The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies
Open accessAbstract
Evidence has accumulated in recent years that suggests that nitrate from the diet, particularly vegetables, is capable of producing bioactive NO in the vasculature, following bioconversion to nitrite by oral bacteria. The aim of the present review was to consider the current body of evidence for potential beneficial effects of dietary nitrate on blood pressure and endothelial function, with emphasis on evidence from acute and chronic human intervention studies. The studies to date suggest that dietary nitrate acutely lowers blood pressure in healthy humans. An inverse relationship was seen between dose of nitrate consumed and corresponding systolic blood pressure reduction, with doses of nitrate as low as 3 mmol of nitrate reducing systolic blood pressure by 3 mmHg. Moreover, the current studies provide some promising evidence on the beneficial effects of dietary nitrate on endothelial function. In vitro studies suggest a number of potential mechanisms by which dietary nitrate and its sequential reduction to NO may reduce blood pressure and improve endothelial function, such as: acting as a substrate for endothelial NO synthase; increasing vasodilation; inhibiting mitochondrial reactive oxygen species production and platelet aggregation. In conclusion, the evidence for beneficial effects of dietary nitrate on blood pressure and endothelial function is promising. Further long-term randomised controlled human intervention studies assessing the potential effects of dietary nitrate on blood pressure and endothelial function are needed, particularly in individuals with hypertension and at risk of CVD.
AI snapshot
Written from the paper’s full text.
TL;DR
This narrative review concludes that dietary nitrate acutely lowers blood pressure in healthy humans, with promising but limited evidence for improved endothelial function. It calls for further long-term randomised controlled trials, especially in hypertension and CVD-risk populations.
Key findings
- Acute dietary nitrate lowered blood pressure in healthy humans; an inverse relationship was observed between nitrate dose and systolic blood pressure reduction, with doses as low as 3 mmol nitrate reducing systolic blood pressure by 3 mmHg.
- In the dose-response analysis, systolic blood pressure reduction was significant (R² 0.45; P=0.033), while diastolic blood pressure reduction did not reach significance (R² 0.233; P=0.27).
- Individual studies reported larger effects: beetroot juice (500 ml; 23 mmol nitrate) reduced systolic and diastolic blood pressure by 10 and 8 mmHg, respectively; in drug-naive grade 1 hypertensives, 3.5 mmol nitrate reduced systolic blood pressure by 12 mmHg.
- Endothelial function evidence was promising but mixed: beetroot juice protected against ischaemia-reperfusion injury and preserved flow-mediated dilatation, whereas 8 mmol potassium nitrate did not alter flow-mediated dilatation but reduced pulse wave velocity by 0.3 m/s and systolic blood pressure by 4 mmHg.
Methods
- Narrative review of human intervention studies examining dietary nitrate effects on blood pressure and endothelial function, with emphasis on acute and chronic studies; animal and in vitro evidence was used to explore mechanisms.
- Data were extracted from randomised placebo-controlled trials summarised in Tables 2 and 3, including beetroot juice and inorganic nitrate salts, with varied doses, controls, populations, and vascular measures.
- A dose-response analysis was presented for acute effects of dietary nitrate from beetroot juice and inorganic salts on peak systolic and diastolic blood pressure changes in healthy normotensive subjects.
Limitations
- The paper states that further long-term randomised controlled human intervention studies are needed, particularly in individuals with hypertension and at risk of CVD.
- The paper states that there are limited human intervention studies on endothelial function and that replication is needed using a wider range of in vivo measures.
- Evident from the text: this is a narrative review without a described systematic search or meta-analysis, and the included studies are heterogeneous in dose, vehicle, population, duration, and outcome measures, with several small samples.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
Statistics
Claims the paper makes
0 of 53 cited sources checked · 0 supported · 0 flagged
- Findingreasoning
Doses of nitrate as low as 3 mmol reduce systolic blood pressure by 3 mmHg.
“with doses of nitrate as low as 3 mmol of nitrate reducing systolic blood pressure by 3 mmHg.”
Quote in the paperSubstantial claim - Findingown data
There is a significant inverse relationship between dose of nitrate consumed and reduction in systolic blood pressure in acute human intervention studies.
“When evaluating the studies investigating the acute effects of dietary nitrate from beetroot juice or inorganic supplements on BP a significant inverse relationship between dose of nitrate and reduction in SBP (R 2 2 0•45; P¼0•033; Fig. 2(a)) was observed”
- Also stated in: § Abstract · plain
“An inverse relationship was seen between dose of nitrate consumed and corresponding systolic blood pressure reduction”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
In healthy normotensive subjects, acute dietary nitrate from beetroot juice and inorganic salts has a dose-dependent effect on peak change in systolic blood pressure (R2=0.45, P=0.033).
“For systolic BP, R 2 0•45 (P¼0•033); for diastolic BP, R 2 0•27 (P¼ 0•233).”
Quote in the paperSubstantial claim0 of 3 sources checked - Findingreasoning
There is a modest but convincing body of evidence from acute and chronic human intervention studies that dietary nitrate lowers blood pressure.
“There is a modest but convincing body of evidence from acute and chronic human intervention studies that show BP-lowering effects of dietary nitrate, with limited but promising evidence for potential beneficial effects on endothelial function.”
Quote in the paperSubstantial claim- Rests on an assumption: The human intervention studies included in the review provide valid estimates of the effect of dietary nitrate on blood pressure and endothelial function.
- Findingown data
In healthy normotensive subjects, acute dietary nitrate from beetroot juice and inorganic salts does not have a significant dose-dependent effect on peak change in diastolic blood pressure (R2=0.27, P=0.233).
“For systolic BP, R 2 0•45 (P¼0•033); for diastolic BP, R 2 0•27 (P¼ 0•233).”
Quote in the paperSubstantial claim0 of 3 sources checked
- Findingcitation
A few studies have found that dietary nitrate inhibits platelet aggregation.
“A few studies have found inhibitory effects of dietary nitrate on platelet aggregation, suggesting that inhibition of abnormal platelet aggregation may be partly responsible for the cardiovascular benefits of nitrate supplementation.”
Quote in the paperNot a substantial claim0 of 2 sources checked - Findingreasoning
There is limited but promising evidence for potential beneficial effects of dietary nitrate on endothelial function.
“There is a modest but convincing body of evidence from acute and chronic human intervention studies that show BP-lowering effects of dietary nitrate, with limited but promising evidence for potential beneficial effects on endothelial function.”
Quote in the paperSubstantial claim- Rests on an assumption: The human intervention studies included in the review provide valid estimates of the effect of dietary nitrate on blood pressure and endothelial function.
- Premisecitation
Dietary nitrate, particularly from vegetables, can produce bioactive NO in the vasculature following bioconversion to nitrite by oral bacteria.
“Evidence has accumulated in recent years that suggests that nitrate from the diet, particularly vegetables, is capable of producing bioactive NO in the vasculature, following bioconversion to nitrite by oral bacteria.”
- Also stated in: § Introduction · hedged
“Evidence has accumulated in recent years to suggest that NO may not be solely generated by NOS, but via a mechanism that relies on the bioconversion of nitrate to nitrite, by oral bacteria and further NO in the vasculature (7) .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] source
Not checked in the free run.
