Cancer from consumption of nitrite-cured meat products?

Summary

The average consumer's nitrite intake from nitrite-cured meat products is compared with nitrite exposure from other sources; these are the reduction of dietary nitrate, mainly from plant foods, and the endogenous synthesis of nitric oxide, NO. Nitrite from meat products represents only a fraction of the total nitrite exposure. Epidemiological studies on the question of a connection between the consumption of nitrite-cured meat products and cancer of the stomach or brain are viewed critically. An indication of a connection between the two parameters cannot be derived from the studies considered.

Introduction

The question of whether the use of nitrite in nitrite curing salt in the manufacture of meat products leads to a health hazard is as old as knowledge about nitrite poisoning and the knowledge that nitrite and amines can, under certain circumstances, produce carcinogenic nitrosamines, and also in meat products. The discussion has recently been reignited by the question of whether organic food production is compatible with the use of nitrite curing salt (LÜCKE, 2003).

This discussion is led from different sides, scientific, health policy, consumer policy, market policy and emotional positions are represented and mixed. In this article, two main questions are to be discussed from a scientific point of view:

1. How much nitrite is the average consumer exposed to from cured meat products and how much from other sources?
2. Does the consumption of nitrite-cured meat products increase the incidence of cancer?

These questions are also the subject of a study organized by the Katalyse-Institut e. V. (Cologne) report (rz-consult, 2000), which comes to the conclusion that studies show “a sometimes drastic increase in the risk of various types of carcinoma with increased consumption of nitrate- and nitrite-cured meat and sausage products”. However, the information and conclusions of this report must be critically examined.

Nitrite from meat products and other sources

The average per capita nitrite intake from meat products can be estimated from the consumed quantities of cured meat products and their nitrite content. The current per capita consumption of meat in Germany is around 60 kg per year; around 40% of this (24 kg) is consumed in the form of meat products (30 kg), of which the bulk, around 90%, is made with nitrite curing salt. In the manufacture of these products, a large part of the added nitrite is consumed through chemical reactions with meat components, e.g. B. by the formation of the desired cured color. As a result, the residual nitrite levels are much lower than the levels calculated from the nitrite addition. According to measurements by the Federal Institute for Meat Research, the residual nitrite levels in cured boiled sausage products are 10-30 mg nitrite/kg (calculated as sodium nitrite), in cured raw meat products 40-50 mg/kg (Irina DEDERER, personal communication). Since the proportion of boiled sausage products is approx. 80% and the raw cured products approx. 20%, the result is a weighted mean value of approx. 30 mg nitrite per kg of cured meat product. The 30 kg of meat products consumed over the course of a year therefore contain 900 mg or 0,9 g of nitrite. This results in an average daily per capita nitrite intake from cured meat products of around 2,5 mg. However, values ​​that are about 6 times higher are reported in the report by the Katalyse-Institut e. V. claims (rz-consult, 2000). However, this information is not factually tenable, since the differences between meat consumption and meat consumption as well as nitrite use and residual nitrite were not taken into account in the report.

Nitrite is also found in other foods, albeit in lower concentrations than in cured meat products, e.g. B. in soups, sauces, spices, ready meals, dairy products, cereals. According to SELENKA and BRAND-GRIMM (1976), the total per capita nitrite intake with food (calculated as sodium nitrite) in Germany is 4,9 mg/day, while SCHULZ (1998) recently reported the much lower value of 0,4 mg/day. indicates day. 3,6-6,3 mg/day are given for the United Kingdom, 2,1 mg/day for Finland and 7,8 mg/day for the Netherlands (GANGOLLI et al., 1994). These values ​​largely reflect the situation in the 70s and 80s; they are probably generally lower today. Last but not least, the nitrite content of the food also depends on how the food is stored and prepared in the household before consumption.

