Arginine

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Arginine

Common Names

  • L-arginine

For Patients & Caregivers

How It Works

Arginine is made in the body and also found in many protein-rich foods. Although it is used in clinical applications, evidence on its use for other conditions is lacking and in some instances may increase the risk for harm.

Arginine is an amino acid that is produced by the body. Clinical applications include its use during recovery from surgery, for heart and blood vessel conditions like angina or high blood pressure, and for some pregnancy complications. Arginine has also been used to enhance immune function and athletic performance or to improve conditions such as migraines and erectile dysfunction, but more studies are needed.

A few trials of arginine supplementation have been conducted in cancer patients. Some show that arginine-enriched nutritional formulas taken around the time of surgery may improve wound healing, enhance immune status, and reduce length of hospital stay. However, an analysis suggests that arginine supplementation may increase inflammatory biomarkers in certain subgroups, including cancer or older patients. Other studies suggest potential harm with long-term supplementation or in those who have had a heart attack. Therefore, additional studies are needed to determine the circumstances under which arginine supplementation could be safe and effective.

Purported Uses
  • To treat angina, hardening of blood vessels, or high blood pressure
    Some studies support the benefits of arginine for angina, atherosclerosis, and hypertension, but there are some conditions where supplementation may increase the risk for harm. Patients should therefore be managed by their treating physician.
  • To speed wound healing
    Data on whether arginine can improve wound healing are mixed.
  • To improve immune function
    Data on whether arginine can improve immune function are mixed.
  • To treat erectile dysfunction
    Preliminary data suggest arginine may help improve sexual function in men, but more studies are needed.
  • To treat migraine headaches
    Preliminary data suggest that arginine taken with ibuprofen may increase pain relief in patients with migraines, but more studies are needed.
Patient Warnings
  • Patients who have had a heart attack should avoid using arginine, as one study suggests it may increase risk for additional harm.
  • Long-term arginine supplementation in patients with peripheral artery disease may be harmful. Patients with this condition should be managed by their treating physician.
  • Some evidence suggests an increase in breast tumor growth after taking arginine supplements, but more studies are needed to confirm this.
Do Not Take If
  • You are taking medicine for high blood pressure, heart conditions, or erectile dysfunction: Arginine may have additional blood pressure-lowering effects.
  • You are a cancer patient: There is some data suggesting increases in inflammatory biomarkers with arginine supplementation, so patients should use caution and discuss any use of arginine with their treating physician.
  • You have had a heart attack: Patients with this condition should use caution and be managed by their treating physician.
  • You have peripheral artery disease: Patients with this condition should use caution and be managed by their treating physician.
Side Effects
  • Abdominal pain
  • Bloating
  • Nausea
  • Diarrhea
  • Large doses can increase removal of the amino acid lysine in urine.

Case Reports

  • Throat pain and inflammation: In a 40-year-old woman after taking l-arginine, selenium, and vitamin E supplements. A few other cases have also pointed to arginine as the suggested cause.
  • Acute pancreatitis: Cases in young adult men, attributed to use of arginine-containing products.
Special Point
  • Some protein powders or products claiming to improve sports performance may contain arginine.
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For Healthcare Professionals

Scientific Name
2-amino-5-guanidinovaleric acid
Clinical Summary

Arginine is an amino acid that is synthesized in the body. Oral arginine has been used for various conditions such as hypertension, angina, atherosclerosis, migraines, and erectile dysfunction. Its vasodilatory properties are thought to be responsible for the beneficial effects. Arginine has also been used to enhance wound healing, immune function, and athletic performance.

Some studies support the use of arginine in coronary artery and peripheral artery diseases (10) (11) (12) (13), but long-term supplementation worsened PAD (14). In addition, oral supplementation in patients who had an acute myocardial infarction did not improve ejection fraction or vascular stiffness, and may be associated with higher mortality (38). A meta-analysis of arginine supplementation on markers for cardiovascular disease, obesity, or diabetes also did not find benefit, except perhaps in a select group of patients (39). Smaller studies suggest supplementation with arginine, glutamine, and HMB may benefit vascular endothelial function in older adults (33), but arginine supplementation alone did not improve blood flow or muscle performance in older women (34).

Along with antioxidant vitamins, arginine reduced preeclampsia incidence in high-risk women (28), but arginine supplements did not improve blood pressure or kidney function in women with preeclampsia (15). Preliminary data suggest potential benefit with arginine supplementation for erectile dysfunction (16) (40). Arginine combined with ibuprofen may increase pain relief in patients with migraines (17). Enteral arginine decreased shock in severely burned patients (4) and may be useful as adjunctive therapy in patients with active tuberculosis (29).

