Aliment Pharmacol Ther 2002; 16: 2029–2035.
doi:10.1046/j.0269-2813.2002.01380.x
Clinical effectiveness of a new antacid chewing gum on heartburn
and oesophageal pH control
K. L. COLLINGS*, S. RODRIGUEZ-STANLEY*, H. M. PR OSKIN , M. ROBINSON * & P. B. M INER JR*
*Oklahoma Foundation for Digestive Research, Oklahoma City, OK, USA; Howard M. Proskin and Associates,
Rochester, NY, USA
Accepted for publication 19 August 2002
SUMMARY
Background: Oesophageal acid neutralization with antacids depends on the duration of oesophageal antacid
exposure and acid neutralizing capacity. A gum that
releases antacid as it is chewed could take advantage of
both mechanisms to enhance heartburn relief.
Methods: Twenty-four subjects were crossed over to
four regimens: placebo, chewable antacid tablets
(1000 mg CaCO3), lower dose gum (600 mg CaCO3)
and higher dose gum (900 mg CaCO3). A dual pH
probe was placed, subjects ate a standardized provocative meal and self-dosed once as needed. Symptoms
were recorded every 15 min using visual analogue
and Likert scales.
INTRODUCTION
Heartburn is a common symptom of substernal discomfort and burning that is treated by most of the
population with either folk remedies or over-the-counter
medications. The pathophysiology of gastro-oesophageal reflux involves the movement of gastric contents
into the oesophagus, often due to abnormal oesophageal
function. These gastric contents include ingested food,
mucus, fluid secreted by the stomach and gastric acid.
A common misperception amongst heartburn sufferers
is that their discomfort is due to acid in the stomach,
when it is, in fact, the refluxed gastric contents which
Correspondence to: Dr P. B. Miner Jr, Oklahoma Foundation for Digestive
Research, 711 Stanton L. Young Blvd Suite 619, Oklahoma City, OK
73104, USA.
E-mail: [email protected]
2002 Blackwell Science Ltd
Results: Symptoms: Both gums decreased heartburn
compared to placebo for 120 min. Higher dose gum
decreased heartburn more than chewable antacids up to
120 min post-dose. pH: Active chewable antacid and
gums immediately increased oesophageal pH, with
significant improvement 15–30 min post-dose.
Summary: (i) both gums promptly decreased heartburn
and elevated oesophageal pH; (ii) both gums provided
sustained relief for 120 min; (iii) antacid gums provided
faster and more prolonged symptom relief and pH
control than chewable antacids.
Conclusions: Calcium carbonate gum effectively neutralizes oesophageal acidity and relieves symptoms following a meal, and is superior to chewable antacids in
terms of the duration of heartburn relief.
may contain acid and may cause a burning sensation
when they come into contact with the oesophageal
mucosa. For this reason, antacids are often selected as
the most popular over-the-counter treatment for occasional episodes of heartburn. Careful and properly
controlled scientific studies also attest to the effectiveness of antacids for the management of heartburn and
to the ability of antacids to reduce the exposure of the
oesophagus to acid, but, interestingly, this improvement
is not reflected in dramatic changes in the gastric
pH.1, 2 In fact, gastric acid neutralization may not be
needed; it may only be necessary to neutralize the small
volume of gastric contents that actually enters the
oesophagus during a reflux episode. This hypothesis is
given credence by the observation that chewable
antacids seem to have a therapeutic advantage over
liquid antacids in providing symptom relief.3 The reason
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K. L. COLLINGS et al.
why chewable antacids are superior to liquid antacids is
unclear. One theory suggests that chewable antacids
stay in the mouth longer and take longer to swallow
than a liquid bolus, exposing the oesophagus to smaller
amounts of antacid over a relatively longer period. The
present study was designed to delineate the details of
chewable antacid pharmacology in subjects with heartburn using a traditional chewable antacid and an
antacid gum that would enable a slow, sustained release
of calcium carbonate.
AIMS
The primary objectives of this study were: (i) to demonstrate symptomatic relief of meal-induced heartburn by
an antacid-containing chewing gum; and (ii) to concurrently monitor the neutralization of oesophageal acid.
MATERIALS AND METHODS
The Western Institutional Review Board approved all
aspects of this single-site, single-blind, placebocontrolled study, and informed consent was obtained
from each study subject prior to enrolment.
Physical examination and medical history
Subjects were seen for a screening visit in order to perform
a physical examination and collect a medical history
confirming good health and a 6-month history of mealrelated heartburn. Once subjects were deemed qualified
to continue, they returned for four meal sessions.
