Effects of Dietary Nitrate on Blood Pressure in Healthy Volunteers
Open accessAbstract
To the Editor: Nitric oxide, generated by nitric oxide synthase, is a key regulator of vascular integrity. This system is dysfunctional in many cardiovascular disorders, including hypertension. A fundamentally different pathway for the generation of nitric oxide was recently described in which the anions nitrate (NO3 ) and nitrite (NO2 ) are converted into nitric oxide and other bioactive nitrogen oxides.1-3 Nitrate is abundant in our diet, and particularly high levels are found in many vegetables.3 We examined the effect of 3-day dietary supplementation with either sodium nitrate (at a dose of 0.1 mmol per kilogram of body weight per day) or placebo (sodium chloride, at a dose of 0.1 mmol per kilogram per day) on blood pressure in 17 physically active, healthy volunteers, none of whom smoked (15 men and 2 women; mean age, 24 years). The study had a randomized, double-blind, crossover design with two different treatment periods during which the subjects received either nitrate or placebo; the treatment periods were separated by a washout period of at least 10 days. The compounds were dissolved in water and could not be distinguished by taste or appearance. During the two treatment periods, the subjects were instructed to avoid all foods with a moderate or high nitrate content.3 Systolic blood pressure Effects of 3-Day Dietary Supplementation with Inorganic Nitrate or Placebo on Systolic (Panel A) and Diastolic (Panel B) Blood Pressure in 17 Healthy Volunteers.) and pulse rate did not change significantly after nitrate supplementation, as compared with placebo supplementation. However, the diastolic blood pressure was on average 3.7 mm Hg lower after nitrate supplementation than after placebo supplementation (P<0.02) (Figure 1B), and the mean arterial pressure was 3.2 mm Hg lower (P<0.03). Plasma nitrate levels were higher after nitrate ingestion than after placebo ingestion (mean [±SD], 178±51 and 26±11 μM, respectively; P<0.001), as were plasma nitrite levels (219±105 and 138±38 nM, respectively; P<0.01). The daily nitrate dose used in the study corresponds to the amount normally found in 150 to 250 g of a nitrate-rich vegetable such as spinach, beetroot, or lettuce. It is clear from earlier studies, such as the Dietary Approaches to Stop Hypertension (DASH) trial, that a diet rich in fruits and vegetables can reduce blood pressure,4,5 but attempts to modify single nutrients have been inconsistent. Therefore, it has been argued that the effect of any individual nutrient is too small to detect in trials. In our study, reduced blood pressure was associated with nitrate supplementation alone; this effect was evident in young normotensive subjects. In fact, it was similar to that seen in the healthy control group in the DASH study.4 The exact mechanism behind the blood-pressure–lowering effect of nitrate needs to be clarified in future studies. We conclude that short-term dietary supplementation with inorganic nitrate reduces diastolic blood pressure in healthy young volunteers.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The balance of evidence indicates that NO3- represents a potent dietary means for reducing systemic blood pressure.
“Although the balance of evidence indicates that NO3- represents an potent dietary means for reducing systemic BP [22], [25], [27], [40], [6]”
From Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans (2018) · cites this paper as [27]
The study reports that three days of dietary nitrate supplementation lowered diastolic blood pressure and mean arterial pressure in 17 healthy young volunteers (p. 1), supporting a blood-pressure-lowering effect. Systolic pressure did not change significantly, and the authors’ conclusion is limited to short-term supplementation and diastolic pressure in healthy young volunteers (p. 2). The broader claim that the balance of evidence establishes nitrate as a potent means of reducing systemic blood pressure exceeds those findings. (LLM, conf=0.86)
Experimental — accuracy not yet measuredDietary nitrate has a range of beneficial vascular effects, including reducing blood pressure, inhibiting platelet aggregation, preserving or improving endothelial dysfunction, enhancing exercise performance in healthy individuals and patients with peripheral arterial disease.
“Dietary nitrate has been demonstrated to have a range of beneficial vascular effects, including reducing blood pressure, inhibiting platelet aggregation, preserving or improving endothelial dysfunction, enhancing exercise performance in healthy individuals and patients with peripheral arterial disease.”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [78]
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredModest dietary supplementation with sodium nitrate lowers blood pressure in healthy volunteers.
“Recently it was shown that modest dietary supplementation with sodium nitrate reduces blood pressure in healthy volunteers36.”
From Nitrate and nitrite in biology, nutrition and therapeutics (2009) · cites this paper as [36]
Dietary NO3- supplementation through NO3- salts or vegetable products such as beetroot juice reduces blood pressure in healthy young and old humans.
