• Subjects
are
enrolled
in
the
study
with
IRB
approval


• Subjects
are
patients
of
record
at
UNMC,
have



medical
diagnoses
of
asthma
and
are
treated
weekly



with

β2‐adrenergic
agonist
inhalers

• Assignment
of
subjects
to
the
herbal
lollipop
or



control
group
is
determined
by
a
randomized
list


• Determine
whether
or
not
herbal
lollipops
should
be



used
as
directive
therapy
for
children
with
asthma.


• The
duration
of
the
study
is
six
months
from



enrollment
to
completion
and
is
conducted
as
follows:

























Dr.
Johnson
completes
a
clinical
DMFT/


dmft
screening
on
an
asthma
patient.§


Bitewings
are
taken
for
the
radiographic


determination
of
DMFT/dmft
scores.§



A
sample
of
the
patient’s
saliva
is
pipetted


onto
the
CRT®
bacteria
test
strip.



The
saliva
samples
are
cultured
at
37oC


for
48
hours.


S.
mutans
colonies
are
counted
and

recorded
after
culture.


Patient
smiles
with
his
first
round

of
orange
lollipops.§


STUDY


FLOWCHART

Patient

Enrolled


Herbal

Group

S.
mutans

Test


Dispense
Herbal

Lollipops


• Subject
demographic
information
is
collected
during



study
enrollment.



General
Subject
Information
(n=13):


Placebo

Group

S.
mutans

Test


DMFT/dmft

score


Dispense
Placebo

Lollipops


General
Characteristics

Male
=
9,
Female
=
4

AA
=
7,
Caucasian
=2,
Hispanic
=
4

9.5

±
2.8
years


Gender

Ethnicity

Average
Age


Average
Yearly
Family
Income


ASTHMA
CLASSIFICATION

17%


Refill
Herbal

Lollipops


Refill
Placebo

Lollipops


Recall

Recall

DMFT/dmft

score


S.
mutans

Test


DMFT/dmft

score


S.
mutans

Test


Disclose


Outcome


• The
DMFT/dmft
scores
and
S.
mutans
tests
for
each



group
are
compared
with
regard
to
the
change



measured
in
each
over
the
six‐month
course.



AFFECTS
ON
QUALITY
OF
LIFE

17%
 8%


33%


50%


Moderate


Severe



ASTHMA‐RELATED
SCHOOL

ABSENCES
IN
THE
LAST
YEAR

8%


0


• Preliminary
results
are
anticipated
in
mid‐April
2010
as



the
earliest
enrolled
subjects
complete
the
study
in
its



entirety.

Enrollment
of
eligible
subjects
is
ongoing
and



will
continue
until
90
subjects
successfully
complete



the
study.
The
efficacy
of
herbal
lollipop
therapy
for



asthmatic
children
will
then
be
determined
statistically.


17%


58%


A
lot


Moderate


A
little


17%


83%


1
to
7


8
to
30


Not
at
all


PARENT
KNOWLEDGE
OF


DENTAL
SIDE‐EFFECTS


42%


50%


Disclose


Outcome


22.8K
±
12.4K


Subject
Asthma
Information
(n=13):


Mild


• Subjects
MUST:



*
Have
a
medical
diagnosis
of
asthma
and
use
a
β2‐

















adrenergic
agonist
inhaler
as
needed
for
symptoms



*
Be
between
the
ages
of
4
and
16
years



*
Be
available
for
recall

• Subjects
MUST
NOT:



*
Be
taking
other
xerostomia
causing
medications







unrelated
to
the
treatment
of
asthma



*
Have
history
of
severe
early
childhood
caries
(SECC)



• CRT®
bacteria



Streptococcus
mutans



tests
were
manufactured




by
Ivoclar
Vivodent,



Amherst,
NY


• The
study
is
double‐blind;
both
the
researcher
and
the



subjects
are
unaware
of
group
assignments


DMFT/dmft

score


• Determine
how
effective
a
six‐month
course
of
herbal



lollipops
is
on
S.
mutans
levels
and
the
dental
caries



experience
of
asthmatic
children
versus
a
placebo


• Herbal
lollipops
were



manufactured
by



Intelliherb
LLC,



Inglewood,
CA
and
are



FDA‐approved



Yes


No


§All
photos
were
taken
and
printed
with
parental
permission.


• Dental
caries
and
asthma
are
two
of
the
most






common
chronic
diseases
of
childhood

• Presently,
9.3%
of
children
in
the
United
States
suffer



from
some
form
of
asthma


• Children
who
are
treated
with
β2‐adrenergic


agonist
inhalers
for
asthma
have
been
shown
to
have:







*
Decreased
salivary
outflow
which
limits










the
protective
buffer
of
saliva







*
Decreased
plaque
pH
below
the
critical
pH










for
enamel
demineralization







*
Higher
DMFT/dfmt
scores

• Studies
strongly
recommend
additional
preventative



programs
for
children
with
asthma
to
keep
dental



caries
risks
under
control

• Herbal
lollipops
contain
Glycyrrihiza
uralensis,
a



compound
extracted
from
Chinese
licorice
root,
which



has
demonstrated
antibacterial
activity
against




Streptococcus
mutans
(S.
mutans),
an
oral
pathogen



responsible
for
dental
caries

• It
is
hypothesized
that
a
six‐month
course
of
herbal




lollipops
will
reduce
S.
mutans
populations
in
saliva



of
children
with
asthma,
and
thereby,
improve
DMFT/


dmft
scores



Special
thanks
to
Jeffery
Payne
DDS,
Peter
Giannini

DDS,
MS,
Michael
Molvar
DDS,
MS
and
Caren
Barnes

RDH,
MS
of
UNMC
College
of
Dentistry.

