insights

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Prevalence of gastroesophageal reflux disease (GERD) has increased an estimated 77% worldwide in the past few decades, with over 783 million cases reported in 2019.¹ Several factors have been associated with an increased risk for developing GERD symptoms, including obesity, tobacco use, older age, and lower socioeconomic status.¹ Increased stress may also be a contributor to GERD symptoms, and clinical studies have suggested a relationship between GERD and anxiety as well as depression.²

The most popular GERD treatments, stomach acid reducers, are a booming business, with both H2 blockers and proton pump inhibitors (PPIs) used widely. A recent systematic review estimated that nearly one-quarter of adults worldwide use a prescribed PPI.³ Taking an over-the-counter acid blocker for occasional heartburn symptoms may not be a big issue, but in practice, many patients with chronic reflux are prescribed acid blockers indefinitely. A significant number of researchers have independently linked PPIs to adverse health problems such as bone fractures,^4,5 chronic kidney disease,⁶ and pneumonia,⁴ among others.

Given these risks, is there a better way to treat the increasingly common issue of GERD? In the following video, IFM educator Shilpa P. Saxena, MD, IFMCP, talks about the non-gastrointestinal symptoms of GERD, such as allergies, and identifies some of the steps she takes when developing a treatment plan.

PPIs: Comparing the Pros and Cons

When establishing treatment for patients who require acid suppression, considering PPI benefits and risks associated with dosage amounts and duration is an important component.

Benefits:

Not all research suggests that PPIs are associated with adverse effects. For example, a three-year randomized trial of pantoprazole completed in 2019 did not find significant adverse events, with the exception of an increased risk of enteric infections.⁷ PPIs continue to be a primary therapy for acute and long-term management of GERD due to their:

• Effectiveness in controlling GERD symptoms and potentially arresting disease progression.⁸
• Improvement of healing rates and fewer relapses in patients with erosive esophagitis compared to H2 blockers.⁹
• Consistent superiority compared to earlier drugs for relieving GERD symptoms.⁹

RISKS:

Guidelines recommend using the lowest dosage of stomach acid reducers for symptom relief; however, these medications are often used in excessive doses or duration.⁸ According to warnings posted by the US Food and Drug Administration (FDA), long-term use of PPIs may not only lower serum magnesium levels but may also increase fracture risk.^10,11 Several recent research studies have noted a range of additional adverse effects from the use of acid blockers:

• A 2017 meta-analysis of 7,703 patients found that the use of gastric acid suppressants was associated with a significantly increased risk of recurrent difficile infection (CDI).¹² Risk factors for recurrent CDI include older age, concomitant antibiotic use, and comorbid conditions.¹²
• Meta-analyses suggest that PPI use is a potential risk factor for small intestinal bacterial overgrowth, spontaneous bacterial peritonitis, community-acquired pneumonia, hepatic encephalopathy, and adverse outcomes in inflammatory bowel disease (IBD).¹³ A 2021 pooled analysis of three prospective cohorts (n=647,407) found that regular PPI users also had an increased risk of developing IBD compared to nonusers (HR: 1.42; CI: 1.22-1.65).¹⁴
• A 2019 cohort study linked the long-term use of these drugs to fatal cases of cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer.¹⁵

Lifestyle-Based Modifications and Therapeutic Approaches

Beyond long-term pharmaceutical use, personalized treatment strategies that include lifestyle modifications and alternate therapies may help patients with chronic reflux conditions find consistent and effective symptom relief and recovery. Common lifestyle modifications that have been studied for GERD include weight loss, head-of-bed elevation, and avoidance of tobacco, alcohol, and late-night meals.^16,17 Other suggested approaches include avoiding both large meals and those foods that may aggravate reflux symptoms—e.g., caffeine, coffee, chocolate, spicy foods, highly acidic foods (oranges, tomatoes), and fatty foods.¹⁶

Alternate and complementary GERD treatments are under continued investigation and include methods such as reflux inhibitors, prokinetics, acupuncture, and hypnotherapy.⁹ A variety of studied GERD interventions have shown promising results, such as alginate-based therapies¹⁸ and breathing exercises^19,20 to reduce symptoms. A 2019 observational study also suggested that mindfulness-based stress reduction may help improve health-related quality of life for patients with GERD.²¹ A 2021 randomized controlled trial (n=70) compared rose oil supplements (Rosa damascena ingredients preserved in sesame oil) with omeprazole (control group) for treatment of GERD symptoms.²² Investigators found that reflux symptoms decreased in both treatment and control groups, without a significant difference between the two, suggesting rose oil’s treatment may be effective without adverse side effects.²²

Clinical Considerations

Going forward, some functional medicine clinicians have successfully transitioned patients from PPIs to H2 blockers, which may have fewer side effects. It is important to note that there has been some concern regarding acid rebound when weaning patients off of PPIs.²³ The functional medicine framework can be particularly useful for clinicians if this tapering process is appropriate for a patient’s personalized treatment plan.

IFM teaches clinicians how to identify the underlying conditions of gastrointestinal concerns and how to develop and organize individual treatment protocols using lifestyle, diet, nutraceuticals, pharmaceuticals, and botanicals, as well as providing educational materials for patients to prioritize their lifestyle treatments. The functional medicine approach uses clinical tools and strategies to help prevent and treat GERD, address problems with the intestinal microbiome, and improve overall gastrointestinal function.

