L-ARGININE

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This monograph is intended to serve as a guide to industry for the preparation of Product Licence Applications (PLAs) and labels for natural health product market authorization. It is not intended to be a comprehensive review of the medicinal ingredient.

Notes

Date

March 28, 2024

Proper name(s), Common name(s), Source Information

Table 1. Proper name(s), Common name(s), Source Information
Proper name(s) Common name(s) Source Information
Source material(s) Preparation(s)
  • (S)-2-Amino-5-[(aminoiminomethyl) amino] pentanoic acid
  • L-Arginine
 L-Arginine
  • DL-Arginine
  • L-Arginine
  • L-Arginine alpha-ketoglutarate
  • L-Arginine ketoisocaproic acid
  • L-Arginine monohydrochloride
 Synthetic

References: Proper names: NIH 2023, RSC 2023; Common name: NIH 2023, RSC 2023; Source information: NIH 2023, BP 2009, USP 32 2009, Ph. Eur. 2007.

Route of Administration

Oral

Dosage Form(s)

This monograph excludes foods or food-like dosage forms as indicated in the Compendium of Monographs Guidance Document.

Acceptable dosage forms for oral use are indicated in the dosage form drop-down list of the web-based Product Licence Application form for Compendial applications.

Use(s) or Purpose(s)

  • May help support a modest improvement in exercise capacity in individuals with stable cardiovascular diseases (CVD) (Doutreleau et al. 2010; Doutreleau et al. 2006; Lim et al. 2004; Palloshi et al. 2004; Bode- Böger et al. 2003; Lekakis et al. 2002; Sydow et al. 2002; Nagaya et al. 2001; Bednarz et al. 2000; Hambrecht et al. 2000; Tangphao et al. 1999; Lerman et al. 1998; Clarkson et al. 1996; Rector et al. 1996).
  • L-Arginine is (a non-essential amino acid) involved in protein synthesis (Shils et al. 2006; IOM 2005; Groff and Gropper 2000).

Dose(s)

Subpopulation(s)

Adults 18 years and older

Quantity(ies)

Improvement in exercise capacity in individuals with stable CVD

6 - 21 grams of L-Arginine, per day; Not to exceed 8 grams per single dose (Doutreleau et al. 2010; Shao and Hathcock 2008; Doutreleau et al. 2006; Evans et al. 2004: Lim et al. 2004; Palloshi et al. 2004; Bode-Bogër et al. 2003; Bednarz et al. 2000; Hambrecht et al. 2000; Lerman et al. 1998; Adams et al. 1997; Ceremuzynski et al. 1997; Clarkson et al. 1996; Rector et al. 1996).

Protein synthesis

0.21 - 21 grams of L-Arginine, per day; Not to exceed 8 grams per single dose (Shao and Hathcock 2008; IOM 2005; Evans et al. 2004; Bode-Bogër et al. 2003; Sydow et al. 2002).

Direction(s) for use

No statement required.

Duration(s) of Use

Products providing 3 g to 9 g of L-Arginine, per day

Ask a health care practitioner/health care provider/health care professional/doctor/physician for use beyond 6 weeks if you have a cardiovascular disease (Salmani et al. 2021; Shao and Hathcock 2008; Sydow et al. 2002; Hambrecht et al. 2000; Clarkson et al.1996; Rector et al. 1996).

Products providing more than 9 g and up to 14 g of L-Arginine, per day

Ask a health care practitioner/health care provider/health care professional/doctor/physician for use beyond 6 months for healthy individuals (Alexander et al. 2005; De Nicola et al. 1999).

Products providing more than 14 g of L-Arginine, per day

Ask a health care practitioner/health care provider/health care professional/doctor/physician for use beyond 12 weeks for healthy individuals (Tangphao et al. 1999).

Risk Information

Caution(s) and warning(s)

All products

Ask a health care practitioner/health care provider/health care professional/doctor/physician before use if you are pregnant or breastfeeding.

Improvement in exercise capacity in individuals with stable CVD

Ask a health care practitioner/health care provider/health care professional/doctor/physician if your symptoms worsen.

