Volume 7, Issue 6, June – 2022 International Journal of Innovative Science and Research Technology

ISSN No:-2456-2165

CPP-ACP in the Treatment of Hyper Sensitivity

Associated with Vital Tooth Bleaching:
A Systematic Review
Pratyusha Giri Sathiyapriya S, Sindhu R., Bharathwaj V. V.
Undergraduate student, Senior Lecturer, Department of Public Health Dentistry,
SRM dental college, Ramapuram, Chennai, India SRM dental college, Ramapuram, Chennai, India

Dinesh Dhamodhar, Rajmohan M

Reader,Department of Public Health Dentistry,
SRM dental college, Ramapuram, Chennai, India

Elakiya S Prabu D
Postgraduate student, Professor and Head of the Department,
Department of Public Health Dentistry, Department of Public Health Dentistry,
SRM dental college, Ramapuram, Chennai, India SRM dental college, Ramapuram, Chennai, India

Abstract:- Hypersensitivity is the most common adverse However, it is contraindicated in patients with severe
effect of vital tooth bleaching. To overcome this, a lot of enamel loss, hypersensitivity, children with large pulp
desensitising agents are introduced. casein chambers, exposed root surface, dental caries etc.
phosphopeptide-amorphous calcium phosphate (CPP-
ACP) is a milk- derived complex that causes Vital tooth bleaching with peroxides has become the
demineralisation of tooth structure. To assess the most popular treatment regimen to brighten the discoloured
efficacy of casein phosphopeptide-amorphous calcium teeth [3]. The spectrum of vital bleaching ranges from
phosphate (CPP-ACP)in treating the hypersensitivity dentist- supervised in-office bleaching and dentist
associated with vital tooth bleaching.A systematic review prescribed at-home bleaching to over-the-counter consumer-
was performed using electronic databases like PubMed, available systems.
science direct, Wiley online library, lilacs and google
scholar using certain keywords. Out of 265 articles, five In-office bleaching is usually done with 35% hydrogen
articles were related to the research topic. The review is peroxide solution by placing it on the teeth followed by the
described according to the PRISMA guidelines.CPP- application of heat. These bleaching agents are
ACP is more effective in the treatment of sensitive teeth commercially available in gel, which prevents the running of
with vital tooth bleaching. The study concludes that material on application. Before application of the gel, it is
casein phosphopeptide-amorphous calcium phosphate important to protect the gingival tissues with Vaseline and
isolate the teeth with a rubber dam. The gel is activated by
complex (CPP-ACP) has the ability to reduce the post-
operative sensitivity caused by at-home and in-office application of heat. Hence it is known as thermocatalytic
vital tooth bleaching without affecting the colour bleaching. The entire treatment time should be less than 30
stability of the bleached tooth. minutes.

Keywords:- CPP-ACP, Hypersensitivity, vital tooth For at-home bleaching usually 10% carbamide
bleaching, at-home bleaching, in-office bleaching. peroxide is used with custom-fit trays. It is important to
clean the teeth surface before application of the bleaching
I. INTRODUCTION agent. The tray should be worn for a time period of 4 hours.
The tooth surface and the trays should be thoroughly
Vital tooth bleaching is an advanced treatment option cleaned followed by the application.
to treat discolouration of teeth without affecting the tooth
vitality [1]. According to American Dental Association These bleaching agents contain peroxides which are
(ADA), bleaching is a treatment involving oxidative oxidative agents that produces unstable free radicals as a
chemical that increases the value of teeth by altering result of oxidation-reduction reaction that penetrates into
reflection/ absorbing the tooth structure.The Desire for a interprismatic area of enamel and breaks down complex
flawless smile with minimum intervention has widened the macromolecules into smaller molecules that reflects the light
scope of vital tooth bleaching [2]. Vital bleaching can be more, and the tooth appears whiter [4].
done in patients with mild fluorosis and tetracycline stains
or to match the crown's colour that is lighter than the natural However, vital tooth bleaching shows adverse effects
teeth. like tooth sensitivity and increase of enamel porosity. In
enamel, it reduces the microhardness. A lot of Invitro
studies have shown that peroxide penetrates the enamel
dentin and enters the pulp. Due to the lower pH of the
bleaching solution causes demineralisation of enamel and

