Long-term PPI use: Side effects, risks & what to know

If you’ve been prescribed proton pump inhibitors (PPIs) or H2 blockers to manage acid reflux, heartburn or other digestive symptoms, you’re not alone. These medicines are among the most commonly prescribed drugs worldwide.¹

For many people, these medicines are an effective and appropriate part of treatment. However, some people remain on them for months or years, sometimes without a regular review of whether they are still needed.

So, what are the potential effects of long-term PPI use, and should you be concerned?

The answer isn’t simply that PPIs are “bad”. These medicines can be very beneficial when there is a clear reason to use them. The important question is whether the benefits of continued treatment still outweigh the potential risks for you.

Their use has become so widespread, that healthcare professionals and researchers are now raising concerns about the long-term effects these drugs may have on health.²

What are PPIs and H2 blockers?

PPIs, or proton pump inhibitors, include medicines such as omeprazole, lansoprazole and pantoprazole. They work by reducing the production of stomach acid.

H2 blockers, also known as H2 receptor antagonists, reduce stomach acid through a different mechanism and include medicines such as famotidine.

Reducing stomach acid can help relieve heartburn and reflux symptoms and give inflammation or damage in the upper digestive tract time to heal. NICE guidance recommends PPIs for certain reflux conditions and advises using the lowest dose needed to control symptoms when treatment continues.³

Why can long-term PPI use be a concern?

Stomach acid has important functions. It helps with digestion and contributes to the absorption of certain nutrients. It also forms part of the body’s defence against microorganisms that enter through the digestive tract.

Because PPIs and H2 blockers deliberately reduce stomach acid, researchers have investigated whether prolonged acid suppression may have unwanted effects.

Some potential problems have been associated with long-term PPI use, although the strength of evidence varies considerably between them. In particular, it is important to distinguish between an association found in observational studies and proof that the medication directly caused a health problem.

Here are some of the areas that have received the most attention:

Nutrient absorption issues

Stomach acid breaks down food for digestion, and helps your body absorb nutrients like vitamin B12 and magnesium.⁴ When acid production is inhibited during long-term PPI use, it makes it harder for your body to get these nutrients. This can lead to deficiencies that affect energy levels and nerve function.

Changes to the gut microbiome

Suppression of stomach acid upsets the balance of bacteria in your gut. Acid helps control harmful microbes and supports your beneficial bacteria, so reducing it can lead to an overgrowth of pathogens.⁵ This can cause bloating, digestive issues and potential infections. Your gut microbiome is a delicate ecosystem, so tipping the balance can cause a lot of disruption.

Bone health & fractures

As with other minerals, calcium absorption depends partly on stomach acid. So the suppression of stomach acid can weaken bones over time, contributing to osteoporosis and a higher chance of fractures.⁶ The risk is higher in older adults, as bones naturally become less dense and more fragile.

Higher risk of infections

Reduced stomach acid makes it easier for harmful bacteria and pathogens to survive and multiply in your digestive tract.⁷ This increases the risk of bacterial infections such as Clostridioides difficile (C. diff), which can cause severe diarrhoea and inflammation of the colon.

The overall risk for an individual depends on several factors, so this association should not be interpreted as meaning that PPIs directly cause C. difficile infection in every person who takes them.

Potential kidney problems

PPIs have been linked to acute interstitial nephritis, a type of inflammation affecting the kidneys. This is considered an uncommon adverse reaction, but it can occur during treatment and may require the medicine to be stopped and the condition treated.

Long-term use can also lead to chronic kidney disease.⁸

Does this mean you should stop taking your PPI?

No. Don’t stop a prescribed PPI suddenly, without medical advice.

PPIs have an important role in treating conditions such as gastro-oesophageal reflux disease (GORD), stomach ulcers and severe oesophagitis. For some people, long-term treatment is appropriate and stopping treatment could allow their underlying condition to return or worsen.

Instead, ask your GP, pharmacist, or consultant:

Do I still need to take this medicine?
Is my current dose still appropriate?
Could I take it less frequently or at a lower dose?
Are there lifestyle changes that could help control my symptoms?
Do I have any risk factors that mean I should continue taking it?

The bottom line on long-term PPI use

PPIs and H2 blockers can be highly effective medicines when they’re used for the right reasons. However, because they change the amount of acid your stomach produces, long-term use has been associated with several potential nutritional, gastrointestinal, bone and kidney-related effects.

That doesn’t mean you should stop taking your medication. Instead, if you’ve been taking a PPI or H2 blocker for a long time, it’s sensible to make sure your treatment is still appropriate for you.

Speak to your GP, pharmacist or consultant before changing your medication, particularly if you’ve been prescribed it for a specific medical condition.

Looking for ways to manage reflux naturally? Check out 12 natural solutions for heartburn & Acid Reflux

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