Proton pump inhibitors (PPIs) are used widely in the management of acid-related disorders and, for the majority of patients, oral therapy is effective. Proton pump inhibitors have enabled improved treatment of various acid-peptic disorders, including gastroesophageal reflux disease, peptic ulcer disease, and nonsteroidal anti-inflammatory drug­induced gastropathy. If you would like to receive a free email newsletter on natural health and medicine, see Newsletter.

Types of Proton Pump Inhibitors

The proton pump inhibitors omeprazole, lansoprazole, rabeprazole, and esomeprazole appear to have similar efficacy.
Omeprazole (Prilosec)
Lansoprazole (Prevacid)

Rabeprazole (Aciphex)

Pantoprazole (Protonix)
Esomeprazole (Nexium)

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Long Term Proton Pump Inhibitor Use
Omeprazole began to be used in 1988, and since then proton-pump inhibitors have remained central to the management of acid-suppression disorders and are unchallenged with regard to their popularity among doctors and patients. 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 proton-pump inhibitor therapy are centred mainly on a possible association with fundic gland polyps and between Helicobacter pylori and gastric atrophic changes. Long-term proton-pump inhibitor usage accounts for the majority of the total proton-pump inhibitor usage. 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.

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.

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.

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, February 2007.

Proton Pump Inhibitors and Risk of Cancer
Does the use of proton pump inhibitor drugs 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.
 

Intravenous Proton Pump Inhibitor Drugs

Intravenous administration of a proton pump inhibitor (PPI) 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 Research
Proton pump inhibitor therapy is a risk factor for Clostridium difficile -associated diarrhoea.
Aliment Pharmacol Ther. 2006 Aug 15;24(4):613-9. 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.

Proton pump inhibitor Questions
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. 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.