Ingested nitrate and nitrite and stomach cancer risk: An updated review

Texas Therapeutics Institute, Brown Foundation Institute of Molecular Medicine, Department of Integrative Biology and Pharmacology, The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas Health Science Center, Houston, TX, USA. Electronic address: .
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association (Impact Factor: 2.9). 08/2012; 50(10):3646-65. DOI: 10.1016/j.fct.2012.07.062
Source: PubMed


Nitrite and nitrate are naturally occurring molecules in vegetables and also added to cured and processed meats to delay spoilage and pathogenic bacteria growth. Research over the past 15years has led to a paradigm change in our ideas about health effects of both nitrite and nitrate. Whereas, historically nitrite and nitrate were considered harmful food additives and listed as probable human carcinogens under conditions where endogenous nitrosation could take place, they are now considered by some as indispensible nutrients essential for cardiovascular health by promoting nitric oxide (NO) production. We provide an update to the literature and knowledge base concerning their safety. Most nitrite and nitrate exposure comes from naturally occurring and endogenous sources and part of the cell signaling effects of NO involve nitrosation. Nitrosation must now be considered broadly in terms of both S- and N-nitrosated species, since S-nitrosation is kinetically favored. Protein S-nitrosation is a significant part of the role of NO in cellular signal transduction and is involved in critical aspects of cardiovascular health. A critical review of the animal toxicology literature of nitrite indicates that in the absence of co-administration of a carcinogenic nitrosamine precursor, there is no evidence for carcinogenesis. Newly published prospective epidemiological cohort studies indicate that there is no association between estimated intake of nitrite and nitrate in the diet and stomach cancer. This new and growing body of evidence calls for a reconsideration of nitrite and nitrate safety.

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    • "This ion can react with amines to form carcinogenic nitrosamines in vivo and in excess in the blood can also react with hemoglobin leading to the formation of metahemoglobin and suppressed oxygen transport [20]. Nitrite ions are known to have potentially harmful effects in spontaneous abortion, intrauterine growth restriction, birth defects, blue baby syndrome and gastric cancer [17] [21]. According to the regulation for nitrite established by the Unite States Environmental Protection Agency (USEPA), the maximum contaminant level is 1.0 mg L –1 in drinking water [19]. "
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    ABSTRACT: A simple and sensitive photoelectrochemical sensor based on the bismuth vanadate (BiVO4) photoanode coupled to visible light excitation was developed for nitrite detection. The BiVO4was prepared by hydrothermal methods and used as photoelectroactive sensor. Photoexcitation with visible light allows nitrite anions to act as highly efficient hole scavenger at lowpotential. The photocurrent response increases linearlywith nitrite concentration in the solution. The proposed device operates in the range of detection (2.5 to 100.0 μmol L–1), with limit of detection (1.5 μmol L–1), and with good reproducibility (4.1%) for nitrite analysis.
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    • "Nitrite ions become important and extensively used because of their high reactivity and may act as an oxidizing, reducing or nitrosing agent, beyond the possibility of being converted to a variety of compounds, including nitrous acid, nitrogen oxides and nitrates, and the possibility to be used as a stabilizer and preservative in meats, canned foods, cheeses, among others food [1]. In contrast, there is evidence that ingestion of large amounts of nitrite may be linked to cancer of the stomach [2] [3], bowel, leukemia and the appearance of brain tumors in children [4]. Then, due to its potential toxicity, a series of rules that restrict their level in drinking water and food products were implemented, such as, the World Health Organization (WHO/SDE/WSH/07.01/16) "
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    ABSTRACT: A biomimetic sensor based on oxo-bridged dinuclear manganese–phenanthroline complex immobilized into an ion-exchange polymeric film deposited on glassy carbon electrode was applied to detection of nitrite ions and studied according to their kinetics parameters. The cyclic voltammetry at the modified electrode in universal buffer showed a two electron oxidation/reduction of the couple MnIV(μ-O)2MnIV/MnIII(μ-O)2MnIII and electrocatalytic property toward nitrite oxidation with a decrease of the overpotential of 320 mV compared with the bare glassy carbon electrode. A plot of the anodic current vs. the nitrite ions concentration for potential fixed (+0.480) at the biomimetic sensor was linear in the 2.49 × 10−6 to 9.90 × 10−6 mol L−1 concentration range with a detection limit of 6.50 × 10−6 mol L−1. The kinetic mechanism was derived by Michaelis–Menten, then, kinetics parameters were calculated through four methods: Lineweaver–Burke, Eadie–Hofstee, Hanes–Woolf and Nonlinear curve fitting. The best results were Michaelis–Menten rate constant = 3.42 μmol L−1, catalytic rate constant = 0.0114 s−1, catalytic efficiency = 3.3 × 103 (mol L)−1 s−1 and heterogeneous electrochemical rate constant = 1.15 × 10−5 cm s−1.
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    • "Other factors, such as smoking, are far more significant. An updated review in 2012 (Bryan et al., 2012) came to the firm conclusion that there is no association, in humans, between nitrosamine formation and gastric cancer. The Netherlands Cohort Study (Keszei et al., 2013), in which 120,000 men and women were tracked for 16.3 years, concluded that, although nitrosamines in the diet may cause oesophageal carcinomas , there was no clear association with other gastric subtypes. "
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    ABSTRACT: The presence of nitrite in the human diet was thought to be a hazard as that could result in the formation of secondary nitrosamines, known to cause gastric cancers in animal models. Nitrite is added to food as an antibacterial agent and can also be formed by the action of reductase enzymes, present in the mouth, on nitrate. However, the epidemiological evidence linking gastric cancers in humans with nitrite and nitrate in the diet is lacking. In addition, recent work has shown that nitrate in the diet has potential benefit as it can cause a fall in blood pressure. The early use of nitrate in traditional Chinese medicine for the treatment of angina is described.
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