On the mechanism by which dietary nitrate improves human skeletal muscle function

Abstract

Inorganic nitrate is present at high levels in beetroot and celery, and in green leafy vegetables such as spinach and lettuce. Though long believed inert, nitrate can be reduced to nitrite in the human mouth and, further, under hypoxia and/or low pH, to nitric oxide. Dietary nitrate has thus been associated favorably with nitric-oxide-regulated processes including blood flow and energy metabolism. Indeed, the therapeutic potential of dietary nitrate in cardiovascular disease and metabolic syndrome-both aging-related medical disorders-has attracted considerable recent research interest. We and others have shown that dietary nitrate supplementation lowers the oxygen cost of human exercise, as less respiratory activity appears to be required for a set rate of skeletal muscle work. This striking observation predicts that nitrate benefits the energy metabolism of human muscle, increasing the efficiency of either mitochondrial ATP synthesis and/or of cellular ATP-consuming processes. In this mini-review, we evaluate experimental support for the dietary nitrate effects on muscle bioenergetics and we critically discuss the likelihood of nitric oxide as the molecular mediator of such effects.

Keywords: ATP turnover; cellular bioenergetics; coupling efficiency of oxidative phosphorylation; dietary nitrate; nitric oxide; nitrite; oxygen cost of human exercise; skeletal muscle mitochondria.

Figure 1

Putative mechanism by which dietary NO${}_3^{-}$ may lower the O₂ cost of human exercise. Dietary NO${}_3^{-}$ increases plasma NO${}_3^{-}$ and NO${}_2^{-}$ levels thus improving efficiency of skeletal muscle ATP supply by oxidative phosphorylation and/or of ATP turnover. Effects on the bioenergetics of skeletal muscle cells may be direct or indirect through formation of NO. Shown reactions are examples of RNS-induced protein modifications (see text for details).