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Sep 6, 2022

Gut Health

PPIs: Are the Long-Term Risks Worth It?

What is a Proton Pump Inhibitor (PPI)?

Proton pump inhibitors, or “PPIs”, are a type of medication used for several issues in your digestive system. They are commonly prescribed to treat gastroesophageal reflux disease (GERD), erosive esophagitis, and ulcers.

  • GERD is a chronic condition where the acidic contents of your stomach frequently come back up into your throat, causing a burning feeling. This can be very uncomfortable and, when left untreated, can lead to long-term damage to your throat.
  • Erosive Esophagitis is the severe form of GERD that results from long-term damage to your esophagus (your throat) from prolonged periods of too much acid. This can be painful and it only gets worse the longer it is left untreated.
  • Ulcers are another serious condition that PPIs are prescribed, often along with 2-3 antibiotics, to treat. Ulcers are sores in your digestive system that can be very painful and dangerous. They have a number of different possible causes, but the acidity of the acid in your stomach can burn those sores and stop them from healing, which can lead to further complications.

How PPIs Work

How PPIs Work

Stomach acid is produced by a ‘pump’ in your stomach. PPIs work by stopping this pump and this results in your body producing less stomach acid. In the case of erosive esophagitis and ulcers, this gives your body a chance to heal from the damage that has occurred from excess stomach acid. It should also help alleviate symptoms such as heartburn.

Some common examples of PPIs include:
omeprazole, pantoprazole, esomeprazole

What are the Risks of PPIs?

Even though these medications are incredibly effective and important, like most medications, they have some risks. Along with the typical side effects, such as nausea, diarrhea, and headache, PPIs also have additional risks when used long-term. Like typical side effects, not everyone who is on long-term PPIs develops these complications, but it is still worth knowing about the risks.

Some of the most common and best studied risks include the following:

  • Lack of absorption of vitamins and minerals, such as vitamins B12 and C, calcium, magnesium, and iron
  • An infection from the bacteria clostridium difficile
  • Increased risk of stomach cancer*
  • Increased risk of urinary tract infections and/or kidney disease*
  • Dementia*
  • Pneumonia*
  • Stroke*
*Some of these risks do not have significant data to support the link between taking PPIs long-term and the actual chance of developing any of these conditions. So, while it’s still important to be aware of the possibility of these risks, it’s not definite that they are a direct result of long-term PPI use.

How Long is Too Long?

This is different for everyone, but in general “long-term” use typically describes the use of PPIs for more than 8 consecutive weeks. However, some of these conditions are only noted to start occurring after years of being on PPIs, so it’s different for everyone. Even though it may take longer for negative effects to occur, it’s still recommended to speak with your healthcare provider after 8 weeks about the possible risks versus benefits of staying on PPIs longer-term.

Why Are There Risks?

The long-term risks are caused by the decrease in acid discussed before. Even though the less acidic stomach environment helps several conditions, there is also a reason the stomach was that acidic in the first place. Taking away this acidity fixes some problems but can cause new ones.

Vitamin and Mineral Deficiencies

One reason that we require acidity in our stomach is for the absorption of certain vitamins and minerals. Certain vitamins and minerals need an acidic environment to be released from food and/or absorbed further along in the digestive system. Long-term use of PPIs decreases the overall acidity of your stomach acid, and therefore can interfere with the release and/or absorption of these vitamins and minerals. This can lead to deficiencies, which can cause problems with your bone strength, immune system, and cardiovascular system. Vitamin B12, calcium, and magnesium have all been found to have decreased levels in the bodies of some people on long-term PPIs.

Vitamin B12

The acid in your stomach helps vitamin B12 get released from your food and allows it to absorb into your body. With the decrease in acidity from chronic PPI use, there is both less release of B12 and less absorbed. We have a storage of B12 in our bodies, so for a short period it’s ok to have decreased intake of this vitamin. However, after a longer period, these stores run out and you start to get low on vitamin B12.

A vitamin b12 deficiency can be serious, since you need this vitamin to make new red blood cells which carry oxygen around our body. With fewer new red blood cells, you may feel tired, short of breath, and start getting headaches.

A simple solution to this is to increase the amount of vitamin B12 you consume. With more B12 coming into your body there is more getting released from the food and absorbed. This can be done with foods and/or with B12 supplements. Foods that have a lot of B12 include animal products such as fish and shellfish, red meat, dairy, poultry, and eggs. From non-animal sources, you can also get B12 in foods that have been fortified with it. When you have a B12 deficiency, it usually means you are not getting enough from food sources, so it is recommended to speak with your healthcare provider about starting a vitamin B12 supplement.


Calcium is another very important component of many foods that we eat. It can be found in dairy products such as milk, cheese, and yogurt, but also in non-animal products such as dark leafy greens and almonds.