“The NO3-- NO2--NO reduction pathway underpins the discovery that dietary NO3- supplementation through consumption of NO3- salts [27] or vegetable products such as beetroot juice [23], [40] reduces blood pressure (BP) in healthy young and old humans.”
From Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans (2018) · cites this paper as [27]
In 2006 Larsen et al. demonstrated that diastolic BP was reduced by 3.7 mmHg following 3 days' dietary supplementation with sodium nitrate (0.1 mmol kg-1 day-1) compared with placebo sodium chloride in 17 healthy volunteers (randomized, double-blind, crossover design).
“in 2006 Larsen et al. demonstrated that diastolic BP was reduced by 3.7 mmHg following 3 days' dietary supplementation with sodium nitrate (0.1 mmol kg -1 day -1 ) compared with placebo sodium chloride in 17 healthy volunteers (randomized, double-blind, crossover design) [78].”
From Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway (2013) · cites this paper as [78]
Dietary nitrate decreased diastolic pressure in as little as 3 days.
“Dietary nitrate decreased DP in as little as 3 days (Larsen et al. 2006)”
From Oral nitrate and citrulline decrease blood pressure and increase vascular conductance in young adults: a potential therapy for heart failure (2016) · cites this paper as Larsen et al. 2006
Larsen et al. found that sodium nitrate lowered diastolic blood pressure significantly in healthy volunteers.
“Larsen et al. (10) tested for the first time in a double-blind crossover study the effects of sodium nitrate on BP in healthy volunteers and reported a significant reduction in diastolic BP (23.7 mm Hg).”
From Inorganic Nitrate and Beetroot Juice Supplementation Reduces Blood Pressure in Adults: A Systematic Review and Meta-Analysis (2013) · cites this paper as [10]
Dietary nitrate supplementation reduces resting blood pressure.
“Dietary nitrate supplementation increases plasma nitrite concentration and reduces resting blood pressure.”
From Dietary Nitrate Supplementation and Exercise Performance (2014) · cites this paper as [30]
The nitrate/nitrite content of fruits and vegetables could contribute to their cardiovascular health benefits in animals and humans.
“the nitrate/nitrite content of the fruits and vegetables could contribute to their cardiovascular health benefits in animals [29,33,78,79,80,81,82,83] and humans [31,84,85,86].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [84]
Dietary sodium nitrate at 0.1 mmol/kg body weight per day reduces diastolic blood pressure in healthy volunteers.
“Larsen et al., reported that the diastolic blood pressure in healthy volunteers was reduced by dietary sodium nitrate (at a dose of 0.1 mmol/kg body weight per day) corresponding to the amount normally found in 150 to 250 g of a nitrate-rich vegetable, such as spinach, beetroot, or lettuce [84].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [84]
The NO-like effects of dietary nitrate include lowering blood pressure, reducing experimental myocardial infarct size, inhibiting platelet aggregation, increasing exercise tolerance in peripheral arterial disease, and improving intrinsic mitochondrial efficiency.
“The NO-like effects of dietary nitrate range from lowering of blood pressure 14,38 to a reduction in experimental myocardial infarct size, 33 inhibition of platelet aggregation, 34 increase in exercise tolerance in peripheral arterial disease, 35 and improvement in intrinsic mitochondrial efficiency.36”
From Dietary nitrate supplementation improves revascularization in chronic ischemia (2012) · cites this paper as [14]
Dietary nitrate causes acute reduction in blood pressure.
“and acute reduction in blood pressure[22–26].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [26]
Several studies have shown that oral nitrate decreases blood pressure and that this effect is dependent on reduction of nitrate to nitrite by commensal bacteria.
“Several studies have shown that oral nitrate decreases blood pressure and that this effect is dependent on reduction of nitrate to nitrite by commensal bacteria [22–26].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [26]
He and MacGregor estimated that reducing BP by 5 mmHg could result in a reduction in stroke death in the UK by 23 %, equating to 13 700 deaths prevented per year.
“He and MacGregor (42) estimated that reducing BP by 5 mmHg could result in a reduction in stroke death in the UK by 23 %, which could equate to 13 700 deaths prevented per year.”
From High-nitrate vegetable diet increases plasma nitrate and nitrite concentrations and reduces blood pressure in healthy women (2015) · cites this paper as [42]
In vivo administration of nitrite via direct infusion, dietary supplementation, or its two-electron oxidized precursor nitrate leads to a decrease in blood pressure in normal and hypertensive patients with a concomitant increase in markers of NO formation.
“in vivo administration of nitrite either via direct infusion [25, 37, 83], dietary supplementation [84-86] or in the form of its two-electron oxidized precursor nitrate [87-89] leads to a decrease in blood pressure in normal and hypertensive patients with a concomitant increase in markers of NO formation”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [88]
Diet is an important source of nitrite, largely via secondary reduction from nitrate.
