Proton Pump Inhibitor Drug benefit and side effects, safety, danger and risk 
September 12 2018 by
Ray Sahelian, M.D.

Proton pump inhibitors (PPIs) are used widely in the management of acid-related disorders and, for the majority of patients, oral therapy is effective. PPI drugs have enabled improved treatment of various acid-peptic disorders, including gastroesophageal reflux disease, peptic ulcer disease, and nonsteroidal anti-inflammatory drug­induced gastropathy. See this informative page gerd diet.
   However, there are many risks to their use. There are a number of clinical studies that associate PPI use with an increased risk for heart problems.


Heartburn medications raise a senior's risk of dementia. Called proton pump inhibitors (PPIs), this group of drugs includes Prilosec, Nexium and Prevacid.


Types of Proton Pump Inhibitors

Omeprazole, lansoprazole, rabeprazole, and esomeprazole appear to have similar efficacy.
Omeprazole (Prilosec)
Email - I have been taking omeprazole for a number of years due to having a hiatal hernia, causing as you well know GERD. In recent months I have been experiencing slight dizziness from time to time. Further, I also recently noticed, that my prescription container has posted a warning as to dizziness. Would you please advise to this possibility as it may solve the reason for my getting dizziness all of a sudden. My primary care physician has led me to believe the problem stems from my ears and ordered a motion sickness drug, that made me feel worse. I discontinued the use of this drug and felt better. However, the dizziness still persists from time to time. This drug has also caused other problems for me, such as vitamin D and calcium deficiency that has ultimately caused severe bone density problems. Is there any solution in resolving all these problems that this drug is doing to me and what can I do to improve these conditions, caused by said drug omeprazole.
Lansoprazole (Prevacid)

Rabeprazole (Aciphex)

Pantoprazole (Protonix)
Esomeprazole Nexium purple pill


Combining with natural supplements
Clin Exp Gastroenterol. 2013. Outcomes in patients with nonerosive reflux disease treated with a proton pump inhibitor and alginic acid ± glycyrrhetinic acid and anthocyanosides. The purpose of this study was to compare the efficacy of alginic acid alone versus alginic acid combined with low doses of pure glycyrrhetinic acid and bilberry anthocyanosides as an addon to conventional proton pump inhibitor therapy in relieving symptoms associated with nonerosive reflux disease. Use of low doses of pure glycyrrhetinic acid + bilberry anthocyanosides, together with alginic acid as addon therapy, substantially improves symptoms in patients with nonerosive reflux disease without increasing side effects or worsening tolerability or compliance.


Long Term Proton Pump Inhibitor use and consequences
Since their introduction in about 1990, the drugs collectively known as proton pump inhibitors (common brand names: Nexium, Prevacid, Prilosec) have become among the most frequently prescribed in the country; they are also available over the counter. They suppress stomach acid more effectively than a previous class of drugs called H2 blockers (Zantac, Tagamet, Pepcid). In recent years, studies have reported associations between prescription P.P.I. use and an array of health problems, including bone fractures, low magnesium levels, kidney injuries and possibly cardiovascular drug interactions.


Proton pump inhibitors increase the risk of carrying antibiotic-resistant bacteria.


Omeprazole began to be used in 1988. They were considered safe but there are some concerns about the possibility of an association with cancer, infection, and gastric atrophy; current concerns about long-term therapy are centered mainly on a possible association with fundic gland polyps and between Helicobacter pylori and gastric atrophic changes. Long-term usage is difficult to define and most patients take proton-pump inhibitors non-continuously. Data indicate that a substantial proportion of long-term users do not have a clear indication for their therapy and there is thus room for reduction or rationalization of treatment. Overall, on-demand therapy is more cost-effective than continuous therapy and should be considered wherever possible.

