GERD and PPI’s

Everything seems to have an acronym these days and medical jargon is no exception. But just the fact that these words are shortened to initials only and that a majority of the world knows what they mean is proof that GERD (gastro-esophageal reflux disease) and PPIs (proton-pump inhibitors) are all too common. GERD is a condition that can drastically decrease quality of life and its sufferers will grasp at anything that promises to relieve their daily symptoms. PPIs do offer relief but it comes at a price. PPI drugs are not benign molecules that decrease acid production without affecting any other aspect of health. They have side effects, some of which can be devastating. On a positive note, there is a path that can eliminate GERD forever, without adverse effects and actually with very beneficial side effects.

Just what is GERD?

GERD is a painful condition and one of the most common disorders of the digestive tract. The characteristic symptoms of GERD are heartburn (unpleasant burning in the chest) and a sour taste in the mouth caused by regurgitation of stomach contents up into the back of the throat. Additional symptoms can include chest pain, difficulty swallowing, nausea and vomiting, dry cough, hoarseness and sore throat (3). Symptoms can be quite severe.

What exactly is happening to cause these symptoms? At the top of the stomach is a sphincter (circular ring of muscle) called the lower esophageal sphincter and its job is to keep the stomach contents in the stomach. When food reaches this sphincter it relaxes and allows the food to enter the stomach. It then squeezes shut to prevent food and acid from backing up into the esophagus (the tube that carries food from the mouth to the stomach). If this muscle relaxes when it should not, stomach contents, including acid produced in the stomach, can enter the esophagus. This is called acid reflux. The tissues of the esophagus, unlike those of the stomach, are not able to withstand the corrosive effects of acid and inflammation results (esophagitis) with bleeding and constriction of the esophagus. In about 10% of people with GERD chronic inflammation will alter the esophageal tissue into cells that resemble those of the intestinal tract. When this happens it is called Barrett’s Esophagus and is a risk factor for esophageal cancer (3,11). Note that in the absence of Barrett’s Esophagus there is no strong evidence that GERD alone is a risk factor for developing cancer (18).

 

GERD is increasing….

Although gastroesophageal reflux disease has been known for centuries, its incidence was historically quite low. Studies show that incidence began increasing during the 1980s. Worldwide GERD incidence has been steadily increasing by about 4% every year but some countries are experiencing a much greater increase than others. The prevalence of weekly GERD symptoms in the USA has tripled from 10% in 1980 to 30% in 2010. GERD was almost unheard of in Asia until around the year 2000 when its incidence of weekly symptoms showed up at around 2%. By 2005 that incidence had increased to about 4% (1). GERD related doctor visits in the US increased by 46.5% between 2002 and 2005. The incidence of esophageal cancer has increased by six times during the last three decades.

What is fueling the increase in GERD and esophageal cancer around the world? Risk factors include obesity, smoking, advanced age and diet and lifestyle issues (1). The data on increased GERD with advancing age is limited, however some studies have indicated that higher GERD incidence is associated with increasing age (2). On the other hand, data regarding a relationship between GERD and obesity is clear (4,5). Many scientific studies on the subject have demonstrated that obesity leads to an increase in relaxation of the sphincter at the top of the stomach as well as an increase in the number of acid reflux episodes (6,7). Fatty foods are another cause of relaxation of the sphincter at the top of the stomach and subsequent acid creep up into the esophagus (8,9,10,16,31). Also, eggs and meat both increase the hormone cholecystokinin which can overly relax the esophageal sphincter, causing stomach contents to rise up into the esophagus (32).

 

Treating GERD with lifestyle

Treatments for GERD include lifestyle changes, medications and surgery. Lifestyle changes are always suggested first. They are powerful and can be completely effective in treating and healing GERD but many people find lifestyle changes to be very difficult and decide to opt for medications which do not require extensive alterations in lifelong habits. Lifestyle changes include weight loss, abstinence from smoking, reducing alcohol and caffeine intake, avoiding “trigger” foods such as spicy or acidic foods, avoidance of carbonated beverages, avoiding large meals by eating small meals several times a day, limiting eating or drinking several hours before going to bed, elevating the head of the bed at night and, the most important one, maintaining a low fat diet that is high in fruits and vegetables and low in eggs and meat (18,32). The sum effect of implementing all these changes targets the actual cause of GERD, the poorly performing lower esophageal sphincter (12,13,15,16,17,18).

