OBES SURG (2015) 25:1071–1072 DOI 10.1007/s11695-015-1659-x

LETTER TO THE EDITOR

Do Proton Pump Inhibitors Contribute to Weight Gain? Yu-Fong Syu 1 & Hsien-Hao Huang 2,4 & Chih-Yen Chen 3,4

Published online: 7 April 2015 # Springer Science+Business Media New York 2015

To the editor: We read with interest Ward et al.’s article “The effect of PPI use on human gut microbiota and weight loss in patients undergoing laparoscopic Roux-en-Y gastric bypass” [1]. We appreciate the authors’ experience regarding the effect of the proton pump inhibitor (PPI) use on gut flora and weight loss after laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. In the study, LRYGB appeared to be associated with trends of an increase in Firmicutes and a decrease in Bacteroidetes, irrespective of PPI usage, among morbidly obese subjects. Importantly, the authors found that the percent excess weight loss at 6 months after LRYGB was smaller in PPI users than in non-PPI users (p=0.067). To confirm whether or not the use of PPI contributes to weight gain, we would like to share our clinical experience. Twenty-one patients with normal body mass index (BMI) and endoscopically proven Helicobacter pylori-negative

* Chih-Yen Chen [email protected] 1

Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2

Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

3

Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Hospital, No. 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, Republic of China

4

Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan

gastric ulcer (6 females and 15 males, age 63.8±15.7 years, baseline BMI 25.7±5.4 kg/m2) were recruited. The study was approved by the ethics committee of Taipei Veterans General Hospital and has been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. Subjects were included if their weight was stable (±3 kg) for at least 3 months and excluded if they had taken steroids for more than 1 month. All subjects with H. pylori-negative gastric ulcer had taken oral rabeprazole sodium 20 mg per day, continuously for 4 months. Subjects’ weight, height, and usage of PPI were recorded. After 4 months of continuous use of oral rabeprazole sodium, no significant change was observed in body weight (67.5±15.6 vs. 68.0±15.8 kg, p=0.294; Fig. 1a) or BMI (25.5±5.4 vs 25.7±5.4 kg/m2, p=0.312; Fig. 1b) as compared with baseline values. Therefore, we concluded that short-term use (4 months) of a PPI does not contribute to weight gain in lean subjects with H. pylorinegative gastric ulcer. Information regarding the effects of PPIs on body weight is essential but unfortunately scarce. Yoshikawa et al. [2] found that long-term (at least 10 months) treatment with various PPIs was associated with weight gain in patients with gastroesophageal reflux disease. However, omeprazole treatment (77 days) was shown to suppress body weight gain and bone mineralization in young male rats [3]. The discrepancies between our findings and Ward et al.’s [1] might be due to differences in the variables of obesity degree, gastrointestinal ulcer sites, H. pylori infection, and history of gastrointestinal surgery. Additionally, different PPIs can have differential metabolic pathways in which the liver cytochrome P450 system

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OBES SURG (2015) 25:1071–1072

Fig. 1 Changes in body weight (a) and body mass index (b) before (M0) and after 4-month continuous use (M4) of oral rabeprazole sodium 20 mg per day in 21 subjects with Helicobacter pylori-negative gastric ulcer. Results are shown as mean±standard deviation (SD)

and its two key enzymes are involved. CYP2C19 will form inactive 5-hydroxy and 5-O-desmethyl metabolites, whereas the CYP3A4 will form an inactive sulfone metabolite [4]. Therefore, future studies are needed to confirm the longterm effects of different PPIs on body weight in both lean and obese subjects.

References 1.

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3. Acknowledgements This paper was sponsored by grants from the Taipei Veterans General Hospital, Taipei, Taiwan (V95C1-096 and V96C1-112) and in part from Taiwan Ministry of Science and Technology (MOST 1032314-B-010-011-). Conflict of interest Dr. Yu-Fong Syu, Dr. Hsien-Hao Huang, and Dr. Chih-Yen Chen disclose no conflict of interest.

4.

Ward EK, Schuster DP, Stowers KH, et al. The effect of PPI use on human gut microbiota and weight loss in patients undergoing laparoscopic Roux-en-Y gastric bypass. Obes Surg. 2014;24(9):1567–71. Yoshikawa I, Nagato M, Yamasaki M, et al. Long-term treatment with proton pump inhibitor is associated with undesired weight gain. World J Gastroenterol. 2009;15(38):4794–8. Cui GL, Syversen U, Zhao CM, et al. Long-term omeprazole treatment suppresses body weight gain and bone mineralization in young male rats. Scand J Gastroenterol. 2001;36(10):1011–5. Egan LJ, Myhre GM, Mays DC, et al. CYP2C19 pharmacogenetics in the clinical use of proton pump inhibitors for gastro-oesophageal reflux disease: variant alleles predict gastric acid suppression, but not oesophageal acid exposure or reflux symptoms. Aliment Pharmacol Ther. 2003;17(12):1521–8.