Products providing more than 0.42 g of L-Arginine, per day

  • Ask a health care practitioner/health care provider/health care professional/doctor/physician before use if you have a cardiovascular disease and are attempting an increase in physical activity (Doutreleau et al. 2010; Doutreleau et al. 2006; Schulman et al. 2006; Goldman and Ausiello 2004; Nagaya et al. 2001; Bednarz et al. 2000; Ceremużyński et al. 1997; Rector et al. 1996).
  • Ask a health care practitioner/health care provider/health care professional/doctor/physician before use if you are taking medication for cardiovascular diseases, erectile dysfunction, and/or blood thinners (Huynh et al. 2002; Parker et al. 2002; Siani et al. 2000; Adams et al. 1995).

Contraindication(s)

Products providing more than 9 g of L-Arginine, per day

Do not use if you have had a heart attack/myocardial infarction (Sun et al. 2009; Schulman et al. 2006; Bednarz et al. 2005).

Known adverse reaction(s)

Products providing more than 9 g of L-Arginine, per day

When using this product you may experience gastrointestinal discomfort/disturbances (Grimble 2007; Evans et al. 2004; IOM 2005; Clarkson et al. 1996).

Non-medicinal ingredients

Must be chosen from the current Natural Health Products Ingredients Database (NHPID) and must meet the limitations outlined in the database.

Storage conditions

Must be established in accordance with the requirements described in the Natural Health Products Regulations.

Specifications

  • The finished product specifications must be established in accordance with the requirements described in the Natural and Non-prescription Health Products Directorate (NNHPD) Quality of Natural Health Products Guide.
  • The medicinal ingredient must comply with the requirements outlined in the NHPID.

EXAMPLE OF PRODUCT FACTS:

Consult the Guidance Document, Labelling of Natural Health Products for more details.

