Abstract/Summary

Context: Inorganic nitrate is an exogenous source of nitric oxide, an established regulator of vascular homeostasis via nitrate-nitrite-nitric oxide pathway. Here, we evaluate the impact of inorganic nitrate on endothelial function, a risk factor for cardiovascular disease. Objective: A systematic review of the existing literature and a meta-analysis were performed. Trials testing inorganic nitrate versus a control were selected and the change in forearm endothelial function (as assessed by flow mediated dilatation; FMD) were included. Data Sources: The following databases were searched: MEDLINE, Web of Science, and Scopus. Data Extraction and Analysis: Standardised mean differences in %FMD were pooled using a random-effects model and thirteen studies were included in the analysis. Quality assessment was performed using the Cochrane risk-of-bias score. Results: Inorganic nitrate was associated with improved ∆%FMD versus the control, standardised mean difference was 1.48% (95% CI: 0.70- 2.27), p< 0.01; high heterogeneity (I2= 98.2%) was observed. The significant effect observed remained irrespective of dose (± 600 mg nitrate), duration (acute or chronic consumption), health status (± health conditions) and type of nitrate (dietary or non-dietary). Notably acute studies had a greater FMD response than chronic studies (1.93%, 95% CI: 0.71, 3.15 versus 0.90%, 95% CI: 0.48, 1.31). More than half of the studies reviewed showed low risk of bias; the rest of the studies were classified as “some concern” due to lack of information about randomisation process and lack of pre-specified analysis plans. Conclusion: Our results show that from a modest number of included trials, inorganic nitrate consumption improves FMD response by more than 1%, a clinically relevant magnitude for the prevention of cardiovascular disease.