“the diet is an important source of nitrite (largely via secondary reduction from nitrate)”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [88]
Diet has the potential to contribute significantly to nitrite-dependent responses.
“several studies have shown that it has the potential to contribute significantly to nitrite-dependent responses [84, 86-89, 118-121]”
From Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy (2011) · cites this paper as [88]
Increasing plasma nitrite levels results in a marked reduction in blood pressure levels in normotensives.
“Their work nicely demonstrated that increasing plasma nitrite levels resulted in a marked reduction in blood pressure levels in normotensives”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [191]
Three-day dietary nitrite supplementation of healthy volunteers with sodium nitrate (0.1 mmol/kg/day) significantly increases plasma nitrite/nitrate levels and decreases diastolic pressure by 3.7 mm Hg.
“An initial study by Larsen et al reported that 3 day dietary nitrite supplementation of healthy volunteers with sodium nitrate (0.1 mmol/kg/day) significantly increased plasma nitrite/nitrate levels and decreased diastolic pressure by 3.7 mm Hg [190].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [190]
Consumption of beetroot juice (~500 mls) acutely lowers arterial BP, augments endothelial function during ischemia, and inhibits platelet aggregation as a result of bioconversion to NO in healthy individuals.
“Webb et al investigated the possibility of increasing plasma nitrite levels through dietary nitrate by consumption of beetroot juice (~500 mls) that was also found to acutely lower arterial BP, augment endothelial function during ischemia, and inhibit platelet aggregation as a result of bioconversion to NO in healthy individuals [191].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [191]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A 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 · see citing works
Nitrate, bacteria and human health
Lundberg, J. O., Weitzberg, E., Cole, J. A., & Benjamin, N. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro929 · Cited by 739 · see citing works
Self-citationThe emerging biology of the nitrite anion
Gladwin, M. T., Schechter, A. N., Kim-Shapiro, D. B., Patel, R. P., Hogg, N., Shiva, S., Cannon, R. O., Kelm, M., Wink, D. A., Espey, M. G., et al. (2005) · Nature Chemical Biology · doi:10.1038/nchembio1105-308 · Cited by 609 · see citing works
Self-citationNO Generation From Nitrite and Its Role in Vascular Control
Lundberg, J. O., & Weitzberg, E. (2005) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000161048.72004.c2 · Cited by 341 · see citing works
Self-citationBLOOD-PRESSURE-LOWERING EFFECT OF A VEGETARIAN DIET: CONTROLLED TRIAL IN NORMOTENSIVE SUBJECTS
ROUSE, I. (1983) · The Lancet · doi:10.1016/s0140-6736(83)91557-x · Cited by 314 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Self-citationWebb, A. J., Patel, N., Loukogeorgakis, S., Okorie, M., Aboud, Z., Misra, S., Rashid, R., Miall, P., Deanfield, J., Benjamin, N., et al. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.103523 · Cited by 1,078 · see citing works
Methods to detect nitric oxide and its metabolites in biological samples
Bryan, N. S., & Grisham, M. B. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.04.026 · Cited by 1,005 · see citing works
Nitric oxide signaling in health and disease
Lundberg, J. O., & Weitzberg, E. (2022) · Cell · doi:10.1016/j.cell.2022.06.010 · Cited by 850 · see citing works
Self-citationNitric oxide signalling in cardiovascular health and disease
Farah, C., Michel, L. Y. M., & Balligand, J.-L. (2018) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.224 · Cited by 779 · see citing works
Dietary Inorganic Nitrate Improves Mitochondrial Efficiency in Humans
Larsen, F. J., Schiffer, T. A., Borniquel, S., Sahlin, K., Ekblom, B., Lundberg, J. O., & Weitzberg, E. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.01.004 · Cited by 689 · see citing works
Self-citationEffects of dietary nitrate on oxygen cost during exercise
Larsen, F. J., Weitzberg, E., Lundberg, J. O., & Ekblom, B. (2007) · Acta Physiologica · doi:10.1111/j.1748-1716.2007.01713.x · Cited by 637 · see citing works
Self-citationInorganic Nitrate Supplementation Lowers Blood Pressure in Humans: Role for Nitrite-Derived NO