- Also stated in: § Introduction · hedged
- Premisecitation
Ingestion of a lower dose of beetroot juice (250 ml; 5 mmol nitrate) reduced systolic BP by 5 mmHg in nine healthy subjects.
“In a later study, the same group showed a 5 mmHg reduction in SBP in nine healthy subjects, using a lower dose of beetroot juice (250 ml; 5 mmol nitrate) (82) .”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [82] source
Not checked in the free run.
- Premisecitation
Lower doses of dietary nitrate (100 g, 2 mmol) reduce diastolic BP.
“In addition, lower doses of dietary nitrate (100 g, 2 mmol) were shown to reduce DBP (86) , suggesting that even relatively small doses, that are easily achievable in the diet, have BP-lowering effects.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [86] source
Not checked in the free run.
- Interpretationreasoning
Dietary nitrate and its sequential reduction to nitrite and NO in the circulation are responsible for the cardioprotective effects observed.
“suggesting that dietary nitrate and its sequential reduction to nitrite and NO in the circulation are responsible for the cardioprotective effects observed.”
Quote in the paperSubstantial claim - Premisecitation
Daily beetroot juice (500 ml; 11 mmol nitrate) for 6 d reduced systolic BP by 8 mmHg in recreationally active male subjects.
“Bailey et al. (94) used beetroot juice (500 ml; 11 mmol nitrate) daily for 6 d in recreationally active male subjects and reported a reduction in SBP of 8 mmHg.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [94] source
Not checked in the free run.
- Premisecitation
There were no significant differences in BP reduction between bread enriched with 100 g red or white beetroot (both 2 mmol nitrate).
“The results of the study showed that there were no significant differences in BP reduction between bread enriched with 100 g red or white beetroot (both 2 mmol nitrate) (86) ,”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [86] source
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- Interpretationcitation
The BP-lowering effects observed with 3.5 mmol nitrate in hypertensives are comparable with those achieved by a single antihypertensive drug.
“The BP-lowering effects observed in this study are comparable with those achieved by a single antihypertensive drug.”
Quote in the paperSubstantial claim - Premisecitation
Potassium nitrate (24 mmol) did not significantly reduce BP compared with potassium chloride control.
“In contrast to the studies detailed above, Lidder et al. (83) did not find a significant reduction in BP with potassium nitrate (24 mmol nitrate) compared with the equivalent potassium chloride as control.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [83] source
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- Premisecitation
The BP reduction with lower dose beetroot juice coincided with an increase in plasma cGMP.
“Furthermore, these effects coincided with an increase in plasma cGMP, which lends itself to the possibility of soluble guanylyl cyclase (sGC) -cGMP-mediated vasodilation.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [82] source
Not checked in the free run.
- Premisecitation
Ingestion of a single dose of beetroot juice (500 ml; 23 mmol nitrate) by fourteen healthy subjects reduced systolic BP and diastolic BP by 10 and 8 mmHg, respectively.
“In 2008, Webb et al. (81) showed that ingestion of a single dose of beetroot juice (500 ml; 23 mmol nitrate) by fourteen healthy subjects reduced systolic BP (SBP) and DBP by 10 and 8 mmHg, respectively.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [81] source
Not checked in the free run.
- Premisecitation
A traditional Japanese diet (18 mmol nitrate) for 10 d produced mean significant reductions in diastolic BP of 5 mmHg in twenty-five healthy and physically active subjects compared with a control diet.
“In addition, Sobko et al. (79) found mean significant reductions in DBP of 5 mmHg in twenty-five healthy and physically active subjects with a traditional Japanese diet (18 mmol nitrate) compared with a control diet for 10 d, which were hypothesised to be due to the dose of nitrate rather than due to other components in the traditional Japanese diet.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [79]
Not checked in the free run.
- Interpretationreasoning
These findings show a promising role for dietary nitrate in the management of hypertension.
“These findings therefore show a promising role for dietary nitrate in the management of hypertension.”
Quote in the paperSubstantial claim - Premisecitation
Elevation of circulating nitrite levels in fifteen drug-naive grade 1 hypertensives using 3.5 mmol nitrate coincided with a substantial reduction in systolic BP by 12 mmHg.
“In line with this, Ghosh et al. (90) investigated the effects of elevation of circulating nitrite levels in fifteen drug-naive grade 1 hypertensives using 3•5 mmol nitrate.The elevation of plasma nitrite levels by approximately 1•5-fold coincided with a substantial reduction in SBP by 12 mmHg (90) .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [90]
Not checked in the free run.
- Interpretationreasoning
Dietary nitrate acutely lowers blood pressure in healthy humans.
“The studies to date suggest that dietary nitrate acutely lowers blood pressure in healthy humans.”
- Also stated in: § Dietary nitrate and blood pressure · hedged
“In summary, human intervention studies to date suggest that dietary nitrate acutely lowers BP in healthy humans.”
Quote in the paperSubstantial claim - Also stated in: § Dietary nitrate and blood pressure · hedged
- Interpretationreasoning
The current studies provide promising evidence that dietary nitrate has beneficial effects on endothelial function.
“Moreover, the current studies provide some promising evidence on the beneficial effects of dietary nitrate on endothelial function.”
- Also stated in: § Dietary nitrate and endothelial function · hedged
“Overall, whilst the current studies provide some promising evidence on the beneficial effects of dietary nitrate on endothelial function, there is need for replication of the positive findings using a wider range of in vivo measures to assess endothelial function.”
Quote in the paperSubstantial claim - Also stated in: § Dietary nitrate and endothelial function · hedged
- Premisecitation
There were no effects of any of the interventions on diastolic BP in the spinach/apple study.
“There were no effects of any of the interventions on DBP.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [92] source
Not checked in the free run.
- Interpretationreasoning
Preliminary studies suggest that dietary nitrate, at doses as low as 2 mmol, may have a role in increasing peripheral vasodilation and therefore lowering blood pressure.
“Preliminary studies suggest that dietary nitrate, at doses as low as 2 mmol, may have a role in increasing peripheral vasodilation and therefore lowering BP, appearing to be dependent on dose.”
Quote in the paperSubstantial claim - Interpretationreasoning
The effect of dietary nitrate on blood pressure appears to be dependent on dose.
“Preliminary studies suggest that dietary nitrate, at doses as low as 2 mmol, may have a role in increasing peripheral vasodilation and therefore lowering BP, appearing to be dependent on dose.”
Quote in the paperSubstantial claim - Interpretationcitation
Activation of sGC by NO results in increased cGMP concentrations in platelets.
“This results in increased cGMP concentrations in platelets, and this is thought to be the mechanism by which platelet function is inhibited (108,109) .”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationcitation
It is likely that NO formed by the sequential reduction of nitrate activates sGC by binding to the haem moiety of the enzyme.
“The exact mechanism by which dietary nitrate attenuates platelet aggregation is still unknown, but it is likely that NO formed by the sequential reduction of nitrate activates sGC by binding to the haem moiety of the enzyme (107) .”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [107] source
Not checked in the free run.
- Premisecitation
Sodium nitrite administration resulted in vascular smooth muscle relaxation in pre-contracted rat mesenteric arteries via cGMP production, an effect amplified in the presence of exogenous guanosine triphosphate.
“Laustiola et al. (103) showed that sodium nitrite administration resulted in vascular smooth muscle relaxation in pre-contracted rat mesenteric arteries via cGMP production, an effect that was amplified in the presence of exogenous guanosine triphosphate.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [103] source
Not checked in the free run.
