Nitrate
•Last Updated: September 28 2022
Inorganic nitrate (NO3-) is an endogenously produced food product that appears to have a critical role in blood pressure and cardiovascular health management; the main ingredient in beetroot, nitrate converts to nitric oxide by various means independent of the NOS enzyme and may aid exercise.
Nitrate is most often used for
Last Updated: September 28 2022
Nitrate (NO3-) is a small molecule produced in the body to limited amounts (as a byproduct of nitric oxide) and is obtainable via consumption of vegetables, particularly beetroot and other low-calorie tuber vegetables such as turnips and leafy green vegetables such as spinach or rocket (arugula). It appears to be a potent regulator of blood flow and vasodilatation via its metabolite nitric oxide, and has greater relative affinity for areas of the body with poor oxygenation as the conversion of nitrite (NO2-, a metabolite of nitrate) to nitric oxide is undergone by deoxygenated blood.
In regards to cardiovascular health, it appears to reduce blood pressure in instances where blood pressure is raised. This appears to occur in people with hypertension and can occur in otherwise healthy persons undergoing exercise with little effect on resting blood pressure in healthy persons. It may exert endothelial protective effects, and is thought to be a link between vegetable intake and cardiovascular health.
It appears to enhance exercise performance secondary to reducing the oxygen cost of exercise (and thus prolonging time to exhaustion, thought to be due to increased mitochondrial efficiency). There is little to no effect on acute power output, but seems to reduce the rate of fatigue seen with continued muscle contractions and as such seems to have most benefit in exercises ranging from 1 minutes up to 10 minutes and as such exerts most benefit during anaerobic cardiovascular exercise or muscular endurance events (sports requiring anaerobic intervals such as hockey or rugby, some benefit to rowing and crossfit-type exercises) but although it does have benefit to prolonged cardiovascular exercise (5km jogs or 10km cycling events) the magnitude of effect appears to be lesser.
Due to interactions with nitric oxide, it appears to also be kidney protective and may help to regulate blood flow during the aging process (which is associated with reduced nitrate levels in circulation); the anti-aging effects, however, are preliminary at this moment in time. Due to endogenous production of nitrate and some disease states with lower circulating nitrate (cardiovascular diseases and aging) nitrate may have pseudovitamin-like properties but more evidence is required to support this claim.
Nitrate has the potential to form carcinogenic nitrosamines, although the practical significance of this in living systems is not known (epidemiological survey research has failed to show a significant link after controlling for other confounds, but some nitrosamines themselves are proven carcinogenic; practical relevance of nitrates and subsequently forming nitrosamines following supplemental or vegetable intake in a mixed diet is not really known). Although the carcinogenic potential cannot be ruled out at this time, it cannot be supported reliably either.
Note that Nitrate is also known as:
- Beetroot extract
Nitrate should not be confused with:
- Nitrite (reduced form)
- nitric oxide (metabolite)
The optimal dosage of nitrate supplementation tends to be 0.1-0.2mmol/kg (or 6.4-12.8mg/kg), which is the range of:
- 440-870mg for a 150lb person
- 580-1,160mg for a 200lb person
- 730-1,450mg for a 250lb person
Supplementation of nitrates via beetroot is equally feasible, and beetroot itself is dosed according to its nitrate content.
A randomized controlled trial noted that a single 2g dose of commercially available amaranth (red spinach) extract can increase nitrate levels for up to 8 hours.
What works and what doesn't?
Unlock the full potential of Examine
Latest ResearchRead all studies
Although the food products that contain nitrates differ widely, the nitrates present in processed meats and vegetables are chemically identical.
From an epidemiological perspective, nitrates are commonly thought to be adverse to health due to a long-standing restriction on how much nitrate can be in drinking water (50mg/L) or ground water (due to accumulating in vegetables) due to the risk of infantile methemoglobinemia (baby blue syndrome)[185][184] which does appear to apply to vegetables.[186][187] More commonly, the association between processed meat products that are pink in color (which very commonly use sodium nitrate as a preservative) and cancer occurrence also paints nitrates in the same negative light...
