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Are you constantly experiencing  the following symptoms which are impacting on your quality of life?

  • A horrible burning or pressure-like sensation in the middle of the chest
  • Heartburn that comes on after eating or lying down
  • A sore throat, due to rising stomach acid, making swallowing difficult
  • A feeling of a lump in the throat
  • Hoarseness and laryngitis
  • A chronic unexplained dry cough, especially at night, and/or
  • Bad breath

Is this you?  Have you been terrified that you were experiencing a heart attack, only to find out that the pain was related to a digestive issue? And have you found unbelievable relief from over-the-counter acid-suppressing medication or prescribed proton pump inhibitors (PPIs) e.g. Nexium?  Do you find that when you stop taking them the symptoms return and are perhaps even more severe? Is it correct to assume that you have been taking them for a long time, perhaps even decades, because you are too scared to stop? What are you suffering from and why do these medicines appear so effective?

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Your heartburn symptoms are the result of a reflux of acid from your stomach backing up into your oesophagus (the tube connecting your mouth to your stomach).  If these symptoms happen often, you could be suffering from a condition known as Gastroesophageal Reflux Disease or GORD (GERD in the US). The reason for this burning sensation is usually due to the relaxation of the lower oesophageal sphincter (LES), a valve located at the stomach end of the oesophagus, which prevents food and acid going the wrong way in your digestive system. This valve plays a very critical role as it is protects the vulnerable tissue which lines the oesophagus from the potential damage caused by the gastric acid. So it makes logical sense that if one suffers from too much acid reflux, in conjunction with lowered LES pressure and a lack of local protection, an effective medication would be one that lowers this acid secretion. PPIs are the most potent inhibitors of gastric acid secretion. While there may be more diseases that rely on PPIs, such as peptic ulcers, GORD is probably the most frequent indication for prescribing this medication. Very often, for patients with symptoms typical of GORD, treatment with PPIs and the subsequent relief, serve to support the diagnosis, and is usually started as a first step (Al-Sohaily, 2008).   Its favourable safety profile is another reason for its popularity, i.e. it is well tolerated, with an adverse event rate of between 1-3%, with only such mild-moderate symptoms as abdominal pain, flatulence, diarrhoea, constipation and nausea/vomiting (Al-Sohaily, 2008).    Indeed, each year, it is estimated that over 113 million PPI prescriptions are filled globally, making it the most commonly prescribed classes of medication worldwide. This, together with over-the-counter use, accounts for the global sales of over $13 billion (Shah et al., 2015).  Here in Australia, PPIs are in the top 10 of prescribed drugs, in regards to prescription counts and cost (Al-Sohaily, 2008).  Why do we need gastric acid?  Is it the enemy or is it our friend? Hydrochloric acid (HCl), which is the primary gastric acid secreted by your parietal cells in the stomach, is responsible for:

  • Regulating the pH (acid/base balance) of the stomach;
  • Sterilising the food we eat, and in so doing, preventing harmful bacteria from entering the gastrointestinal system;
  • Triggering the release of enzymes such as pepsin, which is essential for digesting protein;
  • Triggering the release of alkaline bicarbonate into the first part of the small intestine, and in so doing, activating digestive enzymes and the further breakdown of food particles;
  • The adequate absorption of certain minerals and vitamins, such as iron, magnesium, zinc, and vitamin B12.  Of these minerals, zinc is involved in HCl production.

Accordingly, when HCl levels are reduced, there can be a reduction in digestion efficiency, and an increase in bacterial overgrowth and infections, as well as an inability to utilise several essential nutrients and minerals vital for metabolic processes, which can in turn further reduce stomach acid production and compromise health. In other words, gastric acid IS OUR FRIEND! Consequently, as PPIs lower gastric acid, there is now a growing concern for the potential adverse effects for its long-term use.  interestingly, when PPIs came on the market, they were ONLY intended for SHORT-TERM intake of approximately 4-6 weeks.  Yet, as we discussed earlier, many individuals have been taking them for extended periods.  In fact, there is an increased tendency for health care providers to prescribe PPIs for prolonged, sometimes lifetime, use, often in the absence of appropriate indications.  So are PPIs safe when taken for long durations? Despite there not being sufficient studies assessing conclusively the safety of long-term use, there is still mounting evidence that long-term PPI intake may have the potential of causing many serious health conditions.  Among the recent human and animal studies conducted, it has been shown that long-term PPI use may possibly cause:

