Dietary Nitrate in Vascular and Brain Health

Abstract

Nitric oxide (NO) is a highly reactive molecule that is essential for several biological processes, including the regulation of vascular resistance, neurotransmission and muscular energetics. Sufficient NO production is crucial for the maintenance of a healthy vascular system. With ageing, NO synthesis from arginine, catalysed by NO synthase (NOS), is reduced, which may contribute to increased blood pressure (BP), endothelial dysfunction (ED) and impaired brain function. Dietary nitrate (NO3-) is an important source of NO production via a non-enzymatic pathway involving the progressive conversion of NO3- into nitrite (NO2-) by the action of oral bacteria, and then to NO in low pH and hypoxic environments (i.e., stomach and arterial-tocapillary circulation). Whilst several clinical studies have assessed the effect of supplemental dietary NO3- intake (often supplied as beetroot juice (BJ)) on vascular and cognitive functions, there is a significant gap in the literature concerning the effects of longer-term intervention, especially in older people. This PhD investigated the effects of BJ supplementation in adult population, including healthy younger and older overweight and obese adult population who is at a higher risk of physiological dysfunctions, including cardiovascular disease and cognitive impairment. I conducted a systematic review of observational studies to assess NO3- intake by adults. The review included 55 articles and found that the median daily NO3- intakes were similar in both healthy and patient populations and below the safe upper intake of daily NO3- intake (3.7 mg/kg body weight). Then, I performed a meta-analysis of 18 randomised control trials (RCT) to examine the effect of NO3- or NO2- supplementation on cognitive function and cerebral blood flow (CBF). This meta-analysis revealed no overall effect of NO3- or NO2- supplementation on cognitive function or CBF. This meta-analysis helped to inform the design of the subsequent feasibility study. Next, I conducted a small pilot study to examine the validity and reliability of NO2- salivary strips (against reference standard laboratory measures) with and without the use of mouthwash. This study showed that these strips have a high level of reproducibility and repeatability in detecting changes in salivary NO2-. The study also indicated that the strips can be used to monitor NO3- intake in long-term dietary NO3- interventions. The final phase of this project provided evidence of the acceptability and feasibility of an intervention testing the effects of prolonged consumption of incremental doses of NO3- in overweight and obese older participants. The findings of this study showed that cognitive function and CBF were not affected by long-term BJ supplementation. However, there was a non-significant trend towards on systolic BP (SBP) reduction with lower BJ doses.