Nitrite and the Impact of Advisory Groups

Nitrite has been a component of mixtures used to cure meats for centuries. It is important for a variety of reasons in curing meats, the most important being the inhibition of the growth of, and toxin production by, Clostridium botulinum. It is not accidental that the species name derived from the Latin word for sausage, botulus. However, since the use of nitrite in cured meats became commonplace, there have been no cases of botulism linked to these products.

About 30 years ago, two charges about safety (hypotheses) were leveled at nitrite: first, that nitrite was linked to methemoglobinemia (blue baby syndrome), and second, that nitrite consumption, and therefore the consumption of nitrite-cured meats, increased the risk of certain cancers in adults. In response, the meat industry significantly lowered the levels of nitrite in meat products. Methemoglobinemia, an issue related to nitrites being formed from nitrates in feeding bottles, has been virtually eradicated in developed countries.

To understand the cancer issue better, an understanding of the real sources of nitrite is required, and to gain that understanding, one must understand nitrate metabolism.

Nitrate present in blood plasma has two sources, endogenous (from the metabolism of L-arginine to nitric oxide) and exogenous (80% from vegetables and 10–15% from water). Plasma nitrate is in part passively lost in urine, and actively secreted into the colon and in saliva. About 25% of ingested nitrate is recycled via secretion in saliva, a process known as the enterosalivary circulation of dietary nitrate. About one-fifth of that salivary nitrate is converted by oral-cavity microorganisms to nitrite. The microorganisms are Gram-positive and appear to dwell on the tongue. The amount of nitrite ingested as a food additive in cured meats is less than 5% of the amount of nitrite contributed by endogenous sources.

The thinking was that various cancers were caused by ingested nitrites, which upon entering the stomach, react with amines to form nitrosamines, and since most nitrosamines are human and animal carcinogens, the ingestion of nitrites must therefore lead to cancers. But as stated above, nitrite reaching the stomach comes mainly from endogenous sources, and not from dietary sources (mainly cured meats). Were human beings poorly designed such that we would each be “auto-exposed” to potent carcinogens?

In 1995 and 1996, a curious mixture of scientific literature appeared relative to nitrite. For example, one study researched the possibility of reducing the oral bacteria responsible for nitrite formation from salivary nitrate by the use of various antibacterial mouthwashes and toothpastes, thus reducing the “induction of methemoglobinemia” and the formation of carcinogenic N-nitroso compounds. 

Several other papers had an altogether different character, that of nitrite as a potent antimicrobial substance when ingested and acidified in the stomach. Acidified nitrite was shown to have a potent inhibitory and/or lethal effect on significant gut pathogens such as Yersinia enterocolitica, Salmonella enteritidis, Salmonella typhimurium, Shigella sonnei, and Escherichia coli O157:H7. 

Several groups of investigators speculated that nitrite (especially that derived from dietary nitrate) may provide humans significant protection from gut pathogens, and essentially act as an element of innate immunity. One report correlated the destruction of oral nitrate reductase–producing mouth bacteria during a course of amoxycillin with a significant decrease in salivary nitrite concentration. The implication was that antibiotics may decrease oral production of nitrite and thus lead to an increase in oral and intestinal infections. 

Another report suggested that acidified nitrite may kill Helicobacter pylori, a bacterium that readily survives stomach acid alone and is suspected of leading to gastric cancers. The pendulum has clearly swung toward the beneficial aspects of nitrite. These now include a role as a host defense against gastrointestinal infections, a modulator of platelet activity and possibly gastrointestinal motility and microcirculation. 

In mid-2000, the Board of Scientific Counselors’ Technical Reports Review Subcommittee held a public meeting to consider the National Toxicology Program’s long-term rodent study on the safety of sodium nitrite. The subcommittee, composed of nine outside experts in toxicology and pathology, reviewed the data and testimony presented at the public meeting and concluded that there was no evidence that nitrite is a carcinogen in male and female rats and male mice, and “equivocal” evidence for carcinogenic activity in female mice. The classification of equivocal roughly equates to insufficient evidence. It’s fair to say that the federal scientists who presented the data did not agree, and believed there was evidence for carcinogenicity in female mice. 

Hopefully, the “outside” advisors, whose classification of nitrite stands, have put to rest the charge that the relatively minuscule amount of nitrite ingested from cured meats results in cancers. This is an excellent example of the impact of advisory committees on federal thinking. 

by DOUGLAS L. ARCHER
Contributing Editor