We have observed high nitrate intake in communities where type2 diabetes and renal disease is common and I am wondering if they are linked and what the pathway might be.
You know that pharmacologic doses of NO induce oxidative stress (via TNF-alpha) and theoretically lower doses which compensate for the lacked amount would be good (theoretically) to heart.
How much of nitrate and nitrite people in communities with type 2 diabetes consume?
How much of foods containing nitrate and nitrite are consume?
I am looking for these answers - we know that the water in some communtities is high in nitrates, and I think preserved foods are also high but I don;'t lknow how high or how much is too much - I would be very grateful for information and references.
I think tha nitrate an nitrite ma enhance production of highly toxic peroxynitrite.
However, as in many other situations the consequences will depend on metabolic phenotype. Those, which produce ore superoxide radicals will also produce more.more peroxynitrite, thus increasing the amount of damages.
Although, the following information may not completely match the perspectives of your question, however, academically it is worth to know about from my point of view.
Long term nitrite intake has been shown to reverse metabolic syndrome features as well as reducing both the blood triglycerides level and visceral (abdominal) fat accumulation (Carlstrom M, Larsen FJ, Nystrom T, et al. Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(41):17716-17720.).
The most significant applicable cardiovascular protection effect of nitrite intake is its effect on both vascular function and blood pressure [Lundberg JO, Weitzberg E. NO generation from nitrite and its role in vascular control. Arteriosclerosis, thrombosis, and vascular biology. 2005;25(5):915-922. &
Webb AJ, Patel N, Loukogeorgakis S, et al. Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension. 2008;51(3):784-790.]
Further more, dietary nitrite and nitrate intake can reduce inflammation, lower C-reactive protein levels, and protect from stroke, Diabetes type2 and heart attack (Lundberg JO, Carlstrom M, Larsen FJ, et al. Roles of dietary inorganic nitrate in cardiovascular health and disease. Cardiovascular research. 2011;89(3):525-532.)
Basically Nitrite is the conversion product of nitrate which is found mainly in vegetables particularly in beetroot and leafy greens. As I have already mentioned above, research is showing that nitrites become a significant mediating factor for the cardiovascular and metabolic health benefits.
Consumption of vegetables accounts for ~ 80–85 % of daily nitrate exposure in humans.
Nitrite exerts its effects either; directly or by acting through the nitrate-nitrite-nitric oxide pathway through one of the following mechanisms;
Generation of nitric oxide (NO) an important regulator of vascular homeostasis
Acting as an endocrine mediator of NO-based cellular signalling
Acting as a signalling molecule
and
Acting as a regulator of gene expression (Bryan NS, Fernandez BO, Bauer SM, et al. Nitrite is a signalling molecule and regulator of gene expression in mammalian tissues. Nature chemical biology. 2005;1(5):290-297.)
Nonetheless, changes of the NO system in the diabetic kidney and their role in the pathophysiology of diabetic nephropathy still considered to be a complex and controversial issue; many important mechanisms can comodulate NO activity in a particular system (e.g., duration of the disease, glycemic control, insulin treatment, development of diabetes complications)
In conclusion, although many factors (e.g., intoxications caused by nitrite, potential carcinogenic effects, fertilizer overuse..etc) had contributed to the negative picture of inorganic nitrite and nitrate have had for decades, recent experimental studies as the few I have already referred to, related to the molecular interaction between nitrite and heme proteins in blood and tissues, the potential role of nitrite in hypoxic vasodilatation, and an unexpected protective action of nitrite against ischemia/reperfusion injury, have created a different picture and pointes to potential protective effect in Metabolic Syndrome.
However, it is important to know that at this point of time, the benefit/hazard ratio of inorganic nitrate and its active metabolite nitrite remains not clear enough and requires more future researches to be properly studied and explored further in prospective controlled longitudinal studies.
You can run first a statistical analysis, to see if any correlation between the N intake, OS level and any of diseases of interest alone.
The link below will help, I believe, as far as you better know what kind of nitrogen compounds may be present in excess in the environment of these people.
There have been some studies on the occurrence of diabetes due to nitroso compounds in smoked mutton. There was an increased incidence of diabetes in the children of the consumers, but not the consumers themselves.