Related Articles

The Microbiome, Stress Hormones, and Gut Function

Lifestyle Factors Prevent GERD in Women

PPI Use May Increase Diabetes Risk

References

1. Zhang D, Liu S, Li Z, Wang R. Global, regional and national burden of gastroesophageal reflux disease, 1990-2019: update from the GBD 2019 study. Ann Med. 2022;54(1):1372-1384. doi:1080/07853890.2022.2074535
2. On ZX, Grant J, Shi Z, et al. The association between gastroesophageal reflux disease with sleep quality, depression, and anxiety in a cohort study of Australian men. J Gastroenterol Hepatol. 2017;32(6):1170-1177. doi:1111/jgh.13650
3. Shanika LGT, Reynolds A, Pattison S, Braund R. Proton pump inhibitor use: systematic review of global trends and practices. Eur J Clin Pharmacol. 2023;79(9):1159-1172. doi:1007/s00228-023-03534-z
4. Takagi T, Naito Y, Inoue R, et al. The influence of long-term use of proton pump inhibitors on the gut microbiota: an age-sex-matched case-control study. J Clin Biochem Nutr. 2018;62(1):100-105. doi:3164/jcbn.17-78
5. Yang J, Zhou TJ, Yang J, Bao DN. Use of acid-suppressive drugs and risk of fracture in children and young adults: a meta-analysis of observational studies. Eur J Clin Pharmacol. 2022;78(3):365-373. doi:1007/s00228-021-03245-3
6. Wu CC, Liao MH, Kung WM, Wang YC. Proton pump inhibitors and risk of chronic kidney disease: evidence from observational studies. J Clin Med. 2023;12(6):2262. doi:3390/jcm12062262
7. Moayyedi P, Eikelboom JW, Bosch J, et al. Safety of proton pump inhibitors based on large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology. 2019;157(3):682-691.e2. doi:1053/j.gastro.2019.05.056
8. Schnoll-Sussman F, Niec R, Katz PO. Proton pump inhibitors: the good, bad, and ugly. Gastrointest Endosc Clin N Am. 2020;30(2):239-251. doi:1016/j.giec.2019.12.005
9. Young A, Kumar MA, Thota PN. GERD: a practical approach. Cleve Clin J Med. 2020;87(4):223-230. doi:3949/ccjm.87a.19114
10.  US Food and Drug Administration. FDA drug safety communication: possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors. Reviewed August 3, 2017. Accessed September 6, 2024. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-possible-increased-risk-fractures-hip-wrist-and-spine-use-proton-pump
11.  US Food and Drug Administration. FDA drug safety communication: low magnesium levels can be associated with long-term use of proton pump inhibitor drugs (PPIs). Reviewed August 4, 2017. Accessed September 6, 2024. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-low-magnesium-levels-can-be-associated-long-term-use-proton-pump
12.  Tariq R, Singh S, Gupta A, Pardi DS, Khanna S. Association of gastric acid suppression with recurrent Clostridium difficile infection: a systematic review and meta-analysis. JAMA Intern Med. 2017;177(6):784-791. doi:1001/jamainternmed.2017.0212
13.  Naito Y, Kashiwagi K, Takagi T, Andoh A, Inoue R. Intestinal dysbiosis secondary to proton-pump inhibitor use. Digestion. 2018;97(2):195-204. doi:1159/000481813
14.  Xia B, Yang M, Nguyen LH, et al. Regular use of proton pump inhibitor and the risk of inflammatory bowel disease: pooled analysis of 3 prospective cohorts. Gastroenterology. 2021;161(6):1842-1852.e10. doi:1053/j.gastro.2021.08.005
15.  Xie Y, Bowe B, Yan Y, Xian H, Li T, Al-Aly Z. Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study. BMJ. 2019;365:l1580. doi:1136/bmj.l1580
16.  Katz PO, Dunbar KB, Schnoll-Sussman FH, Greer KB, Yadlapati R, Spechler SJ. ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2022;117(1):27-56. doi:14309/ajg.0000000000001538
17.  Park SK, Lee T, Yang HJ, et al. Weight loss and waist reduction is associated with improvement in gastroesophageal disease reflux symptoms: a longitudinal study of 15,295 subjects undergoing health checkups. Neurogastroenterol Motil. 2017;29(5):e13009. doi:1111/nmo.13009
18.  Leiman DA, Riff BP, Morgan S, et al. Alginate therapy is effective treatment for GERD symptoms: a systematic review and meta-analysis. Dis Esophagus. 2017;30(5):1-9. doi:1093/dote/dow020
19.  Qiu K, Wang J, Chen B, Wang H, Ma C. The effect of breathing exercises on patients with GERD: a meta-analysis. Ann Palliat Med. 2020;9(2):405-413. doi:21037/apm.2020.02.35
20.  Halland M, Bharucha AE, Crowell MD, Ravi K, Katzka DA. Effects of diaphragmatic breathing on the pathophysiology and treatment of upright gastroesophageal reflux: a randomized controlled trial. Am J Gastroenterol. 2021;116(1):86-94. doi:14309/ajg.0000000000000913
21.  Chandran S, Raman R, Kishor M, Nandeesh HP. The effectiveness of mindfulness meditation in relief of symptoms of depression and quality of life in patients with gastroesophageal reflux disease. Indian J Gastroenterol. 2019;38(1):29-38. doi:1007/s12664-019-00940-z
22.  Adel Mehraban MS, Shirzad M, Ahmadian-Attari MM, et al. Effect of rose oil on gastroesophageal reflux disease in comparison with omeprazole: a double-blind controlled trial. Complement Ther Clin Pract. 2021;43:101361. doi:1016/j.ctcp.2021.101361
23.  Pandolfino J. Discontinuation of proton pump inhibitor therapy and the role of esophageal testing. Gastroenterol Hepatol (NY). 2013;9(11):747-764.