Studies have demonstrated nitrite therapy increases adenosine triphosphate (ATP) synthesis in
skeletal muscle mitochondria concomitant with reduced whole-body oxygen cost during steady
state exercise. Our own work has demonstrated safety and efficacy of an FDA investigational
new drug (IND) approved sodium nitrite (10 milligram [mg]) capsule, and its utility to
upregulate the sirtuin 3 adenosine monophosphate protein kinase (SIRT3-AMP) pathway of
skeletal muscle of younger heart failure (HF) patients. It now seems exceptionally logical
and opportune to apply these insights to older HF patients and to delineate mechanisms of
disease and aging that respond to nitrite therapy.