Nitric Oxide

    Last Updated: August 17, 2022

    Nitric oxide (NO) is composed of nitrogen (N) and oxygen (O). The human body creates NO from dietary arginine and nitrate. NO plays a major signaling role in vascular relaxation, and elevated levels are associated with better blood flow and lower blood pressure.

    Overview

    The human body converts nitrate to nitric oxide (NO), which is a signaling molecule associated with several physiological functions involving blood pressure regulation, cardiovascular health, mitochondria production, calcium transport, oxidative stress, and skeletal muscle repair.[23] It plays a prominent role as a vasodilator, which means it relaxes blood vessels and improves blood flow.

    Nitrate supplementation, whether in its pure form (e.g. sodium/potassium nitrate), or via foods (e.g. beetroot juice/powder), may temporarily reduce the body’s oxygen demand during exercise. A decrease in oxygen demand may result in improved exercise and muscular performance.[24][25]

    Examine Database: Nitric Oxide

    B
    Small Increase
    B
    Small Increase
    D
    No effect
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    References

    1. ^Feil R, Kleppisch TNO/cGMP-dependent modulation of synaptic transmissionHandb Exp Pharmacol.(2008)
    2. ^Thompson WJ, Terasaki WL, Epstein PM, Strada SJAssay of cyclic nucleotide phosphodiesterase and resolution of multiple molecular forms of the enzymeAdv Cyclic Nucleotide Res.(1979)
    3. ^Beavo JA, Hansen RS, Harrison SA, Hurwitz RL, Martins TJ, Mumby MCIdentification and properties of cyclic nucleotide phosphodiesterasesMol Cell Endocrinol.(1982 Nov-Dec)
    4. ^Burnett ALThe role of nitric oxide in erectile dysfunction: implications for medical therapyJ Clin Hypertens (Greenwich).(2006 Dec)
    5. ^Pacher P, Beckman JS, Liaudet LNitric oxide and peroxynitrite in health and diseasePhysiol Rev.(2007 Jan)
    6. ^Peroxynitrite: biochemistry, pathophysiology and development of therapeutics
    7. ^Groves JTPeroxynitrite: reactive, invasive and enigmaticCurr Opin Chem Biol.(1999 Apr)
    8. ^Eiserich JP, Patel RP, O'Donnell VBPathophysiology of nitric oxide and related species: free radical reactions and modification of biomoleculesMol Aspects Med.(1998 Aug-Oct)
    9. ^Szabó CMultiple pathways of peroxynitrite cytotoxicityToxicol Lett.(2003 Apr 11)
    10. ^Nathan CNitric oxide as a secretory product of mammalian cellsFASEB J.(1992 Sep)
    11. ^Archer SMeasurement of nitric oxide in biological modelsFASEB J.(1993 Feb 1)
    12. ^Hakim TS, Sugimori K, Camporesi EM, Anderson GHalf-life of nitric oxide in aqueous solutions with and without haemoglobinPhysiol Meas.(1996 Nov)
    13. ^Yoda Y, Otani N, Hasunuma H, Kanegae H, Shima MStorage conditions for stability of offline measurement of fractional exhaled nitric oxide after collection for epidemiologic researchBMC Pulm Med.(2012 Nov 2)
    14. ^Bodini A, Pijnenburg MW, Boner AL, de Jongste JCExhaled nitric oxide in mylar balloons: influence of storage time, humidity and temperatureMediators Inflamm.(2003 Feb)