Chronic use may lead to confusion, delirium, and dementia, brain function loss, memory loss
Heartburn medications raise a senior's risk of dementia. Called proton pump inhibitors (PPIs), this group of drugs includes Prilosec, Nexium and Prevacid. They work by lowering the amount of acid produced by the stomach. But German researchers found that people 75 or older who regularly take the medications had an increased risk of dementia, compared with seniors not using the drugs.


Cancer risk increase
PPIs such as commonly used drugs like Prilosec, Nexium and Prevacid, may increase the risk for stomach cancer.


Heart disease

There are a number of clinical studies that associate PPI use with an increased cardiovascular risk.


Magnesium level decrease
Ann Pharmacotherapy. 2013. Proton pump inhibitor-associated hypomagnesemia: what do FDA data tell us? All PPIs were associated with low magnesium blood levels, with esomeprazole having the lowest risk and pantoprazole having the highest risk.


Proton Pump Inhibitors and risk of cancer
Does the use of these medications that reduce stomach acid, or the use of H2 blockers increase the risk of cancer of the esophagus or stomach? Common H2 blockers are ranitidine (Zantac) and cimetidine (Tagamet); and a common proton pump inhibitor is omeprazole (Prilosec). Dr. Mats Lindblad and colleagues at the Karolinska Institute in Stockholm evaluated 7 years of patient data entered into the UK general practice database. The team identified 287 patients with esophageal cancer and 522 with stomach cancer. These subjects were compared with 10,000 randomly selected subjects without cancer. The authors found some conditions for which acid-suppressing drugs are used, such as acid reflux disease, hiatal hernia and Barrett's esophagus, were associated with an increased risk of stomach and esophagus cancer. However, no apparent cancer risk was seen with other conditions, including peptic ulcer, gastritis, and indigestion. They found no evidence that the proton pump inhibitor drugs themselves increased the risk. However, Dr. Kenneth E.L. McColl, of the Western Infirmary, Glasgow, UK says "a major weakness in the study is the relatively short duration of acid suppressive therapy examined. The development of cancer in humans is a slow process. The period in question is really too short to identify or exclude any direct effect between acid suppressive medication and stomach or esophageal cancers." Gut, November 2006.
   Dr. Sahelian says: I agree with Dr. McColl. It would take at least a 10 to 20 year longitudinal study to determine whether proton pump inhibitor drugs reduce or increase the risk for cancer and other health conditions.


Lakartidningen. 2013. Proton pump inhibitors can cause urticaria.

Circulation J. 2014. Use of Proton Pump Inhibitors Is Associated With Anemia in Cardiovascular Outpatients.

Heart disease, heart attack
People who use certain heartburn drugs for a long period of time may have a slightly heightened risk of suffering a heart attack. Using medical records from nearly 300,000 U.S. adults with acid reflux disease (commonly called heartburn), researchers found that the risk of heart attack was slightly elevated among those using proton pump inhibitors such as Prevacid, Prilosec and Nexium.

Increased risk for kidney disease
People who take popular heartburn pills known as proton pump inhibitors (PPIs) may be more likely to develop chronic kidney disease than individuals who don’t use these drugs. The association is worrisome because tens of millions of people a year take these pills, sold by prescription and over-the-counter in some countries, with brand names including Prilosec, Prevacid and Zegerid.

Vitamin B12 absorption
Proton pump inhibitors also reduce the absorption of vitamin B12 probably by inhibiting intragastric proteolysis and, thus, its release from food required prior to binding to R-proteins and gastric intrinsic factor.

JAMA. Dec 11 2013. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. Previous and current gastric acid inhibitor use was significantly associated with the presence of vitamin B12 deficiency. These findings should be considered when balancing the risks and benefits of using these medications.


I saw a page on your website about these drugs and see from yours and others that they can inhibit absorption of calcium. I am wondering if there has been research on absorbtion of B12? I have taken Prilosec and the over the counter form for several years on a daily basis per my GI doctor. But since then have been deficient on B12. Just wondering if there is anything available on this.
   Long-term use of PPIs may lead to vitamin B12 deficiency, more likely in the elderly, or in persons with Zollinger-Ellison Syndrome who are on high doses of PPI for prolonged periods of time. World J Gastroenterol. 2010. Safety of the long-term use of proton pump inhibitors.


