Vitamin nitrosamine formation

Inhibition of nitrosation is generally accompHshed by substances that compete effectively for the active nitrosating iatermediate. /V-Nitrosamine formation in vitro can be inhibited by ascorbic acid [50-81-7] (vitamin C) and a-tocopherol [59-02-9] (vitamin E) (61,62), as well as by several other classes of compounds including pyrroles, phenols, and a2iridines (63—65). Inhibition of iatragastric nitrosation ia humans by ascorbic acid and by foods such as fmit and vegetable juices or food extracts has been reported ia several instances (26,66,67). 

Ascorbic acid and alpha-tocopherol are effective blocking agents against N-nitroso compound formation. Ascorbic acid is effective particularly in aqueous media, and tocopherol effective particularly in lipid phases. They should be used in conjunction due to the mutually complementary actions of the two vitamins in blocking nitrosamine formation in both aqueous and lipid media. 

In addition to vitamin C and vitamin E as effective blocking agents, there are other substances which also are capable of preventing nitrosamine formation which are present in normal foods. The influence of this factor on the design of experimental studies should not be overlooked. 

Inhibitors of nitrosation generally function by competing with the amine for the nitrosating agent. An inhibitor would thus react with nitrite at a faster rate than with amines. The inhibition reaction has recently been reviewed ( 35). The ability of ascorbate to act as a potent inhibitor of nitrosamine formation has resulted in the use of the vitamin in nitrite-preserved foods and pharmaceuticals. Furthermore, the effectiveness of ascorbate in inhibiting nitrosamine formation is dependent on (1) the concentration of ascorbate (an excess is required) (2) pH (ascorbate is nitrosated 240 times more rapidly than ascorbic acid) (3) the reactivity of the amine toward nitrosation and (4) the extent of oxygenation of the system. 

Nitrites are generally not classified as human carcinogens. Under certain conditions nitrites may combine with amines in the body to form nitrosamines. There are a number of different nitrosamines many are regulated as human carcinogens. Certain chemicals, such as vitamin C (ascorbic acid), can limit the transformation of nitrites to nitrosamines. US Department of Agriculture (USDA) requires the addition of ascorbic acid or erythorbic acid to bacon cure to reduce the risk of nitrosamine formation. 

Vitamin C (ascorbic acid) is known to inhibit nitrosamine formation. For this reason, manufacturers of cured meat are now required to add vitamin C to their meat products. 

Vitamin E (a-tocopherol), a potent antioxidant, appears to offer protection against injuries caused by 02, 03, and N02, and nitrosamine formation. Male rats supplemented with daily doses of 100 mg tocopheryl acetate and exposed to 1.0 ppm 03 have been shown to survive longer than vitamin E-deficient rats. The action of 03 is attributed in part at least to free radical formation. In addition, there is sufficient evidence that vitamin E protects phospholipids of microsomal and mitochondrial membranes from perox-idative damage by reacting with free radicals. Because lipid peroxidation is associated with decrease in oxidase activities, it is expected that the enzyme activity is affected by dietary vitamin E. Maximum activity has been observed when diets included both polyunsaturated fatty acids and vitamin E. 

Nitrosamine is known to be carcinogenic as it leads to liver cancer. Relationships between vitamin E and nitrosamines are attributed to the inhibitory effect of the vitamin on nitrosamine formation, i.e., vitamin E competes for nitrite, a reactant in the formation of nitrosamine. 

Anticarcinogens that either directly antagonize carcinogens, or more likely prevent their activation, are also present in many foods naturally or are added to them. Included in this list of good guys are vitamins A, E, and C, some Bs, chlorophyll, carotene, butylated hydroxytoluene (BHT), and anisole (BHA). Many of these substances are effective antioxidants that presumably may inhibit oxidative carcinogenic activation. Vitamin C is also a potent inhibitor of nitrosamine formation. 

Vitamins E and C have been shown to be effective inhibitors of nitros-amine formation in cured meat products (Mergens et al., 1978). Nitrite is added to inhibit the growth of Clostridium botulinum a potential undesirable side-effect is the formation of nitrosamines, which are potent carcinogens. Meat from vitamin E supplemented animals contains a higher concentration of a-tocopherol and its potential for reduced susceptibility to nitrosamine formation provides an interesting opportunity for further research. 

The antioxidant properties of ascorbate are often cited as the primary factor underlying associations of the vitamin with decreased cancer risk (Gershoff, 1993 Block, 1992) and mortality (Enstrom et al., 1992). However, other actions of the vitamin may also play a part, including enhanced immunocompetence and inhibition of carcinogenic nitrosamine formation. 

If the concepts and facts presented in this paper are correct, a major kind of human cancer in many regions of the world, cancer of the stomach, is due to a type of nitroso compound, a nitrosoureido derivative, even though not a nitrosamine It is quite certain that the formation of such compounds can be blocked by vitamin C and vitamin E, as well as by some other substances such as gallates Thus, the primary prevention of cancer caused by nitroso compounds is readily accomplished through an adequate Intake of such harmless inhibitors with every meal from infancy onwards ... 

Antioxidant activity involving the transfer of two electrons between the ascorbate/dehy-droascorbate redox couple or donation of one electron to inactivate highly reactive free radicals, e.g., protection of vitamin E by reduction of the tocopheryl radical Competitive inhibition in substrate binding reactions, including inhibition of the formation of carcinogenic nitrosamines... 

As discussed in Section 13.3.6, ascorbate may act to inhibit the formation of carcinogenic nitrosamines from nitrite and dietary amines, and thus reduce the risk of cancer. There is some evidence that vitamin C supplements are protective against the development of gastric cancer. 

Review of Ascorbic Acid Mechanisms of Action. Ascorbic acid and AP have antioxidant activity in fats, oils, vitamin A, and carotenoids. In these systems AP is a better antioxidant than are the phenolic antioxidants BHT and BHA, both from these data and others (29,35). Ascorbic acid protects against oxidation of flavor compounds in wine, beer, fruits, artichokes, and cauliflower (29) presumably by oxygen scavenging. The well-known formation of nitric oxide from nitrites by ascorbic acid is used not only for inhibition of nitrosamine fortnation, but also to promote... 

---