Gastroenterology 2018;154:267–276

GASTROESOPHAGEAL REFLUX DISEASE

GERD
Presentation and Epidemiology of Gastroesophageal
Reflux Disease

Joel E. Richter1 Joel H. Rubenstein2,3

1
Joy McCann Culverhouse Center for Swallowing Disorders, Division of Digestive Diseases & Nutrition, University of South
Florida College of Medicine, Tampa, Florida; 2Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan;
3
Barrett’s Esophagus Program, Division of Gastroenterology & Hepatology, University of Michigan Medical School,
Ann Arbor, Michigan

Gastroesophageal reflux disease (GERD) is the most Clinical Presentation

prevalent gastrointestinal disorder in the United States, and Heartburn and acid regurgitation are the classic
leads to substantial morbidity, though associated mortality
symptoms of GERD. Patients generally report a burning
is rare. The prevalence of GERD symptoms appeared to in-
feeling in the retrosternal area, raising into the chest and
crease until 1999. Risk factors for complications of GERD
radiating toward the neck, throat, and occasionally the back.1
include advanced age, male sex, white race, abdominal
It occurs post-prandially, particularly after large fatty meals
obesity, and tobacco use. Most patients with GERD present
with heartburn and effortless regurgitation. Coexistent or the ingestion of spicy foods, citrus products, fats, choco-
dysphagia is considered an alarm symptom, prompting lates, or alcohol. The supine position and bending over may
evaluation. There is substantial overlap between symptoms exacerbate heartburn. Nighttime heartburn may cause
of GERD and those of eosinophilic esophagitis, functional sleeping difficulties and impair next-day function.3 Sleep
dyspepsia, and gastroparesis, posing a challenge for patient deprivation as well as psychological or auditory stress may
management. lower the threshold for symptom perception.4 GERD can be
diagnosed based on symptoms, such as the occurrence of
heartburn 2 or more days a week, although symptoms can be
Keywords: Erosive Esophagitis; Barrett’s Esophagus; Esopha- less frequent if they are troublesome and have adverse effects
geal Stricture. on well-being.1 The frequency and severity of heartburn does
not associate with degree of esophageal damage.
Regurgitation has been more inconsistently described in

B y consensus, gastroesophageal reflux disease

(GERD) has been defined as the effortless move-
ment of stomach contents into the esophagus or mouth
clinical trials and epidemiologic studies on GERD. Per
the Montreal consensus statement, regurgitation is defined
as the “perception of flow of refluxed gastric contents into
causing troublesome symptoms or complications.1 We re- the mouth or hypopharynx.”1 Among patients with daily
view the clinical presentation and epidemiology of GERD. regurgitation, lower esophageal sphincter pressure is often
The cardinal symptoms of GERD are heartburn and low; many patients have associated gastroparesis, and
regurgitation. GERD is exceedingly common, ranking as the esophagitis is common, making this symptom more difficult
most frequent gastrointestinal diagnosis associated with to treat medically than classic heartburn.5
outpatient clinic visits in the United States (US), with The lack of a standard for the diagnosis of GERD has
nearly 9 million visits in 2009.2 Although complications made it difficult to define the accuracy of the typical reflux
such as bleeding erosive esophagitis or peptic stricture are syndrome of troubling heartburn and/or regurgitation. The
becoming less common, individuals with GERD symptoms
have a decrement in their quality of life that is similar to
patients with inflammatory bowel disease.2 To accurately Abbreviations used in this paper: EoE, eosinophilic esophagitis; GERD,
gastroesophageal reflux disease; PPI, proton pump inhibitor; PPI-REE,
diagnose and manage GERD, it is important to recognize PPI-responsive esophageal eosinophilia.
the epidemiologic risk factors for GERD, the variety of Most current article
presenting symptoms and their relative likelihood of rep-
© 2018 by the AGA Institute
resenting pathological reflux, and the potential for overlap 0016-5085/$36.00
with other gastrointestinal disorders. [Link]
 268 Richter and Rubenstein Gastroenterology Vol. 154, No. 2

