Omeprazole is a drug commonly prescribed for stomach and gut disorders. It is praised for its anti-ulcer and anti-acid effects. However, omeprazole also protects the stomach from certain painkillers, reduces chemotherapy side effects, and reduces gut bleeding. Read on to learn more about how omeprazole works and its side effects.
Note: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.
What Is Omeprazole?
Omeprazole is known by the following brand names: Prilosec, Zegerid, and Losec.
Omeprazole is a proton-pump inhibitor, which is a type of drug that blocks the release of acid in the stomach. Stomach acid helps break down proteins from food. However, too much stomach acid can cause problems, like ulcers and heartburn [R].
Omeprazole is FDA-approved for multiple stomach disorders including ulcers, gut bleeding, and GERD.
Omeprazole is available both over-the-counter and as a prescription drug. Over-the-counter omeprazole is only intended for frequent heartburn and acid regurgitation. However, higher doses of omeprazole are prescribed to treat more severe conditions like stomach ulcers and Zollinger-Ellison syndrome [R, R].
Mechanism of Action
Omeprazole reduces acid release in the stomach by blocking the hydrogen-potassium ATPase, which is an enzyme that increases acid levels. This acid release happens in the parietal cells of the stomach [R].
Omeprazole increases superoxide dismutase and aquaporin-4 in the stomach (mucosal cells). Superoxide dismutase is an important antioxidant enzyme, and aquaporin-4 is a molecule that helps maintain water balance in cells [R, R].
Proton Pump Inhibitors vs. H2 Receptor Blocker
H2 blockers are a different kind of drug, which has also been used for gut disorders. They block the histamine H2 receptor and reduce stomach acid levels. Proton pump inhibitors block the hydrogen-potassium ATPase, which is the enzyme that produces stomach acid. H2 receptor blockers have largely been displaced by proton-pump inhibitors [R].
In 1,283 patients (RCT) with internal stomach bleeding, proton-pump inhibitors significantly reduced acid release and recurrent surgery when compared to H2 blockers [R].
In patients with acid-related disorders, omeprazole is more effective in reducing stomach acid than H2 blockers [R].
Esomeprazole vs. Omeprazole
Esomeprazole (Nexium) is another proton-pump inhibitor chemically similar to omeprazole. In multiple studies of patients with GERD, esomeprazole reduced stomach acid levels more than omeprazole did [R, R].
Uses of Omeprazole
1) Omeprazole Helps Dyspepsia
Dyspepsia is characterized by symptoms of pain, discomfort, belching, or reflux, and is caused by things like ulcers and GERD. Functional dyspepsia has the same symptoms as non-functional dyspepsia, but the causes are different for functional dyspepsia and include things like nervous system dysfunction and sensitivity to certain foods [R].
In 471 patients (RCT) with dyspepsia, omeprazole reduced pain at nighttime, especially in those with a high BMI [R].
In 1,262 patients (DB-RCT) with functional dyspepsia, omeprazole showed a modest benefit over placebo. This effect was not seen in patients with poor gut flow and difficulties digesting food [R].
In 24 patients (DB-RCT) with functional dyspepsia, only those who had experienced more than 32 reflux episodes (periods of high stomach acid) had a successful response to omeprazole [R].
In 829 patients (RCT) with acid-related symptoms, such as pain, discomfort, bloating, and nausea, omeprazole reduced symptoms more than placebo. The patients who received omeprazole also returned to the doctor less often over the following year [R].
Note: Placebo effect makes up 30 to 40% of the benefit seen in randomized control trials (RCT) of treating dyspepsia with proton-pump inhibitors like omeprazole [R].
2) Omeprazole Helps Zollinger-Ellison Syndrome
Zollinger-Ellison syndrome is a disorder in which the stomach produces too much acid because of either a tumor or enlargement of the pancreas. This leads to ulcers [R].
In a study (prospective) of 116 patients for 114 months, omeprazole reduced the high levels of stomach acid in those with Zollinger-Ellison syndrome without any toxic side effects [R].
In 49 patients with Zollinger-Ellison syndrome, omeprazole reduced stomach acid hypersecretion in 33 patients [R].
