InteractionsGuide Index Page

Case Analysis Toolclose
Enter Each Substance:

Analysis Search Terms:


Nutrient Name: Arginine.

Summary Table
nutrient description

Chemistry and Forms

Arginine is a complex amino acid often found at the active (or catalytic) site in proteins and enzymes because of its amine-containing side chain. With four nitrogen atoms per molecule, it is the most abundant nitrogen carrier in humans and animals.

Physiology and Function

Arginine's primary function is generally considered to be the transport, storage, detoxification, and excretion of nitrogen, in particular, and metabolism of protein, in general, through the urea cycle. Arginine is also the substrate for nitric oxide synthase and arginase, two important metabolic pathways. Nitric oxide (NO), a key vasodilator, neurotransmitter, and cell-signaling molecule, is formed by the three different nitric oxide synthases from the N-guanido terminal of the amino acidL-arginine and from molecular oxygen. Nitric oxide synthase (NOS) also converts arginine to citrulline. Arginase converts arginine to ornithine and urea. Arginase I and arginase II control the transformation of arginine into ornithine, which subsequently forms proline and polyamines, which exert multiple effects on connective tissue, smooth muscle, and mucus synthesis. The NOS and arginase pathways interfere with each other through substrate competition.

As the precursor to NO, arginine plays a key role in the circulatory and respiratory systems, particularly endothelial function, vasodilation, and airway physiology. Arginine also functions as a key immunomodulator, particularly increasing the number of T cells, enhancing T cell function, and supporting tissue regeneration. Recent studies have reported increases in arginase in conditions including reperfusion injury, asthma, psoriasis, arthritis, and human breast cancer. Helper T cell type 2 (Th2) cytokines induce arginase expression. During allergic inflammation, increased interleukin-4 (IL-4) and/or IL-13 expression results in increased expression of arginase and amplification of the arginase-dependent pathway, with concomitant suppression of NO generation. Furthermore, in relation to neuroendocrine function, arginine strongly influences adrenal and pituitary functions, especially through stimulation of catecholamines, norepinephrine, insulin and glucagon, prolactin, and growth hormone (GH). Lastly, arginine is involved in synthesis of spermine and spermidine, polyamines required for cell division and growth, and numerous aspects of reproductive function. Hepatic metabolism of arginine produces hydrogen ions (H+).

Arginine is generally considered a conditionally essential amino acid because adult humans can generally synthesize it de novo from ornithine, glutamine, glutamate, and proline. However, arginine must be obtained through the diet during the juvenile period in humans and in those not synthesizing adequate amounts to meet metabolic demands, especially after acute trauma, burns, or surgery and during infections, chronic illness, or wound healing. In all situations, dietary intake remains the primary determinant of plasma arginine levels, since the rate of arginine biosynthesis does not increase to compensate for depletion or inadequate supply.

nutrient in clinical practice

Known or Potential Therapeutic Uses

Arginine's central role in promoting NO formation forms the basis of its therapeutic effect in the treatment of cardiovascular disease, asthma, interstitial cystitis, female sexual dysfunction, and male erectile dysfunction. In particular, a growing body of research has focused on arginine's ability to induce vasodilation and improve endothelial function through its role as a substrate for NO synthesis. Arginine hydrochloride has been used clinically in correcting severe metabolic alkalosis because of its high chloride content. Findings from preliminary double-blind trials indicate the efficacy of arginine in the treatment of acquired immunodeficiency syndrome (AIDS) cachexia, angina, congestive heart failure (CHF), endothelial function in type 1 diabetes, erectile dysfunction, hypertension, and other conditions. Arginine has also been used therapeutically to enhance several aspects of healthy function, including supporting wound healing and resistance to infection; elevating production of GH and related hormones; increasing exercise tolerance, lean muscle mass, and total strength; improving sperm motility and sexual vitality; and reducing low-density lipoprotein (LDL) cholesterol.

Historical/Ethnomedicine Precedent

Arginine has not been used historically as an isolated nutrient.

Possible Uses

Angina, athletic performance, burns, chronic renal failure, congestive heart failure, cystic fibrosis, enhancing formation of muscle mass, erectile dysfunction, female infertility (in vitro fertilization), gastritis, hepatic insufficiency, human immunodeficiency virus (HIV) support, hypercholesterolemia, hypertension, inflammatory bowel disease, immunity enhancement, intermittent claudication (intravenous only), interstitial cystitis, male infertility (oligospermia), metabolic alkalosis, peripheral vascular disease, surgery preparation and recovery, trauma, wound healing enhancement.

Deficiency Symptoms

Arginine deficiency is uncommon and is usually related to overall protein malnutrition (especially protein deficiency), compromised health status or elevated physiological stress (e.g., burns, injury, infection), excessive ammonia production, or enzyme deficiency. Primary symptoms include rash, hair loss, poor wound healing, constipation, fatty liver, and cirrhosis.

Dietary Sources

The best dietary sources of arginine are meat (especially lamb), peanuts, soybeans, hazelnuts, shrimp, eggs, and milk products. Other foods containing significant mounts of arginine include: almonds, cashews, Brazil nuts, filberts, pecans, sesame and sunflower seeds, walnuts, raisins, coconut, gelatin, chicken, chocolate, brown rice, barley, buckwheat, corn, and oats.

Lysine competes with arginine for absorption, so a diet low in lysine may enhance the effects of arginine intake.

Dosage Forms Available

Capsules, powder, or tablets, containing a salt ofL-arginine, such asL-arginine hydrochloride, or arginine glutamate; the free base amino acid is also sometimes used, although it is more problematic to use in a capsule or tablet because it is very hygroscopic.

  • Well absorbed orally, with time to peak serum concentration approximately 2 hours.
  • Best taken away from meals, in divided doses, throughout day.
  • Intravenously administered for pituitary function test.