As is well known, nitrite is also formed in the human organism from nitrate: nitrate is ingested with food, part is excreted with the saliva into the oral cavity and there reduced to nitrite by the bacterial flora. Average daily nitrate intake (calculated as sodium nitrate) with food is given by GANGOLLI et al. (1994) and SCHULZ (1998) in Germany with 93, in France 121, in England 95, in the Netherlands 99 mg per person. About 5% of this amount of nitrate is converted into nitrite, so that an additional 5 mg of nitrite (calculated as sodium nitrite) reaches the stomach with the saliva. This indirect nitrite comes mainly from plant food, since it supplies about 80% of the food nitrate.

By far the most important source of nitrite, however, is nitrogen monoxide, NO, which the body produces itself. NO is formed from the amino acid arginine and has important tasks: it acts on the muscles of the blood vessels and thus serves to control blood pressure, it is a signaling substance in the nervous system (neurotransmitter) and it serves as a chemical defense substance for the body's immune system. A healthy adult produces 20 to 30 mg NO daily (MOCHIZUKI et al., 2000), in infections and inflammatory diseases the body's need for NO for the immune system is increased, and NO production is increased. Nitric oxide is short-lived in the body and is first metabolized into nitrite and finally into nitrate. 30 mg of sodium nitrite and ultimately 69 mg of sodium nitrate are produced from 85 mg of NO. The amount of nitrite from NO is about 28 times the amount from cured meat products (2,5 mg per capita and day, see above). The nitrite from NO is produced in many places in the body and does not reach the stomach directly like the nitrite from food. However, nitrosamine formation is not only possible in the stomach. In addition, part of the nitrate from NO is converted into nitrite; on a 5% conversion basis, the 85 mg nitrate yields about 4 mg nitrite.

From the foregoing, it follows that cured meat products account for only a fraction of about 3% of total human exposure to nitrites. Most of the nitrite is formed through normal physiological processes and is independent of nutrition. If health damage caused by nitrite should occur (apart from accidents and acute poisoning), the assumption of a connection between such health damage and the consumption of cured meat products would not be plausible from the outset!

related to cancer?

The hypothesis that there is a connection between human cancer and the consumption of nitrite-cured meat products has been extensively investigated using epidemiological methods, mostly in so-called case-control studies. People with cancer (“cases”) and people without such a disease (“controls”) are questioned about their consumption of cured meat products by means of interviews or questionnaires. It is important not to learn about a person's current diet, but about what they have eaten in the past, decades ago. The reason for this is the development history of a cancer disease, which usually goes back decades. Therefore, in cases like patients, the reliability of the memory plays a large role in the reliability of the results. If in such an investigation a clearly higher consumption of nitrite-cured meat products is found in the case group, ie the cancer patients, than in the control group, this speaks for a connection, but not necessarily for a causal connection. There are numerous other factors, e.g. B. previous illnesses, age, smoking, obesity, alcohol, lifestyle, consumption of protective foods (fruits, vegetables) and unknown factors that may be different in the two groups and could promote or inhibit cancer. These factors must be taken into account as far as possible and incorrect conclusions must be ruled out as far as possible; this is only possible to a limited extent.

In the following, works are critically reviewed that are cited in the above-mentioned report (rz-consult) as evidence of a connection between the consumption of cured meat products and a carcinogenic effect. Stomach cancer is the main concern.

