Quantitative relationship between oral nitrate-reducing activity and the endogenous formation of N-nitrosoamino acids in humans

Food Chem Toxicol. 1991 Nov;29(11):751-5. doi: 10.1016/0278-6915(91)90183-8.


Salivary nitrate and nitrate concentrations, in vitro kinetics of nitrate reduction in saliva, and numbers of salivary nitrate-reducing micro-organisms were each compared with N-nitrosoamino acid excretion in 16 humans eating controlled diets. N-Nitrosoproline (NPRO) and N-nitrosothiazolidine-4-carboxylic acid (NTCA) excretion were measured after intake of nitrate (5.24 mmol) and L-proline (4.35 mmol) before and after treatment with an oral antiseptic (Peridex, 0.12% chlorhexidine gluconate). Peridex treatment resulted in a 94% reduction in the numbers of salivary nitrate-reducing bacteria, a decline from 17 to 4% in the amount of salivary nitrate that was reduced to nitrite in vivo, and an 85% reduction in the rate of in vitro nitrate reduction by saliva. Concurrently, there were 62 and 74% inhibitions of endogenous NPRO and NTCA formation, respectively. Correlations of the numbers of nitrate reductase micro-organisms, in vivo oral nitrate reduction and salivary nitrite concentrations, with individual NPRO excretion, indicated that individuals with higher oral nitrate-reducing capacities formed more N-nitrosoamino acid endogenously. These data suggest that individual differences in oral nitrate reduction are a significant factor in gastric nitrosation and account for a large proportion of the interindividual variability in nitrosoamino acid excretion.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adult
  • Chlorhexidine / analogs & derivatives
  • Chlorhexidine / pharmacology
  • Chromatography, Gas
  • Humans
  • Male
  • Middle Aged
  • Nitrates / administration & dosage
  • Nitrates / metabolism*
  • Nitrites / chemistry
  • Nitrosamines / metabolism*
  • Nitrosamines / urine
  • Nitroso Compounds / metabolism*
  • Nitroso Compounds / urine
  • Saliva / chemistry
  • Saliva / drug effects
  • Saliva / metabolism*
  • Thiazoles / metabolism*
  • Thiazoles / urine
  • Thiazolidines


  • Nitrates
  • Nitrites
  • Nitrosamines
  • Nitroso Compounds
  • Thiazoles
  • Thiazolidines
  • N-nitrosothiazolidine-4-carboxylic acid
  • nitrosoproline
  • chlorhexidine gluconate
  • Chlorhexidine