title: Oral nitrate reductase activity and erosive gastro-esophageal reflux disease: a nitrate hypothesis for GERD pathogenesis.
abstract: BACKGROUND
  Despite the rich literature on GERD, its cause and reason for increased prevalence remain obscure. Currently accepted mechanisms leave many questions unanswered. Nitrite chemistry at the GEJ is well described for carcinogenesis. Recent epidemiological and animal data have linked nitrates to GERD. "Nitrate reductase" of oral bacteria converts nitrates to nitrites. We hypothesized that nitrate reductase activity is higher in patients with erosive GERD, delivering more nitrite at the gastroesophageal-junction for a given nitrate intake.
  
  
  OBJECTIVE
  To compare oral nitrate reductase activity of erosive GERD patients with controls.
  
  
  METHODS
  Patients with erosive GERD and controls without GERD were enrolled. After overnight fasting, nitrite of oral cavity contents was measured at 1-min intervals for 3 min while incubating a 10-mg nitrate-N/L solution in the mouth. Nitrate reductase activity was calculated and compared between groups.
  
  
  RESULTS
  Eleven cases (ten males, mean age: 42.6 ± 11.7 year) and ten controls (eight males, mean age: 37.6 ± 9.2 year) were enrolled. Mean nitrate reductase activity was 3.23 ± 0.99 vs. 2.30 ± 0.83 "μg nitrite-N formed/person/minute" in cases and controls, respectively (p = 0.03).
  
  
  CONCLUSIONS
  Oral nitrate reductase activity in erosive GERD patients is higher than controls. Therefore, any dietary nitrate load generates more nitrite in these patients. This excess nitrite at the gastroesophageal junction, may potentially contribute to the development of GERD. This is the first report linking oral nitrite production to erosive GERD in man. We suggest that a "nitrate hypothesis" may answer yet unanswered questions about GERD pathogenesis. If confirmed, it may change our understanding of mechanisms of GERD and provide novel therapeutic targets.
authors: Digestive Disease Research Institute, Shariati Hospital, North-Kargar Ave., Tehran, 14117, Iran. sianasseri@yahoo.com
authors: Siavosh
authors: S
authors: Nasseri-Moghaddam
authors: Habibeh
authors: H
authors: Nokhbeh-Zaeem
authors: Parastoo
authors: P
authors: Saniee
authors: Shahrzad
authors: S
authors: Pedramnia
authors: Masoud
authors: M
authors: Sotoudeh
authors: Reza
authors: R
authors: Malekzadeh
mesh_terms: D000328:Adult; D005260:Female; D005764:Gastroesophageal Reflux / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000201:enzymology*; D050901:Nitrate Reductase / Q000378:metabolism*; D009573:Nitrites
chemical_list: D009573:Nitrites; D050901:Nitrate Reductase