Also,
thanks

to
Maxwell
H.
Anderson
DDS,
MS,
MEd
and
Justin

Hsiao
of
C3
Jian,
Inc.


 
 
 
 
 

Elizabeth  Ann  Johnson,  DDS  
University  of  Nebraska  Medical  Center  
Pediatric  Dentistry  Post  Graduate  Program  
2011  
 
 
 
 
 
 
 
 
 

Effects  of  herbal  lollipops  on  Streptococcus  Mutans  levels,  
Lactobacilli  levels  and  the  dental  caries  experience  of  children  with  
asthma  taking  beta2-­‐adrenergic  drugs  
E..Johnson  DDS;  A.  Cook  DDS;  S.Hamilton  DDS;  F.Salama  BDS  MS;  B.Lancaster  PhD;  
D.  Finken  MD;  B.  Lange  PhD;  D.  Marx  PhD  
 
Abstract:  
In  this  study,  twenty-­‐eight  (28)  children  between  the  ages  of  four  (4)  and  sixteen  
(16)  with  bronchial  asthma  taking  a  beta2-­‐adrenergic  agonist  inhaler  participated  in  
a  six  (6)  month  regimen  of  herbal  lollipops  as  adjunctive  oral  hygiene  therapy.    The  
objective  of  this  study  was  to  determine  how  effective  the  six-­‐month  regimen  of  
herbal  lollipops  is  at  controlling  the  Streptococcus  Mutans  levels,  Lactobacilli  levels,  
and  the  caries  process  in  the  study  group.    Another  goal  was  to  determine  whether  
or  not  a  case  can  be  made  for  including  herbal  lollipops  in  standard  oral  hygiene  
protocol  for  children  with  asthma.    Relevant  data  was  collected  using  the  following  
method.    The  subjects  of  the  study  were  provided  with  and  instructed  to  dissolve  
two  (2)  herbal  lollipops  by  mouth  per  day  for  the  first  ten  (10)  days  of  the  study  and  
again  for  ten  (10)  days  three  (3)  months  into  the  study.    Each  subject  received  a  
total  of  forty  (40)  lollipops  for  the  study.    The  study  group  was  matched  with  a  
control  group  consisting  of  twenty-­‐two  (22)  children  who  also  have  asthma  and  
take  a  beta2-­‐adrenergic  agonist  inhaler.    The  children  in  the  control  group  were  
given  placebo  lollipops  and  were  instructed  to  use  them  in  the  manner  described  

above.    All  fifty  subjects  were  drawn  from  the  University  of  Nebraska  Medical  Center  
in  Omaha,  Nebraska.    Oral  hygiene  instructions  were  given  to  all  participating  
subjects  at  the  onset  of  the  study.    Entrance  Streptococcus  Mutans  levels,  Lactobacilli  
levels  and  DMFT/dmft  scores  were  determined  on  the  subjects  and  changes  over  
the  six  (6)  month  study  were  compared  and  evaluated.    The  significance  of  this  
study  is  that  adjunctive  oral  hygiene  therapy  that  employs  herbal  lollipops  may  
prove  to  help  children  who  suffer  from  bronchial  asthma  lower  their  dental  caries  
risks  and  have  healthier  oral  environments  unburdened  by  the  effects  of  their  
medications  and  condition.      It  was  concluded  in  this  study  that  compliance  
contributed  to  a  completion  of  only  thirty-­‐one  children.    The  use  of  the  lollipops  in  a  
more  controlled  environment  would  have  provided  a  stronger  and  more  accurate  
study.    The  data  did  not  show  results  that  were  statistically  significant.      
 
Introduction:  
Dental  caries  and  childhood  asthma  are  the  two  of  the  most  common  chronic  
diseases  of  childhood(1,2)  and  are  two  leading  causes  of  school  absenteeism.    A  
majority  of  the  studies  that  have  examined  the  effects  of  asthma  on  the  oral  
environment  have  associated  childhood  asthma  with  increased  dental  caries  
incidence.  (3,5,6,7,8,10)  Some  adverse  changes  in  the  oral  environment  can  be  attributed  
directly  to  frequent  usage  of  beta2-­‐adrenergic  agonist  drugs,  which  can  lead  to  an  
increased  risk  of  dental  caries  in  children  with  asthma.      
 