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Volume 7, Issue 6, June – 2022 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
dentin and irritates the pulp, causing reversible pulpitis and II. MATERIALS AND METHODS
producing tooth sensitivity [5].
A. Study design:
Recently a lot of re-mineralising agents have been A systematic review of randomised control trials done on
introduced to reduce the tooth sensitivity followed by vital the efficacy of CPP- ACP on tooth sensitivity followed by
bleaching. Casein phosphopeptide-amorphous calcium vital tooth bleaching.
phosphate (CPP- ACP) was first postulated in 1998. These
are nanocomplexes that are derived from bovine milk B. Eligibility criteria:
protein. CCP-ACP has anti-cariogenic property. a) Inclusion criteria
 Articles showing the efficacy of CPP-ACP on tooth
CCP has the ability to localise ACP at the tooth sensitivity followed by vital bleaching.
surface. It increases the calcium phosphate level in plaque.  Articles in English.
Casein phosphate maintains the supersaturation of saliva by  Randomised control trials.
providing a pool of calcium and phosphate by forming  Originalarticles.
nanoclusters with amorphous calcium phosphate [6].  Full textarticles.
CPP-ACP provides a higher safety level as it is a b) Exclusion criteria-
unique milk-derived protein [7].  Articles without full text.
Previous systematic reviews have assessed the  Articles in different languages.
remineralisation property of the CPP -ACP on the  Articles with only abstracts.
demineralised tooth surface. The aim of this systematic  Editorials.
review is to assess the effect of CPP-ACP on tooth
hypersensitivity followed by vital bleaching. To evaluate the C. Search strategy:
Articles related to efficacy of CPP-ACP on tooth
efficacy of CPP-ACP on tooth sensitivity followed by vital
sensitivity followed by vital tooth bleaching was thoroughly
bleaching.
searched in databases like Google Scholar, PubMed, Ovid,
Science Direct, Lilacs, Wiley, Cochrane. The MeSH terms
were "CPP-ACP", "tooth sensitivity", "vital tooth bleaching"
using AND

D. Search Engines:
The search engines were used –
 GoogleScholar
 PubMed
 Ovid
 Science Direct
 Lilacs
 Wiley
 Cochrane

E. Search Database

S.NO. DATABASES SEARCH WORDS NUMBER OF

ARTICLES
1. GOOGLE SCHOLAR CPP-ACP AND tooth hypersensitivity AND vital 198
tooth bleaching AND efficacy
2. PUBMED Vital tooth bleaching AND CPP-ACP AND dentin 2
hypersensitivity
3. COCHRANE CPP-ACP AND Vital tooth bleaching 2
4. MEDLINE CPP-ACP AND vital tooth bleaching AND teeth 0
hypersensitivity (in advanced search under key
words)
5. LILACS Tooth hypersensitivity AND Vital tooth bleaching 0
AND CPP-ACP
6. WILEY Vital bleaching AND hypersensitivity AND CPP- 27
ACP (searched under title abstract subject)
7. SCIENCE DIRECT Dentin hypersensitivity AND CPP-ACP AND vital 36
tooth bleaching
Table 1

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Volume 7, Issue 6, June – 2022 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
Record identified through
Identification electronic database searching.
 Google scholar(n=198)
 PubMed(n=2)
 Cochrane(n=2)
 Medline(n=0)
 Lilacs(n=0) Additional record identified
 Wiley(n=27) through other sources (n=0)
 Sciencedirect(n=36)

Total number of articles (n = Records excluded after duplicate

265) (n =210)

Reports excluded (n=179)

Reports assessed for eligibility (n
=210)
Screening

Full-text assessed for eligibility Studies excluded due to other

(n=31) reasons (n=26)
Included

Studies included in
qualitative analysis(n=5)

Fig. 1: Flow diagram showing the number of studies identified, screened, assessed for eligibility, excluded and included in the
systematic review