High fiber foods and high antioxidant foods appear to be protective both for GERD and for esophageal cancer (12,13,31). Conversely, taking antioxidant supplements such as vitamin C and E offers no positive effects. It is food in its natural whole package that offers benefit. Completely vegetarian diets are associated with lower incidence of GERD. The most protective aspects of the diet seem to be red-orange vegetables, dark green leafy vegetables, berries and apples (15,16,17). As far as esophageal cancer is concerned, higher total vegetable intake has been associated with decreased risk while high-fat dairy intake and meat intake are both associated with increased risk (14). It is unclear whether the beneficial effects of vegetarian diets in reducing the incidence of GERD arise from the increased consumption of healthy foods or from the absence of meat. Whatever the reason, diet and lifestyle changes DO STOP REFLUX FROM OCCURRING through their direct effects on the lower esophageal sphincter.

 

Treating GERD with medication

Two types of medication reduce the stomach’s acid production, H2 inhibitors and proton pump inhibitors (PPIs). Because PPIs are the most powerful medications for GERD relief they are the medications that most GERD sufferers are taking. They work by temporarily blocking the parietal cells in the stomach from producing stomach acid and thereby allowing damaged tissue to heal, preventing Barrett’s Esophagus and stomach and duodenal ulcers (3). It is important to understand that these medications DO NOT STOP REFLUX FROM OCCURRING. They are effective in reducing symptoms only and they do that by reducing the amount of acid in the gastric fluid (18). They do not have any direct effect on the root of the problem, the lower esophageal sphincter (22). PPIs are successful in esophageal healing in 80 to 90% of patients. PPI therapy is often required for the rest of a person’s life. PPIs available in Canada are lansoprazole (Prevacid), omeprazole (Losec), rabeprazole (Pariet), pantoprazole (Pantoloc, Tecta), esomeprazole (Nexium) and dexlansoprazole (Dexilant).

The most common side effects of PPIs are headache, abdominal pain, bloating, diarrhea and nausea (18). However, they can also cause more serious side effects including: (19,20,21,23,30,34)
Increased risk for pneumonia – Stomach acid creates an inhospitable environment for bacteria but, if acid levels are reduced by PPIs, bacteria can thrive. Bacteria-laden stomach contents can migrate into the windpipe and lungs where they can cause pneumonia.
Damage to the gut microbiome – PPIs are consistently associated with a less healthy gut biome and increased risk of enteric infections. PPIs have an effect more damaging than the effects of antibiotics (30)
Increased risk for Clostridia Difficile infections – PPIs seem to be able to change conditions in the gut to those more favourable for C. difficile bacteria. C. Difficile infections cause severe diarrhea that can result in death.
Increase in food poisoning – With reduction in stomach acid, risk of bacterial growth increases and studies show associations of PPIs with food poisoning from bacteria such as campylobacter and salmonella.
Increased risk of kidney disease – Studies show a 20% higher risk of kidney disease in those taking PPIs compared with people taking a different class of heartburn drugs known as H2 blockers. It is thought that PPIs interfere with the body’s ability to absorb magnesium which could increase the risk to the kidneys (23).
Increased risk for bone fractures – Low stomach acid can lead to reduced absorption of calcium which is the most likely cause of weaker bones and osteoporosis development that is linked with PPI therapy (19).
Nutrient deficiencies (B12 and iron) – Stomach acid assists in absorption of these two nutrients and so the lowering of stomach acid by PPIs could theoretically lower the absorption. This effect seems to be mild.
Increases risk of all-cause mortality – Very recent observational studies show that, when compared to H2 blockers, PPI use is associated with a 25% increased risk of overall death from all causes. This risk increase occurs even in people who have no gastro-intestinal conditions and no documented medical reason to take the drug. This risk increases with the length of time the drug is taken. (34)

PPIs do not seem to offer any reduction in risk of esophageal cancer (28,29).

