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

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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
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
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Salivary stimulation-could it play a role in GERD
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,
Received: February 12, 2018 | Published: May 02, 2018
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
©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
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
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
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
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/
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
©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.
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.
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
©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.
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]. ...
Full-text available
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]. ...
Full-text available
Esophageal diseases are diagnosed by gastroenterological processing indicated due to typical gastrointestinal symptoms, but typical gastrointestinal symptoms are not the only possible manifestation of esophageal disease. There are also external symptoms such as chronic cough, laryngitis, pharyngitis, oropharyngeal dysphagia, odynophagia, laryngopharyngeal reflux, dysphonia, sinusitis, ear pain, and changes in laryngopharyngeal mucosa (erythema, edema, ventricular obliteration, cricoid hyperplasia and pseudosulcus). Extraesophageal symptoms are common in esophagitis and GERD, and studies show increasing prevalence of LPR in patients with GERD, as well as an association of reflux disease with cough and dysphonia symptoms. The aim of the chapter is to describe these extraesophageal symptoms of esophageal disease and how to recognize and treat them, in order to facilitate gastroenterologists’ diagnostic processing of patients with these symptoms, improve their treatment and assessment of the therapy effectiveness, prevent the development of stronger symptoms, and encourage multidisciplinary cooperation and exchange of knowledge, scientific and clinical work.
Gastroesophageal reflux disease (GERD) is a disorder due to the retrograde flow of refluxate into the esophagus. Although GERD is a common clinical diagnosis, its pathogenesis is quite complex. As a result of its multifactorial development, many patients continue to experience adverse symptoms due to GERD despite prolonged acid suppression with proton pump inhibitor therapy. The pathogenesis of GERD involves an interplay of chemical, mechanical, psychologic, and neurologic mechanisms, which contribute to symptom presentation, diagnosis, and treatment. As such, GERD should be approached as a disorder beyond acid. This review will investigate the major factors that contribute to the development of GERD, including factors related to the refluxate, esophageal defenses, and factors that promote pathologic reflux into the esophagus. In reviewing GERD pathogenesis, this paper will highlight therapeutic advances, with mention of future opportunities of study when approaching GERD. The pathogenesis of gastroesophageal reflux disease (GERD) involves an interplay of chemical, mechanical, psychologic, and neurologic mechanisms, which contribute to symptom presentation, diagnosis, and treatment. As such, GERD should be approached as a disorder beyond acid. This review will investigate the major factors that contribute to the development of GERD, including factors related to the refluxate, esophageal defenses, and factors that promote pathologic reflux into the esophagus.
Full-text available
The aim of this double-blinded, randomized, controlled study was to determine if OraCoat XyliMelts, an over the counter, dissolvable, adhering disc used to reduce excessive day time or night time dry mouth by increasing salivation, would also reduce reflux and heartburn symptoms occurring during sleep among subjects suffering from both GERD and xerostomia. Subjects submitted 14 days of baseline data by answering questions and were then randomized into one of two groups: one receiving a dry mouth gel (control) and a second receiving a disc (product of interest). Neither the identities of the two products nor the manufacturers of the products was revealed to subjects. Answers to the same set of questions were then collected for an additional 14 days as the supplied products were used. The accumulated data were evaluated for pre-post treatment changes within and between groups. Variables included reported heartburn, reflux, reflux taste, hoarseness, dry mouth, and antacid use. The results showed a significant decrease in the severity of the above symptoms of GERD with both disc and gel use, although improvement was greatest for those using the discs. Comparison between the gel and disc groups for most symptoms did not reveal significant differences. For heartburn, subjects using the discs perceived significantly less pain than subjects using the gel. We conclude that the use of certain products intended to reduce dry mouth during sleep, including OraCoat XyliMelts, may be an effective adjunctive remedy for reducing reflux and heartburn symptoms in patients with GERD and xerostomia.
