| dc.description.abstract | The use of nitrate (NO3-) as a dietary supplement to augment health and improve exercise performance has gained considerable attention in the last decade, with substantial evidence supporting its efficacy as a therapeutic and ergogenic aid. Importantly, the documented benefits have primarily been attributed to changes in nitric oxide (NO) bioavailability throughout the body. Pathways related to NO metabolism have been extensively studied.
However, emerging evidence provides novel insights into how the efficacy of dietary NO3-
supplementation may be contingent on additional components such as the oral microbiome and biological tissues (i.e. skin and skeletal muscle). Evidence supporting beneficial effects of dietary NO3- ingestion on indices of cardiovascular and metabolic health, as well as on the physiological responses to exercise is abundant. Nonetheless, certain clinical conditions in which the composition and environment within the mouth may be altered such as with oral disease, diabetes, pulmonary hypertension, obesity, cardiovascular disease (Koch et al. 2017), as well as the use of anti-bacterial mouthwash, may limit the body’s ability to sequester NO3- from foodstuffs.
In an attempt to circumvent the role of the oral microbiome in NO3- metabolism, chapter 5 investigated whether using a NO3- containing skin lotion could be employed to alter circulating NO3- and NO2-, a marker of NO bioavailability. Results from this chapter illustrated that in humans, NO3- does not appear to traverse through skin to reach the circulation and is ineffective at changing circulating NO3- and NO2-. It is therefore unlikely to influence NO3- metabolism or evoke physiological responses.
Chapter 6 highlights the role of habitual NO3- ingestion (or lack thereof) on the microbial profile in the oral cavity. It was found that when human volunteers were deprived of dietary NO3- (30 – 50 mg NO3-), salivary [NO3-] and [NO2-] decreased when compared to the ingestion of a diet containing a standard (180 mg NO3-) or a high (1000 mg NO3-)
NO3- content. Furthermore, exploratory analyses demonstrated that the alterations in the prevalence (relative abundance of OTUs) of certain bacterial genera and species began to occur following as little as 7-days of dietary NO3- deprivation.
Chapters 7 and 8 investigated the effect of NO3- ingestion on the presence of NO3- in skeletal muscle. Chapter 7 demonstrated that, contrary to early rodent work, the elevation of NO3- in human skeletal muscle following dietary NO3- supplementation is short-lived. The profile of changes in skeletal muscle [NO3-] following the ingestion of NO3- closely reflects that seen in biological fluids such as plasma and saliva, with skeletal muscle [NO3-] initially increasing as early as 30 minutes, peaking between 1 and 3 hours and returning to baseline values at around 9 hours post NO3- ingestion. Chapter 8 is the first study to directly quantify the relative contribution of ingested NO3- to changes in [NO3-] in plasma, saliva, urine and skeletal muscle. One hour following the ingestion of a K15NO3 stable isotope tracer, labelled NO3- accounted for 68% of the total NO3- in skeletal muscle, and ~94%, 96% and 89% of total NO3- in plasma, saliva and urine, respectively.
The work that comprises this thesis evidences the importance of the oral microbiome and its NO2- generating properties by illustrating the ineffectiveness of alternative means of inducing change in circulating NO3- and NO2-. This, coupled with the findings that the oral microbiome is malleable following not only increased NO3- ingestion, but also the removal of NO3- from the diet, substantiates the importance of NO3- ingestion for NO metabolism. Furthermore, this thesis indicates that biological tissues are likely an integral component which influence NO- related processes and therefore should be considered when discussing the effect of NO3- ingestion. This is due to the findings that, following NO3- consumption, the circulation and distribution of NO3- is prompt and substantial increases of NO-related metabolites can be detected in biological fluids (i.e. saliva, whole blood, red blood cells, plasma) and tissues (i.e. skeletal muscle) simultaneously. | en_GB |