(iii) two tablets of an over-the-counter chewable antacid
formulation, each containing 500 mg of calcium carbonate (chewable antacid; 1000 mg calcium carbonate
in total; Tums Regular Strength, SmithKline Beecham);
(iv) a swallowed placebo capsule, taken with 60 mL of
water (placebo; 0 mg calcium carbonate).
Oesophageal pH monitoring
At the beginning of each test session, subjects were
intubated transnasally with a dual electrode pH catheter
(15 cm spacing) with an internal reference electrode
(Medtronics Synectics). The catheter was positioned with
the proximal electrode 5 cm above the upper margin of
the manometrically identified lower oesophageal sphincter (oesophagus) and the distal electrode 10 cm below
the lower oesophageal sphincter (stomach). Continuous
electronic recording of the oesophageal pH profile
was accomplished with a Mk III Digitrapper.
Provocative meal
At each session, following a 1-h baseline period,
subjects consumed a provocative meal consisting of: (i)
a sausage, egg and cheese biscuit fortified with 30 g of
raw onion; (ii) 240 mL of chocolate milk; and (iii) a
large peppermint patty.4 Subjects were given 30 min to
consume up to two portions of each of the meal
components. Subjects were required to consume the
same amount at each subsequent meal session as they
did at the initial session.
Symptom assessment
Experimental design and study treatments
This study followed a single-blind, four-treatment crossover design. At the subjects’ first testing session, they
were randomly assigned to a treatment order sequence
that indicated which of the four study treatments would
be administered during each study session. The four
study treatments were: (i) two pellets of an antacid
chewing gum formulation, each containing 300 mg of
calcium carbonate (lower dose gum; 600 mg calcium
carbonate in total; Surpass antacid chewing gum
regular strength, Wrigley Healthcare); (ii) two pellets
of an antacid chewing gum formulation, each containing 450 mg of calcium carbonate (higher dose gum;
900 mg calcium carbonate in total; Surpass antacid
chewing gum extra strength, Wrigley Healthcare);
Symptoms were assessed at 15-min intervals starting
with the end of the 30-min meal session. At each
assessment time point, subjects were given the option of
self-dosing with their respective study treatment as
designated by randomization. During the 15-min period
immediately following self-dosing, subjects provided
additional assessments of heartburn symptoms at
5-min intervals. Symptom assessments were scored
using two methods: (i) by a 100-mm visual analogue
scale, according to which subjects placed a mark on a
line representing the continuum of heartburn severities,
ranging from ‘no symptoms’ to ‘severe symptoms’; and
(ii) by selecting a score on a five-point Likert scale which
provided five discrete scoring categories ranging from
‘none’ to ‘severe’.
2002 Blackwell Science Ltd, Aliment Pharmacol Ther 16, 2029–2035
ANTACID CHEWING GUM FOR HEARTBURN
Data management
The pH measurements recorded using the Digitrappers
were downloaded into ASCII files, from which SAS
databases were developed. Written logs of meal and
symptom assessment times were also produced. From
this information, as well as the symptom assessment
score sheets, a master database was constructed which
provided scores for the following parameters for each
15-min interval of time (and for the three 5-min
intervals immediately following dosing): visual analogue
scale scores for heartburn symptoms, recorded on a
continuous scale ranging from 0 (representing no
symptoms) to 100 (representing severe symptoms);
Likert scale scores for heartburn symptoms, recorded
on a five-point numerical scale ranging from 0 (representing no symptoms) to 4 (representing severe symptoms); oesophageal acid contact time (percentage of time
that the pH was below 4); mean oesophageal pH; and
mean gastric pH. The 15-min intervals were denoted by
the time point at which they ended. The ‘dosing’ time
interval consisted of the 15-min interval which immediately preceded the point at which the subject opted to
self-dose with his or her respective treatment.
Statistical evaluation
Separate statistical analyses were performed for each
parameter for each scoring interval, as previously
described, commencing with the dosing interval. Additionally, analyses were performed for mean pH for each
of the first 20 min after dosing. To account for skewness
and heteroscedasticity (non-uniform variability) in the
data, scores for the parameter ‘percentage of time that
the oesophageal pH was less than 4’ were transformed
via logarithms (base 10) prior to analyses. All parameters were summarized through the calculation of
means and standard deviations. Comparisons between
the treatment groups were made using analysis of
variance (anova), suitable for the analysis of data from a
cross-over experimental design. Included amongst the
factors in this anova were sequence (treatment
sequence order), period (experimental period) and
treatment. The test for significance of the treatment
sequence order, which employs the factor ‘subjects
within sequence’ as its error term, provided a means for
investigating the presence of possible carryover effect.
