Long-term treatment with proton pump inhibitor is associated with undesired weight gain.
ABSTRACT To examine the effects of long-term proton pump inhibitor (PPI) therapy on body weight (BW) and body mass index (BMI) in patients with gastroesophageal reflux disease (GERD).
The subjects were 52 patients with GERD and 58 sex- and age-matched healthy controls. GERD patients were treated with PPI for a mean of 2.2 years (range, 0.8-5.7 years), and also advised on lifestyle modifications (e.g. selective diet, weight management). BW, BMI and other parameters were measured at baseline and end of study.
Twenty-four GERD patients were treated daily with 10 mg omeprazole, 12 with 20 mg omeprazole, 8 with 10 mg rabeprazole, 5 with 15 mg lansoprazole, and 3 patients with 30 mg lansoprazole. At baseline, there were no differences in BW and BMI between reflux patients and controls. Patients with GERD showed increases in BW (baseline: 56.4 +/- 10.4 kg, end: 58.6 +/- 10.8 kg, mean +/- SD, P < 0.0001) and BMI (baseline: 23.1 +/- 3.1 kg/m(2), end: 24.0 +/- 3.1 kg/m(2), P < 0.001), but no such changes were noted in the control group. Mean BW increased by 3.5 kg (6.2% of baseline) in 37 (71%) reflux patients but decreased in only 6 (12%) patients during treatment.
Long-term PPI treatment was associated with BW gain in patients with GERD. Reflux patients receiving PPI should be encouraged to manage BW through lifestyle modifications.
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ABSTRACT: Patients undergoing maintenance hemodialysis (MHD) have a high prevalence of peptic ulcer disease (PUD). Omeprazole is a proton pump inhibitor with proven efficacy in the prevention and treatment of PUD. However, there is little data on the prophylactic use of omeprazole in reducing the risk of PUD among MHD patients. This prospective study included 93 patients undergoing MHD at Zen-Ho Dialysis Center between July 2008 and December 2009. Fifty-three patients were assigned to receive 20 mg of omeprazole daily for 18 months and 40 patients served as control. The Kaplan-Meier method was applied to calculate the cumulative incidence of PUD. The per-protocol population comprised 85 patients (omeprazole group, 49; control group, 36). Both groups had similar baseline characteristics. The need for endoscopy was found to be significantly less (10.2 vs. 44.4%, p = 0.001) in the omeprazole group than in the control group. Dialysis patients in the omeprazole group required fewer blood transfusions and erythropoietin doses than did the control group patients. Kaplan-Meier analysis revealed a higher cumulative ulcer rate in the control group (log-rank test, p = 0.04). However, omeprazole did not reduce the risk of PUD in MHD patients on regular aspirin or warfarin. We conclude that prophylactic use of omeprazole might be effective to lower the incidence of PUD among MHD patients without regular aspirin or warfarin use. Further large-scale controlled trials should be carried out to confirm our findings.Renal Failure 04/2011; 33(3):323-8. · 0.94 Impact Factor
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ABSTRACT: Laparoscopic Roux-en-Y gastric bypass (LRYGB) achieves sustainable weight loss possibly by altering the gut microbiota. The effect of a proton pump inhibitor (PPI) on weight loss and the gut microbiota has not been explored. PPI use and the gut microbiota were assessed before and 6 months after LRYGB in eight patients. Bacterial profiles were generated by 16S ribosomal RNA (rRNA) gene sequencing. Prior to LRYGB, PPI users had a higher percent relative abundance (PRA) of Firmicutes compared to nonusers. PPI users at 6 months post-LRYGB had a higher PRA of Firmicutes [48.6 versus 35.6 %, p = nonsignificant (NS)] and a trend toward significantly lower percent excess weight loss (49.3 versus 61.4 %, p = 0.067) compared to nonusers. PPI use post-LRYGB may impair weight loss by modifying gut microbiota.Obesity Surgery 05/2014; · 3.74 Impact Factor