- Interpretationcitation
Increased cGMP concentrations in platelets are thought to be the mechanism by which platelet function is inhibited.
“This results in increased cGMP concentrations in platelets, and this is thought to be the mechanism by which platelet function is inhibited (108,109) .”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Webb et al. (81) supplementation of healthy individuals with beetroot juice (550 ml; 23 mmol nitrate) had an inhibitory effect on ex vivo platelet aggregation in response to collagen and adenosine diphosphate.
“In a study by Webb et al. (81) supplementation of healthy individuals with beetroot juice (550 ml; 23 mmol nitrate) also had an inhibitory effect on ex vivo platelet aggregation in response to collagen and adenosine diphosphate.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [81] source
Not checked in the free run.
- Premisecitation
Nitrite inhibits mitochondrial ROS overproduction by S-nitrosation of mitochondrial respiratory chain complex I enzyme.
“Nitrite has been shown to inhibit mitochondrial ROS over production by S-nitrosation of mitochondrial respiratory chain complex I enzyme (43,100) .”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationnone given
In vitro studies show that the beneficial effects of dietary and inorganic nitrate on blood pressure and vascular reactivity may be mediated by a pathway that is independent of the endothelium.
“In vitro studies show that the beneficial effects of dietary and inorganic nitrate on BP and vascular reactivity may be mediated by a pathway that is independent of the endothelium and relies initially on the reduction of nitrate to nitrite by oral bacteria and further to NO in blood vessels.”
Quote in the paperSubstantial claim - Premisecitation
Nitrate and nitrite may act as a substrate for eNOS-mediated NO generation, even when oxygen levels are limited.
“However, studies suggest that nitrate and nitrite may act as a substrate for eNOS-mediated NO generation, even when oxygen levels are limited.”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
The pathway mediating the beneficial effects of dietary and inorganic nitrate on blood pressure and vascular reactivity relies initially on the reduction of nitrate to nitrite by oral bacteria and further to NO in blood vessels.
“In vitro studies show that the beneficial effects of dietary and inorganic nitrate on BP and vascular reactivity may be mediated by a pathway that is independent of the endothelium and relies initially on the reduction of nitrate to nitrite by oral bacteria and further to NO in blood vessels.”
Quote in the paperSubstantial claim - Premisecitation
Richardson et al. (106) demonstrated that a single 2 mmol bolus of potassium nitrate inhibited platelet aggregation by up to 31 % in healthy individuals.
“For example, Richardson et al. (106) demonstrated that a single 2 mmol bolus of potassium nitrate inhibited platelet aggregation by up to 31 % in healthy individuals.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [106] source
Not checked in the free run.
- Premisecitation
A proportion of ingested nitrate is converted directly to nitrite by facultative anaerobic bacteria that reside on the dorsum of the tongue during mastication in the mouth.
“A proportion of ingested nitrate (NO 32 , ---Q) is converted directly to nitrite (NO 2 2 , ! ) by facultative anaerobic bacteria, that reside on the dorsum of the tongue, during mastication in the mouth (a); the remainder is swallowed and is rapidly absorbed from the upper gastrointestinal tract.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10] source
Not checked in the free run.
- Premisecitation
Approximately 25 % of ingested nitrate is taken up from the circulation and concentrated in the salivary glands and re-secreted into the mouth, where it is reduced to nitrite.
“Approximately 25 % is taken up from the circulation and concentrated in the salivary glands and re-secreted into the mouth, where it is reduced to nitrite (adapted from Lundberg et al.(10) ).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [10] source
Not checked in the free run.
- May combine two claims. 16
- Classified as probably not a substantial claim. 5
May combine two claims.
FindingcitationIn most studies examined, peak reduction in BP compared with baseline occurred at 2-3 h after consumption of dietary nitrate, which is the same time at which peak plasma nitrite concentrations have been observed.
“In most of the studies examined, peak reduction in BP compared with baseline occurred at 2-3 h after the consumption of dietary nitrate, which is the same time at which peak plasma nitrite concentrations have been observed (81,82,86,87,89,92) ,”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Findingnone givenAnimal studies have provided insight into the potential physiological and molecular mechanisms of action of dietary nitrate.
“In addition, animal studies have provided insight into the potential physiological and molecular mechanisms of action.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationSupplementation with sodium nitrate (0.1 mmol/kg per d) for 3 d increased plasma nitrite and reduced diastolic BP by 4 mmHg in seventeen physically active subjects.
“In 2006, Larsen et al. (95) showed an increase in plasma nitrite and DBP reduction of 4 mmHg after 3 d of supplementation with sodium nitrate (0•1 mmol/kg per d) in seventeen physically active subjects.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [95] source
Not checked in the free run.
May combine two claims.
PremisecitationIngestion of beetroot juice (500 ml; 9 mmol nitrate) resulted in a diastolic BP reduction of 8 mmHg, an increase in onset of claudication pain and prolonged peak walking time in subjects with peripheral artery disease.
“In the study by Kenjale et al. (89) the consumption of beetroot juice (500 ml; 9 mmol nitrate) resulted in a DBP reduction of 8 mmHg, an increase in the onset of claudication pain and prolonged peak walking time (89) .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [89] source
Not checked in the free run.
May combine two claims.
PremisecitationBeetroot juice (500 ml; 23 mmol nitrate) completely reduced endothelial dysfunction induced by ischaemic-reperfusion injury to the forearm and preserved the FMD response, whereas the FMD response was reduced by 60% in control subjects.
“Webb et al. (81) showed that beetroot juice (500 ml; 23 mmol nitrate) completely reduced endothelial dysfunction induced by ischaemicreperfusion injury to the forearm and preserved the FMD response, whereas the FMD response was reduced by 60 % in the control subjects.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [81] source
Not checked in the free run.
May combine two claims.
PremisecitationIngestion of 200 g spinach containing 3 mmol nitrate significantly reduced systolic BP, but not when spinach and apple interventions were given simultaneously.
“The study showed a significant reduction in SBP with 200 g spinach containing 3 mmol nitrate, but not when spinach and apple interventions were given simultaneously (92) .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [92] source
Not checked in the free run.
May combine two claims.
InterpretationreasoningIn vitro studies suggest mechanisms by which dietary nitrate and its sequential reduction to NO may reduce blood pressure and improve endothelial function, including acting as a substrate for eNOS, increasing vasodilation, inhibiting mitochondrial ROS production and platelet aggregation.
“In vitro studies suggest a number of potential mechanisms by which dietary nitrate and its sequential reduction to NO may reduce blood pressure and improve endothelial function, such as: acting as a substrate for endothelial NO synthase; increasing vasodilation; inhibiting mitochondrial reactive oxygen species production and platelet aggregation.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationIngestion of three doses of beetroot juice (100, 250 and 500 g containing 2, 6 and 11 mmol nitrate) dose-dependently reduced systolic BP over 24 h, with dose-dependent effects less apparent for diastolic BP.
“The study by Hobbs et al. (86) demonstrated that the ingestion of three doses of beetroot juice (100, 250 and 500 g containing 2, 6 and 11 mmol nitrate, respectively) dosedependently reduced SBP over a period of 24 h, with dose-dependent effects being less apparent for DBP.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [86] source
Not checked in the free run.