III. RESULTS

S. Author and Type of study Materials and Parameters Methodology

No. year of sample size Pre- experimental Experimental
publication interventions interventions
1. Oula Yassin8 Double- Twenty-four Toothsensitivity Participants were Participants were
(2018) blinded people were is recorded using provided with a provided with a white
randomised randomly divided the visual syringe containing colour coded container
control trial into two groups. analogue scale 20% carbamide either with placebo gel
n=12(Placebo) (VAS)ranked peroxide gel along or CPP-ACP and asked
from '0' no with vacuum to apply it for 30
sensitivity to ‘10’ compressed minutes once a day
severe sensitivity. custom trays and followed by the
instructed to use bleaching procedure for
the bleaching gel seven days.
fourh/day.
2. Burak Triple Sixty-four Tooth sensitivity Participants were
GÜMÜŞTAŞ blinded subjects were is recorded using divided into 4 groups
9
(2021) randomised randomly the visual and each group was
control trial allocated into analogue scale treated with placebo,
four groups. (VAS) and ACP- CPP, Nano

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Volume 7, Issue 6, June – 2022 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
n=16 group A calculated at hydroxyapatite(n- HAP)
n=16 group B fourlevels: and neutral sodium
n=16 group C 0= None 1=Mild fluoride
n=16 group D 2=Moderate (NSF)respectively for 4
3=Considerable minutes.
4=Severe Bleaching was done
using 38% hydrogen
peroxide activated by
light for 45 minutes in 3
intervals. (15 minutes
each)
3. GA Randomised 51 participants All the 35% hydrogen Participants were
Maghaireh10 control trial were randomly participants were peroxide gel was divided into 3
(2014) allocated in 3 provided with a applied on the groups of 17 individuals.
groups. sensitivity sheet tooth surface of A small amount of gel
n=17 (Placebo) to record the post the maxillary applied on the labial
n=17(2% sodium bleaching anterior teeth for surface of teeth from
fluoride) sensitivity with a 15 minutes. The unmarked syringes
n=17(10% CPP- visual analogue agent was washed containing gel without
ACP) scale ranging and washed away desensitising agent, gel
from 1- every 15 minutes with 2% sodium fluoride
10. during a 45 and gel with 10% CPP-
0=none 1-3= minutes ACP. The gel was
mild application. The undisturbed for 3
4-6=moderate 7- whitening agent minutes. After that, the
10=severe was removed with participants were asked
cotton roll and the to expectorate
gingival barrier thoroughly and asked
was removed. not to eat,
Teeth were rinsed drink and rinse after half
thoroughly and an hour. Participants
post-whitening were instructed to use
shade was the assigned gel twice
determined. daily after brushing their
teeth.
4 Shaista Randomised 32 individuals Tooth sensitivity Participants were After two weeks,
Rashid11 , controlled, were randomly was measured instructed to use participants are asked to
(2021) split-mouth allocated into with a visual 15% carbamide apply the bleaching
crossover two groups analogue scale peroxide gel with agent with MI (minimal
design (n=16) ranging from a custom intervention)paste.
clinical trial. Group 1: control 0(no sensitivity) scalloped tray Group 1 was instructed
arch= maxilla to 10(severe after brushing and to use bleach and MI
Interventionarch sensitivity). flossing their paste in the mandibular
=mandible Group teeth. arch and Group 2 was
2: Control Group 1 is instructed to use it in the
arch=mandible instructed to maxillary arch.
Intervention arch bleach the Participants were asked
=maxilla. maxillary arch and to use the non-scalloped
group 2 is tray with MI paste for 5
instructed to minutes after brushing
bleach the and flossing, followed
mandibular arch by application of
for 6-8 hours at bleaching agent for 6-8
night for two hours atnight
weeks. for two weeks
5 Manjot Randomised 45 individuals Tooth sensitivity Pre bleaching 45 individuals were
Singh12 control trial are randomly was recorded shades were divided into 3
(2017) allocated into 3 using a visual determined. The groups. group 1 received
groups. analogue scale experimental teeth the treatment with
Group 1: for 14 days. were isolated with placebo gel, group 2 was
Placebo(n=15) 0=none 1-3=mild a light cure resin given cream with 1.1%

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 Volume 7, Issue 6, June – 2022 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
Group 2: Cream 4-6= moderate 7- dam. The sodium fluoride and
with 1,1% 10=severe bleaching agent group 3 was given cream
sodium fluoride was applied on the with 10% CPP- ACP. A
Group 3: Cream maxillary tooth pea-sized amount of the
with 10% CPP- surface in 2 desensitising agents was
ACP. intervalsfor applied on the labial
20 minutes in surface of the tooth
total 40 minutes
duration and
postbleaching
Table 1: Characteristic of included studies and methodology