1.^Lundberg JO, Weitzberg E, Gladwin MTThe nitrate-nitrite-nitric oxide pathway in physiology and therapeuticsNat Rev Drug Discov.(2008 Feb)
2.^Tamme T, Reinik M, Roasto M, Juhkam K, Tenno T, Kiis ANitrates and nitrites in vegetables and vegetable-based products and their intakes by the Estonian populationFood Addit Contam.(2006 Apr)
3.^Lidder S, Webb AJVascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathwayBr J Clin Pharmacol.(2013 Mar)
4.^Tamme T, Reinik M, Roasto M, Juhkam K, Tenno T, Kiis ANitrates and nitrites in vegetables and vegetable-based products and their intakes by the Estonian populationFood Addit Contam.(2006 Apr)
5.^Chung SY, Kim JS, Kim M, Hong MK, Lee JO, Kim CM, Song ISSurvey of nitrate and nitrite contents of vegetables grown in KoreaFood Addit Contam.(2003 Jul)
7.^Ysart G, Clifford R, Harrison NMonitoring for nitrate in UK-grown lettuce and spinachFood Addit Contam.(1999 Jul)
8.^Petersen A, Stoltze SNitrate and nitrite in vegetables on the Danish market: content and intakeFood Addit Contam.(1999 Jul)
9.^Pardo-Marín O, Yusà-Pelechà V, Villalba-Martín P, Perez-Dasí JAMonitoring programme on nitrates in vegetables and vegetable-based baby foods marketed in the Region of Valencia, Spain: levels and estimated daily intakeFood Addit Contam Part A Chem Anal Control Expo Risk Assess.(2010 Apr)
10.^Lidder S, Webb AJVascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathwayBr J Clin Pharmacol.(2013 Mar)
11.^Gorenjak AH1, Koležnik UR, Cencič ANitrate content in dandelion (Taraxacum officinale) and lettuce (Lactuca sativa) from organic and conventional origin: intake assessmentFood Addit Contam Part B Surveill.(2012)
13.^Aschebrook-Kilfoy B, Heltshe SL, Nuckols JR, Sabra MM, Shuldiner AR, Mitchell BD, Airola M, Holford TR, Zhang Y, Ward MHModeled nitrate levels in well water supplies and prevalence of abnormal thyroid conditions among the Old Order Amish in PennsylvaniaEnviron Health.(2012 Feb 17)
16.^Distribution of nitrate assimilation between the root and shoot of legumes and a comparison with wheat.()
19.^Ysart G, Miller P, Barrett G, Farrington D, Lawrance P, Harrison NDietary exposures to nitrate in the UKFood Addit Contam.(1999 Dec)
20.^Hord NG, Tang Y, Bryan NSFood sources of nitrates and nitrites: the physiologic context for potential health benefitsAm J Clin Nutr.(2009 Jul)
23.^Walker RNitrates, nitrites and N-nitrosocompounds: a review of the occurrence in food and diet and the toxicological implicationsFood Addit Contam.(1990 Nov-Dec)
24.^Menard C, Heraud F, Volatier JL, Leblanc JCAssessment of dietary exposure of nitrate and nitrite in FranceFood Addit Contam Part A Chem Anal Control Expo Risk Assess.(2008 Aug)
25.^Lundberg JO, Weitzberg E, Gladwin MTThe nitrate-nitrite-nitric oxide pathway in physiology and therapeuticsNat Rev Drug Discov.(2008 Feb)
28.^van Velzen AG, Sips AJ, Schothorst RC, Lambers AC, Meulenbelt JThe oral bioavailability of nitrate from nitrate-rich vegetables in humansToxicol Lett.(2008 Oct 1)
29.^Hunault CC, van Velzen AG, Sips AJ, Schothorst RC, Meulenbelt JBioavailability of sodium nitrite from an aqueous solution in healthy adultsToxicol Lett.(2009 Oct 8)
30.^Tannenbaum SR, Weisman M, Fett DThe effect of nitrate intake on nitrite formation in human salivaFood Cosmet Toxicol.(1976 Dec)
31.^Spiegelhalder B, Eisenbrand G, Preussmann RInfluence of dietary nitrate on nitrite content of human saliva: possible relevance to in vivo formation of N-nitroso compoundsFood Cosmet Toxicol.(1976 Dec)
33.^Lundberg JO, Weitzberg E, Lundberg JM, Alving KIntragastric nitric oxide production in humans: measurements in expelled airGut.(1994 Nov)
34.^Lundberg JO, Govoni MInorganic nitrate is a possible source for systemic generation of nitric oxideFree Radic Biol Med.(2004 Aug 1)
35.^Govoni M, Jansson EA, Weitzberg E, Lundberg JOThe increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwashNitric Oxide.(2008 Dec)
36.^Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate.()
37.^Doel JJ, Benjamin N, Hector MP, Rogers M, Allaker RPEvaluation of bacterial nitrate reduction in the human oral cavityEur J Oral Sci.(2005 Feb)
38.^Tsuchiya K, Takiguchi Y, Okamoto M, Izawa Y, Kanematsu Y, Yoshizumi M, Tamaki TMalfunction of vascular control in lifestyle-related diseases: formation of systemic hemoglobin-nitric oxide complex (HbNO) from dietary nitriteJ Pharmacol Sci.(2004 Dec)
39.^Shiva S, Huang Z, Grubina R, Sun J, Ringwood LA, MacArthur PH, Xu X, Murphy E, Darley-Usmar VM, Gladwin MTDeoxymyoglobin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respirationCirc Res.(2007 Mar 16)