  • An increased frequency of vitamin B12 deficiency, especially in elderly individuals (Sheen & Triadafilopoulos, 2011).  This vitamin is an essential cofactor for the synthesis of DNA (our genetic material), protein and blood cells, and is involved in cellular energy production and the myelination (a form of insulation) of nerve and brain fibres.  It is therefore not surprising that a deficiency can lead to anaemia and demyelinating neurologic disease causing muscle weakness and gait disorders, as well as visual disturbances and cognitive decline.
  • A 5 times greater risk of injurious falls or fracture-related hospitilisation for elderly patients (Lewis et al., 2014).
  • Low-grade inflammation, obesity, and the increased risk of some cancers, such as colorectal, neuroendocrine tumours (NETs), liver, pancreatic, or small bowel cancers (Lundell et al., 2016). One mechanism thought to explain why PPIs might increase tumour risk, is via the hormone gastrin, which is responsible for increasing gastric acid production and cell growth. When gastric acid is suppressed, the altered stomach pH stimulates its synthesis, in order to promote gastric acid production.  It has been hypothesized that this increased gastrin secretion might also elevate its pro-growth effects and the potential for increased cancer risk in different organs (Schneider,  Kolitsopoulos & Corley, 2016).
  • Increased risk of gut infections, (particularly in the elderly who already have lowered synthesis and secretion of gastric acid).  A logical explanation for this occurring could be due to the alteration of the stomach pH, making it less acidic and more basic. This causes a reduced destruction of the microbes entering the stomach, allowing more of them to pass unscathed into the small and large intestines. Among these infections are those caused by the Campylobacter species and hospital-acquired  Clostridium difficile (the latter being stongly associated with high doses of PPI therapy), (Al-Sohaily, 2008, Wei et al., 2017, Clooney et al., 2016).   Indeed,  one Australian study, of more than 38,000 adults over age 45, conducted in 2016, found that PPI use increased the risk of hospitalization for infectious gastroenteritis  (Chen et al., 2016).  Furthermore, three meta-analyses showed a 27-39% increased risk of pneumonia with short-term use (Wilhelm, Rjater & Kale-Pradhan, 2013).

 

  • Chronic liver disease. There have been associations between PPI use, encephalopathy and higher end-stage liver disease in patients with cirrhosis (Cole, Pennycook & Hayes, 2016).
  • An increased prevalence of SIBO (Small Intestinal Bacterial Overgrowth) (Pica et al., 2011). The reason for this condition occurring could be that the reduction in acid allows an increased number of bacteria to enter the small intestine.  If these bacteria are not adequately eliminated from the small intestine they will feed off the undigested food particles and multiply, causing an array of symptoms. One very common symptom is bloating caused by gas generated by the bacterial fermentation of carbohydrates. This excess gas increases the intra-abdominal pressure, forcing the LES to open, and the symptom of heartburn seen n GORD. The intake of PPIs to suppress the heartburn further decreases the acid, increasing SIBO and GORD symptoms and the need for more medication, creating a vicious cycle. Consequently, it appears that GORD, as well as SIBO, might actually be the result of too LITTLE stomach acid rather than too MUCH!!
  •  Thrombocytopenia, iron deficiency, rhabdomyolysis and acute interstitial nephritis have also been reported (Wilhelm, Rjater & Kale-Pradhan, 2013).
  • An association with the risk of heart attacks and first-time strokes (Shah et all., 2015; Sehested et al, 2016; Lazarus et al., 2016).
  • Asmtha. A 2017 systematic review showed a 1.3 times greater risk of developing asthma and allergies in children born to mothers who took acid-suppressing medications during pregancy (16). This is of concern considering that heartburn is a common symptom in pregnancy due to hormonal changes and increasing abdominal pressure from the growing fetus.   Furthermore, as acid-suppressing medications have a favourable safety profile since they do not affect fetal development, the pregnant woman might be tempted to take it more often (Devine et al., 2016).

Conclusion: Please do not get me wrong.  PPIs have their place in medicine, and can actually be necessary for certain conditions such as Barrett’s oesophagitis, and scleroderma.  However, in light of the above findings, it appears that while acid-suppression therapy is often considered relatively free from adverse effects, recent studies suggests that there are significant adverse non-infective and infective consequences of their long-term use.   Accordingly, would it not be more beneficial, and make more sense, to uncover the underlying reasons for the heartburn in GORD, such as SIBO, nutrient deficiencies, low stomach acid, stress, constipation, or increased weight, and treat the cause, rather than solely treating the symptoms with  medications that has not been adequately proven to be safe long-term?

If you feel that this blog has touched a chord with you, and you would like to find out why you are experiencing these symptoms, please do not hesitate to contact me.  Also, if you have still not read my other blogs, please click here. Furthermore, I have a facebook page that not only shares some of my blogs and videos but provides valuable health information.  If you gain insight from some of the contributions, don’t forget to click on the “Like” button.ould like to read them, then click here.