Product Facts Table

References Cited

  • Adams MR, McCredie R, Jessup W, Robinson J, Sullivan D, Celermajer DS. 1997. Oral L-arginine improves endothelium-dependent dilatation and reduces monocyte adhesion to the endothelial cells in young men with coronary artery disease. Atherosclerosis 129(2):261-269.
  • Adams MR, Forsyth CJ, Jessup W, Robinson J, Celermajer DS. 1995. Oral L-arginine inhibits platelet aggregation but does not enhance endothelium-dependent dilation in healthy young men. Journal of the American College of Cardiology 26(4):1054-1061.
  • Alexander JW, Metze TJ, McIntosh MJ, Goodman HR, First MR, Munda R, Cardi MA, Austin JN, Goel S, Safdar S, Greenberg N, Chen X, Woodle ES. 2005. The influence of immunomodulatory diets on transplant success and complications. Transplantation 79:460-465. 
  • Bednarz B, Jaxa-Chamiec T, Maciejewski P, Szpajer M, Janik K, Gniot J, Kawka-Urbanek T, Drozdowska D, Gessek J, Laskowski H. 2005. Efficacy and safety of oral l-arginine in acute myocardial infarction. Results of the multicenter, randomized, double-blind, placebo-controlled ARAMI pilot trial. Kardiol Pol. 62(5):421-7.
  • Bednarz B, Wolk R, Chamiec T, Herbaczynska-Cedro K, Winek D, Ceremuzynski L. 2000. Effects of oral L-arginine supplementation on exercise-induced QT dispersion and exercise tolerance in stable angina pectoris. International Journal of Cardiology 75(2-3):205-210.
  • Bode-Böger SM, Muke J, Surdacki A, Brobant G, Böger RH, Frölich J. 2003. Oral L-arginine improves endothelial function in healthy individuals older than 70 years. Vascular Medicine 8(2):77-81.
  • BP 2009: British Pharmacopoeia Commission. 2008. British Pharmacopoeia 2009, Volume II. London (GB): The Stationary Office on behalf of the Medicines and Healthcare products Regulatory Agency (MHRA).
  • Ceremuzynski L, Chamiec T, Herbaczynska-Cedro K. 1997. Effect of supplemental oral L-arginine on exercise capacity in patients with stable angina pectoris. The American Journal of Cardiology 80(3):331-333.
  • Clarkson P, Adams MR, Powe AJ, Donald AE, McCredie R, Robinson J, McCarthy SN, Keech A, Celermajer DS, Deanfield JE. 1996. Oral L-arginine endothelium-dependent dilation in hypercholesterolemic young adults. Journal of Clinical Investigation 97(8):1989-1994.
  • De Nicola L, Bellizzi V, Minutolo R, Andreucci M, Capuano A, Garibotto G, Corso G, Andreucci VE, Cianciaruso B. 1999. Randomized, double-blind, placebo-controlled study of arginine supplementation in chronic renal failure. Kidney International 56:674-684.
  • Doutreleau S, Rouyer O, Di Marco P, Lonsdorfer E, Richard R, Piquard F, Geny B. 2010. L-Arginine supplementation improves exercise capacity after a heart transplant. American Journal of Clinical Nutrition. Doi: 10.3945/ajcn.2009.27881.
  • Doutreleau S, Mettauer B, Piquard F, Rouyer O, Schaefer A, Lonsdorfer J., Beny B. 2006. Chronic L-Arginine Supplementation Enhances Endurance Exercise Tolerance in Heart Failure Patients. International Journal of Sports Medicine 27(7):567-572.
  • Evans WR, Fernstrom JD, Thompson J, Morris SM Jr, Kuller LH. 2004. Biochemical responses of healthy subjects during dietary supplementation with L-arginine. Journal of Nutritional Biochemistry 15(9):534-539.
  • Grimble GK. 2007. Adverse gastrointestinal effects of arginine and related amino acids. The Journal of Nutrition 137(6 Suppl 2):1693S-1701S.
  • Groff J, Gropper S. 2000. Advanced Nutrition and Human Metabolism, 3rd edition. Belmont (CA): Wadsworth/Thomson Learning. 
  • Hambrecht R, Hilbrich L, Erbs S, Gielen S, Fiehn E, Schoene N, Schuler. 2000. Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation. Journal of the American College of Cardiology 35(3):706-713.
  • Huynh NT, Tayek JA. 2002. Oral arginine reduces systemic blood pressure in type 2 diabetes: Its potential role in nitric oxide generation. American College of Nutrition 21(5):422-427.
  • IOM 2006: Otten JJ, Pitzi Hellwig J, Meyers LD, editors. 2006. Institute of Medicine Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington (DC): National Academies Press.
  • IOM 2005: Institute of Medicine. Panel on Dietary Reference Intakes for Electrolytes and Water, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. 2005. Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate. Washington (DC): National Academies Press.