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ABSTRACT: Gastroesophageal reflux can cause inflammation, metaplasia, dysplasia and cancer of the esophagus. Despite the increased use of Proton Pump Inhibitors (PPIs) to treat reflux, the incidence of esophageal adenocarcinoma has increased rapidly in Europe and the United States in the last 25 years. The reasons for this increase remain unclear. In this study we aimed to determine whether the microbiota of the gastric refluxate and esophageal biopsies differs between patients with heartburn and normal appearing esophageal mucosa vs. patients with abnormal esophageal mucosa [esophagitis or Barrett's esophagus (BE)] and to elucidate the effect of PPIs on the bacterial communities using 16S rRNA gene pyrosequencing. Significant differences in the composition of gastric fluid bacteria were found between patients with heartburn and normal esophageal tissue vs. patients with esophagitis or BE, but in the esophagus-associated microbiota differences were relatively modest. Notably, increased levels of Enterobacteriaceae were observed in the gastric fluid of esophagitis and BE patients. In addition, treatment with PPIs had dramatic effects on microbial communities both in the gastric fluids and the esophageal tissue. In conclusion, gastric fluid microbiota is modified in patients with esophagitis and Barrett's esophagus compared to heartburn patients with normal biopsies. Furthermore, PPI treatment markedly alters gastric and esophageal microbial populations. Determining whether the changes in bacterial composition caused by PPIs are beneficial or harmful will require further investigation.Environmental Microbiology 09/2013; · 6.24 Impact Factor
Long-term treatment with proton pump inhibitor is
associated with undesired weight gain
Ichiro Yoshikawa, Makiko Nagato, Masahiro Yamasaki, Keiichiro Kume, Makoto Otsuki
Ichiro Yoshikawa, Makiko Nagato, Masahiro Yamasaki,
Keiichiro Kume, Makoto Otsuki, Third Department of Internal
Medicine, University of Occupational and Environmental
Health, Japan, School of Medicine, 1-1 Iseigaoka, Yahatanishi-
ku, Kitakyushu 807-8555, Japan
Author contributions: Yoshikawa I and Otsuki M contributed
equally to this work and designed the research; Yoshikawa I,
Yamasaki M and Kume K performed the research; Yoshikawa I
and Nagato M analyzed the data and wrote the paper.
Correspondence to: Ichiro Yoshikawa, MD, PhD, Third
Department of Internal Medicine, University of Occupational
and Environmental Health, Japan, School of Medicine, 1-1
Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555,
Telephone: +81-93-6031611 Fax: +81-93-6920107
Received: July 23, 2009 Revised: August 14, 2009
Accepted: August 21, 2009
Published online: October 14, 2009
AIM: To examine the effects of long-term proton pump
inhibitor (PPI) therapy on body weight (BW) and body
mass index (BMI) in patients with gastroesophageal
reflux disease (GERD).
METHODS: The subjects were 52 patients with
GERD and 58 sex- and age-matched healthy controls.
GERD patients were treated with PPI for a mean of
2.2 years (range, 0.8-5.7 years), and also advised
on lifestyle modifications (e.g. selective diet, weight
management). BW, BMI and other parameters were
measured at baseline and end of study.
RESULTS: Twenty-four GERD patients were treated
daily with 10 mg omeprazole, 12 with 20 mg omeprazole,
8 with 10 mg rabeprazole, 5 with 15 mg lansoprazole,
and 3 patients with 30 mg lansoprazole. At baseline,
there were no differences in BW and BMI between
reflux patients and controls. Patients with GERD showed
increases in BW (baseline: 56.4 ± 10.4 kg, end: 58.6 ±
10.8 kg, mean ± SD, P < 0.0001) and BMI (baseline:
23.1 ± 3.1 kg/m2, end: 24.0 ± 3.1 kg/m2, P < 0.001),
but no such changes were noted in the control group.
Mean BW increased by 3.5 kg (6.2% of baseline) in 37
(71%) reflux patients but decreased in only 6 (12%)
patients during treatment.
CONCLUSION: Long-term PPI treatment was associated
with BW gain in patients with GERD. Reflux patients
receiving PPI should be encouraged to manage BW
through lifestyle modifications.
© 2009 The WJG Press and Baishideng. All rights reserved.
Key words: Gastroesophageal reflux disease; Proton
pump inhibitor; Body weight
Peer reviewers: Dr. Katsunori lijima, Division of Gastro-
enterology, Tohoku University Graduate School of Medicine,
1-1 Seiryo-machi, Aobaku., Sendai 980-8574, Japan; Andrew
Ukleja, MD, Assistant Professor, Clinical Assistant Professor
of Medicine, Director of Nutrition Support Team, Director of
Esophageal Motility Laboratory, Cleveland Clinic Florida,
Department of Gastroenterology, 2950 Cleveland Clinic Blvd.,
Weston, FL 33331, United States
Yoshikawa I, Nagato M, Yamasaki M, Kume K, Otsuki M.
