The dangers of proton pump inhibitors
Proton pump inhibitors (PPIs) rank among the top ten prescribed classes of drugs and are commonly used to treat acid reflux, indigestion, and peptic ulcers. Although generally assumed to be safe, recent studies have shown that they have numerous side effects, from an altered gut environment and impaired nutrient absorption, to an increased risk for cardiovascular events, kidney disease, and dementia.
PPIs have become one of the most commonly prescribed classes of drugs in the industrialised world, despite increasingly frequent warnings by researchers about potential risks and complications.
A 2010 study found that of 946 patients receiving PPI therapy in a hospital setting, only 35% were prescribed PPIs for an appropriate upper gastrointestinal problem (1). In 2014, Americans filled more than 170 million prescriptions for acid blockers, falling only behind statins in total cost expenditure worldwide. PPIs are the most common of the acid blockers. They go by a variety of names but typically end in the suffix “-prazole” (omeprazole, pantoprazole, esomeprazole, etc.).
The many roles of proton pumps in the body
Before we get into the potential harmful effects associated with PPIs, it’s important to understand what they do in the body. PPIs are inhibitors of proton pumps, specifically the proton/potassium pump of parietal cells in the stomach. The theory is that heartburn is caused by excess production of stomach acid by these cells, so inhibiting this proton pump will reduce the acidity of the stomach and prevent the burning sensation of acid reflux or the formation of peptic ulcers. However, proton pumps aren’t limited to the stomach; they are present in just about every cell in your body. All of your cells, with the exception of red blood cells, have mitochondria that allow your body to metabolise carbohydrates and fat to produce energy. They do this by pumping protons across the membrane to generate a source of electric potential that can be harnessed to form ATP, the body’s main storage form of energy. Without an efficient proton pumping system, the body must rely on anaerobic systems for energy production, leading to rapid fatigue.
PPIs alter the gut
The composition of microbes that inhabit your gut is incredibly sensitive to changes in the local environment. pH, a measure of the acidity of an environment, is an important facet of gut health and a particularly potent regulator of microbial communities (2). PPI use reduces the amount of acid produced in the stomach, and ultimately the amount of stomach acid that reaches the gut. This causes a significant shift in the pH of the intestines. Indeed, several recent studies have shown that PPI alters the gut microbiota by reducing its overall diversity (3,4). Opportunistic pathogens, including enterococcus, streptococcus, staphylococcus, and e. coli, tended to be more prevalent in the guts of PPI users.
As stomach pH becomes less acidic, many ingested microorganisms that would normally be destroyed are able to make their way into the gut (5). Imhann and colleagues found that oral bacteria, such as the genus rothia, were over-represented in the gut microbiota of PPI users (6). Those who used acid blockers also had an increased chance of acquiring clostridium difficile, campylobacter, salmonella, shigella, listeria, and community-acquired pneumonia than those using other medications (7,8).
PPIs impair nutrient absorption
Another consequence of long term PPI use is impaired nutrient absorption. Stomach acid is essential for the absorption of many macro- and micronutrients. PPI users have been shown to have an increased risk of vitamin and mineral deficiencies, including vitamin B12, vitamin C, calcium, iron, and magnesium (9,10). Achlorhydria (a lack of stomach acid) and atrophic gastritis (stomach inflammation) allow for the overgrowth of bacteria, which compete with the host for consumption of micronutrients like vitamin B12 (11).
PPIs increase the risk of cardiovascular events
Several recent studies have also shed light on PPIs and the cardiovascular system. PPI users have been shown to have a significantly greater risk of heart attack than those on other antacid medication (12,13) . PPIs also reduce production of nitric oxide, a natural substance that promotes the dilation of blood vessels and improves blood flow (14).
PPIs harm the kidneys
The kidneys are also affected by PPIs. A study published in 2016 compared patients using PPIs to patients using H2 blockers, another common antacid drug. They showed that over the course of five years, those in the PPI group were 28% more likely to develop chronic kidney disease and 96% more likely to develop end stage renal disease (15).
PPIs negatively affect cognitive function
PPIs also impair cognitive function. A 2016 study found that regular PPI users had a 44% increased risk of dementia compared with those not using the drugs (16). A different study published in 2015 that assessed cognitive function in PPI users versus controls found statistically significant impairment in visual memory, attention, executive function, and working and planning function among PPI users (17).
PPI withdrawal can lead to rebound reflux
Your body is acutely sensitive changes in physiology and is constantly trying to maintain a stable equilibrium, termed homeostasis. In the case of PPIs, when it senses reduced stomach acid production, your body produces the hormone gastrin to try to compensate. Gastrin normally stimulates gastric (stomach) acid production. Excess gastrin has, in turn, been shown to lead to an expansion of enterochromaffin-like cells (ECLs) (18). ECLs are found in the mucosa of the stomach in close proximity to parietal cells. A greater number of ECLs results in a greater amount of ECL hormones released that can interact with parietal cells. Parietal cells, as you may recall, are the cells responsible for stomach acid production via proton pumps. These parietal cells undergo hypertrophy, or an expansion in the size of each cell leading to more stomach acid (19).