In cancer patients, preliminary results are mixed for perioperative enteral arginine-enriched formulas to improve wound healing (1) (41), and immune function (27) (35) (42), but other studies suggest such formulas may reduce complications and length of hospital stay (30) (36). Some data suggest a prophylactic arginine-containng supplement may reduce incidence of hand-foot syndrome in hepatocellular carcinoma patients taking sorafenib (43). Interestingly, arginine deprivation-based treatments are also being pursued as potential cancer treatments (31) (32) (37).

Although a meta-analysis did not find significant effects with arginine supplementation on inflammatory biomarkers, subgroup analysis suggests it may increase circulating C-reactive protein in cancer patients, those older than age 60 or with higher baseline CRP levels, or with use of enteral formulas (44). Additional studies are needed to determine the circumstances under which arginine supplementation could be safe and effective.

Food Sources

Meat, poultry, fish, dairy products, nuts, seeds, soy foods, legumes, and chocolate

Purported Uses
  • Angina
  • Atherosclerosis
  • Hypertension
  • Wound healing
  • Immune stimulation
  • Erectile dysfunction
  • Migraines
Mechanism of Action

Arginine is unique among amino acids for its vasodilatory properties (11). Arginine acts as a precursor for the synthesis of endogenous nitric oxide (NO) via the action of nitric oxide synthase (NOS). NO functions as a paracrine-signaling molecule mediating vasodilation and inhibition of platelet activation, monocyte and leucocyte adhesion, and smooth muscle cell proliferation. NO also helps to control vascular oxidative stress and redox-regulated gene expression (22). Arginine is also needed for the synthesis of creatine which is important in muscle contraction (22). In colorectal adenoma cells, arginine reduces the expression of survivin, an inhibitor of apoptosis, and induces iNOS expression (23).

Warnings
  • In patients who had an acute myocardial infarction, arginine supplementation may increase risk of mortality (38).
  • Long-term supplementation may worsen peripheral artery disease (14).
  • Limited studies suggest that arginine supplementation may increase breast tumor growth, but more research is needed to examine this (9) (21).
Adverse Reactions
  • Abdominal pain, bloating, nausea, diarrhea (5) (8) (20).

Case Reports
Supplement-induced esophagitis:
In a 40-year-old woman after ingestion of l-arginine, selenium, and vitamin E supplements. A few other cases have also pointed to arginine as the suggested cause (45).
Acute pancreatitis: Upper abdominal pain and increased serum lipase levels in a young adult man, attributed to a protein shake containing arginine. The condition improved with treatment and cessation of the product (46). Another earlier case in a young adult had also been reported (47).

Herb-Drug Interactions
  • Antihypertensives: A small study showed that arginine could temporarily lower blood pressure in patients with diabetes (11). It also has vasodilatory properties (20). Therefore it may have additive hypotensive effects.
Herb Lab Interactions

Large doses of intravenous arginine can increase urinary excretion of lysine (21).