Dosage Range


  • Dietary:   Optimal levels of intake have not been established.
  • Supplemental/Maintenance:   1.5 to 6.0 grams per day, usually 2 to 3 g/day; best in divided doses because absorption of doses greater than 3 g is usually poor. Arginine can be synthesized endogenously, and supplementation is usually not necessary for most individuals.
  • Pharmacological/Therapeutic:   Researchers and practitioners of nutritional therapeutics have used a wide range of dosages, from 2 to 30 g daily, with 6 g daily being representative for most conditions. For example, 6 to 15 g daily has been used in CHF treatment. Long-term use is usually not advisable.

Pediatric (<18 Years)

  • Dietary:   Optimal levels of intake have not been established.
  • Supplemental/Maintenance:   Usually not administered as a nutritional supplement to children.
  • Pharmacological/Therapeutic:   Usually not administered therapeutically to children, except possibly in relation to burns, injuries, or surgery; in such cases, dosage levels would be proportional to typical adult doses by weight.

Laboratory Values

Research laboratory methods for measuring NOS activity are available, but they are not used clinically to any significant degree. Serum and urine amino acid profiles are available, but not likely to be clinically relevant to the status of arginine-derived NO production capability, because more factors are involved than simply the amount of arginine present in tissues and body fluids. Therefore, effects of arginine supplementation are best judged clinically. Various measures of circulatory and endothelial function are most likely to show changes if supplemental arginine enhances NOS activity, as well as blood pressure, erectile function, and exercise tolerance.

safety profile


Dosage levels of 1 to 6 g per day generally are well tolerated by healthy adults. Adverse effects are estimated to occur in 1% to 10% of patients administered arginine, with more severe reactions associated with intravenous (IV) administration.

Nutrient Adverse Effects

General Adverse Effects

Minor gastrointestinal (GI) distress is occasionally associated with supplemental intake; headache also may occur. Excessive doses of arginine (>40 g/day) may cause diarrhea, most likely as a result of poor absorption at higher dosage levels. Rapid IV infusion may produce flushing.

Despite numerous studies demonstrating the immune-enhancing activity of arginine, including research with breast cancer, some researchers have suggested that high doses of arginine can increase the growth of cancer cells in humans. 1-4Clinicians with experience in integrative oncology have observed that amino acids, particularly arginine, can have opposite effects at different stages in the disease process, for tissues at different sites, and for different individuals. Further research into such aspects of nutritional therapeutics within cancer prevention and treatment are warranted to delineate such patterns and determine their implications in developing therapeutic strategies. However, pending such studies, the influence of arginine on growth of cancers can generally be qualified as unpredictable.

Adverse Effects Among Specific Populations

Individuals with a history of gastritis, reflux esophagitis, or peptic ulcer disease may experience exacerbations with arginine administration, possibly from stimulation of gastrin. However, the evidence for such concern is mixed.

Hyperphosphatemia can be induced by arginine in patients with severe hepatic disease and kidney problems. The maximum safe dosage levels for arginine administration in individuals with compromised hepatic function have not been established.

Pregnancy and Nursing

Data on long-term safety for arginine administration in pregnant or lactating women are lacking, and maximum safe dosage levels have not been established.

Infants and Children

Data on long-term safety for arginine administration in infants and children are lacking, and maximum safe dosage levels have not been established.


Administration ofL-arginine after acute myocardial infarction (MI) may lead to worsened clinical outcomes or death, particularly in older patients with diffuse atherosclerosis, and should be avoided except under the direct supervision of a physician trained and experienced in such interventions. 5 As a possible explanation for these results, it has been hypothesized thatL-arginine may only help to alleviate vascular stiffness in patients with preexistingL-arginine deficiency. Continued research is warranted to clarify the role ofL-arginine in cardiovascular health.

Avoidance of arginine supplementation by individuals with active or past herpes simplex virus (HSV) infections has often been asserted based on the theory that elevated arginine levels might stimulate viral replication or provoke an outbreak, especially in the context of low lysine levels. Although supported by broad anecdotal reports and older in vitro data, 6 evidence from clinical trials is lacking to confirm elevated susceptibility and validate this contraindication. Nevertheless, caution is warranted. If herpetic reactivations consistently occur shortly after initiating arginine administration or otherwise increasing intake, clinical anecdotes have suggested that a therapeutic trial of coadministration with equal amounts ofL-lysine may be useful. Currently, no clinical evidence indicates whether or notL-lysine coadministration may interfere withL-arginine's bioavailability, based on the known competition between the two amino acids for intestinal absorption.

Arginine administration is generally contraindicated in individuals with hepatic or renal failure, except when clinically appropriate and then only under direct medical supervision. 7

Individuals with a known history of hypersensitivity to arginine generally need to avoid supplemental intake.

Precautions and Warnings

Arginine administration, at usual dosage levels, is generally considered safe in individuals with stable type 2 diabetes mellitus. However, regular monitoring of blood glucose levels is appropriate in diabetic individuals supplementing with arginine because of possible effects on insulin and glucagon. 6

interactions review

Strategic Considerations

Despite positive findings from a range of disparate studies, scientific research on the therapeutic use of arginine has not matured; evidence of interactions involving arginine, based on well-designed clinical trials and documented case reports, is uneven and often absent. In many cases, well-known pharmacological principles enable us to predict many probable patterns of interaction, but the body of evidence articulating mechanisms, actions, and efficacy has not yet produced a consistent set of clinically applicable knowledge and related practices. Medical conditions and pharmaceutical agents that deplete or impair arginine status inherently influence relationships between NO and arginase and their interdependent levels and functions and consequently affect cardiac, muscular, and respiratory tissues and processes of growth, inflammation, and expansion/contraction. Interactions involving arginine are primarily characterized by their beneficial effect in supporting the therapeutic strategy and reducing drug adverse effects; such action inherently invokes the occasional bimodal interaction that carries potential for adverse or supportive character largely dependent on communication, observation, and responsive clinical management. Thus, for example, drugs that reduce arginase activity would theoretically increase arginine's availability to be converted to NO. Further research into this apparent bimodal activity of NO, and arginine, is warranted because some aspects of current knowledge suggest that excess NO levels might be involved in chronic inflammatory disorders. Any resulting evidence of peroxynitrate/nitrite formation from NO in situations of increased oxidative stress in the context of inadequate antioxidant reserves would suggest that clinicians give further attention to antioxidant reserves when administering arginine.

