Arginine

• How It Works

  Arginine has not been shown to prevent or treat cancer in humans.

  Arginine is an amino acid that is produced by the body. It has been used for various conditions such as high blood pressure, heart conditions, migraines, and erectile dysfunction. Arginine has also been shown in some studies to enhance wound healing, immune function, and athletic performance.

  Arginine supplementation has been studied in cancer patients. Some studies 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.

• Purported Uses
  • Angina
    Studies support the benefits of arginine for angina.
  • Hardening of blood vessel walls
    A few studies have shown that arginine may be effective for atherosclerosis.
  • Wound healing
    This use is supported by evidence from clinical trials.
  • Immune stimulation
    Arginine given in high doses may improve immune function cancer patients.
  • Erectile dysfunction
    Arginine has been shown in clinical trials to help improve sexual function in men.
  • Migraine headache
    When taken with ibuprofen, arginine increased pain relief in patients with migraine headaches.
• Patient Warnings
  • Some evidence suggests an increase in breast tumor growth after taking arginine supplements, but more studies are needed to confirm this.
  • Long-term arginine supplementation in patients with peripheral artery disease may be harmful.
• Do Not Take If
  • If you are taking medicine for high blood pressure, heart conditions, or erectile dysfunction: Arginine may have additive blood pressure lowering effects.
• Side Effects
  • Abdominal pain
  • Bloating
  • Nausea
  • Diarrhea
  • Large doses of arginine can increase excretion of lysine in urine.
• 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, migraine headache, 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 (PADs) ^{(10) (11) (12) (13)}, but long-term supplementation worsened PAD ⁽¹⁴⁾. Arginine has also been studied for its effect on modifying or preventing the development of nitrate tolerance during continuous transdermal nitroglycerin therapy ⁽¹⁸⁾. Supplementation with arginine, glutamine, and HMB and may benefit vascular endothelial function in older adults ⁽³³⁾, but arginine supplementation 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⁾. Large doses of oral arginine improved subjective assessment of sexual function in men with erectile dysfunction ⁽¹⁶⁾. Arginine combined with ibuprofen may increase pain relief in patients with migraine headaches ⁽¹⁷⁾. Arginine supplementation by enteral feeding decreased shock in severely burned patients ⁽⁴⁾ and may be useful as adjunctive therapy in patients with active tuberculosis ⁽²⁹⁾.

  Arginine supplementation has been studied in cancer patients. Perioperative enteral formulas enhanced with arginine may improve wound healing ⁽¹⁾, enhance immune status ⁽²⁷⁾, and reduce length of hospital stay ⁽³⁰⁾. Other results in surgical cancer patients have been mixed ^(35) (36). Interestingly, arginine deprivation-based treatments are also being pursued as potential cancer treatments ^{(31) (32) (37)}.

• Food Sources

  Nuts, seeds, soy foods, legumes, and chocolate

• Purported Uses
  • Hypertension
  • Angina
  • Atherosclerosis
  • Wound healing
  • Immune stimulation
  • Erectile dysfunction
  • Migraine headaches
• 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

  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 and diarrhea have been reported with oral administration ^{(5) (8) (20)}.
• Herb-Drug Interactions
  • Large doses of arginine can increase urinary excretion of lysine ⁽²¹⁾.
  • Due to arginine’s vasodilatory properties, theoretically it may have additive hypotensive effects with drugs such as antihypertensives, sildenafil and nitrates ^(11) (20).
• Herb Lab Interactions

  High doses of intravenous arginine may results in the spillover into urine ⁽²²⁾.

• References

  • 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.

  • 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.

  • 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.

  • 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.

  • Brittenden J, Park KG, Heys SD, et al. L-arginine stimulates host defenses in patients with breast cancer. Surgery. 1994;115(2):205-212.

  • 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.

  • Chander V, Chopra K. Effect of molsidomine and L-arginine in cyclosporine nephrotoxicity: role of nitric oxide. Toxicology. 28 2005;207(3):463-474.

  • 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.

  • 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.

  • Gornik HL, Creager MA. Arginine and endothelial and vascular health. J Nutr. 2004;134(10 Suppl):2880S-2887S; discussion 2895S.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • Cheng JW, Baldwin SN. L-arginine in the management of cardiovascular diseases. Ann Pharmacother. 2001;35(6):755-764.

  • Wilmore D. Enteral and parenteral arginine supplementation to improve medical outcomes in hospitalized patients. J Nutr. 2004;134(10 Suppl):2863S-2867S; discussion 2895S.

  • Boger RH, Bode-Boger SM. The clinical pharmacology of L-arginine. Annu Rev Pharmacol Toxicol. 2001;41:79-99.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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, Jul 23. [Epub ahead of print]

  • 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.

  • Farazi A, Shafaat O, Sofian M, Kahbazi M. Arginine adjunctive therapy in active tuberculosis. Tuberc Res Treat. 2015;2015:205016.

  • 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.

  • Feun LG, Kuo MT, Savaraj N. Arginine deprivation in cancer therapy. Curr Opin Clin Nutr Metab Care. 2015 Jan;18(1):78-82.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.