Arginine




Arginine is an amino acid which plays an important role in our bodies as a precursor of nitric oxide biosynthesized by vascular endothelium.
Its most common commercially available form is L-Arginine which is also the form naturally occurring in nature and in the human body.

The 1998 Nobel Prize in Physiology or Medicine was awarded "for discoveries concerning nitric oxide as a signalling molecule in the cardiovascular system" [3].
Endothelial cells are synthesizing this substance and this production decreases with age. The amounts of nitric oxide could be also too low at a young age for genetic or dietary reasons.
Nitric oxide is an autocrine and paracrine signaling molecule having vasodilatory properties, mediating inhibition of platelet activation, monocyte and leucocyte adhesion, and smooth muscle cell proliferation.
It is also very important for a control of vascular oxidative stress and gene expression [4].
It is currently believed that a substance previously known as EDRF (Endothelium-derived relaxing factor) is simply nitric oxide.
Arginine, a precursor of nitric oxide, is used in biosynthesis of carnitine (needed for muscle contraction) [1].

Until recently it was thought that in case of shortage of arginine in the diet the body could produce it in quantities sufficient to maintain health.
However, recent studies suggest that the amount of this amino acid that our body can obtain as a result of such synthesis is too small and arginine has to be supplemented [2].

Formulations containing Arginine can be helpful and are being used in the following health conditions:
CARDIOVASCULAR DISEASES
Arginine may slow down the process of atherosclerosis [7], which together with the vasodilatory action may have a positive action in coronary ischaemic disease (in stable angina) and in peripheral artery disease (PAD). May also have lowering effect on elevated blood pressure [8].
There is a very promising research showing very good influence of Arginine in congestive heart failure (CHF).
In one of clinical studies after using high doses of Arginine in people with congestive heart failure there was an improvement in peripheral blood flow by 29%, 6 minute walking distance increase by 8%, arterial flexibility increased by 19% [18,19]. Supplementation with this amino acid improves exercise capacity in patients with chronic stable heart failure [22].
Other studies showed an improvement of endothelial function [18,20] and renal function [18,21] in patients with congestive heart failure taking products containing Arginine.
ERECTILE DYSFUNCTION
Because of the relaxing (dilating) effect on blood vessels (through the action of nitric oxide) supplements with Arginine may be helpful in sexual dysfunction in men [5] (without side effects associated with the use of pharmaceuticals [2]). There is also research suggesting a helpful role of Arginine in the treatment of male and female infertility [6].
Rising prevalence of prostate cancer and of benign prostatic hyperplasia (BPH) is causing more and more men every year to undergo urological procedures involving prostate. Erectile dysfunction is a common complication, especially after complete prostatectomy.
Arginine is a supplement potentially helpful (at least worth trying) in those cases, which one can find out not only from Internet forums but also from scientific publications [26].
MIGRAINE HEADACHE
Malfunction of vascular endothelium associated with a deficiency of nitric oxide plays role in the pathophysiology of migraine headaches.
Therefore, supplementation with arginine may help the symptoms [9].
DIABETES TYPE I AND II
The level of Arginine is usually too low in people with diabetes.
Taking Arginine had a positive impact on the restoration of normal vascular function in patients with type I diabetes [12].
The beneficial effect of supplementation with this amino acid was also observed in type II diabetes.
Administration of Arginine may increase production of insulin by the pancreas [13], reduce insulin resistance, improve the level of adiponectin, have a beneficial effect on metabolism and help in losing weight [14,15].
ULCERS AND ESOPHAGEAL REFLUX [16]
IMMUNE STIMULATION
The use of Arginine has a positive effect on the immune system [17].
WOUND HEALING
Surgery and trauma which are leading to the formation of wounds are that kind of burden to the organism in which very often there is shortage of Arginine causing too low production of nitric oxide. Supplementation of this amino acid may accelerate the wound healing [25] and shorten the period of hospitalization after surgery [4].
ATHLETIC PERFORMANCE
Bodybuilders and other athletes use supplements with Arginine believing that this amino acid may increase the production of growth hormone and thus have a beneficial effect on the growth of muscle mass.
Currently there is no research confirming that Arginine may be helpful when it is used for this purpose [2].
However, there is a clinical study of Italian pediatricians showing positive response to Arginine (by influencing the growth hormone) in short children before puberty [10].
COGNITION AND DEMENTIA/ALZHEIMER DISEASE
Due to the very important role of nitric oxide and its declining production in human body during aging process, the use of supplements with Arginine may be useful in treating age related degenerative conditions of central nervous system of which the most common are diagnosed as dementia or Alzheimer disease [11].