Institutionalized older individuals on PPI for more than 12 months may be more likely to be vitamin B12 deficient than non-PPI users. Additionally, treatment of PPI users with cyanocobalamin nasal spray for 8 weeks could improve vitamin B12 status. J Nutr Elder. 2010. Vitamin B 12 deficiency is linked with long-term use of proton pump inhibitors in institutionalized older adults: could a cyanocobalamin nasal spray be beneficial? Department of Health, Nutrition, and Exercise Science, University of Delaware, Newark, Delaware, USA.


Advances in Nutrition, 2018. Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications. There is clear evidence that proton-pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), and metformin can reduce serum vitamin B-12 concentrations by inhibiting the absorption of the vitamin.


Heartburn Medication May not be Safe -- Side effects of proton pump inhibitor drugs
Proton-pump inhibitors that block stomach acid production increase the risk of an increasingly common infectious form of diarrhea. Taking a heartburn medication such as AstraZeneca's Nexium or Losec or their generic versions significantly increases the risk of diarrhea blamed on the Clostridium difficile bacteria. Frequently prescribed anti-heartburn drugs called H2 antagonists that include GlaxoSmithKline's Zantac double the risk of the bacterial diarrhea. PPIs and H2 antagonists reduce gastric acid, allowing for bacteria to multiply in the digestive system. Clostridium is the third-most common type of infectious diarrhea in patients aged 75 and older. Exposure to Clostridium difficile bacteria, which causes infection and inflammation of the intestine, previously occurred mostly during hospital stays, but cases have increasingly been contracted in community settings. While antibiotics formerly blamed for outbreaks of the illness have declined in use, the acid-blocking drugs have become steadily more popular to treat ulcers and conditions such as gastric reflux disease.


Even in those without previous heartburn symptoms, proton pump inhibitors can give rise to such symptoms after the drugs are stopped. "It thus seems that the drugs induce the symptoms they are used to treat, which might lead to dependency on such drugs," says co-author Dr. Christina Reimer, from Køge University Hospital, Denmark. Such dependency might explain why use of the medications is increasing. Gastroenterology, 2009.


The US Food and Drug Administration recommends that the coadministration of omeprazole and Plavix (clopidogrel) be avoided, based on data showing that the proton pump inhibitor reduces the efficacy of Plavix by nearly 50%. Other drugs which inhibit the CYP2C19 drug-metabolising enzyme should also be avoided in combination with clopidogrel.


Common heartburn drugs can cause serious side effects and should be used with caution. Well-known brands of the drugs - called proton pump inhibitors or PPIs - include AstraZeneca's Nexium and Prilosec. Formerly AstraZeneca's biggest seller, Prilosec is available generically as omeprazole and is also sold over the counter by Procter & Gamble Co. While the drugs are a great help to the right patients, they can raise the risk of fractures in post-menopausal women and cause bacterial infections in many patients. Archives of Internal Medicine, 2010.


Popular heartburn drugs, including proton pump inhibitors and histamine-2 receptor antagonists, may raise the risk of pneumonia, according to Dr. Sang Min Park of the department of family medicine at Seoul National University Hospital in Korea.


Hip fracture risk increased with proton pump inhibitors
long-term use of proton pump inhibitors increases the risk of hip fractures in adults over 50.

Postmenopausal women with a history of smoking who take these heartburn drugs for two years or longer may be more likely to sustain a hip fracture.


Extended PPI use accelerates cell aging. Long-term exposure to common nonprescription heartburn medication causes cells in blood vessels to age faster in a laboratory setting, compared with exposure to placebo.


