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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Available from: James Coughlin, Oct 05, 2015
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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.
    Sensors and Actuators B Chemical 01/2015; 217. DOI:10.1016/j.snb.2015.01.021 · 4.10 Impact Factor
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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.
    Journal of Ethnopharmacology 10/2014; 167. DOI:10.1016/j.jep.2014.09.040 · 3.00 Impact Factor
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    • "Furthermore, a series of recent studies have shown beneficial effects of dietary NO 3 − intake in cardiovascular and metabolic disease. Still, long-term high-dose NO 3 − supplementation should still be approached with caution till further scientific research on the safety of high-dose NO 3 − boluses typically used by athletes has been done (Bryan et al., 2012; Weitzberg & Lundberg, 2013). It is well documented that AMPK probably plays an important role in muscular metabolic and structural adaptations to exercise training (Richter & Ruderman, 2009). "
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    ABSTRACT: We investigated whether dietary nitrate (NO3−) supplementation enhances the effect of training in hypoxia on endurance performance at sea level. Twenty-two healthy male volunteers performed high-intensity endurance training on a cycle ergometer (6 weeks, 5×30 min/week at 4–6 mmol/L blood lactate) in normobaric hypoxia (12.5% FiO2), while ingesting either beetroot juice [0.07 mmol NO3−/kg body weight (bw)/day; BR, n = 11] or a control drink (CON, n = 11). During the pretest and the posttest, the subjects performed a 30-min simulated time trial (TT) and an incremental VO2max test. Furthermore, a biopsy was taken from m. vastus lateralis before and after the TT. Power output during the training sessions in both groups increased by ∼6% from week 1 to week 6 (P < 0.05). Compared with the pretest, VO2max in the posttest was increased (P < 0.05) in CON (5%) and BR (9%). Power output corresponding with the 4 mmol/L blood lactate threshold, as well as mean power output during TT increased by ∼16% in both groups (P < 0.05). Muscle phospho-AMP-activated protein kinase, hypoxia inducible factor-1α mRNA content, and glycogen breakdown during the TT were similar between the groups in both the pretest and the posttest. In conclusion, low-dose dietary NO3− supplementation does not enhance the effects of intermittent hypoxic training on endurance exercise performance at sea level.
    Scandinavian Journal of Medicine and Science in Sports 04/2014; 25(2). DOI:10.1111/sms.12199 · 2.90 Impact Factor
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