stomach cancer

RISCH et al. (1985) surveyed 246 gastric cancer patients and an equal number of controls (without gastric cancer) in Canada about the consumption amounts of a large number (94) of foods and beverages. Then, with the help of food analysis databases (Food Composition Data Bank), they calculated the daily intake of nitrite, nitrate, dimethylnitrosamine and a number of other substances. With regard to nitrite, the cancer patients had a (past) average daily intake of 1,4 mg, and the controls (in this case current) 1,2 mg. From the higher number of cases, the authors conclude that there is a significant trend towards increasing gastric cancer risk with increasing nitrite intake. However, the authors expressly point out the shortcomings of the study: 'this study has a number of limitations which should be considered before conclusions are drawn'. The following critical circumstances should be highlighted: The patients were asked about their past diet, the controls about their current diet. In view of increased nutritional awareness and reduced nitrite use in numerous industrialized countries, it can be assumed that the control persons with the current nitrite intake of 1,2 mg also took in more nitrite earlier. The difference in nitrite intake between the two groups would therefore be smaller or no longer exist. Furthermore, the study comes to the conclusion that the consumption of chocolate and carbohydrates are also positively correlated with the risk of gastric cancer; the latter are generally neither known nor suspected as gastric cancer risk factors. In contrast, the intake of dimethylnitrosamine, a prominent carcinogenic nitrosamine, is not correlated with the risk of gastric cancer; however, its formation in the stomach in the presence of nitrite is the cornerstone of the nitrite-nitrosamine cancer hypothesis. Thus, the findings of a positive correlation of gastric cancer with nitrite and a lack of correlation with nitrosamine appear inconsistent and make the overall result questionable. Other fundamental shortcomings are brought forward by the authors themselves. This overall consideration of the work by RISCH et al. shows that it is unsuitable as evidence for the “positive connection between the consumption of cured foods and the risk of gastrointestinal carcinoma” according to the expert opinion.

Another paper (LU and QIN, 1987) investigated the influence of table salt (sodium chloride) on the occurrence of cancer of the esophagus and stomach in different districts of Henan Province, China. In parts of the province, foods preserved with salt ('highly salted pickles') are eaten; the authors report an association of salt consumption with cancer of the esophagus and stomach. There is no mention of nitrite curing salt or meat in the work, the term 'pickles' is not explained, but it does not allow the conclusion that nitrite is implicit in the report. This work is therefore to be considered irrelevant in connection with nitrite-cured meat products. However, it clearly shows a problem that is also latent in other relevant works on the question of nitrite curing salt: a high consumption of nitrite-cured meat products is usually accompanied by a more or less high intake of table salt. Numerous animal experiments and epidemiological studies show a connection between gastric cancer and very high salt intake (FOX et al., 1999). In epidemiological studies on nitrite curing salt, an attempt should therefore be made to distinguish between a common salt effect and a nitrite curing salt effect. In the work by RISCH et al. the possible role of table salt is not discussed. The sodium intake (an indicator of the sodium chloride intake) is given there; it is significantly higher in the cancer patients examined than in the controls!

GONZALEZ et al. (1994) studied the nutrition of 354 gastric cancer patients and 354 patients without gastric cancer in Spain. The diet of all subjects was determined by interview and questionnaire; the nitrosamine intake of the subjects, more precisely the intake of dimethylnitrosamine (DMNA) as presumably the most important nitrosamine, was calculated on the basis of a review (CORNEE et al., 1992); this gives the DMNA content for 26 foods or food groups most consumed in France, with the values ​​for meat products dating from before 1980. These values ​​are therefore tailored to French conditions, particularly with regard to the supply and consumption of meat and meat products. Their adoption of Spanish manufacturing and nutritional habits is unseen and is not backed up by investigations. GONZALEZ et al. calculate on this basis a positive correlation between gastric cancer risk and DMNA intake; However, they interpret this finding with caution and point out the difficulties in reliably determining nitrosamine intake. Salt intake was not taken into account. In view of these circumstances, the relevance of the calculated correlation between gastric cancer risk and nitrosamine intake is questionable. Under today's conditions, the DMNA levels in meat products are generally lower than before 1980, so that the study by GONZALEZ et al. has only limited importance.

Another study in Spain (SANCHEZ-DIEZ et al., 1992) is based on only 109 cases with gastric cancer and 123 controls from a mountainous rural area of ​​north-west Spain with a high incidence of gastric cancer. The research method and the results are only sparsely documented in the publication; only fresh fruit, fresh vegetables and 'home-made' sausage are considered possible risk factors. The consumption quantities were not asked for, only the frequency (daily / 1-2 times a week / never). Apparently some of the cases had already died and could not be questioned; alternatively, close relatives were interviewed, which reduces the reliability of the data. The results are communicated unusually briefly. Homemade sausage – air-dried and smoked together – is described as a risk factor, but neither nitrite nor nitrate is mentioned in the work. The authors name the irritating effect of table salt on the gastric mucosa and the smoking of sausages as conceivable causes of gastric cancer. The work of SANCHEZ-DIEZ et al. thus gives neither proof nor a suspicion of a carcinogenic effect of nitrite-cured meat products, it does not allow any statement at all regarding nitrite curing salt, but points to a possible role of table salt.