Long-term treatment with proton pump inhibitor is associated
with undesired weight gain. World J Gastroenterol 2009;
15(38): 4794-4798 Available from: URL: http://www.wjgnet.
com/1007-9327/15/4794.asp DOI: http://dx.doi.org/10.3748/
Gastroesophageal reflux disease (GERD) is the most
common esophageal disorder, and frequently encountered
in the primary care setting. It has been estimated that
15%-25% of persons experience reflux symptoms at least
weekly, and 5%-12% suffer on a daily basis.
The risk of reflux symptoms, erosive esophagitis,
or esophageal adenocarcinoma increases with excessive
weight and obesity. Accumulating evidence has
confirmed the excellent efficacy and safety of proton
pump inhibitor (PPI) therapy in patients with all
grades of GERD, making these agents the mainstay
of treatment. Consequently, PPIs comprise the largest
outpatient pharmacy expenditure in the United States.
Body weight loss is commonly recommended as part
of a first-line therapeutic measure for GERD, although
lifestyle modifications have been relegated to a minor
role in the therapeutic regime due to the effectiveness
and availability of PPIs as an acid-suppressive therapy.
GERD is a chronic condition, necessitating continu-
ous therapy for many patients to control symptoms and
Online Submissions: wjg.wjgnet.com
firstname.lastname@example.org World Journal of Gastroenterology ISSN 1007-9327
doi:10.3748/wjg.15.4794 © 2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol 2009 October 14; 15(38): 4794-4798
Yoshikawa I et al. Undesired weight gain in long-term PPI treatment of GERD 4795
prevent complications. Long-term therapeutic options
include PPI therapy and surgical or endoscopic proce-
dures. Recently, body weight loss after laparoscopic
Nissen fundoplication was reported. There is an exten-
sive literature database that addresses the efficacy and
safety of long-term PPI therapy. However, the possible
impact of changes in body weight or body mass index
(BMI) in reflux patients while on long-term PPI therapy
has not been examined. We present herein the first re-
port elucidating the effect on nutritional parameters such
as body weight and BMI in patients receiving long-term
MATERIALS AND METHODS
We evaluated 52 adult patients with GERD and 58
healthy controls. We selected patients undergoing daily
maintenance therapy of PPI for at least 10 mo at the
University Hospital of Occupational and Environmental
Health and four Gastroenterology Clinics between
June and November 2005. Patients who had prior
fundoplication or poor compliance with medication were
excluded. Patients with GERD had received advice on
lifestyle modifications such as selective diet and weight
management to accompany the PPI treatment.
The controls were sex- and age-matched subjects
who visited the clinic for a yearly medical examination;
they were free of reflux symptoms, and did not take
PPIs or histamine receptor antagonists. They did not
receive advice on lifestyle modifications. Informed
consent was obtained from all subjects and the study
was performed in accordance with the Declaration of
Helsinki as revised in 1989.
Diagnosis of GERD
The diagnosis of GERD was made based only on the
typical symptoms of troublesome heartburn and/or acid
regurgitation. Endoscopy at presentation was performed
in patients with alarm symptoms such as dysphagia,
odynophagia, bleeding, weight loss, and anemia that
together suggested a complicated disease.
Treatment of GERD
Initial therapy was a standard dose of PPI (omeprazole
20 mg, rabeprazole 20 mg, or lansoprazole 30 mg) once
daily for 8 wk followed by a daily maintenance half-dose
therapy. The patients were followed-up at 4-wk intervals
in the clinics to assess symptom recurrence. Patients
found to have recurring symptoms of heartburn or acid
regurgitation were placed back on their initial PPI dose.
The patients were educated on lifestyle modifications by
their physicians in addition to the PPI treatment. These
instructions included avoidance of overeating, decreased
fat intake, elevation of the head of the bed, cessation of
smoking, avoiding recumbency for postprandial 3 h, and
body weight control.
Nutritional parameters and blood pressure
Body weight, height, and blood pressure, as well as
fasting serum levels of total protein, total cholesterol, and
triglycerides were determined at baseline and at the last visit.
The BMI was calculated as body weight (kg)/[height (m)]2.
These parameters obtained within four weeks before the
commencement of PPI therapy were defined as baseline
All results were expressed as mean ± SD. Categorical
outcome variables were analyzed with Fisher’s exact test.
For continuous variables, the Mann-Whitney U-test and
Student’s t-test were used where appropriate. A P value
less than 0.05 denoted the presence of a statistically
significant difference between the groups.
