Omeprazole and dietary nitrate independently affect levels of vitamin C and nitrite in gastric juice

Background & Aims: Hypochlorhydria is associated with an increased risk of gastric cancer. We have studied the effect of pharmacologically induced hypochlorhydria on the gastric juice ascorbate/nitrite ratio, which regulates the synthesis of potentially carcinogenic N-nitroso compounds. Methods: Saliva, gastric juice, and serum from 20 healthy volunteers (9 positive for Helicobacter pylori), with a mean age of 30 years (range, 20-47 years), were analyzed for nitrite, ascorbic acid, and total vitamin C before and for 2 hours after ingestion of 20 mmol nitrate (nitrate content of a standard salad meal). This was repeated after 4 weeks of treatment with omeprazole, 40 mg daily. Results: Before omeprazole treatment, the nitrate meal lowered gastric ascorbic acid levels from 3.8 to 0.9 mu g/mL (P < 0.05) and increased median salivary nitrite levels from 44 to 262 mu mol/L (P < 0.001); gastric nitrite concentration remained undetected in 10 subjects. Omeprazole increased median fasting gastric nitrite levels from 0 to 13 mu mol/L (P = 0.001) and decreased fasting gastric ascorbic acid levels from 3.8 to 0.7 mu g/mL (P < 0.001). With omeprazole treatment, gastric nitrite levels after the nitrate meal were markedly increased at 154 mu mol/L (range, 49-384 mu mol/L; P < 0.001), In H. pylori-infected subjects, omeprazole also decreased total vitamin C levels in both gastric juice and serum. Conclusions: Omeprazole and dietary nitrate independently decrease the ascorbate/nitrite ratio. This may lead to an increased risk of gastric cancer.