The Side Effects of Nexium After Years of Use

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If taken for long periods of time, proton pump inhibitors like Nexium may lead to nutrient deficiencies, fractures, excessive bacteria in the small intestine and Clostridium difficile infection.

Esomeprazole, sold under the brand name Nexium, belongs to a group of drugs called proton-pump inhibitors (PPIs). These medications reduce the production of stomach acid, which is useful for treating acid-related disorders, such as gastroesophageal reflux disease (GERD) and peptic ulcers.

Although stomach acid worsens these conditions, it also has some beneficial effects. Stomach acid helps your body break down food, absorb nutrients and some medications, and kill bacteria that enter your digestive tract. PPIs are generally very safe, but if taken for a prolonged time, they may lead to nutrient deficiencies, fractures, excessive bacteria in the small intestine and Clostridium difficile infection.

Nutrient Deficiencies

Long-term use of Nexium may cause deficiencies of some nutrients. Absorption of vitamin B12, iron and calcium is aided by stomach acid, so reducing acid production may be expected to interfere with their absorption.

Studies in people taking PPIs have generally found that PPI use can reduce vitamin B12 and iron absorption, usually by just a small amount. The effects on calcium absorption are less clear, with some studies reporting decreased absorption with PPIs and other studies reporting no effect.

Stomach acid generally does not influence the absorption of magnesium, but long-term use of Nexium may interfere with magnesium absorption through other mechanisms. A study in the June 2015 issue of “Renal Failure” compiled the results of several previous studies and found that low magnesium levels were more common in PPI users than in PPI non-users.

The Food and Drug Administration (FDA) has issued a warning about possible low magnesium levels in people taking PPIs for a prolonged time — generally a year or longer — and recommended that periodic blood tests be considered to check magnesium levels in these individuals.

Fractures and Osteoporosis

Long-term PPI use may increase the possibility of developing osteoporosis — a condition characterized by weak bones — and fractures. But this is a complicated issue. Osteoporosis has been attributed to decreased calcium absorption, although it is controversial whether PPIs actually reduce absorption of this mineral.

Initial studies reported that people taking PPIs were more likely to develop fractures, which were assumed to be caused by osteoporosis. This led to a warning from the FDA indicating that PPI use can increase the risk of osteoporosis-related fractures, especially in people taking PPIs for more than 1 year.

A review article published in the February 2018 issue of “Mayo Clinic Proceedings” indicated that the majority of recent studies also reported an increased risk of fractures with PPIs. But the reason is unclear because these studies have found no increased likelihood of osteoporosis with long-term PPI use. At present, no medical societies recommend routine testing for osteoporosis or consuming additional calcium while taking PPIs.

Small Intestinal Bacterial Overgrowth

As stomach acid helps kill bacteria, reducing acidity with Nexium allows more bacteria to survive the stomach and enter the next part of the digestive tract. This may lead to excessive growth of bacteria in the small intestine, called small intestinal bacterial overgrowth (SIBO).

A study published in the January 2018 issue of “Journal of Gastroenterology” compiled the results of several previous studies. It found that the likelihood of developing SIBO was almost 2 times higher in people taking PPIs than in people not taking PPIs. SIBO can produce abdominal bloating, abdominal pain, diarrhea and weight loss.

Clostridium difficile Infection

Long-term use of PPIs may also increase the chances of developing C. difficile infection. This bacterium primarily affects the large intestine, producing inflammation known as colitis. Stomach acid normally destroys the active form of C. difficile, and PPIs interfere with this protective effect.

In the July 2012 issue of “American Journal of Gastroenterology,” a study combining the results of many previous studies reported that C. difficile infection was almost 2 times more likely in PPI users than in PPI non-users. C. difficile causes diarrhea, which can be severe and potentially life-threatening.

Kidney Disease and Dementia

According to a February 2018 review article from “Mayo Clinic Proceedings,” some studies suggest that long-term PPI use may increase the likelihood of kidney disease and dementia. However, not enough studies have been done yet to definitely state that these are true side effects of PPIs.

The article suggests that PPIs may act directly on the kidneys to produce inflammation and kidney damage. It also indicates that animal studies have shown accumulation of amyloid-beta molecules in the brain with PPI use, similar to the accumulation found in Alzheimer disease. Dementia may also be caused by vitamin B12 deficiency, when severe.

Warnings and Precautions

Consult with your doctor before taking Nexium beyond 2 weeks. If your doctor approves, ask how often you should return for follow-up visits to assess whether continued Nexium use is necessary and to determine whether you are developing any side effects.

Also ask your doctor about the symptoms of nutrient deficiency you should watch out for. Consult with your doctor before taking any new supplements or medicines, as all PPIs can interact with a number of medications and supplements.

See your doctor if you have severe diarrhea or symptoms suggestive of SIBO. Seek immediate medical attention if you have chest pain that is different from your GERD pain, especially if it extends into your neck or left arm or is accompanied by shortness of breath or lightheadedness. This may indicate a serious condition, such as a heart attack.

Reviewed and revised by Mary D. Daley, M.D.