May combine two claims.
Premisecitation8 mmol potassium nitrate did not significantly affect FMD, but significantly reduced pulse wave velocity (0.3 m/s) and systolic BP (4 mmHg) at 3 h compared with potassium chloride control in fourteen healthy subjects.
“However, Bahra et al. (87) did not find a significant effect of 8 mmol potassium nitrate on FMD, but reported a significant reduction (0•3 m/s) in pulse wave velocity and SBP (4 mmHg) at 3 h compared with the potassium chloride control in fourteen healthy subjects.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [87] source
Not checked in the free run.
May combine two claims.
InterpretationcitationInorganic nitrate is not able to alter endothelial function but does appear to increase blood flow in combination with reductions in BP.
“This suggests that although inorganic nitrate is not able to alter endothelial function, it does appear to increase blood flow in combination with reductions in BP.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationThe peak effect in BP after beetroot juice occurred at 3 h after ingestion and was associated with an increase in plasma nitrite concentration.
“The peak effect in BP occurred at 3 h after ingestion and in association with an increase in plasma nitrite concentration, supporting the hypothesis that the delayed appearance of nitrite is due to the sequential bioconversion of nitrate to nitrite and further to NO in vivo.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [81] source
Not checked in the free run.
May combine two claims.
InterpretationcitationDietary nitrate present in beetroot was responsible for the BP-lowering effects, whereas betalains had minimal effect.
“suggesting that dietary nitrate present in the beetroot was responsible for the BP-lowering effects, whereas betalains had minimal effect.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [86] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationBoth platelets and endothelial cells produce and secrete chemicals that directly inhibit platelet aggregation, for example NO.
“Indeed, both platelets and endothelial cells produce and secrete chemicals that directly inhibit platelet aggregation, for example NO.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [58] source
Not checked in the free run.
May combine two claims.
PremisecitationNitrite concentrations above physiological levels activated sGC and vasodilated vascular smooth muscle preparations.
“Indeed, earlier studies by Arnold et al. (104) and Gruetter et al. (105) showed that nitrite concentrations above physiological levels activated sGC and vasodilated vascular smooth muscle preparations, thus suggesting a role of nitrite in vasodilation.”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationSome salivary nitrite enters the acidic environment of the stomach where NO is produced non-enzymically from nitrite after formation of nitrous acid and then NO and other nitrogen oxides.
“Some of the salivary nitrite enters the acidic environment of the stomach once swallowed (b), where NO is produced non-enzymically from nitrite after formation of nitrous acid (HNO 2 ) and then NO and other nitrogen oxides.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [10] source
Not checked in the free run.
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PremisecitationThe remainder of ingested nitrate is swallowed and rapidly absorbed from the upper gastrointestinal tract.
“A proportion of ingested nitrate (NO 32 , ---Q) is converted directly to nitrite (NO 2 2 , ! ) by facultative anaerobic bacteria, that reside on the dorsum of the tongue, during mastication in the mouth (a); the remainder is swallowed and is rapidly absorbed from the upper gastrointestinal tract.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [10] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationApproximately 60 % of ingested nitrate is excreted in urine within 48 h.
“Approximately 60 % of ingested nitrate is excreted in urine within 48 h.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [10] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe NO generated in the stomach kills pathogenic bacteria and stimulates mucosal blood flow and mucus generation.
“The NO generated kills pathogenic bacteria and stimulates mucosal blood flow and mucus generation.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [10] source
Not checked in the free run.
May combine two claims.
PremisecitationThe remaining nitrite is absorbed into the circulation; in blood vessels nitrite forms vasodilatory NO after a reaction with deoxygenated Hb.
“The remaining nitrite is absorbed into the circulation; in blood vessels (c) nitrite forms vasodilatory NO after a reaction with deoxygenated Hb (deoxy-Hb).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10] source
Not checked in the free run.
The paper relies on this without support.
The studies included in the review are of sufficient methodological quality and comparability to allow synthesis of their findings.
“When evaluating the studies investigating the acute effects of dietary nitrate from beetroot juice or inorganic supplements on BP a significant inverse relationship between dose of nitrate and reduction in SBP (R 2 2 0•45; P¼0•033; Fig. 2(a)) was observed”
The paper relies on this without support.
The mechanisms observed in in vitro and animal studies are relevant to humans.
“In vitro studies suggest a number of potential mechanisms by which dietary nitrate and its sequential reduction to NO may reduce blood pressure and improve endothelial function, such as: acting as a substrate for endothelial NO synthase; increasing vasodilation; inhibiting mitochondrial reactive oxygen species production and platelet aggregation.”
The paper relies on this without support.
The inverse relationship between nitrate dose and SBP reduction reflects a causal effect of nitrate.
“When evaluating the studies investigating the acute effects of dietary nitrate from beetroot juice or inorganic supplements on BP a significant inverse relationship between dose of nitrate and reduction in SBP (R 2 2 0•45; P¼0•033; Fig. 2(a)) was observed”
The paper relies on this without support.
The human intervention studies included in the review provide valid estimates of the effect of dietary nitrate on blood pressure and endothelial function.
“There is a modest but convincing body of evidence from acute and chronic human intervention studies that show BP-lowering effects of dietary nitrate, with limited but promising evidence for potential beneficial effects on endothelial function.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Antimicrobial mouthwash abolishes the beneficial blood pressure effect of nitrate supplementation both acutely and chronically.
“and that antimicrobial mouthwash abolishes this beneficial effect both acutely and chronically (reviewed in:[108,109]).”
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 [109]
Enterosalivary nitrate reduction depends on living oral microbiota for its biologic activity.
“the global dependency of enterosalivary nitrate reduction on living oral microbiota to enact its biologic activity[73,99,109].”
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 [109]
Dietary nitrate reduces blood pressure in humans.
“A number of publications have demonstrated that dietary nitrate reduces blood pressure in humans [87,88,89].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [88]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Larsen study year differs between text and table
MinorThe text dates the cited Larsen study to 2006, whereas Table 2 dates the same citation (95) to 1996.
“In 2006, Larsen et al. (95) showed an increase in plasma nitrite”
“| Larsen et al. | Healthy and physically | Chronic, double-blind, | 0•1 mmol/kg per d | 0•01 mmol sodium | SBP | NS | | (1996) (95) | active; n 17 (15 M/2 F); | cross-over, 3 d sup- | sodium nitrate | chloride/kg per d | DBP | Mean reduction of 4 mmHg for |”
Diastolic regression statistics are reversed
MinorThe text reports R2 = 0.233 and P = 0.27 for diastolic blood pressure, while the Figure 2 caption assigns 0.27 to R2 and 0.233 to P.
“(R 2 0•233; P¼0•27; Fig. 2(b))”
“for diastolic BP, R 2 0•27 (P¼ 0•233).”
Cabbage 95th percentile is below its median
MinorTable 1 labels the cabbage range as the 5th and 95th percentiles, but its upper value is 2 mmol/kg, below the reported median of 4 mmol/kg.
“| Cabbage | 1198 | 4 | 5 | 0•8 -2 |”
“| | Sample | | | (5th and 95th | | Vegetable | size (n) | Median | Mean | percentiles) |”
Kapil beetroot-juice nitrate dose differs between text and table
MinorThe text gives the 250 ml beetroot-juice dose in the Kapil study as 5 mmol nitrate; Table 2 gives it as 6 mmol.