Kapil, V., Milsom, A. B., Okorie, M., Maleki-Toyserkani, S., Akram, F., Rehman, F., Arghandawi, S., Pearl, V., Benjamin, N., Loukogeorgakis, S., et al. (2010) · Hypertension · doi:10.1161/hypertensionaha.110.153536 · Cited by 621 · see citing works
Nitrate and nitrite in biology, nutrition and therapeutics
Lundberg, J. O., Gladwin, M. T., Ahluwalia, A., Benjamin, N., Bryan, N. S., Butler, A., Cabrales, P., Fago, A., Feelisch, M., Ford, P. C., et al. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.260 · Cited by 617 · see citing works
Self-citationGovoni, M., Jansson, E. Å., Weitzberg, E., & Lundberg, J. O. (2008) · Nitric Oxide · doi:10.1016/j.niox.2008.08.003 · Cited by 585 · see citing works
Self-citationStrategies to increase nitric oxide signalling in cardiovascular disease
Lundberg, J. O., Gladwin, M. T., & Weitzberg, E. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4623 · Cited by 576 · see citing works
Self-citationSources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541 · see citing works
Beetroot juice and exercise: pharmacodynamic and dose-response relationships
Wylie, L. J., Kelly, J., Bailey, S. J., Blackwell, J. R., Skiba, P. F., Winyard, P. G., Jeukendrup, A. E., Vanhatalo, A., & Jones, A. M. (2013) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00372.2013 · Cited by 500 · see citing works
Kapil, V., Khambata, R. S., Robertson, A., Caulfield, M. J., & Ahluwalia, A. (2015) · Hypertension · doi:10.1161/hypertensionaha.114.04675 · Cited by 500 · see citing works
Dietary Nitrate Supplementation and Exercise Performance
Jones, A. M. (2014) · Sports Medicine · doi:10.1007/s40279-014-0149-y · Cited by 442 · see citing works
Physiological role for nitrate-reducing oral bacteria in blood pressure control
Kapil, V., Haydar, S. M. A., Pearl, V., Lundberg, J. O., Weitzberg, E., & Ahluwalia, A. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.11.013 · Cited by 413 · see citing works
Self-citationMaia, L. B., & Moura, J. J. G. (2014) · Chemical Reviews · doi:10.1021/cr400518y · Cited by 401 · see citing works
Carlström, M., Larsen, F. J., Nyström, T., Hezel, M., Borniquel, S., Weitzberg, E., & Lundberg, J. O. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008872107 · Cited by 382 · see citing works
Self-citationGiustarini, D., Rossi, R., Milzani, A., & Dalle‐Donne, I. (2008) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(07)00823-3 · Cited by 381 · see citing works
Siervo, M., Lara, J., Ogbonmwan, I., & Mathers, J. C. (2013) · The Journal of Nutrition · doi:10.3945/jn.112.170233 · Cited by 375 · see citing works
Metabolic Effects of Dietary Nitrate in Health and Disease
Lundberg, J. O., Carlström, M., & Weitzberg, E. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.06.007 · Cited by 374 · see citing works
Self-citationHigher blood flow and circulating NO products offset high-altitude hypoxia among Tibetans
ERZURUM, S. C., Ghosh, S., Janocha, A. J., Xu, W., Bauer, S. M., Bryan, N. S., Tejero, J., Hemann, C. F., Hille, R., Stuehr, D. J., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707462104 · Cited by 364 · see citing works
Lidder, S., & Webb, A. J. (2013) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2012.04420.x · Cited by 360 · see citing works
A mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasis
Jansson, E. Å., Huang, L., Malkey, R., Govoni, M., Nihlén, C., Olsson, A., Stensdotter, M., Petersson, J., Holm, L., Weitzberg, E., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.92 · Cited by 356 · see citing works
Self-citationRoles of dietary inorganic nitrate in cardiovascular health and disease
Lundberg, J. O., Carlström, M., Larsen, F. J., & Weitzberg, E. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvq325 · Cited by 355 · see citing works
Self-citationDietary nitrite supplementation protects against myocardial ischemia-reperfusion injury
Bryan, N. S., Calvert, J. W., Elrod, J. W., Gundewar, S., Ji, S. Y., & Lefer, D. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706579104 · Cited by 347 · see citing works
Novel Aspects of Dietary Nitrate and Human Health
Weitzberg, E., & Lundberg, J. O. (2013) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071812-161159 · Cited by 324 · see citing works
Self-citationLarsen, F. J., Weitzberg, E., Lundberg, J. O., & Ekblom, B. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.11.006 · Cited by 320 · see citing works
Self-citationWhen Does Nitrate Become a Risk for Humans?
