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Lifestyle Intervention in Gastroesophageal Reflux Disease
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Clinical Gastroenterology and Hepatology 2015;-:-–-
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Lifestyle Intervention in Gastroesophageal Reflux Disease Eivind Ness-Jensen,*,‡ Kristian Hveem,‡ Hashem El-Serag,*,§ and Jesper Lagergren*,k *Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; ‡ The Nord-Trøndelag Health Study Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway; §Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas; kSection of Gastrointestinal Cancer, Division of Cancer Studies, King’s College London, United Kingdom BACKGROUND & AIMS:
Gastroesophageal reflux disease (GERD) affects up to 30% of adults in Western populations and is increasing in prevalence. GERD is associated with lifestyle factors, particularly obesity and tobacco smoking, which also threatens the patient’s general health. GERD carries the risk of several adverse outcomes and there is widespread use of potent acid-inhibitors, which are associated with long-term adverse effects. The aim of this systematic review was to assess the role of lifestyle intervention in the treatment of GERD.
METHODS:
Literature searches were performed in PubMed (from 1946), EMBASE (from 1980), and the Cochrane Library (no start date) to October 1, 2014. Meta-analyses, systematic reviews, randomized clinical trials (RCTs), and prospective observational studies were included.
RESULTS:
Weight loss was followed by decreased time with esophageal acid exposure in 2 RCTs (from 5.6% to 3.7% and from 8.0% to 5.5%), and reduced reflux symptoms in prospective observational studies. Tobacco smoking cessation reduced reflux symptoms in normal-weight individuals in a large prospective cohort study (odds ratio, 5.67). In RCTs, late evening meals increased time with supine acid exposure compared with early meals (5.2% point change), and head-of-the-bed elevation decreased time with supine acid exposure compared with a flat position (from 21% to 15%).
CONCLUSIONS:
Weight loss and tobacco smoking cessation should be recommended to GERD patients who are obese and smoke, respectively. Avoiding late evening meals and head-of-the-bed elevation is effective in nocturnal GERD.
Keywords: GERD; Heartburn; Acid Regurgitation; Therapy; Treatment.
astroesophageal reflux disease (GERD), defined by at least weekly symptoms of heartburn or acid regurgitation, is increasingly common.1 The prevalence in adults ranges from 30% in some Western populations to less than 10% in East Asian populations, and the incidence is approximately 5 per 1000 person-years in Western populations.1 GERD is associated with reduced health-related quality of life,2 decreased work productivity3 and increased risk of esophageal adenocarcinoma.4 The annual incidence of esophageal adenocarcinoma is increasing worldwide, from 3.5% in Scotland to 8.1% in Hawaii, which parallels the increasing prevalence of GERD.5 In addition, GERD diagnostic tests and treatments carry high societal costs.6 The pathophysiology of GERD is dominated by functional and anatomic defects at the gastroesophageal junction, including reduced pressure and increased reflux episodes associated with transient relaxations of the lower esophageal sphincter and formation of hiatal hernia, which promotes and facilitates reflux.7–9 Esophageal motility and salivary bicarbonate contribute to
G
esophageal acid clearance and buffering, respectively, and reduce acid contact time in the esophagus.10,11 Visceral obesity increases the pressure over the gastroesophageal junction, thus facilitating reflux,12 and tobacco smoking reduces the lower esophageal sphincter pressure and salivary bicarbonate secretion, which facilitates reflux and decreases acid buffering, respectively.13,14 The main established risk factors of GERD are heredity, obesity, and tobacco smoking.15–18 High dietary fiber intake and moderate physical exercise seem to reduce this risk,18 whereas sex and age do not strongly influence the risk of GERD.19,20 Obesity is of particular interest because it is increasing in prevalence in parallel Abbreviations used in this paper: BMI, body mass index; CI, confidence interval; GERD, gastroesophageal reflux disease; OR, odds ratio; PPI, proton pump inhibitor; RCT, randomized clinical trial. © 2015 by the AGA Institute 1542-3565/$36.00 http://dx.doi.org/10.1016/j.cgh.2015.04.176
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Category Weight loss
Study
Design
Findings Normalization of pH measurements in 3 of 5 with weight loss Reduced acid exposure in sham group (the effect of mere weight loss) Reduced acid exposure in sham group (the effect of mere weight loss) Decreased symptom prevalence and score in both groups
Mathus-Vliegen and Tytgat,37 1996
RCT
Gastric balloon vs sham treatment
Mathus-Vliegen and Tytgat,38 2002
RCT
Gastric balloon vs sham treatment
Mathus-Vliegen et al,39 2003
RCT
Gastric balloon vs sham treatment
Singh et al,40 2013
RCT
Austin et al,41 2006
Nonrandomized prospective study Nonrandomized prospective study Prospective populationbased cohort study Prospective populationbased cohort study
Structured weight loss program vs telephone-based group conference Very lowcarbohydrate diet Dietary advice
Fraser-Moodie et al,42 1999 Jacobson et al,43 2006
Ness-Jensen et al,44 2013
No intervention
No intervention
Low-caloric diet vs control
Cremonini et al,46 2006
Prospective populationbased cohort study
No intervention
ACG (2013)36
Lifestyle modifications are ineffective for frequent or severe symptoms, but may be beneficial if obvious dietary precipitants, obesity or tobacco smoking
Weight loss in obese patients; head of the bed elevation if symptoms when recumbent; other lifestyle modifications tailored to the individual patient
Weight loss recommended for GERD patients with overweight or recent weight gain; head of bed elevation and avoidance of meals 2–3 hour before bedtime recommended if nocturnal GERD; routine global elimination of food that can trigger reflux not recommended
Decreased acid exposure and symptom score Decreased symptom score Dose-dependent decrease in symptom prevalence Dose-dependent decrease in symptoms, improved medical treatment success No effect on symptoms, endoscopic findings, or acid exposure No association with symptoms
No.
RCT
AGA (2008)34,35
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Kjellin et al,45 1996
A
CAG (2005)24
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Intervention
Ness-Jensen et al
Comparison with current guidelines Level of evidencea
2
Table 1. Lifestyle Intervention in GERD
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175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232
233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 Dietary interventions
Kjellin et al,45 1996
Austin et al,41 2006
Decreased symptoms in normal weight individuals
B
Low-caloric diet vs control
No effect on symptoms, endoscopic findings, or acid exposure Decreased acid exposure and symptom score Decreased acid exposure with early evening meal Decreased symptom prevalence and score with dietary fiber No effect on GERD
B (no effect)
Very lowcarbohydrate diet Late vs early evening meal
DiSilvestro et al,49 2011
RCT
Dietary fiber vs placebo
Johnson et al,50 2010
Systematic review of observational studies RCT
Carbonated beverages
Hamilton et al,51 1988
Head of bed elevation vs flat position
Decreased acid exposure with head of bed elevation
B
B
B
B (no effect)
B
ACG, American College of Gastroenterology; AGA, American Gastroenterological Association; CAG, Canadian Association of Gastroenterology. a A, multiple populations were evaluated, data were derived from multiple randomized clinical trials or meta-analyses; B, limited populations were evaluated, data were derived from a single randomized clinical trial or nonrandomized studies; C, very limited populations were evaluated, only consensus opinion of experts, case studies, or standard of care.