In some respects, arginine has already established a role for itself within the inpatient clinical setting, more so than in conventional outpatient care. Within critical care guidelines, arginine hydrochloride is considered a fourth-line treatment for uncompensated metabolic alkalosis after sodium chloride, potassium chloride, and ammonium chloride supplementation has been optimized. The immunomodulatory actions of arginine in nourishing hospitalized patients represent an area of continued research and significant potential benefit. Research on immunonutrition using arginine as part of parenteral formulas in combination with other nutrients has focused on mucosal barrier function, cellular defense, and local or systemic inflammation; results have been promising but mixed.

Within nutritional pharmacology and integrative therapeutic strategies, arginine is primarily used as a component of multifactorial interventions to promote detoxification (especially excretion of ammonia), stimulate immune function and modulate inflammation, aid wound healing, enhance healthy function of cardiac and vascular tissue, and promote secretion of several hormones, including glucagon, insulin, and GH. Thus, the emerging concept of immunonutrition as a proactive component of an integrative therapeutic strategy represents a convergence of conventional practice and nutritive therapies, with further research inevitable.

nutrient-drug interactions
Angiotensin-Converting Enzyme (ACE) Inhibitors

Benazepril (Lotensin), combination drug: benazepril and amlodipine (Lotrel); captopril (Capoten); captopril and hydrochlorothiazide (Acezide, Capto-Co, Captozide, Co-Zidocapt); cilazapril (Inhibace), enalapril (Vasotec); combination drugs: enalapril and felodipine (Lexxel); enalapril and hydrochlorothiazide (Vaseretic); fosinopril (Monopril), lisinopril (Prinivil, Zestril), lisinopril and hydrochlorothiazide (Prinzide, Zestoretic); moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace) trandolapril (Mavik).

