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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.
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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.
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40 Not checked yet · 11 Own interpretation · 4 No basis given · 1 Own result
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“with doses of nitrate as low as 3 mmol of nitrate reducing systolic blood pressure by 3 mmHg.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Abstract
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“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”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
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“For systolic BP, R 2 0•45 (P¼0•033); for diastolic BP, R 2 0•27 (P¼ 0•233).”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
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In the paper
“For systolic BP, R 2 0•45 (P¼0•033); for diastolic BP, R 2 0•27 (P¼ 0•233).”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
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“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Inhibition of platelet aggregation
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
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- 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.
In the paper
“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) .”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Abstract
What the sources say
- Not checked yetcites [7] source
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In the paper
“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) .”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [82] source
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [86] source
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In the paper
“suggesting that dietary nitrate and its sequential reduction to nitrite and NO in the circulation are responsible for the cardioprotective effects observed.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Potential mechanisms by which dietary nitrate may reduce blood pressure and increase endothelial function
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [94] source
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In the paper
“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) ,”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [86] source
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In the paper
“The BP-lowering effects observed in this study are comparable with those achieved by a single antihypertensive drug.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [83] source
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In the paper
“Furthermore, these effects coincided with an increase in plasma cGMP, which lends itself to the possibility of soluble guanylyl cyclase (sGC) -cGMP-mediated vasodilation.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [82] source
hedgedcorrelationaln = 9- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [81] source
plaindirectn = 14- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [79]
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In the paper
“These findings therefore show a promising role for dietary nitrate in the management of hypertension.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
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In the paper
“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) .”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [90]
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Abstract
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- Also stated in: § Dietary nitrate and blood pressure · hedged
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Abstract
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In the paper
“There were no effects of any of the interventions on DBP.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [92] source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
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In the paper
“This results in increased cGMP concentrations in platelets, and this is thought to be the mechanism by which platelet function is inhibited (108,109) .”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Inhibition of platelet aggregation
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In the paper
“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) .”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Inhibition of platelet aggregation
What the sources say
- Not checked yetcites [107] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Increasing vasodilation
What the sources say
- Not checked yetcites [103] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This results in increased cGMP concentrations in platelets, and this is thought to be the mechanism by which platelet function is inhibited (108,109) .”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Inhibition of platelet aggregation
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Inhibition of platelet aggregation
What the sources say
- Not checked yetcites [81] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Nitrite has been shown to inhibit mitochondrial ROS over production by S-nitrosation of mitochondrial respiratory chain complex I enzyme (43,100) .”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Inhibitor of mitochondrial reactive oxygen species
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
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In the paper
“However, studies suggest that nitrate and nitrite may act as a substrate for eNOS-mediated NO generation, even when oxygen levels are limited.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Acting as a substrate to endothelial nitric oxide synthase
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Inhibition of platelet aggregation
What the sources say
- Not checked yetcites [106] source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
What the sources say
- Not checked yetcites [10] source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“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) ).”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
What the sources say
- Not checked yetcites [10] source
plaindirect- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 16
- Probably not a substantial claim. 5
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In the paper
“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) ,”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Potential mechanisms by which dietary nitrate may reduce blood pressure and increase endothelial function
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition, animal studies have provided insight into the potential physiological and molecular mechanisms of action.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
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In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [95] source
plaindirectn = 17- Asserted: passes — The authors put it forward as true.
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In the paper
“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) .”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [89] source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and endothelial function
What the sources say
- Not checked yetcites [81] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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) .”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [92] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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 effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [86] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and endothelial function
What the sources say
- Not checked yetcites [87] source
plaindirectn = 14- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and endothelial function
hedgeddirectn = 14- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [81] source
plaincorrelationaln = 14- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“suggesting that dietary nitrate present in the beetroot was responsible for the BP-lowering effects, whereas betalains had minimal effect.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
What the sources say
- Not checked yetcites [86] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Indeed, both platelets and endothelial cells produce and secrete chemicals that directly inhibit platelet aggregation, for example NO.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Inhibition of platelet aggregation
What the sources say
- Not checked yetcites [58] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Increasing vasodilation
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
What the sources say
- Not checked yetcites [10] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
What the sources say
- Not checked yetcites [10] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Approximately 60 % of ingested nitrate is excreted in urine within 48 h.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
What the sources say
- Not checked yetcites [10] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The NO generated kills pathogenic bacteria and stimulates mucosal blood flow and mucus generation.”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
What the sources say
- Not checked yetcites [10] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The remaining nitrite is absorbed into the circulation; in blood vessels (c) nitrite forms vasodilatory NO after a reaction with deoxygenated Hb (deoxy-Hb).”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
What the sources say
- Not checked yetcites [10] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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?