Lifestyle Intervention in GERD
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No intervention
Nonrandomized prospective study RCT
Piesman et al,48 2007
Head-of-the-bed elevation
Prospective populationbased cohort study RCT
2015
Ness-Jensen et al,47 2014
-
Tobacco smoking cessation
3 Q1
291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348
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with GERD, and several studies have shown an increased risk of GERD and esophagitis with obesity, especially abdominal obesity.21,22 GERD typically is diagnosed by the cardinal symptoms of heartburn or acid regurgitation,23 and by symptom resolution after acid inhibition with a proton pump inhibitor (PPI).24 If symptoms do not resolve, endoscopy usually is performed and mucosal erosions (esophagitis) or peptic strictures are diagnostic of GERD.25 Endoscopy also can show Barrett’s esophagus, a premalignant columnar metaplasia, and esophageal adenocarcinoma. If endoscopy is normal, esophageal pH measurement still can show pathologic acid reflux (pH < 4).26 The pH measurement can be combined with impedance measurement to detect reflux of weakly acidic or nonacidic liquid and gas, which can cause reflux symptoms refractory to acid inhibition.27 The treatment of GERD is primarily by medication with antacids, H2-receptor antagonists, and PPIs, whereas surgery (typically with fundoplication) is used in selected patients. Recent evidence has shown that long-term PPI medication is hampered by adverse effects. This includes secondary hypergastrinemia and rebound acid hypersecretion, inducing reflux symptoms at withdrawal of PPI medication28; increased risk of enteric infections and community-acquired pneumonia, probably owing to increased gastric pH causing reduced host defense29,30; and increased risk of hip and vertebral fractures, probably owing to malabsorption of calcium.31 This review addresses lifestyle interventions in the treatment of GERD and compares existing evidence with current guidelines.
Methods Systematic literature searches on lifestyle interventions for patients with GERD were performed in MEDLINE using PubMed from 1946 and EMBASE using OvidSP from 1980 to October 1, 2014. In addition, the Cochrane Library was searched (last search was performed on October 1, 2014). The searches included the thesaurus terms (MeSH in MEDLINE and EMTREE in EMBASE): “gastroesophageal reflux,” “heartburn,” “peptic esophagitis” (EMBASE)/”esophagitis, peptic” (MEDLINE) and “non-erosive reflux disease” (EMBASE). Randomized clinical trials (RCTs), prospective observational studies, and meta-analyses and systematic reviews of RCTs or observational studies of GERD patients were included. The searches were limited to the English language and research on adult human beings. The evidence of interventions was graded using the American Heart Association’s guidelines, as follows: multiple populations were evaluated, data were derived from multiple RCTs or metaanalyses (level A); limited populations were evaluated, data were derived from a single RCT or nonrandomized studies (level B); and very limited populations were evaluated, only consensus opinion of experts, case studies, or standard of care (level C).
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No.
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Results Literature Searches Literature searches on lifestyle intervention identified 15 original studies that met the inclusion criteria (Table 1 and Supplementary Table 1). In addition, 1 previous systematic review on lifestyle intervention and 1 previous systematic review on conservative and surgical treatment for obesity in GERD were identified.32,33 No relevant Cochrane reviews were identified. Three management guidelines were assessed: the Canadian Association of Gastroenterology consensus (2005),24 the American Gastroenterological Association medical position statement and technical review (2008),34,35 and the American College of Gastroenterology guideline (2013).36
Lifestyle Interventions Lifestyle interventions in GERD traditionally have included avoidance of foods that may precipitate reflux episodes and heartburn (eg, coffee, alcohol, chocolate, peppermint, citrus, carbonated drinks, and spicy foods), and behavioral changes with weight loss, smoking cessation, head-of-the-bed elevation, avoiding large meals, and avoiding recumbence after meals or meals before bedtime.34,35 The previous systematic review on lifestyle intervention in GERD concluded that only weight loss and head-of-the-bed elevation were effective for GERD, whereas the systematic review on conservative and surgical treatment for obesity concluded that dietary and lifestyle intervention may improve GERD in obese patients.32,33 However, new supportive evidence has emerged.
Weight Loss Three RCTs in severely obese individuals compared weight loss by gastric balloon distension with sham treatment combined with dietary guidance, physical exercise, and behavioral therapy, and showed reduced esophageal acid exposure with weight loss.37–39 In the first RCT, including 17 patients, 3 of 5 patients with pathologic pH measurements had normalized pH measurements after weight loss of 31.3 to 44.0 kg after 4 months.37 In the second RCT, 23 patients with a mean weight loss of 11.2 kg within 13 weeks had decreased time with esophageal pH level less than 4 (from 5.60% to 3.72%; P < .05).38 Moreover, there was a strong correlation between decreased waist circumference and acidic reflux time (r ¼ 0.78; P ¼ .000).38 These results were supported by the third RCT of 17 sham-treated patients, in which mean weight loss of 12.5 kg within 13 weeks improved time with upright pH level less than 4 (from 8.0% to 5.5%; P < .05).39 A larger RCT compared obese participants randomized to a structured weight loss program (n ¼ 167) with
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407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432 433 434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464
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465 466 467 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 Q11 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522
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a telephone-based group conference on weight management (n ¼ 165). The prevalence of reflux symptoms decreased (from 37% to 15%; P < .01) and the symptom score improved (Reflux Disease Questionnaire; P < .01) after 6 months of weight loss (mean body mass index [BMI] decreased from 34.7 to 30.2), irrespective of treatment group.40 These results were confirmed in 2 uncontrolled prospective cohort studies of GERD patients.41,42 A study of 8 extremely obese patients (mean BMI, 43.5) showed significant improved total time with pH less than 4 (from 5.1% to 2.5%; P ¼ .022) and reflux symptom score (Distress Subscale of Gastroesophageal Reflux Disease Symptom Assessment Scale from 1.28 to 0.72; P ¼ .0004) after 4 days on a very-low-carbohydrate diet and a mean weight loss of 1.7 kg.41 Moreover, a study of 34 patients with a mean BMI of only 23.5, reflux symptoms, and either normal endoscopy or low-grade esophagitis also showed significant correlation between weight loss after dietary advice (mean BMI decrease, 1.7) and reflux symptom score (modified DeMeester questionnaire, r ¼ 0.548; P < .001).42 Two large prospective population-based cohort studies showed that weight reduction dose-dependently decreased reflux symptoms.43,44 The Nurses’ Health Study, an observational cohort study of 10,545 women, showed a dose-dependently reduced risk of reflux symptoms among women who had a decrease in BMI compared with women with no BMI change (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.42–0.97; BMI decrease, >3.5 units; P for trend < .001).43 The NordTrøndelag health study, a prospective population-based cohort study of 29,610 participants, also showed a dose-dependent association between weight loss and the chance of losing reflux symptoms (OR, 2.42; 95% CI, 1.88–3.11; BMI decrease, >3.5 units; P for trend < .001). In this study, decrease in BMI also was associated with an increased chance of losing reflux symptoms with medical treatment (OR, 1.98; 95% CI, 1.45–2.72; BMI decrease, >3.5 units; and no or less than weekly medication; compared with OR, 3.96; 95% CI, 2.03–7.65; BMI decrease, >3.5 units; and at least weekly medication).44 Challenging these results, a small RCT showed that weight loss (mean, 10.8 kg) did not have significant effects on symptoms, esophagitis, or pH measurements in obese patients (mean BMI, 31.4) with GERD who were randomized to a low-calorie diet (430 kcal/d) for 6 months (n ¼ 10) or not (n ¼ 9).45 In addition, a prospective population-based cohort study of 637 individuals showed no association between weight loss and reflux symptoms, but because weight loss was selfreported it may have been overestimated.46
Tobacco Smoking Cessation A prospective population-based cohort study (the Nord-Trøndelag health study) of 29,610 participants showed that smoking cessation was associated with
5
decreased severe reflux symptoms in normal-weight individuals on medical treatment, compared with participants who continued smoking daily (OR, 5.67; 95% CI, 1.36–23.64).47 However, there was no similar association in overweight (BMI, 25.0–29.9) or obese (BMI, 30.0) individuals (OR, 1.24; 95% CI, 0.57–2.71; and OR, 1.29; 95% CI, 0.53–3.17, respectively). A possible explanation for these findings is that GERD pathophysiology in obese individuals is dictated strongly by weight, while smoking plays a minor role, but smoking is a more important factor in nonobese individuals.