Calcium requires the acidity of the stomach acid to be released from food into a form that can be absorbed. It is very important for the health of your bones as well as your muscles and heart. Without enough calcium absorbed, you can develop a calcium deficiency. In the short term, you may feel tingling sensations, muscle aches, or muscle twitches. If left untreated, long-term calcium deficiency can lead to osteoporosis (fragile bones), eye damage, and an irregular heartbeat.

Calcium deficiencies also require the relatively simple solution of increasing your dietary intake of calcium rich foods as well as potentially starting a calcium supplement following advice from your healthcare provider. Calcium is a little bit different though, and requires a vitamin, vitamin D, to get properly absorbed. So, when taking calcium supplements, it is usually recommended to also start a vitamin D supplement.


Magnesium is a mineral that requires the acidity from stomach acid to get absorbed into your blood. Magnesium’s importance may be less well known, but it’s just as essential as any other vitamin or mineral for your health. Magnesium is mostly important for the health of your heart, blood, and immune system.

When you are low on magnesium, you may feel nauseous, weak, and have muscle twitches or spasms. With long-term loss of magnesium, this can lead to osteoporosis, an irregular heartbeat, and even possibly seizures. It’s therefore very important to maintain a healthy level of magnesium.

Magnesium can be found in foods such as whole grains, dark leafy vegetables, beans, legumes, and nuts. However, like B12 and calcium, if you have a deficiency of magnesium from prolonged PPI use, you may need a supplement to restore your body to healthy levels.

Clostridium difficile Infection

Clostridium difficile (C. diff) is the name of a bacteria that can cause a serious infection in your digestive system. People are usually infected while in a hospital setting. This is because many hospital patients are on antibiotics, which weaken the bacteria in your digestive system (including the good one that are supposed to be there). When these good bacteria aren’t there, this opens the door for “bad” bacteria like C. diff to grow in this new environment with less competition.

The reason that people that are on long-term PPIs get more C. diff infections isn’t well known but is thought to be from one of two reasons. Though C. diff is not killed by acid, it is thought that it may grow better in a less acidic environment. Therefore, with less acidity the C. diff has a better environment to grow. The other explanation is that maybe the lack of acidity is a poor environment for some of the “good” bacteria to live. Therefore, like with antibiotics, less of these good bacteria leaves more room for the C. diff to thrive.

C. diff is an uncomfortable infection and causes very frequent watery diarrhea and abdominal pain. Treating C. diff can also be difficult, but usually a very strong course of an antibiotic called metronidazole is enough to fight off the infection. If you start experiencing unusual digestive system symptoms while on long-term PPI treatment, speak to your health care provider about testing for a potential C. diff infection.

Other Conditions

The other possible conditions associated with long-term PPI use range from relatively minor conditions like urinary tract infections to much more serious conditions such as dementia. The links between these conditions and PPI use are not as well studied as the vitamin and mineral deficiencies and C. diff infections. Studies have shown an association between the conditions and PPI use, but the studies were not strong enough to form firm conclusions. Though the absolute risk for any one of these conditions while on long-term PPIs is not well known, it is still important to know of the possible risks when making medical decisions with your health care provider.

Making an Informed Decision

If your healthcare provider prescribes you a course of PPIs, you should absolutely still take them as prescribed. If the prescription is only for a short course, these long-term risks discussed are not even risks at all. However, if you are prescribed a long-term or indefinite course of a PPI, you can discuss the risks versus the benefits with your healthcare provider. Sometimes the risks are worth the benefit of preventing damage done by your stomach acid. However, other times it may be worth trying to taper off the medication with your healthcare provider.

No matter the medication, it is always the goal of a healthcare provider to try to get patients on the lowest possible dose of any medication for the shortest possible time. This is to minimize any side effects or risks involved with medication use. Some conditions require patients to be on medications for life, and that is something your healthcare provider will have weighed the pros and cons of and decided it is the best option for you. However, it is still important to know the risks, so you can have an open and well-informed conversation with them about all medications you are taking.

  1. Abbas, M., Zaidi, A., Robert, C., Thiha, S., & Malik, B. (2019). The Safety of Long-term Daily Usage of a Proton Pump Inhibitor: A Literature Review. Cureus. doi: 10.7759/cureus.5563
  2. Jaynes, M., & Kumar, A. (2018). The risks of long-term use of proton pump inhibitors: a critical review. Therapeutic Advances In Drug Safety, 10, 204209861880992. doi: 10.1177/2042098618809927
  3. Koyyada, A. (2021). Long-term use of proton pump inhibitors as a risk factor for various adverse manifestations. Therapies, 76(1), 13-21. doi: 10.1016/j.therap.2020.06.019
  4. Nehra, A., Alexander, J., Loftus, C., & Nehra, V. (2018). Proton Pump Inhibitors: Review of Emerging Concerns. Mayo Clinic Proceedings, 93(2), 240-246. doi: 10.1016/j.mayocp.2017.10.022

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