  • Lekakis JP, Papathanassiou S, Papaioannou TG, Papamichael CM, Zakopoulos N, Kotsis V, Dagre AG, Stamatelopoulos K, Protogerou A, Stamatelopoulos SF. 2002. Oral L-arginine improves endothelial dysfunction in patients with essential hypertension. International Journal of Cardiology 86(2-3):317-323.
  • Lerman A, Burnett JC, Higano ST, McKinley LJ, Holmes Jr DR. 1998. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation 97(21):2123-2128.
  • Lim SD, Mooradian SJ, Goldberg CS, Gomez C, Crowley DC, Rocchini AP, Charpie JR. 2004. Effect of oral L-arginine on oxidant stress, endothelial dysfunction, and systemic arterial pressure in young cardiac transplant recipients. The American Journal of Cardiology 94(6):828-831.
  • Nagaya N, Uematsu M, Oya H, Sato N, Sakamaki F, Kyotani S, Ueno K, Nakanishi N, Yamagishi M, Miyatake K. 2001. Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension. American Journal of Respiratory and Critical Care Medicine 163(4):887-891.
  • NIH 2023: National Institutes of Health. PubChem. Bethesda (MD): National Library of Medicine, US Department of Health & Human Services. [Accessed 2023 October 23]. Available from: https://pubchem.ncbi.nlm.nih.gov/
  • Palloshi A, Fragasso G, Piatti P, Monti LD, Setola E, Valsecchi G, Galluccio E, Chierchia SL, Morgonato A. 2004. Effect of oral L-arginine on blood pressure and symptoms and endothelial function in patients with systemic hypertension, positive exercise tests, and normal coronary arteries. The American Journal of Cardiology 93(7):933-935.
  • Parker JO, Parker JD, Caldwell RW, Farrell B, Kaesemeyer WH. 2002. The effect of supplemental L-arginine on tolerance development during continuous transdermal nitroglycerin therapy. Journal of the American College of Cardiology 39(7):1199-1203.
  • Ph. Eur. 2007: European Pharmacopoeia Commission. 2007. European Pharmacopoeia, 6th edition, Volume 1. Strasbourg (FR): Directorate for the Quality of Medicines and HealthCare of the Council of Europe (EDQM).
  • Rector TS, Bank AJ, Mullen KA, Tschumperlin LK, Sih R, Pillai K, Kubo SH. 1996. Randomized, double-blind, placebo-controlled study of supplemental oral –arginine in patients with heart failure. Circulation 93(12):2135-2141.
  • RSC 2023: Royal Society of Chemistry: The Merck Index Online [Accessed 2023 August 14]. Available from: https://merckindex.rsc.org/
  • Salmani M, Alipoor E, Navid H, Farahbakhsh P, Yaseri M, Imani H. 2021. Effect of l-arginine on cardiac reverse remodeling and quality of life in patients with heart failure. Clin Nutr. 40(5):3037-3044.
  • Schulman SP, Becker LC, Kass DA, Champion HC, Terrin ML, Forman S, Ernst KV, Kelemen MD, Townsend SN, Capriotti A, Hare JM, Gerstenblith G. 2006. L-Arginine therapy in acute myocardial infarction: the vascular interaction with age in myocardial infarction (VINTAGE MI) randomised clinical trial. Journal of American Medical Association 295(1):58-64.
  • Shao A, Hathcock JN. 2008. Risk assessment for the amino acids taurine, L-glutamine and Larginine. Regulatory Toxicology and Pharmacology 50:376-399.
  • Shils ME, Olson JA, Shike M, Ross AC, editors. Modern Nutrition in Health and Disease, 10th edition. Philadelphia (PA): Lippincott Williams and Wilkins; 2006.
  • Siani A, Pagano E, Iacone R, Iacoviello L, Scopacasa F, Strazzullo P. 2000. Blood pressure and metabolic changes during dietary L-arginine supplementation in humans. American Journal of Hypertension 13(5):547-551.
  • Sun T, Zhou WB, Luo XP, Tang YL, Shi HM. 2009. Oral L-arginine supplementation in acute myocardial infarction therapy: a meta-analysis of randomized controlled trials. Clin Cardiol. 32(11):649-52.
  • Sydow K, Schwedhelm E, Arakawa N, Bode-Böger SM, Tsikas D, Hornig B, Frölich, Böger RH. ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst(e)inemia: effects of L-arginine and B vitamins. Cardiovascular Research 57(1):244-252.
  • Tangphao O, Chalon S, Moreno HJr, Hoffman BB, Blaschke TF. Pharmacokinetics of L-arginine during chronic administration to patients with hypercholesterolaemia. Clinical Science 96:199-207.
  • USP-NF 2023: United States Pharmacopeial Convention. 2009. United States Pharmacopeia and the National Formulary. Rockville (MD): United States Pharmacopeial Convention, Inc.; 2023.