Dietary Interventions A RCT showed no influence of weight loss after a 6-month period of low-caloric diet (430 kcal/d) on GERD.45 However, a small nonrandomized study of 8 severely obese patients (mean BMI, 43.5) who lost weight (1.7 kg) on a 4-day, very-low-carbohydrate diet (<20 g/d) showed a decreased total time with pH less than 4 (from 5.1% to 2.5%; P ¼ .022) and reflux symptoms score (from 1.28 to 0.72; P ¼ .0004).41 A cross-over RCT of 30 patients randomized to a late meal (2 hours before bedtime) or an early meal (6 hours before bedtime) showed more pH-verified supine reflux after the late evening meal (mean change, 5.2%; P ¼ .002).48 A RCT that compared patients using a dietary fiber product (n ¼ 15) with placebo (n ¼ 15) for 2 weeks, showed an increased number of days without heartburn (mean, 1.87 and 0.73, respectively; P < .05) and reduced severity score (mean, 7.7 and 13.3, respectively; P < .05) in the fiber group.49 A systematic review based on observational studies showed no evidence of carbonated beverages promoting GERD.50 Regarding other potential dietary interventions there were no studies meeting the search criteria.
Head-of-Bed Elevation A cross-over RCT of 15 GERD participants showed that elevation of the head of the bed by a 10-inch wedge decreased the time that esophageal pH was less than 4 compared with a flat position (15% and 21%, respectively; P < .05).51
Discussion RCTs have shown reduced reflux symptoms and esophageal acid exposure with weight loss,37–40 findings supported by well-designed observational studies showing a dose-dependent decreased presence of reflux symptoms after weight reduction. A large prospective observational study showed reduced reflux symptoms with tobacco smoking cessation in normal-weight individuals.47 RCTs also showed that early evening meals48
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and head-of-the-bed elevation51 decreased the esophageal acid exposure time, and dietary fiber decreased reflux symptoms.49 Based on the present review, we believe that the evidence of lifestyle modifications in GERD has been strengthened compared with the statements in the 3 current treatment guidelines.24,34–36 The Canadian Association of Gastroenterology guideline concludes that lifestyle modifications are ineffective for frequent or severe reflux symptoms and that data are insufficient to support lifestyle modifications in mild reflux.24 The American Gastroenterological Association guideline recommends weight loss in obese GERD patients and elevation of the head of the bed in patients experiencing reflux symptoms when recumbent, while other lifestyle modifications should be individually tailored.34,35 The American College of Gastroenterology guideline supports avoidance of meals 2 to 3 hours before bedtime, in addition to weight loss and head-of-bed elevation. However, it does not recommend elimination of food that can trigger reflux.36 We believe that patients suffering from GERD should be recommended to lose weight if they are obese, that tobacco smoking cessation and increased dietary fiber should be encouraged, and that late evening meals should be avoided and head-of-the-bed elevation recommended for patients with supine reflux. Based on the pathophysiologic mechanisms, weight loss in obese patients presumably will reduce the increased pressure on the gastroesophageal junction, reducing reflux.12 Smoking cessation will normalize the lower esophageal sphincter pressure and salivary bicarbonate production.13,14 It is speculated that dietary fiber expands with water to form a barrier to the acid rising into the esophagus.49 Avoiding late evening meals and head-ofthe-bed elevation will reduce nighttime supine reflux.48,51 Any effect of a very-low-carbohydrate diet is uncertain because the study cannot separate the effects of weight loss from those of diet.41 However, a small case series showed a significant and almost immediate resolution of GERD symptoms in obese individuals initiating a very-low-carbohydrate diet.52 Lifestyle interventions, especially weight loss and tobacco smoking cessation, also are beneficial from other perspectives, including low economic costs, no harmful side effects, and overall health benefits. In addition, observational studies have shown that weight loss and tobacco smoking cessation are associated with improved success with medical treatment.44,47 Extensive data exist on the effects of acid-inhibiting medication in GERD, compared with only a few and heterogeneous RCTs or observational studies of lifestyle intervention. Commercial interests are probably the main reason for this imbalance of studies. Noncommercial funding should focus on performing larger RCTs on lifestyle interventions to verify these results and obtain more reliable conclusions. Nevertheless, the available evidence is reasonably consistent and supported by the
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No.
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pathophysiology and epidemiology. The effects of these interventions on reflux symptoms, acid exposure, and endoscopic findings should be assessed in future studies. Because obesity and smoking are risk factors of GERD, a reduced prevalence of these exposures in the populations also could reduce the incidence of GERD.
Conclusions Recent evidence supports lifestyle intervention in the treatment of GERD. These include weight loss, tobacco smoking cessation, avoiding late evening meals, and head-of-the-bed elevation. Meanwhile, the awareness of adverse effects of medical treatment has increased, questioning long-term and continuous PPI therapy, at least in mild GERD.
Supplementary Material Note: To access the supplementary material accompanying this article, visit the online version of Clinical Gastroenterology and Hepatology at www.cghjournal.org, and at http://dx.doi.org/10.1016/j.cgh.2015.04.176.
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43. Jacobson BC, Somers SC, Fuchs CS, et al. Body-mass index and symptoms of gastroesophageal reflux in women. N Engl J Med 2006;354:2340–2348.
26. Kahrilas PJ, Quigley EM. Clinical esophageal pH recording: a technical review for practice guideline development. Gastroenterology 1996;110:1982–1996.
44. Ness-Jensen E, Lindam A, Lagergren J, et al. Weight loss and reduction in gastroesophageal reflux. A prospective populationbased cohort study: the HUNT study. Am J Gastroenterol 2013; 108:376–382.
27. Hirano I, Richter JE. ACG practice guidelines: esophageal reflux testing. Am J Gastroenterol 2007;102:668–685. 28. Reimer C, Sondergaard B, Hilsted L, et al. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology 2009;137:80–87, 87 e81. 29. Bavishi C, Dupont HL. Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection. Aliment Pharmacol Ther 2011;34:1269–1281.
45. Kjellin A, Ramel S, Rossner S, et al. Gastroesophageal reflux in obese patients is not reduced by weight reduction. Scand J Gastroenterol 1996;31:1047–1051. 46. Cremonini F, Locke GR 3rd, Schleck CD, et al. Relationship between upper gastrointestinal symptoms and changes in body weight in a population-based cohort. Neurogastroenterol Motil 2006;18:987–994.
30. Johnstone J, Nerenberg K, Loeb M. Meta-analysis: proton pump inhibitor use and the risk of community-acquired pneumonia. Aliment Pharmacol Ther 2010;31:1165–1177.
47. Ness-Jensen E, Lindam A, Lagergren J, et al. Tobacco smoking cessation and improved gastroesophageal reflux: a prospective population-based cohort study: the HUNT study. Am J Gastroenterol 2014;109:171–177.
31. Ngamruengphong S, Leontiadis GI, Radhi S, et al. Proton pump inhibitors and risk of fracture: a systematic review and metaanalysis of observational studies. Am J Gastroenterol 2011; 106:1209–1218; quiz 1219.
48. Piesman M, Hwang I, Maydonovitch C, et al. Nocturnal reflux episodes following the administration of a standardized meal. Does timing matter? Am J Gastroenterol 2007; 102:2128–2134.
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49. DiSilvestro RA, Verbruggen MA, Offutt EJ. Anti-heartburn effects of a fenugreek fiber product. Phytother Res 2011;25:88–91. 50. Johnson T, Gerson L, Hershcovici T, et al. Systematic review: the effects of carbonated beverages on gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2010;31:607–614. 51. Hamilton JW, Boisen RJ, Yamamoto DT, et al. Sleeping on a wedge diminishes exposure of the esophagus to refluxed acid. Dig Dis Sci 1988;33:518–522. 52. Yancy WS Jr, Provenzale D, Westman EC. Improvement of gastroesophageal reflux disease after initiation of a lowcarbohydrate diet: five brief case reports. Altern Ther Health Med 2001;7:116–129.