Powlson, D. S., Addiscott, T. M., Benjamin, N., Cassman, K. G., de Kok, T. M., van Grinsven, H., L'hirondel, J., Avery, A. A., & van Kessel, C. (2008) · Journal of Environmental Quality · doi:10.2134/jeq2007.0177 · Cited by 313 · see citing works
Wruss, J., Waldenberger, G., Huemer, S., Uygun, P., Lanzerstorfer, P., Müller, U. C., Höglinger, O., & Weghuber, J. (2015) · Journal of Food Composition and Analysis · doi:10.1016/j.jfca.2015.03.005 · Cited by 312 · see citing works
Bondonno, C. P., Yang, X., Croft, K. D., Considine, M. J., Ward, N. C., Rich, L., Puddey, I. B., Swinny, E., Mubarak, A., & Hodgson, J. M. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.09.028 · Cited by 292 · 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
Nutrition and Supplement Update for the Endurance Athlete: Review and Recommendations
Vitale, K., & Getzin, A. R. (2019) · Nutrients · doi:10.3390/nu11061289 · Cited by 290 · see citing works
Gilchrist, M., Winyard, P. G., Aizawa, K., Anning, C., Shore, A., & Benjamin, N. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.01.024 · Cited by 261 · see citing works
Carlström, M., Persson, A. E. G., Larsson, E., Hezel, M., Scheffer, P. G., Teerlink, T., Weitzberg, E., & Lundberg, J. O. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvq366 · Cited by 261 · see citing works
Self-citationNitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans
Vanhatalo, A., Blackwell, J. R., L’Heureux, J. E., Williams, D. W., Smith, A., van der Giezen, M., Winyard, P. G., Kelly, J., & Jones, A. M. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.05.078 · Cited by 256 · see citing works
Discovery of the nitric oxide signaling pathway and targets for drug development
Nathan, S. B. (2009) · Frontiers in bioscience · doi:10.2741/3228 · Cited by 256 · see citing works
Nitric oxide signalling in kidney regulation and cardiometabolic health
Carlström, M. (2021) · Nature Reviews Nephrology · doi:10.1038/s41581-021-00429-z · Cited by 264 · see citing works
Meat consumption, diabetes, and its complications
Feskens, E. J. M., Sluik, D., & van Woudenbergh, G. J. (2013) · Current Diabetes Reports · doi:10.1007/s11892-013-0365-0 · Cited by 248 · see citing works
Kapil, V., Khambata, R. S., Jones, D. A., Rathod, K., Primus, C., Massimo, G., Fukuto, J. M., & Ahluwalia, A. (2020) · Pharmacological Reviews · doi:10.1124/pr.120.019240 · Cited by 248 · see citing works
Nitrate and nitrite in the diet: How to assess their benefit and risk for human health
Habermeyer, M., Roth, A., Guth, S., Diel, P. R., Engel, K., Epe, B., Fürst, P., Heinz, V., Humpf, H., Joost, H., et al. (2014) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201400286 · Cited by 244 · see citing works
Acute effect of a high nitrate diet on brain perfusion in older adults
Presley, T. D., Morgan, A. R., Bechtold, E., Clodfelter, W., Dove, R. W., Jennings, J. M., Kraft, R. A., Bruce King, S., Laurienti, P. J., Jack Rejeski, W., et al. (2011) · Nitric Oxide · doi:10.1016/j.niox.2010.10.002 · Cited by 238 · see citing works
Petersson, J., Carlström, M., Schreiber, O., Phillipson, M., Christoffersson, G., Jägare, A., Roos, S., Jansson, E. Å., Persson, A. E. G., Lundberg, J. O., et al. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.01.011 · Cited by 235 · see citing works
Self-citationKelly, J., Fulford, J., Vanhatalo, A., Blackwell, J. R., French, O., Bailey, S. J., Gilchrist, M., Winyard, P. G., & Jones, A. M. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00406.2012 · Cited by 232 · see citing works
Ghosh, S. M., Kapil, V., Fuentes-Calvo, I., Bubb, K. J., Pearl, V., Milsom, A. B., Khambata, R., Maleki-Toyserkani, S., Yousuf, M., Benjamin, N., et al. (2013) · Hypertension · doi:10.1161/hypertensionaha.111.00933 · Cited by 218 · see citing works
Nitrite regulates hypoxic vasodilation via myoglobin-dependent nitric oxide generation
Totzeck, M., Hendgen-Cotta, U. B., Luedike, P., Berenbrink, M., Klare, J. P., Steinhoff, H.-J., Semmler, D., Shiva, S., Williams, D., Kipar, A., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.087155 · Cited by 202 · see citing works