Dosage (OneMSK Only)
References
  1. Farreras N, Artigas V, Cardona D, Rius X, Trias M, Gonzalez JA. Effect of early postoperative enteral immunonutrition on wound healing in patients undergoing surgery for gastric cancer. Clin Nutr. 2005;24(1):55-65.
  2. de Luis DA, Izaola O, Cuellar L, Terroba MC, Aller R. Randomized clinical trial with an enteral arginine-enhanced formula in early postsurgical head and neck cancer patients. Eur J Clin Nutr. 2004;58(11):1505-1508.
  3. Casas-Rodera P, Gomez-Candela C, Benitez S, et al. Immunoenhanced enteral nutrition formulas in head and neck cancer surgery: a prospective, randomized clinical trial. Nutr Hosp. Mar-Apr 2008;23(2):105-110.
  4. Yan H, Peng X, Huang Y, Zhao M, Li F, Wang P. Effects of early enteral arginine supplementation on resuscitation of severe burn patients. Burns. Mar 2007;33(2):179-184.
  5. Brittenden J, Park KG, Heys SD, et al. L-arginine stimulates host defenses in patients with breast cancer. Surgery. 1994;115(2):205-212.
  6. Heys SD, Ogston K, Miller I, et al. Potentiation of the response to chemotherapy in patients with breast cancer by dietary supplementation with L-arginine: results of a randomised controlled trial. Int J Oncol. 1998;12(1):221-225.
  7. Chander V, Chopra K. Effect of molsidomine and L-arginine in cyclosporine nephrotoxicity: role of nitric oxide. Toxicology. 28 2005;207(3):463-474.
  8. Shihab FS, Bennett WM, Isaac J, Yi H, Andoh TF. Nitric oxide modulates vascular endothelial growth factor and receptors in chronic cyclosporine nephrotoxicity. Kidney Int. 2003;63(2):522-533.
  9. Park KG, Heys SD, Blessing K, et al. Stimulation of human breast cancers by dietary L-arginine. Clin Sci (Lond) 1992;82(4):413-417.
  10. Gornik HL, Creager MA. Arginine and endothelial and vascular health. J Nutr. 2004;134(10 Suppl):2880S-2887S; discussion 2895S.
  11. 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.
  12. Palloshi A, Fragasso G, Piatti P, et al. 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. Am J Cardiol. 2004;93(7):933-935.
  13. Siasos G, Tousoulis D, Vlachopoulos C, et al. Short-term treatment with L-arginine prevents the smoking-induced impairment of endothelial function and vascular elastic properties in young individuals.Int J Cardiol. Jun 6 2008;126(3):394-399.
  14. Wilson AM, Harada R, Nair N, Balasubramanian N, Cooke JP. L-arginine supplementation in peripheral arterial disease: no benefit and possible harm.Circulation. Jul 10 2007;116(2):188-195.
  15. Hladunewich MA, Derby GC, Lafayette RA, Blouch KL, Druzin ML, Myers BD. Effect of L-arginine therapy on the glomerular injury of preeclampsia: a randomized controlled trial. Obstet Gynecol. 2006;107(4):886-895.
  16. Chen J, Wollman Y, Chernichovsky T, Iaina A, Sofer M, Matzkin H. 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(3):269-273.
  17. Sandrini G, Franchini S, Lanfranchi S, Granella F, Manzoni GC, Nappi G. Effectiveness of ibuprofen-arginine in the treatment of acute migraine attacks. Int J Clin Pharmacol Res. 1998;18(3):145-150.
  18. Parker JO, Parker JD, Caldwell RW, Farrell B, Kaesemeyer WH. The effect of supplemental L-arginine on tolerance development during continuous transdermal nitroglycerin therapy. J Am Coll Cardiol. 3 2002;39(7):1199-1203.
  19. Loche S, Carta D, Muntoni AC, Corda R, Pintor C. Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children. Acta Paediatr. 1993;82(10):883-884.
  20. Cheng JW, Baldwin SN. L-arginine in the management of cardiovascular diseases. Ann Pharmacother. 2001;35(6):755-764.
  21. Wilmore D. Enteral and parenteral arginine supplementation to improve medical outcomes in hospitalized patients. J Nutr. 2004;134(10 Suppl):2863S-2867S; discussion 2895S.
  22. Boger RH, Bode-Boger SM. The clinical pharmacology of L-arginine. Annu Rev Pharmacol Toxicol. 2001;41:79-99.
  23. Ma Q, Wang Y, Gao X, Ma Z, Song Z. L-arginine reduces cell proliferation and ornithine decarboxylase activity in patients with colorectal adenoma and adenocarcinoma. Clin Cancer Res. Dec 15 2007;13(24):7407-7412.
  24. Paddon-Jones D, Borsheim E, Wolfe RR. Potential ergogenic effects of arginine and creatine supplementation. J Nutr. 2004;134(10 Suppl):2888S-2894S; discussion 2895S.
  25. Lucotti P, Setola E, Monti LD, et al. Beneficial 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 patients. Am J Physiol Endocrinol Metab. Nov 2006;291(5):E906-912.
  26. Matsuda A, Furukawa K, Takasaki H, et al. Preoperative oral immune-enhancing nutritional supplementation corrects TH1/TH2 imbalance in patients undergoing elective surgery for colorectal cancer. Dis Colon Rectum. Apr 2006;49(4):507-516.