 

A quick note on the best time to take a PPI:

Many recommendations advise taking a PPI on an empty stomach 30 or even 60 minutes before the first meal of the day. Research has shown that they work better if given just 15 minutes before a meal. This is because the medication is more effective at inhibiting parietal cells in the stomach that are actively secreting acid. (33)

The bottom line is that PPIs are potent medications that should not be taken lightly or used for a mild case of heartburn. H2 inhibitors such as cimetidine (Tagamet), famotidine (Pepcid), ranitidine (Zantac) and nizatidine (Axid) are safer alternatives, although unfortunately not nearly as effective. PPIs should be taken at the lowest effective dose and should not be continued long-term without periodic review.

 

Treating GERD with surgery

If PPIs do not provide sufficient relief, procedures are the next step. Surgery was once the only procedure available but recently developed endoscopic incisionless treatment is now available for sphincter repair. The technique uses stitching or radiofrequency-produced heat to affect the adjustment. Success rates for this technique of 75 to 80% have been reported three to six years post-procedure (24,25,26,27). Actual surgery is a more invasive procedure but it can repair the sphincter. Immediate side-effects of surgery occur in 5 to 20% of patients with the most common being difficulty swallowing or impairment of the ability to burp or vomit. These adverse effects are often temporary but can persist for life. Unfortunately, anti-reflux surgery can break down. The recurrence rate is in the range of 10 to 30% over twenty years (18).

So what does all this boil down to? Drugs and surgery are often perceived as an easy solution to a problem because they do not require the overwhelming changes that lifestyle alterations seem to demand. However, their many side effects including potentially major adverse effects should not be disregarded. The recent discovery of the link between PPIs and increased death from all causes should sound an additional warning bell and, at the very least, PPIs should be used only when medically indicated and for the shortest duration possible. Doesn’t it make more sense to put your effort into changing unhealthy habits and creating new life routines that will not only clear up GERD but also improve your overall health and prevent and even reverse many other chronic conditions that our society today takes for granted?

 

SOURCES;

1 William D. Chey, MD, AGAF, FACG, FACP. The Global GERD Epidemic: Definitions, Demographics, and the Clinical Implications of Changing Population Trends. Medscape. May 6, 2017

2 El-Serag, H.B., Petersen, N.J. et al. Gastroesophageal Reflux among different racial groups in the United States. Gastroenterology. 2004 Jun; 126 (7):1692-1699

3 http://www.mayoclinic.org/diseases-conditions/gerd/basics/symptoms/con-20025201

4 Corley, D.A., Kubo, A. Body Mass Index and Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2006; 101: 2619 -2628.

5 Jacobson, B.C., Somers, S.C. et al. Body-Mass Index and Symptoms of Gastroesophageal Reflux in Women. N Engl J Med 2006; 354:2340-2348

6 Wu, J.C. et al. Obesity is associated with increased transient lower esophageal sphincter relaxation. Gastroenterology. 2007; 132: 883–889

7 Shah, A. et al. Gastroesophageal Reflux Disease and Obesity. Gastroenterol Clin North Am 34 (1), 35-43.

8 Becker,D.J., Sinclair, J., et al. A comparison of high and low fat meals on postprandial esophageal acid exposure. Am J Gastroenterol. 1989 Jul; 84(7):782-6.

9 Bhatia, S.J., Reddy, D.N., Ghoshal, U.C. et al. Epidemiology and symptom profile of gastroesophageal reflux in the Indian population: report of the Indian Society of Gastroenterology Task Force. Indian J Gastroenterol. 2011 May; 30(3):118-27.

10 Holloway, R.H., Lyrenas, E. et al. Effect of intraduodenal fat on lower oesophageal sphincter function and gastro-oesophageaul reflux. Gut. 1997 Apr; 40(4): 449–453.

11 Parasa, S., Sharma, P. Complications of gastro-oesophageal reflux disease. Best Pract Res Clin Gastroenterol. 2013 Jun; 27(3):433-42.

12 De Ceglie, A., Fisher, D.A., Filiberti, R. et al. Barrett’s esophagus, esophageal and esophagogastric junction adenocarcinomas: the role of diet. Clin Res Hepatol Gastroenterol. 2011 Jan; 35(1):7-16.

13 Terry, P., Lagergren, J., Ye, W. et al. Antioxidants and cancers of the esophagus and gastric cardia. Int J Cancer. 2000 Sep 1; 87(5):750-4.

