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Salivary stimulation-could it play a role in GERD management?

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Overview
GERD (gastro-esophageal reux disease) describes a condition
in which the lower esophageal sphincter (LES) relaxes and allows
stomach acid to ow up into the esophagus and towards/into the
mouth. Symptoms develop when reux is excessive and the esophagus
and mouth is bathed in acid for a long enough period of time to cause
mucosal damage. GERD is estimated to occur in ten to thirty percent
of the population in developed countries.1
Nocturnal GERD involves reux of acid into the esophagus during
sleep. The condition is estimated to occur once a month in up to 43%
of individuals and once a week in 20% of the population.2,3 GERD is
associated with heartburn (upper chest pain), an acid taste at the back
of the throat (regurgitation or reux)4,5 as well as voice hoarseness and
sleep disturbance.6,7
In the primary care setting, GERD is typically diagnosed via
symptom presentation and response to empiric trials of proton pump
inhibitors (PPIs). Specialized tests are only considered necessary if
there is suspicion of more severe esophageal abnormality.8 Guidelines
for diagnosing GERD have been published by the American
College of Gastroenterology and the American Gastroenterological
Association.9,10
There are several ‘defense’ elements that help to mitigate GERD
including the lower esophageal sphincter (LES) which keeps acid
within the stomach, esophageal peristalsis which mechanically
propels uid (including saliva) into the stomach, and saliva ow
which serves to neutralize and dilute acid that escapes the stomach.11,12
Prolonged contact with stomach acid can lead to mucosal damage in
the esophagus and to oral structures. The physiologic abnormalities
that cause GERD include poor functioning of the LES, abnormal
esophageal clearance, reduced salivary production, altered esophageal
mucosal resistance, and delayed gastric emptying.13
Saliva and GERD
It has been proposed that increased salivation resulting from
esophageal acidication is mediated through an ‘esophago-salivary’
reex.14 Acid accumulating in the upper region of the esophagus is
reported to reexively initiate saliva production.15 But this reexive
stimulation does not appear to occur as readily when stomach acid is
infused into the lower esophagus and when it does not reach the upper
regions of the GI track.16 Thus saliva, with its innate acid buffering
capacity, appears to play a role in mediating some of the symptoms
of GERD, and its affect may be more pronounced when saliva is
stimulated by acid reaching the upper esophagus.
Saliva is acknowledged to play in important role in protecting the
esophageal lining, partly by diluting and partly by buffering stomach
acid that enters the esophagus through reux.17–20 Swallowing occurs
at the rate of about once per minute during the day under normal
circumstances while moving saliva, and food, into the esophagus21
but is apparently altered by food consumption and age.18 Saliva at
rest and during stimulation differs signicantly. The normal resting, or
unstimulated, whole salivary ow rate is 0.25-0.50 mL (or gram)/min.
Symptomatic dryness may not be reliably observed until the level
falls below 0.10 mL (or gram)/min. The normal, whole stimulated (by
chewing parafn) salivary ow rate is 1-3 mL (or gram)/min. As a
general rule, 0.7 ml/min is the cut off point for dening normal versus
abnormal stimulated ow of whole saliva and 0.1 ml/min22 is the
cutoff for below-normal unstimulated whole salivary ow.
Saliva production is reduced during sleep. Age also plays a
signicant role in the production of saliva and, in addition, may also
contribute to disturbances in esophageal motility and peristalsis as
well as nonpropulsive and repetitive contractions. Saliva production
is also reduced by numerous medications such as the anti-convulsants,
anti-parkinsonian agents, anti-psychotics, anti-depressants,
anti-pruritics, anti-histamines, anti-hypertensives, anxiolytics,
expectorants, decongestants, diuretics, narcotics, monoamine oxidase
inhibitors, sedatives, systemic bronchodilators, cardiac antiarrhythics,
and skeletal muscle relaxants. In addition, medical conditions
that common occur in the elderly, such as cerebrovascular disease,
cardiovascular disease, pulmonary disease, diabetes mellitus, and
Parkinson’s disease23,24 are associated with reduced salivation as well
as altered esophageal motility and sphincter function.
Current treatment of GERD
The medical standard of care for treating GERD is pharmacotherapy
that involves prescribed and over-the-counter (OTC) medications
J Otolaryngol ENT Res. 2018;10(3):127130. 127
© 2018 Burgess. This is an open access article distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and build upon your work non-commercially.
Salivary stimulation-could it play a role in GERD
management?