“a lower dose of beetroot juice (250 ml; 5 mmol nitrate) (82)”
“| Kapil et al. | Healthy; n 9; mean age 25 | Acute, single-blind, | 6 mmol £ 1, | Low-nitrate mineral water | SBP | Peak change at 3 h with 5 mmHg |”
Cites
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Dietary inorganic nitrate mobilizes circulating angiogenic cells
Heiß, C., Meyer, C. G., Totzeck, M., Hendgen-Cotta, U. B., Heinen, Y., Luedike, P., Keymel, S., Ayoub, N., Lundberg, J. O., Weitzberg, E., et al. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.02.051 · Cited by 78 · see citing works
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Is measurement of endothelial dysfunction clinically useful?
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Role of the vascular endothelium
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Effects of Glucose on Blood Pressure and Production of Vascular Aldosterone and Corticosterone
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Lidder, S., Hunt, J., Omar, S., & Webb, A. (2011) · Nitric Oxide · doi:10.1016/j.niox.2011.03.277 · Cited by 6 · see citing works
DASH食の発展であるDASH‐ナトリウム食実践によるナトリウム摂取量と血圧 理論的根拠とデザイン
Svetkey, L. P., Sacks, F. M., Obarzanek, E., Vollmer, W. M., Appel, L., P‐H, L., KARANJA, N. M., Harsha, D. W., & Laws, R. L. (1999) · Journal of the American Dietetic Association · Cited by 3 · see citing works
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The Potential Benefits of Red Beetroot Supplementation in Health and Disease
Clifford, T., Howatson, G., West, D., & Stevenson, E. (2015) · Nutrients · doi:10.3390/nu7042801 · Cited by 635 · see citing works
“Nitrate itself is not considered to mediate any specific physiological function; rather, nitrates beneficial effects are attributed to its in vivo reduction to nitric oxide (NO), a multifarious messenger molecule with important vascular and metabolic functions [14,18].”
BackgroundBioactive compounds of beetroot and utilization in food processing industry: A critical review
Chhikara, N., Kushwaha, K., Sharma, P., Gat, Y., & Panghal, A. (2019) · Food Chemistry · doi:10.1016/j.foodchem.2018.08.022 · Cited by 488 · see citing works
Dietary nitrate and nitrite: Benefits, risks, and evolving perceptions
Bedale, W. A., Sindelar, J. J., & Milkowski, A. L. (2016) · Meat Science · doi:10.1016/j.meatsci.2016.03.009 · Cited by 285 · see citing works
Koch, C. D., Gladwin, M. T., Freeman, B. A., Lundberg, J. O., Weitzberg, E., & Morris, A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.015 · Cited by 186 · see citing works
“beneficial effect both acutely and chronically (reviewed in [108,109]:).”
BackgroundTherapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases
Omar, S. A., Webb, A. J., Lundberg, J. O., & Weitzberg, E. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12441 · Cited by 175 · see citing works
Biological effects of red beetroot and betalains: A review
Hadipour, E., Taleghani, A., Tayarani‐Najaran, N., & Tayarani‐Najaran, Z. (2020) · Phytotherapy Research · doi:10.1002/ptr.6653 · Cited by 165 · see citing works
Jackson, J. K., Patterson, A. J., MacDonald‐Wicks, L. K., Oldmeadow, C. J., & McEvoy, M. (2018) · Nutrition Reviews · doi:10.1093/nutrit/nuy005 · Cited by 151 · see citing works
“This finding could be linked to the fact that, after a dietary nitrate load, the plasma levels of nitrate can rise for up to 5–6 hours after ingestion and represent a period of time in which you could expect to see BP changes due to NO activity.(17,82) After this point, however, plasma nitrate levels will rapidly dimi…”
BackgroundThe Microbiome and Blood Pressure: Can Microbes Regulate Our Blood Pressure?
Khodor, S. A., Reichert, B., & Shatat, I. F. (2017) · Frontiers in Pediatrics · doi:10.3389/fped.2017.00138 · Cited by 120 · see citing works
NO-Rich Diet for Lifestyle-Related Diseases
Kobayashi, J., Ohtake, K., & Uchida, H. (2015) · Nutrients · doi:10.3390/nu7064911 · Cited by 94 · see citing works
Anti-obesity and anti-diabetic effects of nitrate and nitrite
Ghasemi, A., & Jeddi, S. (2017) · Nitric Oxide · doi:10.1016/j.niox.2017.08.003 · Cited by 89 · see citing works
Nutrition and other lifestyle influences on arterial aging
LaRocca, T. J., Martens, C. R., & Seals, D. R. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.002 · Cited by 83 · see citing works
Dietary inorganic nitrate: From villain to hero in metabolic disease?
McNally, B. D., Griffin, J. L., & Roberts, L. D. (2015) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500153 · Cited by 80 · see citing works
“The potential for dietary nitrate to provide the muchneeded supply of NO in these pathological situations has been examined in a number of recent studies in humans [104].”
BackgroundDietary nitrate and nitrite and human health: a narrative review by intake source
Kotopoulou, S., Zampelas, A., & Magriplis, E. (2021) · Nutrition Reviews · doi:10.1093/nutrit/nuab113 · Cited by 79 · see citing works
Dietary nitrate and blood pressure: evolution of a new nutrient?
Ashworth, A., & Bescós, R. (2017) · Nutrition Research Reviews · doi:10.1017/s0954422417000063 · Cited by 65 · see citing works
“Similarly, a review by Hobbs et al. of studies up to 2012 found a significant inverse relationship between nitrate dose and systolic blood pressure (53) .”
BackgroundInfluentialBakker, E., Engan, H. K., Patrician, A., Schagatay, E. K. A., Karlsen, T., Wisløff, U., & Gaustad, S. E. (2015) · Nitric Oxide · doi:10.1016/j.niox.2015.08.006 · Cited by 60 · see citing works
Raish, M., Ahmad, A., Ansari, M. A., Alkharfy, K. M., Ahad, A., Khan, A., Ali, N., Ganaie, M. A., & Hamidaddin, M. A. A. (2019) · 3 Biotech · doi:10.1007/s13205-019-1677-9 · Cited by 58 · see citing works
Microbiome and hypertension: where are we now?
Vallianou, N. G., Geladari, E. V., & Kounatidis, D. C. (2019) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0000000000000900 · Cited by 53 · see citing works
Optimization of Betalain Pigments Extraction Using Beetroot by-Products as a Valuable Source
Lazăr, S., Constantin, O. E., Stănciuc, N., Aprodu, I., Croitoru, C., & Gabriela Râpeanu, B. (2021) · Inventions · doi:10.3390/inventions6030050 · Cited by 52 · see citing works
“Some effects attributed to these compounds include antioxidants [7,8], antiproliferative [9], cardioprotective [10], anti-inflammatory [11], and antimicrobial effects [12].”
BackgroundBeneficial Effects of Dietary Nitrate on Endothelial Function and Blood Pressure Levels
d’El-Rei, J., Cunha, A. R., Trindade, M., & Neves, M. F. (2016) · International Journal of Hypertension · doi:10.1155/2016/6791519 · Cited by 50 · see citing works
“Therefore, an improvement in the NO bioavailability can have a major effect on endothelial function and, consequently, on CVD prevention and treatment [9, 10].”