Characteristics and demographics of subjects
Table 1 details the characteristics of the 52 reflux patients
and 58 healthy controls. There were no significant
differences between the patient and control groups with
regard to age, sex, duration of observation, body weight,
body height, BMI, blood pressure, and serum values of
total protein, total cholesterol, and triglycerides. Helicobacter
pylori status, endoscopic findings, and PPI regimens of
daily maintenance therapy in reflux patients are listed in
Effect of long-term daily PPI maintenance therapy on
nutritional parameters and blood pressure
No significant differences were found between patient
and control groups with respect to changes in blood
pressure or serum values of total protein, total cholesterol,
and triglycerides. In contrast, patients treated with PPI
experienced significantly greater increases from the
baseline to the last visit in body weight (P < 0.0001) and
BMI (P < 0.0005) than controls (Table 3).
The differences in body weight and BMI between
the baseline and the last visit were analyzed separately
Table 1 Baseline demographics and characteristics of reflux
patients treated with long-term daily maintenance proton
pump inhibitor therapy and healthy controls (mean ± SD)
68.1 ± 10.4
68.8 ± 1.5
Number of subjects
Duration of observation (yr)
Body weight (kg)
Body mass index (kg/m2)
Blood pressure (mmHg)
Serum total protein (g/dL)
Serum total cholesterol (mg/dL)
Serum triglyceride (mg/dL)
2.1 ± 1.1
56.4 ± 10.4
156.0 ± 9.8
23.1 ± 3.1
2.0 ± 0.4
58.6 ± 8.4
156.0 ± 8.9
24.1 ± 2.7
133 ± 17
75 ± 11
7.2 ± 0.3
210 ± 39
121 ± 52
132 ± 16
75 ± 9
7.2 ± 0.3
210 ± 25
107 ± 43
PPI: Proton pump inhibitor.
for both groups (Table 3). Body weight (P < 0.0001) and
BMI (P < 0.0001) significantly increased at the last visit
in reflux patients. In contrast, there was no significant
difference in body weight or BMI at the last visit in
Categorical changes in body weight at the last visit
compared to the baseline values are shown in Figure 1.
Most of the control group (91%) remained stable,
defined by a change of no more than 5% compared to
baseline weight; however, only 60% of the PPI group
remained stable. In addition, 36% of these patients had
an increase in body weight above baseline of more than
5%, compared with 4% of the control group (P < 0.0001).
This study demonstrated for the first time that long-
term PPI treatment is associated with undesirable body
weight gain in patients with GERD, despite lifestyle
modification recommendations by their physicians.
Heartburn is the classical symptom of GERD, with
patients generally reporting a burning feeling, rising
from the stomach and radiating toward the neck and
throat. It usually occurs postprandially, particularly
after large meals or the consumption of fats. Untreated
patients suffering from reflux symptoms find it difficult
to have large meals, because this generally aggravates
their symptoms. Untreated patients may therefore
reduce their meal sizes and intake of fats intentionally
or unintentionally. It is conceivable, therefore, that the
resolution of reflux symptoms by PPI treatment leads to
a higher food intake resulting in body weight gain.
Laparoscopic Nissen fundoplication has evolved
as a gold standard in antireflux surgery. This surgical
therapy induces a significant and persistent reduction in
body weight, possibly due to postoperative dysphagia
or delayed gastric emptying. In contrast, the option of
long-term PPI therapy was associated with a significant
body weight gain in the present study. Omeprazole
and other PPIs delay gastric emptying[6-9], which
induces postprandial fullness, dyspeptic symptoms,
gastrointestinal bacterial overgrowth, and subsequent
weight loss[10,11]. Our results have clearly demonstrated
that long-term PPI therapy contributed significantly to
body weight changes in patients with GERD by relieving
the adverse symptoms rather than altering the state of
Numerous circulating peptides influence appetite.
Ghrelin is produced in the stomach and acts as a meal
initiator. A recent report revealed that long-term PPI
therapy did not change the serum ghrelin level.
Another peptide, leptin, is produced in the stomach and
acts as an enteric signal involved in energy homeostasis.
Change of this peptide associated with PPI therapy has
not been reported.