Volume 10 Issue 3 - 2018
Jeffrey Burgess
Oral Care Research Associates, USA
Correspondence: Jeffrey Burgess, Oral Care Research
Associates, 2006 NE 63rd Street Seattle, Washington 98115,
USA, Tel 206 450 2640,
Email oral.care.research.assoc@gmail.com
Received: February 12, 2018 | Published: May 02, 2018
Abstract
Multiple diverse studies indicate that swallowed saliva plays an important role
in neutralizing stomach acid refluxed into the esophagus and mouth; the acid that
causes the symptoms of gastro-esophageal reflux disease (GERD). This article briefly
reviews the epidemiology of GERD, its pathogenesis and symptom presentation, its
connection to salivation, and its medical management and presents results from a
study suggesting that an increase in salivation during sleep can significantly improve
symptoms associated with the condition. The presented study demonstrates that
an OTC product currently on the market (OraCoat XyliMelts) that is specifically
designed to increase salivation through the slow release of flavoring is an effective
adjunctive remedy for reducing reflux and heartburn symptoms associated with sleep
related GERD.
Journal of Otolaryngology-ENT Research
Research Article Open Access
Salivary stimulation-could it play a role in GERD management? 128
Copyright:
©2018 Burgess
Citation: Burgess J. Salivary stimulation-could it play a role in GERD management?. J Otolaryngol ENT Res. 2018;10(3):127130.
DOI: 10.15406/joentr.2018.10.00328
which inhibit acid secretion (proton pump inhibitors: PPI’s), histamine
receptor antagonists (H2 blockers), and prokinetics that increase
tone in the lower esophageal sphincter. Alternative remedies include
dietary modication, avoiding meals and alcohol shortly before sleep
and raising the head of the bed, and over-the-counter (OTC) alkaline
agents (e.g. calcium carbonate) that help to neutralize stomach acid.
In at least one study, PPI’s and H2 blockers were found to be
equivalent in terms of symptomatic relief.25 Other studies suggest
greater symptomatic improvement may occur with use of the PPIs22.
However, the management of GERD with PPIs may not be helpful
in all cases. It has been suggested that up to one-third of GERD
patients may not respond to - PPI intervention.27 PPI use has also been
associated with an increased risk of bone fracture as well asVitamin
B-12 deciency.28
The use of histamine-2 receptor antagonists29 may also be limited
by their side effects and, due to their inhibition of the liver P450
system, the potential for drug interactions.30 This class of medication
has not been well studied in pregnant women. Hence, the literature
suggests that patients planning on becoming pregnant or who are
pregnant should consult their family physician prior to their use.
Caution should also be used in those individuals who have allergies
to certain medicines, foods, kidney or liver problems; or certain
lung diseases such as COPD, diabetes, or a history of porphyria.31,32
Medications that increase tone in the esophageal sphincter have also
been recommended for use in severe cases of GERD. These prokinetic
medications are only recommended for short term use and their
side effect spectrum (e.g. depression and severe muscle twitching,
dizziness or lightheadedness, potentially fatal heart arrhythmias)
limits their general usefulness.33
Antacids are effective in managing acute GERD but are not
considered reasonable for long term use34 due to their side effects.
Further, for GERD occurring at night, it is not until sleep is disturbed
that these medications are taken, which reduces their overall benet
in terms of sleep quality of life.35,36 Given the fact that many people
do not gain relief from PPIs, that histamine-2 receptor antagonists
are associated with multiple side effects and interactions with other
drugs, and that the benet of antacids is limited by associated sleep
disturbance (having to repeatedly awaken to take the medication) and
by the fact that they may not be appropriate for chronic use, additional
approaches to the treatment of GERD occurring during sleep need to
be considered.37
Study rationale
The study was conducted by Peter Van der Ven, Michael Karcher,
and myself and published in August 2017.38 The aim of this study
was to see if OraCoat XyliMelts, an OTC dissolvable, adhering disc
used to reduce excessive day time or night time dry mouth, would
also reduce reux and heartburn occurring during sleep. OraCoat
XyliMelts are made from food grade ingredients and stimulate saliva
via slowly released avor when used as directed. Reux symptoms
are sometimes more prominent at night because acid can more readily
enter the esophagus while patients are lying down. Anecdotal reports
and research suggest that salivary stimulants can reduce the sensation
of dry mouth. As noted, the literature suggests that salivation can
ameliorate reux and heartburn39. Hence, we hypothesized that the
stimulation of salivation by a slowly dissolving avored intraoral
adhering disc could also signicantly alter reux and heartburn
symptoms associated with GERD during night-time sleep.