40.^Petersen MG, Dewilde S, Fago AReactions of ferrous neuroglobin and cytoglobin with nitrite under anaerobic conditionsJ Inorg Biochem.(2008 Sep)
41.^Tiso M, Tejero J, Basu S, Azarov I, Wang X, Simplaceanu V, Frizzell S, Jayaraman T, Geary L, Shapiro C, Ho C, Shiva S, Kim-Shapiro DB, Gladwin MTHuman neuroglobin functions as a redox-regulated nitrite reductaseJ Biol Chem.(2011 May 20)
42.^Webb AJ, Milsom AB, Rathod KS, Chu WL, Qureshi S, Lovell MJ, Lecomte FM, Perrett D, Raimondo C, Khoshbin E, Ahmed Z, Uppal R, Benjamin N, Hobbs AJ, Ahluwalia AMechanisms underlying erythrocyte and endothelial nitrite reduction to nitric oxide in hypoxia: role for xanthine oxidoreductase and endothelial nitric oxide synthaseCirc Res.(2008 Oct 24)
43.^Li H, Cui H, Kundu TK, Alzawahra W, Zweier JLNitric oxide production from nitrite occurs primarily in tissues not in the blood: critical role of xanthine oxidase and aldehyde oxidaseJ Biol Chem.(2008 Jun 27)
44.^Aamand R, Dalsgaard T, Jensen FB, Simonsen U, Roepstorff A, Fago AGeneration of nitric oxide from nitrite by carbonic anhydrase: a possible link between metabolic activity and vasodilationAm J Physiol Heart Circ Physiol.(2009 Dec)
45.^Duthu GS, Shertzer HGEffect of nitrite on rabbit liver mixed-function oxidase activityDrug Metab Dispos.(1979 Sep-Oct)
46.^Reutov VP, Sorokina EGNO-synthase and nitrite-reductase components of nitric oxide cycleBiochemistry (Mosc).(1998 Jul)
47.^Gautier C, van Faassen E, Mikula I, Martasek P, Slama-Schwok AEndothelial nitric oxide synthase reduces nitrite anions to NO under anoxiaBiochem Biophys Res Commun.(2006 Mar 17)
48.^Vanin AF, Bevers LM, Slama-Schwok A, van Faassen EENitric oxide synthase reduces nitrite to NO under anoxiaCell Mol Life Sci.(2007 Jan)
49.^Kleinbongard P, Dejam A, Lauer T, Rassaf T, Schindler A, Picker O, Scheeren T, Gödecke A, Schrader J, Schulz R, Heusch G, Schaub GA, Bryan NS, Feelisch M, Kelm MPlasma nitrite reflects constitutive nitric oxide synthase activity in mammalsFree Radic Biol Med.(2003 Oct 1)
50.^Rhodes P, Leone AM, Francis PL, Struthers AD, Moncada S, Rhodes PM {corrected to Rhodes P}The L-arginine:nitric oxide pathway is the major source of plasma nitrite in fasted humansBiochem Biophys Res Commun.(1995 Apr 17)
51.^Gago B, Lundberg JO, Barbosa RM, Laranjinha JRed wine-dependent reduction of nitrite to nitric oxide in the stomachFree Radic Biol Med.(2007 Nov 1)
52.^Benjamin N, O'Driscoll F, Dougall H, Duncan C, Smith L, Golden M, McKenzie HStomach NO synthesisNature.(1994 Apr 7)
53.^Kapil V, Milsom AB, Okorie M, Maleki-Toyserkani S, Akram F, Rehman F, Arghandawi S, Pearl V, Benjamin N, Loukogeorgakis S, Macallister R, Hobbs AJ, Webb AJ, Ahluwalia AInorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NOHypertension.(2010 Aug)
54.^McKnight GM, Smith LM, Drummond RS, Duncan CW, Golden M, Benjamin NChemical synthesis of nitric oxide in the stomach from dietary nitrate in humansGut.(1997 Feb)
55.^Lundberg JO, Weitzberg ENO generation from nitrite and its role in vascular controlArterioscler Thromb Vasc Biol.(2005 May)
56.^Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S, Rashid R, Miall P, Deanfield J, Benjamin N, MacAllister R, Hobbs AJ, Ahluwalia AAcute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitriteHypertension.(2008 Mar)
57.^Bryan NS, Fernandez BO, Bauer SM, Garcia-Saura MF, Milsom AB, Rassaf T, Maloney RE, Bharti A, Rodriguez J, Feelisch MNitrite is a signaling molecule and regulator of gene expression in mammalian tissuesNat Chem Biol.(2005 Oct)
58.^Dejam A, Hunter CJ, Tremonti C, Pluta RM, Hon YY, Grimes G, Partovi K, Pelletier MM, Oldfield EH, Cannon RO 3rd, Schechter AN, Gladwin MTNitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formationCirculation.(2007 Oct 16)
59.^Wylie LJ, Mohr M, Krustrup P, Jackman SR, Ermιdis G, Kelly J, Black MI, Bailey SJ, Vanhatalo A, Jones AMDietary nitrate supplementation improves team sport-specific intense intermittent exercise performanceEur J Appl Physiol.(2013 Feb 1)
60.^Subramanian D, Gupta SPharmacokinetic study of amaranth extract in healthy humans: A randomized trialNutrition.(2016 Jul-Aug)
61.^Wagner DA, Schultz DS, Deen WM, Young VR, Tannenbaum SRMetabolic fate of an oral dose of 15N-labeled nitrate in humans: effect of diet supplementation with ascorbic acidCancer Res.(1983 Apr)