Email - I have been diagnoses with acid reflux, hiatal hernia and diviticulitis. My dx was 2 years ago and I was hospitalized 4 times. I have been on protonpump inhibitors for this whole period switching a few times from protonix, tonexium and landsoprozole. Recently, i have been experiencing achy muscles, feet, calves and my arms and throbbing hands. Each day a different joint hurt even my hip. I now woke up one day with what was a sore arm for a few weeks to not being able to move it and was in excruciating pain.


I was wondering if there was any research / evidence on the relationship between muscle weakness / tightness with long term use of PPI or GERD disease progression? Muscle weakness / tightness is pretty much all over especially hips, knees and back.


Withdrawal symptoms
Dr. Anna Niklasson, from Sahlgrenska University Hospital, Goteborg reports that healthy volunteers who took pantoprazole for 4 weeks had dyspeptic symptoms when they stopped, probably from rebound secretion of gastric acid. Dr. Anna Niklasson says, "A 4-week course of pantoprazole seems to induce dyspeptic symptoms in previously asymptomatic healthy H. pylori-negative subjects. The correlation between symptom score and gastrin levels suggests that these symptoms are due to acid rebound hypersecretion and seem to be related to the degree of acid inhibition. Am J Gastroenterology, March 2010.


GERD disease and proton pump inhibitors - acid reflux
Drugs such as Nexium and Prilosec, referred to as proton pump inhibitors, are effective treatments for gastroesophageal reflux. But when these drugs fail to bring relief, persistent heartburn may be the result of an increase in non-acidic reflux. Gastroesophageal reflux disease, or ( GERD ), occurs when fluid in the stomach, which is highly acidic, moves into the esophagus, typically causing heartburn. Because of the change in body position, reflux is often worse during sleep. Persistent reflux can cause permanent changes in the lining of the esophagus, which can lead to cancer. Dr. Suanne Goodrich and her associates at the Lynn Health Science Institute in Oklahoma City point out that the role of non-acid reflux during sleep has not been evaluated. They theorized that non-acidic reflux during sleep could cause prolonged esophageal exposure to bile salts and pancreatic enzymes, and increase the risk of inhalation of the reflux fluid. Fifteen subjects with heartburn were randomly assigned to treatment with the proton pump inhibitor Nexium (esomeprazole) or to inactive "placebo" for 1 week. After the week of treatment, the subjects spent a night in the researchers' lab, where they underwent various reflux tests. Prior to going to bed, the subjects ate pizza, brownies and grape juice to increase the likelihood of reflux. Treatment with proton pump inhibitor Nexium reduced the rate of reflux episodes by approximately half, but the number of non-acid reflux events rose from 6 to 27. Reflux may cause arousal during sleep, which actually protects the esophagus by increasing salivation and swallowing. Most reflux events, either acidic or non-acidic, result in an arousal response within 2 minutes. The fact that the esophagus is equally responsive to acidic and nonacid reflux indicates no increased risk of damage to the esophagus. Chest, 2007.


Intravenous Proton Pump Inhibitor Drugs

Intravenous administration is a faster way to achieve gastric acid suppression than oral administration of the same agent. Peak suppression after IV administration occurs within hours, compared with several days later after oral administration. Thus the IV route of administration offers a faster onset of gastric suppression, achievement of intragastric pH closer to neutrality, and better bioavailability. The proton pump inhibitors that have IV formulations in the United States (esomeprazole, lansoprazole, and pantoprazole) are approved for different indications.

   Randomised controlled trials evaluating the clinical effect of proton pump inhibitors (PPIs) in peptic ulcer (PU) bleeding have yielded conflicting results. PPI treatment in PU bleeding reduces rebleeding and surgery compared with placebo or H(2)RA, but there is no evidence of an overall effect on all-cause mortality.
   At equivalent doses, oral and intravenous (IV) PPIs produce comparable acid suppression; thus there are very few clinical indications for IV PPI therapy. IV PPIs are an appropriate substitute for oral PPIs, at an equivalent dose, for patients with, for example, gastroesophageal reflux disease, peptic ulceration, or Zollinger-Ellison syndrome, who cannot take oral medication.


