Table 2 Key epidemiological studies exploring associations between inorganic nitrate consumption and non-cancer related health outcomes
Author, year | Population Size | Study Design | Duration of Follow up (y) | Nitrate Assessment | Health Outcome | Key Findings |
|---|---|---|---|---|---|---|
Bahadoran et al., [99] | 4920 | Prospective (Tehran Lipid and Glucose Study) | 5.8 | FFQ | Type 2 Diabetes (T2D) | No significant association between NO3− intake and the risk of T2D in fully adjusted model |
Kang et al. [100] | Nurses’ Health Study (63,893 women) Health Professionals Follow-up Study (41,094 men) | Prospective | ~ 30 years for both | FFQ | Primary open-angle glaucoma (POAG) | Higher dietary NO3− and green leafy vegetable intake was associated with a lower POAG risk, particularly POAG with early paracentral VF loss at diagnosis. |
Mirmiran et al. [101] | 1546 | Prospective (Tehran Lipid and Glucose Study) | 3 | FFQ | Chronic Kidney Disease (CKD) | At baseline, higher intake of high-vegetable NO3− intake was associated with a 48% higher chance of having CKD (OR 1.48, 95% CI 1.05–2.13). After 3 years of follow-up, there was no significant association with the occurrence of CKD |
Blekkenhorst et al. [102] | 1227 | Prospective (Perth Longitudinal Study of Aging in Women) | 15 | FFQ | Atherosclerotic vascular disease (ASVD) mortality | A high vegetable NO3− intake was associated with a lower risk of ASVD (HR: 0.79 95% CI: 0.68, 0.93, P = 0.004) and all-cause mortality (HR: 0.87 95% CI: 0.78, 0.97, P = 0.011) |
Bondonno et al. [103] | 1226 | Prospective (Perth Longitudinal Study of Aging in Women) | 14.5 | FFQ | CCA-IMT, plaque severity and risk of an ischemic cerebrovascular disease event | Higher intake of vegetable NO3− was associated with 17% lower risk of cerebrovascular disease events (P = 0.02) and lower CCA-IMT (P = 0.002). |
Gumanova et al. [104] | 1087 | Cross-sectional (Stress Aging and Health Study) | – | Plasma NOx | Diabetes type II, hyperthyroidism, coronary heart disease, gout and thrombosis/stroke, osteoporosis, cancer | NOx over 44.7 μM were associated with increased prevalence of diabetes type II, hyperthyroidism, coronary heart disease, gout and thrombosis/stroke |
Kuhnle et al. [105] | 7598 | Cross-sectional (EPIC Norfolk) | – | Drinking water NO3− concentrations | Blood pressure (BP) | At low sulfate concentrations, NO3− was inversely associated with BP (− 4 mmHg in top quintile) whereas this was reversed at higher concentrations (+ 3 mmHg in top quintile) |
Maas et al. [106] | 2855 | Prospective (Framingham Offspring Study) | 17.3 | Plasma NO3− | All-cause mortality and incident CVD | Plasma NO3− was weakly associated with an increased risk of death (HR, 1.16; 95%CI, 1.00–1.35 P = 0.057) but not with incident CVD |
Smallwood et al. [107] | 919 | Cross-Sectional (InChianti) | – | 24-h urinary NO3− | Blood pressure | Systolic blood pressure in the ≥2 mmol urinary NO3− excretion group was 3.9 (CI: − 7.1 to − 0.7) mm Hg lower than in the comparison < 1 mmol excretion group. |
Liu et al. [108] | 2900 | Prospective (Blue Mountains Eye Study) | 15 | FFQ | CVD mortality | In multivariable-adjusted analysis, participants in quartile 4 [>  137.8 mg/d; HR 0.63 (95% CI 0.41, 0.95)] of vegetable NO3− intake had lower hazards for CVD mortality compared to participants in quartile 1 (<  69.5 mg/d) |
Mendy et al. [109] | 17,618 | Prospective (NHANES) | 4.3 | Urinary NO3− in spot urine samples | Hypertension and CVD prevalence and all-cause mortality | 1-unit increase in log-transformed urinary NO3− was associated with a > 30% decrease in the odds of hypertension (odds ratio, 0.67; 95% confidence interval [CI], 0.55–0.81), stroke (OR, 0.61, 95% CI, 0.43–0.87) and cardiovascular mortality (HR, 0.44; 95% CI, 0.26–0.73) |
Jackson et al. [110] | 5324 | Prospective (Australian Longitudinal Study on Women’s Health) | 15 | FFQ | Incidence of self-reported CVD-related complications | Women reporting higher total dietary NO3− intakes (Q4 > 78.2 mg/d) and vegetable NO3− intakes (Q4 > 64.4 mg/d) were 25 and 27% reduced risk of developing CVD-related complications, respectively. |
Jackson et al. [111] | Nurses’ Health Study and Health (62,535 women) | Prospective | 26 | FFQ | Coronary heart disease | Dietary NO3− intake was not related to risk of CHD after adjustment for other lifestyle and non-vegetable dietary factors |
Sim et al. [112] | 1420 | Cross-sectional (Perth Longitudinal Study of Aging in Women) | – | FFQ | Hand-grip strength and time up and go (TUG) | Higher NO3− intake (31.2 mg/d) was associated with lower odds for weak grip strength (OR 0.84, 95% CI 0.74–0.95, P = 0.005) and slow TUG (OR 0.86, 95% CI 0.76–0.98, P = 0.021) |
Riddell et al. [113] | 2656 | Prospective | 1.5 | Urinary NO3− to creatinine ratio (uNCR) | Prediction of renal transplant rejection | Overall uNCR was highly variable with no diagnostic threshold for kidney transplant rejection |
Wu et al. [114] 2020 | 14,894 | Cross-sectional (NHANES) | – | Urinary NO3− in spot urine samples | Congestive heart failure, coronary heart disease, angina pectoris, myocardial infarction | Significant association between urinary NO3− and congestive heart failure (OR = 0.651, 95% CI 0.507–0.838, P < 0.001) |
Pereira et al. [98] | 1015 | Cross-sectional (NHANES) | – | Urinary NO3− in spot urine samples | Cognitive function | Urinary NO3− concentrations were not associated with cognitive performance on any of the cognitive tests. |