Medically reviewed by: Dr John Hsiang, Senior Consultant Gastroenterologist
MBChB (NZ), FRACP (Australasia), MD (Doctorate), FRCP (Edinburgh), FAMS (Gastro)
A few weeks of indigestion. A prescription for a stomach pill. Then years pass and the medication continues without anyone revisiting why it was needed in the first place.
It is a common pattern. PPIs can be effective and important medicines, but long-term use should have a clear reason. Here is what prolonged acid suppression can mean for the body, when treatment may still be necessary and when it may be worth reviewing.
Are PPIs safe to take long-term?
Proton pump inhibitors are effective and important medicines. For some conditions, they may be needed long-term. But taking them daily for months or years without a clear reason may carry additional risks, particularly at higher doses.
If you have been taking a PPI for several months without a clear diagnosis, it may be worth reviewing why it is still needed and whether the underlying cause of your symptoms has been identified.
What are PPIs and which ones are prescribed in Singapore?
Proton pump inhibitors, or PPIs, reduce the amount of acid produced by the stomach. They are widely prescribed for conditions such as acid reflux and stomach ulcers and are available in several forms in Singapore. You may recognise them more readily by their brand names than their generic names.
| Generic name | Brands | Usual daily dose | Relative strength |
|---|---|---|---|
| Omeprazole | Losec, Olit, Omepradex, Omezole, Omicap, Penrazol, Probitor, Proceptin, Ramezol, Zenpro | 20 mg | Reference strength |
| Esomeprazole | Nexium | 20 to 40 mg | Stronger than omeprazole |
| Pantoprazole | Controloc | 40 mg | Mildest of the group |
| Rabeprazole | Pariet | 10 to 20 mg | Among the strongest per milligram |
| Dexlansoprazole | Dexilant | 30 to 60 mg | Dual release, acts like a split dose |
Two things surprise most patients.
Not all PPIs have the same strength. Research comparing PPIs using omeprazole equivalents shows that the same number of tablets does not necessarily mean the same level of acid suppression. Pantoprazole 40 mg, for example, is roughly equivalent to 9 mg of omeprazole, while rabeprazole 20 mg is closer to 36 mg.
Some are available without a prescription. Certain omeprazole products in Singapore can be obtained directly from a pharmacist. While this makes them more accessible, it may also mean they are taken for longer periods without a medical review.
Short-term side effects
PPIs are generally well tolerated when taken for a short period. Common side effects include:
- headache
- nausea or stomach pain
- diarrhoea or constipation
- wind and bloating
More rarely, PPIs can cause allergic reactions, including skin rashes. Symptoms such as muscle twitching, palpitations, dizziness or seizures may be a sign of low magnesium and should be assessed promptly.
PPIs can also interact with other medicines, including clopidogrel, some antifungals and certain HIV medications.
They can affect some test results too. For example, PPIs can lead to a false-negative H. pylori breath test if they are not stopped for the recommended period beforehand.
What happens when weeks turn into years
PPIs reduce the amount of acid produced by the stomach. Over a few weeks, this is generally well tolerated. But when treatment continues for months or years, prolonged acid suppression can have wider effects on the body.
Research has linked long-term PPI use with changes to gut bacteria, nutrient absorption and other health risks. But the evidence is stronger for some of these effects than others.
Your gut bacteria shift
With less stomach acid, more bacteria from the mouth can survive and reach the intestine. In a Singapore study co-authored by Dr John Hsiang, just one week of omeprazole 20 mg increased levels of oral-type bacteria, including Streptococcus and Veillonella, in the gut. These changes largely reversed within a week of stopping the medication.
Long-term PPI use has also been linked to small intestinal bacterial overgrowth (SIBO), which can cause symptoms such as bloating, wind and abdominal discomfort.
Gut infections
This is the risk with the strongest evidence behind it. The COMPASS trial randomised 17,598 people to pantoprazole or placebo for about three years. Of everything studied, only gut infections increased: 1.4% versus 1.0%. C. difficile, a serious bowel infection, was twice as common, though the numbers were small.
The risk may be more relevant for older people, those who frequently take antibiotics or those who have previously had a C. difficile infection. Recurrent C. difficile may require further treatment, including faecal microbiota transplant in selected cases.
Calcium absorption and bone health
Acid helps dissolve calcium carbonate, the most common form in supplements. Pooled data link PPI use with roughly a 26% higher risk of hip fracture. One large study found no increase for up to six years, but roughly double the odds of an osteoporosis-related fracture after seven or more years.
COMPASS found no increase in fractures over three years. So think of this as a small risk that builds over a long time, not something that happens in a year.
Practical tip: calcium citrate does not depend on stomach acid, so it is the better choice if you must stay on a PPI.
Vitamin B12, iron and magnesium
- Vitamin B12: Long-term PPI use may reduce vitamin B12 absorption. One large study found that two or more years of use was associated with a 65% higher risk of deficiency, with a greater risk at higher doses. Symptoms can include tiredness, numbness and memory problems.
- Iron: Lower stomach acid can reduce iron absorption, which may be more relevant for people who already have low iron levels or are at risk of deficiency.
- Magnesium: Low magnesium is uncommon but can be serious. It has been reported in people taking PPIs for prolonged periods, often for a year or more.
These deficiencies can be checked with blood tests. For people taking PPIs long-term, your gastroenterologist may recommend testing where clinically appropriate.
Changes to the stomach lining
When stomach acid is suppressed, levels of a hormone called gastrin can rise. Over time, long-term PPI use may be associated with visible changes to the stomach lining, including fundic gland polyps and other changes that can be seen during a gastroscopy.
