1. Nitrate

Nitrate is a vital plant nutrient that is absorbed by plants from the soil in large quantities and serve as primary source of nitrogen. Nitrate is found naturally in all fruits, vegetables and cereals but its highest concentration is found in the organs of green plants like spinach leaves (White, 1975; Anonymous, 1992 and 1998b). The content of nitrates in plants is increased by both mineral and organic fertilizers (Greenwood and Hunt, 1986) and there exist a dramatic increase in the concentration in case the growth of the plants happens in little light. (Roorda Van Eysinga, 1984). The content level in produce of the “northern” horticulture are therefore very high.

Most of the consumed nitrates, more so in a vegetarian diet can be found in fresh vegetables (76-85%; Anonymous, 1992; Gangolli el al., 1994). The highest level is mostly contained in leafy vegetables that are green (~318mg/kg (5.12 mmoles/kg), in the root vegetables grown in UK like potatoes ((-140 mg/kg (2.25 mmoles/kg). However, though, they contain lower nitrate levels, have more contribution of nitrate in diet because of the amount consumed (Anonymous, 1992 and 1998b). The vegetables have very low levels of nitrate. Therefore, the amount of nitrate the vegetables contribute is very small. The contribution of fish and cured meat towards the nitrate and its intake is quite substantial. For over 3,000 years, many civilizations have used nitrate and /or sodium nitrate during the treatment fish and meat (Binkerd and Kolari, 1975). The level of nitrite and nitrate is determined by the amount added in the curing process. For instance, the range contained in UK bacon is 1.4 to 440 mg/kg (with a mean of 62mg/kg), or 0.02 moles /kg to 7.1 mmoles/kg, (with a mean of 1 mmole/kg) for nitrate. The levels of nitrite content range from 0.2 to 120 mg/kg (with a mean of 24 mg/kg) or 0.004 mmoles /kg to 2.61 mmoles/kg (with a mean of 0.52 mmoles/kg) (Anonymous, 1988d). The levels indicate a steady decrease over the past years as result of change in manufacturing practice (Anonymous, 1978, 1992 and 1988d). As a matter of fact the levels of nitrite and nitrate in USA cured meat declined between 1925 and 1981 by 75% (Howson et al., 1986).

Different regions, land use or seasons influence differently the amount of nitrate gotten from drinking water. The drinking water from surface found in most parts of Europe rarely has nitrate content levels exceeding 10mg/1 (0.161 mmoles/1; Gangolli et al., 1994). Most of the drinking water supplied in UK observe the EC Directive 80/778/EEC, that puts limitation on concentration of nitrate to 50 mg/1 (0.8 mmoles/1) with nitrite limits being 0.1 mg/1(0.0002 mmoles/1) (Anonymous,1992). Though water supplied to about 2.4 people exceed the set limit, non goes beyond 100mg/1 (1.6 mmoles/1) of nitrate (Anonymous, 1988). All exposure to nitrite and nitrate cannot be considered as dietary. The demonstration by Green et al. (1981) showed that endogenous production by normal adults is 0.69 to 0.89 mmoles nitrate/day which doubles the estimation of non-vegetarian intake in UK adults. Endogenous nitrate means the stable nitric oxide’s end product, produced by inducible and constitutive synthase of nitric oxide from arginine (reviewed by Moncada et al., 1991). This rises significantly in the time of infection (Dykhuizen et al., 1996a) as a result of synthase of inducible nitric oxide being stimulated by cytokine (Hibbs et al., 1992). 80 % of swallowed nitrite, representing the majority, is obtained endogenously after salivary nitrate is orally reduced (Forman et al., 1985), and therefore various significantly based on the intake of nitrate.

1.2.1 Dietary Nitrate/Nitrite Intake

In 1985, the estimation of UK intake of nitrate for non-vegetarian adults stood at 54 mg/person/day (or 0.87 mmoles/person/day) and 2.98-3.13 mmoles/person/day (185 to 194 mg/person/day) for vegetarians (demi-, lacto-ovo and vegan) in 1978 (Anonymous, 1992). A study on total diet done in 1997 ( Anonymous,1998b), that used many groups of food, estimated the intake of nitrate as being 88 mg/person/day (88 mg/person/day) for average adult consumer, and an adult consumer in the upper range as being 2.19 mmoles/person/day (136 mg/person/day). Estimation on dietary intake of nitrate for vegetarians was found be the same ; a mean of 1.14 mmoles/person/day (70.5 mg/person/day) and upper 2.66 mmoles/person/day (165 mg/person/day) (Anonymous,1988c). All the levels were lower than daily intake expectation fixed by EU: 3.53 mmoles/day (219 mg/day) for a person weighing 60 kg. (Anonynous, 1998b).

1.2.2 Health risks

 Various studies done over the last 20-50 years indicates the risk of cancers and infantile methaemoglobinaemia associated with taking high quantity of nitrate as a result of N-nitrosamines production (Anonymous, 1992). Due to restrictions by legislation on the levels nitrate in drinking water and foods and curing of meat using nitrite and nitrate salts, this has also been introduced in a lot of countries. It is also the intention of European Union to limit amount of nitrate in vegetables (Gangolli et al., 1994). Together with a limit of 50 mg/1 on drinking water already in place, this is raising alarm to vegetable producers and water companies in Northern Europe countries (Anonymous, 1994 a and b; Monckton, 1996).