    15. ^Lewis SJ, Bhopatkar MY, Walton TM, Bates JNRole of voltage-sensitive calcium-channels in nitric oxide-mediated vasodilation in spontaneously hypertensive ratsEur J Pharmacol.(2005 Dec 28)
    16. ^Tozer AJ, Forsythe ID, Steinert JRNitric oxide signalling augments neuronal voltage-gated L-type (Ca(v)1) and P/q-type (Ca(v)2.1) channels in the mouse medial nucleus of the trapezoid bodyPLoS One.(2012)
    17. ^Brenman JE, Chao DS, Gee SH, McGee AW, Craven SE, Santillano DR, Wu Z, Huang F, Xia H, Peters MF, Froehner SC, Bredt DSInteraction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domainsCell.(1996 Mar 8)
    18. ^Tochio H, Mok YK, Zhang Q, Kan HM, Bredt DS, Zhang MFormation of nNOS/PSD-95 PDZ dimer requires a preformed beta-finger structure from the nNOS PDZ domainJ Mol Biol.(2000 Oct 27)
    19. ^Doucet MV, Levine H, Dev KK, Harkin ASmall-Molecule Inhibitors at the PSD-95/nNOS Interface have Antidepressant-Like Properties in MiceNeuropsychopharmacology.(2013 Feb 27)
    20. ^Guix FX, Uribesalgo I, Coma M, Muñoz FJThe physiology and pathophysiology of nitric oxide in the brainProg Neurobiol.(2005 Jun)
    21. ^Naghavi N, de Mel A, Alavijeh OS, Cousins BG, Seifalian AMNitric Oxide Donors for Cardiovascular Implant ApplicationsSmall.(2012 Nov 8)
    22. ^Beigi F, Gonzalez DR, Minhas KM, Sun QA, Foster MW, Khan SA, Treuer AV, Dulce RA, Harrison RW, Saraiva RM, Premer C, Schulman IH, Stamler JS, Hare JMDynamic denitrosylation via S-nitrosoglutathione reductase regulates cardiovascular functionProc Natl Acad Sci U S A.(2012 Mar 13)
    23. ^J S Stamler, G MeissnerPhysiology of nitric oxide in skeletal musclePhysiol Rev.(2001 Jan)
    24. ^Stephen J Bailey, Paul Winyard, Anni Vanhatalo, Jamie R Blackwell, Fred J Dimenna, Daryl P Wilkerson, Joanna Tarr, Nigel Benjamin, Andrew M JonesDietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humansJ Appl Physiol (1985).(2009 Oct)
    25. ^Bescós R, Sureda A, Tur JA, Pons AThe effect of nitric-oxide-related supplements on human performanceSports Med.(2012 Feb 1)
    26. ^Yvette C Luiking, Mariëlle P K J Engelen, Nicolaas E P DeutzRegulation of nitric oxide production in health and diseaseCurr Opin Clin Nutr Metab Care.(2010 Jan)
    27. ^Dimitrios TsikasMethods of quantitative analysis of the nitric oxide metabolites nitrite and nitrate in human biological fluidsFree Radic Res.(2005 Aug)
    28. ^William T Clements, Sang-Rok Lee, Richard J BloomerNitrate ingestion: a review of the health and physical performance effectsNutrients.(2014 Nov 18)
    29. ^Hord NG, Tang Y, Bryan NSFood sources of nitrates and nitrites: the physiologic context for potential health benefitsAm J Clin Nutr.(2009 Jul)
    30. ^Jackson J, Patterson AJ, MacDonald-Wicks L, McEvoy MThe role of inorganic nitrate and nitrite in CVDNutr Res Rev.(2017 Dec)
    31. ^Chambliss KL, Shaul PWEstrogen modulation of endothelial nitric oxide synthaseEndocr Rev.(2002 Oct)

