Health Risks of Proton Pump Inhibitors (PPIs)

Proton Pump Inhibitors (PPIs) are drugs that are often prescribed for heartburn, peptic ulcers and  “hearburn-like” disorders of the upper gastrointestinal tract.

PPIs are among the most frequently (over)prescribed drugs overall and their use has been increasing sharply, especially among the elderly.


“Unfortunately, overprescribing of PPIs is reported frequently,” said researcher Britta Haenisch, PhD, from the German Center for Neurodegenerative Diseases. According to some research, up to 70% of all PPI prescriptions could be inappropriate, she added. “In general, clinicians should follow guidelines for PPI prescription to avoid overprescribing PPIs and inappropriate use.”

This post highlights some of the reasons why you should avoid being on them for any considerable amount of time.

Proton Pump Inhibitors (PPIs) Linked to Dementia

A new study has confirmed an association between proton pump inhibitors (PPIs) and increased risk for dementia in older patients.

The new study, by Willy Gomm, PhD, from the German Center for Neurodegenerative Diseases, Bonn, Germany, and colleagues and published online February 15 in JAMA Neurology. It is important because PPI use is so widespread and also because this was a large study of nearly 80,000 people aged 75 and over.

The results showed that 2950 patients were regularly using a PPI. These users had a significantly higher risk for dementia compared with those not taking this drug (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.36 – 1.52; P < .001).

Several confounding factors were significantly associated with increased dementia risk; for example, depression (HR, 1.28; 95% CI, 1.24 – 1.32; P < .001) and stroke (HR, 1.37; 95% CI, 1.29 – 1.46; P < .001).

Having diabetes and being prescribed five or more drugs other than the PPI (defined as polypharmacy) were also associated with significantly elevated dementia risk.

Researchers are not clear on how PPI use might raise dementia risk. Evidence suggests some PPIs may cross the blood–brain barrier and interact with brain enzymes and, in mice, may increase beta amyloid levels in the brain.

Although the current study did not include vitamin B12 levels, other research has linked PPI use to vitamin B12 deficiency, which has been shown to be associated with cognitive decline, Dr Haenisch noted.

The study can only provide a statistical association between PPI prescription and occurrence of dementia and does not prove that PPIs cause dementia: to evaluate the cause-and-effect relationships in the elderly, randomized, prospective clinical trials are needed.


  1. Lewis H. Kuller, MD, DrPH, from the Graduate School of Public Health, Department of Epidemiology, University of Pittsburgh, Pennsylvania, notes that even a relatively small increased risk for dementia could translate into many more people in the population having dementia.For example, he writes, a 1.4-fold increased risk, as suggested by the study, would increase the estimated incidence rate of dementia from 6.0% to about 8.4% per year.
  2. There are several alternatives to PPIs to treat gastrointestinal disorders in the elderly. According to Dr Haenisch, these include histamine H2 receptor antagonists, prostaglandins, and antacids. Holistic therapists would be able to suggest other options that are safer and more effective in the long run.

Proton Pump Inhibitors Increase Risk of  Vascular Dementia

A higher risk of heart attack, dementia and renal failure has been observed in chronic and long-term antacid users for some time. A recent study offers insights as to why this may be.

The recent study found that prolonged taking of antacids can lead to a much more rapid aging of these endothelial cells. The acidity levels within their lysosomes are also reduced; lysosomes are like the cells’ garbage disposals and require optimal acid levels to function properly. An accumulation of waste in endothelial cells also accelerates vascular decline.

Proton Pump Inhibitors Increase Risk of Ischaemic Stroke

2016: Researchers at the Danish Heart Foundation in Denmark add ischaemic stroke—the most common type—to the lethal roll call. It happens when clots block blood flowing to and from the brain.

The risk increased by up to 94 per cent for one PPI, Protonix (pantoprazole), and by 30 per cent for Prevacid (lansoprazole) if people were taking them at the highest dose. The average risk was 21 per cent.

No increase in ischaemic stroke risk was found for H2 blockers, which include Pepcid (famotidine) and Zantac (ranitidine). However,  the researchers said this did not necessarily mean the drugs were any safer.

Proton Pump Inhibitors and Hypomagnesemia in General Population

A Prospective cohort study of  9,818 individuals from the general population (Rotterdam Study) found  lower serum magnesium levels in people taking PPIs for long periods of time:

  • Serum magnesium level was 0.022 mEq/L lower in PPI users (n = 724; 95% CI, −0.032 to −0.014 mEq/L) versus those with no use. PPI use was associated with increased risk of hypomagnesemia (n = 36; OR, 2.00; 95% CI, 1.36–2.93) compared to no use.

