Inhibition of Nitrosamine Formation by Ascorbate

In addition to dietary sources, a significant amount of nitrate is formed en-dogenously by the metabolism of nitric oxide - 1 mg per kg of body weight per day (about the same as the average dietary intake), increasing 20-fold in response to inflammation and immune stimulation. There is considerable secretion of nitrate in saliva, and up to 20% of this may be reduced to nitrite by oral bacteria. Under the acidic conditions of the stomach, nitrite can react with amines in foods to form carcinogenic N-nitrosamines, although it is not known to what extent this occurs in vivo.

Ascorbate reacts with nitrite forming NO, NO2, and N2, thus preventing the formation of nitrosamines. In addition to ascorbate in foods, there is considerable secretion of ascorbate in the gastric juice, and inhibition of gastric secretion for treatment of gastric ulcers, as well as reducing vitamin B12 absorption (Section 10.9.7), also inhibits this presumably protective gastric secretion of ascorbate (Mowat and McColl, 2001). As a result of secretion in gastric juice, the ratio of ascorbate in gastric juice to that in plasma is normally 4 to 5:1, but infection with Helicobacter pylori reduces this to 1:1. Loss of the protective effect against nitrosamine formation may be part of the mechanism by which H. pylori causes gastric cancer (Banerjee et al., 1994).

Although ascorbate can deplete nitrosating compounds under anaerobic conditions, the situation may be reversed in the presence of oxygen. Nitric oxide reacts with oxygen to form N2O3 and N2O4, both of which are nitrosat-ing reagents, and can also react with ascorbate to form NO and monodehy-droascorbate. It is thus possible for ascorbate to be depleted, with no significant effect on the total concentration of nitrosating species (Tannenbaum and Wishnok, 1987). There is, however, some evidence of a protective effect of vitamin C supplements against the development of gastric cancer (Feiz and Mobarhan, 2002).

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  • Dionisia
    What inhibits nitrosamines?
    12 months ago

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