Potassium-Sparing Diuretics
Sildenafil and Related Phosphodiesterase-5 Inhibitors
theoretical, speculative, and preliminary interactions research, including overstated interactions claims
Estrogen-Progestin Combinations
Oral Contraceptives: Monophasic, Biphasic, and Triphasic Estrogen Preparations (Synthetic Estrogen and Progesterone Analogs)
Hormone Replacement Therapy, Estrogen-Containing and Synthetic Estrogen and Progesterone Analog Medications
nutrient-nutrient interactions
Omega-3 Fatty Acids (Fish Oils)
Parenteral and Enteral Nutrition Formulations Containing Antioxidants, Fatty Acids, and Other Nutrients
herb-nutrient interactions
Citations and Reference Literature
  • 1.Takeda Y, Tominaga T, Tei N et al. Inhibitory effect of l-arginine on growth of rat mammarytumors induced by 7,12-dimethylbenz(a)anthracene. Cancer Res 1975;35:2390-2393.
  • 2.Park KG. The Sir David Cuthbertson Medal Lecture 1992. The immunological and metabolic effects of l-arginine in human cancer. Proc Nutr Soc 1993;52:387-401.View Abstract
  • 3.Brittenden J, Heys SD, Miller I et al. Dietary supplementation with l-arginine in patients with breast cancer (>4 cm) receiving multimodality treatment: report of a feasibility study. Br J Cancer 1994;69:918-921.View Abstract
  • 4.Brittenden J, Heys SD, Eremin O. l-Arginine and malignant disease: a potential therapeutic role? Eur J Surg Oncol 1994;20:189-192.
  • 5.Schulman SP, Becker LC, Kass DA et al. l-Arginine therapy in acute myocardial infarction: the Vascular Interaction with Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA 2006;295:58-64.View Abstract
  • 6.Tankersley RW Jr. Amino acid requirements of herpes simplex virus in human cells. J Bacteriol 1964;87:609-613.View Abstract
  • 7.Saibara T, Ono M, Iwasaki S et al. Effects of ethanol on l-arginine transport in rat Ito cells in relation to nitric oxide production. Alcohol Clin Exp Res 2001;25:39S-45S.View Abstract
  • 8.Rush JE, Merrill DD. The safety and tolerability of lisinopril in clinical trials. J Cardiovasc Pharmacol 1987;9 Suppl 3:S99-S107.View Abstract
  • 9.Good CB, McDermott L, McCloskey B. Diet and serum potassium in patients on ACE inhibitors. JAMA 1995;274:538.View Abstract
  • 10.Sifton DW et al. Physicians’ Desk Reference. Montvale, NJ: Medical Economics Company; 2000:1965-1968.
  • 11.Massara F, Martelli S, Ghigo E et al. Arginine-induced hypophosphatemia and hyperkaliemia in man. Diabete Metab 1979;5:297-300.View Abstract
  • 12.Pezza V, Bernardini F, Pezza E et al. Study of supplemental oral l-arginine in hypertensives treated with enalapril + hydrochlorothiazide. Am J Hypertens 1998;11:1267-1270.View Abstract
  • 13.Abbott KC, Bakris GL. Treatment of the diabetic patient: focus on cardiovascular and renal risk reduction. Prog Brain Res 2002;139:289-298.View Abstract
  • 14.Andoh TF, Gardner MP, Bennett WM. Protective effects of dietary l-arginine supplementation on chronic cyclosporine nephrotoxicity. Transplantation 1997;64:1236-1240.View Abstract
  • 15.Alexander JW, Levy A, Custer D et al. Arginine, fish oil, and donor-specific transfusions independently improve cardiac allograft survival in rats given subtherapeutic doses of cyclosporin. JPEN J Parenter Enteral Nutr 1998;22:152-155.View Abstract
  • 16.Lee J, Kim SW, Kook H et al. Effects of l-arginine on cyclosporin-induced alterations of vascular NO/cGMP generation. Nephrol Dial Transplant 1999;14:2634-2638.View Abstract
  • 17.Marcinkiewicz J, Grabowska A, Chain B. Nitric oxide up-regulates the release of inflammatory mediators by mouse macrophages. Eur J Immunol 1995;25:947-951.View Abstract
  • 18.Zhang XZ, Ardissino G, Ghio L et al. l-Arginine supplementation in young renal allograft recipients with chronic transplant dysfunction. Clin Nephrol 2001;55:453-459.View Abstract
  • 19.Mantovani F, Patelli E, Colombo F et al. [Erectile dysfunction after non–nerve sparing radical pelvic surgery: therapeutical experience with sildenafil and l-arginine evaluated by Buckling test]. Minerva Med 2001;92:285-287.View Abstract
  • 20.Glossmann H, Petrischor G, Bartsch G. Molecular mechanisms of the effects of sildenafil (Viagra). Exp Gerontol 1999;34:305-318.View Abstract
  • 21.Vardi Y, Gruenwald I. Cardiovascular effects of oral pharmacotherapy in erectile dysfunction. Curr Med Res Opin 2000;16 Suppl 1:s42-s47.View Abstract
  • 22.Zorgniotti AW, Lizza EF. Effect of large doses of the nitric oxide precursor, l-arginine, on erectile dysfunction. Int J Impot Res 1994;6:33-35; discussion 36.View Abstract
  • 23.Chen J, Wollman Y, Chernichovsky T et al. 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 Int 1999;83:269-273.View Abstract
  • 24.Meurs H, Maarsingh H, Zaagsma J. Arginase and asthma: novel insights into nitric oxide homeostasis and airway hyperresponsiveness. Trends Pharmacol Sci 2003;24:450-455.View Abstract
  • 25.Nikolic J, Bjelakovic G, Stojanovic I. Effect of caffeine on metabolism of l-arginine in the brain. Mol Cell Biochem 2003;244:125-128.View Abstract
  • 26.Fischer A, Folkerts G, Geppetti P, Groneberg DA. Mediators of asthma: nitric oxide. Pulm Pharmacol Ther 2002;15:73-81.View Abstract
  • 27.Zimmermann N, King NE, Laporte J et al. Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis. J Clin Invest 2003;111:1863-1874.View Abstract
  • 28.Vercelli D. Arginase: marker, effector, or candidate gene for asthma? J Clin Invest 2003;111:1815-1817.
  • 29.Meurs H, McKay S, Maarsingh H et al. Increased arginase activity underlies allergen-induced deficiency of cNOS-derived nitric oxide and airway hyperresponsiveness. Br J Pharmacol 2002;136:391-398.View Abstract
  • 30.Wei LH, Jacobs AT, Morris SM Jr, Ignarro LJ. IL-4 and IL-13 upregulate arginase I expression by cAMP and JAK/STAT6 pathways in vascular smooth muscle cells. Am J Physiol Cell Physiol 2000;279:C248-C256.View Abstract