References Reviewed

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  • Andrés A, Morales JM, Prega M, Campo C, Lahera V, García-Robles R, Rodicio JL, Ruilope LM. 1997. L-arginine reverses the antinatriuretic effect of cyclosporine in renal transplant patients. Nephrology Dialysis Transplantation 12(7):1437-1440.
  • Becker Y, Olshevsky U, Levitt J. 1967. The role of arginine in the replication of Herpes simplex virus. The Journal of General Virology 1(4):471-478.
  • Bednarz B, Jaxa-Chamiec T, Gebalska J, Herbaczynska-Cedro K, Ceremuzynski L. 2004. L-
  • Arginine supplementation prolongs duration of exercise in congestive heart failure. Kardiologia Polska 60(4):348-353.
  • Bednarz B, Jaxa-Chamiec T, Maciejewski P, Szpajer M, Janik K, Gniot J, Kawka-Urbanek T, Drozdowska D, Gessek J, Laskowski H. 2005. Efficacy and safety of oral L-arginine in acute myocardial infarction. Results of multicenter, randomised, double-blind, placebo-controlled ARAMI pilot trial. Kardiologia Polska 62(5):421-427.
  • Blum A, Cannon III RO, Costello R, Schenke WH, Csako G. 2000. Endocrine and lipid effects of oral L-arginine treatment in healthy postmenopausal women. The Journal of Laboratory and Clinical Medicine 135(3):231-237.
  • Blum A, Hathaway L, Mincemoyer RN, Schenke WH Kirby M, Csako G, Waclawiw MA, Panza JA, Cannon III RO. 1999. Oral L-arginine in patients with coronary artery disease on medical management. Circulation 101(18):2160-2464. 
  • Blum A, Porat R, Rosenchein Uri, Keren G, Roth A, Laniado S, Miller H. 1999. Clinical and inflammatory effects of dietary L-arginine in patients with intractable angina pectoris. American Journal of Cardiology 83(10):1488-1490.
  • Cannon RA III. 2002. Oral L-arginine (and other active ingredients) for ischemic heart disease? Journal of the American College of Cardiology 39(1):46-48.
  • Carrier M, Pellerin M, Pagé PL, Searle NR, Martineau R, Caron C, Solymoss C, Pelletier LC. 1998. Can L-arginine improve myocardial protection during cardioplegic arrest? Results of phase I pilot study. The Annals of Thoracic Surgery 66(1):108-112.
  • Carrier M, Pellerin M, Perrault LP, Bouchard D, Pagé P, Searle N, Lavoie J. 2002. Cardioplegic arrest with L-arginine improves myocardial protection: results of a prospective randomized clinical trial. The Annals of Thoracic Surgery 73(3):837-842.
  • Cartledge JJ, Davies AM, Eardley I. 2000. A randomized double-blind placebo-controlled crossover trial of the efficacy of L-arginine in the treatment of interstitial cystitis. BJU International 85(4):421-426.
  • Chen J, Wollman Y, Chernichovsky T, Iaina A, Sofer M, Matzkin H. 1999. Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double-blind, randomized, placebo-controlled study. BJU International 83(3):269-273.
  • Coman D, Yaplito-Lee J, Boneh A. 2008. New indications and controversies in arginine therapy. 27(4):489-496.
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  • Dinh H, Nathan L. 2002. Medroxyprogesterone acetate does not antagonize estrogen-induced increases in endothelium-dependent vasodilation: potential clinical implications. American Society for Reproductive Medicine 78(1):122-127.
  • Facchinetti F, Saade GR, Neri I, Pizzi C, Longo M, Volpe A. 2007. L-Arginine supplementation in patients with gestational hypertension: a pilot study. Hypertension in Pregnancy 26(1):121-130.
  • Fahs CA, Heffernan KS, Fernhall B. 2009. Hemodynamic and vascular response to resistance exercise with L-arginine. Medicine and Science in Sports and Exercise 41(4):773-779.
  • Faldetta MC, Laurenti O, Desideri G, Bravi MC, De Luca O, Marinucci MC, De Mattai G, Ferri C. 2002. L-Arginine infusion decreases plasma total homocysteine concentrations through increased nitric oxide production and decreased oxidative status in type II diabetic patients. Diabetologia 45(8):1120-1127. 
  • Fricke O, Baecker N, Heer M, Tutlewski B, Schoenau E. 2008. The effect of L-arginine administration on muscle force and power in postmenopausal women. Clinical Physiology and Functional Imaging 28(5):307-311.
