The Nitrate-Nitrite-Nitric Oxide Pathway: Findings from 20 Years of the Tehran Lipid and Glucose Study

Context: We describe here the contributions of the Tehran lipid and glucose study (TLGS) to understanding different aspects of the nitrate (NO3)-nitrite (NO2)-nitric oxide (NO) pathway in health and disease. Evidence Acquisition: All English-language documents from the TLGS, focused on NO pathway were searched using the PubMed, Scopus, and Embase databases. Results: Reference values of serum concentrations of NO metabolites (nitrate+nitrite or NOx) were 11.5 - 76.4, 10.1 - 65.6, and 10.3 - 66.8mol/L inmen, women, andthe total population, respectively. CirculatingNOxwasaffected by age, smokinghabits, menopause status, thyroid hormones, and various pathologic conditions. Elevated serum NOx was related to increased incidence of metabolic syndrome (odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.19 - 2.59), hypertriglyceridemic-waist phenotype (OR = 1.39, 95% CI = 1.05 - 1.93), chronic kidney disease (OR = 1.86, 95% CI = 1.10 - 3.14) in women, and cardiovascular disease (hazard ratio (HR) = 1.35, 95% CI = 1.01 - 1.80] in the total population. In participants with low vitamin C intake, higher intakes of NO2 ( 8.77 mg/d) were accompanied with increased risk of diabetes (HR = 2.43, 95% CI = 1.45 - 4.05). A decreased risk of hypertension (OR = 0.58, 95% CI = 0.33 - 0.98) and chronic kidney disease (OR = 0.50, 95% CI = 0.24 - 0.89) was observed in response to higher intakes of NO2. Conclusions: Circulating NOx is associated with and could predict the risk of metabolic disorders in a general population. Moreover, dietary NO3/NO2 exposure from usual diets seems to contribute to development of noncommunicable diseases.