Diamond Study from the United Kingdom attempted to Eosinophilic Esophagitis

address this question in patients presenting to family The issue of how to differentiate eosinophilic esophagitis
practitioners with complaints of upper gastrointestinal (EoE) from GERD has confounded clinicians and researchers
GERD

symptoms.6 GERD was present in 203 of 308 patients since the recognition of the disease. This diagnostic dilemma
(66%), based on endoscopic esophagitis and/or abnormal began with a pathology study of pediatric patients in 1982,
acid exposure or a positive symptom association probability which found that eosinophils in the esophageal squamous
from 24-hour pH tests. Only 49% of patients with GERD epithelium could be a manifestation of GERD, documented
selected either heartburn or regurgitation as their most by 24-hour pH tests.12 Pathologists rapidly accepted the
troublesome symptom, followed by dyspepsia, bloating, concept, and it became common clinical practice to attribute
regurgitation, and abdominal pain or discomfort that was esophageal eosinophilia to GERD. The first report describing
not characterized as dyspepsia. Sensitivity and specificity EoE as a unique syndrome, characterized by solid food
values for symptom-based diagnosis of GERD were 63% and dysphagia and distinct from GERD by esophageal tests, was
63% by family practitioners and 67% and 70% by gastro- published in 1993.13 Subsequently, EoE was considered a
enterologists, respectively. Questionnaires about reflux chronic immune- or antigen-mediated esophageal disease.
symptoms did not perform any better; they identified However, many cases still overlapped with GERD, so the PPI
patients with GERD with only 62% sensitivity and 67% trial became the most logical and convenient means to
specificity. Nor could response of symptoms to treatment differentiate GERD from EoE. This practice was based on
with the proton pump inhibitor (PPI) esomeprazole (40 mg the assumption that the only major effect of PPIs is to
for 2 weeks) increase diagnostic precision (a positive inhibit gastric acid production. Accordingly, in 2007, the
response to the PPI test was observed in 69% of patients American Gastroenterological Association’s consensus
with GERD and 51% of patients without GERD).7 Similarly, a report defined EoE as a primary disorder characterized by
well-performed meta-analysis cast doubt on the diagnostic esophageal symptoms, esophageal biopsies with more
accuracy of the PPI trial, finding that it identified patients than 15 eosinophils per high-powered field, and the
with GERD with 78% sensitivity and 54% specificity.8 “absence” of pathologic GERD, evidenced either by normal
Less-common symptoms of GERD include dysphagia, results from pH tests or lack of response to PPIs.14
chest pain, water brash, odynophagia, burping, hiccups, This mutually exclusive paradigm began to fall apart as
nausea, and vomiting. Dysphagia is considered an alarm editorials raised the possibilities of a complex interaction
symptom in patients with GERD that warrants upper between GERD and EoE. These raised questions such as:
endoscopy.9 Dysphagia usually occurs in patients with does EoE cause GERD? Does GERD cause EoE? Or do these
long-standing heartburn with slowly progressive dysphagia merely co-exist, because GERD is such a common dis-
for solids. Weight loss is uncommon because patients have ease?15 Subsequently, Ngo et al16 described 3 patients with
good appetites. The most common causes are peptic stric- EoE and significant mucosal eosinophilia who improved,
ture and severe inflammation, but dysphagia can be the first based on clinical and histologic features, after 2 months of
symptom of Barrett’s esophagus with esophageal cancer. PPI therapy. Several years later, Molina-Infante et al17
The chest pain associated with GERD can be indistinguish- published findings from 35 patients with mucosal eosino-
able from that of ischemic cardiac pain. GERD is a more philia (more than 15 eosinophils per high-powered field);
frequent cause of non-cardiac chest pain than esophageal 75% responded to rabeprazole (20 mg, twice daily) for
motor disorders.1 The most problematic and controversial 2 months. All 17 of the patients with GERD profile and
symptoms associated with GERD are chronic cough, chronic objective acid reflux, based on endoscopy or pH tests,
laryngitis (including hoarseness, globus sensation, and responded to this treatment. However, 50% of the patients
throat clearing), and asthma. Although potential mecha- with an EoE-like profile and normal pH test results also
nisms of pathogenesis have been identified, trials of medical responded to the rabeprazole.
and surgical anti-reflux treatments have produced uncertain The recognition of this condition, which was termed PPI-
and inconsistent results.1 responsive esophageal eosinophilia (PPI-REE), caused
Some patients with GERD are asymptomatic. This is further confusion. Studies documented that 23% to 61% of
particularly true in older patients, perhaps because of patients with symptomatic esophageal eosinophilia respond
decreased acidity of the reflux material or decreased pain to PPI treatment.18 Furthermore, the clinical, endoscopic,
perception. Many older patients present first with com- histologic, and even esophageal gene-expression features of
plications of GERD because of long-standing disease with PPI-REE and EoE are virtually identical.19 Therefore, PPI-
minimal symptoms. This is a particular problem for REE resembles EoE far more than it resembles GERD.
patients with Barrett’s esophagus. European population An exciting discovery around this controversy has been
studies found that 44%–46% of patients did not report the recognition that EoE and GERD could each arise via
symptoms of GERD.10,11 cytokine-mediated esophageal injury. In contrast to the
model in which refluxed acid causes a chemical injury that
destroys esophageal cells, studies from patients and animal
Overlap With Other Disorders models indicated that the esophageal damage found in
GERD symptoms overlap with those of other syndromes. patients with GERD was caused by inflammatory cells that
This poses a challenge to diagnosis and can alter medical are attracted to the esophagus by cytokines produced by
and surgical treatments. esophageal epithelial cells following exposure to refluxed
January 2018 Epidemiology of GERD 269