    Examine Database References

    1. Arginine - Lucotti P, Setola E, Monti LD, Galluccio E, Costa S, Sandoli EP, Fermo I, Rabaiotti G, Gatti R, Piatti PBeneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patientsAm J Physiol Endocrinol Metab.(2006 Nov)
    2. Arginine - Willoughby DS, Boucher T, Reid J, Skelton G, Clark MEffects of 7 days of arginine-alpha-ketoglutarate supplementation on blood flow, plasma L-arginine, nitric oxide metabolites, and asymmetric dimethyl arginine after resistance exerciseInt J Sport Nutr Exerc Metab.(2011 Aug)
    3. Arginine - Stephen J. Bailey, Paul G. Winyard, Anni Vanhatalo, Jamie R. Blackwell, Fred J. DiMenna, Daryl Paul Wilkerson, and Andrew M. JonesAcute L-arginine supplementation reduces the O2 cost of moderate-intensity exercise and enhances high-intensity exercise toleranceJournal of Applied Physiology.()
    4. Cocoa Extract - Loffredo L, Perri L, Catasca E, Pignatelli P, Brancorsini M, Nocella C, De Falco E, Bartimoccia S, Frati G, Carnevale R, Violi FDark chocolate acutely improves walking autonomy in patients with peripheral artery diseaseJ Am Heart Assoc.(2014 Jul 2)
    5. Blueberry - Johnson SA, Figueroa A, Navaei N, Wong A, Kalfon R, Ormsbee LT, Feresin RG, Elam ML, Hooshmand S, Payton ME, Arjmandi BHDaily blueberry consumption improves blood pressure and arterial stiffness in postmenopausal women with pre- and stage 1-hypertension: a randomized, double-blind, placebo-controlled clinical trialJ Acad Nutr Diet.(2015 Mar)
    6. Ginkgo Biloba - Li XS, Zheng WY, Lou SX, Lu XW, Ye SHEffect of Ginkgo leaf extract on vascular endothelial function in patients with early stage diabetic nephropathyChin J Integr Med.(2009 Feb)
    7. Grape Juice - Albers AR, Varghese S, Vitseva O, Vita JA, Freedman JEThe antiinflammatory effects of purple grape juice consumption in subjects with stable coronary artery diseaseArterioscler Thromb Vasc Biol.(2004 Nov)
    8. Arginine - Schwedhelm E, Maas R, Freese R, Jung D, Lukacs Z, Jambrecina A, Spickler W, Schulze F, Böger RHPharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolismBr J Clin Pharmacol.(2008 Jan)
    9. Garlic - Mau Bhattacharyya, G V Girish, Soumendra K Karmohapatra, S A Samad, Asru K SinhaSystemic production of IFN-alpha by garlic (Allium sativum) in humansJ Interferon Cytokine Res.(2007 May)
    10. Betaine - 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)
    11. Fish Oil - Filaire E, Massart A, Portier H, Rouveix M, Rosado F, Bage AS, Gobert M, Durand DEffect of 6 Weeks of n-3 fatty-acid supplementation on oxidative stress in Judo athletesInt J Sport Nutr Exerc Metab.(2010 Dec)
    12. Arginine - Jabłecka A, Bogdański P, Balcer N, Cieślewicz A, Skołuda A, Musialik KThe effect of oral L-arginine supplementation on fasting glucose, HbA1c, nitric oxide and total antioxidant status in diabetic patients with atherosclerotic peripheral arterial disease of lower extremitiesEur Rev Med Pharmacol Sci.(2012 Mar)
    13. Ginkgo Biloba - Rodríguez M, Ringstad L, Schäfer P, Just S, Hofer HW, Malmsten M, Siegel GReduction of atherosclerotic nanoplaque formation and size by Ginkgo biloba (EGb 761) in cardiovascular high-risk patientsAtherosclerosis.(2007 Jun)
    14. Arginine - Böger RH, Bode-Böger SM, Thiele W, Creutzig A, Alexander K, Frölich JCRestoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive diseaseJ Am Coll Cardiol.(1998 Nov)
    15. Cocoa Extract - Verawati Sudarma, Sri Sukmaniah, Parlindungan SiregarEffect of dark chocolate on nitric oxide serum levels and blood pressure in prehypertension subjectsActa Med Indones.(2011 Oct)
    16. Astaxanthin - Petyaev IM, Klochkov VA, Chalyk NE, Pristensky DV, Chernyshova MP, Kyle NH, Bashmakov YKMarkers of Hypoxia and Oxidative Stress in Aging Volunteers Ingesting Lycosomal Formulation of Dark Chocolate Containing AstaxanthinJ Nutr Health Aging.(2018)
    17. Curcumin - DiSilvestro RA, Joseph E, Zhao S, Bomser JDiverse effects of a low dose supplement of lipidated curcumin in healthy middle aged peopleNutr J.(2012 Sep 26)
    18. L-Carnitine - Bloomer RJ, Tschume LC, Smith WAGlycine propionyl-L-carnitine modulates lipid peroxidation and nitric oxide in human subjectsInt J Vitam Nutr Res.(2009 May)
    19. L-Carnitine - Hamid Reza Talari, Zeinab Jafari Azad, Yaser Hamidian, Mansooreh Samimi, Hamid Reza Gilasi, Faraneh Ebrahimi Afshar, Vahidreza Ostadmohammadi, Zatollah AsemiEffects of Carnitine Administration on Carotid Intima-media Thickness and Inflammatory Factors in Patients with Polycystic Ovary Syndrome: A Randomized, Double-blind, Placebo-controlled TrialInt J Prev Med.(2019 Jun 7)