62.^Chobanyan-Jürgens K, Schwarz A, Böhmer A, Beckmann B, Gutzki FM, Michaelsen JT, Stichtenoth DO, Tsikas DRenal carbonic anhydrases are involved in the reabsorption of endogenous nitriteNitric Oxide.(2012 Feb 15)
63.^Rabbitt P, Scott M, Thacker N, Lowe C, Jackson A, Horan M, Pendleton NLosses in gross brain volume and cerebral blood flow account for age-related differences in speed but not in fluid intelligenceNeuropsychology.(2006 Sep)
64.^Spilt A, Weverling-Rijnsburger AW, Middelkoop HA, van Der Flier WM, Gussekloo J, de Craen AJ, Bollen EL, Blauw GJ, van Buchem MA, Westendorp RGLate-onset dementia: structural brain damage and total cerebral blood flowRadiology.(2005 Sep)
65.^Holland CM, Smith EE, Csapo I, Gurol ME, Brylka DA, Killiany RJ, Blacker D, Albert MS, Guttmann CR, Greenberg SMSpatial distribution of white-matter hyperintensities in Alzheimer disease, cerebral amyloid angiopathy, and healthy agingStroke.(2008 Apr)
66.^Morris JS, Friston KJ, Büchel C, Frith CD, Young AW, Calder AJ, Dolan RJA neuromodulatory role for the human amygdala in processing emotional facial expressionsBrain.(1998 Jan)
67.^Moody DM, Brown WR, Challa VR, Anderson RLPeriventricular venous collagenosis: association with leukoaraiosisRadiology.(1995 Feb)
68.^Moody DM, Brown WR, Challa VR, Ghazi-Birry HS, Reboussin DMCerebral microvascular alterations in aging, leukoaraiosis, and Alzheimer's diseaseAnn N Y Acad Sci.(1997 Sep 26)
69.^Presley TD, Morgan AR, Bechtold E, Clodfelter W, Dove RW, Jennings JM, Kraft RA, King SB, Laurienti PJ, Rejeski WJ, Burdette JH, Kim-Shapiro DB, Miller GDAcute effect of a high nitrate diet on brain perfusion in older adultsNitric Oxide.(2011 Jan 1)
70.^Kelly J, Fulford J, Vanhatalo A, Blackwell JR, French O, Bailey SJ, Gilchrist M, Winyard PG, Jones AMEffects of short-term dietary nitrate supplementation on blood pressure, O2 uptake kinetics, and muscle and cognitive function in older adultsAm J Physiol Regul Integr Comp Physiol.(2013 Jan 15)
71.^Vanhatalo A, Fulford J, Bailey SJ, Blackwell JR, Winyard PG, Jones AMDietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxiaJ Physiol.(2011 Nov 15)
72.^Masschelein E, Van Thienen R, Wang X, Van Schepdael A, Thomis M, Hespel PDietary nitrate improves muscle but not cerebral oxygenation status during exercise in hypoxiaJ Appl Physiol.(2012 Sep 1)
73.^Ashmore T1, Fernandez BO2, Branco-Price C3, West JA4, Cowburn AS3, Heather LC5, Griffin JL4, Johnson RS3, Feelisch M2, Murray AJ6Dietary nitrate increases arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heartJ Physiol.(2014 Nov 1)
74.^Palmer RM, Ashton DS, Moncada SVascular endothelial cells synthesize nitric oxide from L-arginineNature.(1988 Jun 16)
75.^Moncada S, Palmer RM, Higgs EAThe discovery of nitric oxide as the endogenous nitrovasodilatorHypertension.(1988 Oct)
76.^Cosby K, Partovi KS, Crawford JH, Patel RP, Reiter CD, Martyr S, Yang BK, Waclawiw MA, Zalos G, Xu X, Huang KT, Shields H, Kim-Shapiro DB, Schechter AN, Cannon RO 3rd, Gladwin MTNitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulationNat Med.(2003 Dec)
77.^Modin A, Björne H, Herulf M, Alving K, Weitzberg E, Lundberg JONitrite-derived nitric oxide: a possible mediator of 'acidic-metabolic' vasodilationActa Physiol Scand.(2001 Jan)
78.^Demoncheaux EA, Higenbottam TW, Foster PJ, Borland CD, Smith AP, Marriott HM, Bee D, Akamine S, Davies MBCirculating nitrite anions are a directly acting vasodilator and are donors for nitric oxideClin Sci (Lond).(2002 Jan)
79.^van Faassen EE, Bahrami S, Feelisch M, Hogg N, Kelm M, Kim-Shapiro DB, Kozlov AV, Li H, Lundberg JO, Mason R, Nohl H, Rassaf T, Samouilov A, Slama-Schwok A, Shiva S, Vanin AF, Weitzberg E, Zweier J, Gladwin MTNitrite as regulator of hypoxic signaling in mammalian physiologyMed Res Rev.(2009 Sep)
80.^Huang Z, Shiva S, Kim-Shapiro DB, Patel RP, Ringwood LA, Irby CE, Huang KT, Ho C, Hogg N, Schechter AN, Gladwin MTEnzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric controlJ Clin Invest.(2005 Aug)
81.^Kleinbongard P, Dejam A, Lauer T, Jax T, Kerber S, Gharini P, Balzer J, Zotz RB, Scharf RE, Willers R, Schechter AN, Feelisch M, Kelm MPlasma nitrite concentrations reflect the degree of endothelial dysfunction in humansFree Radic Biol Med.(2006 Jan 15)
82.^Ferguson SK, Hirai DM, Copp SW, Holdsworth CT, Allen JD, Jones AM, Musch TI, Poole DCImpact of dietary nitrate supplementation via beetroot juice on exercising muscle vascular control in ratsJ Physiol.(2013 Jan 15)