acid and bile.20,21 Studies of cultured esophageal epithelial were lower in patients with epigastric pain (51.5%), post-
cells revealed anti-cytokine effects of PPIs that were entirely prandial distress with fullness (66.7%), or early satiation
independent of effects on gastric acid production; these (41.1%). A study of 626 patients with erosive GERD treated

GERD
could heal GERD and EoE. Omeprazole was found to block with pantoprazole to esophagitis healing observed a 62%
eotaxin-3 secretion stimulated by T-helper 2 cytokines pro- overlap between GERD and dyspepsia symptoms.30
duced by esophageal cells from patients with EoE or GERD22 Remarkably, the dyspepsia symptoms improved by 50%
and block secretion of interleukin 8, a mediator of eosino- during PPI treatment and unlike the reflux symptoms, which
philic inflammation, after exposure to acid and bile salts in usually relapsed with treatment cessation, the dyspepsia
esophageal epithelial cells from patients with GERD.23 symptoms showed a trend to further decrease.
The current focus on how to distinguish EoE from
GERD may therefore be counterproductive because the 2
diseases often co-exist with complex interactions. Patients
Gastroparesis
with GERD with the typical reflux syndrome associated The importance of delayed gastric emptying in the path-
with erosive esophagitis and hiatal hernia can have ogenesis of GERD is controversial. Early studies indicated that
mucosal eosinophilia, which often is confined to the distal up to 50% of patients with reflux had delayed emptying of
esophagus. It is not clear what proportion of patients with solids.31 However, more recent studies, using a standardized
GERD present with these features, but it is likely to be less 4-hour gastric emptying test, found an overlap in 8%–20% of
patients.32 Conceptually, impaired gastric emptying results in
than 10%.24 The etiology of their mucosal eosinophilia
a greater volume of material in the stomach, which could be
may be secondary to direct acid injury or secondary to the
effects of GERD on esophageal barrier function, which available to directly reflux into the esophagus or generate
renders the epithelium permeable to food antigens distension of the proximal stomach, triggering transient lower
and causes antigen-induced esophageal eosinophilia.25 esophageal sphincter relaxations. Recent studies with
Regardless, PPIs can reduce both mechanisms of patho- impedance-pH testing found that acid reflux values were not
genesis; careful separation by esophageal manometry and increased, but consistent with the reflux of meal contents, the
pH – impedance testing is necessary for only patients who increase was in post-prandial liquid or mixed reflux events
require surgical anti-reflux treatment. and non/weakly acid reflux.33 Women and diabetics are more
likely to have gastroparesis with secondary GERD. Complaints
of abdominal bloating, pain, nausea, vomiting, or constipation
Functional Dyspepsia should be helpful clues and manometry often shows a normal
lower esophageal sphincter pressure. Treating the gastro-
Population-based studies have identified GERD and
dyspepsia, defined as pain or discomfort centered in the paresis with diet and prokinetics can alleviate the need for
upper abdomen, as some of the most common upper PPIs or anti-reflux surgery.
gastrointestinal tract symptoms; estimated prevalence
values are approximately 20% for each.26 Therefore, it
should not be surprising that the distinction between GERD
Prevalence and Trends
and functional dyspepsia may not be clear cut. More than Symptoms
33% of patients with functional dyspepsia also report The pooled prevalence of at least weekly GERD
heartburn and acid regurgitation and vice versa. This was symptoms reported from population-based studies world-
well illustrated in the Diamond study, in which 42% of the wide is approximately 13%, but there is considerable
patients without GERD reported dyspepsia as their first- or geographic variation.34 Accurate estimates are difficult
second-most troubling symptom, whereas this value was because of heterogeneity in study designs, but the preva-
37% in patients subsequently found to have GERD.6 lence of GERD appears to be highest in South Asia and
Furthermore, endoscopy and pH tests do not separate Southeast Europe (more than 25%), and lowest in Southeast
these groups with a high level of confidence. A large sys- Asia, Canada, and France (below 10%) (Figure 1).34 There
tematic review of more than 5000 patients with a primary are no data on the prevalence of GERD in Africa. In the US,
complaint of dyspepsia found endoscopic evidence of estimates of the prevalence of GERD symptoms have ranged
esophagitis in 13.4% of patients, followed by peptic ulcers from 6% to 30%, with heterogeneity related to the partic-
in 8.0%.27 Several studies identified patients with functional ular questionnaire used, including the threshold frequency
dyspepsia using Rome II or III criteria and performed and duration of symptoms required to be classified as
24-hour pH tests. Tack et al28 reported that 23% of patients GERD.34 The prevalence of at least weekly GERD symptoms
with functional dyspepsia had abnormal acid exposure in the US is approximately 20%.35 There are approximately
times, and their symptom profile was mainly epigastric pain. 110,000 hospital admissions annually in the US for GERD.36
A similar study of an Asian population, performed by Xiao Importantly, the prevalence of GERD symptoms in North
et al,29 found that 31.7% of patients had abnormal acid America, Europe, and Southeast Asia has increased
exposure times, with the highest percentage (48.9%) in approximately 50% relative to the baseline prevalence in
patients who claimed epigastric burning was their pre- the early to middle 1990s, but has plateaued since then.35 In
dominate symptom. In this study, the proportion of patients a population-based longitudinal study of a Norwegian
with a response to PPI therapy at 1 month was highest county from 1995 through 2009, the annual incidence of
(85%) in those with epigastric burning; the proportions any new GERD symptoms was 3.1%, and of severe GERD
 270 Richter and Rubenstein Gastroenterology Vol. 154, No. 2
GERD