  • Garhöfer G, Resh H, Lung S, Weigert G, Schmetterer L. 2005. Intravenous administration of Larginine increases retinal and choroidal blood flow. American Journal of Ophthalmology 140(1):69-76.
  • Gornik HL, Creaher MA. 2004. Arginine and endothelial and vascular health. Journal of Nutrition 134(10 Suppl):2880S-2887S.
  • Griffith RS, DeLong DC, Nelson JD. 1981. Relation of arginine-lysine antagonism to herpes simplex growth in tissue culture. Chemotherapy 27(3):209-213.
  • Inglis VBM. 1968. Requirement of arginine for the replication of herpes virus. The Journal of General Virology 3(1):9-17.
  • Jahangir E, Handy D, Palmisano J, Loscalzo J. 2009. The effect of L-arginine and creatine on vascular function and homocysteine metabolism. Vascular Medicine 14(3): 239-248.
  • Kiziltepe U, Tunçtan B, Eyileten ZB, Sirlak M, Arikbuku M, Tasoz R, Uysalel A, Ozyurda U. 2004. Efficiency of L-arginine enriched cardioplegia and non-cardioplegic reperfusion in ischemic hearts. International Journal of Cardiology 97(1):93-100.
  • Klotz T, Mathers MJ, Braun M, Bloch W, Engelmann U. 1999. Effectiveness of Oral L-Arginine in First-Line Treatment of Erectile Dysfunction in a Controlled Crossover Study. Urologia Internationalis 63(4):220-223. 
  • Lauer T, Kleinbongart P, Rath J, Schultz R, Kelm M, Rassaf T. 2008. L-Arginine preferentially dilates stenotic segments of coronary arteries thereby increasing coronary flow. Journal of Internal Medicine 264(3):237-244.
  • Lebret T, Hervé JM, Gorny P, Worcel M, Botto H. 2002. Efficacy and safety of a novel combination of L-arginine glutamate and yohimbine hydrochloride: a new oral therapy for erectile dysfunction. European Urology 41(6):608-613.
  • Lee J, Ryu H, Farrante RJ, Morris SM Jr, Ratan RR. 2003. Translational control of inducible nitric oxide synthase expression by arginine can explain the arginine paradox. Neuroscience 100(8):4843-4848.
  • Loï C, Zazzo JF, Delpierre E, Niddam C, Neveux N, Curis E, Arnaud-Bettandier F, Cynober L. 2009. Increasing plasma glutamine in postoperative patients fed an arginine-rich immune-enhancing diet-A pharmacokinetic randomized controlled study. Critical Care Medicine 37(2):501-509.
  • Loscalzo J. 2000. What we know and don’t know about L-arginine and NO. Circulation 101(18):2126-2129.
  • Loscalzo J. 2003. Adverse effects of supplemental L-arginine in atherosclerosis: Consequences of methylation stress in a complex catabolism? Arteriosclerosis & thrombosis and Vascular Biology 23(1):3-5.
  • Lucotti P, Setola E, Monti LD, Galluccio E, Costa S, Sandoli EP, Fermo I, Rabaiotti G, Gatti R, Piatti PM. 2006. Beneficial effects of long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients. American Journal of Physiology, Endocrinology and Metabolism 291(5):906-912.
  • Marchesi S, Lupattelli G, Siepi D, Roscini AR, Vaudo G, Sinzinger H, Monnarino E. 2001. Oral L-arginine administration attenuates postprandial endothelial dysfunction in young healthy males. Journal of Clinical Pharmacy and Therapeutics 26(5):343-349. 
  • Mariotti F, Huneau JF, Szczepanski I, Petzke KJ, Aggoun Y, Tomé D, Bonnet D. 2007. Meal amino acids with varied levels of arginine do not affect postprandial vascular endothelial function in healthy young men. The Journal of Nutrition 137(6):1383-1389.
  • Martina V, Masha A, Gigliardi RV, Brocato L, Manzato E, Berchio A, Massarenti P, Settanni F, Casa LD, Bergamini S, Iannone A. 2008. Long-term N-acetylcysteine and L-arginine administration reduces endothelial activation and systolic blood pressure in hypertensive patients with type 2 diabetes. Diabetes Care 31(5):940-944. 
  • Maxwell AJ, Zapien MP, Pearce GL, MacCallum G, Stone PH. 2002. Randomized trial of a medical food for the dietary management of chronic stable angina. Journal of American College of Cardiology 39(1):37-45. 
  • Mikami T, Onuma M, Hayashi TTA. 1974. Requirement of arginine for the replication of Marek’s Disease herpes virus. The Journal of General Virology 22(1):115-128.
  • Morris CR, Kuypers FA, Larkin S, Sweeters N, Simon J, Vichinsky EP, Styles LA. 2000.
