Nutritional epidemiology in the context of nitric oxide biology: A risk-benefit evaluation for dietary nitrite and nitrate

Muscle Biology Laboratory, Department of Animal Sciences, University of Wisconsin, Madison, WI, USA.
Nitric Oxide (Impact Factor: 3.52). 09/2009; 22(2):110-9. DOI: 10.1016/j.niox.2009.08.004
Source: PubMed


The discovery of the nitric oxide (NO) pathway in the 1980s represented a critical advance in understanding cardiovascular disease, and today a number of human diseases are characterized by NO insufficiency. In the interim, recent biomedical research has demonstrated that NO can be modulated by the diet independent of its enzymatic synthesis from l-arginine, e.g., the consumption of nitrite- and nitrate-rich foods such as fruits, leafy vegetables, and cured meats along with antioxidants. Regular intake of nitrate-containing food such as green leafy vegetables may ensure that blood and tissue levels of nitrite and NO pools are maintained at a level sufficient to compensate for any disturbances in endogenous NO synthesis. However, some in the public perceive that dietary sources of nitrite and nitrate are harmful, and some epidemiological studies reveal a weak association between foods that contain nitrite and nitrate, namely cured and processed meats, and cancer. This paradigm needs revisiting in the face of undisputed health benefits of nitrite- and nitrate-enriched diets. This review will address and interpret the epidemiological data and discuss the risk-benefit evaluation of dietary nitrite and nitrate in the context of nitric oxide biology. The weak and inconclusive data on the cancer risk of nitrite, nitrate and processed meats are far outweighed by the health benefits of restoring NO homeostasis via dietary nitrite and nitrate. This risk/benefit balance should be a strong consideration before there are any suggestions for new regulatory or public health guidelines for dietary nitrite and nitrate exposures.

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Available from: James Coughlin, Jul 25, 2014
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    • "Whether nitrites and nitrates in foods and drinking water affect human health adversely is a controversial issue (Milkowski et al., 2010). However, as discussed below, high levels of Ntyr, Lpx and carbonyls in mastitic milk are associated with a high level of nitrite and nitrate in that milk. "
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    • "Although modestly increased associations between consumption of foods containing nitrite and nitrate and certain cancers have been reported in some prospective epidemiologic studies (Larsson et al., 2006a,b; van Loon et al., 1998) overall, findings across studies have been largely inconsistent and equivocal (Cross et al., 2011; Jakszyn et al., 2006; Jakszyn and Gonzalez, 2006; Knekt et al., 1999). Consequently, the overall burden of proof remains inconclusive (Adami et al., 2011; Alexander, 2010; Alexander et al., submitted for publication; Boyle et al., 2008; Cho and Smith-Warner, 2004; Eichholzer and Gutzwiller, 1998; Milkowski et al., 2010; Truswell, 2002). A biologically plausible mechanism for the carcinogenicity of ingested nitrate and nitrite involves endogenous Nnitrosation reactions. "
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