Metabolic Effects of Dietary Nitrate in Health and Disease
Open accessAbstract
Nitric oxide (NO), generated from L-arginine and oxygen by NO synthases, is a pleiotropic signaling molecule involved in cardiovascular and metabolic regulation. More recently, an alternative pathway for the formation of this free radical has been explored. The inorganic anions nitrate (NO 3-) and nitrite (NO 2-), originating from dietary and endogenous sources, generate NO bioactivity in a process involving seemingly symbiotic oral bacteria and host enzymes in blood and tissues. The described cardio-metabolic effects of dietary nitrate from experimental and clinical studies include lowering of blood pressure, improved endothelial function, increased exercise performance, and reversal of metabolic syndrome, as well as antidiabetic effects. The mechanisms underlying the salutary metabolic effects of nitrate are being revealed and include interaction with mitochondrial respiration, activation of key metabolic regulatory pathways, and reduction of oxidative stress. Here we review the recent advances in the nitrate-nitrite-NO pathway, focusing on metabolic effects in health and disease.
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While dietary nitrate can increase NO production, a high oxidative burden may reduce its effectiveness by accelerating NO degradation.
“While dietary nitrate can increase NO production, a high oxidative burden may reduce its effectiveness by accelerating NO degradation [128,234,256].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [256]
Cites
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 · see citing works
The L-Arginine-Nitric Oxide Pathway
Epstein, F. H., Moncada, S., & Higgs, A. (1993) · New England Journal of Medicine · doi:10.1056/nejm199312303292706 · Cited by 6,678 · see citing works
Oxidative stress and diabetic complications
Giacco, F., & Brownlee, M. (2010) · Circulation Research · doi:10.1161/circresaha.110.223545 · Cited by 5,461 · see citing works
The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice
Turnbaugh, P. J., Ridaura, V. K., Faith, J. J., Rey, F. E., Knight, R., & Gordon, J. I. (2009) · Science Translational Medicine · doi:10.1126/scitranslmed.3000322 · Cited by 3,058 · see citing works
The AMPK signalling pathway coordinates cell growth, autophagy and metabolism
Mihaylova, M. M., & Shaw, R. J. (2011) · Nature Cell Biology · doi:10.1038/ncb2329 · Cited by 2,923 · see citing works
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-citationMechanisms underlying the resistance to diet-induced obesity in germ-free mice
Bäckhed, F., Manchester, J. K., Semenkovich, C. F., & Gordon, J. I. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605374104 · Cited by 2,615 · see citing works
Metabolic control through the PGC-1 family of transcription coactivators
Lin, J., Handschin, C., & Spiegelman, B. M. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.004 · Cited by 2,130 · see citing works
De Filippis, F., Pellegrini, N., Vannini, L., Jeffery, I. B., La Storia, A., Laghi, L., Serrazanetti, D. I., Di Cagno, R., Ferrocino, I., Lazzi, C., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-309957 · Cited by 1,638 · see citing works
Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis
Diehl, A. M., & Day, C. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1503519 · Cited by 1,283 · see citing works
Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS
Nisoli, E., Tonello, C., Cardile, A., Cozzi, V., Bracale, R., Tedesco, L., Falcone, S., Valerio, A., Cantoni, O., Clementi, E., et al. (2005) · Science · doi:10.1126/science.1117728 · Cited by 1,107 · see citing works