Analyses of the subjective heartburn severity scores
were adjusted for the level of symptom indicated
2002 Blackwell Science Ltd, Aliment Pharmacol Ther 16, 2029–2035
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immediately prior to dosing. Post-anova pairwise treatment comparisons were performed using two-tailed
t-tests. All statistical tests of hypotheses employed a level
of significance of P ¼ 0.05.
RESULTS
Patient population
Twenty-six subjects (17 females and nine males; mean
age, 43.5 years; range, 18–60 years) with at least a
2-month history of heartburn were recruited for this
study. As dosing was dependent on each subject’s selfassessment of heartburn symptoms, it was possible that
some subjects would not dose after each meal. Two
subjects did not have heartburn at one of the meal
sessions, and therefore did not receive their study
treatment and did not provide a complete set of data
for all four treatment periods. To maintain balance in
the cross-over analyses, the remaining data from these
subjects were excluded from all statistical analyses. No
significant carryover effect was noted for any of the
parameters measured over the course of this study.
Subjective measurements of heartburn severity — visual
analogue scale
The mean scores for subjective heartburn severity using
the visual analogue scale are illustrated in Figure 1. All
three of the active study treatments provided significantly lower levels of heartburn severity than did
placebo at all post-dosing assessment time points up to
120 min post-dose. The higher dose gum yielded
significantly lower scores than did the chewable antacid
at both the 5-min and 105-min assessment time points.
No other statistically significant difference was indicated
between the active treatment groups.
Subjective measurements of heartburn severity — Likert
scale
The mean scores for subjective heartburn severity using
the Likert scale are illustrated in Figure 2. Both the
higher dose and lower dose gum provided significantly
lower heartburn severity scores than did placebo at all
post-dosing assessment time points up to 120 min postdose. Chewable antacid tablets provided significantly
lower scores at all post-dosing assessment time points
than did placebo up to 45 min post-dose, and again at
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K. L. COLLINGS et al.
Mean VAS heartburn severity
60
50
40
30
20
Placebo
Chewable Antacid
Lower Dose Gum
HigherDose Gum
10
0
0 5 10 15
30
45
60
75
90
105
120
Marking time point (min post-dosing)
Figure 1. Self-assessment of heartburn
severity–VAS (100-point visual analogue
scale). Mean visual analogue scale (VAS)
heartburn assessments (range 0–100) were
taken at 5-min intervals for the first 15 min
post-dosing and at 15-min intervals thereafter. Both gums were better than placebo
after dosing up to 120 min (P < 0.05).
Mean Likert heartburn severity
4
Placebo
Chewable Antacid
Lower Dose Gum
Higher Dose Gum
3
2
1
0
0 5 10 15
45
75
30
60
90
Marking time point (min post-dosing)
the 75-min post-dose assessment time point. Higher
dose gum provided significantly lower scores than did
chewable antacid at the 5-, 10-, 15-, 75-, 105- and
120-min post-dose assessment time points. Lower dose
gum provided significantly lower scores than did the
chewable antacid at the 10-, 60-, 75- and 90-min postdose assessment time points. Lower dose gum provided
a significantly lower score than did the higher dose gum
at the 5-min post-dose assessment time point.
Oesophageal acid contact time (percentage of time that
the oesophageal pH < 4.0)
The mean scores for the percentage of time that the
oesophageal pH was below 4.0 are illustrated in
Figure 3. The scores for all three active treatment
groups were significantly lower than those for the
placebo group over the span of time between dosing and
60 min post-dosing. Additionally, the scores for both
the higher dose and lower dose gum were significantly
105
120
Figure 2. Self-assessment heartburn severity–Likert (5-point scale). Mean Likert
assessments (0–5) were taken at 5-min
intervals for the first 15 min post-dosing
and at 15-min intervals thereafter. Both
gums provided significantly lower heartburn severity scores than placebo after
dosing up to 120 min (P < 0.05).
lower than the placebo scores between 60 min and
75 min post-dosing. Both the higher dose and lower
dose gum provided significantly lower scores than did
the chewable antacid over the span of time between 10
and 30 min post-dosing.
