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.

Download full-text


Available from: James Coughlin, Jul 25, 2014
38 Reads
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this work was to study the effects of mastitis induced by intramammary lipopolysaccharide (LPS) challenge on milk oxidative stability, as well as to understand the underlying biochemical processes that cause such changes. LPS challenge was associated with nitric oxide burst from the surrounding mammary epithelial cells and consequently induced nitrosative stress that was induced by the formation of NO2• from nitrite by lactoperoxidase. This response was associated with an ∼3-fold increased formation of hazardous compounds: nitrotyrosines, carbonyls and lipid peroxides. We sustained the involvement of xanthine oxidase as a major source of hydrogen peroxide. In consistent with previous findings, catalase has been shown to play a major role in modulating the nitrosative stress by oxidizing nitrite to nitrate. The current hygienic quality criteria cannot detect mixing of low-quality milk, such as milk with high somatic cells, and nitrite with high-quality milk. Thus, development of an improved quality control methodology may be important for the production of high-quality milk.
    animal 08/2012; 6(09):1451 - 1459. DOI:10.1017/S1751731112000201 · 1.84 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 08/2012; 50(10):3646-65. DOI:10.1016/j.fct.2012.07.062 · 2.90 Impact Factor
  • Source
    • "A number of publications have reported that increases in nitric oxide (NO) levels are beneficial, especially for cardiovascular health [54]. NO can be destroyed by reactive oxygen species, and PRB has antioxidant properties [55]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Measuring the effects of the acute intake of natural products on human biomarker concentrations, such as those related to oxidation and inflammation, can be an advantageous strategy for early clinical research on an ingredient or product. 31 total healthy subjects were randomized in a double-blinded, placebo-controlled, acute pilot study with post-hoc subgroup analysis on 20 of the subjects. The study examined the effects of a single dose of a polyphenol-rich beverage (PRB), commercially marketed as "SoZo(®)", on serum anti-inflammatory and antioxidant markers. In addition, phytochemical analyses of PRB, and in vitro antioxidant capacity were also performed. At 1 hour post-intake, serum values for 8-iso-PGF2-alpha and advanced oxidation protein products decreased significantly by 40% and 39%, respectively. Additionally, there was a trend toward decreased C-reactive protein, and increased nitric oxide levels. Both placebo and PRB treatment resulted in statistically significant increases in hydroxyl radical antioxidant capacity (HORAC) compared to baseline; PRB showed a higher percent change (55-75% versus 23-74% in placebo group), but the two groups did not differ significantly from each other. PRB produced statistically significant changes in several blood biomarkers related to antioxidant/anti-inflammatory effects. Future studies are justified to verify results and test for cumulative effects of repeated intakes of PRB. The study demonstrates the potential utility of acute biomarker measurements for evaluating antioxidant/anti-inflammatory effects of natural products.
    Nutrition Journal 06/2011; 10(1, article 67):67. DOI:10.1186/1475-2891-10-67 · 2.60 Impact Factor
Show more