References:

Al-Sohaily, S. (2008). Long-term management of patients taking proton pump inhibitors. Issues, 1.  Retrieved from: https://www.nps.org.au/australian-prescriber/articles/long-term-management-of-patients-taking-proton-pump-inhibitors

Chen, Y., Liu, B., Glass, K., Du, W., Banks, E., & Kirk, M. (2016). Use of proton pump inhibitors and the risk of hospitalization for infectious gastroenteritis. PloS one, 11(12), e0168618.

Clooney, A. G., Bernstein, C. N., Leslie, W. D., Vagianos, K., Sargent, M., Laserna‐Mendieta, E. J., … & Targownik, L. E. (2016). A comparison of the gut microbiome between long‐term users and non‐users of proton pump inhibitors. Alimentary pharmacology & therapeutics, 43(9), 974-984.

Cole, H. L., Pennycook, S., & Hayes, P. C. (2016). The impact of proton pump inhibitor therapy on patients with liver disease. Alimentary pharmacology & therapeutics, 44(11-12), 1213-1223.

D., Pica, L., Rocco, A., De Giorgi, F., Cuomo, R., Sarnelli, G., … & Nardone, G. (2011). Compare effects of long‐term PPI treatment on producing bowel symptoms and SIBO. European journal of clinical investigation, 41(4), 380-386.

Devine, R. E., McCleary, N., Sheikh, A., & Nwaru, B. I. (2017). Acid-suppressive medications during pregnancy and risk of asthma and allergy in children: A systematic review and meta-analysis. Journal of Allergy and Clinical Immunology, 139(6), 1985-1988.

Lazarus, B., Chen, Y., Wilson, F. P., Sang, Y., Chang, A. R., Coresh, J., & Grams, M. E. (2016). Proton pump inhibitor use and the risk of chronic kidney disease. JAMA internal medicine, 176(2), 238-246.

Lewis, J. R., Barre, D., Zhu, K., Ivey, K. L., Lim, E. E., Hughes, J., & Prince, R. L. (2014). Lewis, J. R., Barre, D., Zhu, K., Ivey, K. L., Lim, E. E., Hughes, J., & Prince, R. L. (2014). Long‐Term Proton Pump Inhibitor Therapy and Falls and Fractures in Elderly Women: A Prospective Cohort Study. Journal of bone and Mineral Research, 29(11), 2489-2497.  Lundell, L., Vieth, M., Gibson, F., Nagy, P., & Kahrilas, P. J. (2015).

Schneider, J. L., Kolitsopoulos, F., & Corley, D. A. (2016).   Lundell, L., Vieth, M., Gibson, F., Nagy, P., & Kahrilas, P. J. (2015). Systematic review: the effects of long‐term proton pump inhibitor use on serum gastrin levels and gastric histology. Alimentary pharmacology & therapeutics, 42(6), 649-663.

Pica, L., Rocco, A., De Giorgi, F., Cuomo, R., Sarnelli, G., … & Nardone, G. (2011). Effects of long‐term PPI treatment on producing bowel symptoms and SIBO. European journal of clinical investigation, 41(4), 380-386.)

Schneider, J. L., Kolitsopoulos, F., & Corley, D. A. (2016). Risk of gastric cancer, gastrointestinal cancers and other cancers: a comparison of treatment with pantoprazole and other proton pump inhibitors. Alimentary pharmacology & therapeutics, 43(1), 73-82.

Sehested, T. S., Gerds, T. A., Fosbøl, E. L., Hansen, P. W., Charlot, M. G., Carlson, N., … & Gislason, G. H. (2017). Long‐term use of proton pump inhibitors, dose–response relationship and associated risk of ischemic stroke and myocardial infarction. Journal of Internal Medicine.

Shah, N. H., LePendu, P., Bauer-Mehren, A., Ghebremariam, Y. T., Iyer, S. V., Marcus, J., … & Leeper, N. J. (2015). Proton pump inhibitor usage and the risk of myocardial infarction in the general population. PLoS One, 10(6), e0124653.

Sheen & Triadafilopoulos, 2011).  Sheen, E., & Triadafilopoulos, G. (2011). Adverse effects of long-term proton pump inhibitor therapy. Digestive diseases and sciences, 56(4), 931-950.

Wei, L., Ratnayake, L., Phillips, G., McGuigan, C. C., Morant, S. V., Flynn, R. W., … & MacDonald, T. M. (2017). Acid‐suppression medications and bacterial gastroenteritis: a population‐based cohort study. British journal of clinical pharmacology, 83(6), 1298-1308.

Wilhelm, S. M., Rjater, R. G., & Kale-Pradhan, P. B. (2013). Perils and pitfalls of long-term effects of proton pump inhibitors. Expert review of clinical pharmacology, 6(4), 443-451.

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