BackgroundPethybridge, S. J., Kikkert, J. R., Hanson, L. E., & Nelson, S. (2018) · Agronomy · doi:10.3390/agronomy8070112 · Cited by 46 · see citing works
“Among the most commonly reported physiological changes associated with beet consumption include improvements in cardiovascular health and sugar metabolism attributed to the rich source of dietary nitrate [6,7], the antioxidant and anti-inflammatory effects of betalains [8] and the potential to improve stamina in exerc…”
BackgroundMcDonagh, S. T. J., Wylie, L. J., Webster, J., Vanhatalo, A., & JONES, A. M. (2017) · Nitric Oxide · doi:10.1016/j.niox.2017.12.001 · Cited by 45 · see citing works
Betalains: colours for human health
Calvi, P., Terzo, S., & Amato, A. (2022) · Natural Product Research · doi:10.1080/14786419.2022.2106481 · Cited by 41 · see citing works
“Red beetroot-enriched bread results in a 34% increase in vascular vasodilation in young male volunteers compared to control (Hobbs et al. 2013).”
BackgroundLiu, A. H., Bondonno, C. P., Russell, J. C., Flood, V. M., Lewis, J. R., Croft, K. D., Woodman, R. J., Lim, W. H., Kifley, A., Wong, G., et al. (2018) · European Journal of Nutrition · doi:10.1007/s00394-018-1823-x · Cited by 40 · see citing works
Mechanisms of the protective effects of nitrate and nitrite in cardiovascular and metabolic diseases
Liu, Y., Croft, K. D., Hodgson, J. M., Mori, T., & Ward, N. C. (2020) · Nitric Oxide · doi:10.1016/j.niox.2020.01.006 · Cited by 41 · see citing works
Kerley, C. P., Dolan, E., James, P. E., & Cormican, L. J. (2018) · British Journal Of Nutrition · doi:10.1017/s0007114518000144 · Cited by 38 · see citing works
“This and another review((17)) noted inverse associations between nitrate dose of SBP reduction (r(2) 0·45; P= 0·033).”
BackgroundRole of flavonoids and nitrates in cardiovascular health
Lovegrove, J. A., Stainer, A. R., & Hobbs, D. A. (2017) · Proceedings of The Nutrition Society · doi:10.1017/s0029665116002871 · Cited by 37 · see citing works
“Dietary nitrate has been shown to reduced SBP and/or DBP, and increase circulating nitrate/nitrite 399 (see review((115))).”
Self-citationThe role of inorganic nitrate and nitrite in CVD
Jackson, J. K., Patterson, A. J., MacDonald‐Wicks, L. K., & McEvoy, M. (2017) · Nutrition Research Reviews · doi:10.1017/s0954422417000105 · Cited by 37 · see citing works
“In addition it has been suggested that the nitrate–nitrite–NO pathway may play a significant role in maintaining levels of bioactive NO and may be critical for maintaining cardiovascular homeostasis in the body((27,53,60)).”
Papadopoulos, S., Δίπλα, Κ., Triantafyllou, Α., Nikolaidis, M. G., Kyparos, A., Touplikioti, P., Vrabas, I. S., & Zafeiridis, A. (2018) · Journal of the American College of Nutrition · doi:10.1080/07315724.2017.1401497 · Cited by 37 · see citing works
Inorganic nitrate alleviates the senescence-related decline in liver function
Wang, H., Hu, L., Li, L., Wu, X., Fan, Z., Zhang, C., Wang, J., Jia, J., & Wang, S. (2018) · Science China Life Sciences · doi:10.1007/s11427-017-9207-x · Cited by 36 · see citing works
The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia
Zhang, X., Chen, Z., Xiong, Y., Zhou, Q., Zhu, L., & Liu, D. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01353 · Cited by 39 · see citing works
“For instance, butterhead lettuce, beetroot, and other green leafy vegetables have a high concentration of nitrates (Hobbs et al., 2013).”
BackgroundEffects of a dietary strawberry powder on parameters of vascular health in adolescent males
Djurica, D., Holt, R. R., Ren, J., Shindel, A. W., Hackman, R. M., & Keen, C. L. (2016) · British Journal Of Nutrition · doi:10.1017/s0007114516002348 · Cited by 34 · see citing works
Golzarand, M., Bahadoran, Z., Mirmiran, P., Zadeh–Vakili, A., & Azizi, F. (2015) · Journal of Nephrology · doi:10.1007/s40620-015-0229-6 · Cited by 33 · see citing works
Toit, L. D., Sundqvist, M. L., Redondo-Río, Á., Brookes, Z. L. S., Casas‐Agustench, P., Hickson, M., Benavente, A., Montagut, G., Weitzberg, E., Gabaldón, T., et al. (2024) · Journal of Nutrition · doi:10.1016/j.tjnut.2024.07.002 · Cited by 30 · see citing works
Nora, M. A.-A. (2018) · ISABB Journal of Food and Agricultural Sciences · doi:10.5897/isabb-jfas2017.0070 · Cited by 30 · see citing works
“…many therapeutic interventions and there are numerous studies that show beetroot, delivered acutely as a juice supplement (Bailey et al., 2009; Webb et al., 2008; Jajja et al., 2014) or in bread (Hobbs et al., 2013; Hobbs et al., 2012) to significantly reduce systolic and diastolic blood pressure.”
BackgroundSweazea, K. L., Johnston, C. S., Miller, B., & Gumpricht, E. (2018) · Journal of Nutrition and Metabolism · doi:10.1155/2018/1729653 · Cited by 29 · see citing works
“For example, while some investigations noted a lack of influence of dietary nitrates on FMD [28, 49], others found a greater FMD in response to dietary nitrate consumption [1, 50].”
ResultMirmiran, P., Bahadoran, Z., Golzarand, M., Asghari, G., & Azizi, F. (2016) · Renal Failure · doi:10.3109/0886022x.2016.1165118 · Cited by 27 · see citing works
The role of probiotics in improving food safety; detoxification of heavy metals and chemicals
Ansari, F., Lee, C., Rashidimehr, A., Eskandari, S., Ashaolu, T. J., Mirzakhani, E., Pourjafar, H., & Jafari, S. M. (2023) · Toxin Reviews · doi:10.1080/15569543.2023.2283768 · Cited by 29 · see citing works
“2012, Hobbs et al .”
Haun, C. T., Kephart, W. C., Holland, A. M., Mobley, C. B., McCloskey, A. E., Shake, J. J., Pascoe, D. D., Roberts, M. D., & Martin, J. S. (2016) · European Journal of Applied Physiology · doi:10.1007/s00421-016-3478-8 · Cited by 26 · see citing works
“The acute effects of inorganic nitrate ingestion on flowmediated dilation (FMD), a bioassay of NO bioavailability and endothelial function, have been conflicting (Hobbs et al. 2013).”
BackgroundInfluentialLarsen, R. G., Thomsen, J. M., Hirata, R. P., Steffensen, R., Poulsen, E. R., Frøkjær, J. B., & Graven‐Nielsen, T. (2019) · Physiological Reports · doi:10.14814/phy2.14162 · Cited by 25 · see citing works
“Among many functions, NO plays an important role in smooth muscle cell relaxation, and lower NO bioavailability is linked with reduced vascular endothelial function (Hobbs et al., 2013; Sindler et al., 2014).”