Karguel  et  al  (1998)  demonstrated  a  significant  decrease  in  the  pH  of  plaque  below  
the  critical  pH  for  5.5  for  enamel  demineralization  thirty  (30)  minutes  after  
treatment  with  a  beta2-­‐adrenergic  agonist  inhaler.(3)    The  low  pH  environment  
caused  the  subjects  with  asthma  to  be  at  a  greater  risk  for  dental  caries  formation.  
 
Ryberg  et  al  (1987)  attributed  higher  dental  caries  incidence  in  asthmatic  children  
to  a  significant  decrease  in  salivary  outflow  due  to  the  xerostomic  effects  of  beta2-­‐
adrenergic  agonist  inhalers.    This  study  showed  a  26%  and  36%  decrease  in  whole  
and  parotid  saliva,  respectively,  in  children  with  asthma  compared  to  the  control.(4)    
A  decrease  in  salivary  outflow  limits  the  protective  functions  of  saliva,  such  as  its  
buffering  capacity  and  ability  to  quickly  clear  fermentable  substances  from  the  oral  
environment.      
 
In  a  four  (4)  year  follow-­‐up  study,  Ryberg  et  al  (1991)  found  that  compared  to  the  
control  group,  the  subjects  with  asthma  from  the  previous  study  demonstrated  
higher  decayed,  missing,  and  filled  (DMF)  scores.(5)  
 
Reddy  et  al  (2003)  found  a  statistically  significant  increase  in  caries  in  both  the  
primary  and  mixed  dentitions  in  children  who  used  various  anti-­‐asthmatic  
medications  to  control  their  symptoms.    Also,  this  study  identified  a  statistical  
correlation  between  an  increased  level  of  dental  caries  and  an  increased  severity  of  
asthma,  most  likely  due  to  the  increased  dosage  and  frequency  of  anti-­‐asthmatic  
medication.(6)      

 
McDerra  et  al  (1999)  showed  that  British  children  taking  an  inhaler  for  asthma  had  
a  higher  incidence  of  dental  caries  in  both  permanent  and  primary  teeth  compared  
to  a  control  group.  However,  only  the  incidence  in  caries  in  the  permanent  dentition  
was  shown  to  be  statistically  significant.(7)      
 
In  a  U.S.  study,  Milano  et  all  (1999)  found  asthmatic  children  experienced  more  
decay  than  non-­‐asthmatic  children  in  both  primary  and  mixed  dentitions,  although  
only  primary  dentition  results  were  significant.(8)      
 
Another  study  from  Texas,  compared  asthmatic  children  in  two  age  groups  (4-­‐10  
and  11-­‐16)  to  a  control  group.    They  found  similar  DMFT  scores  in  the  4-­‐10  asthma  
group  and  the  control  group,  and  lower  DMFT  scores  in  the  11-­‐16  asthma  group  
compared  to  the  control  group.    However,  of  the  1,129  subjects  in  the  study  only  
52%  reported  using  a  beta2-­‐adrenergic  agonist  inhaler  to  control  their  asthma  (34%  
were  severe  asthmatics,  15.4%  were  moderate  asthmatics  and  3.0%  were  mild  
asthmatics.)(9)  
 
Milano  et  al  (2006)  examined  the  relationship  between  types  of  asthma  
medications,  length  of  use,  frequency  of  use  and  dosing  time  of  day,  and  dental  
caries.    This  study  fond  that  among  children  with  asthma  those  who  used  
medication  more  than  twice  daily  were  more  prone  to  dental  caries  in  the  primary  
and  mixed  dentitions.(10)    The  most  frequently  used  medication  in  this  study  was  a  

beta2-­‐adrenergic  agonist  inhaler  (73%)  while  the  others  (27%)  used  a  combination  
of  beta2-­‐adrenergic  agonist  drug  and  other  medications.      
 
While  not  all  studies  show  statistical  significance,  the  general  consensus  is  that  
beta2-­‐adrenergic  agonist  medications  have  adverse  effects  on  the  oral  cavity  and  can  
contribute  to  an  increased  dental  caries  incidence  in  children  with  asthma.    Many  
studies  have  recommended  that  children  with  asthma  adopt  more  precautionary  
oral  hygiene  habits  and  visit  their  dental  care  providers  on  a  more  frequent  basis  to  
keep  their  dental  caries  risks  under  control.    
 
An  additional  precautionary  step  that  could  be  utilized  for  the  control  of  dental  
caries  in  asthmatic  children  is  herbal  lollipops.    The  beneficial  effects  of  herbal  
lollipops  on  the  oral  environment  are  a  newer  development  and  have  only  just  
begun  to  be  explored  in  the  literature.    The  active  ingredient  in  herbal  lollipops  
comes  from  the  roots  of  Glycyrrhiza  uralensis  or  Chinese  licorice.    The  therapeutic  
effects  of  Glycyrrihiza  uralensis  have  been  utilized  by  mainland  China  and  other  
eastern  countries  for  thousands  of  years.(11)    Over  the  past  few  decades,  researchers  
have  sought  to  isolate  the  active  compounds  in  Glycyrrihiza  uralensis  responsible  for  
its  therapeutic  effects,  and  specifically,  the  compound  shown  to  have  antibacterial  
activity  against  Streptococcus  Mutans.    In  2006,  researchers  at  the  UCLA  School  of  
Dentistry  identified  Glycyrrhizol  A  to  be  the  compound  with  very  potent  
antibacterial  activity.(11)    This  compound  was  shown  to  have  an  in  vitro  minimum  
inhibitory  concentration  (MIC)  of  15.6  ug/mL  against  Streptococcus  Mutans.  (11)    MIC  

