Arginine

Last Updated: January 23, 2023

Arginine is an amino acid involved in the regulation of vascular function and blood flow. Supplementation may improve high blood pressure and erectile dysfunction.

Arginine is most often used for

What is arginine?

Arginine, also called L-arginine, is an amino acid used by the body as a protein building block. It’s also an intermediate metabolite in the urea cycle and the nitric oxide cycle.[1][2][3] The urea cycle removes excess ammonia, a toxic molecule, from the body, and the nitric oxide cycle produces nitric oxide, which is an important signaling molecule involved in vascular function.[1][2][3] Although the body can synthesize arginine, arginine can also be obtained in the diet through protein-containing foods or dietary supplements.[1][2][3]

What are arginine’s main benefits?

Daily supplementation with arginine can reduce blood pressure in people with healthy blood pressure and people with hypertension (high blood pressure).[4] Evidence also supports the use of arginine to help improve birth outcomes in pregnant women who have conditions like hypertension and preeclampsia, or who have a history of poor pregnancy outcomes. The improved outcomes include a reduced risk of small for gestational age infants[5] and a reduced risk of intrauterine growth restriction of the baby.[6] Arginine can also improve maternal outcomes by reducing the risk of preeclampsia in the pregnant mother.[7][8][9] Additionally, arginine can reduce blood triglycerides,[10][11] particularly in people older than 50 or in people with metabolic syndrome or type 2 diabetes.[10]

In men with erectile dysfunction, daily supplementation with arginine can alleviate symptoms.[12] Furthermore, the combination of arginine with phosphodiesterase type 5 inhibitors (PDE5Is), like Viagra, improves sexual function in men with erectile dysfunction more than treatment with PDE5Is alone.[13]

Evidence also shows that daily supplementation with arginine might increase VO2max, but the magnitude of improvement is negligible and unlikely to be clinically meaningful.[14] Furthermore, most studies find no beneficial effect of arginine on exercise performance.[15] It is only when highly-varied types of exercise (aerobic, anaerobic, resistance, etc.) and performance outcomes (time-to-exhaustion, time-trials, sprint time, 1-rep-max, reps-to-failure, etc.) are inappropriately pooled that meta-analyses find a performance benefit from arginine.[15]

What are arginine’s main drawbacks?

Animal studies show that neither oral nor intravenous delivery of arginine causes toxicity, even at high doses.[16][17] However, supplementation with arginine has been reported to cause adverse gastrointestinal effects in humans, including nausea, vomiting, and diarrhea.[18] For this reason, upper-limit guidelines of approximately 20 to 30 grams per day have been proposed for supplemental arginine intake,[19][20] but more long-term safety data in humans are needed to accurately define a tolerable upper intake level.

How does arginine work?

Nitric oxide is a key molecule involved in vasodilation (the relaxation and widening of blood vessels to increase blood flow to tissues that lack oxygen or nutrients).[21][2] The beneficial effects of arginine on high blood pressure[4][7][8] and erectile dysfunction[12][13] are likely related to vasodilation because arginine increases nitric oxide synthesis.[21][2][3]

A similar mechanism may explain how arginine might increase VO2max.[22][23][14] Additionally, nitric oxide might have direct effects on muscle contractile function.[22][24] Furthermore, arginine’s role in the urea cycle helps with the excretion of ammonia[1], the accumulation of which might induce fatigue during exercise.[25][26][27]

What else is Arginine known as?
Note that Arginine is also known as:
  • L-Arginine
Dosage information

The standard preworkout dose for arginine is 3–6 grams.

Taking more than 10 grams of arginine at once can result in gastrointestinal distress and diarrhea, but it is possible to maintain elevated arginine levels throughout the day by taking three spaced doses (15–18 grams/day). However, citrulline supplementation is more effective at maintaining elevated arginine levels for long periods of time.

Examine Database: Arginine
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Update History
2023-01-23 00:30:03

Small database additions

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We added new studies to the database and updated some of the clinical effects. No meaningful changes to the take-home concepts of the page.