83.^Bahra M, Kapil V, Pearl V, Ghosh S, Ahluwalia AInorganic nitrate ingestion improves vascular compliance but does not alter flow-mediated dilatation in healthy volunteersNitric Oxide.(2012 May 15)
84.^Bondonno CP, Yang X, Croft KD, Considine MJ, Ward NC, Rich L, Puddey IB, Swinny E, Mubarak A, Hodgson JMFlavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: a randomized controlled trialFree Radic Biol Med.(2012 Jan 1)
85.^Gilchrist M, Winyard PG, Aizawa K, Anning C, Shore A, Benjamin NEffect of dietary nitrate on blood pressure, endothelial function, and insulin sensitivity in type 2 diabetesFree Radic Biol Med.(2013 Feb 7)
86.^Coles LT, Clifton PMEffect of beetroot juice on lowering blood pressure in free-living, disease-free adults: a randomized, placebo-controlled trialNutr J.(2012 Dec 11)
87.^Bondonno CP, Liu AH, Croft KD, Ward NC, Shinde S, Moodley Y, Lundberg JO, Puddey IB, Woodman RJ, Hodgson JMAbsence of an effect of high nitrate intake from beetroot juice on blood pressure in treated hypertensive individuals: a randomized controlled trialAm J Clin Nutr.(2015 Aug)
88.^Radomski MW, Palmer RM, Moncada SEndogenous nitric oxide inhibits human platelet adhesion to vascular endotheliumLancet.(1987 Nov 7)
89.^Radomski MW, Palmer RM, Moncada SAn L-arginine/nitric oxide pathway present in human platelets regulates aggregationProc Natl Acad Sci U S A.(1990 Jul)
90.^Lauer T, Preik M, Rassaf T, Strauer BE, Deussen A, Feelisch M, Kelm MPlasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator actionProc Natl Acad Sci U S A.(2001 Oct 23)
92.^Piknova B, Schechter ANComments on Vascular effects of dietary nitrate (as found in green leafy vegetables & beetroot) via the nitrate-nitrite-nitric oxide pathwayBr J Clin Pharmacol.(2012 Nov 16)
93.^Richardson G, Hicks SL, O'Byrne S, Frost MT, Moore K, Benjamin N, McKnight GMThe ingestion of inorganic nitrate increases gastric S-nitrosothiol levels and inhibits platelet function in humansNitric Oxide.(2002 Aug)
94.^Cleeter MW, Cooper JM, Darley-Usmar VM, Moncada S, Schapira AHReversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseasesFEBS Lett.(1994 May 23)
95.^Bolaños JP, Peuchen S, Heales SJ, Land JM, Clark JBNitric oxide-mediated inhibition of the mitochondrial respiratory chain in cultured astrocytesJ Neurochem.(1994 Sep)
96.^Shen W, Xu X, Ochoa M, Zhao G, Wolin MS, Hintze THRole of nitric oxide in the regulation of oxygen consumption in conscious dogsCirc Res.(1994 Dec)
97.^Lacerda AC, Marubayashi U, Balthazar CH, Coimbra CCEvidence that brain nitric oxide inhibition increases metabolic cost of exercise, reducing running performance in ratsNeurosci Lett.(2006 Jan 30)
98.^Larsen FJ, Weitzberg E, Lundberg JO, Ekblom BEffects of dietary nitrate on oxygen cost during exerciseActa Physiol (Oxf).(2007 Sep)
99.^Lansley KE, Winyard PG, Fulford J, Vanhatalo A, Bailey SJ, Blackwell JR, DiMenna FJ, Gilchrist M, Benjamin N, Jones AMDietary nitrate supplementation reduces the O2 cost of walking and running: a placebo-controlled studyJ Appl Physiol.(2011 Mar)
100.^Larsen FJ, Weitzberg E, Lundberg JO, Ekblom BDietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exerciseFree Radic Biol Med.(2010 Jan 15)
101.^Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, Dimenna FJ, Wilkerson DP, Tarr J, Benjamin N, Jones AMDietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humansJ Appl Physiol.(2009 Oct)
102.^Bescós R, Rodríguez FA, Iglesias X, Ferrer MD, Iborra E, Pons AAcute administration of inorganic nitrate reduces VO(2peak) in endurance athletesMed Sci Sports Exerc.(2011 Oct)
103.^Larsen FJ, Schiffer TA, Borniquel S, Sahlin K, Ekblom B, Lundberg JO, Weitzberg EDietary inorganic nitrate improves mitochondrial efficiency in humansCell Metab.(2011 Feb 2)
104.^Hernández A, Schiffer TA, Ivarsson N, Cheng AJ, Bruton JD, Lundberg JO, Weitzberg E, Westerblad HDietary nitrate increases tetanic {Ca2+}i and contractile force in mouse fast-twitch muscleJ Physiol.(2012 Aug 1)
105.^Fulford J, Winyard PG, Vanhatalo A, Bailey SJ, Blackwell JR, Jones AMInfluence of dietary nitrate supplementation on human skeletal muscle metabolism and force production during maximum voluntary contractionsPflugers Arch.(2013 Jan 26)
106.^Bailey SJ, Fulford J, Vanhatalo A, Winyard PG, Blackwell JR, DiMenna FJ, Wilkerson DP, Benjamin N, Jones AMDietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humansJ Appl Physiol.(2010 Jul)
107.^Christensen PM, Nyberg M, Bangsbo JInfluence of nitrate supplementation on VO₂ kinetics and endurance of elite cyclistsScand J Med Sci Sports.(2013 Feb)
