A Backgrounder of the Institute of Food Technologists
This backgrounder was drawn from IFT's 1987 Scientific Status Summary "Nitrate, Nitrite, and Nitroso Compounds in Foods," a publication of IFT's Expert Panel on Food Safety and Nutrition, Joseph H. Hotchkiss, Ph.D., and Robert G. Cassens, Ph.D., principal authors. Updated information was obtained from the Georgetown Center for Food and Nutrition Policy conference "Nitrite as a Food Additive: State of the Science" in Washington, D.C., Dec. 10-11, 1997.
Nitrite has been used as a food preservative and anti-botulinal agent for decades. It has also been a subject of controversy since the 1970s, when some of its reaction-products (i.e., nitrosamines) were associated with cancer in laboratory animals. However, following a 1981 review of all scientific data on nitrite, the National Academy of Sciences/ National Research Council indicated that 1) nitrite does not directly act as a carcinogen in animals 2) nitrate, converted to nitrite in the human body, is neither carcinogenic nor mutagenic and 3) nitrite-preserved or nitrate-containing foods account for only a very small proportion of the human body's total exposure to nitrosamines. Today, it is clear that the benefits of nitrite in cured foods far outweigh any potential risks.
What are nitrite and nitrate?
Nitrite is a salt used to preserve meat, fish, and poultry. It is also a chemical substance in the human body, formed through normal physiological processes and the digestion of foods containing nitrite or nitrate. The latter, a salt of nitric acid, is an essential plant nutrient taken up by plants from soil as their principal nitrogen source. Therefore, nitrate is a natural component of all fruits, vegetables, and cereals.
Why is nitrite added to food?
Nitrite is added to certain foods to prevent the growth of the spore-forming bacterium Clostridium botulinum, whose toxin causes botulism, leading to paralysis and potentially death. Botulinum toxins are the most toxic compounds known, 15,000 times greater than nerve gas and 100,000 times greater than sarin. The word botulinum comes from the Latin word botulus, meaning sausage, which was responsible for many deaths centuries ago before cured with nitrite.
In addition to serving as an antimicrobial, nitrite is used to produce the characteristic flavor, texture, and pink color of cured meats.
What are sources of nitrite and nitrate?
Green leafy and root vegetables, such as spinach and carrots, provide more than 85 percent of dietary nitrate, which may be converted to nitrite by the human body during digestion. Though the majority of ingested nitrate is cleared rapidly from the body via excretion, some of it is transported to the salivary glands and secreted in the mouth. There it may be reduced by existing bacteria to nitrite and carried to the stomach upon swallowing.
Dietary nitrate may also come from drinking water. Though the U.S. Environmental Protection Agency has set a maximum limit for nitrate in drinking water, the levels of nitrate in water vary greatly and may be quite high in some locations. Nitrate content in both drinking water and vegetables is influenced by the use of nitrate fertilizers.
Foods to which nitrite is added include bacon, fermented sausage, hot dogs, bologna, salami, corned beef, ham, and other smoked or cured meat, fish, and poultry. Overall, however, the dietary intake of nitrite from cured meats is only a minor source of the body's total exposure.
A significant amount of nitrite in the body is produced endogenously (internally), rather than introduced from dietary sources.
Why does the human body produce nitrite?
The body generates nitrite through normal nitrogen metabolism in which nitric oxide is produced, then converted to nitrite or nitrate in order to be excreted. At normal levels, nitric oxide is a life-supporting biological messenger that helps heal wounds and burns, promotes blood clotting, controls blood pressure, enhances brain function, and boosts immunity to kill tumor cells and intracellular parasites. Scientific studies have shown that a wound in the process of healing has a significant amount of nitric oxide.
Moreover, when nitrite is acidified in the stomach, it stimulates antimicrobial activity. Just as nitrite protects food against C. botulinum, it may also protect the human stomach against other food borne pathogens.
Are foods containing nitrite or nitrate safe?
Yes, scientific evidence indicates that foods with added nitrite and naturally containing nitrate are safe for human consumption. No restrictions of these foods are supported by science.
Although vegetables are a major source of dietary nitrate, scientists have concluded that the benefits of eating them far outweigh any potential risk of their contribution to nitrite levels in the body. In fact, the conversion of dietary nitrate to nitrite has antimicrobial benefits in the mouth and stomach. Some epidemiological studies show a reduced rate of gastric and intestinal cancer in groups with a high vegetable-based nitrate intake.
What is the regulatory status of nitrite?
Nitrite is regulated as either a prior-sanctioned ingredient (approved for specific use before 1958) or as a food additive, depending on the type of food to which it is added. For curing red meat and poultry products, nitrite is a prior-sanctioned ingredient, not requiring pre-market approval. However, for curing certain fish and use in curing mixes, nitrite is considered a food additive and requires pre-market clearance. Examples of food additive uses for nitrite include smoked or cured chub, tuna fish, sablefish, salmon, shad, and home meat-curing preparations.
Nitrite use is strictly regulated in the United States. The U.S. Department of Agriculture (USDA) is responsible for regulating the use of nitrite in red meat and poultry products. The U.S. Food and Drug Administration oversees matters concerning the safety of cured fish and products using nitrite as a food additive. Permitted uses are limited.
How are foods with added nitrite labeled?
Sodium or potassium nitrite is included in the ingredients list of cured foods. It is usually listed last because ingredients are listed in order from greatest to lowest quantity, and nitrite is used in very small quantities (parts per million).
Does nitrite cause cancer?