14 Navarro Silvera, S.A. Mayne, S.T., Risch, H. et al. Food group intake and risk of subtypes of esophageal and gastric cancer. Int J Cancer. 2008 Aug 15; 123(4):852-60.

15 Jung, J.G., Kang, H.W., Hahn, S.J. et al. Vegetarianism as a protective factor for reflux esophagitis: a retrospective, cross-sectional study between Buddhist priests and general population. Dig Dis Sci. 2013 Aug; 58(8):2244-52.

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17 Nebel, O.T., Castell, D.O. Lower esophageal sphincter pressure changes after food ingestion. Gastroenterology. 1972 Nov; 63(5):778-83.

18 International Foundation for Functional Gastrointestinal Disorders. http://www.aboutgerd.org/medications/proton-pump-inhibitors-ppis.html

19 Yag, Y.X., Lewis, J.D., Epstein, S., Metz, D.C. Long-term proton pump inhibitor therapy and risk of hip fracture.
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20 Harvard Health Education. http://www.health.harvard.edu/diseases-and-conditions/proton-pump-inhibitors

21 http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2013/26523a-eng.php

22 Dent, J., Downton, J., Buckle, P. et al. Omeprazole heals peptic oesophagitis by elevation of intragastric pH. Gastroenterology 1985; 88:1363.

23 Xie, Y., Bowe, B., Tingting, L. et al. Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD.
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24 Trad, K., Barnes, W., Simoni, G. et al. Transoral incisionless fundoplication effective in eliminating GERD symptoms in partial responders to proton pump inhibitor therapy at 6 months: The TEMPO randomized clinical trial. Surg Innov. 2015; 22: 26-40.

25 Witteman, B.P., Conchillo, J.M., Rinsma, N.F. et al. Randomized controlled trial of transoral incisionless fundoplication vs. proton pump inhibitors for treatment of gastroesophageal reflux disease. Am J Gastroenterol 2015; 110: 531-42.

26 Testoni, P.A., Testoni, S., Mazzoleni, G. et al. Long-term efficacy of transoral incisionless fundoplication with Esophyx (Tif 2.0) and factors affecting outcomes in GERD patients followed for up to 6 years: a prospective single-center study. Surg Endosc 2014.

27 Muls, V., Eckardt, A.J., Marchese, M. et al. Three-year results of a multicenter prospective study of transoral incisionless fundoplication. Surg Innov 2013; 20: 321-30.

28 Dall’Olmo, L., Fassan,M., Dassie, E. et al. Role of Proton Pump Inhibitor on Esophageal Carcinogenesis and Pancreatic Acinar Cell Metaplasia Development: An Experimental In Vivo Study. PLos One. November 21, 2014.

29 Miyashita, T., Furhawn, A., Shah, J et al. Do proton pump inhibitors protect against cancer progression in GERD?
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30 Imhann, F., Bonder, M.J., Villa, A.V. et al. Proton pump inhibitors affect the gut microbiome. Brit Med Jour. 2015. Volume 65 Issue 5.

31 Bredenoord, A.J., Pandolfino, J.E., Smout, A.J. Gastro-oesophageal reflux disease. Lancet. 2013 Jun 1;381(9881):1933-42.

32 Matsuki, N., Watanabe, N., Sugahara, A. et al. Lifestyle factors associated with gastroesophageal reflux disease in the Japanese population. J Gastroenterol. 2013 Mar;48(3):340-9.

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34 Xie, Y., et al. Research: Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open. 2017 July 3.

Promoting a healthy adventurous lifestyle powered by plants and the strength of scientific evidence.

My name is Debra Harley (BScPhm) and I welcome you to my retirement project, this website. Over the course of a life many lessons are learned, altering deeply-rooted ideas and creating new passions.

2 Comments

  1. Kirk Howell on February 17, 2018 at 10:49 am

    Thank you Deb for another well received (and well researched) article.

    Once again – you’ve focused our personal lifestyle on more positive eating habits!

    I agree – lifestyle is what people seem to struggle with in terms of change – however, simple lifestyle changes regarding diet lead to such an amazing experience!

    Thank you again,

    Kirk

    • Deb on February 22, 2018 at 9:18 am

      Thanks so much for your positive comment. You’ve hit the nail on the head – lifestyle changes are so simple to do but incredibly life changing in so many ways.
      Deb

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