People taking both PPIs and loop diuretics had even lower serum magnesium levels.

  • Effect modification was found between the use of PPIs and loop diuretics; in participants using loop diuretics (n = 270), PPI use was associated with a further increased risk of hypomagnesemia (n = 5; OR, 7.22; 95% CI, 1.69–30.83) compared to no use.

Including dietary magnesium intake into the model did not alter results (available for 2,504 participants, including 231 PPI users).

NOTE: The increased risk with PPIs was only seen after prolonged use (range, 182–2,618 days; OR, 2.99; 95% CI, 1.73–5.15).

Why should we care?

Severe hypomagnesemia may result in tetany, convulsions, or cardiac arrhythmias. Although mild hypomagnesemia is often asymptomatic, it may still be relevant because population studies have shown that even mild hypomagnesemia is associated with increased risk of diabetes mellitus, osteoporosis, cardiovascular disease, and mortality.

You can find out more here:


PPI usage may increase the risk of infections

PPI intake favours bacterial infections including:

  • spontaneous bacterial peritonitis (SBP) in cirrhotic patients
  • pneumonia or Clostridium difficile colitis


PPIs, Liver Disease, and Mortality in Patients With Cirrhosis

Proton pump inhibitors (PPI) are widely used in patients with liver diseases

Yet, this study found that PPI use is an independent risk factor for mortality in patients with cirrhosis.


PPIs and Osteoporosis / Fractures

PPIs are also suspected of increasing the risk of osteoporotic fractures.

In recent years, the FDA (Food and Drug Administratio, in 2010) and the EMA (European Medicines Agency, in 2012) have issued safety warnings about the risk of fractures of the hip, wrist and spine associated with use of PPIs (see references). As is often the case, the risk was not recognised in RCTs prior to post-marketing epidemiological studies. Both regulators reported there was a possible increase in fracture risk particularly if PPIs are used in high dose and over prolonged periods (> 1 year).

The most recent meta-analysis of observational studies (mostly of postmenopausal women and older men), found the risk of hip fracture was increased in those taking PPIs by 10%- 50% while the risk for spine fractures increased 30%-80%, although heterogeneity was seen in the data leading to wide confidence intervals. The elevated risk remained when the data were stratified according to duration of use, with either short- (<1 year) or longer-term use (>1 year).

In 2014, an Australian publication for Health Professionals was recommending that health professionals regularly review prescriptions for PPIs, prescribe the lowest dose needed, and only for the period of time needed (many people do not relapse after the first course). This seems sensible advice, along with considering alternative measures (alternative medications and also lifestyle interventions, which should be the first line of defense).

If you are at increased risk of osteoporosis for any reason (genetics, comorbidities), you would be better off avoiding taking PPIs, especially for long periods of time. Talk to your doctor about alternatives to PPIs. Holistic practitioners like myself also have a whole arsenal of lifestyle interventions that can help you avoid the need for PPIs in most cases. Let me know if you are struggling with this or similar issues.

Heartburn issues? Other related issues?

Feel free to contact me for health coaching:

Holistic Therapist & Pilates Specialist



Study Finds Growing Reason to Be Wary of Some Reflux Drugs

Proton Pump Inhibitors (PPIs) Linked to Dementia

Heartburn Drugs Prematurely Ages Blood Vessels

Chronic use of antacid drugs may speed up aging of blood vessels

Proton Pump Inhibitors and Hypomagnesemia in General Population

PPIs, Liver Disease, and Mortality in Patients With Cirrhosis

Ramsay EN, Pratt NL, Ryan P, Roughead EE. Proton pump inhibitors and the risk of pneumonia: a comparison of cohort and self-controlled case series designs. BMC Med Res Methodol 2013; 13: 82

MacLaren R, Reynolds PM, Allen RR. Histamine-2 receptor antagonists vs proton pump inhibitors on gastrointestinal tract hemorrhage and infectious complications in the intensive care unit. JAMA Intern Med 2014; 174: 564–74.

Indigestion Tablets Nearly Double the Risk of Stroke, so Add That to Heart Attack, Kidney Disease and Dementia, Proceedings of the American Heart Association scientific sessions, 2016. These results were by the Danish Heart Foundation in a study which looked at the health profiles of 244,679 Danish people with an average age of 57.

PPIs in Older People: Do You Know the Risks? Published in Health News and Evidence, Date published:

European Medicines Agency.  Proton-pump inhibitors – risk of bone fracture.  Pharmacovigilance Working Party (PHVWP). Monthly report on safety concerns, guidelines and general matters 2012.

Food and Drug Administration. FDA Drug Safety Communication: Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors. 2010

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