Inorganic nitrate, a dietary approach for prevention of cardiovascular disease

We study the chemical biology, physiology, and therapeutic effects of nitric oxide (NO) and related reactive nitrogen oxides. NO is a central signaling molecule involved in the regulation of cardiovascular and metabolic function. While NO is classically generated in cells by specific enzymes called NO synthases, we unexpectedly discovered a novel pathway for generating this signaling molecule. Inorganic nitrate, a major oxidation product of NO in our bodies, can be recycled endogenously through a reductive pathway known as the nitrate-nitrite-nitric oxide pathway. This cycle depends entirely on the nitrate reductase activity of oral commensal bacteria through an enterosalivary circulation of this anion. Interestingly, nitrate is also found in our everyday food, particularly in green leafy vegetables. Numerous studies in humans have shown that dietary nitrate increases NO bioactivity, benefiting cardiovascular and metabolic function. Athletes worldwide use dietary nitrate to enhance exercise performance. Nitrate also reduces blood pressure, and a recent phase 2 clinical trial showed remarkable cardioprotective and reno-protective effects of nitrate in patients with acute coronary syndrome. The primary aim of the current project is to design and plan a major phase 3 clinical trial on dietary nitrate to prevent myocardial infarction in at-risk patients. A successful trial could quickly implement this affordable dietary intervention strategy worldwide.