1.2.2.2 Formation of carcinogenic N-nitrosamines

 N-nitrosamines formation, from ancillary amines or nitrite inside someone’s stomach is another concern for public health regarding a dietary intake that is high. (E.g. Sen et al., 1969; Tannenbaum et al., 1974; Ohshima and Bartsch, 1981). There has been restriction on nitrite and nitrate in food products due to this (Tannenbaum, 1983; Anonymous, 1992; Gangolli et al., 1994). There has been , however , a contradiction about a weak relationship that exist between dietary nitrate and stomach cancer over the past 20-30 years meaning that are confounding factors that are major. In fact, Forman et al. (1985) showed that there is little connection between the risk of stomach cancer, nitrite levels as well as salivary nitrate. Moreover, most of epidemiological studies done recently regard nitrate as not being one of gastric cancer’s risk factors (e.g. Buiatti et al., 1990; Gonzalez et al, 1994; Hansson et al., 1994a; Pobel et al., 1995). The studies have all been on controlled cases but the one study done prospectively has shown nitrate as not being a risk factor (van Loon et al., 1998). This appears to be applicable for other cancers, notably colon and oesophageal cancers (Hubbard et al., 1994).

The evidence linking nitrate to stomach cancer also causes contradiction. Gonzalez et al. (1994) and Buiatti et al. (1990) found out that there is a high gastric cancer risk related to consumption of nitrite. A study by BuIatti et al. (1990) found a reduction of the risk after intake was adjusted to allow inclusion of other nutrients. Moreover, as previously noted, a demonstration by Forman et al. (1985) showed substantial negative link between the levels of salivary nitrite and risk for gastric cancer and findings by Loon et al.(1988) indicated no increased gastric cancer risk posed by nitrite. Therefore, the epidemiological evidence can be considered inconclusive or holds dietary nitrate as averting cancer regardless of the possibility of nitrosamines formation, and to prove that in experimental animals, some nitrosamines are carcinogenic (Sander et al., 1971). In fact, it is high time for a formal systematic review of the evidence associating nitrite/nitrate with cancer.

Most (80-90%) of dietary diet is derived from vegetables, specifically the ones that are green and leafy. Since the vegetarians’ intake of nitrate is generally high (Anonymous, 1992 and 1998b and c), there should be a high gastric cancer risk for them were nitrate to be a critical factor. Various epidemiological studies, however, show the contrary. Several long-term studies show standardized mortality ratios (SMR) for vegetarians’ deaths resulting from cancer in comparison with non-vegetarians (Thorogood, 1995). The rate of cancer deaths in vegetarian groups reduce to 40 %. Since the basis of these studies is voluntary statistics, they are prone proof bias. The Norwegian Adventist study that used data collected indiscriminately (Fonnebo, 1994) indicated the same mortality ratios for vegetarians and non-vegetarians. Jointly, these data demonstrate that there is no increased risk of cancer development linked to intake of high nitrate levels from vegetables and may in fact be protective.

Nitrosamine formation is subdued by reducing agents like ascorbic acid that is normally found in fruits and vegetables (Tannenbaum et al., 1991; Hansson et al., 1994a) ; a possible description of why intake of vegetable high in nitrate is not harmful. Furthermore, a study by Boeing (1991) indicated that there is a steady negative relationship that exist between gastric cancer and consuming raw vegetables, but consuming cooked vegetables where protective antioxidants like vitamin C are partly lost, does not decrease cancer development. McKnight et al. (1997a) demonstrated a rise in nitric oxide gas concentration in the stomach at 60 minutes to 90ppm (mean), after a solution of 2mmoles nitrate is ingested , while gastric nitrite concentration continued being low (105 pmoles/1). Therefore, it appears that there is a rapid conversion of nitrite getting into the stomach that is normally acidic, to nitrogen oxides which usually do not lead to formation of N-nitroso particles that are carcinogenic. In accordance with research by Perciballi et al. (1989), most of nitrosoproline (NPRO) found in the ferrets urine that had been fed on meats cured with nitrite was attributed to NPRO that had been formed before and only an insignificant attributed to formation of intragastric.

The past century has seen a fast decrease in the gastric cancer incidence in USA (Howson et al., 1986) and majority of other developed nations, but not in several countries found in far eastern like Korea and Japan or developing countries (Boring et al., 1993). The gastric cancer incidence in Far East which has been persistent has been linked to consumption of particular foods like Korean Kimchi (a dish of fermented cabbage) (Lee et al., 1995) and some methods of food preparation , for instance , meat broiling, salting and traditional salad preparation style in Japan (Kato et al., 1992). High content of salt in these foods is seen as leading to the high risk (Lee et al., 1995) and /or big amount of nitrosoamines that has been pre-formed (Zou et al., 1994) and similar mutagens (Chu and Li, 1994)

Moreover, Hwang et al. (1994) attributes the reduced cases of gastric cancer in developing countries is because of better hygiene , increased raw vegetable intake containing a lot of antioxidants  , improved methods of preparing food , which result in low incidents of infection by  Helicobacter pylori. Several other researchers have also demonstrated a relationship between gastric cancer and Helicobacter pylori infection (e.g. Bolin et al., 1995; Correa, 1995; Wu et al., 1998). Incidence of gastric cancer has also been attributed to Smoking of tobacco (Hansson et al., 1994b), consumption of salt Joossens et al., 1996) and poverty (Hansson et al., 1994c)