Figure 1. Prevalence of weekly gastroesophageal reflux symptoms worldwide, based on symptoms at a frequency of once
a week or more. (Adapted with permission from Eusebi et al. Gut 2017. [Link]

symptoms was 0.2%.37 Among individuals with any GERD at year in 1968 through 1972 to 2.1 per million in 1988
baseline and excluding those who were using anti-reflux through 1992.43 But recurrent strictures requiring repeat
medications, symptoms resolved spontaneously in 2.3% endoscopic dilation in individuals with a prior dilation
per year; among those with severe GERD, 1.2% spontane- decreased from 16% in 1992 to 8% in 2000, possibly
ously resolved per year. related to the increase in use of PPIs.44 From 2003 to 2006,
there were approximately 10,570 hospital admissions
annually for erosive esophagitis, and 14,000 admissions for
Complications esophageal stricture.36 Esophageal adenocarcinoma is the
The predominant complications of GERD include most feared complication of GERD, and its precursor lesion,
dysphagia (including from peptic strictures, Schatzki’s Barrett’s esophagus, is also a sequelae of GERD. Barrett’s
rings), bleeding from erosive esophagitis, and esophageal esophagus and esophageal adenocarcinoma are discussed in
adenocarcinoma (discussed in other sections of this issue). detail in other articles in this issue of Gastroenterology.
In 3 population-based studies of patients agreeing to
undergo endoscopy regardless of symptoms, the prevalence
of erosive esophagitis ranged from 6.4% in China to 15.5% Demographic Risk Factors
in Sweden.38–40 Among individuals without symptoms of There are a number of well-recognized risk factors for
GERD, the prevalence of erosive esophagitis ranged from GERD and its complications (Table 1). In North America and
6.1% in China to 9.5% in Sweden. Erosive esophagitis may in Europe, there is no association between sex and symp-
frequently be a transient phenomenon. In a prospective, toms of GERD, but in South America and in the Middle East,
longitudinal study, 26% of individuals with non-erosive women are approximately 40% more likely to report GERD
reflux disease at baseline were found to have erosive symptoms than men.34 There is no clear association
esophagitis on repeat endoscopy 2 years later, and in between sex and esophageal stricture.36,44 However, men
another similar study, erosive esophagitis was found in 10% are at greater risk than women for erosive esophagitis
of individuals 5 years later.41,42 And among those with Los (summary odds ratio, 1.57; 95% CI, 1.40–1.76).45 Also, men
Angeles Grade A erosive esophagitis at baseline, 21% had are at greater risk for Barrett’s esophagus and much greater
more severe findings at 5 years. risk for esophageal adenocarcinoma than women.
Though death from erosive esophagitis is rare, mortality Advancing age has been inconsistently associated with
increased in the US from 1.0 per million individuals per an increased risk for GERD symptoms. In a meta-analysis,
January 2018 Epidemiology of GERD 271

Table [Link] Factors for GERD and Complications

Risk factor Symptoms Esophagitis Stricture Esophageal Adenocarcinoma

GERD
Age þ/- þ þ þþ
Male sex þ/- þ þ/- þþ
White race þ/- þ þ þþ
Obesity þ þ þþ
H pylori þ/- – –
Tobacco þ þ þ þþ

þ: positive association; þþ: strongly positive association; -: negative association; –: strongly negative association; þ/-: no
association or heterogeneous findings for association.

the summary odds ratio for 50 years or more vs less than 50 esophagitis suggests a cohort effect, whereby individuals born
years of age was 1.32, but with an I2 value of 91.5%, indi- in an earlier generation may have been less likely to develop
cating substantial heterogeneity among study results.34 erosive esophagitis than later generations when they reached
However, advancing age is more strongly associated with the same age. Such a cohort effect would most likely be
complications of GERD (Figure 2).36 Age is clearly associ- explained by changes in environmental exposures (described
ated with hospitalizations for esophageal strictures.36,46 in sections below). Esophageal adenocarcinoma is also asso-
Most recently, advancing age was strongly associated with ciated with increased age, but there too, a cohort effect appears
hospitalizations for erosive esophagitis.36 However, in the to be responsible for the increasing incidence.47
late 1980s, advanced age was inversely associated with In the US, there appears to be similar prevalence of
hospitalization for erosive esophagitis (odds ratio for more GERD symptoms among different races.44,48 However,
than 85 years vs 65–69 years of age, 0.66; 95% CI, 0.65– whites are at greater risk for erosive esophagitis, strictures,
0.67).46 This reversal in association of age with erosive Barrett’s esophagus, and esophageal adenocarcinoma.36,48,49