Mean oesophageal pH
The mean scores for the mean oesophageal pH over each
1-min time interval between dosing and 20 min postdosing are illustrated in Figure 4(a) (In this figure, values
illustrated for each dosing time point represent mean
values for the 15 min immediately preceding the administration of the study treatment.) The mean oesophageal pH was significantly higher for all three active
treatment groups for every 1-min time interval between
1 min and 20 min post-dose (and for all but the higher
dose gum over the 1-min time interval between dosing
and 1-min post-dose) vs. placebo. Furthermore, both the
higher dose and lower dose gum provided significantly
2002 Blackwell Science Ltd, Aliment Pharmacol Ther 16, 2029–2035
ANTACID CHEWING GUM FOR HEARTBURN
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45
Figure 3. Percentage of time oesophageal
pH is less than 4.0. The mean percentage of
time that the oesophageal pH was less than
4.0 was assessed over time periods corresponding to the post-dose diary markings
(5-min periods for the first 15 min, 15-min
periods for the remainder of the session).
Both gums were better than placebo after
dosing up to 75 min (P < 0.05).
Mean percentage of time
oesophageal pH < 4.0
40
Placebo
Chewable Antacid
Lower Dose Gum
Higher Dose Gum
35
30
25
20
15
10
5
0
0 5 10 15
30
45
75
60
Time post-dose (min)
90
105
120
Mean oesophageal pH
(a) 7.0
6.5
6.0
5.5
5.0
Placebo
Chewable Antacid
Lower Dose Gum
Higher Dose Gum
4.5
4.0
0 1
3
4
5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Time post-dose (min)
(b) 7.0
Mean oesophageal pH
Figure 4. (a) Mean oesophageal pH (by
minute). The mean oesophageal pH scores
for all subjects were calculated over each
minute post-dosing from 1 to 20 min. Both
gums did better than placebo over each of
the 1-min periods between 1 min and
20 min post-dose (P < 0.05). (b) Mean
oesophageal pH. The mean oesophageal pH
scores for all subjects were calculated over
time periods corresponding to the post-dose
diary markings (5-min periods for the first
15 min, 15-min periods for the remainder
of the session). Both chewing gums provided significantly higher oesophageal pH
than placebo after dosing up to 75 min
(P < 0.05).
2
6.5
Placebo
Chewable Antacid
Lower Dose Gum
Higher Dose Gum
6.0
5.5
5.0
4.5
4.0
0 5 10 15
higher mean pH scores for every 1-min interval between
3 min post-dose and 20 min post-dose when compared
to the effects of the chewable antacid tablets.
The mean oesophageal pH over the ‘usual’ time spans
is illustrated in Figure 4(b). The scores for all three
active treatment groups were significantly higher than
2002 Blackwell Science Ltd, Aliment Pharmacol Ther 16, 2029–2035
30
45
60
75
90
105
120
Time post-dose (min)
for placebo between dosing and 45 min post-dosing.
Additionally, scores for both the higher dose and lower
dose gum were significantly higher than for placebo for
the interval between 45 and 75 min post-dosing. The
score for chewable antacid tablets was significantly
lower than for placebo between 90 min and 105 min
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K. L. COLLINGS et al.
post-dosing. Both the higher dose and lower dose gum
provided significantly higher scores than the chewable
antacid tablets between 5 min and 90 min post-dosing.
Additionally, the score for the higher dose gum was
significantly higher than that for the chewable antacid
tablets between 90 min and 105 min post-dosing.
Mean gastric pH
The mean scores for the mean gastric pH are illustrated
in Figure 5. Scores for the higher dose gum were
significantly higher than for placebo between 5 min and
120 min post-dosing. The gastric pH was higher with
the lower dose gum than with placebo between 5 min
and 90 min post-dosing. The scores for chewable
antacid were significantly higher than for placebo
between 10 min and 45 min post-dosing, and between
75 and 120 min post-dosing. Additionally, the score for
the higher dose gum was significantly higher than for
chewable antacid tablets between 30 min and 45 min
post-dosing, and higher than for lower dose gum
between 105 min and 120 min post-dosing. The mean
gastric pH did not exceed 3.0 for all treatments.
by the Likert scale. Post-dose symptom assessment for
chewable antacids and gum preparations revealed both
a faster onset of action and more prolonged symptom
relief with both the lower and higher dose gums.