Sl. no Author and Year of Outcome Assessment P-value Notes

publication
1. Oula Yassin8 (2018) Patients treated with CPP-ACP followed by P=0.002 There was no deteriorating effect on
bleaching has shown significant reduction in colour change when compared with
tooth sensitivity on 3rd and 7th day than the placebo.
control group.
2. Burak Control and CPP-ACP showed significantly P<000.8 There was no significant color
GÜMÜŞTAŞ9(2021) higher tooth hypersensitivity than NSF and n- alteration of the teeth on application
HAP. CPP-ACP shows reduction in tooth of remineralising agents.
hypersensitivity than placebo but there was
significant difference with NSF and
n-HAP.
3. GA Maghaireh 10 (2014) The participants of the placebo group Day The participants with fluoride have
experienced sensitivity over 14days. The 1;p=0.112 better colour stability than CPP-
participants of CPP-ACP group had sensitivity Day ACP.
up to 4th day and the fluoride group showed 2;p=0.532
presence of sensitivity up to 10 days.
4. Shaista Rashid11 (2021) At baseline: No significant difference in test and P=0.063 There is no significant shade
control groups. change occurred in the test and
After treatment: The thermal sensitivity control subjects.
score was greater in bleaching without MI paste P=0.011
than with MIpaste.
2weeks: There was no significant
difference in tooth sensitivity for both thegroups.
During a period of 14 days, the test group
showed lower tooth sensitivity than the control P=0.214
group.
P=0.002
5. Manjot Singh12 (2017) There was a significant difference between Group 1= 0.1 There is no significant difference in
group 1 and group 2 and3. shades change in all 3 groups.
There was no significant difference between Group 2=
group 2 and3. 0.001

Group 3=0.001
Table 2: Outcome assessment and result

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 Volume 7, Issue 6, June – 2022 International Journal of Innovative Science and Research Technology
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S. No Author and year of Random Allocation Selective Other Blinding Blinding Incomplete
publication sequence concealment reporting source of (participants (outcome outcome data
generation bias and personnel) assessment)
1. Oula Yassin8 (2018) + ? + ? + + ?
2. Burak ? + - + + + +
GÜMÜŞTAŞ9(2021)
3. GA Maghaireh10 ? ? ? + ? ? +
(2014)
4. Shaista Rashid11 + + + + + + +
(2021)
5. Manjot Singh12 (2017) ? ? + ? + + +
Table 3: Assessment of risk of bias in included studies