PRECAUTIONS
Arginine may potentiate blood pressure-lowering effect of certain pharmaceuticals, for example drugs used to treat cardiological conditions (Nitroglicerine, ACE inhibitors, diuretics) and erectile dysfunction (Sildenafil/Viagra, Cialis). Arginine may add to the effect of these pharmaceuticals [2].

In the case of long-term use of Arginine with potassium-sparing diuretics (n.e. amiloride, triamterene, spironolactone) it is recommended to monitor the levels of potassium in the blood (because it may be too high) [27].

Supplements with Arginine probably should not be taken after acute myocardial infarction.
There is a study showing worse prognosis of people taking Arginine together with appropriate pharmaceuticals following myocardial infarction comparing to placebo group [23].
However, there is also newer Chinese research suggesting no influence of Arginine on prognosis in case of unstable angina and acute myocardial infarction [24].





[1] PDR
( Physicians' Desk Reference )
For Nutritional Supplements

2nd Edition
Sheldon Saul Hendler, PhD, MD, FACP, FACN, FAIC
with David M. Rorvik, MS
2008 Published by Physicians' Desk Reference Inc. at Montvale, NJ

[2] Solve It With Supplements
The Best Herbal and Nutritional Supplements to Prevent and Heal More Than 100 Common Health Problems.
Robert A. Schulman, MD
physiatrist and medical acupuncturist
with Carolyn Dean, MD, ND, medical advisor
2007 by Rodale Inc.

[3] http://www.nobelprize.org/nobel_prizes/medicine/laureates/1998/

[4] https://www.mskcc.org/cancer-care/integrative-medicine/herbs/arginine

[5] BJU Int. 1999 Feb;83(3):269-73.
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.

Chen J1, Wollman Y, Chernichovsky T, Iaina A, Sofer M, Matzkin H.
1Department of Urology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

[6] J Reprod Med. 2004 Apr;49(4):289-93.
A nutritional supplement for improving fertility in women: a pilot study.
Westphal LM1, Polan ML, Trant AS, Mooney SB.
1Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, California 94305, USA. lynnw@stanford.edu

[7] Atherosclerosis. 2002 May;162(1):1-15.
Vascular effects of dietary L-arginine supplementation.
Preli RB1, Klein KP, Herrington DM.
1Department of Internal Medicine/Cardiology, School of Medicine, Wake Forest University, Medical Center Boulevard, Winston-Salem, NC 27157-1045, USA.

[8] J Nutr. 2004 Oct;134(10 Suppl):2807S-2811S; discussion 2818S-2819S.
L-arginine and hypertension.
Gokce N1.
1Evans Department of Medicine, Cardiology Section, and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA. Noyan.Gokce@bmc.org

[9] Headache. 2015 Jan;55(1):35-54. doi: 10.1111/head.12494. Epub 2014 Dec 24.
Endothelial function in migraine with aura - a systematic review.
Butt JH1, Franzmann U, Kruuse C.
1Department of Neurology, Neurovascular Research Unit, Copenhagen University Hospital Herlev, Herlev, Denmark.

[10] Acta Paediatr. 1993 Oct;82(10):883-4.
Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children.
Loche S1, Carta D, Muntoni AC, Corda R, Pintor C.
1Istituto di Clinica Pediatrica, Università di Cagliari, Italy.