is  defined  as  the  lowest  concentration  that  visibly  inhibits  bacterial  growth  after  
incubation  at  thirty-­‐seven  degrees  Celsius  (37°)  for  sixteen  (16)  to  twenty  (20)  
hours.    Later  researchers  at  the  same  institution  incorporated  Glycyrrhizol  A  into  a  
sugar-­‐free  herbal  lollipop  carrier  to  evaluate  its  effectiveness  on  oral  Streptococcus  
Mutans  in  human  subjects.(12)    In  a  ten  (10)  day  trial,  subjects  were  given  the  herbal  
lollipop  twice  a  day  and  in  the  majority  of  subjects,  dramatic  reductions  in  salivary  
Streptococcus  Mutans  levels  were  seen.(12)    The  total  number  of  subjects  in  the  UCLA  
study  was  twenty-­‐six(26).    Twenty  (20)  of  those  subjects  were  patients  at  the  UCLA  
Childrens  Dental  Clinic.    The  study  does  not  mention  any  adverse  events  and/or  
study  outcomes.    Additionally,  correspondence  with  Maxwell  H.  Anderson  D.D.S.  ,  
M.S.,  M.Ed.,  President  and  CEO  of  C3  Jian  Inc.    (the  company  of  which  Intelliherb  LLC  
is  a  wholly-­‐owned  subsidiary)  stated  that  of  the  hundreds  of  patients  enrolled  in  
past  and  present  trials,  there  is  yet  to  be  any  cases  of  allergy  to  the  licorice  root.    
Further  research  is  being  planned  by  Intelliherb  LLC  to  determine  the  exact  anti-­‐
bacterial  mechanism  by  which  Glycyrrhizol  A  exerts  its  effects  intra-­‐orally.    Because  
Streptococcus  Mutans  is  an  oral  pathogen  responsible  for  dental  caries,(13)  if  herbal  
lollipops  can  reduce  their  levels,  a  resultant  effect  should  be  lowered  DMFT/dmft  
scores  and  increased  tooth  remineralization.    This  avenue  has  not  yet  been  explored.      
 
Given  the  oral  health  benefits  of  herbal  lollipops,  this  study  examined  the  
effectiveness  of  an  herbal  lollipops  regimen  among  children  using  beta2-­‐adrenergic  
agonist  drugs  for  asthma.    Past  studies  regarding  Streptococcus  Mutans  levels  and  
caries  rates  in  children  with  asthma,  regardless  of  the  specific  results,  strongly  

recommended  preventative  programs.    However,  no  study  to  date  has  implemented  
an  herbal  lollipops  regimen  for  children  with  asthma.      
 
Materials  and  Methods:  
Twenty-­‐eight  (28)  children  diagnosed  with  bronchial  asthma  from  the  University  of  
Nebraska  Medical  Center  Pediatric  Dental  Clinic  were  randomly  selected  to  
participate  in  a  6-­‐month  regimen  of  herbal  lollipops.    Those  selected  to  be  in  the  
study  group  were  randomized  statistically.    The  Herbal  lollipops  were  Manufactured  
by  Intelliherb  LLC,  Inglewood  CA.    Herbal  lollipops  are  FDA  approved.    The  
qualifications  to  participate  in  this  study  include:  a  clinical  diagnosis  of  asthma,  
using  a  beta2-­‐adrenergic  agonist  PRN,  between  the  age  of  four  (4)  and  sixteen  (16)  
for  males  and  four  (4)  and  age  of  menarche  for  females.    These  lollipops  have  not  
been  tested  on  the  fetus  so  to  exclude  the  possibility  of  a  subject  being  pregnant,  if  
she  had  reached  the  age  of  menarche  she  could  not  participate  in  the  study.    The  
subjects  could  not  be  on  an  antibiotic,  antimicrobial  mouthrinse,  or  any  medications  
that  caused  xerostomia  with  an  exception  of  medications  associated  with  their  
asthma  such  as  seasonal  allergy  medications.      
 
All  subjects  parents/legal  guardians  were  given  risks,  benefits  and  alternatives  to  
the  study  before  signing  a  consent  for  their  child  to  participate  in  the  study.    All  
subjects  over  the  age  of  seven  (7)  also  signed  an  assent  form.    A  questionnaire  about  
the  subjects  oral  hygiene,  dental  history  and  asthma  history  was  filled  out  by  the  
subjects  parent/legal  guardian.    Each  subjects  was  given  verbal  oral  hygiene  

instructions.  It  was  recommended  that  each  subject  brush  twice  daily  (once  in  the  
morning  and  once  before  bed)  with  a  fluoride-­‐containing  toothpaste  and  floss.      
 
