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The Dangers of Proton Pump Inhibitors

Though medications are intended to be beneficial and potentially life-saving, they often come with possible warnings and adverse side effects. With proton pump inhibitors being one of the most frequently used medications globally, the growing dangers of PPIs warrants caution and ongoing evaluation to ensure safety at a population level.

Though medications are intended to be beneficial and potentially life-saving, they often come with possible warnings and adverse side effects. But some cautions are more alarming than others, especially when it comes to long-term use of proton pump inhibitors (PPIs). With proton pump inhibitors being one of the most frequently used medications globally, the growing dangers of PPIs warrants caution and ongoing evaluation to ensure safety at a population level.

What Is a Proton Pump Inhibitor?

Medically known as proton pump inhibitors, PPIs are among one of the most commonly used drugs to treat gastroesophageal reflux disease (GERD), while also healing stomach ulcers or protecting those at risk for one trailing long-term use of anti-inflammatories or aspirin. PPIs work by blocking acid production in the stomach to ultimately calm symptoms, along with treating damage to the lower esophagus caused by acid reflux. Though PPIs regularly work similarly and equally as well, numerous names and brands with potentially varying side effects. But according to Medline Plus, PPI’s side effects are rare, but may include headache, diarrhea, constipation, nausea, or itching. Frequently used PPIs include Prilosec, Nexium, Prevacid, Protonix, and Aciphex and may be purchased over-the-counter or prescribed by a primary care physician.

Dangers of Proton Pump Inhibitors

While PPIs are considered mostly safe with short and interim use, the following dangers have been observed following long-term usage:

• Nutritional Deficiencies
Chronic suppression of stomach acid can compromise the digestive process of a number of nutrients, including calcium, iron, folate, and vitamin B12, subsequently increasing the risk of a number of chronic health conditions. For instance, deficiencies in iron, folate, and vitamin B12 put anemia at risk. Anemia is a condition that develops when blood lacks sufficient red blood cells or hemoglobin, consequently decreasing oxygenated blood flow. Additionally, a calcium deficiency can increase the risk of bone fractures and osteoporosis. But the worry of PPIs does not stop with adulthood, but expands to even the youngest generations. Emerging research suggests PPI use in infants younger than six months of age is associated with a higher risk of bone fractures later in childhood.

• Drug Interactions
The alteration of stomach acid not only impedes on nutrient absorption, but may alter the ability to absorb a number of drugs and medications. These interactions can be quite harmful and interfere with effective clinical treatment, including reducing the effectiveness of clopidogrel (Plavix), a blood thinner shown to prevent stroke, heart attack, and other heart problems.

• Infection
The potency of stomach acid helps combat harmful bacteria trying to target the body, potentially causing undigested food to grow and house bacteria. Harboring bacteria increases the risk of a host of infections, including small intestine bacterial overgrowth (SIBO), Clostridium difficile (C. diff), and pneumonia.

• Organ Damage
Prolonged use of PPIs has shown to lead to organ damage, including of the kidneys and heart. A study published in JAMA Internal Medicine associated people who use PPIs have a 20 to 50 percent higher risk of chronic kidney disease (CKD) compared to nonusers. Additionally, based on a 2015 study, PPI use increases the likelihood of suffering a heart attack compared to those not taking the drugs.

• Stomach Cancer
Though the link between stomach cancer and PPI are noted and concerning, correlations have consistently been in the presence of Helicobacter pylori. But even after removing the bacteria, a very current study published in Gut identified an association between long-term use of the drug and a 2.4 times higher risk of developing stomach cancer.

• Dementia
Despite the uncertainty, yet evolving research, surrounding the prognosis and progression of dementia, research published in JAMA Neurology suggests participants who filled a prescription for a PPI at least once every three months were more than 40 percent more likely to develop dementia than their PPI-free counterparts.

• Premature Death
Although the health risks of common acid refluxes are noteworthy, perhaps the greatest danger is premature death. Researchers from the VA Saint Louis Health Care System, Washington University School of Medicine, and Saint Louis University discovered an association between PPI drug usage and an increased risk early death; the longer the PPI duration, the greater the risk.

Reducing Danger Risk

Most PPIs are confined to four weeks with some brands suggested to not exceed over 16 weeks, though some researchers suggest their use may be prolonged or even inappropriate. So can these danger risks become minimized? Researchers and experts advocate for the following considerations and tips:

• Implement Lifestyle Factors
For treating acid reflux, individuals can implement lifestyle factors to help mitigate associated symptoms. Weight loss and maintenance is considerably encouraged, as research shows even gradually increasing in a healthy BMI range (rising from a BMI of 22 to 24) doubles the risk of acid reflux. Individuals are also encouraged to quit smoking and tobacco use, avoid wearing tight fitting clothing, and identify and avoid trigger foods such as caffeine and chocolate.

• Avoid Over-the-Counter PPIs
Some researchers believe PPIs should not be allowed over-the-counter (OTC) and prescribed via doctor only. Despite the packaged instructions, prescribing PPIs allows tighter control over their use and the opportunity to monitor the patient’s symptoms at a clinical level. Doctors are further encouraged to reevaluate GERD treatment, as doing so can lessen the risk of overprescribing.

• Evaluate the Pros and Cons
If the benefits of the drugs outweigh the risks, individuals should carry-on with PPI use under medical supervision. Though long-term acid reflux may warrant PPIs, individuals should be educated on the risks and made aware of other treatments, including switching to H2 blockers or potentially undergoing a surgical operation.

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