  • 31.Wechsler ME, Grasemann H, Deykin A et al. Exhaled nitric oxide in patients with asthma: association with NOS1 genotype. Am J Respir Crit Care Med 2000;162:2043-2047.
  • 32.Morris CR, Poljakovic M, Lavrisha L et al. Decreased arginine bioavailability and increased serum arginase activity in asthma. Am J Respir Crit Care Med 2004;170:148-153.View Abstract
  • 33.Tentolouris C, Tousoulis D, Goumas G et al. l-Arginine in coronary atherosclerosis. Int J Cardiol 2000;75:123-128.View Abstract
  • 34.Walsh DE, Griffith RS, Behforooz A. Subjective response to lysine in the therapy of herpes simplex. J Antimicrob Chemother 1983;12:489-496.View Abstract
  • 35.DiGiovanna JJ, Blank H. Failure of lysine in frequently recurrent herpes simplex infection: treatment and prophylaxis. Arch Dermatol 1984;120:48-51.View Abstract
  • 36.McCune MA, Perry HO, Muller SA, O’Fallon WM. Treatment of recurrent herpes simplex infections with l-lysine monohydrochloride. Cutis 1984;34:366-373.
  • 37.Simon CA, Van Melle GD, Ramelet AA. Failure of lysine in frequently recurrent herpes simplex infection. Arch Dermatol 1985;121:167-168.View Abstract
  • 38.Griffith RS, Walsh DE, Myrmel KH et al. Success of l-lysine therapy in frequently recurrent herpes simplex infection: treatment and prophylaxis. Dermatologica 1987;175:183-190.View Abstract
  • 39.Pichard C, Sudre P, Karsegard V et al. A randomized double-blind controlled study of 6 months of oral nutritional supplementation with arginine and omega-3 fatty acids in HIV-infected patients. Swiss HIV Cohort Study. AIDS 1998;12:53-63.View Abstract
  • 40.Castillo L, Sanchez M, Vogt J et al. Plasma arginine, citrulline, and ornithine kinetics in adults, with observations on nitric oxide synthesis. Am J Physiol 1995;268:E360-E367.View Abstract
  • 41.Elam RP. Morphological changes in adult males from resistance exercise and amino acid supplementation. J Sports Med Phys Fitness 1988;28:35-39.View Abstract
  • 42.Elam RP, Hardin DH, Sutton RA, Hagen L. Effects of arginine and ornithine on strength, lean body mass and urinary hydroxyproline in adult males. J Sports Med Phys Fitness 1989;29:52-56.View Abstract
  • 43.Marcell TJ, Taaffe DR, Hawkins SA et al. Oral arginine does not stimulate basal or augment exercise-induced GH secretion in either young or old adults. J Gerontol A Biol Sci Med Sci 1999;54:M395-M399.
  • 44.Beale RJ, Bryg DJ, Bihari DJ. Immunonutrition in the critically ill: a systematic review of clinical outcome. Crit Care Med 1999;27:2799-2805.View Abstract
  • 45.Heys SD, Walker LG, Smith I, Eremin O. Enteral nutritional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized controlled clinical trials. Ann Surg 1999;229:467-477.View Abstract
  • 46.Suchner U, Kuhn KS, Furst P. The scientific basis of immunonutrition. Proc Nutr Soc 2000;59:553-563.View Abstract
  • 47.Heyland DK, Novak F, Drover JW et al. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA 2001;286:944-953.View Abstract
  • 48.Suchner U, Heyland DK, Peter K. Immune-modulatory actions of arginine in the critically ill. Br J Nutr 2002;87 Suppl 1:S121-S132.View Abstract
  • 49.Calder PC. Immunonutrition. BMJ 2003;327:117-118.View Abstract
  • 50.Kemen M, Senkal M, Homann HH et al. Early postoperative enteral nutrition with arginine-omega-3 fatty acids and ribonucleic acid–supplemented diet versus placebo in cancer patients: an immunologic evaluation of Impact. Crit Care Med 1995;23:652-659.View Abstract
  • 51.Bower RH, Cerra FB, Bershadsky B et al. Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial. Crit Care Med 1995;23:436-449.View Abstract
  • 52.Weimann A, Bastian L, Bischoff WE et al. Influence of arginine, omega-3 fatty acids and nucleotide-supplemented enteral support on systemic inflammatory response syndrome and multiple organ failure in patients after severe trauma. Nutrition 1998;14:165-172.View Abstract
  • 53.Gianotti L, Braga M, Fortis C et al. A prospective, randomized clinical trial on perioperative feeding with an arginine-, omega-3 fatty acid-, and RNA-enriched enteral diet: effect on host response and nutritional status. JPEN J Parenter Enteral Nutr 1999;23:314-320.View Abstract
  • 54.Van Bokhorst-de van der Schueren MA, Quak JJ, von Blomberg-van der Flier BM et al. Effect of perioperative nutrition, with and without arginine supplementation, on nutritional status, immune function, postoperative morbidity, and survival in severely malnourished head and neck cancer patients. Am J Clin Nutr 2001;73:323-332.
  • 55.Caparros T, Lopez J, Grau T. Early enteral nutrition in critically ill patients with a high-protein diet enriched with arginine, fiber, and antioxidants compared with a standard high-protein diet. The effect on nosocomial infections and outcome. JPEN J Parenter Enteral Nutr 2001;25(6):299-308; discussion 308-309.View Abstract
  • 56.Lebret T, Herve JM, Gorny P et al. Efficacy and safety of a novel combination of l-arginine glutamate and yohimbine hydrochloride: a new oral therapy for erectile dysfunction. Eur Urol 2002;41:608-613; discussion 613.View Abstract
  • .Abbott KC, Bakris GL. Treatment of the diabetic patient: focus on cardiovascular and renal risk reduction. Prog Brain Res 2002;139:289-298.
  • .American Society of Health-System Pharmacists. AHFS drug information. Bethesda, MD: American Society of Health-System Pharmacists; 2000.
  • .Appleton J: Arginine: clinical potential of a semi-essential amino. Altern Med Rev 2002;7(6):512-522. (Review)
  • .Andoh TF, Gardner MP, Bennett WM. Protective effects of dietary L-arginine supplementation on chronic cyclosporine nephrotoxicity. Transplantation 1997;64(9):1236-1240.
  • .Assis SM, Monteiro JL, Seguro AC: L-Arginine and allopurinol protect against cyclosporine nephrotoxicity. Transplantation 1997; 63(8):1070-1073.
  • .Baligan M, Giardina A, Giovannini G, et al. L-Arginine and immunity: study of pediatric subjects. Minerva Pediatr 1997;49(11):537-542. [Italian]