In 9 patients with Zollinger-Ellison syndrome, omeprazole reduced acid secretion by 77% to 100%. This effect lasted up to 2 years and treatment showed no negative side effects [R].
In patients with Zollinger-Ellison syndrome, omeprazole was safe and effective for up to 4.5 years at 180 mg, and for 9 years at doses up to 60 mg. A small minority of patients experienced side effects such as a headache, rash, and constipation [R, R].
3) Omeprazole Helps with Gut Bleeding
In patients with gut bleeding, omeprazole was more effective than H2 blockers at preventing rebleeding [R].
In 142 patients (RCT) with acute peptic ulcer bleeding, a low dose of omeprazole (intravenous 30 mg once per day for 3 days) prevented peptic ulcer rebleeding [R].
However, in a study (prospective) of healthy patients given high doses of omeprazole (continuous 24 intravenous infusions), the patients still had substantial levels of stomach acid, which can lead to bleeding [R].
In 220 patients (DB-RCT) with gut ulcers and signs of recent bleeding, omeprazole significantly reduced recurrent bleeding and recurrent surgery compared to placebo (but not in those with arterial sprouting or oozing) [R].
In 149 patients (DB-RCT) with a high-risk peptic ulcer, omeprazole decreased the duration of hospital stay (average 11.3 hours less than placebo), rebleeding, and the need for blood transfusions [R].
In 41 patients (RCT) with upper gut bleeding, a single dose (80 mg) of omeprazole followed by 3-day treatment (8 mg per hour, intravenously) reduced stomach acid levels more than periodic treatments (40 mg given intravenously every 12 hours) [R].
4) Omeprazole Provides Protection from NSAIDs
NSAIDs, which are common anti-inflammatory drugs (aspirin, ibuprofen, naproxen, etc.), increase the risk of peptic ulcers. Omeprazole is commonly prescribed along with NSAIDs to reduce acid levels and protect the stomach [R, R].
In patients with inflammatory disorders, omeprazole combined with NSAIDs like ketoprofen prevented ulcers and decreased dyspepsia symptoms [R].
In 156 patients with ulcers (DB-RCT) receiving long-term NSAID treatment, 20 mg of omeprazole reduced ulcers [R].
In 935 patients (RCT) taking NSAIDs over a prolonged period of time, omeprazole reduced ulcers, pain, and heartburn. Omeprazole was better tolerated and reduced the return of ulcers compared to misoprostol, another drug used to treat ulcers [R, R].
In 541 patients (DB-RCT) taking NSAIDs over a prolonged period of time, omeprazole healed and prevented ulcers more effectively than did ranitidine, which is an H2 receptor blocker used to reduce stomach acid levels [R].
5) Omeprazole Helps Heartburn and GERD
In 355 patients with GERD (DB-RCT), 20 mg of omeprazole reduced heartburn, regurgitation, nausea, pain, and difficulty swallowing [R].
In 216 patients with mild GERD (RCT), daily omeprazole reduced the return of symptoms compared to taking it as needed [R].
For patients with erosive GERD (meta-analysis), omeprazole reduced symptoms more than H2 blockers or antacids. Omeprazole seems to be the best treatment option for patients with GERD who have not had success with other treatments [R].
In 230 patients with reflux esophagitis, omeprazole use for up to 6.5 years was effective in reducing pain and heartburn, despite periodic relapses. The long-term use of omeprazole (up to 11 years) seems to be safe and helpful for those with reflux esophagitis [R].
In 41 patients (DB-RCT) with GERD, omeprazole was taken for 1 month effectively reduced symptoms. However, relapse occurred rapidly after omeprazole was stopped [R].
6) Omeprazole Helps H. pylori Infections
H. pylori is a bacteria with a high presence in the gut. It is common for people throughout the world. While it does not always lead to symptoms, it can eventually cause ulcers and lead to stomach cancer [R].
Omeprazole given with 2 antibiotics (amoxicillin, clarithromycin, or metronidazole), also known as triple therapy, can eradicate H. pylori. This same treatment seems to also be effective for children with H. pylori [R, R].
In 89 patients (meta-analysis) with H. pylori, omeprazole given along with 2 antibiotics (clarithromycin and metronidazole) eradicated H. pylori in 85 to 95% of patients [R].
