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Table 2 Key epidemiological studies exploring associations between inorganic nitrate consumption and non-cancer related health outcomes

From: Dietary nitrate and population health: a narrative review of the translational potential of existing laboratory studies

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.
  1. EPIC European Prospective Investigation of Cancer, FFQ Food Frequency Questionnaire, CCA-IMT Common Carotid Intimal Medial Thickness, NO3 Nitrate, NO2 nitrite, NOx Nitrate + Nitrite Concentration, CVD Cardiovascular Disease, OR Odds Ratio, HR Hazard Ratio, NHANES National Health and Nutrition Examination Survey, uNCR Urinary nitrate to creatinine ratio