Debunking the Myth: Safety Issues with Proton Pump Inhibitors
Dave Peura, MD, FACP, MACG, AGAF
Professor of medicine, University of Virginia Health Sciences Center
Heartburn occurs when stomach acid refluxes into the esophagus (swallowing tube) which occasionally causes a burning sensation. To help relieve the symptoms of heartburn, many people take prescription and over-the-counter (OTC) medications. The most effective heartburn medications include proton pump inhibitors (PPIs), which are used to treat frequent heartburn, gastroesophageal reflux disease (GERD) and many other conditions caused by stomach acid.
The stomach produces hydrochloric acid after you eat to aid in the digestion of food.
So to an extent, some amount of stomach acid is a good thing. It not only aides in digestion, but also the absorption of certain minerals and vitamins, as well as kills bacteria that are in the food we eat every day.
When PPIs are taken for the treatment of heartburn, they temporarily stop the acid-producing cells from making stomach acid. This allows any irritation in the lining of the esophagus and stomach to heal, and symptoms such as heartburn to improve. People using PPIs for two weeks to treat frequent heartburn will still make enough acid for normal digestion and absorption and to destroy most bacteria.
PPI safety issues have been the subject of a number of news reports. Millions of people around the world have been safely prescribed daily PPIs for months and years at a time. Although a few people using PPIs develop problems, it is uncertain whether these problems are medication-related. Let’s look at these issues more carefully:
Heart Attacks
Most recently the Food and Drug Administration (FDA), the government agency that oversees medication safety, reviewed a concern that PPIs might cause heart attacks. This issue surfaced when the results of a study comparing surgery and PPIs (omeprazole and esomeprazole) for the treatment of GERD suggested that long-term use of medication could increase the risk of heart problems1.
A careful review of this information pointed out that people who took the medication rather than undergoing surgery were older and more likely to have heart problems from the start. It was unlikely that medication caused any additional heart problems. As part of its analysis, the FDA looked at 14 other studies in which people were treated for up to two years with omeprazole. Their final conclusion was that the PPIs, omeprazole and esomeprazole, do not increase the risk of cardiovascular disease.
Hip Fractures
Another widely publicized issue relates to hip fractures and PPI use2. A large study of European patients found that older individuals, primarily women, had a greater risk of breaking a hip if they were prescribed a PPI, especially a high dose, for a long period of time. Although the chance of someone actually breaking a hip is very small-- four out of every 1,000 PPI users fractured a hip compared to 1.8 out of every 1,000 who did not use a PPI.
While it is not supported through literature, the slight increase in fracture rate in people using PPIs might be explained by less calcium absorption in individuals whose acid is suppressed. This could lead to thinner, weaker bones. Literature does show that calcium absorption is completely normal in the total absence of stomach acid. Additionally, most people absorb adequate amounts of calcium from their diet even if they are using PPIs. Stopping the use of PPIs in people who need them is not the way to avoid a broken hip. The best ways to prevent hip fractures is to eat a balanced diet high in calcium, exercise regularly, maintain a healthy weight, avoid excessive alcohol and discuss screening for thin bones (bone density scan) with a health care provider who might recommend calcium supplements and bone strengthening medications if appropriate.
Nutrient Absorption
Iron and vitamin B12 are two important nutrients for healthy blood and nerve function, and stomach acid improves absorption of both from the foods you eat. Most people can absorb enough of these nutrients even when acid production is lowered by PPIs. In rare cases iron and vitamin B12 levels can drop slightly, but generally not enough to cause any difficulty.
A well-balanced diet alone, or in combination with a once-daily vitamin nutrient supplement, is sufficient to prevent any problems with nutrient absorption. Anyone who requires long-term PPI treatment should discuss any concerns he or she might have about nutrient absorption with their health care provider.
Bacteria
Stomach acid is important to reduce the amount of bacteria entering the upper gastrointestinal tract from ingested food and drink. People who take acid-suppressing medications, like PPIs, may be slightly more susceptible to food- and water-borne infections3. Whether or not people are using acid- suppressing medication, it is a good practice to make sure that fruits and vegetables are carefully washed and meat and poultry adequately cooked before eating to avoid gastroenteritis. They should also be careful when traveling, especially to less developed areas of the world, where drinking water and food might not be completely clean, and sanitary conditions might be less than ideal.
Antibiotics
Strong antibiotics kill good bacteria as well as bad ones. If good bacteria in the intestine are destroyed, sometimes bad bacteria called Clostridium difficile take over and cause severe diarrhea. This occurs much more frequently in hospitalized patients. Although Clostridium difficile infection does occur outside the hospital, it is much less common. Recent reports suggest that the risk of developing Clostridium difficile infection may be slightly greater in people receiving PPIs3. However, stopping PPIs in patients who need them is not likely to make any significant impact on Clostridium difficle infection. The best approach to preventing the infection is to avoid using strong antibiotics unless absolutely necessary, and to use soap and hot water to wash hands to avoid the spread of infection in the hospital setting.
Pneumonia
Pneumonia can be a serious problem, particularly in people who have poor health. A well publicized study suggested that people using acid suppressive medication, like PPIs, might be more likely to develop pneumonia4.
A problem with this study was that the people prescribed PPIs were sicker than those not using the medication. The PPI users were more likely to have lung disease, heart disease, cancer and diabetes. All these conditions increase risk for pneumonia and, by themselves, could explain the findings. Another study problem was that pneumonia was diagnosed in many instances without relying on a chest X-ray. Despite this, the incidence of pneumonia was still quite low (less than 1 percent) whether or not people were using PPIs. Therefore, stopping PPIs when they are needed to manage acid-related conditions may not prevent many cases of pneumonia but would make symptoms such as heartburn, worse. A better strategy to prevent lung infections would be to get a flu shot and pneumonia vaccination every year, and stop smoking.
Proton-Pump Inhibitors in the Long-Term
PPIs are very effective in managing acid-related conditions. They are generally very safe when used short-term for the treatment of frequent heartburn or prescribed long-term by a health care provider in situations where chronic acid-suppression is appropriate. PPI safety is supported by numbers; millions world-wide have used these medications without difficulty. PPI safety has also passed the test of time; these medications have been widely available for almost two decades and only rare safety issues have been raised. It appears for most individuals the benefits of PPIs (their ability to control heartburn, treat GERD, and manage ulcers) outweigh any potential risk. However, if you have any concerns about PPIs safety, ask your health care provider for their opinion.
References:
1. http://www.fda.gov/cder/drug/early_comm/omeprazole_esomeprazole.htm.
2. Yang et al JAMA 2006; 296:2947.
3. Leonard Am J gastro 2007 102: 2047.
4. Laheij JAMA 2004;292: 1955.
