The nitrate content of foods and water is highly variable, which has implications for the compilation of food-composition databases and assessment of dietary nitrate intake. A systematic review was conducted to ascertain the dietary assessment methods used and to provide estimates of daily nitrate intake in humans. Relevant articles were identified by a systematic search of 3 electronic databases (PubMed, Web of Science, and Embase) from inception until February 2018. Observational studies conducted in adult populations and reporting information on dietary assessment methods and daily nitrate intake were included. Ecological analyses were conducted to explore the association of nitrate intake with indexes of economic development [Gross Domestic Product (GDP) and KOF Index of Globalization]. A total of 55 articles were included. Forty-two studies investigated associations between nitrate intake and disease risk; 36 (87%) of these studies examined the association between nitrate intake and cancer risk, whereas only 6 studies explored the association of nitrate intake with the risk of diabetes, glaucoma, kidney failure, hypertension, and atherosclerotic vascular disease. The majority of studies used food-frequency questionnaires to assess nitrate intake (n = 43). The median daily nitrate intakes in healthy and patient populations were 108 and 110 mg/d, respectively. We found a significant inverse correlation of nitrate intake with GDP (r = −0.46, P < 0.001) and KOF index (r = −0.31, P = 0.002). The median estimated daily nitrate intakes by healthy and patient populations were similar, and these values were below the safe upper intake of daily intake (3.7 mg nitrate ion/kg body weight). However, there is considerable heterogeneity in the application of food-composition tables, which may have implications for the accuracy of estimated daily nitrate intake. The association between nitrate intake and risk of cardiometabolic diseases needs further investigation. The protocol for this systematic review has been registered in the PROSPERO database (https://www.crd.york.ac.uk/prospero; CRD number: 42017060354).

We conducted a systematic review and meta-analysis of randomized clinical trials examining the effect of inorganic nitrate or nitrite supplementation on cognitive function (CF) and cerebral blood flow (CBF). Two databases (PubMed, Embase) were searched for articles from inception until May 2017. Inclusion criteria were: randomized clinical trials; participants >18 years old; trials comparing a nitrate/nitrite intervention with a control. Thirteen and nine trials were included in the meta-analysis to assess CF and CBF, respectively. Random-effects models were used and the effect size described as standardized mean differences (SMDs). A total of 297 participants (median of 23 per trial) were included for CF; 163 participants (median of 16 per trial) were included for CBF. Nitrate/nitrite supplementation did not influence CF (SMD +0.06, 95% CI: -0.06, 0.18, P = 0.32) or CBF under resting (SMD +0.14, 95% CI: -0.13, 0.41, P = 0.31), or stimulated conditions (SMD + 0.23, 95% CI: -0.11, 0.56, P = 0.19). The meta-regression showed an inverse association between duration of the intervention and CBF (P = 0.02) but no influence of age, BMI or dose (P < 0.05). Nitrate and nitrite supplementation did not modify CBF or CF. Further trials employing larger samples sizes and interventions with longer duration are warranted.

Nitrate-rich food can increase nitric oxide production and improve vascular and brain functions. This study examines the feasibility of a randomised controlled trial (RCT) testing the effects of prolonged consumption of different doses of dietary nitrate (NO₃⁻) in the form of beetroot juice (BJ) in overweight and obese older participants. A single-blind, four-arm parallel pilot RCT was conducted in 62 overweight and obese (30.4 ± 4 kg/m²) older participants (mean ± standard deviation (SD), 66 ± 4 years). Participants were randomized to: (1) high-NO₃⁻ (HN: 2 × 70 mL BJ/day) (2) medium-NO₃⁻ (MN: 70 mL BJ/day), (3) low-NO₃⁻ (LN: 70 mL BJ on alternate days) or (4) Placebo (PL: 70 mL of NO₃⁻-depleted BJ on alternate days), for 13 weeks. Compliance was checked by a daily log of consumed BJ, NO₃⁻ intake, and by measuring NO₃⁻ and NO₂⁻ concentrations in plasma, saliva, and urine samples. Fifty participants completed the study. Self-reported compliance to the interventions was >90%. There were significant positive linear relationships between NO₃⁻ dose and the increase in plasma and urinary NO₃⁻ concentration (R² = 0.71, p < 0.001 and R² = 0.46 p < 0.001, respectively), but relationships between NO₃⁻ dose and changes in salivary NO₃⁻ and NO₂⁻ were non-linear (R² = 0.35, p = 0.002 and R² = 0.23, p = 0.007, respectively). The results confirm the feasibility of prolonged BJ supplementation in older overweight and obese adults.

Nitrate-rich food increases nitric oxide (NO) production and may have beneficial effects on vascular, metabolic, and brain function. This pilot study tested the effects of prolonged consumption of a range of doses of dietary nitrate (NO₃⁻), provided as beetroot juice, on cognitive function and cerebral blood flow (CBF) in overweight and obese older participants. The study had a 13-week single-blind, randomised, parallel design, and 62 overweight and obese older participants (aged 60 to 75 years) received the following interventions: (1) high NO₃⁻ (2 × 70 mL beetroot juice/day) (2) medium NO₃⁻ (70 mL beetroot juice/day), (3) low NO₃⁻ (70 mL beetroot juice on alternate days), or (4) placebo (70 mL of NO₃⁻-depleted beetroot juice on alternate days). Cognitive functions were assessed using the Computerised Mental Performance Assessment System (COMPASS) assessment battery. CBF, monitored by concentration changes in oxygenated and deoxygenated haemoglobin, was assessed in the frontal cortex using near-infrared spectroscopy. The findings of this pilot study showed that cognitive function and CBF were not affected by supplementation with NO₃⁻-rich beetroot juice for 13 weeks, irrespective of the NO₃⁻ dose administered. These findings require confirmation in larger studies using more sophisticated imaging methods (i.e., MRI) to determine whether prolonged dietary NO₃⁻ supplementation influences brain function in older overweight people.

Nitrate-rich food can increase NO production and may induce positive effects on brain function. This study examined the feasibility of a randomized clinical trial (RCT) testing the effects of prolonged consumption of incremental doses of dietary nitrate (NO3-) in overweight and obese older participants. Secondary aims tested dose-dependent changes in cognitive, vascular and pulmonary functions and cerebral blood flow (CBF). This was a single blind, four-arm parallel RCT conducted in 60 overweight and obese older participants. Eligible participants were randomized to:1) high NO3- (140 ml of beetroot juice (BJ) per day, ~800 mg of NO3-/day), 2) moderate NO3- (70 ml of BJ per day, ~400 mg of NO3-/day), 3) low NO3- (70 ml on alternate days, ~400 mg of NO3-) or 4) NO3- depleted (70 ml on alternate days, ~0.001 mg of NO3). Measurements of cognitive, vascular and pulmonary functions and CBF were conducted at baseline and 13-weeks NO3- intake was assessed by six 24-h recalls, and by measuring NO3- intake biomarkers. Feasibility was assessed by obtaining qualitative feedback and evaluating trial recruitment, retention, compliance with study visits and measurement protocols. Participant recruitment started in July 2018 and ended in April 2019. Of all the recruitment strategies that were used, advertisement of the study via Facebook generated the highest response rate. Sixty-two participants consented and were enrolled. Overall, characteristics of included participants matched our recruitment criteria. The findings from this study provide evidence of the acceptability and feasibility of an intervention investigating the effects of incremental doses of high-nitrate BJ over a prolonged period. The intervention study was registered with clinical trial ISRCTN registry (ISRCTN14746723) on 27 December 2018.