BackgroundHaynes, J. T., Townsend, J. R., Aziz, M. A., Jones, M. D., Littlefield, L. A., Ruiz, M. D., Johnson, K. D., & Gonzalez, A. M. (2021) · Sports · doi:10.3390/sports9060077 · Cited by 25 · see citing works
“In turn, cGMP initiates a signaling cascade resulting in relaxation of smooth muscle cells, inducing vasodilation, subsequently improving blood flow [45].”
BackgroundRed Spinach Extract Increases Ventilatory Threshold during Graded Exercise Testing
Moore, A. N., Haun, C. T., Kephart, W. C., Holland, A. M., Mobley, C. B., Pascoe, D. D., Roberts, M., & Martin, J. S. (2017) · Sports · doi:10.3390/sports5040080 · Cited by 24 · see citing works
“Given the acute nature of our study, more immediate and plausible proposed mechanisms by which NO− 3 supplementation may influence oxygen uptake and utilization could include a reduction of NO− 3 to NO, directly influencing mitochondrial efficiency [28], and vascular tone [8] and/or tissue oxygenation [11,29].”
BackgroundBaranauskas, M. N., Freemas, J. A., Tan, R., & Carter, S. J. (2021) · Nitric Oxide · doi:10.1016/j.niox.2021.11.001 · Cited by 22 · see citing works
Benefit-risk analysis for foods (BRAFO): Evaluation of exposure to dietary nitrates
Wikoff, D. S., Thompson, C. M., Rager, J. E., Chappell, G. A., Fitch, S., & Doepker, C. L. (2018) · Food and Chemical Toxicology · doi:10.1016/j.fct.2018.08.031 · Cited by 21 · see citing works
Inorganic Nitrate Supplementation for Cardiovascular Health
Ivy, J. L. (2019) · Methodist DeBakey Cardiovascular Journal · doi:10.14797/mdcj-15-3-200 · Cited by 25 · see citing works
León, V. M., & Luzardo, O. P. (2020) · Food and Chemical Toxicology · doi:10.1016/j.fct.2020.111812 · Cited by 22 · see citing works
Yang, Z., Du, C., Chang, Z., Yang, Y., & Hu, L. (2025) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1612223 · Cited by 19 · see citing works
Association of Dietary Nitrate Intake with the 15-Year Incidence of Age-Related Macular Degeneration
Gopinath, B., Liew, G., Kifley, A., Lewis, J. R., Bondonno, C. P., Joachim, N., Hodgson, J. M., & Mitchell, P. (2018) · Journal of the Academy of Nutrition and Dietetics · doi:10.1016/j.jand.2018.07.012 · Cited by 19 · see citing works
Broadhead, G., Agrón, E., Peprah, D., Keenan, T. D. L., Lawler, T. P., Mares, J. A., Chew, E. Y., AREDS/AREDS2 Investigators, SanGiovanni, J., Ferris, F., et al. (2022) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2022.5404 · Cited by 18 · see citing works
Holt, R. R., Zuelch, M. L., Charoenwoodhipong, P., Al-Dashti, Y. A., Hackman, R. M., & Keen, C. L. (2019) · Food & Function · doi:10.1039/c9fo01844a · Cited by 18 · see citing works
Plant-based diets in patients with chronic kidney disease
Wathanavasin, W., Kittiskulnam, P., & Johansen, K. L. (2024) · Asian Biomedicine · doi:10.2478/abm-2024-0002 · Cited by 17 · see citing works
“It is hypothesized that high potassium and nitrate intake promotes vasodilation and improves endothelial function while inhibiting reactive oxygen species production and platelet aggregation [59, 60].”
BackgroundAhles, S., Cuijpers, I., Hartgens, F., & Troost, F. J. (2022) · The journal of nutrition health & aging · doi:10.1007/s12603-022-1834-4 · Cited by 15 · see citing works
“Nitrate is considered to be an important signaling molecule involved in endothelial function by causing vasodilation in smooth muscle cells, thereby improving blood flow (59).”
BackgroundErectile Dysfunction: A Review of Comprehensive Treatment Options for Optimal Outcome
Retzler, K. (2019) · Journal of Restorative Medicine · doi:10.14200/jrm.2019.0104 · Cited by 15 · see citing works
Red Beetroot (Beta Vulgaris L.)
Székely, D., & Máté, M. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.106692 · Cited by 16 · see citing works
Nutraceuticals as a potential adjunct therapy toward improving vascular health in CKD
Kruse, N. T. (2019) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00152.2019 · Cited by 14 · see citing works
Circulating angiogenic cell population responses to 10 days of reduced physical activity
Guhanarayan, G., Jablonski, J., & Witkowski, S. (2014) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00087.2014 · Cited by 13 · see citing works
“Because dietary nitrate may influence blood pressure and endothelial function (30), participants adhered to a low-nitrate diet for 72 h prior to testing.”
Nitric Oxide Formation From Inorganic Nitrate
Lundberg, J. O., & Weitzberg, E. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804273-1.00012-0 · Cited by 12 · see citing works
Bezerra, Á. D. D. L., Costa, E. C., Pacheco, D. A., Souza, D., Farias-Junior, L. F., Ritti‐Dias, R. M., Grigolo, G. B., de Bittencourt, P. I. H., Krause, M. D. S., & Fayh, A. P. T. (2019) · Europe PMC (PubMed Central) · Cited by 13 · see citing works
Reciprocal regulation of sulfite oxidation and nitrite reduction by mitochondrial sulfite oxidase
Kaczmarek, A. T., Strampraad, M. J. F., Hagedoorn, P., & Schwarz, G. (2019) · Nitric Oxide · doi:10.1016/j.niox.2019.04.004 · Cited by 13 · see citing works
Food for thought: Physiological considerations for nutritional ergogenic efficacy
Wickham, K. A., & Spriet, L. L. (2023) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/sms.14307 · Cited by 13 · see citing works
“130,131 Accordingly, it is feasible to use the non-invasive and cost-effective measurement of blood pressure lowering over a 2– 2.5 h window to demonstrate the efficacy of the supplementation program.”
InfluentialGriffiths, A., Alhulaefi, S. S., Hayes, E. J., Matu, J., Brandt, K., Watson, A., Siervo, M., & Shannon, O. M. (2023) · Applied Sciences · doi:10.3390/app13127319 · Cited by 12 · see citing works
“In addition, dietary nitrate supplementation has been shown to improve endothelial function [17,21], decrease platelet aggregation [17,19], and, albeit less reliably, enhance cerebral blood flow and cognitive function [22–24].”
BackgroundGonçalves‐Rizzi, V. H., Nascimento, R. A., Possomato‐Vieira, J. S., & Dias-Junior, C. A. (2015) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.12480 · Cited by 12 · see citing works
Association of dietary nitrate intake with retinal microvascular structure in older adults
Gopinath, B., Liew, G., Lewis, J. R., Blekkenhorst, L. C., Bondonno, C. P., Burlutsky, G., Hodgson, J. M., & Mitchell, P. (2019) · European Journal of Nutrition · doi:10.1007/s00394-019-02055-9 · Cited by 11 · see citing works
Oral and systemic diseases under the framework of homeostatic medicine
Zhou, J., Li, X., Hu, L., & Wang, S. (2026) · Dental Research · doi:10.1016/j.dtrs.2026.100027 · Cited by 11 · see citing works
Dietary nitrate as modulator of physical performance and cardiovascular health
Kerley, C. P. (2017) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000414 · Cited by 10 · see citing works
Does the Oral Microbiome Play a Role in Hypertensive Pregnancies?
