Intragastric volatile N-nitrosamines, nitrite, pH, and Helicobacter pylori during long-term treatment with omeprazole

Gastroenterology. 2001 Sep;121(3):517-25. doi: 10.1053/gast.2001.27098.


Background & aims: This study evaluated the effect of long-term gastric acid suppressive therapy with omeprazole on intragastric levels of carcinogenic N-nitrosamines and related parameters.

Methods: Forty-five patients on long-term omeprazole medication (mean, 35 months) and 13 healthy subjects without medication participated. Volatile N-nitrosamines were determined in gastric juice and urine. Intragastric pH, nitrite, nitrate, and H. pylori status were determined. DNA isolated from gastric biopsy specimens was analyzed for precarcinogenic alkyl-DNA adducts.

Results: The intragastric pH in patients was significantly higher compared with controls (P = 0.0001). Gastric nitrite levels in patients were nonsignificantly higher. There was no difference in total levels of intragastric volatile N-nitrosamines between patients and controls, however, urinary N-nitrosodimethylamine excretion was higher in patients (P = 0.001). On omeprazole, Helicobacter pylori-positive vs. -negative patients had a nonsignificantly higher intragastric nitrite level and higher urinary N-nitrosodimethylamine excretion. No alkyl-DNA adducts could be detected in gastric epithelium.

Conclusions: Increased intragastric pH caused by long-term treatment with omeprazole does not result in increased intragastric levels of nitrite and volatile N-nitrosamines. The significantly higher urinary N-nitrosamine excretion implies the risk of increased endogenous formation of N-nitrosamines during long-term omeprazole treatment. This risk may be higher in H. pylori-positive patients.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Ulcer Agents / adverse effects*
  • Biopsy
  • Female
  • Gastric Juice / chemistry
  • Gastric Juice / microbiology
  • Helicobacter Infections / epidemiology
  • Helicobacter Infections / pathology*
  • Helicobacter pylori / isolation & purification*
  • Humans
  • Hydrogen-Ion Concentration / drug effects*
  • Male
  • Middle Aged
  • Nitrites / analysis*
  • Nitrosamines / analysis*
  • Omeprazole / adverse effects*
  • Proton Pump Inhibitors
  • Risk Factors
  • Stomach Neoplasms / epidemiology
  • Stomach Neoplasms / pathology


  • Anti-Ulcer Agents
  • Nitrites
  • Nitrosamines
  • Proton Pump Inhibitors
  • Omeprazole