The oral microbiome and nitric oxide homoeostasis
Hezel, M., & Weitzberg, E. (2015) · Oral Diseases · doi:10.1111/odi.12157 · Cited by 201 · see citing works
Self-citationBiology of nitrogen oxides in the gastrointestinal tract
Lundberg, J. O., & Weitzberg, E. (2013) · Gut · doi:10.1136/gutjnl-2011-301649 · Cited by 200 · see citing works
Self-citationRole of the anion nitrite in ischemia-reperfusion cytoprotection and therapeutics
DEZFULIAN, C., RAAT, N., SHIVA, S., & GLADWIN, M. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.05.001 · Cited by 198 · see citing works
Hobbs, D. A., Kaffa, N., George, T. W., Methven, L., & Lovegrove, J. A. (2012) · British Journal Of Nutrition · doi:10.1017/s0007114512000190 · Cited by 194 · see citing works
Aerobic Fitness Affects the Exercise Performance Responses to Nitrate Supplementation
PORCELLI, S., RAMAGLIA, M., BELLISTRI, G., PAVEI, G., PUGLIESE, L., MONTORSI, M., RASICA, L., & MARZORATI, M. (2015) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000577 · Cited by 187 · see citing works
Dietary nitrate in Japanese traditional foods lowers diastolic blood pressure in healthy volunteers
Sobko, T., Marcus, C., Govoni, M., & Kamiya, S. (2010) · Nitric Oxide · doi:10.1016/j.niox.2009.10.007 · Cited by 185 · see citing works
Therapeutic Uses of Inorganic Nitrite and Nitrate: From the Past to the Future
Butler, A. R., & Feelisch, M. (2008) · Circulation · doi:10.1161/circulationaha.107.753814 · Cited by 184 · see citing works
Bath, P. M., & Wardlaw, J. M. (2015) · International Journal of Stroke · doi:10.1111/ijs.12466 · Cited by 179 · see citing works
Opländer, C., Volkmar, C. M., Paunel‐Görgülü, A., van Faassen, E. E., Heiß, C., Kelm, M., Halmer, D., Mürtz, M., Pallua, N., & Suschek, C. V. (2009) · Circulation Research · doi:10.1161/circresaha.109.207019 · Cited by 172 · see citing works
Therapeutic 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
Self-citationJonvik, K. L., Nyakayiru, J., Pinckaers, P. J., Senden, J. M., van Loon, L. J., & Verdijk, L. B. (2016) · The Journal of Nutrition · doi:10.3945/jn.116.229807 · Cited by 172 · see citing works
NO-synthase independent NO generation in mammals
Lundberg, J. O., & Weitzberg, E. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.02.136 · Cited by 172 · see citing works
Self-citationStokes, K. Y., Dugas, T. R., Tang, Y., Garg, H., Guidry, E., & Bryan, N. S. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01291.2008 · Cited by 171 · see citing works
The oral microbiome in the pathophysiology of cardiovascular disease
Tonelli, A., Lumngwena, E. N., & Ntusi, N. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00825-3 · Cited by 171 · see citing works
Gilchrist, M., Winyard, P. G., Fulford, J., Anning, C., Shore, A. C., & Benjamin, N. (2014) · Nitric Oxide · doi:10.1016/j.niox.2014.05.003 · Cited by 167 · see citing works
Nitrate Supplementation Enhances the Contractile Properties of Human Skeletal Muscle
HAIDER, G., & FOLLAND, J. P. (2014) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000351 · Cited by 166 · see citing works
Rammos, C., Hendgen-Cotta, U. B., Sobierajski, J., Bernard, A., Kelm, M., & Rassaf, T. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.08.691 · Cited by 165 · see citing works
Lara, J., Ashor, A. W., Oggioni, C., Ahluwalia, A., Mathers, J. C., & Siervo, M. (2016) · European Journal of Nutrition · doi:10.1007/s00394-015-0872-7 · Cited by 163 · see citing works
Bryan, N. S., Calvert, J. W., Gundewar, S., & Lefer, D. J. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.04.040 · Cited by 161 · see citing works
Mechanisms of nitrite bioactivation
Kim-Shapiro, D. B., & Gladwin, M. T. (2014) · Nitric Oxide · doi:10.1016/j.niox.2013.11.002 · Cited by 157 · see citing works
Gilchrist, M., Winyard, P. G., & Benjamin, N. (2010) · Nitric Oxide · doi:10.1016/j.niox.2009.10.005 · Cited by 157 · see citing works
Nitrite and nitrate chemical biology and signalling
DeMartino, A. W., Kim‐Shapiro, D. B., Patel, R. P., & Gladwin, M. T. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14484 · Cited by 156 · see citing works