In 40 patients (RCT) with ulcers and H. pylori, omeprazole combined only with amoxicillin was as good as triple therapy in eradicating H. pylori [R].
7) Omeprazole Reduces Chemotherapy Side Effects
In 125 rectal-cancer patients (retrospective analysis), omeprazole increased the effectiveness of the chemoradiotherapy and decreased the return of tumors [R].
In 228 cancer patients (DB-RCT) receiving chemotherapy, omeprazole significantly reduced ulcers, pain, and heartburn compared to ranitidine and placebo [R].
In 128 cancer (breast and colon) patients (DB-RCT), omeprazole significantly reduced ulcers, blocked stomach erosion, and reduced pain and heartburn compared to misoprostol, (another drug used to treat ulcers) and placebo [R, R].
8) Omeprazole Reduces Stomach and Esophagus Inflammation
In 96 patients (DB-RCT) with stomach inflammation, omeprazole reduced inflammation levels by 75% (and by 97.92% when combined with domperidone) [R].
In 196 patients (DB-RCT) with severe inflammation and ulcers of the esophagus, omeprazole significantly reduced symptoms and ulcers [R].
9) Omeprazole Reduces Peptic Ulcers
Omeprazole healed peptic ulcers in 29 out of 30 patients who previously had no success with other anti-ulcer drugs [R].
In more than 600 patients with stomach ulcers, omeprazole healed ulcers more effectively than ranitidine, an H2 blocker [R].
10) Omeprazole May Reduce Cancer Growth
In 125 rectal-cancer patients (meta-analysis) being treated with chemotherapy, omeprazole decreased the return of tumors [R].
Omeprazole blocked tumor growth in the esophagus (blocks Hh/Gli1 in esophagus cells) [R].
The exact mechanism of omeprazole against tumor growth is unknown. However, omeprazole may sensitize tumors to chemotherapy, induce tumor cell death (apoptosis and autophagy), and may improve the immune response to cancer growth [R, R, R, R].
In 19,000 individuals who have taken omeprazole, no serious side effects were found. The most common side effects are [R]:
- A headache
Proton-pump inhibitors can cause fundic gland polyps, which are abnormal growths of tissue at the top of the stomach. Polyps are often harmless but can turn into cancer. These are known to go away after quitting proton-pump inhibitors [R].
Proton-pump inhibitors may also cause higher blood levels of gastrin, a hormone that releases acid in the stomach [R].
Proton-pump inhibitors may increase the risk for community-acquired pneumonia, which is an infection that causes inflammation of the air sacs of the lungs [R].
Eradicating H. pylori may worsen reflux disease by increasing stomach acid levels [R].
Rare Side Effects
- Multiple studies have linked omeprazole to various types of epidermal necrosis (TEN, ADEN, Stevens-Johnson syndrome), a set of life-threatening conditions [R, R, R, R, R, R].
- Chronic use of omeprazole may be a risk factor for dementia and Alzheimer’s disease [R, R, R, R, R].
- Omeprazole increases the risk of bone fractures [R, R, R, R, R].
- Omeprazole may cause heart problems, but results are mixed [R, R, R, R].
- Rarely, patients may develop allergic reactions to omeprazole over time, with symptoms ranging from minor rashes to severe, flu-like symptoms and widespread blisters [R, R, R].
- Omeprazole may cause Clostridium difficile-related diarrhea [R].
- In patients with H. pylori, omeprazole increased bacterial infection with non-H. pylori species, increased nitrite levels, and reduced vitamin C levels in the stomach [R].
- Omeprazole use was associated with streptococcus meningitis in a 9-month old [R].
- Treating patients with H. pylori and inflammation of the esophagus with omeprazole may increase levels of stomach inflammation [R].
- In 63,397 patients, long-term omeprazole use (average of 3 years) increased the risk of stomach cancer, even after eliminating H. pylori [R].
- Some patients taking omeprazole experienced [R]:
- Stomach pain
- Reduced white blood cell count
- Increased enzymes like aminotransferases
- In 17 patients, omeprazole caused inflammation of the kidneys (acute interstitial nephritis) [R].
- Omeprazole increased impotence and increased male breast tissue (gynecomastia) in 15 men taking 20 to 60 mg [R].