Figure 2. Age distribution of GERD-related US hospitalization discharge diagnoses. Upper graphs: age fractions expressed as
percent of all patients with a given diagnosis. Lower left graph: age-specific rates of first-listed adenocarcinoma per 100,000,
reflux esophagitis per 100,000, esophageal reflux per 10,000, Barrett’s esophagus per 100,000, hiatal hernia per 10,000, and
esophageal stricture per 10,000 US population. Lower right graph: age-specific rates of all-listed adenocarcinoma per
100,000, reflux esophagitis per 10,000, esophageal reflux per 10,000, Barrett’s esophagus 10,000, hiatal hernia per 1000, and
esophageal stricture per 10,000 US population. (Reprinted with permission from Thukkani N, Sonnenberg A. Alimentary
Pharmacology and Therapeutics.36).
 272 Richter and Rubenstein Gastroenterology Vol. 154, No. 2

Genetics activity are associated with an increased risk of GERD. For

Estimates of the proportion of phenotypic variance in instance, activities in a stooped posture, bicycle riding,
weight lifting, swimming, and even surfing have been
GERD

GERD symptoms explained by genetic factors have ranged

from 0% to 22%.50–52 In a twin study, 13% of the variance associated with increased risk of GERD, particularly during
in GERD symptoms was estimated to be because of genetic or shortly after the activity.62–64 On the other hand, mod-
effects, but even that proportion appeared to be mediated erate, regular aerobic exercise has been inversely associ-
by anxiety and depression.52 The genetic risk for GERD is ated with GERD symptoms.58,60 Physical activity at work
polygenic, with no individual mutation found to be signifi- has a positive association with GERD symptoms, and yet
cantly associated with GERD in genome-wide association leisure physical activity has had a negative association with
studies, though larger studies might yet still be able to GERD symptoms.56
identify statistically significant individual mutations.50,51 In addition to the increasing prevalence of obesity, the
Given the recent increase in prevalence of GERD symp- falling prevalence of H pylori gastritis might explain
toms relative to the broad sweep of evolutionary history, the trends in GERD and its complications.43 A proportion
the etiology of GERD seems to be largely related to of patients with H pylori infection develop atrophy in the
environmental exposures. gastric body and decreased gastric acid secretion. It has
been proposed, therefore, that H pylori infection might
prevent GERD in patients who are otherwise susceptible to
Environmental Risk Factors it. Barrett’s esophagus and esophageal adenocarcinoma
Two major factors that may explain the trends are have been inversely associated with H pylori infection,
the obesity epidemic and the decreasing prevalence of particularly the cytotoxin-associated gene A (cagAþ)
Helicobacter pylori-associated gastritis. Obesity is a major strain.65,66 A meta-analysis has likewise found an inverse
risk factor for GERD symptoms, with an odds ratio of 1.73.34 association between H pylori and erosive esophagitis.67
Obesity is also associated with erosive esophagitis (odds However, there is a much stronger inverse association in
ratio, 1.59), Barrett’s esophagus (odds ratio, 1.24), and East Asia than in North America, and equivocal evidence
esophageal adenocarcinoma (odds ratio, 2.45).53 In partic- for an association in Europe. Although H pylori gastritis
ular, a body distribution of abdominal obesity has been tends to be predominantly in the gastric body in Asia, it is
