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Elizabeth Ann Johnson, DDS

University of Nebraska Medical Center
Pediatric Dentistry Post Graduate Program

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

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.

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

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

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

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.

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 childs
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 (CFUs) 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 (CFUs) 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)
Treatment Group

Control Group


1 (3.1%)

4 (12.5%)


9 (28.1 %)

6 (18.8 %)

African American

7 (21.9%)

4 (12.5%)


0 (0%)

1 (3.1%)


12 (37.5%)

10 (31.3%)


5 (15.6%)

5 (15.6%)


5 (15.6%)

4 (12.5%)


6 (18.8 %)

5 (15.6%)


4 (12.5 %)

3 (9.4%)


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
Parents answer

Frequency (Percent)


10 (32%)


22 (68%)

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

Mean Change Score


p value


Streptococcus Mutans




p = .09





p = .65




p = .24


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.

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.

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