NO generation from inorganic nitrate and nitrite: Role in physiology, nutrition and therapeutics
Lundberg, J. O., & Weitzberg, E. (2009) · Archives of Pharmacal Research · doi:10.1007/s12272-009-1803-z · Cited by 153 · see citing works
Self-citationMontenegro, M. F., Amaral, J. H., Pinheiro, L. C., Sakamoto, E. K., Ferreira, G. C., Reis, R. I., Marçal, D. M. O., Pereira, R. P., & Tanus-Santos, J. E. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.04.005 · Cited by 152 · see citing works
Dietary flavonoids and nitrate: effects on nitric oxide and vascular function
Bondonno, C. P., Croft, K. D., Ward, N., Considine, M. J., & Hodgson, J. M. (2015) · Nutrition Reviews · doi:10.1093/nutrit/nuu014 · Cited by 150 · see citing works
Hypoxic Vasodilation by Red Blood Cells
Diesen, D. L., Hess, D. T., & Stamler, J. S. (2008) · Circulation Research · doi:10.1161/circresaha.108.176867 · Cited by 145 · see citing works
Hemoglobin-mediated nitric oxide signaling
Helms, C., & Kim-Shapiro, D. B. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.04.028 · Cited by 146 · see citing works
Dietary nitrite and nitrate: a review of potential mechanisms of cardiovascular benefits
Machha, A., & Schechter, A. N. (2011) · European Journal of Nutrition · doi:10.1007/s00394-011-0192-5 · Cited by 146 · see citing works
Nitrate-Nitrite-Nitric Oxide Pathway: Implications for Anesthesiology and Intensive Care
Weitzberg, E., Hezel, M., Lundberg, J. O., & Warner, D. S. (2010) · Anesthesiology · doi:10.1097/aln.0b013e3181fcf3cc · Cited by 145 · see citing works
Self-citationRoberts, L. D., Ashmore, T., Kotwica, A. O., Murfitt, S. A., Fernandez, B. O., Feelisch, M., Murray, A. J., & Griffin, J. L. (2014) · Diabetes · doi:10.2337/db14-0496 · Cited by 145 · see citing works
Jones, A. M. (2014) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2014-0036 · Cited by 144 · see citing works
Oral Microbiome and Nitric Oxide: the Missing Link in the Management of Blood Pressure
Bryan, N. S., Tribble, G., & Angelov, N. (2017) · Current Hypertension Reports · doi:10.1007/s11906-017-0725-2 · Cited by 137 · see citing works
Dietary Nitrate, Nitric Oxide, and Cardiovascular Health
Bondonno, C. P., Croft, K. D., & Hodgson, J. M. (2016) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2013.811212 · Cited by 141 · see citing works
Beetroot supplementation lowers daily systolic blood pressure in older, overweight subjects
Jajja, A., Sutyarjoko, A., Lara, J., Rennie, K., Brandt, K., Qadir, O., & Siervo, M. (2014) · Nutrition Research · doi:10.1016/j.nutres.2014.09.007 · Cited by 138 · see citing works
Acute Administration of Inorganic Nitrate Reduces V˙O2peak in Endurance Athletes
BESCÓS, R., RODRÍGUEZ, F. A., IGLESIAS, X., FERRER, M. D., IBORRA, E., & PONS, A. (2011) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e318217d439 · Cited by 137 · see citing works
Woessner, M., Smoliga, J. M., Tarzia, B., Stabler, T., Van Bruggen, M., & Allen, J. D. (2016) · Nitric Oxide · doi:10.1016/j.niox.2016.01.002 · Cited by 137 · see citing works
Berry, M. J., Justus, N. W., Hauser, J. I., Case, A. H., Helms, C. C., Basu, S., Rogers, Z., Lewis, M. T., & Miller, G. D. (2015) · Nitric Oxide · doi:10.1016/j.niox.2014.10.007 · Cited by 134 · see citing works
Mechanisms of nitrite reduction to nitric oxide in the heart and vessel wall
Zweier, J. L., Li, H., Samouilov, A., & Liu, X. (2010) · Nitric Oxide · doi:10.1016/j.niox.2009.12.004 · Cited by 132 · see citing works
Trivedi, M. K., & Branton, A. (2015) · Journal of Chromatography & Separation Techniques · doi:10.4172/2157-7064.1000282 · Cited by 132 · see citing works
Inorganic nitrite and nitrate: evidence to support consideration as dietary nutrients
Bryan, N. S., & Ivy, J. L. (2015) · Nutrition Research · doi:10.1016/j.nutres.2015.06.001 · Cited by 131 · see citing works
Dietary nitrate supplementation improves sprint and high-intensity intermittent running performance
Thompson, C., Vanhatalo, A., Jell, H., Fulford, J., Carter, J., Nyman, L., Bailey, S. J., & Jones, A. M. (2016) · Nitric Oxide · doi:10.1016/j.niox.2016.10.006 · Cited by 130 · see citing works