Willmott, T., McBain, A. J., Humphreys, G. J., Myers, J., & Cottrell, E. C. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00389 · Cited by 10 · see citing works
“Consumption of these vegetables form the largest proportion of overall nitrate intake in humans (Hobbs et al., 2013).”
BackgroundWillmott, T., Serrage, H. J., Cottrell, E. C., Humphreys, G. J., Myers, J., Campbell, P. M., & McBain, A. J. (2024) · Applied and Environmental Microbiology · doi:10.1128/aem.02035-23 · Cited by 9 · see citing works
“Dietary nitrates originate from the fixation of environmental nitrogen by bacteria and are accumulated in high abundance in green, leafy vegetables, such as spinach and lettuce [11].”
BackgroundSpleen contraction and Hb elevation after dietary nitrate intake
Engan, H. K., Patrician, A., Lodin‐Sundström, A., Johansson, H., Melin, M., & Schagatay, E. K. A. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00236.2020 · Cited by 9 · see citing works
Nitrate Metabolism and Ischemic Cerebrovascular Disease: A Narrative Review
Wang, Y., Chen, W., Zhou, J., Wang, Y., Wang, H., & Wang, Y. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.735181 · Cited by 11 · see citing works
“Further, animal experiments and clinical trials are needed to evaluate prevention and treatment strategies (45).”
BackgroundMethodDietary Beetroot Juice – Effects in Patients with COPD: A Review
Chen, M., Chang, S., Xu, Y., Parke, H. G., & Liu, J. (2024) · International Journal of COPD · doi:10.2147/copd.s473397 · Cited by 8 · see citing works
“74 A systematic review and meta-analysis incorporating 13 high-quality original studies revealed that dietary nitrate supplementation in the form of beetroot juice improves vascular endothelial function in subjects.”
BackgroundBaranauskas, M. N., Altherr, C. A., Gruber, A. H., Coggan, A. R., Raglin, J. S., Gupta, S. K., & Carter, S. J. (2020) · Contemporary Clinical Trials Communications · doi:10.1016/j.conctc.2020.100693 · Cited by 8 · see citing works
Cabo, R. N., Hernes, S., Slettan, A., Haugen, M. A., Ye, S., Blomhoff, R., & Mansoor, M. A. (2014) · Nutrition · doi:10.1016/j.nut.2014.08.009 · Cited by 8 · see citing works
“A number of dietary intervention studies, based on consumption of vegetable juice and NO3 salts, have been conducted to increase the concentration of NO3 in the blood similarly, various types of herbs have been tested for increasing the concentration of NO3 in the blood [21–23].”
BackgroundLinoby, A., Azrin, A. A., Adnan, M. A., Za’don, N. H. A., Sariman, M. H., Nasir, M. Z. M., & Hussain, R. N. J. R. (2020) · Lecture notes in bioengineering · doi:10.1007/978-981-15-3270-2_41 · Cited by 7 · see citing works
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Nitratos y nitritos, la doble cara de la moneda
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“Los beneficios potenciales del nitrato y ON en el sistema cardiovascular y en condiciones isquémicas se han relacionado por sus efectos antiinflamatorios(29), antihipertensivos(30), antiplaquetarios y antihipertróficos(31).”
BackgroundElsahoryi, N. A., Cardwell, C. R., Gilchrist, S. E. C. M., & Woodside, J. V. (2022) · Journal of Nutritional Science · doi:10.1017/jns.2022.34 · Cited by 6 · see citing works
“Since then the interest in the effects of dietary nitrate on cardiovascular health has grown, and several studies have confirmed the lowering effects of dietary nitrate on chronic and acute BP, which have been reviewed((2)).”
BackgroundInfluentialSignificance of Inorganic Nitrate Supplement in Cardiovascular Health
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Salivary-Gland-Mediated Nitrate Recirculation as a Modulator for Cardiovascular Diseases
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“The endothelium plays an essential role in vascular homeostasis, and endothelial dysfunction is strongly associated with the development of heart failure, high systemic vascular resistance, and hypertension [87].”
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“Nitrite is then converted to nitric oxide (NO) within the stomach or circulation, and acts as an effective vasodilator, resulting in acute and chronic BP reduction [34,35].”
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“While known phytochemicals in GBC can reduce blood pressure [20, 21], we did not observe significant differences in blood pressure between SHRs consuming the purified diet and GBC.”
Supplementation: Its Evolving Role in Prevention
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Dietary Patterns and Hypertension
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“6 , 24–26 Increased availability of NO could potentially improve cerebral blood flow and cognitive abilities.”
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“…thereby reducing blood pressure and improving blood flow (and thus oxygen and glucose delivery) [120], processes that highlight the potential of dietary nitrate to prevent diabetic-induced endothelial dysfunction as supported by pre-clinical [114, 121] and clinical studies [103, 105, 122, 123].”
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The Oral Microbiome–Nitrate–Nitrite–Nitric Oxide Axis and Cardiovascular Health: A Narrative Review
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“…function, plasma nitrite concentrations, and vascular responsiveness, evidence linking the oral microbiome–nitrate–nitrite–nitric oxide axis to reductions in myocardial infarction, stroke, heart failure, major adverse cardiovascular events, or cardiovascular mortality remains limited [16,21,46].”
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Combination of Metformin and Inorganic Nitrate: Effects on Metabolic Disease and Lactic Acidosis
Jahandideh, A. (2017) · UTUPub (University of Turku)
Is dietary nitrate supplementation necessary to ensure proper endothelial function at altitude
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Whole Plant Foods and Hypertension
Dreher, M. L. (2018) · Springer eBooks · doi:10.1007/978-3-319-59180-3_14
- Authors
- Hobbs, D. A., George, T. W., & Lovegrove, J. A.
- Affiliations
- University of Reading (GB)
- Northumbria University (GB)
- Corresponding author
- Lovegrove, Julie A.
- Venue
- Nutrition Research Reviews
- Publisher
- Cambridge University Press (CUP)
- Published
- 2013-10-18
- Volume
- 26
- Issue
- 2
- Pages
- 210-222
- ISSN
- 0954-4224 (ISSN-L)
- 1475-2700
- OpenAlex
- W2168363136
- Semantic Scholar
- 506a952435a185558a3a7b63147c067d9a1f3c03
- Cited by
- 114
- References
- 110
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 8 · 2020: 8 · 2019: 13 · 2018: 15 · 2017: 10 · 2016: 8 · 2015: 12 · 2014: 3
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nutrition Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Northumbria Research Link (Northumbria University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
- Keywords
- dietary nitrate, blood pressure, endothelial function, nitric oxide, oral bacteria, hypertension, cardiovascular disease, endothelial nitric oxide synthase, vasodilation, platelet aggregation, reactive oxygen species
- MeSH terms
- Blood Pressure, Diet, Endothelium, Vascular, Humans, Hypertension, Mitochondria, Nitrates, Nitric Oxide, Platelet Aggregation, Vasodilation, Reactive Oxygen Species, Nitric Oxide Synthase
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