  27. Okamoto Y, Okano K, Izuishi K, et al. Attenuation of the Systemic Inflammatory Response and Infectious Complications After Gastrectomy with Preoperative Oral Arginine and omega-3 Fatty Acids Supplemented Immunonutrition. World J Surg. 2009 Sep;33(9):1815-21.
  28. Vadillo-Ortega F, Perichart-Perera O, Espino S, et al. Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial. BMJ. 2011 May 19;342:d2901.
  29. Farazi A, Shafaat O, Sofian M, Kahbazi M. Arginine adjunctive therapy in active tuberculosis. Tuberc Res Treat. 2015;2015:205016.
  30. De Luis DA, Izaola O, Terroba MC, Cuellar L, Ventosa M, Martin T. Effect of three different doses of arginine enhanced enteral nutrition on nutritional status and outcomes in well nourished postsurgical cancer patients: a randomized single blinded prospective trial. Eur Rev Med Pharmacol Sci. 2015 Mar;19(6):950-955.
  31. Feun LG, Kuo MT, Savaraj N. Arginine deprivation in cancer therapy. Curr Opin Clin Nutr Metab Care. 2015 Jan;18(1):78-82.
  32. Pavlyk I, Rzhepetskyy Y, Jagielski AK, et al. Arginine deprivation affects glioblastoma cell adhesion, invasiveness and actin cytoskeleton organization by impairment of β-actin arginylation. Amino Acids. 2015 Jan;47(1):199-212.
  33. Ellis AC, Patterson M, Dudenbostel T, et al. Effects of 6-month supplementation with beta-hydroxy-beta-methylbutyrate, glutamine and arginine on vascular endothelial function of older adults. Eur J Clin Nutr. Feb 2016;70(2):269-273.
  34. Aguiar AF, Balvedi MC, Buzzachera CF, et al. L-Arginine supplementation does not enhance blood flow and muscle performance in healthy and physically active older women. Eur J Nutr. Sep 2016;55(6):2053-2062.
  35. Seguin P, Locher C, Boudjema K, et al. Effect of a Perioperative Nutritional Supplementation with Oral Impact(R) in Patients undergoing Hepatic Surgery for Liver Cancer: A Prospective, Placebo-Controlled, Randomized, Double-Blind Study. Nutr Cancer. 2016;68(3):464-472.
  36. Martin RC, 2nd, Agle S, Schlegel M, et al. Efficacy of preoperative immunonutrition in locally advanced pancreatic cancer undergoing irreversible electroporation (IRE). Eur J Surg Oncol. Apr 2017;43(4):772-779.
  37. Szlosarek PW, Steele JP, Nolan L, et al. Arginine Deprivation With Pegylated Arginine Deiminase in Patients With Argininosuccinate Synthetase 1-Deficient Malignant Pleural Mesothelioma: A Randomized Clinical Trial. JAMA Oncol. Jan 1 2017;3(1):58-66.
  38. 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. Jan 4 2006;295(1):58-64.
  39. Rodrigues-Krause J, Krause M, Rocha I, et al. Association of l-Arginine Supplementation with Markers of Endothelial Function in Patients with Cardiovascular or Metabolic Disorders: A Systematic Review and Meta-Analysis. Nutrients. Dec 20 2018;11(1).
  40. Rhim HC, Kim MS, Park YJ, et al. The Potential Role of Arginine Supplements on Erectile Dysfunction: A Systemic Review and Meta-Analysis. J Sex Med. Feb 2019;16(2):223-234.
  41. Wada N, Kurokawa Y, Tanaka K, et al. Perioperative Nutritional Support With Beta-hydroxy-beta-methylbutyrate, Arginine, and Glutamine in Surgery for Abdominal Malignancies. Wounds. Sep 2018;30(9):251-256.
  42. Ma C, Tsai H, Su W, et al. Combination of arginine, glutamine, and omega-3 fatty acid supplements for perioperative enteral nutrition in surgical patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST): A prospective, randomized, double-blind study. J Postgrad Med. Jul-Sep 2018;64(3):155-163.
  43. Naganuma A, Hoshino T, Ohno N, et al. β-Hydroxy-β-methyl Butyrate/L-Arginine/L-Glutamine Supplementation for Preventing Hand-Foot Skin Reaction in Sorafenib for Advanced Hepatocellular Carcinoma. In Vivo. Jan-Feb 2019;33(1):155-161.
  44. Nazarian B, Fazeli Moghadam E, Asbaghi O, et al. Effect of l-arginine supplementation on C-reactive protein and other inflammatory biomarkers: A systematic review and meta-analysis of randomized controlled trials. Complement Ther Med. Dec 2019;47:102226.
  45. O’Donnell C, Tandon P, Govardhanam V, et al. Pill-Induced Esophagitis From Intake of Dietary Supplements. ACG Case Rep J. Jun 2019;6(6):e00106.
  46. Binet Q, Dufour I, Agneessens E, et al. The second case of a young man with L-arginine-induced acute pancreatitis. Clin J Gastroenterol. Oct 2018;11(5):424-427.
  47. Saka M, Tüzün A, Ateş Y, et al. Acute pancreatitis possibly due to arginine use: a case report. Turk J Gastroenterol. Mar 2004;15(1):56-58.
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