Meta-analysis2025Open access

Plasma nitrate, dietary nitrate, blood pressure, and vascular health biomarkers: a GRADE-Assessed systematic review and dose-response meta-analysis of randomized controlled trials

Norouzzadeh M, Hasan Rashedi M, Ghaemi S, Saber N, Mirdar Harijani A, Habibi H, Mostafavi S, Sarv F, Farhadnejad H, Teymoori F, Khaleghian M, Mirmiran P

Nutrition journal · 4 citations

How it was studied

Design
Meta-analysis (indexed by PubMed)
Studied in
People
Main outcome
Health markers and function
Intake measured by
Not stated

Who paid for it

Funding
Independent funding

Based on full-text disclosure statement.

Publication

Published
2025-03-24 · Nutr J · vol. 24 · issue 1 · p. 47
Publisher
BioMed Central
Cited
11 citations · more than 87% of similar papers · 2.3× the field average
References
180 works
Access
Open access (journal) · CC-BY-NC-ND
Research areas
Nitric Oxide and Endothelin Effects · Sodium Intake and Health · Medical and Biological Ozone Research
Keywords
Medicine, Confidence interval, Blood pressure, Internal medicine, Clinical nutrition, Randomized controlled trial, Meta-analysis, Nitrite, Pulse wave velocity, Gastroenterology, Endocrinology, Nitrate
MeSH
humans, hypertension, nitrates, nitrites, diet, blood pressure, dose-response relationship, drug, adult, middle aged, female, male, randomized controlled trials as topic, biomarkers

12 authors

From IR

  • Mostafa NorouzzadehIran University of Medical Sciences
  • Minoo Hasan RashediIran University of Medical Sciences
  • Shadi GhaemiTehran University of Medical Sciences
  • Niloufar SaberResearch Institute for Endocrine Sciences; Shahid Beheshti University of Medical Sciences
  • Artemiss Mirdar HarijaniIran University of Medical Sciences
  • Hamzeh HabibiIran University of Medical Sciences

Abstract

Background

Hypertension and vascular dysfunction are major health concerns, and studies have suggested different interventions, including dietary nitrate (NO3), to improve it. We sought to elucidate the effects of dietary NO3 on plasma NO3 and nitrite (NO2) levels and to determine the shape of the effect of dietary NO3 on blood pressure (BP) and vascular health biomarkers.

Methods

PubMed, Scopus, and Web of Science were searched up to February 2024 for eligible randomized controlled trials (RCTs). The pooled results were reported as weighted mean differences (WMD) and 95% confidence intervals (CIs).

Results

Our analysis of 75 RCTs involving 1823 participants revealed that per each millimole (mmol) increase in the administered NO3 dose, both acute (WMD: 32.7µmol/L; 95%CI: 26.1, 39.4) and chronic-term (WMD: 19.6µmol/L; 95%CI: 9.95, 29.3) plasma NO3 levels increased. Per each mmol increase in NO3 intake, a reduction in systolic BP levels was observed in the acute (WMD: -0.28mmHg; 95%CI: -0.40, -0.17), short-term (WMD: -0.24mmHg; 95%CI: -0.40, -0.07), and medium-term (WMD: -0.48mmHg; 95%CI: -0.71, -0.25) periods. Furthermore, a decrease in diastolic BP for each mmol increase in NO3 intake (WMD: -0.12 mmHg; 95% CI: -0.21, -0.03) was shown. Moreover, a linear dose-response relationship was indicated between each mmol of NO3 intake and medium-term pulse wave velocity (WMD: -0.07 m/s; 95%CI: -0.11, -0.03), medium-term flow-mediated dilation (WMD: 0.30%; 95%CI: 0.15, 0.46), and medium-term augmentation index (WMD: -0.57%; 95%CI: -0.98, -0.15).

Conclusion

We observed dose-dependent increases in plasma NO3 and NO2 levels, along with consequent reductions in BP and enhancements in vascular health following dietary NO3 supplementation. Future high-quality, population-specific studies with optimized dietary NO3 dosages are needed to strengthen the certainty of the evidence.

Registration

The protocol for this systematic review was registered in PROSPERO under the registration number CRD42024535335.

Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC-ND).

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