    20. Cocoa Extract - Loffredo L, Carnevale R, Perri L, Catasca E, Augelletti T, Cangemi R, Albanese F, Piccheri C, Nocella C, Pignatelli P, Violi FNOX2-mediated arterial dysfunction in smokers: acute effect of dark chocolateHeart.(2011 Nov)
    21. Hesperidin - Morand C, Dubray C, Milenkovic D, Lioger D, Martin JF, Scalbert A, Mazur AHesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteersAm J Clin Nutr.(2011 Jan)
    22. Coenzyme Q10 - Jahangard L, Yasrebifar F, Haghighi M, Ranjbar A, Mehrpooya MInfluence of adjuvant Coenzyme Q10 on inflammatory and oxidative stress biomarkers in patients with bipolar disorders during the depressive episodeMol Biol Rep.(2019 Oct)
    23. Citrulline - Sureda A, Córdova A, Ferrer MD, Pérez G, Tur JA, Pons AL-citrulline-malate influence over branched chain amino acid utilization during exerciseEur J Appl Physiol.(2010 Sep)
    24. Rooibos - Persson IA, Persson K, Hägg S, Andersson RGEffects of green tea, black tea and Rooibos tea on angiotensin-converting enzyme and nitric oxide in healthy volunteersPublic Health Nutr.(2010 May)
    25. Blueberry - Del Bo C, Riso P, Campolo J, Møller P, Loft S, Klimis-Zacas D, Brambilla A, Rizzolo A, Porrini MA single portion of blueberry (Vaccinium corymbosum L) improves protection against DNA damage but not vascular function in healthy male volunteersNutr Res.(2013 Mar)
    26. Arginine - Liu TH, Wu CL, Chiang CW, Lo YW, Tseng HF, Chang CKNo effect of short-term arginine supplementation on nitric oxide production, metabolism and performance in intermittent exercise in athletesJ Nutr Biochem.(2009 Jun)
    27. Cocoa Extract - Hammer A, Koppensteiner R, Steiner S, Niessner A, Goliasch G, Gschwandtner M, Hoke MDark chocolate and vascular function in patients with peripheral artery disease: a randomized, controlled cross-over trialClin Hemorheol Microcirc.(2015)
    28. Pycnogenol - Liu X, Wei J, Tan F, Zhou S, Würthwein G, Rohdewald PPycnogenol, French maritime pine bark extract, improves endothelial function of hypertensive patientsLife Sci.(2004 Jan 2)
    29. Citrulline - Ochiai M, Hayashi T, Morita M, Ina K, Maeda M, Watanabe F, Morishita KShort-term effects of L-citrulline supplementation on arterial stiffness in middle-aged menInt J Cardiol.(2012 Mar 8)
    30. DHEA - Martina V, Benso A, Gigliardi VR, Masha A, Origlia C, Granata R, Ghigo EShort-term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjectsClin Endocrinol (Oxf).(2006 Mar)
    31. Punicalagins - Pantuck AJ, Leppert JT, Zomorodian N, Aronson W, Hong J, Barnard RJ, Seeram N, Liker H, Wang H, Elashoff R, Heber D, Aviram M, Ignarro L, Belldegrun APhase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancerClin Cancer Res.(2006 Jul 1)
    32. Schisandra - Panossian AG, Oganessian AS, Ambartsumian M, Gabrielian ES, Wagner H, Wikman GEffects of heavy physical exercise and adaptogens on nitric oxide content in human salivaPhytomedicine.(1999 Mar)
    33. Tart Cherry Juice - Chai SC, Davis K, Zhang Z, Zha L, Kirschner KFEffects of Tart Cherry Juice on Biomarkers of Inflammation and Oxidative Stress in Older Adults.Nutrients.(2019-Jan-22)
    34. Tart Cherry Juice - Keane KM, Bailey SJ, Vanhatalo A, Jones AM, Howatson GEffects of montmorency tart cherry (L. Prunus Cerasus) consumption on nitric oxide biomarkers and exercise performance.Scand J Med Sci Sports.(2018-Jul)
    35. Tart Cherry Juice - Keane KM, George TW, Constantinou CL, Brown MA, Clifford T, Howatson GEffects of Montmorency tart cherry (Prunus Cerasus L.) consumption on vascular function in men with early hypertension.Am J Clin Nutr.(2016-Jun)
    36. Magnesium - Nicola Veronese, Damiano Pizzol, Lee Smith, Ligia J Dominguez, Mario BarbagalloEffect of Magnesium Supplementation on Inflammatory Parameters: A Meta-Analysis of Randomized Controlled TrialsNutrients.(2022 Feb 5)
    37. Magnesium - Chua FB, Cinco JE, Paz-Pacheco EEfficacy of Magnesium Supplementation on Glycemic Control in Type 2 Diabetes Patients: A Meta-analysis.J ASEAN Fed Endocr Soc.(2017)
    38. Whey Protein - Hajizadeh-Sharafabad F, Sharifi Zahabi E, Tarighat-Esfanjani ARole of whey protein in vascular function: a systematic review and meta-analysis of human intervention studies.Br J Nutr.(2022-Aug-28)
    39. Folic Acid (Vitamin B9) - Asbaghi O, Ghanavati M, Ashtary-Larky D, Bagheri R, Rezaei Kelishadi M, Nazarian B, Nordvall M, Wong A, Dutheil F, Suzuki K, Alavi Naeini AEffects of Folic Acid Supplementation on Oxidative Stress Markers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Antioxidants (Basel).(2021-May-28)