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References
  1. ^Wu G, Morris SMArginine metabolism: nitric oxide and beyond.Biochem J.(1998-Nov-15)
  2. ^Luiking YC, Ten Have GA, Wolfe RR, Deutz NEArginine de novo and nitric oxide production in disease states.Am J Physiol Endocrinol Metab.(2012-Nov-15)
  3. ^Gambardella J, Khondkar W, Morelli MB, Wang X, Santulli G, Trimarco VArginine and Endothelial Function.Biomedicines.(2020-Aug-06)
  4. ^Shiraseb F, Asbaghi O, Bagheri R, Wong A, Figueroa A, Mirzaei KEffect of l-Arginine Supplementation on Blood Pressure in Adults: A Systematic Review and Dose-Response Meta-analysis of Randomized Clinical Trials.Adv Nutr.(2022-Aug-01)
  5. ^Xu L, Wang X, Wang C, Li W, Liu Hl-arginine supplementation improved neonatal outcomes in pregnancies with hypertensive disorder or intrauterine growth restriction: A systematic review and meta-analysis of randomized controlled trials.Clin Nutr.(2022-Jul)
  6. ^Goto EEffects of prenatal oral L-arginine on birth outcomes: a meta-analysis.Sci Rep.(2021-Nov-23)
  7. ^Dorniak-Wall T, Grivell RM, Dekker GA, Hague W, Dodd JMThe role of L-arginine in the prevention and treatment of pre-eclampsia: a systematic review of randomised trials.J Hum Hypertens.(2014-Apr)
  8. ^Gui S, Jia J, Niu X, Bai Y, Zou H, Deng J, Zhou RArginine supplementation for improving maternal and neonatal outcomes in hypertensive disorder of pregnancy: a systematic review.J Renin Angiotensin Aldosterone Syst.(2014-Mar)
  9. ^Menichini D, Feliciello L, Neri I, Facchinetti FL-Arginine supplementation in pregnancy: a systematic review of maternal and fetal outcomes.J Matern Fetal Neonatal Med.(2023-Dec)
  10. ^Hadi A, Arab A, Moradi S, Pantovic A, Clark CCT, Ghaedi EThe effect of l-arginine supplementation on lipid profile: a systematic review and meta-analysis of randomised controlled trials.Br J Nutr.(2019-Nov-14)
  11. ^Sepandi M, Abbaszadeh S, Qobady S, Taghdir MEffect of L-Arginine supplementation on lipid profiles and inflammatory markers: A systematic review and meta-analysis of randomized controlled trials.Pharmacol Res.(2019-Oct)
  12. ^Hye Chang Rhim, Min Seo Kim, Young-Jin Park, Woo Suk Choi, Hyoung Keun Park, Hyeong Gon Kim, Aram Kim, Sung Hyun PaickThe Potential Role of Arginine Supplements on Erectile Dysfunction: A Systemic Review and Meta-AnalysisJ Sex Med.(2019 Feb)
  13. ^Xu Z, Liu C, Liu S, Zhou ZComparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials.Andrologia.(2021-May)
  14. ^Rezaei S, Gholamalizadeh M, Tabrizi R, Nowrouzi-Sohrabi P, Rastgoo S, Doaei SThe effect of L-arginine supplementation on maximal oxygen uptake: A systematic review and meta-analysis.Physiol Rep.(2021-Feb)
  15. ^Aitor Viribay, José Burgos, Julen Fernández-Landa, Jesús Seco-Calvo, Juan Mielgo-AyusoEffects of Arginine Supplementation on Athletic Performance Based on Energy Metabolism: A Systematic Review and Meta-AnalysisNutrients.(2020 May 2)
  16. ^Zhenlong Wu, Yongqing Hou, Shengdi Hu, Fuller W Bazer, Cynthia J Meininger, Catherine J McNeal, Guoyao WuCatabolism and safety of supplemental L-arginine in animalsAmino Acids.(2016 Jul)
  17. ^Guoyao Wu, Fuller W Bazer, Timothy A Cudd, Wenjuan S Jobgen, Sung Woo Kim, Arantzatzu Lassala, Peng Li, James H Matis, Cynthia J Meininger, Thomas E SpencerPharmacokinetics and safety of arginine supplementation in animalsJ Nutr.(2007 Jun)
  18. ^Grimble GKAdverse gastrointestinal effects of arginine and related amino acids.J Nutr.(2007-Jun)
  19. ^Andrew Shao, John N HathcockRisk assessment for the amino acids taurine, L-glutamine and L-arginineRegul Toxicol Pharmacol.(2008 Apr)
