Does dietary nitrate say NO to cardiovascular ageing? Current evidence and implications for research

Abstract

CVD are characterised by a multi-factorial pathogenesis. Key pathogenetic steps in the development of CVD are the occurrence of endothelial dysfunction and formation of atherosclerotic lesions. Reduced nitric oxide (NO) bioavailability is a primary event in the initiation of the atherosclerotic cascade. NO is a free radical with multiple physiological functions including the regulation of vascular resistance, coagulation, immunity and oxidative metabolism. The synthesis of NO proceeds via two distinct pathways identified as enzymatic and non-enzymatic. The former involves the conversion of arginine into NO by the NO synthases, whilst the latter comprises a two-step reducing process converting inorganic nitrate into nitrite and subsequently NO.Inorganic is present in water and food, particularly beetroot and green leafy vegetables. Several investigations have therefore used the non-enzymatic NO pathway as a target for nutritional supplementation ( salts) or dietary interventions (high- foods) to increase NO bioavailability and impact on cardiovascular outcomes. Some studies have reported positive effects of dietary on systolic blood pressure and endothelial function in patients with hypertension and chronic heart failure. Nevertheless, results have been inconsistent and the size of the effect appears to be declining in older individuals. Additionally, there is a paucity of studies for disorders such as diabetes, CHD and chronic kidney failure. Thus, whilst dietary supplementation could represent an effective and viable strategy for the primary and secondary prevention of age-related cardiovascular and metabolic diseases, more large-scale, robust studies are awaited to confirm or refute this notion.

Mediterranean Diet Increases Endothelial Function in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Indeed, in the large-scale PREDIMED trial, CVD incidence was reduced by 31% and 28% with an There are several mechanisms through which the MedDiet could improve endothelial function, which may account for the beneficial effects observed in this study. Firstly, the MedDiet augments the bioavailability of nitric oxide (NO) (38), which is essential for healthy endothelial function due to its vasodilatory, anti-atherogenic and anti-proliferative actions (5). The NO 'boosting' effects of the MedDiet may be due to antioxidant effects minimising superoxide scavenging of NO (38,39), the provision of the NO precursors inorganic nitrate (green leafy vegetables) and L-arginine (nuts, grains, legumes, and fish) (39), and/ or the upregulation of endothelial NO synthase (oily fish) (40,41).…”

“…Loss of functional and structural integrity of the endothelium is thought to be an early pathogenic step in the development of atherosclerotic lesions and the subsequent onset of cardiovascular diseases (CVD) (3). Therefore, the endothelium has been identified as a tractable physiological target for therapeutic interventions designed to reduce risk for CVD such as stroke, coronary heart disease or peripheral arterial disease (4,5).…”

Knowledge and beliefs about dietary inorganic nitrate among UK-based nutrition professionals: development and application of the KINDS online questionnaire

“…A key catalyst for this change was the discovery that nitrate is a substrate for production of the multifunctional gasotransmitter nitric oxide11 12 and, so, may influence a range of nitric oxide-mediated physiological processes with potentially beneficial effects. For example, several investigations have demonstrated that dietary supplementation with inorganic nitrate, typically in doses between 4 and 12 mmol/day (~250–750 mg/day), can reduce blood pressure (BP),13–17 improve endothelial function14 17 18 and, at least in recreationally active and moderately trained individuals, enhance exercise performance 19–24. In addition, several recent observational studies have linked increased nitrate intake with reduced risk of cardiovascular disease mortality,25 atherosclerotic vascular disease26 and ischaemic cerebrovascular disease 27…”

NuBrain: UK consortium for optimal nutrition for healthy brain ageing

“…This suggests that, with correct implementation, the MedDiet could represent an effective dietary strategy to aid healthy brain ageing in non‐Mediterranean countries such as the UK. Mechanistically, these effects may be related to favourable alterations in blood glucose and lipid profiles (Rodríguez‐Rejón et al 2014; Ros et al 2014), decreased oxidative stress and inflammation (Mena et al 2009; Urquiaga et al 2010; Casas et al 2014), augmented nitric oxide (NO) bioavailability (Siervo et al 2018; Shannon et al 2018) and modulation of the gut microbiome (Filippis et al 2016; Tosti et al 2018). In NuBrain, we will extend these encouraging initial findings using data from other large UK cohorts as outlined below (see Work Package 2).…”