The  initial  exam  included  2  to  4  bitewing  radiographs  used  to  diagnose  
interproximal  caries.    Thus,  all  subjects  participating  in  this  study  underwent  
additional  radiation  exposure  due  to  radiographs  at  the  beginning  and  end  of  this  
study.    The  six  (6)  month  interval  between  radiographic  sessions  is  normal  for  
children  experiencing  high  caries  rates  but  is  more  frequent  than  necessary  for  
children  experiencing  a  low  caries  rate.    Thus,  those  potential  risks  were  discussed  
with  the  parent/legal  guardian.    The  subjects  then  chewed  on  paraffin  wax  supplied  
by  CRT  bacteria  Streptococcus  mutans  tests:  Manufacured  by  Ivoclar  Vivodent,  
Amerherst,  NY  in  order  to  stimulate  saliva  production.    The  subjects  spit  into  a  cup  
and  then  1  mL  of  saliva  was  placed  onto  the  agar  test  strip  provided  by  the  CRT  
bacteria  test  kit.    The  vial  including  the  test  strip  was  then  placed  into  an  incubator  
at  thirty-­‐seven  degrees  Celsius  (37°  C)  for  forty-­‐eight  (48)  hours.    A  clinical  exam  
was  also  performed  by  one  practioner  at  the  initial  appointment  to  check  for  any  
other  visual  caries.    Decayed,  missing,  and  filled  teeth  (DMFT/dmft)  scores  for  both  
the  primary  and  permanent  dentitions  were  used  to  describe  the  severity  of  dental  
caries  in  each  participant.    The  sum  of  the  component  parts  of  DMFT/dmft  scores  
equals  the  overall  DMFT/dmft  score,  which  means  a  DMFT/dmft  score  cannot  
decrease  even  if  a  primary  tooth  is  exfoliated.    Those  component  parts  included  the  
number  of  teeth  that  had  carious  lesions  (“D”  or  “d”  for  decayed),  the  number  of  
teeth  that  have  been  lost  due  to  tooth  decay  (“M”  or  “m”  for  missing),  and  the  

number  of  teeth  that  have  been  filled  or  crowned  (“F”  or  “f”  for  filled.)    In  this  study,  
entrance  and  exit  DMFT/dmft  scores  were  collected  by  one  researcher  to  eliminate  
individual  biasis.    The  researcher  was  blind  to  which  participants  were  receiving  the  
herbal  lollipop  regimen  and  which  were  receiving  the  placebo  lollipops.    The  control  
group  lollipops  were  placed  in  a  paper  bag  with  a  start  attached.    The  study  group  
lollipops  were  placed  in  a  paper  bag  with  a  heart  attached.    This  allowed  the  
researcher  to  give  the  patients  the  lollipops  and  keep  the  two  groups  separate  while  
remaining  blind  to  which  group  was  which.    The  control  group  can  be  interchanged  
with  the  star  group  and  the  study/experimental  group  can  be  interchanged  with  the  
heart  group.      
 
Herbal  lollipops  were  provided  to  the  participants  in  the  study  group  and  each  
member  was  instructed  to  dissolve  two  (2)  lollipops  by  mouth  every  day  for  ten  
(10)  days  at  the  onset  of  the  study  and  again  after  a  three  (3)  month  period.    It  was  
recommended  that  each  member  in  the  study  group  dissolve  the  herbal  lollipop  in  
their  mouth  (without  chewing)  in  the  morning  after  breakfast  and  in  the  evening  
after  dinner.    It  was  instructed  that  it  should  take  approximately  ten  (10)  to  fifteen  
(15)  minutes  for  the  lollipops  to  dissolve  completely.    Parents/Guardians  of  the  
study  group  were  given  a  chart  on  which  to  document  the  delivery  of  the  twice-­‐daily  
herbal  lollipops.    It  was  the  hope  that  this  chart  would  have  a  positive  influence  on  
compliance  and  would  be  able  to  be  reviewed  for  inclusion  of  the  subject  in  the  final  
data  set.      
 

All  ingredients  used  in  the  herbal  lollipops,  manufactured  by  Intelliherb  LLC,  are  
FDA-­‐approved  and  safe  for  human  consumption.    The  formula  for  the  lollipops  is:  
hydrogenated  starch  hydolysate  (HSH)  (a  solidifying  agent),  citric  acid  and  mint  (for  
flavoring),  FD  &  C  Blue  #1,  2:  Red  3,  40;  Yellow  5,  6  (for  coloring),  and  acesulfame  
potassium  (a  non-­‐caloric  sweetener).    The  active  ingredient  Glycyrrhizol  A  is  
extracted  from  licorice  root,  a  substance  that  has  been  used  for  thousands  of  years  
and  has  been  shown  to  be  a  safe  medicinal  herb.    Licorice  root  is  listed  by  the  FDA  as  
“generally  regarded  as  safe”  (GRAS)  when  used  as  a  sweetener  or  flavoring.    
Depending  on  the  concentration  of  the  active  ingredient  Glycyrrhizol  A  in  a  batch  of  
licorice  root  extract,  licorice  root  extracts  are  added  to  each  lollipop  for  a  
standardized  concentration  of  Glycyrrhizol  A.      
 