  20. ^Cynober L, Bier DM, Kadowaki M, Morris SM, Elango R, Smriga MProposals for Upper Limits of Safe Intake for Arginine and Tryptophan in Young Adults and an Upper Limit of Safe Intake for Leucine in the Elderly.J Nutr.(2016-Dec)
  21. ^Böger RH, Bode-Böger SMThe clinical pharmacology of L-arginine.Annu Rev Pharmacol Toxicol.(2001)
  22. ^J S Stamler, G MeissnerPhysiology of nitric oxide in skeletal musclePhysiol Rev.(2001 Jan)
  23. ^Tschakovsky ME, Joyner MJNitric oxide and muscle blood flow in exercise.Appl Physiol Nutr Metab.(2008-Feb)
  24. ^Kumar R, Coggan AR, Ferreira LFNitric oxide and skeletal muscle contractile function.Nitric Oxide.(2022-May-01)
  25. ^Mutch BJ, Banister EWAmmonia metabolism in exercise and fatigue: a reviewMed Sci Sports Exerc.(1983)
  26. ^Graham TE, MacLean DAAmmonia and amino acid metabolism in human skeletal muscle during exercise.Can J Physiol Pharmacol.(1992-Jan)
  27. ^Wilkinson DJ, Smeeton NJ, Watt PWAmmonia metabolism, the brain and fatigue; revisiting the link.Prog Neurobiol.(2010-Jul)
Examine Database References
  1. Blood glucose - Monti LD, Setola E, Lucotti PC, Marrocco-Trischitta MM, Comola M, Galluccio E, Poggi A, Mammì S, Catapano AL, Comi G, Chiesa R, Bosi E, Piatti PMEffect of a long-term oral l-arginine supplementation on glucose metabolism: a randomized, double-blind, placebo-controlled trialDiabetes Obes Metab.(2012 Oct)
  2. Nitric Oxide - 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)
  3. General Oxidation - 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)
  4. Insulin - Isidori A, Lo Monaco A, Cappa MA study of growth hormone release in man after oral administration of amino acidsCurr Med Res Opin.(1981)
  5. Growth Hormone - Collier SR, Casey DP, Kanaley JAGrowth hormone responses to varying doses of oral arginineGrowth Horm IGF Res.(2005 Apr)
  6. Nitric Oxide - 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)
  7. Plasma Arginine - Wilson AM, Harada R, Nair N, Balasubramanian N, Cooke JPL-arginine supplementation in peripheral arterial disease: no benefit and possible harmCirculation.(2007 Jul 10)
  8. Nitric Oxide - 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)
  9. Nitric Oxide - 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)
  10. Endothelial Function - Fahs CA, Heffernan KS, Fernhall BHemodynamic and vascular response to resistance exercise with L-arginineMed Sci Sports Exerc.(2009 Apr)
  11. Plasma Arginine - Bode-Böger SM, Böger RH, Galland A, Tsikas D, Frölich JCL-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationshipBr J Clin Pharmacol.(1998 Nov)
  12. Nitric Oxide - 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.()
  13. Growth Hormone - Marcell TJ, Taaffe DR, Hawkins SA, Tarpenning KM, Pyka G, Kohlmeier L, Wiswell RA, Marcus ROral arginine does not stimulate basal or augment exercise-induced GH secretion in either young or old adultsJ Gerontol A Biol Sci Med Sci.(1999 Aug)
  14. Heart Rate - Wax B, Kavazis AN, Webb HE, Brown SPAcute L-arginine alpha ketoglutarate supplementation fails to improve muscular performance in resistance trained and untrained menJ Int Soc Sports Nutr.(2012 Apr 17)
  15. Blood Flow - 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)
  16. Growth Hormone - Abel T, Knechtle B, Perret C, Eser P, von Arx P, Knecht HInfluence of chronic supplementation of arginine aspartate in endurance athletes on performance and substrate metabolism - a randomized, double-blind, placebo-controlled studyInt J Sports Med.(2005 Jun)