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
“In 2006, Larsen et al. (95) showed an increase in plasma nitrite”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
“| 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 |”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
“(R 2 0•233; P¼0•27; Fig. 2(b))”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
“for diastolic BP, R 2 0•27 (P¼ 0•233).”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
“| Cabbage | 1198 | 4 | 5 | 0•8 -2 |”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
“| | Sample | | | (5th and 95th | | Vegetable | size (n) | Median | Mean | percentiles) |”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Dietary nitrate and blood pressure
“a lower dose of beetroot juice (250 ml; 5 mmol nitrate) (82)”
§ The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies > Conclusion
“| 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 |”
Citations
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Nitric oxide: physiology, pathophysiology, and pharmacology.
Moncada, S., Palmer, R. M., & Higgs, E. A. (1991) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06663-3 · Cited by 15,525
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704 · cited 1×
“Endothelium-derived NO diffuses into underlying vascular smooth muscle cells where the classical NO–cyclic guanylate monophosphate (cGMP)–protein kinase G signalling pathway causes vascular relaxation((57)).”
BackgroundA Clinical Trial of the Effects of Dietary Patterns on Blood Pressure
Appel, L. J., Moore, T. J., Obarzanek, E., Vollmer, W. M., Svetkey, L. P., Sacks, F. M., Bray, G. A., Vogt, T. M., Cutler, J. A., Windhauser, M. M., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199704173361601 · Cited by 5,981
Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis
Celermajer, D. S., Sorensen, K. E., Gooch, V. M., Spiegelhalter, D. J., Miller, O. I., Sullivan, I. D., Lloyd, J. K., & Deanfield, J. E. (1992) · The Lancet · doi:10.1016/0140-6736(92)93147-f · Cited by 4,742
Blood pressure, stroke, and coronary heart disease
Collins, R., Peto, R., MacMahon, S., Godwin, J., Qizilbash, N., Collins, R., MacMahon, S., Hebert, P., Eberlein, K. A., Taylor, J. O., et al. (1990) · The Lancet · doi:10.1016/0140-6736(90)90944-z · Cited by 4,491
The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics
Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2466 · Cited by 2,739 · cited 1×
“4·3 mmol nitrate per d, almost four times greater than the average diet((10)).”
BackgroundSchächinger, V., Britten, M. B., & Zeiher, A. M. (2000) · Circulation · doi:10.1161/01.cir.101.16.1899 · Cited by 2,589
Paradoxical Vasoconstriction Induced by Acetylcholine in Atherosclerotic Coronary Arteries
Ludmer, P. L., Selwyn, A. P., Shook, T., Wayne, R. R., Mudge, G. H., Alexander, R. W., & Ganz, P. (1986) · New England Journal of Medicine · doi:10.1056/nejm198610233151702 · Cited by 2,422
Close Relation of Endothelial Function in the Human Coronary and Peripheral Circulations
Anderson, T. J., Uehata, A., Gerhard, M. D., Meredith, I. T., Knab, S., Delagrange, D., Lieberman, E. H., Ganz, P., Creager, M. A., Yeung, A. C., et al. (1995) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(95)00327-4 · Cited by 2,033 · cited 9×
“FMD has been shown to correlate with measures of coronary endothelial function((63)).”
InfluentialRole of endothelium in responses of vascular smooth muscle.
Furchgott, R. F. (1983) · Circulation Research · doi:10.1161/01.res.53.5.557 · Cited by 1,961
Research works printed but not linked: 1
- 2006, Hypertension: Management of Hypertension in Adults in Primary Care. NICE Clinical Guideline 34
Cited by
Sorted by citations
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
“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
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 300
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
“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
Metadata
- 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 (medical) › 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
About these checks
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.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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