  • .Barbul A, Lazarou SA, Efron DT, et al. Arginine enhances wound healing and lymphocyte immune responses in humans. Surgery 1990;108(2):331-336.
  • .Barbul A, Rettura G, Levenson SM, et al. Wound healing and thymotropic effects of arginine: a pituitary mechanism of action. Am J Clin Nutr 1983;37(5):786-794.
  • .Bednarz B, Wolk R, Chamiec T, et al. Effects of oral L-arginine supplementation on exercise-induced QT dispersion and exercise tolerance in stable angina pectoris. Int J Cardiol 2000;75:205-210.
  • .Besset A, Bonardet A, Rondouin G, et al. Increase in sleep related GH and Prl secretion after chronic arginine aspartate administration in man. Acta Endocrinol (Copenh) 1982;99(1):18-23.
  • .Blum A, Porat R, Rosenschein U, et al. Clinical and inflammatory effects of dietary L-arginine in patients with intractable angina pectoris. Am J Cardiol 1999;83:1488-1490.
  • .Boger RH, Bode-Boger SM, Thiele W, et al. Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease. J Am Coll Cardiol 1998;32:1336-1344.
  • .Brittenden J, Heys SD, Ross J, et al. Natural cytotoxicity in breast cancer patients receiving neoadjuvant chemotherapy: effects of L-arginine supplementation. Eur J Surg Oncol 1994;20(4):467-472.
  • .Brittenden J, Heys SD, Ross J, et al. Nutritional pharmacology: effects of L-arginine on host defences, response to trauma and tumour growth. Clin Sci (Colch) 1994;86(2):123-132.
  • .Brittenden J, Park KG, Heys SD, et al. L-arginine stimulates host defenses in patients with breast cancer. Surgery 1994;115(2):205-212.
  • .Bruch-Gerharz D, Schnorr O, Suschek C, et al. Arginase 1 overexpression in psoriasis: limitation of inducible nitric oxide synthase activity as a molecular mechanism for keratinocyte hyperproliferation. Am J Pathol 2003;162(1):203-211.
  • .Bruinsma VA, Anderson BE, Prendergast JJ, et al. Effects of an L-arginine-enriched medical food in patients with type II diabetes. Diabetes 2001;50(Suppl 2):Abstract #1796-PO. (Abstract).
  • .Bushinsky DA, Gennari FJ. Life-threatening hyperkalemia induced by arginine. Ann Intern Med 1978;89(5 Pt 1):632-634.
  • .Caparros T, Lopez J, Grau T. Early enteral nutrition in critically ill patients with a high-protein diet enriched with arginine, fiber, and antioxidants compared with a standard high-protein diet: the effect on nosocomial infections and outcome. JPEN J Parenter Enteral Nutr 2001;25(6):299-309.
  • .Cartledge JJ, Davies AM, Eardley I. A randomized double-blind placebo-controlled crossover trial of the efficacy of L-arginine in the treatment of interstitial cystitis. BJU Int 2000;85:421-426.
  • .Cartledge J, Minhas S, Eardley I. The role of nitric oxide in penile erection. Expert Opin Pharmacother 2001;2(1):95-107. (Review)
  • .Castillo L, Sanchez M, Vogt J, et al. Plasma arginine, citrulline, and ornithine kinetics in adults, with observations on nitric oxide synthesis. Am J Physiol 1995;268:E360-E367.
  • .Cavdar Z, Onvural B, Guner G. Arginase in patients with breast cancer. Clin Chim Acta 2003;338(1-2):171-172.
  • .Ceremuzynski L, Chamiec T, Herbaczynska-Cedro K. Effect of supplemental oral L-arginine on exercise capacity in patients with stable angina pectoris. Am J Cardiol 1997;80:331-333.
  • .Cheng JW, Baldwin SN, Balwin SN. L-arginine in the management of cardiovascular diseases. Ann Pharmacother 2001;35(6):755-764.
  • .Clark RH, Feleke G, Din M, et al. Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study. JPEN J Parenter Enteral Nutr 2000;24:133-139.
  • .Corraliza I, Moncada S. Increased expression of arginase II in patients with different forms of arthritis: implications of the regulation of nitric oxide. J Rheumatol 2002;29(11):2261-2265.
  • .De Aloysio O, Mantuano R, Mauloni M, et al. The clinical use of arginine aspartate in male infertility. Acta Eur Fertil 1982;13:133-167.
  • .de Gouw HW, Verbruggen MB, Twiss IM, et al. Effect of oral L-arginine on airway hyperresponsiveness to histamine in asthma. Thorax 1999;54:1033-1035.
  • .De Nicola L, Bellizzi V, Minutolo R, et al. Randomized, double-blind, placebo-controlled study of arginine supplementation in chronic renal failure. Kidney Int 1999;56:674-684.
  • .Duggan C, Gannon J, Walker WA. Protective nutrients and functional foods for the gastrointestinal tract. Am J Clin Nutr 2002;75(5):789-808. (Review)
  • .Doutreleau S, Mettauer B, Piquard F, et al. Chronic L-arginine supplementation enhances endurance exercise tolerance in heart failure patients. Int J Sports Med 2006;27(7):567-572.
  • .Ehren I, Lundberg JON, Adolfsson J, et al. Effects of L-arginine treatment on symptoms arid bladder nitric oxide levels in patients with interstitial cystitis. Urology 1998;52:1026-l029.
  • .Esposito K, Giugliano F, Di Palo C, et al. Effect of lifestyle changes on erectile dysfunction in obese men. JAMA 2004;291:2978-2984.
  • .Fischer A, Folkerts G, Geppetti P, et al. Mediators of asthma: nitric oxide. Pulm Pharmacol Ther 2002;15(2):73-81. (Review)
  • .Flakoll P, Sharp R, Baier S, et al. Effect of beta-hydroxy-beta-methylbutyrate, arginine, and lysine supplementation on strength, functionality, body composition, and protein metabolism in elderly women. Nutrition 2004;20(5):445-451.
  • .Gennari R, Alexander JW. Arginine, glutamine, and dehydroepiandrosterone reverse the immunosuppressive effect of prednisone during gut-derived sepsis. Crit Care Med 1997;25(7):1207-1214.
  • .Ghigo E, Miola C, Aimaretti G, et al. Arginine abolishes the inhibitory effect of glucose on the growth hormone response to growth hormone-releasing hormone in man. Metabolism 1992;41(9):1000-1003.
  • .Hambrecht R, Hilbrich L, Erbs S, et al. Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation. J Am Coll Cardiol 2000;35(3):706-713.
  • .Hein TW, Zhang C, Wang W, et al. Ischemia-reperfusion selectively impairs nitric oxide-mediated dilation in coronary arterioles: counteracting role of arginase. FASEB J 2003;17(15):2328-2330.