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Dysphagia may worsen due to fatigue of the infrahyoid and suprahyoid muscle groups as a result of repetitive swallowing during a meal. We investigated the hypothesis that meal consumption may reduce tongue strength and endurance in older adults (OAs). Tongue-palate pressure, oral diadochokinesis, repetitive saliva swallowing, and surface electromyography activity before and after a meal were measured in 23 young adults (YAs) and 23 OA volunteers. There was a statistically significant difference in both tongue pressure and the number of voluntary swallows between YAs and OAs. Peak tongue pressure was significantly lower in OAs than YAs both before and after meal consumption. The most notable finding was that the first time interval (the time from test initiation to the beginning of the first swallow) was prolonged after meal consumption only in OAs, whereas the first time interval showed no difference between YAs and OAs before meal consumption with reference to the repetitive saliva swallowing test. The initiation of swallowing was prolonged by both meal consumption and aging; there was a significant interaction between these two factors. The number of repetitions of the monosyllable/pa/was statistically similar between YAs and OAs before meal consumption, but it was significantly lower in OAs after meal consumption. Aging leads to declining tongue pressure and motor function of the lips. It is possible that swallowing function declines in older individuals when meal consumption is prolonged, especially at the end of mealtime, as a result of their efforts in mastication and swallowing.
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Objectives: Gastroesophageal reflux disease (GERD) in primary care practice presents symptomatically, and resources to distinguish promptly between erosive esophagitis and endoscopy-negative reflux disease (ENRD) are limited. It is therefore important to determine the roles of proton pump inhibitors and histamine-2-receptor antagonists for first-line symptom-based therapy in patients with erosive esophagitis and ENRD. The aim of this study was to compare pantoprazole 40 mg once daily versus nizatidine 150 mg b.i.d. in a mixed GERD patient population with ENRD or erosive esophagitis (Savary-Miller grades 1-3). Methods: A 4-wk randomized, double-blind, parallel-group, multicenter study conducted in Canada. Eligible patients had experienced GERD symptoms > or = 4 times weekly for > 6 months. Patients were randomized to pantoprazole 40 mg once daily or nizatidine 150 mg b.i.d.. Endoscopy was performed before randomization and after 4 wk of therapy. Results: Of 220 patients randomized to therapy, 208 were available for a modified intent-to-treat analysis. Erosive esophagitis was present in 125 patients; 35 patients were Helicobacter pylori positive. There was complete symptom relief after 7 days of therapy in 14% of patients on nizatidine and in 40% of those on pantoprazole (p < 0.0001), and after 28 days of treatment in 36% and 63% of patients, respectively (p < 0.0001). After 28 days of treatment, adequate heartburn control was reported by 58% of the nizatidine group and in 88% of the pantoprazole (p < 0.0001); erosive esophagitis healing rates were 44% for nizatidine and 79% for pantoprazole (p < 0.001). Rescue antacid was needed by a greater number of patients using nizatidine than of those using pantoprazole (p < 0.001). H. pylori infection was associated with an increased probability of erosive esophagitis healing. Conclusions: Pantoprazole once daily was superior to nizatidine b.i.d. in producing complete heartburn relief in a mixed population of GERD patients and in achieving erosion healing. The proportions of patients with complete symptom relief were greater with pantoprazole after 7 days of therapy than with nizatidine after 28 days. The present study data suggest that pantoprazole is a highly effective first-line therapy for the management of gastroesophageal reflux disease in a primary care practice setting.
