Acute Blood Pressure Lowering, Vasoprotective, and Antiplatelet Properties of Dietary Nitrate via Bioconversion to Nitrite
Open accessAbstract
Diets rich in fruits and vegetables reduce blood pressure (BP) and the risk of adverse cardiovascular events. However, the mechanisms of this effect have not been elucidated. Certain vegetables possess a high nitrate content, and we hypothesized that this might represent a source of vasoprotective nitric oxide via bioactivation. In healthy volunteers, approximately 3 hours after ingestion of a dietary nitrate load (beetroot juice 500 mL), BP was substantially reduced (Δ max −10.4/8 mm Hg); an effect that correlated with peak increases in plasma nitrite concentration. The dietary nitrate load also prevented endothelial dysfunction induced by an acute ischemic insult in the human forearm and significantly attenuated ex vivo platelet aggregation in response to collagen and ADP. Interruption of the enterosalivary conversion of nitrate to nitrite (facilitated by bacterial anaerobes situated on the surface of the tongue) prevented the rise in plasma nitrite, blocked the decrease in BP, and abolished the inhibitory effects on platelet aggregation, confirming that these vasoprotective effects were attributable to the activity of nitrite converted from the ingested nitrate. These findings suggest that dietary nitrate underlies the beneficial effects of a vegetable-rich diet and highlights the potential of a “natural” low cost approach for the treatment of cardiovascular disease.
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Nitrate dosing amounts (300-600 mg or 0.1 mmol/kg/day) appear to be well tolerated without significant alterations in hemodynamics or clinical boundaries of hepatorenal and muscle enzyme status.
“These dosing amounts appear to be well tolerated when consumed as both supplemental [587] and supplemental sources [588] without significant alterations in hemodynamics or clinical boundaries of hepatorenal and muscle enzyme status [478, 589].”
From ISSN exercise & sports nutrition review update: research & recommendations (2018) · cites this paper as [588]
The Results state that beetroot juice was generally well tolerated. But the Results section ‘Dietary nitrate lowers BP’ reports significant reductions in blood pressure, contrary to the claim of no significant hemodynamic alteration. The paper does not report hepatorenal or muscle enzyme safety measurements; its Discussion mentions 0.1 mmol/kg/day only when describing another study. (LLM, conf=0.90)
Experimental — accuracy not yet measuredDietary NO3- supplementation through NO3- salts or vegetable products such as beetroot juice reduces blood pressure in healthy young and old humans.
“The NO3-- NO2--NO reduction pathway underpins the discovery that dietary NO3- supplementation through consumption of NO3- salts [27] or vegetable products such as beetroot juice [23], [40] reduces blood pressure (BP) in healthy young and old humans.”
From Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans (2018) · cites this paper as [40]
The Results ('Dietary nitrate lowers BP'; page unavailable) report that beetroot juice lowered blood pressure compared with water, and the Methods ('BP study'; page unavailable) identify the participants as healthy volunteers. Our copy does not establish that this finding applies to both young and old humans; the sodium-nitrate salt finding is discussed as a separate study. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe magnitude of the blood pressure response to NO3- supplementation is correlated with baseline blood pressure.
“The magnitude of the BP response to NO3-supplementation is correlated with baseline blood pressure [22], [40]”
From Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans (2018) · cites this paper as [40]
The Results section reports that beetroot juice lowered blood pressure, but its reported correlation is between the change in plasma nitrite and the change in systolic blood pressure—not between baseline blood pressure and the size of the response. The Discussion notes a larger response to a fruit-and-vegetable diet in hypertensive than normotensive people and suggests nitrate's effect might likewise be greater; it does not establish the claimed correlation for nitrate supplementation. No page numbers are available in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredDietary nitrate has a range of beneficial vascular effects, including reducing blood pressure, inhibiting platelet aggregation, preserving or improving endothelial dysfunction, enhancing exercise performance in healthy individuals and patients with peripheral arterial disease.