After  six  (6  )  months  a  final  exam  was  performed,  which  was  identical  to  the  initial  
entrance  exam.    All  data  was  collected  in  the  same  manner  described  above.    
All  steps  of  the  study  for  the  control  group  were  identical  to  the  study  group  except  
the  control  group  consisted  of  twenty-­‐two  (22)  subjects  and  each  subject  was  given  
the  placebo  lollipop,  which  was  also  manufactured  by  Intelliherb  LLC  and  is  a  true  
placebo,  meaning  that  the  formulation  is  exactly  the  same  as  the  active  herbal  
lollipop  except  it  lacks  the  Glycyrrhizol  A.      
 
Data  from  the  DMFT/dmft  scores,  Streptococus  Mutans  CFUs  and  Lactobacilli  CFUs  
were  collected  at  the  beginning  and  end  of  the  study  for  all  the  subjects.    
Mathematical  changes  in  these  scores  were  compared  for  each  individual  subject  of  

the  six  (6)  month  period.    The  mean  change  score  of  the  experimental  group  (i.e.,  the  
herbal  lollipop  group)  was  compared  with  the  mean  change  in  the  control  group  
using  a  one-­‐way  Multivariate  Analysis  of  Variance  (MANOVA).    The  MANOVA  was  
chosen  as  the  method  for  statistical  analysis  to  simultaneously  analyze  all  
dependent  variable  change  scores  of  the  lollipop  group  compared  to  the  control  
group.    The  MANOVA  allows  for  better  control  of  the  overall  error  in  the  statistical  
analysis.    Conducting  separate  comparisons  for  each  of  the  dependent  variables  
could  allow  the  error  rate  to  exponentially  rise  and  distort  comparison  results  of  the  
lollipop  group  versus  the  control  group.      
 
Results:  
Matriculation  in  this  study  was  high.    Twenty-­‐eight  (28)  subjects  in  the  study  group  
started  the  study,  however  only  seventeen  (17)  completed  the  six  (6)  month  
regimen  of  herbal  lollipops.      Twenty-­‐two  (22)  subjects  in  the  control  group  started  
the  study,  however  only  fifteen  (15)  completed  the  six  (6)  month  regimen  of  the  
placebo  lollipops.      (See  Table  1)    Twenty-­‐two  (22)  of  the  participants  were  male,  
while  ten  (10)  of  the  participants  were  female.  (see  Table  2)        The  ethnic  
distribution  of  the  participants  included  forty-­‐seven  percent  (47%)  Hispanic,  thirty-­‐
four  percent  (34%)  African  American,  sixteen  percent  (16%)  Caucasian,  and  three  
percent  (3%)  Asian.    (see  Table  2)  No  tests  were  run  to  determine  the  change  in  
bacteria  or  DMFT/dmft  for  each  individual  ethnicity.    The  annual  income  
distribution  of  the  participants  included  thirty-­‐four  percent  (34%)  with  an  annual  
income  of  fifteen  thousand  dollars  to  twenty-­‐four  thousand,  nine  hundred  and  

ninety  nine  dollars  ($15,000-­‐$24,999).    Twenty-­‐eight  percent  (28%)  had  an  annual  
income  of  less  than  fifteen  thousand  dollars  (<$15,000).    Twenty-­‐two  percent  (22%)  
had  an  annual  income  of  twenty-­‐five  thousand  dollars  to  forty-­‐nine  thousand  nine  
hundred  and  ninety  nine  dollars  ($25,000-­‐$49,999).    Three  percent  (3%)  had  an  
annual  income  with  in  the  range  of  fifty-­‐thousand  dollars  to  seventy-­‐four  thousand  
nine  hundred  and  ninety  nine  dollars  ($50,000-­‐$74,999).    Thirteen  percent  (13%)  
chose  not  to  answer  their  household  annual  income.    (see  Table  2)  
 
One  question  on  the  questionnaire  prior  to  the  study  was  “Are  you  aware  that  
asthma  medication  causes  an  increase  in  dental  caries?”    Sixty-­‐eight  percent  (68%)  
of  the  participants  parents/legal  guardians  answered  “No.”    Thirty-­‐two  percent  
(32%)  of  the  participants  parents/legal  guardians  were  aware  that  their  child’s  
asthma  medication  caused  an  increase  in  dental  caries  and  answered  “yes.”    (see  
Table  3)  
 
A  MANOVA  was  run  to  compare  the  Streptococcus  Mutans  pre  test  and  post  test  
scores  as  well  as  the  Lactobacilli  pre  test  and  post  test  scores.  (see  table  4)  The  pre  
test  score  was  subtracted  from  the  post  test  score  to  determine  the  change  in  
bacteria  levels.    The  study  group  had  an  average  of  a  2.6  decrease  of  Streptococcus  
Mutans  colony  forming  units  (CFU’s)  per  1  ML  of  saliva  from  the  pre  test  to  the  post  
test.    The  control  group  had  an  average  of  a  71.3  increase  of  Streptococcus  Mutans  
colony  forming  units  (CFU’s)  per  1  mL  of  saliva  from  the  pre  test  to  the  post  test.    
The  results  of  the  MANOVA  comparing  mean  Streptococcus  Mutans  change  scores  

between  the  lollipop  and  control  groups  were  not  statistically  significant,  F(1,30)  =  
0.22,  p  =  0.65.      
 