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Reprint requests Address requests for reprints to: Eivind Ness-Jensen, MD, PhD, Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, NS 67, 171 76 Stockholm, Sweden. e-mail: eivind. [email protected]; fax: (46) 8-51776280. Conflicts of interest The authors disclose no conflicts. Funding Supported by the Norwegian and Swedish Research Councils (E.N.-J.); by National Institutes of Health grant K24 DK04-107 and the Houston VA Health Services Research and Development Center of Excellence (HFP90-020) (H.E.-S.); and by grants from the Swedish Research Council (J.L.).
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871 872 873 Q2 874 875 876 Q3 877 878 879 880 Q4 881 882 883 884 885 886 887 888 889 890 891 892 893 894 895 896 897 898 899 900 901 902 903 904 905 906 907 908 909 910 911 912 913 914 915 916 917 918 919 920 921 922 923 924 925 926 927 928
929 930 931 932 933 934 935 936 937 938 939 940 941 942 943 944 945 946 947 948 949 950 951 952 953 954 955 956 957 958 959 960 961 962 963 964 965 966 967 968 969 970 971 972 973 974 975 976 977 978 979 980 981 982 983 984 985 986 Source
Search terms
201
10
Systematic review
Randomized clinical trial
2
4
Kaltenbach Singh et al, et al, 2006 2013 De Groot et al, Kjellin et al, 2009 1996 Mathus-Vliegen et al, 2002 Mathus-Vliegen et al, 2003 Excluding obesity surgery “Smoking cessation” [Mesh]
“Diet therapy” [Mesh]
140
21
3
88
1
4
22
4
1
1
2
27
1
1
8
0
12
1
1
11
3
4
Ness-Jensen et al, 2013 2
68
22
6 53
1 8
2 21
4
12
5
17
1
10
1
3
2
72
6 54
0 1
1
Ness-Jensen et al, 2013 Cremonini et al, 2006 Jacobson et al, 2006 Fraser-Moodie et al, 1999
51
0
1
1
De Groot et al, Kjellin et al, 2009 1996
“Meals”[Mesh] “Dietary fats” [Mesh]
4
Not Retrospective/ No NonCase/ relevant crossexperimental patients/ systematic abstract Conf. sectional available abstract Dupl. Other review study outcome study
1
4
2
3
Austin et al, 2006 Fraser-Moodie et al, 1999 3 3
Kaltenbach et al, 2006 “Dietary carbohydrates” [Mesh] “Cacao”[Mesh] “Mentha piperita” [Mesh]
17
0
5 1
0 1
1
5 0
2
2
1
Kaltenbach et al, 2006 “Coffee”[Mesh] “Ethanol”[Mesh] “Citrus”[Mesh]
20 32 18
0 0 1
1 Kaltenbach et al, 2006
20 32 17
4 12
4 1
1 8 4
3
5 4 3
5 3 6
2 2
1 1
Lifestyle Intervention in GERD
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MEDLINE/ “Body weight PubMeda changes” [Mesh] 1946 to October 1, 2014
Id. Metaarticles Included analysis
Prospective observational Not Not Not study Excluded English human adult
2015
Q15
Q13 Q14
-
Supplementary Table 1. Summary of Literature Search
8.e1
987 988 989 990 991 992 993 994 995 996 997 998 999 1000 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015 1016 1017 1018 1019 1020 1021 1022 1023 1024 1025 1026 1027 1028 1029 1030 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 1044
1045 1046 1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 1057 1058 1059 1060 1061 1062 1063 1064 1065 1066 1067 1068 1069 1070 1071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 1084 1085 1086 1087 1088 1089 1090 1091 1092 1093 1094 1095 1096 1097 1098 1099 1100 1101 1102 Search terms “Carbonated beverages” [Mesh]
Id. Metaarticles Included analysis 37
Systematic review
Randomized clinical trial
Prospective observational Not Not Not study Excluded English human adult
1
36
1
13
Johnson et al, 2010 1 Kaltenbach et al, 2006
5
1
3
22
3
70
6
54 72
4 3
63
“Spices”[Mesh]
6
1
“Dietary fiber” [Mesh]
23
1
“Posture”[Mesh]c
73
3
“Exercise”[Mesh] Weight reduction EMBASE/ b OvidSP 1980 to October 1, 2014
54 104
0 8
1 DiSilvestro et al, 2011 1 2 Kaltenbach Piesman et al, et al, 2006 2007 Hamilton et al, 1988 2
4
2
2
1
5
12
1
1
3
1
2
2
5
28
1
8
27
12 35
10
6
21 1
6 26
2
0
42
1
16
35
5
5
22
50
10
6
21
11 6
2
1 1
Kaltenbach Singh et al, Ness-Jensen et al, 2006 2013 et al, 2013 De Groot et al, Mathus-Vliegen Fraser-Moodie 2009 et al, 1996 et al, 1999 Mathus-Vliegen et al, 2002 Mathus-Vliegen et al, 2003 24
0
65
2
Diet therapy
38
3
Diet
51
1
Meals Fat
11 6
0 0
Excluding obesity surgery Smoking cessation
0 1 Kaltenbach et al, 2006 2 Kaltenbach et al, 2006 De Groot et al, 2009 1 Kaltenbach et al, 2006
1 Ness-Jensen et al. 2013 1 Austin et al. 2006
4 2
2
3
3
1
9
2 3
3 1
-,
7
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Retrospective/ Not crossCase/ relevant NonNo sectional experimental patients/ systematic abstract Conf. study study outcome review available abstract Dupl. Other
Ness-Jensen et al
Source
8.e2
Supplementary Table 1. Continued
No. -
1103 1104 1105 1106 1107 1108 1109 1110 1111 1112 1113 1114 1115 1116 1117 1118 1119 1120 1121 1122 1123 1124 1125 1126 1127 1128 1129 1130 1131 1132 1133 1134 1135 1136 1137 1138 1139 1140 1141 1142 1143 1144 1145 1146 1147 1148 1149 1150 1151 1152 1153 1154 1155 1156 1157 1158 1159 1160
1161 1162 1163 1164 1165 1166 1167 1168 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 1179 1180 1181 1182 1183 1184 1185 1186 1187 1188 1189 1190 1191 1192 1193 1194 1195 1196 1197 1198 1199 1200 1201 1202 1203 1204 1205 1206 1207 1208 1209 1210 1211 1212 1213 1214 1215 1216 1217 1218 1219 1220 1221 1222 1223 Search terms
Id. Metaarticles Included analysis 6 2
0 1
Mentha piperita
1
1
Coffee
14
1
Alcohol Citrus Carbonated beverages
44 0 10
0 0 1
1 Kaltenbach et al, 2006 1 Kaltenbach et al, 2006 1 Kaltenbach et al, 2006
1
Randomized clinical trial
6 1
Not Retrospective/ No Nonrelevant Case/ crossexperimental patients/ systematic abstract Conf. sectional available abstract Dupl. Other review outcome study study
3
2 1
1
0
13
1
44 0 9
11
7
1
1
3
4
16
1
2
7
1
5
8 2
9 23 24
1
2
3
Kaltenbach et al, 2006 Spices Dietary fiber Posture Exercise OR physical activity
1 21 47 57
0 0 0 0
1 21 47 57
5 3
1 1 5
2 6 13
1 7 3 8
1 1 1
1 1
MeSH terms (exploded, including all subheadings): (“Gastroesophageal Reflux”[Mesh] OR “Heartburn”[Mesh] OR “Esophagitis, Peptic”[Mesh]) AND (.). EMTREEE terms (exploded outcome, focused intervention, including all subheadings): (gastroesophageal reflux OR heartburn OR non erosive reflux disease OR reflux esophagitis) AND (.). c Search was limited to meta-analysis, systematic review, clinical trial, and observational study. a
b
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Carbohydrate Cacao
Systematic review
Prospective observational Not Not Not study Excluded English human adult
2015
Source
-
Supplementary Table 1. Continued
8.e3 1224 1225 1226 1227 1228 1229 1230 1231 1232 1233 1234 1235 1236 1237 1238 1239 1240 1241 1242 1243 1244 1245 1246 1247 1248 1249 1250 1251 1252 1253 1254 1255 1256 1257 1258 1259 1260 1261 1262 1263 1264 1265 1266 1267 1268 1269 1270 1271 1272 1273 1274 1275 1276 1277 1278 1279 1280 1281 1282 1283 1284 1285 1286
Clinical Gastroenterology and Hepatology 2015;-:-–-
1 2 3 4 5 6 7 Q16 8 9 10 11 12 13 Q5 14 15Q6 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 Q7 Q8 39 Q9 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58
Lifestyle Intervention in Gastroesophageal Reflux Disease Eivind Ness-Jensen,*,‡ Kristian Hveem,‡ Hashem El-Serag,*,§ and Jesper Lagergren*,k *Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; ‡ The Nord-Trøndelag Health Study Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway; §Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas; kSection of Gastrointestinal Cancer, Division of Cancer Studies, King’s College London, United Kingdom BACKGROUND & AIMS:
Gastroesophageal reflux disease (GERD) affects up to 30% of adults in Western populations and is increasing in prevalence. GERD is associated with lifestyle factors, particularly obesity and tobacco smoking, which also threatens the patient’s general health. GERD carries the risk of several adverse outcomes and there is widespread use of potent acid-inhibitors, which are associated with long-term adverse effects. The aim of this systematic review was to assess the role of lifestyle intervention in the treatment of GERD.
