieved by the chewing of regular, sugar-free gum.

The main hurdle in demonstrating oral health care benefits of active ingredients

added to chewing gums is the same as with many other nutraceuticals: their potency is

generally low. This implies that when evaluated in vitro, nutraceuticals will always do

significantly less well than the “positive controls”, that are often used therapeutically. The in

vitro comparison of nutraceuticals, including chewing gum additives, with a therapeutic

drug however, is not a valid one, as nutraceuticals are seldom or never used

therapeutically but most prophylactically.

Owing to the low potency of their active ingredients, chewing gums with active

ingredients incorporated as a nutraceutical, may and must be used several times a day

and for prolonged periods of time to demonstrate clinical efficacy. It has been proposed

that such studies should preferably last more than one year to map clinical effects of

chewing gums on oral health (66,78,119), which adds a major cost factor to the translation

of new additives to the market. Unfortunately, demonstration of clinical oral health care

benefits is easily clouded by other factors, particularly since the oral cavity is under the

influence of many environmental factors that are hard to control over longer periods of

time. As an alternative, it might be proposed that for nutraceuticals, such as chewing gums

with active ingredients with a low potency, significance levels greater than p < 0.05 should

be adopted with respect to a control in one and the same volunteer group.

The low antimicrobial potency of many chewing gum additives might turn into an

advantage when viewed with respect to gradually changing the composition of oral biofilm

into a less pathogenic one (120). Gradual is the preferred way of changing a microbiome in

order to make changes lasting (121) and to maintain a symbiotic relation with the host

(120). Chewing of gum has already been demonstrated to yield non-specific removal of

around 108 oral bacteria with a single chew (86) either from the planktonic, salivary or

biofilm microbiome. Although removal of 108 bacteria with a single chew may be

CHEWING GUM: FROM CANDY TO NUTRACEUTICAL

21

2

considered low compared to the total microbial load in the oral cavity, chewing gum can be

modified to specifically bind pathogenic bacteria and remove them from the oral cavity, for

instance by adding porous type calcium carbonate (122). Also inclusion of additives that

increase the surface hydrophobicity of specific bacteria may facilitate their removal from

the oral cavity by the subsequent administration of hydrophobic ligands, as has also been

demonstrated for the use of a triclosan containing toothpaste in combination with a

mouthrinse based on essential oils (123). As a final option to advance chewing gum further

to a nutraceutical that drives the oral microflora into a healthy direction, probiotics such as

lactobacilli can be added (124,125) to compete for a position on oral surfaces with oral

pathogens, similar to the events occurring in the gastro-intestinal tract between probiotics

and other members of the gastro-intestinal microbiome (126,127).

In summary, whereas evidence for oral health care benefits of chewing gum

additives is hard to obtain viz a viz additives in advanced toothpaste formulations or

mouthrinses due to their relatively low concentrations and rapid wash-out, the basic

benefits of the long-term chewing of sugar-free gum due to increased mastication and

salivation are mostly beyond dispute. Given the fact that the chewing of gum non-

specifically removes bacteria from the oral cavity by entrapment in gum with only temporal

effects, it seems feasible to construct gum formulations that do so in a more specific

fashion. Therewith long-term use of such gums may aid to restore and maintain a more

healthy oral microbiome, further contributing to the recognition of chewing gum as a

nutraceutical.

Conflict of interest This work was funded by Wm. Wrigley Jr. Co, Chicago, USA and SASA BV, Thesinge, NL.

Authors were employed by their own organizations. HJB is also director-owner of a

consulting company SASA BV. AM and MD are employees of the Wm. Wrigley Jr.

Company. Opinions and assertions contained herein are those of the authors and are not

meant to be construed as necessarily representing views of the organizations to which the

authors are affiliated.

CHAPTER 2

22

2

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CHAPTER 2

26

2

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