Most of these changes are considered harmless and may improve after PPIs are stopped. Their presence does not necessarily mean that treatment should be discontinued, particularly when there is a clear reason for long-term PPI use.
Gastric cancer risk
Long-term PPI use has been studied for a possible link with gastric cancer, particularly after H. pylori infection. A Hong Kong study of more than 63,000 people found an association with around 2.4 times the risk, although the overall evidence remains mixed.
This is an association, not proof that PPIs cause gastric cancer. Appropriate H. pylori testing and treatment are important, while people with gastric intestinal metaplasia may require ongoing surveillance.
Kidneys, pneumonia and dementia
Some reported risks of long-term PPI use have not been consistently supported by stronger evidence.
- Kidneys: PPIs can rarely cause acute kidney inflammation. Evidence linking them to chronic kidney disease is less certain.
- Pneumonia: Some studies have reported an increased risk, particularly early in treatment, but the COMPASS trial found no increase.
- Dementia: Earlier studies raised concerns, but later research, including COMPASS, did not confirm the association.
Cumulative dose matters
The potential risks of PPIs can depend on both dose and duration. Studies have linked greater exposure with higher rates of vitamin B12 deficiency, gut infections and some changes to the stomach.
PPIs also vary in strength, so taking “one tablet a day” does not always mean the same level of acid suppression. The dose, type of PPI and length of treatment all matter.
Who should stay on treatment
Long-term PPI treatment is necessary for some conditions and should not be stopped without medical advice. These include:
- Severe or persistent acid reflux (GERD)
- Barrett’s oesophagus
- Severe erosive oesophagitis or narrowing of the oesophagus
- Ulcer prevention in people at high risk of bleeding while taking aspirin, anti-inflammatory medicines or blood thinners
- A previous bleeding peptic ulcer
- Zollinger-Ellison syndrome
For these patients, the benefits of continued treatment may outweigh the potential risks. The aim is to use the appropriate dose for as long as it is needed.
“In my practice, I often see patients who started taking omeprazole for indigestion years ago and simply continued. The medication may be controlling their symptoms, but the original reason for treatment has not always been revisited. The aim is not simply to stop PPIs, but to make sure they are being used for the right reason, at the right dose and for the right length of time.”
Dr John Hsiang
When should long-term PPI use be reviewed?
For people who need long-term PPIs, treatment may continue as advised. But if you have been taking a PPI for months or years without a clear diagnosis, it may be worth reviewing why you still need it.
- Understand what is causing your symptoms. A gastroscopy may be recommended to look for inflammation, ulcers, Barrett’s oesophagus or other possible causes. The findings can help determine whether long-term acid suppression is needed.
- Test for H. pylori. This stomach infection is an important risk factor for gastric cancer and should be treated when identified. For some people, treating H. pylori may also change the need for ongoing acid suppression.
- Review the dose. Where appropriate, a doctor may recommend stepping down to a lower dose or using PPIs only when needed. This will depend on the underlying condition and whether there is significant oesophageal damage.
- Be aware of rebound symptoms. Stopping PPIs suddenly after prolonged use can temporarily increase acid production and cause heartburn. This does not necessarily mean long-term treatment is still required.
- Address factors that contribute to reflux. Weight, late meals, alcohol, trigger foods and sleeping position can all affect symptoms.
- Consider whether further checks are needed. After prolonged treatment, vitamin B12, magnesium, iron or bone health may be reviewed where clinically appropriate.
When should you speak to a gastroenterologist about your PPI?
Consider speaking to a gastroenterologist if:
- you have been taking a PPI for more than eight weeks without a clear diagnosis
- you have ongoing symptoms but have never had a gastroscopy
- you have never been tested for H. pylori
- your symptoms repeatedly return when you stop taking the medication
- you are taking a higher dose, such as two tablets a day
Seek prompt medical attention if you develop difficulty swallowing, persistent vomiting, unexplained weight loss, anaemia or black stools.
The bigger picture on long-term PPI use
PPIs remain an important treatment for acid reflux and other digestive conditions. For some people, long-term use is appropriate and necessary. For others, treatment may have continued for years without the original reason being revisited.
A review can help establish whether treatment is still needed, whether the dose can be adjusted and whether further investigation is appropriate.
References:
1. Freedberg DE et al. AGA Clinical Practice Update on the Risks and Benefits of Long-term Use of PPIs. Gastroenterology 2017.
2. Targownik LE et al. AGA Clinical Practice Update on De-Prescribing of PPIs. Gastroenterology 2022. PMID 35183361.
3. Moayyedi P et al. Safety of PPIs based on a large randomised trial (COMPASS). Gastroenterology 2019.
4. Nehra AK et al. PPIs: review of emerging concerns. Mayo Clin Proc 2018.
5. Adverse effects associated with long-term use of PPIs. Chonnam Med J 2023. PMID 37303818.
6. Sekar Lakshmisai S et al. Systematic review of adverse effects of long-term PPI use on the GI system. Cureus 2025. doi:10.7759/cureus.90606.
7. Graham DY, Tansel A. Interchangeable use of PPIs based on relative potency. Clin Gastroenterol Hepatol 2018. PMID 28964908.
8. Koo SH, Hsiang JC, Ang TL et al. Effects of PPI on the gut microbiome in multi-ethnic groups in Singapore. Singapore Med J 2019. PMID 30488079.
9. Cheung KS et al. Long-term PPIs and gastric cancer after H. pylori eradication. Gut 2018.
10. Lam JR et al. PPI use and vitamin B12 deficiency. JAMA 2013.
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