Metabolic Flexibility in Health and Disease
Goodpaster, B. H., & Sparks, L. M. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.04.015 · Cited by 995 · see citing works
Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets
Drummond, G. R., Selemidis, S., Griendling, K. K., & Sobey, C. G. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3403 · Cited by 899 · see citing works
Clementi, E., Brown, G. C., Feelisch, M., & Moncada, S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7631 · Cited by 863 · 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-citationDuncan, C., Dougall, H., Johnston, P., Green, S., Brogan, R., Leifert, C., Smith, L., Golden, M., & Benjamin, N. (1995) · Nature Medicine · doi:10.1038/nm0695-546 · Cited by 734 · 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-citationBenjamin, N., O'Driscoll, F., Dougall, H., Duncan, C., Smith, L., Golden, M., & McKenzie, H. (1994) · Nature · doi:10.1038/368502a0 · Cited by 665 · see citing works
Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I
Chouchani, E. T., Methner, C., Nadtochiy, S. M., Logan, A., Pell, V. R., Ding, S., James, A. M., Cochemé, H. M., Reinhold, J., Lilley, K. S., et al. (2013) · Nature Medicine · doi:10.1038/nm.3212 · Cited by 619 · 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-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-citationBailey, S. J., Fulford, J., Vanhatalo, A., Winyard, P. G., Blackwell, J. R., DiMenna, F. J., Wilkerson, D. P., Benjamin, N., & Jones, A. M. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00046.2010 · Cited by 607 · see citing works
Effects of Dietary Nitrate on Blood Pressure in Healthy Volunteers
Larsen, F. J., Ekblom, B., Sahlin, K., Lundberg, J. O., & Weitzberg, E. (2006) · New England Journal of Medicine · doi:10.1056/nejmc062800 · Cited by 587 · 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-citationShiva, S., Sack, M. N., Greer, J. J., Duranski, M., Ringwood, L. A., Burwell, L., Wang, X., MacArthur, P. H., Shoja, A., Raghavachari, N., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070198 · Cited by 555 · 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
Intake of Fruit, Vegetables, and Fruit Juices and Risk of Diabetes in Women
Bazzano, L. A., Li, T. Y., Joshipura, K. J., & Hu, F. B. (2008) · Diabetes Care · doi:10.2337/dc08-0080 · Cited by 437 · 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-citationA 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-citationNovel 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-citationDietary nitrate supplementation enhances exercise performance in peripheral arterial disease
Kenjale, A. A., Ham, K. L., Stabler, T., Robbins, J. L., Johnson, J. L., VanBruggen, M., Privette, G., Yim, E., Kraus, W. E., & Allen, J. D. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00071.2011 · Cited by 316 · see citing works
Lai, Y.-C., Tabima, D. M., Dube, J. J., Hughan, K. S., Vanderpool, R. R., Goncharov, D. A., St. Croix, C. M., Garcia-Ocaña, A., Goncharova, E. A., Tofovic, S. P., et al. (2016) · Circulation · doi:10.1161/circulationaha.115.018935 · Cited by 270 · see citing works
Bauer, P. V., Duca, F. A., Waise, T. M. Z., Rasmussen, B. A., Abraham, M. A., Dranse, H. J., Puri, A., O’Brien, C. A., & Lam, T. K. T. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.09.019 · Cited by 265 · 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-citationGilchrist, 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
Nitrite in nitric oxide biology: Cause or consequence?