Subjects and methods
Study design
This study was approved by the Western Institutional Review
Board on September 16, 2014 (WIRB; 1019 39th Ave S, Ste 120,
Puyallup, WA 98374). It was designed as a randomized, placebo-
controlled trial involving two over the counter products currently on
the market for use in the management of dry mouth symptoms. The
product of interest was cleared by the FDA for investigation in the
context of GERD on September 4, 2014 (Investigational New Drug
Application number 123574 US FDA). Study information/results can
be found on ClinicalTrials.gov.
Study participants and the research coordinator were blinded
as to the product received by the subjects who were independently
randomized. The product of interest was OraCoat XyliMelts, produced
by OraHealth Corporation in Bellevue, Washington. The ingredients
in OraCoat XyliMelts are all-natural and commonly used in foods:
xylitol for sweetness, mild mint for additional avor, cellulose gum
to slow dissolution and lubricate the mouth, an acacia gum adhesive
layer, and calcium carbonate to neutralize the acidity of acacia gum and
oral bacteria. It has been reported that when the product is dissolved in
5 parts water the resulting pH is 8.138. Product users also report that
OraCoat XyliMelts discs slowly dissolve over several hours during
sleep and their avor can still be sensed upon awakening 8 hours later.
The product used as a placebo was a water based gel containing
cellulose hydrocolloid gums with sorbitol and xylitol sweeteners. As
it is a soluble gel introduced prior to sleep, it was presumed to be
eliminated from the oral cavity fairly quickly via salivary stimulation.
For this reason it was selected as a placebo.
Study population/subjects
Subjects were drawn from individuals living in major metropolitan
cities in the United States who responded to an ad soliciting paid
volunteers.
Those qualifying for the study based on inclusion and exclusion
criteria were, after consent, assigned to a baseline information
collecting period of two weeks. Each day subjects were required to
complete a short questionnaire that included the following questions:
a. Did you taste reuxed stomach acid during your sleep last night
(yes/no);
b. How severe was the reux (mild, moderate, severe, very severe);
c. Did you have heartburn when you slept (yes/no);
d. How severe was the heartburn (mild, moderate, severe, very
severe);
e. Did you keep water by your bedside because of dry mouth
occurring during sleep (yes/no);
f. Did you have uncomfortable dry mouth when you slept or upon
awakening (yes/no);
g. Did you experience hoarseness of your voice in the morning (yes/
no);
h. Did you need to take antacids during sleep (yes/no); and
i. If so, how many did you take (number).
Salivary stimulation-could it play a role in GERD management? 129
Copyright:
©2018 Burgess
Citation: Burgess J. Salivary stimulation-could it play a role in GERD management?. J Otolaryngol ENT Res. 2018;10(3):127130.
DOI: 10.15406/joentr.2018.10.00328
Upon completion of this rst baseline phase, qualied subjects
were then entered into the product phase of the study (phase two).
Qualication for entry into phase two was based on having reported
reux taste on eight of the 14 days of baseline and dry mouth seven
of the same mornings. Randomization was to one of two groups:
treatment or control. Each subject then received by mail either the
adhering discs disguised in unmarked packaging (treatment), or a
sweet, water based gel in an unmarked white tube (control), with
printed instructions copied from the manufacturer’s recommendations
for their method of use at bedtime. The analyzed variables of interest
included reux taste, reux severity, heartburn sensation, heartburn
severity, morning voice hoarseness and antacid use during sleep time.
53 subjects were ultimately selected to receive the disc or gel to use
during sleep for two additional weeks. Comparisons were then made
within and between groups for all outcome variables.
Results
Subjects in the two nal intervention groups were not signicantly
different when compared on the basis of gender, age, or prior medical
diagnosis of reux. For the symptom of heartburn, Subjects using
the discs demonstrated a signicant reduction in reported pain of
heartburn when compared with baseline (one sided U-test p value
<.001). Subjects using the gel also experienced a signicant reduction
in pain when compared to baseline (U-test p value <.001). When
these two remedies were compared via U-test, disc intervention
demonstrated signicantly greater improvement in heartburn pain
than gel intervention (U-test p value <.01) (Figure 1).
Figure 1 Heartburn.
In terms of reux severity, subjects using the disc intervention
reported a signicant reduction in reux severity when compared
with baseline (one sided U-test p value <.001). (Figure 2) Subjects
using the gel also experienced a signicant reduction in reux severity
when compared to baseline values (U-test p value <.001). When the
performance between the disc and gel treatments was compared, a
statistically signicant difference was not observed (U-test p> 0.13).