Oesophageal pH findings
The abrupt increase in oesophageal pH with dosing
confirms the efficacy of chewable antacid and demonstrates the efficacy of antacid gum in neutralizing
oesophageal acid. This can be seen within the minute
by minute mean oesophageal pH measurements for the
first 20 min after dosing. The beneficial impact of these
products is corroborated by the traditional method of
assessing the effect of acidity in subjects with gastrooesophageal reflux: the percentage of time that the
oesophageal pH is below 4.0. Each active treatment
was effective in changing this important parameter of
oesophageal pathophysiology. One of the most interesting observations made during this study was the
apparent prolonged decrement in oesophageal acid
exposure that persisted long after discontinuation of
gum chewing and swallowing of the chewable antacid.
Gastric pH findings
DISCUSSION
Effect on symptoms
Both the visual analogue scale and categorical Likert
assessments demonstrated that all three active treatments promptly relieved heartburn symptoms compared
to placebo. However, heartburn severity was significantly lower with higher and lower dose gum vs.
chewable antacid at significant time frames directly after
the meal and in the extended time periods, as measured
In the past, it has been widely accepted that antacids
control heartburn symptoms by increasing the gastric
pH through the neutralization of gastric contents that
might subsequently reflux into the oesophagus. The
gastric pH data presented in the current study clearly
refute this hypothesis, as the mean gastric pH remained
below 3.0 following dosing with either chewable
antacid or lower and higher dose gum preparations,
despite the profound effects on oesophageal pH by all
4.0
Mean gastric pH
3.5
Placebo
Chewable Antacid
Lower Dose Gum
Higher Dose Gum
3.0
2.5
2.0
1.5
1.0
0.5
0.0
0 5 10 15
30
45
60
75
Time post-dose (min)
90
105
120
Figure 5. Mean gastric pH. The mean gastric pH scores for all subjects were calculated over time periods corresponding to the
post-dose diary markings (5-min periods for
the first 15 min, 15-min periods for the
remainder of the session). The mean gastric
pH did not exceed 3.0 for all treatments.
2002 Blackwell Science Ltd, Aliment Pharmacol Ther 16, 2029–2035
ANTACID CHEWING GUM FOR HEARTBURN
active antacid agents. The neutralizing effect of the
antacids is profound in the oesophagus, but only arrests
the continued fall in gastric pH and does not abruptly
neutralize gastric contents, nor even raise the gastric pH
to levels greater than pH 4.0.
Comparison of the two strengths of gum
There were no significant differences between the two
gum preparations, suggesting that oesophageal acid
neutralization is saturated at the lower dose. This may
explain why the lower strength gum occasionally outperformed the gum with more calcium carbonate.
Although the data do not provide definitive evidence
for the precise mechanism of action for such striking
effects on oesophageal pH, they are certainly consistent
with predominant intra-oesophageal acid neutralization.
Mode of action of the gum product
Swallowing is a complex physiological process which
influences heartburn in a number of ways that may
either benefit or complicate the problem of gastrooesophageal reflux. Each swallow induces relaxation of
the lower oesophageal sphincter, the muscular barrier
which protects the oesophagus from the reflux of gastric
contents. This relaxation prepares the lower oesophagus
to receive the swallowed bolus for transfer into the
stomach. Early physiological experiments demonstrated
that carefully timed, repetitive swallowing can significantly lower the lower oesophageal sphincter barrier.5–7
Chewing gum is associated with repetitive swallowing
which might theoretically increase the risk of gastrooesophageal reflux. However, there is no evidence that
any such effect occurred in this study.
Enhanced salivary secretion by gum chewing may be
beneficial in gastro-oesophageal reflux by inducing the
secretion of alkaline saliva to assist in the process of
neutralization, as well as providing a volume bolus to
clear the oesophagus of any noxious irritants.
It is obvious and easily demonstrated statistically that,
within the first minute of treatment usage, the chewable
2002 Blackwell Science Ltd, Aliment Pharmacol Ther 16, 2029–2035
2035
antacid and lower and higher dose chewing gums
neutralized oesophageal acid. From these data, it is
hypothesized that the amount of antacid released by
chewing these preparations promptly neutralizes the
relatively small amount of acid present in the oesophageal lumen. The hypothesis of acid neutralization
depends only on the chemical properties of the antacid
and saliva within the oesophagus and is independent of
changes in oesophageal physiology.
In conclusion, chewable antacid gum relieves the
symptoms of meal-induced heartburn rapidly, with
neutralization of the oesophageal pH immediately and
long after chewing has been completed. Unlike other
approaches to the management of acid reflux, this
product does not change the gastric pH with treatment.
ACKNOWLEDGEMENTS
This study was funded by an unrestricted grant from
Wrigley Healthcare.
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