The nitrate-nitrite-nitric oxide pathway: Its role in human exercise physiology

Nitric oxide (NO) is a potent signalling molecule that influences an array of physiological responses. It was traditionally assumed that NO was derived exclusively via the nitric oxide synthase (NOS) family of enzymes. This complex reaction requires a five electron oxidation of L-arginine and is contingent on the presence of numerous essential substrates (including O-2) and co-factors. Recently an additional, O-2-independent, NO generating pathway has been identified, where nitrite (NO2-) can undergo a simple one electron reduction to yield NO center dot NO2- is produced endogenously from the oxidation of NO and also from the reduction of dietary nitrate (NO3-) by facultative bacteria residing on the tongue. Recent data show that dietary NO3- supplementation, which increases the circulating plasma [NO2-], reduces the O-2 cost of submaximal exercise in healthy humans. This finding is striking given that efficiency during moderate-intensity exercise has been considered to be immutable. There is evidence that the muscle ATP turnover at a fixed work rate is reduced and the mitochondrial P/O ratio is increased following NO3- supplementation, which offers important insights into the physiological bases for the reduced (V) over dotO(2) during exercise. NO3- supplementation has also been shown to improve exercise performance in both healthy and patient populations. Therefore, dietary NO3- supplementation may represent a practical and cost-effective method to improve exercise efficiency and exercise tolerance in humans. Given that a NO3--rich diet may have numerous cardiovascular and other health benefits, dietary NO3- intake may have important implications for human lifelong health and performance.