“Dietary nitrate has been demonstrated to have a range of beneficial vascular effects, including reducing blood pressure, inhibiting platelet aggregation, preserving or improving endothelial dysfunction, enhancing exercise performance in healthy individuals and patients with peripheral arterial disease.”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [79]
Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIn healthy volunteers, beetroot juice as a nitrate source reduces blood pressure by about 10 mm Hg, coinciding with peak plasma nitrite levels.
“Andrew Webb (Barts and The London Medical School) and colleagues used beetroot juice as a source of nitrate in healthy volunteers and found a reduction in blood pressure of ~10 mm Hg that coincided with peak plasma levels of nitrite37.”
From Nitrate and nitrite in biology, nutrition and therapeutics (2009) · cites this paper as [37]
Interruption of the enterosalivary circulation by asking volunteers to spit out all their saliva for 3 h immediately following beetroot juice ingestion completely blocked the rise in plasma nitrite and the reduction in BP.
“Indeed, interruption of this process by asking volunteers to spit out all their saliva for 3 h immediately following beetroot juice ingestion completely blocked the rise in plasma nitrite and the reduction BP.”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [79]
The half-life of nitrate is 5-8 h, much longer than that of nitrite, which has been reported as 1-5 min ex vivo and ~20-45 min in vivo.
“The half-life of nitrate is 5-8 h [77,79,111,141,142], which is much longer than that of nitrite, which has been reported as being 1-5 min ex vivo [77,142] and ~20-45 min in vivo [86,112].”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [79]
In healthy human subjects, nitrate supplementation in the form of beetroot juice attenuated endothelial function impairment following ischaemia-reperfusion injury during FMD of the brachial artery.
“Webb et al. translated this into a forearm model of ischaemia-reperfusion and demonstrated that nitrate supplementation in the form of beetroot juice attenuated endothelial function impairment following ischaemia-reperfusion injury during FMD of the brachial artery in healthy human subjects [79].”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [79]
Webb et al. reported that in healthy participants, a single 500 mL beetroot juice dose reduced systolic and diastolic blood pressure by 10.4 and 8.0 mm Hg at 24 h.
“For example, Webb et al. (12) showed in healthy participants that 24 h after a single dose of 500 mL beetroot juice, systolic and diastolic BP were reduced by 10.4 and 8.0 mm Hg, respectively.”
From Inorganic Nitrate and Beetroot Juice Supplementation Reduces Blood Pressure in Adults: A Systematic Review and Meta-Analysis (2013) · cites this paper as [12]
Two studies reported a significant association between changes in plasma nitrite and systolic blood pressure after oral inorganic nitrate supplementation.
“Two studies found a significant association between changes in plasma nitrite concentrations and changes in systolic BP after oral inorganic nitrate supplementation (12,33), which supports our hypothesis on the lack of standardization of the measurement protocols.”
From Inorganic Nitrate and Beetroot Juice Supplementation Reduces Blood Pressure in Adults: A Systematic Review and Meta-Analysis (2013) · cites this paper as [12]
Dietary nitrate supplementation reduces resting blood pressure.
“Dietary nitrate supplementation increases plasma nitrite concentration and reduces resting blood pressure.”
From Dietary Nitrate Supplementation and Exercise Performance (2014) · cites this paper as [13]
Following bolus nitrate ingestion, plasma nitrate peaks after 1-2 h and plasma nitrite peaks after 2-3 h, returning to baseline after about 24 h.
“Following bolus nitrate ingestion, plasma nitrate concentration ([nitrate]) peaks after 1–2 h and plasma [nitrite] peaks after 2–3 h, after which both gradually fall, arriving back at baseline values after about 24 h [13].”
From Dietary Nitrate Supplementation and Exercise Performance (2014) · cites this paper as [13]
These reactions can beneficially regulate cardio-metabolic function and will be attenuated or abolished by chemical or physical destruction of the oral microbiota.
“These reactions can beneficially regulate cardio-metabolic function and will be attenuated or abolished by chemical or physical destruction of the oral microbiota[60,75,76,97–99].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [97]
Oral supplementation with either nitrite or nitrate increases circulating nitrite levels and prevents and reverses endothelial dysfunction in a dose-dependent manner in mice and in healthy, hypertensive, and obese individuals, or in those with hypercholesterolemia and peripheral arterial disease.