Hoarseness was also signicantly reduced with disc and gel
treatment (p <.001) with comparison between the two products not
statistically signicant (p = 0.41) (Figure 3). The disc treatment
resulted in a 60% reduction in antacid use while the gel intervention
demonstrated a 45% reduction. Values were signicantly different for
both treatments. A T-test comparing the two treatments did not show a
signicant difference (p = 0.89) (Figure 3).
Figure 2 Reux Severities with Disc.
Figure 3 Antacid Uses, Nights with Taste of Acid, and Hoarseness.
Discussion
Nightly use of both adhering discs and gel dry mouth remedies that
stimulate saliva via avor appear to signicantly reduced symptoms
associated with GERD, including morning hoarseness, reux acid
taste, night time heartburn, and perceived reux. Subjects who used
the discs and gel for two weeks also demonstrated a signicant
reduction in antacid use during the night in comparison to two weeks
of baseline use. The discs were found to be generally more effective
in reducing symptoms than the gel, although most of the differences
were not statistically signicant. The exception was heartburn, where
improvement was found to be signicantly better for subjects using
the discs than the gel. Signicant side effects were not reported in
either group during product use.
This reviewed study suggests that two available OTC products
used to manage dry mouth during sleep may provide an effective
adjunctive remedy for reducing reux and heartburn symptoms in
patients with concomitant xerostomia. The adhering discs and the gel
were well tolerated and not associated with adverse reactions during
use. Further, the data appear to support the hypothesis that an increase
in salivation during sleep may be the reason for symptom reduction.
The ndings of this study are novel and medically relevant as
prolonged salivary stimulation via the introduction of a persistent oral
avor during sleep may provide an additional strategy for managing
symptoms arising from nocturnal GERD.
This study was limited by the lack of inclusion of different
population cohorts and study duration. A prospective study involving
Salivary stimulation-could it play a role in GERD management? 130
Copyright:
©2018 Burgess
Citation: Burgess J. Salivary stimulation-could it play a role in GERD management?. J Otolaryngol ENT Res. 2018;10(3):127130.
DOI: 10.15406/joentr.2018.10.00328
different population groups (e.g. individuals with post radiation
xerostomia or dryness associated with autoimmune disease) would
help to further clarify the idea.
Acknowledgments
None.
Conict of interest
The authors declare no conict of interest.
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... The quantity of stimulated saliva at 5 min we found in our study was lower in GERD patients then in healthy individuals, although the mean value was in the normal range of 5-15 mL (1-3 mL/min) [33]. These results are consistent with current data from the literature. ...
... Collaboration between physicians and dentists is strongly advocated to prevent or ameliorate possible adverse oral effects from both endogenous and exogenous acids, and to promote adequate saliva production in patients with GERD [41]. Numerous researches present the correlation between the values of salivary pH, the disturbances in salivary quantity, and the GERD symptoms [33][34][35]42,43]. Oral cavity diseases may be developed as a result of changes in the oral fluid characteristics, including pH, which can modify the properties of dental materials [1,[44][45][46]. ...
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The oral cavity has specific and individualized characteristics, with pH, saliva flow, buffer capacity, temperature, and microorganisms content influencing oral health. Currently, the prevalence of gastroesophageal reflux disease (GERD) is constantly increasing. The objective of this study was to evaluate and compare the saliva quantity at 5 min, salivary pH, and salivary buffer capacity in patients with and without GERD, necessary for establishing the correct dental treatment plan. A Saliva-Check Buffer (GC) kit was used for the determination of salivary variables. The total number of 80 patients included in the study were divided into a study group and a control group, each containing 40 patients. Saliva quantity at 5 min was lower in patients suffering from GERD. The salivary pH of these patients turned to acid values compared to the salivary pH of controls, where the values were within the normal range. In patients with GERD, the determined salivary buffer capacity was low or very low. The use of the Saliva-Check Buffer (GC) kit is a simple, easy, non-invasive and patient-accepted method, which can also be used in the dentist’s office to assess the saliva buffer capacity and pH, variables that are important for establishing a correct dental treatment plan.