  • .Hurson M, Regan MC, Kirk SJ, et al. Metabolic effects of arginine in a healthy elderly population. J Parenter Enteral Nutr 1995;19(3):227-230.
  • .Huynh NT, Tayek JA. Oral arginine reduces systemic blood pressure in type 2 diabetes: its potential role in nitric oxide generation. J Am Coll Nutr 2002;21(5):422-427.
  • .Hyndman ME, Verma S, Rosenfeld RJ, et al. Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial function. Am J Physiol Heart Circ Physiol 2002;282(6):H2167-H2172.
  • .Ignarro LJ, Buga GM, Wei LH, et al. Role of the arginine-nitric oxide pathway in the regulation of vascular smooth muscle cell proliferation. Proc Natl Acad Sci U S A 2001;98(7):4202-4208.
  • .Jain NK, Patil CS, Singh A, et al. Sildenafil-induced peripheral analgesia and activation of the nitric oxide-cyclic GMP pathway. Brain Res 2001;909(1-2):170-178.
  • .Kakumitsu S, Shijo H, Yokoyama M, et al. Effects of L-arginine on the systemic, mesenteric, and hepatic circulation in patients with cirrhosis. Hepatology 1998;27(2):377-382.
  • .Kavey R-EW, Allada V, Daniels SR, et al. Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation 2006;114:2710-2738.
  • .Kelly BS, Alexander JW, Dreyer D, et al. Oral arginine improves blood pressure in renal transplant and hemodialysis patients. JPEN J Parenter Enteral Nutr 2001;25(4):194-202.
  • .Kilroy RA, et al. Acid-base disorders. In: DiPiro JT, et al., eds. Pharmacotherapy: a pathophysiologic approach. 4th ed. Stamford, CT: Appleton and Lange; 1999:931.
  • .Kirk SJ, Hurson M, Regan MC, et al. Arginine stimulates wound healing and immune function in elderly human beings. Surgery 1993;114(2):155-159.
  • .Klotz T, Mathers MJ, Braun M, et al. Effectiveness of oral L-arginine in first-line treatment of erectile dysfunction ins controlled crossover study. Urol Int 1999;63(4):220-223.
  • .Knopf RF, Conn JW, Fajans SS, et al. Plasma growth hormone response to intravenous administration of amino acids. J Clin Endocrinol Metab 1965;25:1140-1144.
  • .Kohls KJ, Kies C, Fox HM. Serum lipid levels of humans given arginine, lysine and tryptophan supplements without food. Nutr Rep Int 1987;35:5-13.
  • .Koifman B, Wollman Y, Bogomolny N, et al. Improvement of cardiac performance by intravenous infusion of L-arginine in patients with moderate congestive heart failure. J Am Coll Cardiol 1995;26(5):1251-1256.
  • .Korting GE, Smith SD, Wheeler MA, et al. A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis. J Urol 1999;161:558-565.
  • .Langkamp-Henken B, Herrlinger-Garcia KA, Stechmiller JK. Arginine supplementation is well tolerated but does not enhance mitogen-induced lymphocyte proliferation in elderly nursing home residents with pressure ulcers. J Parenter Enteral Nutr 2000;24(5):280-287.
  • .Lebret T, Herve JM, Gorny P, et al. Efficacy and safety of a novel combination of L-arginine glutamate and yohimbine hydrochloride: a new oral therapy for erectile dysfunction. Eur Urol 2002;41(6):608-613.
  • .Luiking YC, Weusten BL, Portincasa P, et al. Effects of long-term oral L-arginine on esophageal motility and gallbladder dynamics in healthy humans. Am J Physiol 1998;274(6 Pt 1):G984-G991.
  • .Lundberg JO, Adolfsson J. Effects of L-arginine treatment on symptoms and bladder nitric oxide levels in patients with interstitial cystitis. Urology 1998;52:1026-1029.
  • .Maes M, Verkerk R, Vandoolaeghe E, et al. Serum levels of excitatory amino acids, serine, glycine, histidine, threonine, taurine, alanine and arginine in treatment-resistant depression: modulation by treatment with antidepressants and prediction of clinical responsivity. Acta Psychiatr Scand 1998;97(4):302-308.
  • .Marz R. Medical nutrition from Marz. 2nd ed. Portland, OR: Omni Press; 1997.
  • .Massara F, Martelli S, Ghigo E, et al. Arginine-induced hypophosphatemia and hyperkaliemia in man. Diabetes Metab 1979;5(4):297-300.
  • .Maxwell AJ, Anderson BE, Cooke JP. Nutritional therapy for peripheral arterial disease: a double-blind, placebo-controlled, randomized trial of HeartBar. Vasc Med 2000;5(1):11-19.
  • .Maxwell AJ, Zapien MP, Pearce GL, et al. Randomized trial of a medical food for the dietary management of chronic, stable angina. J Am Coll Cardiol 2002;39(1):37-45.
  • .McAuley IW, Kim NN, Min K, et al. Intracavernosal sildenafil facilitates penile erection independent of the nitric oxide pathway. J Androl 2001;22(4):623-628.
  • .Melman A. This month in investigative urology: L-arginine and penile erection. J Urol 1997;158:686.
  • .Merimee TJ, Lillicrap DA, Rabinowitz D. Effect of arginine on serum-levels of human growth-hormone. Lancet 1965;2:668-670.
  • .Meurs H, Maarsingh H, Zaagsma J. Response to Ricciardolo: the functional significance of arginase in asthma is supported by gene expression. Trends Pharmacol Sci 2003;24(11):562-563.
  • .Meurs H, Maarsingh H, Zaagsma J. Arginase and asthma: novel insights into nitric oxide homeostasis and airway hyperresponsiveness. Trends Pharmacol Sci 2003;24(9):450-455. (Review)
  • .Meurs H, McKay S, Maarsingh H, et al. Increased arginase activity underlies allergen-induced deficiency of cNOS-derived nitric oxide and airway hyperresponsiveness. Br J Pharmacol 2002;136(3):391-398.
  • .Moody JA, Vernet D, Laidlaw S, et al. Effects of long-term administration of L-arginine on the rat erectile response. J Urol 1997;l58:942-947.
  • .Morris CR, Poljakovic M, Lavrisha L, et al. Decreased arginine bioavailability and increased serum arginase activity in asthma. Am J Respir Crit Care Med 2004. Epub ahead of print.
  • .Mroueh A. Effect of arginine on oligospermia. Fertil Steril 1970;21:217-219.
  • .Ohwada T, Ishibashi T, Yaoita H, et al. Different contribution of apoptosis to the antiproliferative effects of L-arginine, enalapril and losartan on neointimal growth inhibition after balloon arterial injury. Circ J 2002;66(10):965-971.