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Gastroesophageal reflux disease is mediated principally by acid. Today, we recognise reflux reaches beyond the esophagus, where pepsin, not acid, causes damage. Extraesophageal reflux occurs both as liquid and probably aerosol, the latter with a further reach. Pepsin is stable up to pH 7 and regains activity after reacidification. The enzyme adheres to laryngeal cells, depletes its defences, and causes further damage internally after its endocytosis. Extraesophageal reflux can today be detected by recognising pharyngeal acidification using a miniaturised pH probe and by the identification of pepsin in saliva and in exhaled breath condensate by a rapid, sensitive, and specific immunoassay. Proton pump inhibitors do not help the majority with extraesophageal reflux but specifically formulated alginates, which sieve pepsin, give benefit. These new insights may lead to the development of novel drugs that dramatically reduce pepsinogen secretion, block the effects of adherent pepsin, and give corresponding clinical benefit. “For now we see through a glass, darkly.” —First epistle, Chapter 13, Corinthians
We studied the effect of esophageal acid perfusion on salivation in patients with reflux esophagitis and in normal subjects. Serial 10-min saliva collections were obtained by expectoration during perfusion of the esophagus with water, and then 0.1 N HCl (pH 1.2) for 50 min or 0.01 N HCl (pH 2.1) for 120 min. Within 1–5 min of beginning 0.1 N HCl perfusion, all 8 patients with esophagitis developed heartburn accompanied by an increase in saliva flow. By the time the severity of heartburn required discontinuation of HCl perfusion (10–40 min), saliva flow had increased nearly fourfold. With 0.1 N HCl perfusion, 8 of 10 volunteers developed mild heartburn after 22 ± 3 min (mean ± SE), whereas 0.01 N HCl induced heartburn in 6 of 10 volunteers after 57 ± 12 min of perfusion. Saliva flow increased concurrently with the onset of heartburn and doubled in those volunteers who developed heartburn. Saliva flow did not change in those volunteers who were without heartburn. We conclude that esophageal acid perfusion unaccompanied by heartburn does not affect salivation. However, saliva flow increases concurrently with the onset of heartburn, a phenomenon called “water brash” when clinically evident. The increased saliva flow that accompanies heartburn may act as an endogenous antacid that serves as a protective response to symptomatic gastroesophageal reflux.
It has been previously demonstrated that the exposure of the lower esophageal mucosa to acid and pepsin results in significant increase in salivary protective factors secretion, mediated by the esophago-salivary reflex. The impact of the upper esophageal mucosal exposure to acid and pepsin on salivary secretory response remains unknown. To investigate the rate of salivary protective factors secretion during the upper esophageal mucosal exposure to acid and pepsin and to compare with the corresponding results recorded during the lower esophageal mucosal exposure, in the same group of asymptomatic volunteers. The study was conducted in 10 asymptomatic volunteers. Salivary samples were collected during the esophageal mucosal exposure to saline, followed by acid/pepsin and the final saline, using the esophageal perfusion catheter. Salivary bicarbonate and non-bicarbonate buffers were analyzed using TitraLab. Salivary mucin and protein were quantified through PAS and Lowry methodologies, respectively, whereas PE2 using radioimmunoassay. Statistical analysis was performed using Σ-Stat software. The rate of salivary bicarbonate secretion was significantly higher (3.1-fold) during the upper versus the lower esophageal mucosal exposure to acid and pepsin (87.5 ± 14.4 vs. 28.0 ± 7.70 μEq/min, p < 0.05). The volumes of saliva, pH, salivary protein, mucin and PE2 were similar in both esophageal perfusions. Threefold stronger secretion of salivary bicarbonate could be a major factor protecting the upper esophageal mucosa. This phenomenon may represent an ultimate defense mechanism potentially preventing further complications within the upper esophageal mucosa; however, it needs to be confirmed in patients of gastroesophageal reflux disease.
The mainstay of pharmacological therapy for GERD is gastric acid suppression with proton pump inhibitors (PPIs), which are superior to histamine-2 receptor antagonists for healing erosive esophagitis and achieving symptomatic relief. However, up to one-third of patients may not respond to PPI therapy, creating the need for alternative treatments. Potential approaches include transient lower esophageal sphincter relaxation inhibitors, augmentation esophageal defense mechanisms by improving esophageal clearance or enhancing epithelial repair, and modulation of sensory pathways responsible for GERD symptoms. This review discusses the effectiveness of acid suppression and the data on alternative pharmacological approaches for the treatment of GERD.
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.
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.
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.