PROTON PUMP INHIBITORS (PPIs): THE FINAL NAIL IN THE COFFIN

LCG

Used to treat acid reflux, proton pump inhibitors (PPIs), are the most popular class of acid-suppressive medications. They are also among the most widely used drugs in the U.S. as more than 50 million Americans take PPIs on a daily basis at an annual cost of $10 billion a year. A recent report linking PPI use with depression prompted this blog that examines the risks and benefits of PPI use. Spoiler alert: the risks far exceed the benefits.

COMMONLY USED ACID-SUPPRESSIVE
ANTI-REFLUX MEDICATIONS

Proton Pump Inhibitors
Prilosec (omeprazole)
Protonix (pantaprozole)
Prevacid (lansoprazole)
Aciphex (rabeprazole)
Dexilant (dexlansoprazole)
Zegerid (omeprazole/bicarbonate)
Nexium (esomeprazole)

H2-Antogonists (H2As) (Safe)
Zantac (ranitidine)
Pepcid (famotidine)
Tagamet (cimetidine)

Along with the PPIs, listed above are the other (safer) class of readily available acid-suppressive meds, H2-antagonists (H2As)

Doctors prescribe proton pump inhibitors (PPIs) almost routinely for heartburn and frequently tell patients that they will need to stay on them for life. That’s a really a bad idea, because PPIs don’t work that well, and they have many serious side effects and complications, some of which are life-threatening.

WHAT ARE PROTON PUMPS ARE WHY ARE THEY IMPORTANT?

Most people have seen TV ads showing tiny, cartoonish, little stomach pumps churning out acid, and then just giving up at the sight of a purple pill. Those purple pills (PPIs) don’t actually turn off the acid pumps, they just turn the volume, but that’s only part of the story.

It is important to note that the proton pumps in the stomach are specialized to produce acid. Proton pumps are found in almost all of the body’s tissues and organs where they perform functions that have nothing to do with acid production. In fact, proton pumps are integral parts of virtually every cell membrane and are related to cell energy regulation, nutrient uptake, and cell-cell communication.

Proton pumps are found throughout the gastrointestinal tract, all muscle (including cardiac muscle), and in all neural tissue (including brain). It is no wonder that we are beginning to discover many unintended consequences of widespread PPI use. We are just beginning to recognize that PPIs cause serious problems in many organs.

REBOUND HYPERACIDITY & OTHER SIDE EFFECTS

It’s not just physicians who prescribe PPIs; they are also widely advertised on television and available over-the-counter (OTC). In my opinion, the Food and Drug Administration never should have allowed PPIs to be sold OTC. That is because when they are stopped abruptly, many patients experience “rebound hyperacidity,” which means that reflux symptoms get much worse. And since the package label states that PPIs should be taken for just two weeks, people usually comply. But after days or weeks of misery after stopping, people feel that it is necessary to go back on the PPI. While this start-and-stop self-medication is good for drug sales, it is not good for reflux sufferers.

By the way, the proper way to taper off PPIs is by taking the other class of acid-suppressive, H2-antagonists (H2As); see above. H2As, available OTC, may be taken before each meal and before bed, four times a day at first. Then, after a few weeks, after the rebound has passed, the H2As can be tapered as well, over a few weeks 4-3-2-1 (per day) as symptoms ease. H2As are a safe class of drugs and have fewer side effects and generally less serious complications compared to PPIs.

Rebound hyperacidity is the most common side effect of PPIs, but the other common side effects of PPIs are headache, diarrhea, constipation, gas/flatulence, nausea, vomiting, and abdominal (stomach) pain. The latter seems to be a fairly common side effect, but it is often misdiagnosed, that is, doctors get a lot of unnecessary diagnostic tests to work up the pain while forgetting that PPIs can cause this particular symptom.

COMPLICATIONS AND LIFE-THREATENING UNTOWARD EVENTS

With 2014 publication of the Danish Study—that showed that log-term use of PPIs increases ones risk of developing reflux-caused esophageal cancer—I completely stopped using PPIs in my practice. What that study made clear was that even if a PPI improves a patient’s symptoms, it does not control the underlying reflux disease.

Death? Last year, another worrisome study was published that also got my attention; it was a Veterans Administration report with a large cohort of study subjects. Comparing reflux patients on H2As (n=73,335) with those on PPIs (n=275,977), the death rate was 25% higher in the PPI group.

In the table that follows, summarized are the data from several of the most compelling reports on PPI complications. (By no means is this list comprehensive.)  Note: These types of statistical studies do not prove causality; that said, the data do suggest credible relationships. (I believe that there is overwhelming evidence that PPIs are more harmful than beneficial.)