  • .Padma-Nathan H, Giuliano F. Oral drug therapy for erectile dysfunction. Urol Clin North Am 2001;28(2):321-334. (Review)
  • .Park KG. The Sir David Cuthbertson Medal Lecture 1992: the immunological and metabolic effects of L-arginine in human cancer. Proc Nutr Soc 1993;52(3):387-401. (Review)
  • .Piatti P, Fragasso G, Monti LD, et al. Acute intravenous L-arginine infusion decreases endothelin-1 levels and improves endothelial function in patients with angina pectoris and normal coronary arteriograms: correlation with asymmetric dimethylarginine levels. Circulation 2003;107(3):429-436.
  • .Piatti PM, Monti LD, Valsecchi G, et al. Long-term oral L-arginine administration improves peripheral and hepatic insulin sensitivity in type 2 diabetic patients. Diabetes Care 2001;24:875-880.
  • .Piepho RW. Overview of the angiotensin-converting-enzyme inhibitors. Am J Health Syst Pharm 2000;57(Suppl 1):S3-57. (Review)
  • .Polat MF, Taysi S, Polat S, et al. Elevated serum arginase activity levels in patients with breast cancer. Surg Today 2003;33(9):655-661.
  • .Porembska Z, Luboinski G, Chrzanowska A, et al. Arginase in patients with breast cancer. Clin Chim Acta 2003;328(1-2):105-111.
  • .Preiser JC, Berre PJ, Van Gossum A, et al. Metabolic effects of arginine addition to the enteral feeding of critically ill patients. JPEN J Parenter Enteral Nutr 2001;25:182-187.
  • .Pryor JP, Blandy JP, Evans P, et al. Controlled clinical trial of arginine for infertile men with oligozoospermia. Br J Urol 1978;50(1):47-50.
  • .Rajamohan T, Kurup PA. Lysine: arginine ratio of a protein influences cholesterol metabolism: part 1 studies on sesame protein having low lysine: arginine ratio. J Exp Biol 1997;35(11):1218-1223.
  • .Rakoff JS, Siler TM, Sinha YN, et al. Prolactin and growth hormone release in response to sequential stimulation by arginine and synthetic TRF. J Clin Endocrinol Metab 1973;37:641-644.
  • .Rector TS, Bank AJ, Mullen KA, et al. Randomized, double-blind, placebo-controlled study of supplement oral L-arginine in patients with heart failure. Circulation 1996;93:2135-2141.
  • .Resnick DJ, Softness B, Murphy AR, et al. Case report of an anaphylactoid reaction to arginine. Ann Allergy Asthma Immunol 2002;88:67-68.
  • .Sato Y, Zhao W, Christ GJ. Central modulation of the NO/cGMP pathway affects the MPOA-induced intracavernous pressure response. Am J Physiol Regul Integr Comp Physiol 2001;281(1):R269-R278.
  • .Sax HC. Arginine stimulates wound healing and immune function in elderly human beings. JPEN J Parenter Enteral Nutr 1994;18(6):559-560.
  • .Schachter A, Friedman S, Goldman JA, et al. Treatment of oligospermia with the amino acid arginine. Int J Gynaecol Obstet 1973;11(5):206-209.
  • .Schacter A, Goldman JA, Zukerman Z. Treatment of oligospermia with the amino acid arginine. J Urol 1973;110:311-313.
  • .Scibona M, Meschini P, Capparelli S, et al. L-arginine and male infertility. Minerva Urol Nefrol 1994;46(4):251-253.
  • .Smith SD, Wheeler MA, Foster HE Jr, et al. Improvement in interstitial cystitis symptom scores during treatment with oral L-arginine. J Urol 1997;158(3 Pt 1):703-708.
  • .Staff AC, Berge L, Haugen G, et al. Dietary supplementation with L-arginine or placebo in women with pre-eclampsia. Acta Obstet Gynecol Scand 2004;83(1):103-107.
  • .Straathof JW, Adamse M, Onkenhout WI, et al. Effect of L-arginine on lower oesophageal sphincter motility in man. Eur J Gastroenterol Hepatol 2000;12:419-424.
  • .Suchner U, Heyland DK, Peter K. Immune-modulatory actions of arginine in the critically ill. Br J Nutr 2002;87:s121-132.
  • .Swanson B, Keithley JK, Zeller JM, et al. A pilot study of the safety and efficacy of supplemental arginine to enhance immune function in persons with HIV/AIDS. Nutrition 2002;18:688-690.
  • .Tanimura J. Studies on arginine in human semen, part II: the effects of medication with L-arginine-HCL on male infertility. Bull Osaka Med School 1967;13:84-89.
  • .Tentolouris C, Tousoulis D, Goumas G, et al. L-Arginine in coronary atherosclerosis. Int J Cardiol. 2000;75(2-3):123-128. (Review)
  • .Theilmeier G, Chan JR, Zalpour C, et al. Adhesiveness of mononuclear cells in hypercholesterolemic humans is normalized by dietary L-arginine. Arterioscler Thromb Vasc Biol 1997;17(12):3557-3564.
  • .Tomita R, Tanjoh K. Role of nitric oxide in the colon of patients with ulcerative colitis. World J Surg 1998;22(1):88-91.
  • .USP DI. Approved drug products and legal requirements. 20th ed, vol. III. Rockville, MD: United States Pharmacopeial Convention; 2000.
  • .Vardi Y, Gruenwald I. Cardiovascular effects of oral pharmacotherapy in erectile dysfunction. Curr Med Res Opin 2000;16(Suppl 1):s42-s47. (Review)
  • .Walker HA, McGing E, Fisher I, et al. Endothelium-dependent vasodilation is independent of the plasma L-arginine/ADMA ratio in men with stable angina: lack of effect of oral L-arginine on endothelial function, oxidative stress and exercise performance. J Am Coll Cardiol 2001;38:499-505.
  • .Watanabe G, Tomiyama H, Doba N. Effects of oral administration of L-arginine on renal function in patients with heart failure. J Hypertens 2000;18:229-234.
  • .Werbach MR. Foundations of nutritional medicine. Tarzana, CA: Third Line Press; 1997. (Review)
  • .Williams JZ. Nutrition and wound healing. Surg Clin North Am 2003;83(3):571-596.
  • .Wolf A, Zalpour C, Theilmeier G, et al. Dietary L-arginine supplementation normalizes platelet aggregation in hypercholesterolemic humans. J Am Coll Cardiol 1997;29(3):479-485.
  • .Wu G, Meininger CJ. Arginine nutrition and cardiovascular function. J Nutr 2000;130:2626-2629.
  • .Yang CW, Kim YS, Kim J, et al. Oral supplementation of L-arginine prevents chronic cyclosporine nephrotoxicity in rats. Exp Nephrol 1998;6(1):50-56.
  • .Zorgniotti AW, Lizza EF. Effect of large doses of the nitric oxide precursor, L-arginine, on erectile dysfunction. Int J Impot Res 1994;6:33-36.