... However, hypersalivation, although uncomfortable and disruptive, does not necessarily have to be negative since saliva plays an important role in protecting the esophageal mucosa. There are studies on the importance of ingested saliva that neutralizes the pH of gastric acid regurgitated into the esophagus [21] and on the buffering of gastric acid that enters the esophagus by reflux [22]. The acid that accumulates in the upper part of the esophagus reflexively initiates the formation of saliva [23], which is not the case when the acid accumulates in the lower part of the esophagus [24]. ...
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Proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs) suppress the production of gastric acid and thus may lead to malabsorption of vitamin B12. However, few data exist regarding the associations between long-term exposure to these medications and vitamin B12 deficiency in large population-based studies. To study the association between use of PPIs and H2RAs and vitamin B12 deficiency in a community-based setting in the United States. We evaluated the association between vitamin B12 deficiency and prior use of acid-suppressing medication using a case-control study within the Kaiser Permanente Northern California population. We compared 25,956 patients having incident diagnoses of vitamin B12 deficiency between January 1997 and June 2011 with 184,199 patients without B12 deficiency. Exposures and outcomes were ascertained via electronic pharmacy, laboratory, and diagnostic databases. Risk of vitamin B12 deficiency was estimated using odds ratios (ORs) from conditional logistic regression. Among patients with incident diagnoses of vitamin B12 deficiency, 3120 (12.0%) were dispensed a 2 or more years' supply of PPIs, 1087 (4.2%) were dispensed a 2 or more years' supply of H2RAs (without any PPI use), and 21,749 (83.8%) had not received prescriptions for either PPIs or H2RAs. Among patients without vitamin B12 deficiency, 13,210 (7.2%) were dispensed a 2 or more years' supply of PPIs, 5897 (3.2%) were dispensed a 2 or more years' supply of H2RAs (without any PPI use), and 165,092 (89.6%) had not received prescriptions for either PPIs or H2RAs. Both a 2 or more years' supply of PPIs (OR, 1.65 [95% CI, 1.58-1.73]) and a 2 or more years' supply of H2RAs (OR, 1.25 [95% CI, 1.17-1.34]) were associated with an increased risk for vitamin B12 deficiency. Doses more than 1.5 PPI pills/d were more strongly associated with vitamin B12 deficiency (OR, 1.95 [95% CI, 1.77-2.15]) than were doses less than 0.75 pills/d (OR, 1.63 [95% CI, 1.48-1.78]; P = .007 for interaction). Previous and current gastric acid inhibitor use was significantly associated with the presence of vitamin B12 deficiency. These findings should be considered when balancing the risks and benefits of using these medications.
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Gastroesophageal reflux disease (GERD) is the most common upper gastrointestinal disorder seen in the elderly. The worldwide incidence of GERD is increasing as the incidence of Helicobacter pylori is decreasing. Although elderly patients with GERD have fewer symptoms, their disease is more often severe. They have more esophageal and extraesophageal complications that may be potentially life threatening. Esophageal complications include erosive esophagitis, esophageal stricture, Barrett's esophagus and adenocarcinoma of the esophagus. Extraesophageal complications include atypical chest pain that can simulate angina pectoris; ear, nose, and throat manifestations such as globus sensation, laryngitis, and dental problems; pulmonary problems such as chronic cough, asthma, and pulmonary aspiration. A more aggressive approach may be warranted in the elderly patient, because of the higher incidence of severe complications. Although the evaluation and management of GERD are generally the same in elderly patients as for all adults, there are specific issues of causation, evaluation and treatment that must be considered when dealing with the elderly.
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The pathogenesis of gastro-oesophageal reflux disease includes increased acid reflux, reduced salivation and impaired peristalsis. This may depend upon the height of acid wave and magnitude of oesophageal mucosal exposure. Interestingly, the effect of site of acid infusion upon salivary secretion and heartburn has not been examined in any detail. To examine whether acid infusion in the upper oesophagus may cause increased salivation and heartburn as compared with acid infusion in the lower oesophagus. Methods: Twelve healthy male subjects (mean age 30) received infusions of HCl, citric acid and acetic acid at 10 and 20 cm above the lower oesophageal sphincter (LES) for fixed time periods. Parotid saliva collected periodically and heartburn severity scored using standardized scale. Standard statistical methods (paired t-tests, analysis of variance) were used to determine the significance of results. Acid infusion in the upper oesophagus increased parotid flow rate as compared with that in the lower oesophagus (P < 0.05). Likewise, there was a significantly increased heartburn score at 20 cm as well as 10 cm above LES (P < 0.05) as compared with that in the stomach. These data suggest a significant increase in salivation and heartburn in response to acid infusion in the upper vs. lower part of the oesophagus.