A practice guideline for patients with GERD
recommends the use of lifestyle modifications such as
elevation of the bed head, a decreased intake of fat,
chocolate, alcohol, peppermint, coffee, onions and
garlic, cessation of smoking, and avoiding recumbency
for three hours postprandially, in addition to taking
antireflux medications. However, the positive
advantage of such lifestyle modifications on the patient’s
condition is not well substantiated. Among these lifestyle
interventions, elevation of the bed head, left lateral
decubitus positioning, and weight loss are associated
n = 58
n = 52
Figure 1 Categorical change in body weight at the last visit compared to
the baseline reading. Most of the control group (91%) remained stable, within
a 5% change, compared to weight at the baseline. However, only 60% of the
PPI group remained stable. In addition, compared with 4% of the control group,
36% of patients had a more than 5% increase above the baseline in body
weight (P < 0.0001). n: Number of patients or control subjects.
Table 2 Patient demographics
Patients (n = 52)
Helicobacter pylori status
LA grade A
LA grade B
LA grade C
LA grade D
Number of patients according to PPI regimens
Omeprazole 10 mg once daily
Omeprazole 20 mg once daily
Rabeprazole 10 mg once daily
Lansoprazole 15 mg once daily
Lansoprazole 30 mg once daily
LA: Los Angeles classification; ND: Not determined.
Table 3 Mean changes in nutritional parameters and blood
pressure at the last visit compared to the baseline
(n = 52)
(n = 58)
Body weight (kg)
Body mass index (kg/m2)
Blood pressure (mmHg)
Serum total protein (g/dL)
Serum total cholesterol (mg/dL)
Serum Triglyceride (mg/dL)
aNS vs baseline; bP < 0.0001 vs baseline; NS: Not significant.
4796 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol October 14, 2009 Volume 15 Number 38
with improvement in reflux symptoms in case-control
studies[14,15]. These modifications alone, however, are
unlikely to control symptoms in the majority of patients.
Our results support the finding that lifestyle modifications
are an essential component of the treatment for GERD
and the prevention of weight gain during PPI treatment.
There is a growing body of literature regarding the
association between BMI and GERD[2,16-24]. A recent large
meta-analysis of previous studies demonstrated a strong
positive relationship between BMI and reflux symptoms.
In addition, moderate weight gains, even among normal-
weight persons, resulted in the development or exacerb-
ation of symptoms in GERD patients. In the present
study, the patients significantly increased their body weight
during PPI therapy. Appropriate management of body
weight during PPI treatment should reduce the duration
of PPI use or PPI dosage.
Excessive weight is associated with an increased risk
of coronary heart disease, hypertension, angina, stroke,
and diabetes, and constitutes an important cardiovascular
health burden. Body weight gain associated with
lifetime GERD treatment may induce further medical
costs in addition to the PPI therapy. Unfortunately,
potentially effective diet modifications are often
underestimated in the presence of various PPI regimens.
Healthcare providers still recommend lifestyle changes in
a moderate percentage of GERD patients, and while
PPIs have become of pivotal importance for the initial
and maintenance treatment of GERD, repeated lifestyle
modification recommendations are required.
In conclusion, we elucidated in the present study
the impact of long-term PPI therapy on body weight.
Undesired body weight gain was observed in GERD
patients on long-term PPI treatment. Reflux patients
treated with a daily maintenance therapy of PPI should
be strongly encouraged to manage their body weight
through lifestyle modifications such as proper diet and
avoidance of overeating. This measure may reduce the
overall medical costs associated with obesity-related
illness as well as GERD. Lifestyle modification must
therefore remain the backbone of treatment for all
patients with GERD, even in the PPI era.
Gastroesophageal reflux disease (GERD) is the most common esophageal
disorder, and frequently encountered in the primary care setting. The risk of
reflux symptoms and erosive esophagitis increases with excessive weight and
Many studies have confirmed the efficacy and safety of proton pump inhibitor
(PPI) therapy in patients with GERD, making these agents the mainstay of
Innovations and breakthroughs
This study demonstrated for the first time that long-term PPI treatment is
associated with undesirable body weight gain in reflux patients, despite lifestyle
modification recommendations by their physicians.
Reflux patients treated with a daily maintenance therapy of PPI should be
strongly encouraged to manage their body weight through lifestyle modifications
such as proper diet and avoidance of overeating.
GERD is a common esophageal disorder which is becoming increasingly
prevalent in the population in parallel with similar rises in the frequency of
This study showed that long-term PPI treatment is associated with body weight
gain and that lifestyle modification must therefore remain the backbone of
treatment for patients with GERD. This report would impact on the ongoing
treatment of GERD.
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4798 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol October 14, 2009 Volume 15 Number 38