METHODS:
Literature searches were performed in PubMed (from 1946), EMBASE (from 1980), and the Cochrane Library (no start date) to October 1, 2014. Meta-analyses, systematic reviews, randomized clinical trials (RCTs), and prospective observational studies were included.
RESULTS:
Weight loss was followed by decreased time with esophageal acid exposure in 2 RCTs (from 5.6% to 3.7% and from 8.0% to 5.5%), and reduced reflux symptoms in prospective observational studies. Tobacco smoking cessation reduced reflux symptoms in normal-weight individuals in a large prospective cohort study (odds ratio, 5.67). In RCTs, late evening meals increased time with supine acid exposure compared with early meals (5.2% point change), and head-of-the-bed elevation decreased time with supine acid exposure compared with a flat position (from 21% to 15%).
CONCLUSIONS:
Weight loss and tobacco smoking cessation should be recommended to GERD patients who are obese and smoke, respectively. Avoiding late evening meals and head-of-the-bed elevation is effective in nocturnal GERD.
Keywords: GERD; Heartburn; Acid Regurgitation; Therapy; Treatment.
astroesophageal reflux disease (GERD), defined by at least weekly symptoms of heartburn or acid regurgitation, is increasingly common.1 The prevalence in adults ranges from 30% in some Western populations to less than 10% in East Asian populations, and the incidence is approximately 5 per 1000 person-years in Western populations.1 GERD is associated with reduced health-related quality of life,2 decreased work productivity3 and increased risk of esophageal adenocarcinoma.4 The annual incidence of esophageal adenocarcinoma is increasing worldwide, from 3.5% in Scotland to 8.1% in Hawaii, which parallels the increasing prevalence of GERD.5 In addition, GERD diagnostic tests and treatments carry high societal costs.6 The pathophysiology of GERD is dominated by functional and anatomic defects at the gastroesophageal junction, including reduced pressure and increased reflux episodes associated with transient relaxations of the lower esophageal sphincter and formation of hiatal hernia, which promotes and facilitates reflux.7–9 Esophageal motility and salivary bicarbonate contribute to
G
esophageal acid clearance and buffering, respectively, and reduce acid contact time in the esophagus.10,11 Visceral obesity increases the pressure over the gastroesophageal junction, thus facilitating reflux,12 and tobacco smoking reduces the lower esophageal sphincter pressure and salivary bicarbonate secretion, which facilitates reflux and decreases acid buffering, respectively.13,14 The main established risk factors of GERD are heredity, obesity, and tobacco smoking.15–18 High dietary fiber intake and moderate physical exercise seem to reduce this risk,18 whereas sex and age do not strongly influence the risk of GERD.19,20 Obesity is of particular interest because it is increasing in prevalence in parallel Abbreviations used in this paper: BMI, body mass index; CI, confidence interval; GERD, gastroesophageal reflux disease; OR, odds ratio; PPI, proton pump inhibitor; RCT, randomized clinical trial. © 2015 by the AGA Institute 1542-3565/$36.00 http://dx.doi.org/10.1016/j.cgh.2015.04.176
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59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116
117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 Q12
Category Weight loss
Study
Design
Findings Normalization of pH measurements in 3 of 5 with weight loss Reduced acid exposure in sham group (the effect of mere weight loss) Reduced acid exposure in sham group (the effect of mere weight loss) Decreased symptom prevalence and score in both groups
Mathus-Vliegen and Tytgat,37 1996
RCT
Gastric balloon vs sham treatment
Mathus-Vliegen and Tytgat,38 2002
RCT
Gastric balloon vs sham treatment
Mathus-Vliegen et al,39 2003
RCT
Gastric balloon vs sham treatment
Singh et al,40 2013
RCT
Austin et al,41 2006
Nonrandomized prospective study Nonrandomized prospective study Prospective populationbased cohort study Prospective populationbased cohort study
Structured weight loss program vs telephone-based group conference Very lowcarbohydrate diet Dietary advice
Fraser-Moodie et al,42 1999 Jacobson et al,43 2006
Ness-Jensen et al,44 2013
No intervention
No intervention
Low-caloric diet vs control
Cremonini et al,46 2006
Prospective populationbased cohort study
No intervention
ACG (2013)36
Lifestyle modifications are ineffective for frequent or severe symptoms, but may be beneficial if obvious dietary precipitants, obesity or tobacco smoking
Weight loss in obese patients; head of the bed elevation if symptoms when recumbent; other lifestyle modifications tailored to the individual patient
Weight loss recommended for GERD patients with overweight or recent weight gain; head of bed elevation and avoidance of meals 2–3 hour before bedtime recommended if nocturnal GERD; routine global elimination of food that can trigger reflux not recommended
Decreased acid exposure and symptom score Decreased symptom score Dose-dependent decrease in symptom prevalence Dose-dependent decrease in symptoms, improved medical treatment success No effect on symptoms, endoscopic findings, or acid exposure No association with symptoms
No.
RCT
AGA (2008)34,35
-,
Kjellin et al,45 1996
A
CAG (2005)24
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Comparison with current guidelines Level of evidencea
2
Table 1. Lifestyle Intervention in GERD
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175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232
233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 Dietary interventions
Kjellin et al,45 1996
Austin et al,41 2006
Decreased symptoms in normal weight individuals
B
Low-caloric diet vs control
No effect on symptoms, endoscopic findings, or acid exposure Decreased acid exposure and symptom score Decreased acid exposure with early evening meal Decreased symptom prevalence and score with dietary fiber No effect on GERD
B (no effect)
Very lowcarbohydrate diet Late vs early evening meal
DiSilvestro et al,49 2011
RCT
Dietary fiber vs placebo
Johnson et al,50 2010
Systematic review of observational studies RCT
Carbonated beverages
Hamilton et al,51 1988
Head of bed elevation vs flat position
Decreased acid exposure with head of bed elevation
B
B
B
B (no effect)
B
ACG, American College of Gastroenterology; AGA, American Gastroenterological Association; CAG, Canadian Association of Gastroenterology. a A, multiple populations were evaluated, data were derived from multiple randomized clinical trials or meta-analyses; B, limited populations were evaluated, data were derived from a single randomized clinical trial or nonrandomized studies; C, very limited populations were evaluated, only consensus opinion of experts, case studies, or standard of care.