108.^Bond H, Morton L, Braakhuis AJDietary nitrate supplementation improves rowing performance in well-trained rowersInt J Sport Nutr Exerc Metab.(2012 Aug)
109.^Vanhatalo A, Bailey SJ, Blackwell JR, DiMenna FJ, Pavey TG, Wilkerson DP, Benjamin N, Winyard PG, Jones AMAcute and chronic effects of dietary nitrate supplementation on blood pressure and the physiological responses to moderate-intensity and incremental exerciseAm J Physiol Regul Integr Comp Physiol.(2010 Oct)
110.^Jones AM, Bailey SJ, Vanhatalo ADietary nitrate and O₂ consumption during exerciseMed Sport Sci.(2012)
111.^Murphy M, Eliot K, Heuertz RM, Weiss EWhole beetroot consumption acutely improves running performanceJ Acad Nutr Diet.(2012 Apr)
112.^Lansley KE, Winyard PG, Bailey SJ, Vanhatalo A, Wilkerson DP, Blackwell JR, Gilchrist M, Benjamin N, Jones AMAcute dietary nitrate supplementation improves cycling time trial performanceMed Sci Sports Exerc.(2011 Jun)
113.^Cermak NM, Res P, Stinkens R, Lundberg JO, Gibala MJ, van Loon L JCNo improvement in endurance performance after a single dose of beetroot juiceInt J Sport Nutr Exerc Metab.(2012 Dec)
114.^Cermak NM, Gibala MJ, van Loon LJNitrate supplementation's improvement of 10-km time-trial performance in trained cyclistsInt J Sport Nutr Exerc Metab.(2012 Feb)
115.^Mirvish SS, Reimers KJ, Kutler B, Chen SC, Haorah J, Morris CR, Grandjean AC, Lyden ERNitrate and nitrite concentrations in human saliva for men and women at different ages and times of the day and their consistency over timeEur J Cancer Prev.(2000 Oct)
116.^De Groef B, Decallonne BR, Van der Geyten S, Darras VM, Bouillon RPerchlorate versus other environmental sodium/iodide symporter inhibitors: potential thyroid-related health effectsEur J Endocrinol.(2006 Jul)
117.^BLOOMFIELD RA, WELSCH CW, GARNER GB, MUHRER METhyroid compensation under the influence of dietary nitrateProc Soc Exp Biol Med.(1962 Nov)
118.^Tonacchera M, Pinchera A, Dimida A, Ferrarini E, Agretti P, Vitti P, Santini F, Crump K, Gibbs JRelative potencies and additivity of perchlorate, thiocyanate, nitrate, and iodide on the inhibition of radioactive iodide uptake by the human sodium iodide symporterThyroid.(2004 Dec)
119.^BLOOMFIELD RA, WELSCH CW, GARNER GB, MUHRER MEEffect of dietary nitrate on thyroid functionScience.(1961 Nov 24)
120.^Ward MH, Kilfoy BA, Weyer PJ, Anderson KE, Folsom AR, Cerhan JRNitrate intake and the risk of thyroid cancer and thyroid diseaseEpidemiology.(2010 May)
122.^Capen CCMechanistic data and risk assessment of selected toxic end points of the thyroid glandToxicol Pathol.(1997 Jan-Feb)
123.^Tajtáková M, Semanová Z, Tomková Z, Szökeová E, Majoros J, Rádiková Z, Seböková E, Klimes I, Langer PIncreased thyroid volume and frequency of thyroid disorders signs in schoolchildren from nitrate polluted areaChemosphere.(2006 Jan)
124.^van Maanen JM, van Dijk A, Mulder K, de Baets MH, Menheere PC, van der Heide D, Mertens PL, Kleinjans JCConsumption of drinking water with high nitrate levels causes hypertrophy of the thyroidToxicol Lett.(1994 Jun)
125.^Jansson EA, Huang L, Malkey R, Govoni M, Nihlén C, Olsson A, Stensdotter M, Petersson J, Holm L, Weitzberg E, Lundberg JOA mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasisNat Chem Biol.(2008 Jul)
126.^Dougall HT, Smith L, Duncan C, Benjamin NThe effect of amoxycillin on salivary nitrite concentrations: an important mechanism of adverse reactionsBr J Clin Pharmacol.(1995 Apr)
127.^Machha A, Schechter ANDietary nitrite and nitrate: a review of potential mechanisms of cardiovascular benefitsEur J Nutr.(2011 Aug)
128.^Tsuchiya K, Tomita S, Ishizawa K, Abe S, Ikeda Y, Kihira Y, Tamaki TDietary nitrite ameliorates renal injury in L-NAME-induced hypertensive ratsNitric Oxide.(2010 Feb 15)
129.^Carlström M, Persson AE, Larsson E, Hezel M, Scheffer PG, Teerlink T, Weitzberg E, Lundberg JODietary nitrate attenuates oxidative stress, prevents cardiac and renal injuries, and reduces blood pressure in salt-induced hypertensionCardiovasc Res.(2011 Feb 15)
130.^Ito K, Chen J, Vaughan ED Jr, Seshan SV, Poppas DP, Felsen DDietary L-arginine supplementation improves the glomerular filtration rate and renal blood flow after 24 hours of unilateral ureteral obstruction in ratsJ Urol.(2004 Feb)
131.^Xiao DS, Jiang L, Che LL, Lu LNitric oxide and iron metabolism in exercised rat with L-arginine supplementationMol Cell Biochem.(2003 Oct)
132.^Baylis CNitric oxide synthase derangements and hypertension in kidney diseaseCurr Opin Nephrol Hypertens.(2012 Jan)