The  study  group  had  an  average  of  an  81.6  decrease  of  Lactobacilli  colony  forming  
units  per  1  mL  of  saliva  from  the  pretest  to  the  post  test.    The  control  group  had  an  
average  of  a  36.1  decrease  of  Lacobacilli  colony  forming  units  per  1  mL  of  saliva  
from  the  pretest  to  the  post  test.    The  results  of  the  MANOVA  comparing  mean  
Lactobacilli  change  scores  in  the  lollipop  group  to  the  control  group  were  not  
statistically  significant,  F(1,30)  =3.09,  p  =  0.09.    
 
The  control  group  had  a  mean  increase  of  .20  DMFT/dmft  score.    The  study  group  
showed  a  mean  increase  of  .06  DMFT/dmft  score.      The  results  of  the  MANOVA  
comparing  mean  DMFT  change  scores  in  the  lollipop  group  to  the  control  group  
were  not  statistically  significant,  F(1,30)  =  1.43,  p  =  0.24.    
 

Table 1
Distribution of Participants assigned to Star or Heart Group
Participant Group

Frequency (Percent)

Star (control) group

15 (46.9%)

Heart (experimental) group

17 (53.1%)

Table 2
Participant Demographics
Frequency (Percent)
Demographic
Treatment Group

Control Group

Ethnicity
Caucasian

1 (3.1%)

4 (12.5%)

Hispanic

9 (28.1 %)

6 (18.8 %)

African American

7 (21.9%)

4 (12.5%)

Asian

0 (0%)

1 (3.1%)

Gender
Male

12 (37.5%)

10 (31.3%)

Female

5 (15.6%)

5 (15.6%)

<$15,000

5 (15.6%)

4 (12.5%)

$15,000-$24,999

6 (18.8 %)

5 (15.6%)

$25,000-$49,999

4 (12.5 %)

3 (9.4%)

>50,000

1 (3.1%)

0 (0%)

Did not answer

1 (3.1%)

3 (9.4%)

Annual income

Table 3
Did you know that frequent use of asthma medication could lead to a higher rate of tooth
decay?
Parents answer

Frequency (Percent)

Yes

10 (32%)

No

22 (68%)

 
 
 
 
 
Table 4
MANOVA Comparing Mean Change Scores of the Lollipop vs. Control Group
Measure

Mean Change Score

Control

F

p value

Experimental

Streptococcus  Mutans  

71.27

-2.76

3.09

p = .09

Lactobacilli  

-36.13

-81.65

0.21

p = .65

0.20

0.06

1.42

p = .24

DMFT
 

 
Discussion:  
The  experimental  group  (herbal  lollipop)  showed  a  mean  decrease  in  bacteria  for  
both  Streptococcus  Mutans  and  Lactobacilli  supporting  the  notion  the  lollipops  work.    
The  DMFT  of  the  experimental  group  had  less  of  an  increase  than  the  control  group.    
Results  were  not  statistically  significant  because  of  a  power  issue  and  a  variance  
issue  (SD),  and  likely  would  have  been  significant  with  more  subjects.        
 
Many  challenges  were  faced  with  completing  this  study.    The  study  began  trying  to  
find  participants  with  a  narrow  qualifying  window.    The  participants  needed  to  use  
a  Beta2-­‐adrenergic  agonist  inhaler  at  least  1  time  a  week.    It  was  found  that  most  
kids  with  a  medical  diagnosis  of  asthma  are  controlled  with  a  corticosteroid  and  the  
use  of  their  beta2-­‐adreneric  inhaler  was  needed  for  emergency  purposes  only,  which  
occurred  less  than  one  time  a  week.    Some  participants  used  their  beta2-­‐adrenergic  
inhaler  more  during  the  winter  and  less  during  the  summer  seasons,  where  some  
used  it  more  during  the  allergy  season.    After  finding  very  few  subjects  who  used  
their  inhaler  more  than  one  time  a  week  the  criteria  changed  to  having  a  medical  
diagnosis  of  asthma  and  using  a  beta2-­‐adrenergic  agonist  PRN.      
 
A  high  no-­‐show  rate  occurred  when  trying  to  get  the  qualified  subjects  to  arrive  for  
the  first  visit.    This  is  partially  due  to  the  patient  population;  the  population  has  a  
high  no-­‐show  rate  for  all  dental  appointments.      The  subjects  were  told  prior  to  their  
first  appointment  that  they  would  receive  a  spin  brush  if  the  study  was  completed.    