Summary Data: Serious PPI Complications with Links and Percent Increased Risk (+%)

Atrial fibrillation      +98%

Depression     +138%

Esophageal cancer     +120%

Esophageal dysplasia (precancer)     +240%

Heart failure & Death     +128%

Heat attacks     +100%

Hip fractures      +26%

Kidney Disease      +152%

THE ALTERNATIVES TO PPIs

PPIs don’t work for many reflux patients; and in my practice, almost all of my patients come to me already on PPIs or having been on them without benefit in the past. If they are on them, we stop them the day of the first visit, tapering with H2As as described above. NB: I have successfully managed reflux in thousands of patients without using PPIs. Diet and lifestyle are effective treatment for reflux, especially respiratory reflux, along with H2As and Gaviscon Advance. Reflux is curable with effort and commitment to change, which includes early eating, no soft drinks, and a diet that is lean, clean, green and alkaline. I have written four books about these topics:

Dropping Acid: The Reflux Diet Cookbook & Cure

The Chronic Cough Enigma

Dr. Koufman’s Acid Reflux Diet

Acid Reflux in Children: How Healthy Eating Can Fix Your Child’s Asthma, Allergies, Obesity, Nasal Congestion, Cough & Croup (On Amazon and soon to be released)

POTENTIAL REGULATORY AND CONSUMER ACTION POINTS

Consumers can boycott PPIs; tell your doctor that you don’t want to be on a PPI; and tell your doctor to view this post

PPIs should never have been allowed to be sold OTC, and they should be removed now. (The Food and Drug Administration (FDA) should be petitioned to take PPIs off the OTC shelves in our drugstores.)

PPIs should be regulated (max. use: 8 weeks per year) except in extraordinary cases; again FDA action required

PPIs should have warning labels on them (like cigarettes) … that they can cause death: again FDA action required

Removal of PPIs from the market completely? FDA action required

Here’s an idea for an enterprising attorney: A class action law suit against PPI manufacturers by people who developed esophageal cancer while on PPIs. Those patients assumed that the PPI was protecting them and effectively treating their reflux disease, when in fact the opposite was/is the case.

CONCLUSIONS

The proton pump inhibitor (PPI) ship has sailed. The new article (Laudisio 2018) associating PPIs with depression is just one last huge nail in the PPI coffin. In my practice, overwhelmingly dominated by patients with acid reflux, I stopped using PPIs altogether almost five years ago. As troublesome data on the adverse effects of PPIs continue to accumulate, PPIs should be regulated if not simply removed from the market.

REFERENCES

Amin MR, Postma GN, Johnson P, Digges N, Koufman JA. Proton pump inhibitor resistance in the treatment of laryngopharyngeal reflux. Otolaryngol Head Neck Surg. 2001; 125:374–378.

Antoniou T, Macdonald EM, Hollands S, et al. Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ Open. 2015 Apr 2;3(2):E166-71. doi: 10.9778/cmajo.20140074. eCollection 2015 Apr-Jun.

Cicala M, Emerenziani S, Luca MP, et al. Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease. World J Gastroenterol. 2013; 19: 6529–6535. https://doi.org/10.1371/journal.pone.0126432

Hughes D.  Proton Pump Inhibitors and Atrial Fibrillation. Doctoral Thesis, University of Kentucky, 2015.

Hvid-Jensen F, Pedersen L, Funch-Jensen P, Drewes AM. Proton pump inhibitor use may not prevent high-grade dysplasia and oesophageal adenocarcinoma in Barrett’s oesophagus: a nationwide study of 9883 patients. Aliment Pharmacol Ther. 2014 May;39(9):984-91. doi: 10.1111/apt.12693. Epub 2014 Mar 11.

Juurlink DN, DormuthCR, Huang A. et al. Proton Pump Inhibitors and the Risk of Adverse Cardiac Events. PLoS One. 2013; 8(12): e84890. Published online December 27, 2013.

Kresser C. The Dangers of Proton Pump Inhibitors. Kressler Institute for Functional and Evolutionary Medicine. August 2, 2016.

Laudisio A, Antonelli Incalzi R, Gemma A, et al. Use of proton-pump inhibitors is associated with depression: a population-based study. Int Psychogeriatr. 2018 Jan;30:153-159. doi: 10.1017/S1041610217001715. Epub 2017 Sep 13.

Nordqvist C. Proton Pump Inhibitors Should Have Black-box Warnings, Group Tell FDA. Medical News Today, August 24, 2011.

Tabares L. Multiple Functions of the Vesicular Proton Pump in Nerve Terminals. Neuron. DOI: https://doi.org/10.1016/j.neuron.2010.12.012

Wang J, Barbuskaite D, Tozzi M, et al. Proton Pump Inhibitors Inhibit Pancreatic Secretion: Role of Gastric and Non-Gastric H+/K+-ATPases. Plos May 18, 2015.

Xie Y, Bowe B, Li T, et al. Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open.

Zhou B, Huang Y, Li H, et al. Proton-pump inhibitors and risk of fractures: an update meta-analysis. Osteoporos Int. 2016 Jan;27(1):339-47.

 

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