133.^Binkerd EF, Kolari OEThe history and use of nitrate and nitrite in the curing of meatFood Cosmet Toxicol.(1975 Dec)
134.^Sakshaug J, Sögnen E, Hansen MA, Koppang NDimethylnitrosamine; its hepatotoxic effect in sheep and its occurrence in toxic batches of herring mealNature.(1965 Jun 19)
135.^Sander JCan nitrites in the human diet be the cause of cancerogenesis through formation of nitrosamines?Arch Hyg Bakteriol.(1967 May)
136.^The Production of Malignant Primary Hepatic Tumours in the Rat by Feeding Dimethylnitrosamine.()
137.^Bartsch H, Ohshima H, Pignatelli BInhibitors of endogenous nitrosation. Mechanisms and implications in human cancer preventionMutat Res.(1988 Dec)
139.^Mensinga TT, Speijers GJ, Meulenbelt JHealth implications of exposure to environmental nitrogenous compoundsToxicol Rev.(2003)
140.^Aschebrook-Kilfoy B, Ward MH, Gierach GL, Schatzkin A, Hollenbeck AR, Sinha R, Cross AJEpithelial ovarian cancer and exposure to dietary nitrate and nitrite in the NIH-AARP Diet and Health StudyEur J Cancer Prev.(2012 Jan)
141.^Aschebrook-Kilfoy B, Cross AJ, Stolzenberg-Solomon RZ, Schatzkin A, Hollenbeck AR, Sinha R, Ward MHPancreatic cancer and exposure to dietary nitrate and nitrite in the NIH-AARP Diet and Health StudyAm J Epidemiol.(2011 Aug 1)
142.^Ward MH, Heineman EF, Markin RS, Weisenburger DDAdenocarcinoma of the stomach and esophagus and drinking water and dietary sources of nitrate and nitriteInt J Occup Environ Health.(2008 Jul-Sep)
143.^Ward MH, Cerhan JR, Colt JS, Hartge PRisk of non-Hodgkin lymphoma and nitrate and nitrite from drinking water and dietEpidemiology.(2006 Jul)
144.^Ward MH, Rusiecki JA, Lynch CF, Cantor KPNitrate in public water supplies and the risk of renal cell carcinomaCancer Causes Control.(2007 Dec)
145.^Milkowski A, Garg HK, Coughlin JR, Bryan NSNutritional epidemiology in the context of nitric oxide biology: a risk-benefit evaluation for dietary nitrite and nitrateNitric Oxide.(2010 Feb 15)
146.^Mirvish SS, Wallcave L, Eagen M, Shubik PAscorbate-nitrite reaction: possible means of blocking the formation of carcinogenic N-nitroso compoundsScience.(1972 Jul 7)
147.^Combet E, El Mesmari A, Preston T, Crozier A, McColl KEDietary phenolic acids and ascorbic acid: Influence on acid-catalyzed nitrosative chemistry in the presence and absence of lipidsFree Radic Biol Med.(2010 Mar 15)
148.^Combet E, Paterson S, Iijima K, Winter J, Mullen W, Crozier A, Preston T, McColl KEFat transforms ascorbic acid from inhibiting to promoting acid-catalysed N-nitrosationGut.(2007 Dec)
149.^Miyauchi M, Nakamura H, Furukawa F, Son HY, Nishikawa A, Hirose MPromoting effects of combined antioxidant and sodium nitrite treatment on forestomach carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidineCancer Lett.(2002 Apr 8)
150.^Kuroiwa Y, Ishii Y, Umemura T, Kanki K, Mitsumori K, Nishikawa A, Nakazawa H, Hirose MCombined treatment with green tea catechins and sodium nitrite selectively promotes rat forestomach carcinogenesis after initiation with N-methyl-N'- nitro-N-nitrosoguanidineCancer Sci.(2007 Jul)
151.^Brown GC, Cooper CENanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidaseFEBS Lett.(1994 Dec 19)
154.^Poderoso JJ, Peralta JG, Lisdero CL, Carreras MC, Radisic M, Schöpfer F, Cadenas E, Boveris ANitric oxide regulates oxygen uptake and hydrogen peroxide release by the isolated beating rat heartAm J Physiol.(1998 Jan)
155.^Shen W, Hintze TH, Wolin MSNitric oxide. An important signaling mechanism between vascular endothelium and parenchymal cells in the regulation of oxygen consumptionCirculation.(1995 Dec 15)
156.^Brown GC, Borutaite VInhibition of mitochondrial respiratory complex I by nitric oxide, peroxynitrite and S-nitrosothiolsBiochim Biophys Acta.(2004 Jul 23)
157.^Yamamoto T, Maruyama W, Kato Y, Yi H, Shamoto-Nagai M, Tanaka M, Sato Y, Naoi MSelective nitration of mitochondrial complex I by peroxynitrite: involvement in mitochondria dysfunction and cell death of dopaminergic SH-SY5Y cellsJ Neural Transm.(2002)
158.^Riobó NA, Clementi E, Melani M, Boveris A, Cadenas E, Moncada S, Poderoso JJNitric oxide inhibits mitochondrial NADH:ubiquinone reductase activity through peroxynitrite formationBiochem J.(2001 Oct 1)
159.^Murray J, Taylor SW, Zhang B, Ghosh SS, Capaldi RAOxidative damage to mitochondrial complex I due to peroxynitrite: identification of reactive tyrosines by mass spectrometryJ Biol Chem.(2003 Sep 26)