“Oral supplementation with either nitrite or nitrate increases circulating nitrite levels and prevents and reverses endothelial dysfunction in a dose-dependent manner both in mice[68,69] and in healthy[70,71,97,111,112], hypertensive[113], and obese individuals[114], or in those with hypercholesterolemia[115] and peripheral arterial disease[116].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [97]
Nitrate supplementation prevents or limits ischemia-reperfusion injury and endothelial dysfunction in both animal and human models of ischemia-reperfusion.
“while nitrate supplementation prevents or limits ischemia-reperfusion injury and endothelial dysfunction in both animal[98,120–124] and human[97,125] models of ischemia-reperfusion.”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [97]
Oral administration of nitrate and nitrite provides protection from ischemia-reperfusion injury.
“protection from ischemia-reperfusion injury[97,98,272]”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [97]
The vasoprotective effects of a single dose of 500 mL beetroot juice containing 45.0 ± 2.6 mmol/L nitrate in healthy volunteers are attributable to nitrite converted from ingested nitrate.
“Webb et al., studied the blood pressure and flow-mediated dilation of healthy volunteers, and showed that the vasoprotective effects of dietary nitrate (a single dose of 500 mL of beetroot juice containing 45.0 ± 2.6 mmol/L nitrate), were attributable to the activity of nitrite converted from the ingested nitrate [86].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [86]
The physiological effects of dietary nitrate are eliminated and nitrite levels decreased when volunteers either spit or use mouthwash.
“These effects are eliminated and nitrite levels decreased when volunteers either spit or use mouthwash [22, 23]”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [23]
Dietary nitrate causes acute reduction in blood pressure.
“and acute reduction in blood pressure[22–26].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [23]
Nitrate reduction to nitrite by oral bacteria is important for the physiological effects of dietary nitrate.
“thereby implicating the importance of nitrate reduction to nitrite by oral bacteria.”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [23]
Several studies have shown that oral nitrate decreases blood pressure and that this effect is dependent on reduction of nitrate to nitrite by commensal bacteria.
“Several studies have shown that oral nitrate decreases blood pressure and that this effect is dependent on reduction of nitrate to nitrite by commensal bacteria [22–26].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [23]
The reduction in platelet aggregation after beetroot juice was reduced when volunteers spit, which interrupts the conversion of nitrate to nitrite.
“and the reduction in platelet aggregation was reduced when volunteers spit, which interrupts the conversion of nitrate to nitrite [23].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [23]
Platelet aggregation induced by ADP or collagen in blood from individuals who consumed a single dose of beetroot juice was reduced compared to a control group.
“Platelet aggregation induced by ADP or collagen measured in blood taken from individuals who consumed a single dose of beetroot juice (containing high nitrate) was reduced compared to a control group”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [23]
In vivo administration of nitrite via direct infusion, dietary supplementation, or its two-electron oxidized precursor nitrate leads to a decrease in blood pressure in normal and hypertensive patients with a concomitant increase in markers of NO formation.
“in vivo administration of nitrite either via direct infusion [25, 37, 83], dietary supplementation [84-86] or in the form of its two-electron oxidized precursor nitrate [87-89] leads to a decrease in blood pressure in normal and hypertensive patients with a concomitant increase in markers of NO formation”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [89]
Diet has the potential to contribute significantly to nitrite-dependent responses.
“several studies have shown that it has the potential to contribute significantly to nitrite-dependent responses [84, 86-89, 118-121]”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [89]
Diet is an important source of nitrite, largely via secondary reduction from nitrate.
“the diet is an important source of nitrite (largely via secondary reduction from nitrate)”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [89]
The blood-pressure-lowering effects of nitrate in healthy humans were ascribed to nitrate bioconversion to nitrite, which ultimately generates NO.
“these effects were ascribed to nitrate bioconversion to nitrite, which ultimately generates NO [28,30].”
From Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension (2011) · cites this paper as [28]
Inorganic nitrate supplementation, as well as a nitrate-rich meal, reduced blood pressure in healthy humans.
“inorganic nitrate supplementation, as well as a nitraterich meal, reduced blood pressure in healthy humans [28,30]”
From Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension (2011) · cites this paper as [28]
Elevations in [NO3−] and [NO2−] following NO3− supplementation have been observed in skeletal muscle and plasma.
“Elevations in [NO3−] and [NO2−] following NO3− supplementation have been observed in skeletal muscle [88,89,90,91] and plasma [53,64,92], and are associated with positive physiological effects [41,64,74,93] that facilitate a greater capacity for muscular work [51,53,59] and/or improved muscle contractile efficiency (i.e., a lower high-energy phosphate cost of force production) [51,94].”
From Effects of Dietary Nitrate Supplementation on Weightlifting Exercise Performance in Healthy Adults: A Systematic Review (2020) · cites this paper as [92]
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Food sources of nitrates and nitrites: The physiologic context for potential health benefits
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From Nitrate to Nitric Oxide: The Role of Salivary Glands and Oral Bacteria
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Platelet Inhibition by Nitrite Is Dependent on Erythrocytes and Deoxygenation
Srihirun, S., Sriwantana, T., Unchern, S., Kittikool, D., Noulsri, E., Pattanapanyasat, K., Fucharoen, S., Piknova, B., Schechter, A. N., & Sibmooh, N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030380 · Cited by 109 · see citing works
Thompson, K. G., Turner, L., Prichard, J., Dodd, F., Kennedy, D. O., Haskell, C., Blackwell, J. R., & Jones, A. M. (2014) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2013.12.015 · Cited by 109 · see citing works
Baliga, R. S., Milsom, A. B., Ghosh, S. M., Trinder, S. L., MacAllister, R. J., Ahluwalia, A., & Hobbs, A. J. (2012) · Circulation · doi:10.1161/circulationaha.112.100586 · Cited by 110 · see citing works
Self-citationMuggeridge, D. J., Howe, C. C. F., Spendiff, O., Pedlar, C., James, P. E., & Easton, C. (2013) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.23.5.498 · Cited by 108 · see citing works
A comparison of organic and inorganic nitrates/nitrites
Omar, S. A., Artime, E., & Webb, A. J. (2012) · Nitric Oxide · doi:10.1016/j.niox.2012.03.008 · Cited by 106 · see citing works
Self-citationDietary nitrite improves insulin signaling through GLUT4 translocation
Jiang, H., Torregrossa, A. C., Potts, A., Pierini, D., Aranke, M., Garg, H. K., & Bryan, N. S. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.10.809 · Cited by 105 · see citing works
- Authors
- Webb, A. J., Patel, N., Loukogeorgakis, S., Okorie, M., Aboud, Z., Misra, S., Rashid, R., Miall, P., Deanfield, J., Benjamin, N., MacAllister, R., Hobbs, A. J., & Ahluwalia, A.
- Affiliations
- Queen Mary University of London (GB)
- ORCID
- Venue
- Hypertension
- Published
- 2008-03
- Volume
- 51
- Issue
- 3
- Pages
- 784-790
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC2839282
- OpenAlex
- W2161221966
- Cited by
- 1,078
- References
- 51
- Citations by year
- 2026: 35 · 2025: 33 · 2024: 47 · 2023: 59 · 2022: 59 · 2021: 55 · 2020: 73 · 2019: 69 · 2018: 78 · 2017: 80 · 2016: 73 · 2015: 74 · 2014: 79 · 2013: 59 · 2012: 65
- FWCI
- 30.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust (067422)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Keywords
- dietary nitrate, beetroot juice, blood pressure reduction, nitric oxide, endothelial dysfunction, platelet aggregation, cardiovascular disease
- MeSH terms
- Adolescent, Adult, Blood Pressure, Diet, Endothelium, Vascular, Humans, Hypertension, Middle Aged, Nitrates, Nitrites, Platelet Aggregation, Saliva, Tongue, Reperfusion Injury, Cross-Over Studies, Beta vulgaris
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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