[11] Int J Clin Exp Pathol. 2009; 2(3): 211–238.
Published online 2008 Oct 2.
L-Arginine and Alzheimer's Disease
Jing Yi,1 Laura L. Horky,2 Avi L. Friedlich,1 Ying Shi,3 Jack T. Rogers,1 Xudong Huang1,3
1Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
2Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
3Conjugate and Medicinal Chemistry Laboratory, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology,
Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
Please address all correspondences to Xudong Huang, Ph.D., Conjugate and Medicinal Chemistry Laboratory,
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA

[12] Eur J Nutr. 2013 Apr;52(3):975-83. doi: 10.1007/s00394-012-0404-7. Epub 2012 Jul 6.
Effects of L-arginine supplementation on blood flow, oxidative stress status and exercise responses in young adults with uncomplicated type I diabetes.
Fayh AP1, Krause M, Rodrigues-Krause J, Ribeiro JL, Ribeiro JP, Friedman R, Moreira JC, Reischak-Oliveira A.
1Laboratório de Pesquisa do Exercício, Escola de Educação Física, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

[13] Amino Acids. 2001;21(2):205-9.
L-arginine stimulates insulin secretion from the pancreas of normal and diabetic rats.
Adeghate E1, Ponery AS, El-Sharkawy T, Parvez H.
1Department of Human Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain.

[14] Eur Rev Med Pharmacol Sci. 2012 Jun;16(6):816-23.
Effect of 3-month L-arginine supplementation on insulin resistance and tumor necrosis factor activity in patients with visceral obesity.
Bogdanski P1, Suliburska J, Grabanska K, Musialik K, Cieslewicz A, Skoluda A, Jablecka A.
1Department of Internal Medicine, Metabolic Disorders and Hypertension, Poznan University of Medical Sciences, Poznan, Poland.

[15] Int J Clin Exp Med. 2015; 8(7): 10358–10366.
Published online 2015 Jul 15.
Effect of L-arginine supplementation on insulin resistance and serum adiponectin concentration in rats with fat diet.
Anna Miczke,1 Joanna Suliburska,2 Danuta Pupek-Musialik,1 Lucyna Ostrowska,3 Anna Jabłecka, 4 Zbigniew Krejpcio,2 Damian Skrypnik,1 and Paweł Bogdański5
1Department of Internal Medicine, Metabolic Disorders and Hypertension, Poznan University of Medical Sciences, Poznan, Poland
2Department of Human Nutrition and Hygiene, Poznan University of Life Sciences, Poznan, Poland
3Department of Dietetics and Clinical Nutrition Medical University of Białystok, Poland
4Department of Clinical Pharmacology, Poznan University of Medical Sciences, Poznan, Poland
5Department of Education and Obesity Treatment and Metabolic Disorders, Poznan University of Medical Sciences, Poznan, Poland
Address correspondence to: Paweł Bogdański, Department of Education and Obesity Treatment and Metabolic Disorders, Poznan University of Medical Sciences, Szamarzewskiego 84 Str., Poznan 60-569, Poland.

[16] Biomed Res Int. 2014; 2014: 532594.
Published online 2014 Feb 2. doi: 10.1155/2014/532594
Animal Model of Acid-Reflux Esophagitis: Pathogenic Roles of Acid/Pepsin, Prostaglandins, and Amino Acids
Koji Takeuchi 1 , 2 ,* and Kenji Nagahama 1
1Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan
2General Incorporated Association, Kyoto Research Center for Gastrointestinal Diseases, Karasuma-Oike 671, Kyoto 604-8106, Japan

[17] J Nutr. 2007 Jun;137(6 Suppl 2):1681S-1686S.
Arginine and immunity.
Popovic PJ1, Zeh HJ 3rd, Ochoa JB.
1Department of Surgery, University of Pittsburgh Medical School, Pittsburgh, PA 15213, USA.

[18] The Encyclopedia of Natural Medicine
Third Edition
Michael T. Murray, ND & Joseph Pizzorno, ND
By the authors of The Encyclopedia of Healing Foods
First Atria Paperback edition July 2012

[19] Circulation. 1996 Jun 15;93(12):2135-41.
Randomized, double-blind, placebo-controlled study of supplemental oral L-arginine in patients with heart failure.
Rector TS1, Bank AJ, Mullen KA, Tschumperlin LK, Sih R, Pillai K, Kubo SH.
1Department of Medicine, University of Minnesota Medical School, Minneapolis 55455, USA.

