Medication·Interactions & depletion·Reviewed June 9, 2026
Omeprazole interactions.
Omeprazole has 15 documented interactions in the NutriStack database, including 1 flagged to avoid or as a serious conflict. Prolonged use is also associated with lower Magnesium, Vitamin B12, Calcium, and Iron. The full interaction list, depletion table, and replacement suggestions are below. None of this is a substitute for your prescriber's advice.
Omeprazole at a glance.
A quick, data-grounded summary. The full tables are below.
Omeprazole has 15 documented interactions in the NutriStack database, including 1 flagged to avoid or as a serious conflict. Prolonged use is also associated with lower Magnesium, Vitamin B12, Calcium, and Iron. The full interaction list, depletion table, and replacement suggestions are below. None of this is a substitute for your prescriber's advice.
Substances that interact with omeprazole.
Every supplement and medication in the NutriStack database with a documented interaction with this drug, highest-severity first. Open any pair for the mechanism and sources.
| Substance | Interaction | What happens |
|---|---|---|
| Betaine HCL | Conflict | Betaine HCL is taken specifically to lower gastric pH, while omeprazole is taken to raise it. The two are pharmacodynamically opposed: betaine HCL... details → |
| Beta-Carotene | Caution | Omeprazole-induced hypochlorhydria reduces the absorption of beta-carotene. In a crossover trial, raising gastric pH above 4.5 with omeprazole... |
| Calcium | Caution | Long-term omeprazole use reduces calcium absorption, particularly from calcium carbonate which requires an acidic environment for dissolution. This... details → |
| Iron | Caution | Omeprazole reduces gastric acid production, which is essential for converting dietary and supplemental iron to its absorbable ferrous (Fe2+) form.... details → |
| Magnesium Glycinate | Caution | Long-term omeprazole use (>1 year) has been associated with clinically significant magnesium depletion (hypomagnesemia). The FDA issued a safety... details → |
| Vitamin B12 | Caution | Long-term omeprazole use significantly impairs vitamin B12 absorption. Gastric acid and pepsin are required to release B12 from food proteins before... details → |
| Zinc | Caution | Long-term omeprazole therapy reduces zinc absorption and lowers body zinc stores. In one controlled study, plasma zinc rose 126% with... details → |
| Iron Bisglycinate | Synergy | Iron bisglycinate is a chelated form of iron whose absorption is less dependent on gastric acid than conventional ferrous sulfate. For patients on... details → |
| Melatonin | Synergy | Melatonin has gastroprotective and lower esophageal sphincter-tonifying effects and shows additive symptom relief when combined with omeprazole for... |
| Methylcobalamin | Synergy | Methylcobalamin, the active coenzyme form of vitamin B12, does not require gastric acid or pepsin to be released from food protein, making it a more... details → |
| Probiotics | Synergy | Omeprazole shifts the gut microbiome and roughly doubles the risk of Clostridioides difficile and small intestinal bacterial overgrowth. A 2017... details → |
| Saccharomyces Boulardii | Synergy | Saccharomyces boulardii is a non-pathogenic yeast probiotic with strong evidence for preventing antibiotic-associated and C. difficile-associated... details → |
| Turmeric/Curcumin | Synergy | A 2023 randomized, double-blind trial in patients with functional dyspepsia found curcumin alone, omeprazole alone, and the combination produced... details → |
| Vitamin C | Synergy | PPIs like omeprazole reduce gastric vitamin C levels by increasing gastric pH, which oxidizes ascorbic acid to its less bioavailable form. Vitamin C... details → |
| Zinc Carnosine | Synergy | Zinc-L-carnosine (polaprezinc) is a mucosal-protective chelate widely used in Japan for gastritis and ulcer healing. It is well studied as an... details → |
What omeprazole can deplete.
Nutrients this medication is associated with lowering over time, with the mechanism, a suggested replacement where one applies, and the biomarker to monitor. Discuss any replacement with your prescriber first.
| Nutrient | Severity | How it happens | Replace with | Monitor |
|---|---|---|---|---|
| Magnesium | Significant | Chronic acid suppression impairs active intestinal magnesium transport, especially via TRPM6/7-mediated uptake. | Magnesium Glycinate | Serum magnesium or RBC magnesium |
| Vitamin B12 | Moderate | Reduced gastric acid impairs release of food-bound vitamin B12 from proteins, lowering long-term absorption. | Methylcobalamin | Serum B12 + methylmalonic acid |
| Calcium | Moderate | Lower gastric acidity reduces dissolution and absorption of less-soluble calcium salts, especially calcium carbonate. | Calcium | Serum calcium or bone density trend |
| Iron | Moderate | Reduced gastric acidity lowers conversion and solubility of non-heme iron, decreasing long-term absorption. | Iron Bisglycinate | Ferritin + transferrin saturation |
The full omeprazole profile.
Uses, typical dosing, side effects, and the cited evidence for this medication.
Common omeprazole questions.
Quick answers drawn from the tables above.
What interacts with Omeprazole?
In the NutriStack database, Omeprazole has 15 documented interactions. The most notable include Betaine HCL, Beta-Carotene, Calcium, Iron, and Magnesium Glycinate. Check any specific combination before taking it and confirm with your prescriber.
Which substances should I avoid with Omeprazole?
Omeprazole is flagged against 1 substance in the database, including Betaine HCL. These pairings carry a higher risk and should be reviewed with a clinician before combining.
Does Omeprazole deplete any nutrients?
Omeprazole is associated with lowering Magnesium, Vitamin B12, Calcium, and Iron with prolonged use. Useful biomarkers to monitor include Serum magnesium or RBC magnesium, Serum B12 + methylmalonic acid, and Serum calcium or bone density trend. Ask your prescriber before adding any replacement supplement.
Is it safe to take Betaine HCL with Omeprazole?
NutriStack classifies the Betaine HCL and Omeprazole pairing as conflict: Betaine HCL is taken specifically to lower gastric pH, while omeprazole is taken to raise it. The two are pharmacodynamically opposed: betaine HCL only partially and... Do not take betaine HCL while on omeprazole. If you believe you have low stomach acid rather than high, discuss this with your prescriber before... Always confirm with your prescriber.
Check your whole stack
See how omeprazole fits your supplements.
NutriStack screens your full routine for interactions and depletions, and updates the moment you change it.