associated with complications of GERD (erosive esophagitis predominantly in the antrum in Western countries.68
odds ratio, 1.87; Barrett’s esophagus odds ratio, 1.98; and Antral gastritis would be more prone to having excessive
esophageal adenocarcinoma odds ratio, 2.51).53 Observa- rather than diminished gastric acid secretion because of
tional studies have demonstrated that reducing the body positive feedback causing corpus acid secretion. There
mass index by at least 3.5 kg/m2 increases odds for were some early reports describing an increase in GERD
disappearance of GERD symptoms by 1.5- to 2.4-fold.54 symptoms following eradication of H pylori,69,70 but a
Randomized trials have confirmed that weight loss, and subsequent meta-analysis found no such effect.71 There is
in particular a decrease in waist circumference, result in little evidence that H pylori prevents symptoms of GERD
improved GERD symptoms and decrease in esophageal in Western populations, and the inverse association
acid exposure.54 between H pylori with erosive esophagitis, Barrett’s
Obesity is largely related to caloric excess and/or lack esophagus, and esophageal adenocarcinoma may be
of physical activity, so the association of obesity with GERD independent of an effect on reflux.72
and its complications could be confounded by diet or There are additional environmental exposures that
physical activity. Certain foods can induce symptoms of are associated with GERD, but they may not explain the
GERD (eg, fatty foods, chocolate, soda pop), and obese trend in prevalence of GERD. For instance, tobacco use is
individuals may consume those foods more regularly than weakly associated with GERD symptoms in cross-sectional
non-obese individuals. However, from a cross-sectional studies (summary odds ratio, 1.26).34 This relationship is
epidemiologic study, it would be difficult to find signifi- supported by an 18-year longitudinal study in which
cant associations with specific components of the diet individuals who decreased tobacco smoking were 3-fold
because many patients with GERD symptoms would natu- more likely to have reductions in symptoms of acid
rally try to avoid those foods. There are few data from regurgitation and heartburn than individuals who
epidemiologic studies to demonstrate an association continued to smoke tobacco.73 Tobacco is also an impor-
between GERD symptoms and specific foods that cause tant risk factor for erosive esophagitis,74–78 and esopha-
them.54,55 There have been weak associations between geal adenocarcinoma.79,80 Though there are few data on
diets low in fruits and fiber and high in sweets and fat peptic strictures, tobacco is associated with esophageal
with GERD symptoms.56–60 Furthermore, a small prospec- strictures in patients with endoscopic mucosal resection or
tive study demonstrated that even before losing substantial with radiation therapy.81,82
weight, obese patients experienced improvement in their Similarly, in observational studies, alcohol use was
GERD within only 6 days of initiating a low-carbohydrate not strongly associated with GERD symptoms (summary
diet, demonstrating that diet is an important risk factor odds ratio, 1.11), but there is substantial heterogeneity in
for GERD.61 results among studies.34 Patients with GERD symptoms
Likewise, the relationship between physical activity and often report that symptoms are made worse by drinking
GERD is complex. On one hand, certain forms of physical alcohol, and randomized studies have demonstrated that
January 2018 Epidemiology of GERD 273