[20] J Am Coll Cardiol. 2000 Mar 1;35(3):706-13.
Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation.
Hambrecht R1, Hilbrich L, Erbs S, Gielen S, Fiehn E, Schoene N, Schuler G.
1University of Leipzig, Heart Center, Division of Cardiology, Germany.

[21] J Hypertens. 2000 Feb;18(2):229-34.
Effects of oral administration of L-arginine on renal function in patients with heart failure.
Watanabe G1, Tomiyama H, Doba N.
1The Third Department of Internal Medicine, Teikyo University Ichihara Hospital, Chiba, Japan.

[22] Kardiol Pol. 2004 Apr;60(4):348-53.
L-arginine supplementation prolongs exercise capacity in congestive heart failure.
Bednarz B1, Jaxa-Chamiec T, Gebalska J, Herbaczyńska-Cedro K, Ceremuzyński L.
1Department of Cardiology, Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland.

[23] JAMA. 2006 Jan 4;295(1):58-64.
L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial.
Schulman SP1, Becker LC, Kass DA, Champion HC, Terrin ML, Forman S, Ernst KV, Kelemen MD, Townsend SN, Capriotti A, Hare JM, Gerstenblith G.
1Division of Cardiology, Johns Hopkins Medical Institutions, Baltimore, USA.

[24] Clin Cardiol. 2009 Nov;32(11):649-52. doi: 10.1002/clc.20616.
Oral L-arginine supplementation in acute myocardial infarction therapy: a meta-analysis of randomized controlled trials.
Sun T1, Zhou WB, Luo XP, Tang YL, Shi HM.
1Department of Cardiology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, P.R. China.

[25] Nutr Clin Pract. 2005 Feb;20(1):52-61.
Arginine supplementation and wound healing.
Stechmiller JK1, Childress B, Cowan L.
1University of Florida College of Nursing, Adult & Elderly Nursing, PO Box 100187, Gainesville, FL 32605, USA.

[26] Res Rep Urol. 2015; 7: 19–33.
Published online 2015 Feb 23. doi: 10.2147/RRU.S58974
Management of erectile dysfunction post-radical prostatectomy
Alan Saleh, Hamid Abboudi, MB Ghazal-Aswad, Erik K Mayer, and Justin A Vale
Division of Surgery and Cancer, Imperial College Healthcare NHS Trust, St Mary’s Hospital, London, UK
Correspondence: Hamid Abboudi, Division of Surgery and Cancer, Imperial College Healthcare NHS Trust, St Mary’s Hospital, Praed Street, London W2 1NY, UK

[27] https://medlineplus.gov/druginfo/natural/875.html






ABSTRACT:
Arginine is an amino acid that is used by the vascular endothelium in the biosynthesis of nitric oxide, which has very important biological functions in the body. The most significant one seems to be vasodilation caused by relaxation of smooth muscle cells in arteries.

The Nobel Prize in Physiology or Medicine 1998 was awarded "for discoveries concerning nitric oxide as a signalling molecule in the cardiovascular system".
It is currently believed that a substance previously known as endothelium-derived relaxing factor (EDRF) is actually nitric oxide.

Arginine is mostly available (as a dietary supplement) as L-Arginine, which is also the form present in nature and in the human body. When nutritional deficiency occurs Arginine probably cannot be biosynthesized and should be supplemented. The demand for Arginine (as a precursor of nitric oxide) increases with age and its insufficient amounts may be responsible for health problems associated with aging.

Supplements with Arginine are mostly used in the following conditions:
coronary artery disease (in stable angina), peripheral artery disease, atherosclerosis, hypertension, erectile dysfunction, migraine headache, for athletic performance, to improve immune functions, for wound healing which may reduce length of hospital stay after surgery.

It is recommended not to use Arginine or to use with caution (under medical supervision) in unstable angina and acute myocardial infarction.

Arginine has an additive effect when used with certain pharmaceuticals which lower blood pressure (Nitroglicerine, ACE inhibitors, diuretics, Viagra, Cialis). It is also recommended to monitor potassium level while using this supplement with potassium-sparing diuretics (amiloride, spironolactone, triamterene) because it could be elevated.

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