160.^Dahm CC, Moore K, Murphy MPPersistent S-nitrosation of complex I and other mitochondrial membrane proteins by S-nitrosothiols but not nitric oxide or peroxynitrite: implications for the interaction of nitric oxide with mitochondriaJ Biol Chem.(2006 Apr 14)
161.^Brown GC, Borutaite VNitric oxide and mitochondrial respiration in the heartCardiovasc Res.(2007 Jul 15)
162.^Bailey SJ, Winyard PG, Vanhatalo A, Blackwell JR, DiMenna FJ, Wilkerson DP, Jones AMAcute L-arginine supplementation reduces the O2 cost of moderate-intensity exercise and enhances high-intensity exercise toleranceJ Appl Physiol.(2010 Nov)
163.^Sindler AL, Fleenor BS, Calvert JW, Marshall KD, Zigler ML, Lefer DJ, Seals DRNitrite supplementation reverses vascular endothelial dysfunction and large elastic artery stiffness with agingAging Cell.(2011 Jun)
164.^Olthof MR, Verhoef PEffects of betaine intake on plasma homocysteine concentrations and consequences for healthCurr Drug Metab.(2005 Feb)
165.^Detopoulou P, Panagiotakos DB, Antonopoulou S, Pitsavos C, Stefanadis CDietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA studyAm J Clin Nutr.(2008 Feb)
166.^Lee EC, Maresh CM, Kraemer WJ, Yamamoto LM, Hatfield DL, Bailey BL, Armstrong LE, Volek JS, McDermott BP, Craig SAErgogenic effects of betaine supplementation on strength and power performanceJ Int Soc Sports Nutr.(2010 Jul 19)
167.^Hoffman JR, Ratamess NA, Kang J, Rashti SL, Faigenbaum ADEffect of betaine supplementation on power performance and fatigueJ Int Soc Sports Nutr.(2009 Feb 27)
168.^Bloomer RJ, Farney TM, Trepanowski JF, McCarthy CG, Canale REEffect of betaine supplementation on plasma nitrate/nitrite in exercise-trained menJ Int Soc Sports Nutr.(2011 Mar 18)
169.^Trepanowski JF, Farney TM, McCarthy CG, Schilling BK, Craig SA, Bloomer RJThe effects of chronic betaine supplementation on exercise performance, skeletal muscle oxygen saturation and associated biochemical parameters in resistance trained menJ Strength Cond Res.(2011 Dec)
170.^Münzel T, Heitzer T, Kurz S, Harrison DG, Luhman C, Pape L, Olschewski M, Just HDissociation of coronary vascular tolerance and neurohormonal adjustments during long-term nitroglycerin therapy in patients with stable coronary artery diseaseJ Am Coll Cardiol.(1996 Feb)
171.^Münzel T, Daiber A, Gori TNitrate therapy: new aspects concerning molecular action and toleranceCirculation.(2011 May 17)
172.^Kim D, Rybalkin SD, Pi X, Wang Y, Zhang C, Munzel T, Beavo JA, Berk BC, Yan CUpregulation of phosphodiesterase 1A1 expression is associated with the development of nitrate toleranceCirculation.(2001 Nov 6)
173.^Feil R, Kleppisch TNO/cGMP-dependent modulation of synaptic transmissionHandb Exp Pharmacol.(2008)
174.^Sonnenburg WK, Seger D, Kwak KS, Huang J, Charbonneau H, Beavo JAIdentification of inhibitory and calmodulin-binding domains of the PDE1A1 and PDE1A2 calmodulin-stimulated cyclic nucleotide phosphodiesterasesJ Biol Chem.(1995 Dec 29)
175.^Sharma RK, Wang JHDifferential regulation of bovine brain calmodulin-dependent cyclic nucleotide phosphodiesterase isoenzymes by cyclic AMP-dependent protein kinase and calmodulin-dependent phosphataseProc Natl Acad Sci U S A.(1985 May)
177.^Bönöczk P, Gulyás B, Adam-Vizi V, Nemes A, Kárpáti E, Kiss B, Kapás M, Szántay C, Koncz I, Zelles T, Vas ARole of sodium channel inhibition in neuroprotection: effect of vinpocetineBrain Res Bull.(2000 Oct)
178.^Hagiwara M, Endo T, Hidaka HEffects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscleBiochem Pharmacol.(1984 Feb 1)
179.^Münzel T, Heitzer T, Kurz S, Harrison DG, Luhman C, Pape L, Olschewski M, Just HDissociation of coronary vascular tolerance and neurohormonal adjustments during long-term nitroglycerin therapy in patients with stable coronary artery diseaseJ Am Coll Cardiol.(1996 Feb)
180.^Münzel T, Daiber A, Gori TNitrate therapy: new aspects concerning molecular action and toleranceCirculation.(2011 May 17)
181.^Lim HK, Lim HK, Ryoo S, Benjo A, Shuleri K, Miriel V, Baraban E, Camara A, Soucy K, Nyhan D, Shoukas A, Berkowitz DEMitochondrial arginase II constrains endothelial NOS-3 activityAm J Physiol Heart Circ Physiol.(2007 Dec)
182.^Abou-Mohamed G, Kaesemeyer WH, Caldwell RB, Caldwell RWRole of L-arginine in the vascular actions and development of tolerance to nitroglycerinBr J Pharmacol.(2000 May)
183.^Parker JO, Parker JD, Caldwell RW, Farrell B, Kaesemeyer WHThe effect of supplemental L-arginine on tolerance development during continuous transdermal nitroglycerin therapyJ Am Coll Cardiol.(2002 Apr 3)
Primary Use