Inorganic nitrite and nitrate: evidence to support consideration as dietary nutrients

There are now indisputable health benefits of nitrite and nitrate derived from food sources or when administered in a clinical setting for specific diseases. Most of the published reports identify the production of nitric oxide (NO) as the mechanism of action for nitrite and nitrate. Basic science as well as clinical studies demonstrates that nitrite and/or nitrate can restore NO homeostasis as an endothelium-independent source of NO that may be a redundant system for endogenous NO production. Nitrate must first be reduced to nitrite by oral commensal bacteria and then nitrite must be further reduced to NO along the physiological oxygen gradient. The purpose of this review is to define their role as indispensable nutrients needed for maintaining NO homeostasis and describe the daily intake required to achieve a threshold of activation as well as define the upper tolerable limits based on published literature in PubMed databases. Optimal ranges of intake will be discussed to maximize the benefits while mitigating any potential risks of overexposure to these naturally occurring anions. This information will allow for future research using safe and effective doses of nitrite and nitrate in long-term clinical trials to effectively test their roles in disease prevention or treatment. (C) 2015 Elsevier Inc. All rights reserved.