Lifestyle Intervention in GERD
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No intervention
Nonrandomized prospective study RCT
Piesman et al,48 2007
Head-of-the-bed elevation
Prospective populationbased cohort study RCT
2015
Ness-Jensen et al,47 2014
-
Tobacco smoking cessation
3 Q1
291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348
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with GERD, and several studies have shown an increased risk of GERD and esophagitis with obesity, especially abdominal obesity.21,22 GERD typically is diagnosed by the cardinal symptoms of heartburn or acid regurgitation,23 and by symptom resolution after acid inhibition with a proton pump inhibitor (PPI).24 If symptoms do not resolve, endoscopy usually is performed and mucosal erosions (esophagitis) or peptic strictures are diagnostic of GERD.25 Endoscopy also can show Barrett’s esophagus, a premalignant columnar metaplasia, and esophageal adenocarcinoma. If endoscopy is normal, esophageal pH measurement still can show pathologic acid reflux (pH < 4).26 The pH measurement can be combined with impedance measurement to detect reflux of weakly acidic or nonacidic liquid and gas, which can cause reflux symptoms refractory to acid inhibition.27 The treatment of GERD is primarily by medication with antacids, H2-receptor antagonists, and PPIs, whereas surgery (typically with fundoplication) is used in selected patients. Recent evidence has shown that long-term PPI medication is hampered by adverse effects. This includes secondary hypergastrinemia and rebound acid hypersecretion, inducing reflux symptoms at withdrawal of PPI medication28; increased risk of enteric infections and community-acquired pneumonia, probably owing to increased gastric pH causing reduced host defense29,30; and increased risk of hip and vertebral fractures, probably owing to malabsorption of calcium.31 This review addresses lifestyle interventions in the treatment of GERD and compares existing evidence with current guidelines.
Methods Systematic literature searches on lifestyle interventions for patients with GERD were performed in MEDLINE using PubMed from 1946 and EMBASE using OvidSP from 1980 to October 1, 2014. In addition, the Cochrane Library was searched (last search was performed on October 1, 2014). The searches included the thesaurus terms (MeSH in MEDLINE and EMTREE in EMBASE): “gastroesophageal reflux,” “heartburn,” “peptic esophagitis” (EMBASE)/”esophagitis, peptic” (MEDLINE) and “non-erosive reflux disease” (EMBASE). Randomized clinical trials (RCTs), prospective observational studies, and meta-analyses and systematic reviews of RCTs or observational studies of GERD patients were included. The searches were limited to the English language and research on adult human beings. The evidence of interventions was graded using the American Heart Association’s guidelines, as follows: multiple populations were evaluated, data were derived from multiple RCTs or metaanalyses (level A); limited populations were evaluated, data were derived from a single RCT or nonrandomized studies (level B); and very limited populations were evaluated, only consensus opinion of experts, case studies, or standard of care (level C).
-,
No.
-
Results Literature Searches Literature searches on lifestyle intervention identified 15 original studies that met the inclusion criteria (Table 1 and Supplementary Table 1). In addition, 1 previous systematic review on lifestyle intervention and 1 previous systematic review on conservative and surgical treatment for obesity in GERD were identified.32,33 No relevant Cochrane reviews were identified. Three management guidelines were assessed: the Canadian Association of Gastroenterology consensus (2005),24 the American Gastroenterological Association medical position statement and technical review (2008),34,35 and the American College of Gastroenterology guideline (2013).36
Lifestyle Interventions Lifestyle interventions in GERD traditionally have included avoidance of foods that may precipitate reflux episodes and heartburn (eg, coffee, alcohol, chocolate, peppermint, citrus, carbonated drinks, and spicy foods), and behavioral changes with weight loss, smoking cessation, head-of-the-bed elevation, avoiding large meals, and avoiding recumbence after meals or meals before bedtime.34,35 The previous systematic review on lifestyle intervention in GERD concluded that only weight loss and head-of-the-bed elevation were effective for GERD, whereas the systematic review on conservative and surgical treatment for obesity concluded that dietary and lifestyle intervention may improve GERD in obese patients.32,33 However, new supportive evidence has emerged.
Weight Loss Three RCTs in severely obese individuals compared weight loss by gastric balloon distension with sham treatment combined with dietary guidance, physical exercise, and behavioral therapy, and showed reduced esophageal acid exposure with weight loss.37–39 In the first RCT, including 17 patients, 3 of 5 patients with pathologic pH measurements had normalized pH measurements after weight loss of 31.3 to 44.0 kg after 4 months.37 In the second RCT, 23 patients with a mean weight loss of 11.2 kg within 13 weeks had decreased time with esophageal pH level less than 4 (from 5.60% to 3.72%; P < .05).38 Moreover, there was a strong correlation between decreased waist circumference and acidic reflux time (r ¼ 0.78; P ¼ .000).38 These results were supported by the third RCT of 17 sham-treated patients, in which mean weight loss of 12.5 kg within 13 weeks improved time with upright pH level less than 4 (from 8.0% to 5.5%; P < .05).39 A larger RCT compared obese participants randomized to a structured weight loss program (n ¼ 167) with
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465 466 467 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 Q11 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522
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a telephone-based group conference on weight management (n ¼ 165). The prevalence of reflux symptoms decreased (from 37% to 15%; P < .01) and the symptom score improved (Reflux Disease Questionnaire; P < .01) after 6 months of weight loss (mean body mass index [BMI] decreased from 34.7 to 30.2), irrespective of treatment group.40 These results were confirmed in 2 uncontrolled prospective cohort studies of GERD patients.41,42 A study of 8 extremely obese patients (mean BMI, 43.5) showed significant improved total time with pH less than 4 (from 5.1% to 2.5%; P ¼ .022) and reflux symptom score (Distress Subscale of Gastroesophageal Reflux Disease Symptom Assessment Scale from 1.28 to 0.72; P ¼ .0004) after 4 days on a very-low-carbohydrate diet and a mean weight loss of 1.7 kg.41 Moreover, a study of 34 patients with a mean BMI of only 23.5, reflux symptoms, and either normal endoscopy or low-grade esophagitis also showed significant correlation between weight loss after dietary advice (mean BMI decrease, 1.7) and reflux symptom score (modified DeMeester questionnaire, r ¼ 0.548; P < .001).42 Two large prospective population-based cohort studies showed that weight reduction dose-dependently decreased reflux symptoms.43,44 The Nurses’ Health Study, an observational cohort study of 10,545 women, showed a dose-dependently reduced risk of reflux symptoms among women who had a decrease in BMI compared with women with no BMI change (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.42–0.97; BMI decrease, >3.5 units; P for trend < .001).43 The NordTrøndelag health study, a prospective population-based cohort study of 29,610 participants, also showed a dose-dependent association between weight loss and the chance of losing reflux symptoms (OR, 2.42; 95% CI, 1.88–3.11; BMI decrease, >3.5 units; P for trend < .001). In this study, decrease in BMI also was associated with an increased chance of losing reflux symptoms with medical treatment (OR, 1.98; 95% CI, 1.45–2.72; BMI decrease, >3.5 units; and no or less than weekly medication; compared with OR, 3.96; 95% CI, 2.03–7.65; BMI decrease, >3.5 units; and at least weekly medication).44 Challenging these results, a small RCT showed that weight loss (mean, 10.8 kg) did not have significant effects on symptoms, esophagitis, or pH measurements in obese patients (mean BMI, 31.4) with GERD who were randomized to a low-calorie diet (430 kcal/d) for 6 months (n ¼ 10) or not (n ¼ 9).45 In addition, a prospective population-based cohort study of 637 individuals showed no association between weight loss and reflux symptoms, but because weight loss was selfreported it may have been overestimated.46
Tobacco Smoking Cessation A prospective population-based cohort study (the Nord-Trøndelag health study) of 29,610 participants showed that smoking cessation was associated with
5
decreased severe reflux symptoms in normal-weight individuals on medical treatment, compared with participants who continued smoking daily (OR, 5.67; 95% CI, 1.36–23.64).47 However, there was no similar association in overweight (BMI, 25.0–29.9) or obese (BMI, 30.0) individuals (OR, 1.24; 95% CI, 0.57–2.71; and OR, 1.29; 95% CI, 0.53–3.17, respectively). A possible explanation for these findings is that GERD pathophysiology in obese individuals is dictated strongly by weight, while smoking plays a minor role, but smoking is a more important factor in nonobese individuals.