Throughout  the  course  of  the  study  there  was  too  many  opportunities  for  the  
patient  to  drop  out.    Some  of  the  incomplete  participants  did  not  finish  the  first  
batch  of  lollipops  with  reasons  of  “did  not  like  the  taste”  or  “gave  me  a  stomach  
ache”  or  “just  forget  to  suck  on  them.”  Some  of  the  incomplete  participants  did  not  
return  to  pick  up  the  second  batch  of  lollipops  three  (3)  months  into  the  study.      A  
few  participants  did  not  finish  the  second  batch  of  lollipops  and  some  did  not  return  
for  the  final  evaluation/visit.      
 
Most  children  liked  the  taste  of  the  lollipops  in  the  control  group  and  the  
experimental  group.    There  were  not  any  side  effects  with  most  children,  except  a  
few  stated  it  gave  them  a  stomachache.      
 
The  study  would  be  stronger  if  the  lollipops  were  given  in  a  more  controlled  
situation.    I  would  recommend  a  school  nurse  give  the  participants  the  lollipops  at  
the  same  time  everyday  to  assure  that  the  participants  are  using  their  lollipops.    
Upon  completion  of  the  study  it  was  simply  the  parent/legal  guardians  word  that  
they  finished  all  the  lollipops.    A  few  families  had  multiple  children  participating  in  
the  study  with  one  child  being  in  the  control  group  and  the  other  the  study  group.    It  
was  our  hope  that  the  lollipops  did  not  get  switched  between  the  two  children.      
 
Bacteria  levels  increased  in  many  participants  in  both  control  group  and  study  
group.    A  benenficial  test  would  be  to  take  a  pre  and  post  plaque  index.    It  is  
important  to  realize  that  these  lollipops  are  adjunctive  therapy  and  brushing  and  

flossing  are  still  the  most  important  oral  hygiene  therapy.    A  plaque  index  was  not  
completed  but  it  is  my  hypothesis  that  increases  in  Streptococcus  Mutans  and  
Lactobacilli  were  due  to  increased  amounts  of  plaque  in  patients  who  were  either  
not  brushing  effectively  or  not  brushing  at  all.    A  few  participants  had  an  increase  in  
bacteria,  but  also  had  new  caries.    With  active  caries  in  the  oral  cavity  it  would  be  
suspected  that  there  would  be  an  increase  in  bacteria.      
 
Conclusion:  
This  study  may  not  be  statistically  significant,  but  still  showed  evidence  that  the  
herbal  lollipops  decrease  bacterial  levels  in  the  oral  cavity.      A  decrease  in  bacteria,  
aids  in  decreasing  the  caries  process,  which  most  children  using  a  beta2-­‐adrenergic  
agonist  would  benefit  from.      It  is  a  hope  that  this  study  can  be  used  to  build  off  for  
future  studies.  Herbal  lollipops  appear  to  be  good  adjunctive  oral  hygiene  therapy  
and  hopefully  in  the  future  more  studies  can  be  completed.      
 
 
 
 
 
 
 
 
 

References:  
(1) office  of  the  Surgeon  General  (internet).    US  Dept  of  Health  and  Human  
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http://www.surgeongeneral.gov/news/speeches/oralhealth042903.htm.    
 
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(4) Ryberg  M.,  Moller  C.,  Ericson  T.  Effect  of  Beta  2-­‐adrenoceptor  agonists  on  
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(5) Ryberg  M.,  Moller  C.,  Ericson  T.    Saliva  composition  and  caries  development  
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(6) Reddy  D.  K.,  Hedge.  M.,  Munshi  A.  K.  Dental  caries  status  of  children  with  
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(7) McDerra  E.  J.,  Pollard  M.A.,  Curzon  M.E.J.  The  dental  status  of  asthmatic  
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(8)  Milano  M.  Increased  risk  for  dental  caries  in  asthmatic  children.  Texas  Dent  J  
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(9) Shulman  J.D.,  Taylor  S.E.,  Nunn  M.E.  The  Association  between  Asthma  and  
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Milan  M.,  Lee  J.Y,  Donovan  K.,  Chen  J.  A  cross-­‐sectional  study  of  

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(11)

He.  J.,  Chen  L.,  Heber  D.,  Shi  W.,  Lu  Q.    Antibacterial  compounds  from  

Glycyrrhiza  uralensis.  J  Nat  Prod  2006:  69:  121-­‐4.  
 
 
 

(12)

Hu  C.,  He  J.,  Eckert  R.,  Wu  X.,  Li  L.,  Tian  Y.,  Lux  R.,  Shuffer  J.,  Gelman  F.,  

Mentes  J.,  Spackman  S.,  Bauer  J.,  Anderson  M.,  Shi  W.  Development  and  
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Johnson,  N.W.  Risk  Markers  for  Oral  Diseases;  Cambridge  University  

Press:  Cambridge.  U.K.,  1991  
 
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White,  Stuart  C.,  Pharoah,  Michael  J.  Oral  Radiology:  Principles  and  

Interpretation  (S.  Louis,  Missouri:  Mosby  Elesevier,  2009),  35.    
 
 
 
 

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