+ =Low risk; -=High risk; ? = Unclear

IV. DISCUSSION difference between the test and control group after two
weeks.
The systematic review yielded 265 articles screened for
duplicates and eligibility criteria, and five final articles were A study conducted by Manjot Singh [12] with 45
selected to be included in this study. participants divided into 3 groups receiving treatment with
CPP-ACP, sodium fluoride and placebo gel. The experiment
The aim of this study is to evaluate the efficacy of shows there is a significant reduction in tooth sensitivity in
CPP-ACP on tooth sensitivity followed by vital tooth CPP-ACP and sodium fluoride group when compared with
bleaching. The results from 5 articles reveal that CPP-ACP the placebo group. There was a significant reduction in
causes reduction in the tooth sensitivity caused due to vital sensitivity on 3rd day in CPP-ACP and sodium fluoride
bleaching. group. The pain intensity was reduced to moderate level for
both CPP-ACP and sodium fluoride but sodium fluoride
Oula Yassin [8] conducted a double-blinded showed the lowest intensity of pain.
randomised control trial that shows there was increased
surface roughness due to the use of 20% carbamide peroxide All the 5 studies above have shown that the CPP-ACP
(at home) which caused increased tooth sensitivity due to causes reduction in tooth sensitivity after vital tooth
penetration of bleaching agent into the pulp chamber. Use of bleaching. It is effective for both in-office, i.e., treatment
CPP-ACP increases the mineral content and improves the with hydrogen peroxide as well as carbamide peroxide
microhardness of the enamel. Thus reduces the penetration which is usually used as at-home bleaching agents.
of bleaching agent and reduces the tooth sensitivity.
The main advantage of vital tooth bleaching is rapid
The study by Burak gümüştaş [9] has included 3 lightening of the shade of the tooth. It causes transient and
remineralising agents to compare the tooth sensitivity by intolerable sensitivity to the teeth [13]. According to some
vital in-office tooth bleaching. 3 agents are CPP-ACP, Nano studies, the oxygen bubbles produced by the peroxides
hydroxyapatite crystals (n-HAP) and neutral sodium moves in the intratubular fluid and activates the interdental
fluoride (NSF). When compared, the experiment shows all nerves and causes hypersensitivity [14]. To overcome this
the 3 agents has reduction in tooth sensitivity with placebo drawback desensitising agents are introduced to reduce the
group. There was significantly higher tooth sensitivity in pain intensity due to hypersensitivity. CPP-ACP increases
CPP-ACP than the other two groups. But when compared the concentration of calcium and promotes remineralisation
with placebo CPP-ACP showed a reduction in of enamel by maintaining a supersaturated solution [15]. It
hypersensitivity. causes the remineralisation of the enamel surface by filling
the CPP-ACP in the enamel surface defects and makes the
In the study by GA Maghaireh [10] CPP-ACP and surface smoother stronger and reduces sensitivity. There are
sodium fluoride were compared with the placebo group. The a lot of desensitising agents available. Mainly fluorides
study showed there is reduction in tooth sensitivity in 4th day derivatives are used for post bleaching sensitivity which is
for CPP- ACP group and on 10th day for the sodium fluoride equally effective as CPP-ACP. But fluoride occludes the
group. The intensity of pain was lower in sodium fluoride dentinal tubules and reduces the hypersensitivity [16]. In the
group when compared with CPP-ACP and the placebo study conducted by Burak gümüştaş [9] includes two
group. material n-HAP and neural sodium fluoride. These two have
Shaista Rashid [11] conducted a split-mouth better efficacy on post bleaching sensitivity than CPP-ACP.
randomised control trial where one arch was used as control However, it is evident that CPP-ACP has a potential to
and the opposite arch as the test group. Immediately after reduce the pain intensity followed by vital tooth bleaching
treatment, there was a significant reduction in the tooth immediately or within 3 dayspost-application.
sensitivity of arch treated with CPP-ACP when compared The above studies showed that there is a low risk of
with arch without mi paste. But there was no significant bias. Moreover, CPP-ACP is already proven to be effective
on early carious lesion due to its remineralisation property.

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Volume 7, Issue 6, June – 2022 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165
Being a naturally occurring milk derivative product it can associated with in-office vital tooth whitening.
reduce the tooth sensitivity followed by at home and in- Operative dentistry. 2014;39(3):239- 247.
office vital tooth sensitivity. However, there is a difference [11.] Rashid S, ElSalhy M. Efficacy of MI Paste® on
in time and duration of application, randomisation, Bleaching-Related Sensitivity: Randomised Clinical
intervention methods, outcome assessment and blinding of Trial. International Journal of Dentistry.2021;1-8.
the participants from which trial result can be affected. [12.] Singh M, Mahajan P, Monga P, Mahajan S, Singla D,
Kaur N. Comparative evaluation of sodium fluoride
V. CONCLUSION and casein phosphopeptide-amorphous calcium
phosphate (CPP-ACP) in treating post-operative
Within the limitation of this systematic review, there is sensitivity associated with in- office vital tooth
sufficient evidence to conclude that casein phosphopeptide- bleaching: A clinical study.
amorphous calcium phosphate complex (CPP-ACP) has the Endodontology.2017;29(1):26.
ability to reduce the post-operative sensitivity caused by at- [13.] Bizhang M, Chun YP, Damerau K, Singh P, Raab WH,
home and in-office vital tooth bleaching without affecting Zimmer S. Comparative clinical study of the
the colour stability of the bleached tooth. effectiveness of three different bleaching methods.
ACKNOWLEDGEMENT Operative dentistry.2009;34(6):635-641.
[14.] Alexandrino LD, Alencar CD, Silveira AD, Alves EB,
Nil Silva CM. A randomised clinical trial of the effect of
NovaMin and CPP-ACPF in combination with dental
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