Dietary Interventions A RCT showed no influence of weight loss after a 6-month period of low-caloric diet (430 kcal/d) on GERD.45 However, a small nonrandomized study of 8 severely obese patients (mean BMI, 43.5) who lost weight (1.7 kg) on a 4-day, very-low-carbohydrate diet (<20 g/d) showed a decreased total time with pH less than 4 (from 5.1% to 2.5%; P ¼ .022) and reflux symptoms score (from 1.28 to 0.72; P ¼ .0004).41 A cross-over RCT of 30 patients randomized to a late meal (2 hours before bedtime) or an early meal (6 hours before bedtime) showed more pH-verified supine reflux after the late evening meal (mean change, 5.2%; P ¼ .002).48 A RCT that compared patients using a dietary fiber product (n ¼ 15) with placebo (n ¼ 15) for 2 weeks, showed an increased number of days without heartburn (mean, 1.87 and 0.73, respectively; P < .05) and reduced severity score (mean, 7.7 and 13.3, respectively; P < .05) in the fiber group.49 A systematic review based on observational studies showed no evidence of carbonated beverages promoting GERD.50 Regarding other potential dietary interventions there were no studies meeting the search criteria.
Head-of-Bed Elevation A cross-over RCT of 15 GERD participants showed that elevation of the head of the bed by a 10-inch wedge decreased the time that esophageal pH was less than 4 compared with a flat position (15% and 21%, respectively; P < .05).51
Discussion RCTs have shown reduced reflux symptoms and esophageal acid exposure with weight loss,37–40 findings supported by well-designed observational studies showing a dose-dependent decreased presence of reflux symptoms after weight reduction. A large prospective observational study showed reduced reflux symptoms with tobacco smoking cessation in normal-weight individuals.47 RCTs also showed that early evening meals48
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and head-of-the-bed elevation51 decreased the esophageal acid exposure time, and dietary fiber decreased reflux symptoms.49 Based on the present review, we believe that the evidence of lifestyle modifications in GERD has been strengthened compared with the statements in the 3 current treatment guidelines.24,34–36 The Canadian Association of Gastroenterology guideline concludes that lifestyle modifications are ineffective for frequent or severe reflux symptoms and that data are insufficient to support lifestyle modifications in mild reflux.24 The American Gastroenterological Association guideline recommends weight loss in obese GERD patients and elevation of the head of the bed in patients experiencing reflux symptoms when recumbent, while other lifestyle modifications should be individually tailored.34,35 The American College of Gastroenterology guideline supports avoidance of meals 2 to 3 hours before bedtime, in addition to weight loss and head-of-bed elevation. However, it does not recommend elimination of food that can trigger reflux.36 We believe that patients suffering from GERD should be recommended to lose weight if they are obese, that tobacco smoking cessation and increased dietary fiber should be encouraged, and that late evening meals should be avoided and head-of-the-bed elevation recommended for patients with supine reflux. Based on the pathophysiologic mechanisms, weight loss in obese patients presumably will reduce the increased pressure on the gastroesophageal junction, reducing reflux.12 Smoking cessation will normalize the lower esophageal sphincter pressure and salivary bicarbonate production.13,14 It is speculated that dietary fiber expands with water to form a barrier to the acid rising into the esophagus.49 Avoiding late evening meals and head-ofthe-bed elevation will reduce nighttime supine reflux.48,51 Any effect of a very-low-carbohydrate diet is uncertain because the study cannot separate the effects of weight loss from those of diet.41 However, a small case series showed a significant and almost immediate resolution of GERD symptoms in obese individuals initiating a very-low-carbohydrate diet.52 Lifestyle interventions, especially weight loss and tobacco smoking cessation, also are beneficial from other perspectives, including low economic costs, no harmful side effects, and overall health benefits. In addition, observational studies have shown that weight loss and tobacco smoking cessation are associated with improved success with medical treatment.44,47 Extensive data exist on the effects of acid-inhibiting medication in GERD, compared with only a few and heterogeneous RCTs or observational studies of lifestyle intervention. Commercial interests are probably the main reason for this imbalance of studies. Noncommercial funding should focus on performing larger RCTs on lifestyle interventions to verify these results and obtain more reliable conclusions. Nevertheless, the available evidence is reasonably consistent and supported by the
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pathophysiology and epidemiology. The effects of these interventions on reflux symptoms, acid exposure, and endoscopic findings should be assessed in future studies. Because obesity and smoking are risk factors of GERD, a reduced prevalence of these exposures in the populations also could reduce the incidence of GERD.
Conclusions Recent evidence supports lifestyle intervention in the treatment of GERD. These include weight loss, tobacco smoking cessation, avoiding late evening meals, and head-of-the-bed elevation. Meanwhile, the awareness of adverse effects of medical treatment has increased, questioning long-term and continuous PPI therapy, at least in mild GERD.
Supplementary Material Note: To access the supplementary material accompanying this article, visit the online version of Clinical Gastroenterology and Hepatology at www.cghjournal.org, and at http://dx.doi.org/10.1016/j.cgh.2015.04.176.
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49. DiSilvestro RA, Verbruggen MA, Offutt EJ. Anti-heartburn effects of a fenugreek fiber product. Phytother Res 2011;25:88–91. 50. Johnson T, Gerson L, Hershcovici T, et al. Systematic review: the effects of carbonated beverages on gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2010;31:607–614. 51. Hamilton JW, Boisen RJ, Yamamoto DT, et al. Sleeping on a wedge diminishes exposure of the esophagus to refluxed acid. Dig Dis Sci 1988;33:518–522. 52. Yancy WS Jr, Provenzale D, Westman EC. Improvement of gastroesophageal reflux disease after initiation of a lowcarbohydrate diet: five brief case reports. Altern Ther Health Med 2001;7:116–129.
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Reprint requests Address requests for reprints to: Eivind Ness-Jensen, MD, PhD, Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, NS 67, 171 76 Stockholm, Sweden. e-mail: eivind. [email protected]; fax: (46) 8-51776280. Conflicts of interest The authors disclose no conflicts. Funding Supported by the Norwegian and Swedish Research Councils (E.N.-J.); by National Institutes of Health grant K24 DK04-107 and the Houston VA Health Services Research and Development Center of Excellence (HFP90-020) (H.E.-S.); and by grants from the Swedish Research Council (J.L.).
