<h3>Proton Pump Inhibitors</h3>
<p>Proton Pump Inhibitors (PPIs) are the mainstay of treatment for gastro-oesophageal reflux. They are one of the most prescribed group of drugs in the western world. A study published in 2020 that evaluated their use in the UK over 15 years found that 20% of adults had been prescribed these powerful drugs and in most western countries 5-10% of the adult population take them regularly. Worldwide annual sales amount to nearly $15billion. First line treatment of anyone complaining of symptoms possibly caused by reflux in the absence of alarm symptoms suggesting cancer is PPIs, and often at increasing doses even if they don&rsquo;t initially help. And yet while PPIs are undoubtedly effective for many people they are not without problems and increasingly doctors and patients are deciding they&rsquo;d prefer not to prescribe or take them. So, what are the facts?</p>
<h4>What are Proton Pump Inhibitors?</h4>
<p>PPIs are very powerful antacid drugs. Taken twice a day they virtually halt all acid production from the stomach. Since acid can be the cause of symptoms and indeed injury to the lining of the stomach and oesophagus, by preventing its production PPIs are very useful in patients suffering with gastro-oesophageal disease, stomach or duodenal ulcers as well as preventing problems for instance when taking other drugs such as anti-inflammatory pain killers.</p>
<h4>How effective are PPIs?</h4>
<p>PPIs are not the universal panacea that some doctors would have you believe. The symptomatic response depends on what is being treated. Studies have shown that when used to treat inflammation of the oesophagus caused by reflux, called oesophagitis, PPIs are extremely effective; in 80-90% the oesophagus will heal and symptoms of heartburn and chest pain resolve. As inflammation gets more severe, reflecting more advanced reflux disease, response diminishes but many people will still enjoy reasonable symptom control even with high grades of oesophagitis.</p>
<p>However, in other situations the evidence is that PPIs are less effective. In patients suffering with regurgitation, perhaps only 10-20% will experience symptom resolution. And when used to treat laryngo-pharyngeal (LPR) symptoms, 70-80% of patients will find that they don&rsquo;t help significantly. Overall, about 20-30% of patients treated with PPIs will find that their symptoms either do not respond or do so only incompletely and that they continue to be troubled by them.</p>
<h4>Why is this?</h4>
<p>Firstly, when the Lower Oesophageal Valve (LOS) fails to the extent that stomach contents regurgitate up the oesophagus and sometimes to the throat and mouth, PPIs can reduce the acid content but not the volume of the refluxate. So, patients will often observe that their heartburn is improved but that they still experience troubling regurgitation. And in many patients with reflux, especially LPR it&rsquo;s thought that other components of the stomach contents including bile and the enzyme Pepsin which is produced in the stomach are partly responsible for irritating the throat and mouth and these remain biologically active even in nearly neutral acid environments; consequently, preventing acid production doesn&rsquo;t help prevent symptoms when this is the case. And of course, sometimes patients have conditions causing symptoms which aren&rsquo;t primarily caused by excessive reflux and so often respond incompletely if at all to PPIs. These include so-called reflux hypersensitivity, functional heartburn and eosinophilic oesophagitis as well as non-oesophageal disease including gastritis, ulcers and gallbladder disease all of which can cause symptoms similar that can be attributed to reflux.</p>
<h4>The problems with PPIs</h4>
<p><strong>Side effects</strong>&nbsp;It&rsquo;s always been recognised that some people just can&rsquo;t take PPIs as they experience side effects. Usually, if one type of PPI causes this type of problem, they all will. These can include aching joints, dizziness, rashes, depression and gastrointestinal symptoms including bloating, pain, constipation and diarrhoea (see below).</p>
<p><strong>Serious associated conditions</strong>&nbsp;However, in recent years there have been a series of scientific studies that have associations PPIs with other serious health conditions.</p>
<p>These include:</p>
<ul>
<li>Osteoporosis</li>
<li>Bone fractures</li>
<li>Liver disease</li>
<li>Dementia</li>
<li>Renal disease</li>
<li>Cardiac disease</li>
<li>Stomach cancer</li>
<li>Drug interactions</li>
<li>Vitamin and mineral deficiencies</li>
</ul>
<p>Many of these studies have shown statistical associations in populations taking PPIs. And because PPIs can potentially influence the functioning of virtually every cell in the body, not just acid producing gastric parietal cells, there are plausible physiological mechanisms by which they may influence disease beyond the gut. However, this doesn&rsquo;t prove causation and in most cases the existing evidence for risk is either not strong or conflicting. But clearly these reports do raise concern and current guidance advises doctors to prescribe PPIs only when necessary and if possible, only in the short term. At the very least anyone considering taking PPIs long-term should ensure they&rsquo;re taking them for the right reasons and be made aware of the potential risks and alternative treatment options.</p>
<p>What we do know from published studies with reasonable certainty is that taking PPIs long-term are associated with an approximately 45% increased chance of developing stomach cancer compared with less powerful antacid H2- blockers. There is a 65% chance of developing the serious gastro-intestinal infection&nbsp;<em>c. difficle</em>as well as other infections such as campylobacter and respiratory infections in some specific groups of patients. In some people low levels of calcium, folate, vitamin B12 and magnesium have all been reported. This last problem, although rare can be life-threatening. Low magnesium can cause muscle weakness, dizziness, seizures, mental illness, ataxia, neurological problems, tetany and cardiac arrhythmias. In anyone taking PPIs who develop these symptoms this problem should be considered and the drugs stopped while magnesium levels in the blood are measured.</p>

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