Bryan, N. S. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.05.019 · Cited by 260 · see citing works
Liese, A. D., Nichols, M., Sun, X., D'Agostino, R. B., & Haffner, S. M. (2009) · Diabetes Care · doi:10.2337/dc09-0228 · Cited by 256 · see citing works
The L-Arginine: Nitric Oxide Pathway Is the Major Source of Plasma Nitrite in Fasted Humans
Rhodes, P. M., Leone, A. M., Francis, P. L., Struthers, A. D., & Moncada, S. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.1541 · Cited by 254 · see citing works
Nitrite in Human Saliva. Its Possible Relationship to Nitrosamine Formation23
Tannenbaum, S. R., Sinskey, A. J., Weisman, M., & Bishop, W. (1974) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/53.1.79 · Cited by 237 · see citing works
Human Brown Adipose Tissue: What We Have Learned So Far
Betz, M. J., & Enerbäck, S. (2015) · Diabetes · doi:10.2337/db15-0146 · Cited by 223 · see citing works
Sindler, A. L., Fleenor, B. S., Calvert, J. W., Marshall, K. D., Zigler, M. L., Lefer, D. J., & Seals, D. R. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00679.x · Cited by 218 · see citing works
Chronic sodium nitrite therapy augments ischemia-induced angiogenesis and arteriogenesis
Kumar, D., Branch, B. G., Pattillo, C. B., Hood, J., Thoma, S., Simpson, S., Illum, S., Arora, N., Chidlow, J. H., Langston, W., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711480105 · Cited by 187 · see citing works
No Improvement in Endurance Performance after a Single Dose of Beetroot Juice
Cermak, N. M., Res, P., Stinkens, R., Lundberg, J. O., Gibala, M. J., & van Loon, L. J. C. (2012) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.22.6.470 · Cited by 144 · see citing works
Self-citationDietary nitrite improves insulin signaling through GLUT4 translocation
Jiang, H., Torregrossa, A. C., Potts, A., Pierini, D., Aranke, M., Garg, H. K., & Bryan, N. S. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.10.809 · Cited by 105 · see citing works
Nitrite and nitrate-dependent generation of anti-inflammatory fatty acid nitroalkenes
Delmastro-Greenwood, M., Hughan, K. S., Vitturi, D. A., Salvatore, S. R., Grimes, G., Potti, G., Shiva, S., Schopfer, F. J., Gladwin, M. T., Freeman, B. A., et al. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.07.149 · Cited by 97 · see citing works
Nitrate and gastric cancer risks
TANNENBAUM, S. R., & CORREA, P. (1985) · Nature · doi:10.1038/317675b0 · Cited by 96 · see citing works
Kelley, E. E., Baust, J., Bonacci, G., Golin-Bisello, F., Devlin, J. E., St. Croix, C. M., Watkins, S. C., Gor, S., Cantu-Medellin, N., Weidert, E. R., et al. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvt341 · Cited by 95 · see citing works
Roberts, L. D., Ashmore, T., McNally, B. D., Murfitt, S. A., Fernandez, B. O., Feelisch, M., Lindsay, R., Siervo, M., Williams, E. A., Murray, A. J., et al. (2017) · Diabetes · doi:10.2337/db16-0843 · Cited by 57 · see citing works
Can elite athletes benefit from dietary nitrate supplementation?
Jonvik, K. L., Nyakayiru, J., van Loon, L. J. C., & Verdijk, L. B. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00232.2015 · Cited by 55 · see citing works
Gago, B., Nyström, T., Cavaleiro, C., Rocha, B. S., Barbosa, R. M., Laranjinha, J., & Lundberg, J. O. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.04.027 · Cited by 48 · see citing works
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“While dietary nitrate can increase NO production, a high oxidative burden may reduce its effectiveness by accelerating NO degradation [128,234,256].”
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- Authors
- Lundberg, J. O., Carlström, M., & Weitzberg, E.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Lundberg, Jon O.
- Carlström, Mattias
- Weitzberg, Eddie
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 28
- Issue
- 1
- Pages
- 9-22
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2811416510
- Cited by
- 374
- References
- 52
- Citations by year
- 2026: 36 · 2025: 52 · 2024: 52 · 2023: 49 · 2022: 60 · 2021: 54 · 2020: 42 · 2019: 26 · 2018: 3
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vetenskapsrådet (2016-01381, 2015-02880)
- Karolinska Institutet (2-560/2015)
- Kommunfullmäktige, Stockholms Stad (LS 2016-1376)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Keywords
- dietary nitrate, nitrate-nitrite-NO pathway, nitric oxide bioactivity, blood pressure, endothelial function, exercise performance, metabolic syndrome, antidiabetic effect, mitochondrial respiration, oxidative stress, oral bacteria, cardiometabolic health
- MeSH terms
- Animals, Cardiovascular System, Diabetes Mellitus, Type 2, Diet, Humans, Mitochondria, Nitrates, Nitric Oxide, Nitrites, Oxidative Stress, Metabolic Syndrome, Mice, Rats
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