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871 872 873 Q2 874 875 876 Q3 877 878 879 880 Q4 881 882 883 884 885 886 887 888 889 890 891 892 893 894 895 896 897 898 899 900 901 902 903 904 905 906 907 908 909 910 911 912 913 914 915 916 917 918 919 920 921 922 923 924 925 926 927 928
929 930 931 932 933 934 935 936 937 938 939 940 941 942 943 944 945 946 947 948 949 950 951 952 953 954 955 956 957 958 959 960 961 962 963 964 965 966 967 968 969 970 971 972 973 974 975 976 977 978 979 980 981 982 983 984 985 986 Source
Search terms
201
10
Systematic review
Randomized clinical trial
2
4
Kaltenbach Singh et al, et al, 2006 2013 De Groot et al, Kjellin et al, 2009 1996 Mathus-Vliegen et al, 2002 Mathus-Vliegen et al, 2003 Excluding obesity surgery “Smoking cessation” [Mesh]
“Diet therapy” [Mesh]
140
21
3
88
1
4
22
4
1
1
2
27
1
1
8
0
12
1
1
11
3
4
Ness-Jensen et al, 2013 2
68
22
6 53
1 8
2 21
4
12
5
17
1
10
1
3
2
72
6 54
0 1
1
Ness-Jensen et al, 2013 Cremonini et al, 2006 Jacobson et al, 2006 Fraser-Moodie et al, 1999
51
0
1
1
De Groot et al, Kjellin et al, 2009 1996
“Meals”[Mesh] “Dietary fats” [Mesh]
4
Not Retrospective/ No NonCase/ relevant crossexperimental patients/ systematic abstract Conf. sectional available abstract Dupl. Other review study outcome study
1
4
2
3
Austin et al, 2006 Fraser-Moodie et al, 1999 3 3
Kaltenbach et al, 2006 “Dietary carbohydrates” [Mesh] “Cacao”[Mesh] “Mentha piperita” [Mesh]
17
0
5 1
0 1
1
5 0
2
2
1
Kaltenbach et al, 2006 “Coffee”[Mesh] “Ethanol”[Mesh] “Citrus”[Mesh]
20 32 18
0 0 1
1 Kaltenbach et al, 2006
20 32 17
4 12
4 1
1 8 4
3
5 4 3
5 3 6
2 2
1 1
Lifestyle Intervention in GERD
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MEDLINE/ “Body weight PubMeda changes” [Mesh] 1946 to October 1, 2014
Id. Metaarticles Included analysis
Prospective observational Not Not Not study Excluded English human adult
2015
Q15
Q13 Q14
-
Supplementary Table 1. Summary of Literature Search
8.e1
987 988 989 990 991 992 993 994 995 996 997 998 999 1000 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 1012 1013 1014 1015 1016 1017 1018 1019 1020 1021 1022 1023 1024 1025 1026 1027 1028 1029 1030 1031 1032 1033 1034 1035 1036 1037 1038 1039 1040 1041 1042 1043 1044
1045 1046 1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 1057 1058 1059 1060 1061 1062 1063 1064 1065 1066 1067 1068 1069 1070 1071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 1084 1085 1086 1087 1088 1089 1090 1091 1092 1093 1094 1095 1096 1097 1098 1099 1100 1101 1102 Search terms “Carbonated beverages” [Mesh]
Id. Metaarticles Included analysis 37
Systematic review
Randomized clinical trial
Prospective observational Not Not Not study Excluded English human adult
1
36
1
13
Johnson et al, 2010 1 Kaltenbach et al, 2006
5
1
3
22
3
70
6
54 72
4 3
63
“Spices”[Mesh]
6
1
“Dietary fiber” [Mesh]
23
1
“Posture”[Mesh]c
73
3
“Exercise”[Mesh] Weight reduction EMBASE/ b OvidSP 1980 to October 1, 2014
54 104
0 8
1 DiSilvestro et al, 2011 1 2 Kaltenbach Piesman et al, et al, 2006 2007 Hamilton et al, 1988 2
4
2
2
1
5
12
1
1
3
1
2
2
5
28
1
8
27
12 35
10
6
21 1
6 26
2
0
42
1
16
35
5
5
22
50
10
6
21
11 6
2
1 1
Kaltenbach Singh et al, Ness-Jensen et al, 2006 2013 et al, 2013 De Groot et al, Mathus-Vliegen Fraser-Moodie 2009 et al, 1996 et al, 1999 Mathus-Vliegen et al, 2002 Mathus-Vliegen et al, 2003 24
0
65
2
Diet therapy
38
3
Diet
51
1
Meals Fat
11 6
0 0
Excluding obesity surgery Smoking cessation
0 1 Kaltenbach et al, 2006 2 Kaltenbach et al, 2006 De Groot et al, 2009 1 Kaltenbach et al, 2006
1 Ness-Jensen et al. 2013 1 Austin et al. 2006
4 2
2
3
3
1
9
2 3
3 1
-,
7
Clinical Gastroenterology and Hepatology Vol.
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1
Retrospective/ Not crossCase/ relevant NonNo sectional experimental patients/ systematic abstract Conf. study study outcome review available abstract Dupl. Other
Ness-Jensen et al
Source
8.e2
Supplementary Table 1. Continued
No. -
1103 1104 1105 1106 1107 1108 1109 1110 1111 1112 1113 1114 1115 1116 1117 1118 1119 1120 1121 1122 1123 1124 1125 1126 1127 1128 1129 1130 1131 1132 1133 1134 1135 1136 1137 1138 1139 1140 1141 1142 1143 1144 1145 1146 1147 1148 1149 1150 1151 1152 1153 1154 1155 1156 1157 1158 1159 1160
1161 1162 1163 1164 1165 1166 1167 1168 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 1179 1180 1181 1182 1183 1184 1185 1186 1187 1188 1189 1190 1191 1192 1193 1194 1195 1196 1197 1198 1199 1200 1201 1202 1203 1204 1205 1206 1207 1208 1209 1210 1211 1212 1213 1214 1215 1216 1217 1218 1219 1220 1221 1222 1223 Search terms
Id. Metaarticles Included analysis 6 2
0 1
Mentha piperita
1
1
Coffee
14
1
Alcohol Citrus Carbonated beverages
44 0 10
0 0 1
1 Kaltenbach et al, 2006 1 Kaltenbach et al, 2006 1 Kaltenbach et al, 2006
1
Randomized clinical trial
6 1
Not Retrospective/ No Nonrelevant Case/ crossexperimental patients/ systematic abstract Conf. sectional available abstract Dupl. Other review outcome study study
3
2 1
1
0
13
1
44 0 9
11
7
1
1
3
4
16
1
2
7
1
5
8 2
9 23 24
1
2
3
Kaltenbach et al, 2006 Spices Dietary fiber Posture Exercise OR physical activity
1 21 47 57
0 0 0 0
1 21 47 57
5 3
1 1 5
2 6 13
1 7 3 8
1 1 1
1 1
MeSH terms (exploded, including all subheadings): (“Gastroesophageal Reflux”[Mesh] OR “Heartburn”[Mesh] OR “Esophagitis, Peptic”[Mesh]) AND (.). EMTREEE terms (exploded outcome, focused intervention, including all subheadings): (gastroesophageal reflux OR heartburn OR non erosive reflux disease OR reflux esophagitis) AND (.). c Search was limited to meta-analysis, systematic review, clinical trial, and observational study. a
b
Lifestyle Intervention in GERD
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Carbohydrate Cacao
Systematic review
Prospective observational Not Not Not study Excluded English human adult
2015
Source
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Supplementary Table 1. Continued
8.e3 1224 1225 1226 1227 1228 1229 1230 1231 1232 1233 1234 1235 1236 1237 1238 1239 1240 1241 1242 1243 1244 1245 1246 1247 1248 1249 1250 1251 1252 1253 1254 1255 1256 1257 1258 1259 1260 1261 1262 1263 1264 1265 1266 1267 1268 1269 1270 1271 1272 1273 1274 1275 1276 1277 1278 1279 1280 1281 1282 1283 1284 1285 1286