Nitrite has never been shown to cause cancer in humans or animals. The American Cancer Society concluded in its 1996 dietary guidelines that "nitrites in foods are not a significant cause of cancer among Americans." A 1996 National Research Council (NRC) report entitled "Carcinogens and Anticarcinogens in the Human Diet" made no mention of cancer risk associated with cured meat consumption.
After much debate about 1974 and 1978 rodent studies that indicated that nitrite digestive reaction-products (N-nitroso compounds) were carcinogenic, the National Academy of Sciences (NAS)/NRC conducted a review of the safety of nitrite. In 1981, the NAS Committee on Nitrite and Alternative Curing Agents in Foods issued a report that concluded that neither nitrite nor nitrate
directly caused cancer in animals. Studies did not provide sufficient evidence to conclude otherwise.
However, due to remaining questions, the NRC called for further studies on the metabolism of nitrate in humans, dietary components that inhibit or enhance nitrosation, and sources of human exposure to N-nitroso compounds (NOCs) in order to develop ways to minimize them.
The NRC also recommended that the food industry 1) reduce nitrite in products to the greatest extent possible without compromising protection against botulism and 2) eliminate the use of nitrate in most cured meat and poultry products. In its 1982 follow-up report, the NRC examined alternatives to nitrites but found none with antibotulinal effects.
In the late 1980s, the U.S. government's Interagency Working Group on Nitrite Research evaluated all data on nitrite and suggested protocols for new rodent studies. The National Toxicology Program (NTP) recently conducted studies for two years based on these protocols. A final report will be issued on its findings in late 1999 or early 2000.
How did the food industry respond to concerns about N-nitroso compounds?
The food industry responded to concerns about NOCs in the 1970s and 1980s by virtually eliminating the addition of nitrate to foods and reducing residual nitrite (analytically detectable) levels in cured meat products five-fold without compromising antibotulinal effects. Today, cured meats on average have one-fifth the amount of residual nitrite present 20 years ago.
The industry also began using agents to block or inhibit the formation of NOCs from nitrite. Such agents include ascorbate (vitamin C), erythorbate (chemically similar to vitamin C), and tocopherol (vitamin E). Most cured meats produced in the United States contain ascorbate or erythorbate. For bacon, adding one of these inhibitors is mandatory.
Are rodent studies effective in evaluating the safety of nitrite?
Animal studies are useful in evaluating effects on human health to a greater or lesser degree, depending on factors of comparison. As it is unethical to perform carcinogenicity tests on humans, laboratory animals are the best models for comparison. However, they do have limitations.
Key questions that surround all nitrite rodent studies are: Do rodents metabolize nitrite the same way that humans do? If not, are rodent studies relevant to the evaluation of nitrite's effects on humans? As scientific consensus is still out on these questions, the forthcoming NTP study results may not reveal any new information about nitrite.
It is also important to note that the doses of NOCs to which rodents were exposed in laboratory tests far exceeded those to which humans are exposed during a lifetime.
Does nitrite cause childhood cancers or leukemia?
No, there is no credible scientific evidence that nitrite or cured foods cause or contribute to childhood cancers or leukemia. At one time, epidemiological reports associating these factors garnered much media attention. However, these studies had limitations, mixed findings and, as all epidemiological studies, could not prove cause and effect.
Evidence from animal studies of the biological plausibility of nitrite causing childhood cancers is too limited to give weight to the epidemiological reports.
How are NOCs formed?
NOCs, including nitrosamines and nitrosamides, are formed by a process called N-nitrosation. With the presence of nitrite, this process can take place in the human stomach. (Because nitrosamines are much more stable after food processing than nitrosamides, they are of greater potential concern.) Nitrite can be introduced in the stomach by consuming foods that contain it and from
endogenous conversion of nitrate to nitrite. Nitrate can be derived from dietary sources or from the body's normal nitrogen metabolism.
Ascorbate, erythorbate, and tocopherol inhibit nitrosamine formation in the body resulting from dietary nitrite or nitrate exposure. This may be why the intake of nitrate from vegetables is of little human health concern; they tend to be rich in antioxidants, such as vitamin C, that inhibit potential nitrosamine formation.
Of greatest concern is exposure to preformed nitrosamines, which mainly come from non-dietary sources.
What are sources of preformed nitrosamines?
Tobacco products are the No. 1 source of preformed nitrosamines. Smoking directly exposes the body to these carcinogens.
Foods are minor contributors to overall exposure to preformed nitrosamines. The use of nitrite in bacon results in very low levels of nitrosamines, which at higher levels, have been shown to be carcinogenic in laboratory animals. As a result, the USDA established a surveillance program for preformed nitrosamines in bacon more than a decade ago.
Beer, whiskey, and other malt-brewed alcoholic beverages have also been shown to contain very low levels of preformed nitrosamines. However, manufacturers have substantially reduced these substances in beverages and foods through
The Institute of Food Technologists has reviewed the scientific issues concerning nitrite and concluded that:
Nitrite is critical to the safety of cured foods. It prevents the outgrowth of C botulinum spores;
Nitrite is responsible for the characteristic flavor and pink color of cured meats;
Foods containing added nitrite or naturally-occurring nitrate do not cause human cancers;
Nitrite levels in U.S. cured foods are currently as low as possible and strictly regulated.
Victoria M. Getty, M.Ed., R.D.
IFAN editor and Extension Specialist
Department of Foods and Nutrition
1264 Stone Hall
West Lafayette, IN 47907-1264
April 29, 1998
Document Number: 121012637