False negative urea breath tests with H2-receptor antagonists: interactions between Helicobacter pylori density and pH

Helicobacter. 2004 Feb;9(1):17-27. doi: 10.1111/j.1083-4389.2004.00191.x.


Background: We studied the effects of famotidine, sodium bicarbonate, and citric acid on the 13C-urea breath test (UBT).

Methods: Helicobacter pylori-infected volunteers received a UBT, 40 mg of famotidine at bedtime, and a second UBT (pudding test meal, 648 mg NaHCO3 tablet then 125 mg of urea in 200 ml of water containing 650 mg of NaHCO3). Experiment 2 consisted of four UBTs. Two were standard citric acid UBTs with 75 mg of urea and 2 g citric acid and two were sequential bicarbonate-citric acid UBTs. Sequential UBTs consisted of administration of a 648 mg bicarbonate tablet with 50 g of Polycose in 200 ml of water. Five minutes later, 125 mg of 13C-urea was given in 75 ml of water containing 650 mg of NaHCO3. Breath samples were collected after 15 minutes. Then, to acutely acidify the stomach, 4 g of citric acid was given in 200 ml of water. A second breath sample was collected 15 minutes after the citric acid. The standard UBTs were done before and after 6 days of famotidine (40 mg b.i.d.). Sequential UBTs were done after 1 and 6 days of famotidine therapy. Gastric biopsies for histology, culture, and mucosal cytokines were assessed before and after 6 days of famotidine.

Results: Eighteen subjects participated, 10 in each experiment; seven had endoscopy with biopsy. Famotidine/ bicarbonate resulted an approximately 50% fall in UBT values (p = .021) with 10% becoming negative. The gastric pH increased from 5.1 +/- 0.5 to 6.7 +/- 0.2 (p = .03) although no pH value predicted the occurrence of false negative results. Under famotidine acid suppression, NaHCO3 reduced the delta over baseline (DOB) by 63% (p = .021). This was reversed with citric acid. Histology showed a H2-receptor antagonist-associated increase in the depth of gastric corpus inflammation.

Conclusions: H2-receptor antagonists differ from proton pump inhibitors as high intragastric pH may cause a reduction in urease activity, unrelated to a reduced bacterial load and reversed by citric acid.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biopsy
  • Breath Tests*
  • Citric Acid / administration & dosage
  • Endoscopy, Gastrointestinal
  • False Negative Reactions
  • Famotidine / administration & dosage
  • Famotidine / pharmacology
  • Female
  • Gastric Mucosa / microbiology
  • Gastric Mucosa / pathology
  • Gastritis / microbiology
  • Gastritis / pathology
  • Helicobacter Infections / diagnosis*
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology
  • Helicobacter pylori / growth & development*
  • Histamine H2 Antagonists / administration & dosage*
  • Histamine H2 Antagonists / pharmacology
  • Humans
  • Hydrogen-Ion Concentration
  • Male
  • Middle Aged
  • Sodium Bicarbonate / administration & dosage
  • Urea / analysis*
  • Urea / metabolism


  • Histamine H2 Antagonists
  • Citric Acid
  • Famotidine
  • Sodium Bicarbonate
  • Urea