ingestion of alcohol induces acid reflux more so than diagnostic test characteristics. Ann Intern Med 2004;
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Received May 1, 2017. Accepted July 18, 2017.
white and red wine on lower esophageal sphincter
pressure and gastroesophageal reflux. Scand J Gastro- Reprint requests
GERD

enterol 1998;33:118–122. Address requests for reprints to: Joel E. Richter, MD, Professor of Medicine, Hugh
F. Culverhouse Chair for Esophageal Disorders, Director, Division of Digestive
86. Anderson LA, Cantwell MM, Watson RG, et al. Diseases & Nutrition, Director, Joy McCann Culverhouse Center for Swallowing
The association between alcohol and reflux esophagitis, Disorders, University of South Florida College of Medicine, 12901 Bruce B.
Downs Blvd, MDC 72, Tampa, Florida 33612. e-mail: Jrichte1@[Link].
Barrett’s esophagus, and esophageal adenocarcinoma.
Gastroenterology 2009;136:799–805. Conflicts of interest
J.H.R. has received research funding from Shire, and has no other potential
87. Thrift AP, Cook MB, Vaughan TL, et al. Alcohol and the conflicts of interest. J.E.R reports no conflicts.
risk of Barrett’s esophagus: a pooled analysis from the
Funding
International BEACON Consortium. Am J Gastroenterol J.H.R. was funded by the US Department of Veterans Affairs (I01-CX000899)
2014;109:1586–1594. and the National Institutes of Health (U01CA199336).