A study in Italy included 1016 gastric cancer patients and 1159 controls. The frequency and portion size of 146 foods and drinks 2 years before the illness or examination were surveyed. A certain type of test analysis revealed an increase in the risk of stomach cancer with increasing consumption of nitrite: the people with the highest nitrite consumption had a 1,2-fold higher risk than the people with the lowest. In a different evaluation of the experiment, however, the effect of the nitrite disappeared (BUIATTI et al., 1990). A close connection between cured meat products and stomach cancer can therefore not be derived from the work. Incidentally, the work does not provide any information about the consumption of table salt.

In this context, a study from the Netherlands must be cited (van LOON et al., 1998), which was overlooked in the report mentioned. This is a prospective cohort study. This means that, unlike in a case-control study, a large group of people who are not ill (“cohort”) is examined over a number of years with regard to their lifestyle and emerging diseases. Studies of this type take much longer and are more expensive than case-control studies, but they are less prone to error. The above Dutch survey started in 1986 and covered 120 people aged 852-55. After 69 years, the gastric cancers that had occurred were evaluated in relation to the nitrate and nitrite intake of the individuals. Neither for nitrate nor for nitrite was there a higher risk of gastric cancer with higher intake. In terms of approach, the statement of this work is stronger than that of a case-control study, and it also refers to a population whose nutritional behavior is more comparable to that of the Germans than e.g. For example, that in a Chinese province or rural mountainous region of Spain.

Finally, the Cancer Atlas of the Federal Republic of Germany (BECKER and WAHREN-DORF, 1997) on the etiology of gastric cancer is quoted: “A number of studies indicate that preservation methods, which were particularly prevalent in the past, represent a risk factor for gastric cancer. It is primarily about the salting, pickling or smoking of fish and meat products... . In summary, these findings can be interpreted to the effect that a change in lifestyle has taken place within the framework of a rising standard of living with the increasing availability of fresh fruit and vegetables, together with a change in preservation techniques to keeping them fresh by refrigeration, which has a de facto preventive effect against gastric cancer and led to the observed sharp decline in gastric cancer mortality”.

brain cancer

There are also a number of studies on brain tumors in children and a relationship to nitrite-cured meat products. In particular, the question of whether the intake of cured meat products by the pregnant mother is associated with childhood brain tumors was examined. In a review (BLOT et al., 1999), 14 relevant works were examined. The authors come to the conclusion that the hypothesis that the consumption of nitrite-cured meat products leads to an increased risk of childhood brain tumors cannot be completely rejected, but it is not conclusively proven by the published work either: 'at this time it cannot be concluded that eating cured meat has increased the risk of childhood brain cancer or any other cancers'. The expert opinion of the Katalyse-Institut comes to the conclusion on the basis of 7 relevant works: "The problem cannot be finally clarified at the moment."

Conclusions

1. Meat products cured with nitrite only make a very small contribution of around 3% to the total nitrite load on the human organism. Most of the nitrite exposure comes from the body's own production of nitric oxide, another part from nitrate intake from food, mainly from plant foods.
2. The epidemiological studies considered here do not prove an association between the consumption of nitrite-cured meat products and cancer of the stomach or brain.
3. A high consumption of nitrite-cured meat products is and was accompanied by a high consumption of common salt, especially in the past. The consumption of very heavily salted food, which is hardly common in this country, is known to be a risk factor for stomach cancer. This is a source of error when evaluating the epidemiological results: Studies that do not take salt consumption into account run the risk of incorrectly attributing the consequences of high salt consumption to the high consumption of cured meat products and their nitrite content. In this way, nitrite-cured meat products would be wrongly blamed as the cancer risk factors. Most of the research discussed above suffers from this deficiency by neglecting table salt as a risk factor.

