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Background: Dietary inorganic nitrate (NO3−) is a polyatomic ion, which is present in large quantities in green leafy vegetables and beetroot, and has attracted considerable attention in recent years as a potential health-promoting dietary compound. Numerous small, well-controlled laboratory studies have reported beneficial health effects of inorganic NO3− consumption on blood pressure, endothelial function, cerebrovascular blood flow, cognitive function, and exercise performance. Translating the findings from small laboratory studies into 'real-world' applications requires careful consideration. Main body: This article provides a brief overview of the existing empirical evidence basis for the purported health-promoting effects of dietary NO3− consumption. Key areas for future research are then proposed to evaluate whether promising findings observed in small animal and human laboratory studies can effectively translate into clinically relevant improvements in population health. These proposals include: 1) conducting large-scale, longer duration trials with hard clinical endpoints (e.g. cardiovascular disease incidence); 2) exploring the feasibility and acceptability of different strategies to facilitate a prolonged increase in dietary NO3− intake; 3) exploitation of existing cohort studies to explore associations between NO3− intake and health outcomes, a research approach allowing larger samples sizes and longer duration follow up than is feasible in randomised controlled trials; 4) identifying factors which might account for individual differences in the response to inorganic NO3− (e.g. sex, genetics, habitual diet) and could assist with targeted/personalised nutritional interventions; 5) exploring the influence of oral health and medication on the therapeutic potential of NO3− supplementation; and 6) examining potential risk of adverse events with long term high- NO3− diets. Conclusion: The salutary effects of dietary NO3− are well established in small, well-controlled laboratory studies. Much less is known about the feasibility and efficacy of long-term dietary NO3− enrichment for promoting health, and the factors which might explain the variable responsiveness to dietary NO3− supplementation between individuals. Future research focussing on the translation of laboratory data will provide valuable insight into the potential applications of dietary NO3− supplementation to improve population health. [ABSTRACT FROM AUTHOR]

Background: Circulating nitric oxide (NO) and lipid levels are closely associated with coronary artery disease (CAD). It is unclear whether the rs1799983 polymorphism in endothelial nitric oxide synthase (NOS3) gene is associated with plasma levels of NO and lipids. This systematic review and meta-analysis (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) aimed to clarify the relationships between the rs1799983 polymorphism and plasma levels of NO and lipids.Methods: Sixteen studies (2702 subjects) and 59 studies (14 148 subjects) were identified for the association analyses for NO and lipids, respectively. Mean difference (MD) and 95% CI were used to estimate the effects of the rs1799983 polymorphism on plasma NO and lipid levels. The primary outcome variable was NO, and the secondary outcomes included triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C).Results: Carriers of the T allele had lower levels of NO (MD -0.27 μmol/L, 95% CI -0.42 to -0.12 μmol/L, p<0.001) and HDL-C (MD -0.07 mmol/L, 95% CI -0.14 to -0.00 mmol/L, p=0.04), and higher levels of TC (MD 0.13 mmol/L, 95% CI 0.06 to 0.20 mmol/L, p<0.001) and LDL-C (MD 0.14 mmol/L, 95% CI 0.05 to 0.22 mmol/L, p=0.002) than the non-carriers. Triglyceride levels were comparable between the genotypes.Conclusion: The association between the NOS3 rs1799983 polymorphism and CAD may be partly mediated by abnormal NO and lipid levels caused by the T allele. [ABSTRACT FROM AUTHOR]