Cross-talk Between Nitrate-Nitrite-NO and NO Synthase Pathways in Control of Vascular NO Homeostasis
Carlström, M., Liu, M., Yang, T., Zollbrecht, C., Huang, L., Peleli, M., Borniquel, S., Kishikawa, H., Hezel, M., Persson, A. E. G., et al. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5481 · Cited by 130 · see citing works
Self-citationThe reemergence of nitric oxide and cancer
Wink, D. A., Ridnour, L. A., Hussain, S. P., & Harris, C. C. (2008) · Nitric Oxide · doi:10.1016/j.niox.2008.05.003 · Cited by 130 · see citing works
Burleigh, M. C., Liddle, L., Monaghan, C., Muggeridge, D. J., Sculthorpe, N., Butcher, J. P., Henriquez, F. L., Allen, J. D., & Easton, C. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.03.023 · Cited by 127 · see citing works
Clinical evidence demonstrating the utility of inorganic nitrate in cardiovascular health
Kapil, V., Weitzberg, E., Lundberg, J. O., & Ahluwalia, A. (2014) · Nitric Oxide · doi:10.1016/j.niox.2014.03.162 · Cited by 126 · see citing works
Self-citationNitric oxide synthase-derived plasma nitrite predicts exercise capacity
Rassaf, T., Lauer, T., Heiss, C., Balzer, J., Mangold, S., Leyendecker, T., Rottler, J., Drexhage, C., Meyer, C., & Kelm, M. (2007) · British Journal of Sports Medicine · doi:10.1136/bjsm.2007.035758 · Cited by 122 · see citing works
Hobbs, D. A., Goulding, M. G., Nguyen, A., Malaver, T., Walker, C. F., George, T. W., Methven, L., & Lovegrove, J. A. (2013) · Journal of Nutrition · doi:10.3945/jn.113.175778 · Cited by 123 · see citing works
The Role of Nitrate in Human Health
Bryan, N. S., & van Grinsven, H. J. M. (2013) · Advances in agronomy · doi:10.1016/b978-0-12-407247-3.00003-2 · Cited by 121 · see citing works
Nitrite Reduction and Cardiovascular Protection
Omar, S. A., & Webb, A. J. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.01.012 · Cited by 121 · see citing works
Bell, P. G., Walshe, I. H., Davison, G. W., Stevenson, E., & Howatson, G. (2014) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2014-0244 · Cited by 121 · see citing works
Differential Modulation of Nitric Oxide Synthases in Aging: Therapeutic Opportunities
Cáu, S. B. D. A., Carneiro, F. S., & Tostes, R. C. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00218 · Cited by 121 · see citing works
Bahra, M., Kapil, V., Pearl, V., Ghosh, S., & Ahluwalia, A. (2012) · Nitric Oxide · doi:10.1016/j.niox.2012.01.004 · Cited by 116 · see citing works
Association of Dietary Nitrate Intake With Primary Open-Angle Glaucoma
Kang, J. H., Willett, W. C., ROSNER, B. A., Buys, E. S., Wiggs, J. L., & Pasquale, L. R. (2016) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2015.5601 · Cited by 116 · see citing works
Is sunlight good for our heart?
Feelisch, M., Kolb-Bachofen, V., Liu, D., Lundberg, J. O., Revelo, L. P., Suschek, C. V., & Weller, R. (2010) · European Heart Journal · doi:10.1093/eurheartj/ehq069 · Cited by 113 · see citing works
Self-citation
- Authors
- Larsen, F. J., Ekblom, B., Sahlin, K., Lundberg, J. O., & Weitzberg, E.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2006-12-28
- Volume
- 355
- Issue
- 26
- Pages
- 2792-2793
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2051071984
- Cited by
- 587
- References
- 5
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 29 · 2023: 24 · 2022: 17 · 2021: 26 · 2020: 33 · 2019: 27 · 2018: 47 · 2017: 44 · 2016: 42 · 2015: 44 · 2014: 42 · 2013: 38 · 2012: 36
- FWCI
- 10.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Diva portal (Dalarna University Library) (submittedVersion, other-oa)
- 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, nitric oxide, nitrite, plasma nitrate, plasma nitrite, hypertension, healthy volunteers, mean arterial pressure, diastolic blood pressure, pulse rate, nitric oxide synthase, cardiovascular health, exercise training, nitrate-nitrite-nitric oxide pathway
- MeSH terms
- Adult, Blood Pressure, Double-Blind Method, Female, Humans, Male, Nitrates, Cross-Over Studies, Dietary Supplements
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