Selected Literature

• Becker N, Wahrendorf J (1997) Cancer Atlas of the Federal Republic of Germany, 3rd edition, Springer-Verlag, Berlin
• Blot WJ, Henderson BE, Boice JD Jr. (1999) Childhood cancer in relation to cured meat intake: review of the epidemiological evidence; nutr. Cancer, 34:111-118
• Buiatti E, Palli D, Decarli A, Amadori D, Avellini C, Bianchi S, Bonaguri C, Cipriani F, Cocco P, Giacosa A et al. (1990) A case-control study of gastric cancer and diet in Italy: II. Association with nutrients; international J. Cancer, 15:896-901
• Cornée J, Lairon D, Velema J, Guyader M, Berthezene P (1992) An estimate of nitrate, nitrite, and N-nitroso-dimethylamine concentrations in french food products or food groups; Sciences of Alimentation, 12:155-197
• Fox JG, Dangler CA, Taylor NS, King A, Koh TJ, Wang TC (1999) High-salt diet induces gastric epithelial hyperplasia and parietal cell loss, and enhances
  Helicobacter pylori colonization in C57Bl/6 mice; Cancer Res., 59: 4823-4828
• Gangolli SD, van den Brandt PQ, Feron VJ et al (1994) Nitrates, nitrite and N-nitroso compounds; Eur. J. Pharmacol., Env.
  Toxicol. Pharmacol. Sect., 292:1-38
• Gonzalez CA, Riboli E, Badosa J, Batiste E, Cardona T, Pita S, Sanz M, Torrent M, Agudo A (1994) Nutritional factors and gastric cancer in Spain; At the. J. Epide-miol., 139:466-473
• Lu Jian-Bang, Qin Yu-Min (1987) Correlation between high salt intake and mortality rates for oesophageal and gastric cancers in Henan province, China; Inter-natl. J. Epidemiol. 16:171-176
• Gap F.-K. (2003) Use of nitrite and nitrate in organic meat processing: advantages and disadvantages; Bulletin of the Federal Institute for Meat Research, Kulmbach, 42, No. 160: 95-104
• Mochizuki S, Toyota E, Hiramatsu O, Kajita T, Shigeto F, Takemoto M, Tanaka Y, Kawahara K, Kajiya F (2000) Effect of dietary control of plasma nitrate level and estimation of basal systemic nitric oxide production rate in humans; Heart and Vessels, 15:274-279
• Risch HA, Jain M, Choi NW, Fodor JG, Pfeiffer CJ, Howe GR, Harrison LW, Craib KJP, Miller AB (1985) Dietary factors and the incidence of cancer of the stomach; At the. J. Epidemiol., 122:947-959
• rz-consult (2000) report on the risk situation in humans from the consumption of nitrite/nitrate-cured meat products; http://www.nitrat.de/Gesundheit/A-Gutachten-Ziegler.pdf
• Sanchez-Diez A, Hernandez-Mejia R, Cueto-Espinar A (1992) Study of the relation between diet and gastric cancer in a rural area of ​​the province of Leon, Spain; Eur. J. Epidemiol., 8:233-237
• Schulz C (1998) Environmental Survey - exposure of the German resident population to environmental pollutants; Federal Health Gazette, 41: 118-124
• Selenka F, Brand-Grimm D (1976) Nitrate and nitrite in human nutrition - calculation of the mean daily intake and estimation of the fluctuation range; Zbl. Bakt. Hyg., I. Dept.
  Original B 162: 449-466
• van Loon AJ, Botterweck AA, Goldbohm RA, Brants HA, van Klaveren JD, van den Brandt PA (1998) Intake of nitrate and nitrite and the risk of gastric cancer: a prospective cohort study; Br J
  Cancer, 78:129-135

Source: Kulmbach [ D. WILD ]