Proton pump inhibitor therapy is a risk factor for Clostridium difficile -associated diarrhoea.
Aliment Pharmacol Ther. 2006. Department of Adult Medicine, Royal Gwent Hospital, Newport, South Wales, UK.
Inhibition of gastric acid removes a defence against ingested bacteria and spores, increasing the risk of some forms of gastroenteritis. Previous studies investigating a possible link between acid suppression therapy and Clostridium difficile -associated diarrhoea have reported conflicting results. Conclusion: The risk of C. difficile-associated diarrhea in hospitalized patients receiving antibiotics may be compounded by exposure to proton pump inhibitor therapy.


Q. Are there any herbs that work the same way as PPIs?
   A. I am not aware of specific research with herbs that have found them to work the same way as a proton pump inhibitor. However, certain herbs have begun to be evaluated in ulcer healing, such as prickly pear or cactus pear. Research is still quite early with herbs. See the ulcer link at the top of the page.

Q. Is it okay to take alpha lipoic acid or resveratrol with a proton pump inhibitor drug?
   A. I have not seen studies regarding this combination, but it would seem that taking 50 mg or less of lipoic acid a few times a week should be fine.


Q.  I take a Proton Pump Inhibitor prescription medication every day for gastro esophageal reflux disease. Are there any natural sex booster supplements that you would recommend someone taking a proton pump inhibitor should avoid?
   A. We have not seen any studies that have looked into the combination of proton pump inhibitors and natural aphrodisiac herbs or supplements. As a general rule, small amounts or dosages, such as half a capsule, of the sex herbs should be safe in most people, but have approval from your doctor.


Q. I am going off of Prilosec and Prevacid. I have taken them off and on (not at the same time, of course,) over several years now. I have terrible diarrhea. I cannot leave the house for an hour after eating. So I stopped taking Prilosec about a week ago. I feel better, but wonder if I should have just quit taking it abruptly. Any danger that you know of in that?
   A. We are not aware of any withdrawal symptoms from stopping Prilosec or Prevacid proton pump inhibitors but much depends on the condition of a person's stomach and intestines and overall health condition. The decision to stop these proton pump inhibitors depends on a number of factors that you and your doctor would need to discuss.


Big fan of your vitamins and input on herbal supplements. I have a 13 year old son that was just diagnosed with gastritis and acid reflux. He has been put on proton pump inhibitor Prilosec 20mg x3 daily and Carafate 10ml x3 daily. Are there any supplements that could heal and provide relief?
   A. Perhaps his doctor can read this page, the page on gerd diet, along with the page on ulcer.


At the age of 19 my son was diagnosed with hairy cell leukemia. It was treated with Kemo new drug klydrobin (might be spelled wrong). when he was 15 or so he was put on Protonix for acid reflex. He became constipated at the time he was 19 and was diagnosed with leukemia after all was tested through bone marrow biopsy. Today he has to have another biopsy done WBC is under 2000. But my reason for this email is to find out if acid drugs might have connection between constipation and his disease. I had just found out that he is now taking Prilosec. Bottom line 2 acid drugs second time for low blood count. I am not sure were to go with this i am looking  for any answers. no help from local doctor.


Proton pump inhibitors (PPIs) are a group of medications that decreases the amount of acid in the stomach and intestines. Doctors prescribe PPIs to treat people with GERD, ulcers in the stomach or intestine, or other digestive disorders that may cause excess stomach acid. Does the administration of a PPI have any pronounced effect on the pH of the duodenum?
    Since the stomach makes acid, and PPIs reduce the acid formation, the mixture of food and reduced acid reaches the duodenum and thus the administration of a PPI will most likely result in a lower duodenal pH. I am not an expert in this topic but this is my best understanding.


Do you have any suggestions for treatment of a hiatal hernia other than a proton pump inhibitor? Those meds are toxic and horrible to my system.
    I have not studied this topic in enough detail yet as far as natural treatment, but the page on gerd diet may be helpful.