Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults
Oral Nitrite and Nitrate in Healthy Normal Volunteer Adults
This proposal hypothesizes that oral supplementation with sodium nitrite or nitrate will
 result in in vivo conversion of nitrate to nitrite and nitrite to nitric oxide with limited
 toxicity in the doses proposed in healthy adult normal volunteers. We utilize a powerful in
 vivo technique (pharmacokinetic testing) and are the first to design inorganic nitrate and
 nitrite capsules for cardiovascular disease.
Preclinical and clinical research over the last decade has revealed the important
 vasoprotective effects of nitrates and nitrites with regards to reduction in blood pressure,
 vascular inflammation and endothelial dysfunction. New findings suggest an effect of nitrate
 and nitrite therapy in the regulation of glucose-insulin homeostasis. Development of an oral
 formulation of nitrate and nitrite salts is attractive, whereby nitrite would ensure rapid
 acting effects upon absorption, while the nitrate would continuously provide a slow formation
 of nitrite over a prolonged period of time via the enterosalivary circulation pathway.

 For this reason, development of an oral formulation of nitrate and nitrite salts is
 attractive, whereby nitrite would ensure rapid acting effects upon absorption, while the
 nitrate would continuously provide a slow formation of nitrite over a prolonged period of
 time via the enterosalivary circulation pathway. This study aims to establish the
 pharmacokinetics, metabolism and interconversion of nitrate to nitrite and nitrite to nitric
 oxide in vivo in healthy adult normal volunteers.
Inclusion Criteria:

 -  Age 18-60 years

 -  Systolic blood pressure ≤130 and diastolic blood pressure ≤85 mm Hg

 Exclusion Criteria:

 -  Positive urine pregnancy test or breastfeeding

 -  Concurrent use of medications affecting glucose or lipid metabolism

 -  Recent addition or change in dosing of hormonal contraceptive medications (oral
 contraceptive pill, intrauterine device, DepoProvera)

 -  Current use of ≥2 anti-hypertensive agents regardless of blood pressure control or
 normotensive on a single agent

 -  Current use of phosphodiesterase 5 inhibitors or organic nitrates

 -  Not stable on treatments for the prior three months or not planning to remain on
 current dose of medications for blood pressure, contraception, etc

 -  Known chronic psychiatric or medical conditions including diabetes, liver or kidney
 disease or obesity syndromes

 -  Smoker