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[5
]. 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 gastric emptying.
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[12
]. 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[13
]. 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 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[13
]. 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[2
]. In addition, moderate weight gains, even among normal-weight persons, resulted in the development or exacerbation of symptoms in GERD patients[16
]. 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[25
]. 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[26
], 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.