- In 52 patients with GERD (RCT), taking omeprazole at doses ranging from 10 to 20 mg for an average of 2.2 years resulted in weight gain when compared to healthy controls [R].
- In patients receiving liver transplants, stopping omeprazole may cause ulcers [R].
- Male rats (RCT) who were given 400 micrograms of omeprazole daily for 77 days had reduced weight and reduced bone density [R].
Omeprazole and Mineral/Vitamin Deficiency
Omeprazole increases the risk of deficiencies of vitamin C, vitamin B12, calcium, iron, and magnesium. This risk is relatively low for most people, but it may be a concern for elderly or malnourished patients, including those on chronic dialysis (filtering of the blood) [R].
In at least 40 cases, proton-pump inhibitors caused magnesium deficiencies. The FDA issued a warning statement in 2011 regarding this possible side effect of proton-pump inhibitors. Cell studies confirmed this blocking of magnesium absorption by omeprazole (blocking TRPM 6 and 7 channels) [R].
However, in 109 patients with Zollinger-Ellison syndrome, continuous omeprazole treatment for 6 years did not reduce iron levels [R].
Limitations and Caveats
Omeprazole is widely used and has been studied in humans over long periods of time. However, the FDA has classified omeprazole as category C, which means animal studies have shown risk but human studies are lacking. Therefore, it is unclear whether omeprazole is safe to take during pregnancy [R, R].
Omeprazole may interact with any drug broken down by the enzymes CYP2C19 or CYP3A4, since omeprazole blocks these enzymes. This increases the amount of the following drugs in the blood [R, R, R, R, R, R]:
- Diazepam (Valium)
- Disulfiram (Antabuse)
- Iron-containing medicines (ferrous fumarate, ferrous gluconate, ferrous sulfate, and others)
- Mycophenolate mofetil
- St. John’s Wort
- Warfarin (Coumadin, Jantoven)
- Antibiotics (ampicillin, amoxicillin, clarithromycin, rifampin)
- Antifungal medicine (ketoconazole, voriconazole)
- HIV or AIDS medication (atazanavir, nelfinavir, saquinavir)
Analyze your genome with SelfDecode and find out if you’re a fast or slow metabolizer for these drugs.
Ten healthy men were given 40 mg of omeprazole every morning for 10 days. This treatment reduced secretin levels and increased gastrin levels, which may decrease the absorption of some drugs including ketoconazole, cefpodoxime, enoxacin, atazanavir, itraconazole, and dipyridamole [R, R].
In 93 patients undergoing maintenance hemodialysis, omeprazole reduced the risk of peptic ulcer [R].
Genetic Variations that May Influence Response to Omeprazole
Certain genes may increase or decrease your response to omeprazole:
- CYP3A4 and CYP2C19: Omeprazole inhibits the enzymes CYP3A4 and CYP2C19, which break down many molecules, including omeprazole. Therefore, your genes for these enzymes may increase or decrease your response to omeprazole [R, R, R, R, R, R].
- CYP1A1 and CYP1A2: Omeprazole activates the enzymes CYP1A1 and CYP1A2, which break down many molecules [R, R].
- TRPM6: Variations in the TRPM6 gene, which code for channels (claudin-16) that allow magnesium in and out of the cell, may lead to magnesium deficiency when taking omeprazole [R].
Understand your genes at SelfDecode.
Joe’s take: I’ve had a lot of clients who experienced longstanding gut problems after taking a PPI. People can develop SIBO and it can trigger inflammation.
One user taking 20 mg of omeprazole per day for 1 year for GERD said that it did not work as well as expected. Switching to the drug pantoprazole was more helpful.
Another user who had heartburn for years, and had tried many antacids with no benefit, said taking omeprazole for 14 days eliminated the heartburn with no side effects.
One user taking it for GERD said that it increased fatigue and lowered his/her vitamin D and vitamin B12 levels, requiring the addition of these vitamins in supplement form to get the levels back up.
One user said taking it made them feel a million times better, and they could eat all of their favorite foods again.
Another user said that it works wonders for their acid reflux.
One user said they experienced “severe” weight gain while on omeprazole, and lowering calories did not help with losing the weight.
Another user said that 20 mg per day of omeprazole caused swelling in the ankles and feet.