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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.
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“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
In the citing paper
“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
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“and acute reduction in blood pressure[22–26].”
From Mechanisms of nitrite bioactivation (2014) · cites this paper as [26]
In the citing paper
“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]
In the citing paper
“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 the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
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“The micronutrient inorganic nitrate, abundant in vegetables, acutely lowered diastolic blood pressure (DBP) in healthy young volunteers and improved vascular remodeling in animals (3,4).”
BackgroundLara, 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
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
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
Gilchrist, M., Winyard, P. G., & Benjamin, N. (2010) · Nitric Oxide · doi:10.1016/j.niox.2009.10.005 · Cited by 157
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 162
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
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
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
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
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
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
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
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 150
Jones, A. M. (2014) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2014-0036 · Cited by 144
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
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
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 139
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
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
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
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
Trivedi, M. K., & Branton, A. (2015) · Journal of Chromatography & Separation Techniques · doi:10.4172/2157-7064.1000282 · Cited by 132
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
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
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
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
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
“In line with previous research [26,27,39], the ingestion of NO3 rich beetroot juice resulted in a marked elevation of NO metabolites in the plasma and saliva.”
ResultClinical 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 130
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
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 126
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 126
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
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 126
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 131
Bahra, M., Kapil, V., Pearl, V., Ghosh, S., & Ahluwalia, A. (2012) · Nitric Oxide · doi:10.1016/j.niox.2012.01.004 · Cited by 116
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
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
Self-citation
Metadata
- 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 (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, 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
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