  • Arginine therapy: a novel strategy to induce nitric oxide production in sickle cell disease. British Journal of Haematology 111(2):498-500.
  • Morris CR, Morris SM, Hagar W, van Warmerdam J, Claster SKepka-Lenhart D, Machado L, Kuypers FA, Vichinsky EP. 2003. Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? American Journal of Respiratory and Critical Care Medicine 168(1):63-69.
  • Naito T, Irei H, Tsujimoto K, Ikeda K, Arakawa T, Koyama AH. 2009. Antiviral effect of arginine against herpes simplex virus type 1. International Journal of Molecular Medicine 23(4):495-499.
  • Napoli C, Farzati B, Sica V, Iannuzzi E, Coppola G, Silvestroni A, Balestrieri ML, Florio A, Matarazzo A. 2008. Beneficial effects of autologous bone marrow cell infusion and antioxidants/L-arginine in patients with chronic critical limb ischemia. European Journal of Cardiovascular Prevention and Rehabilitation 15(6):709-718.
  • Oka RK, Szuba A, Giacomini JC, Cooke JP. 2005. A pilot study of L-arginine supplementation on functional capacity in peripheral arterial disease. Vascular Medicine 10:265-274.
  • Oomen CM, van Erk J, Feskens EJM, Kok FJ, Kromhout D. 2007. Arginine intake and risk of coronary heart disease mortality in elderly men. Arteriosclerosis, Thrombosis and Vascular Biology 20(9):2134-2139.
  • Palloshi A, Fragasso G, Piatti P, Monti LD, Setola E, Valsecchi G, Galluccio E, Chierchia SL, Morgonato A. 2004. Effect of oral L-arginine on blood pressure and symptoms and endothelial function in patients with systemic hypertension, positive exercise tests, and normal coronary arteries. The American Journal of Cardiology 93(7):933-935.
  • Parnell MM, Holst DP, Kaye DM. 2005. Augmentation of endothelial function following exercise training is associated with increased L-arginine transport in human heart failure. Clinical Science 109(6):523-530.
  • Perusquía M, Villalón, Navarrete E, García GA, Pérez-Palacios G, Lemus AE. 2003.
  • Vasodilating effect of norethisterone and its 5α metabolites: a novel nongenomic action. European Journal of Pharmacology 475(1-3):161-169.
  • Peters N, Freilinger T, Opherk C, Pfefferkorn T, Dichgans M. 2008. Enhanced L-arginine-induced vasoreactivity suggests endothelial dysfunction in CADASIL. Journal of Neurology 255(8):1203-1208.
  • Polan ML, Hochberg RB, Trant AS, Wuh HCK. 2004. Estrogen bioassay of ginseng extract and
  • Arginmax, a nutritional supplement for the enhancement of female sexual function. Journal of Women’s Health 13(4):427-430.
  • Preli RB, Potvin Klein K, Herrington DM. 2002. Vascular effects of dietary L-arginine supplementation. Atherosclerosis 162(1):1-15.
  • Pretnar-Oblak J, Sabovic M, Zaletel M. 2007. Associations between systemic and cerebral endothelial impairment determined by cerebrovascular reactivity to L-arginine. Endothelium 14(2):73-80.
  • Rajapakse NW, Mattson DL. 2009. Role of L-arginine in nitric oxide production in health and hypertension. Clinical and Experimental Pharmacology and Physiology 36(3):249-255.
  • Ruel M, Beanlands RS, Lortie M, Chan V, Camack N, deKemp RA, Suuronen EJ, Rubens FD, DeSilva JN, Sellke FW, Steward DJ, Mesana TG. 2008. Concomitant treatment with oral L-arginine improves the efficacy of surgical angiogenesis in patients with severe diffuse coronary artery disease: The Endothelial Modulation in Angiogenic Therapy randomized clinical trial. The Journal of Thoracic and Cardiovascular Surgery 135(4):762-770.
  • Rytlewski K, Olszanecki R, Lauterbach R, Grzyb A, Basta A. 2006. Effects of oral L-arginine on the foetal condition and neonatal outcome in preeclampsia: A preliminary study. Basic & Clinical Pharmacology & Toxicology 99(2):146-152.
  • Rytlewski K, Olszanecki R, Lauterbach R, Grzyb A, Kiec-Wilk B, Dembinska-Kiec, Basta A. 2008. Effects of oral L-arginine on the pulsatility indices of umbilical artery and middle cerebral artery in preterm labor. European Journal of Obstetrics & Gynecology and Reproductive Biology 138(1):23-28.
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