Arginine is a semi-essential amino acid that is vital for the production of nitric oxide1,2.
Many of the activities of L-arginine, including its possible anti-atherogenic action, can be explained by its role as a precursor of nitric oxide (NO), a molecule produced by all of the tissues of the body and able to play very important roles in the cardiovascular system, the immune system and the nervous system5.
Melcalin® Pralginina (negative-PRAL L-arginine) is a food supplement containing buffered L-arginine; its formulation has been designed with the addition of minerals such as potassium and magnesium because the acid-base balance is extremely important for the wellbeing of the entire body. Acidifying load increases correlate to a number of issues such as higher systolic and diastolic pressure, higher total cholesterol, higher LDL, lower mineral content in the bone tissue as well as lean mass loss26,27,28,29,30. Achieving proper body pH is therefore vital for maintaining general health25.
This association combines the multiple properties of L-arginine with the buffering action of the minerals that support its activity.
Arginine and Cardiovascular Risk (CVR)
The endothelium is a fundamental regulator of vascular homeostasis; its functionality can be altered by various factors such as smoking, hypertension, high cholesterol and diabetes mellitus7.
An important role in the regulation of the endothelial functionality is played by nitric oxide (NO), a substance released by the endothelium7 starting from L-arginine. Several studies have proven that the administration of L-arginine improves the endothelial function in subjects with high cholesterol and atherosclerosis, so much so that it has been hypothesized that it could be used as a possible treatment for coronary disease and peripheral artheriopathies3,5,6,7.
It has been proven that both the intake of arginine-rich food and long-term administration of L-arginine reduce cardiovascular complications and are inversely associated to endothelial dysfunction in high-cholesterol patients because nitric oxide plays an important function in fat metabolism4.
L-arginine supplementation is able to decrease blood pressure and homocysteine levels: indeed, nitrogen oxide triggers a number of reactions that lead to the relaxation of smooth muscles and hence decreases blood pressure4.
Other researchers have highlighted that use of L-arginine leads to an increase in HDL and a decrease in cholesterol and triglycerides; specifically, a 7-day study on overweight men supplemented with L-arginine has shown a reduction of LDL and an increase in HDL3,4.
L-arginine plays a significant role in lowering glycemia: it has been proven that its use has improved glucose metabolism after 3-7 days of supplementation. It has been seen that L-arginine supplementation reduces glycemia in diabetic patients and scientific evidence shows that if taken for a prolonged period of time it can boost insulin sensitivity and improve glycemic indices; it seems that this results from its anti-oxidant activity3,4.
Arginine and BAT (Brown Adipose Tissue)
The Brown Adipose Tissue (BAT) present in man plays an important role in the oxidation of fatty acids and glucose.
Several studies in the literature have proven that L-arginine can stimulate the development of BAT mitochondria and induce gene expression regulation4.
L-arginine enhances the growth and development of BAT through mechanisms which involve gene expression and protein synthesis, which improves the oxidation of these energy substrates and hence reduces white fat buildups in the body: for this reason, L-arginine is believed to be very promising in the prevention and treatment of obesity in humans8.
Arginine and the Central Nervous System (CNS)
Nitric oxide (NO) is also an important regulator of the physiological processes in the central nervous system (SNC) in that it promotes optimal cerebral blood flow, consolidates memory processes, maintains the sleep-wake cycle and helps olfaction9.
Arginine and the Immune System
For several years, arginine has been used as a food supplement, often combined with other substances, as a mechanism to boost the immune system.
L-arginine plays an important role in regulating the immune system as it influences immune responses and inflammation. A piece of research has proven that subjects supplemented with L-arginine showed a lower incidence of infectious complications compared to the control group14.
As the production of nitric oxide (NO) starting from arginine is essential to defend the host from a number of pathogens, the availability of arginine is decisive for infection resistance; it has been seen that some pathogens are able to develop pathways that make it possible to degrade arginine in such a way as to avoid the immune system15.
Recent research has confirmed this, revealing that tumor cells express arginase (an arginine-degrading enzyme) and that this also occurs in cells after trauma or surgery16.
Arginine and Wounds
Arginine is classified as a non-essential amino acid that becomes a conditionally essential substrate in stressed adults.
Arginine is an amino acid that plays a number of different key roles in cell physiology. Like every amino acid, it is involved in the synthesis of proteins, but it is also intimately involved in cell signaling through the production of nitric oxide and cell proliferation. As a result of these multiple functions, arginine is an essential substrate for wound healing, so much so that some studies have highlighted that arginine increases wound resistance and collagen deposition in the area of injury and have proposed arginine supplementation to improve wound healing10,11.
Use of arginine can also be advised for diabetes as this condition impairs wound healing and as few therapeutic options are available to solve this issue. Data suggests that arginine supplementation improves the healing process by normalizing the production of nitric oxide, the latter being extremely important for wound scarring12,13.
Arginine and Sport
Arginine is a precursor of nitric oxide (NO); this molecule acts as signal to facilitate blood vessel dilatation and decrease vascular resistance. NO is synthesized by arginine, under the enzymatic control of nitric oxide synthase (NOS).
In the muscle, NO regulates the production of strength (excitation-contraction coupling), self-regulation of the blood flow, myocyte differentiation, breathing and glucose homeostasis. The contractile activity significantly increases the production of NO in the muscle, which, in turn, increases the release and absorption of fuel substrates through its vasodilating effects19.
Exercise performance has been analyzed after supplementation with L-arginine and physical performance has been found to be significantly improved by L-arginine as it promotes vasodilation and hence boosts the production of nitric oxide (NO) in the muscle and, as a result, improves strength, power and muscle recovery22.
Other research on sport performance (VO2 max) has shown that taking L-arginine results in an increase in muscular fatigue resistance and a significant increase in performance20.
It is well known that eccentric exercise interrupts sarcolemmal integrity and induces damage to skeletal muscle fibers; supplementation of L-arginine before eccentric exercise decreases the damage so induced23.
Satisfactory results have also been seen in post-menopausal women, in whom it has been found that the administration of L-arginine has increased maximum strength24.
The effects of oral supplementation of arginine on the ability to do exercise have been studied also in patients with pulmonary hypertension. A significant increase in the consumption of oxygen has been found and it has been hypothesized that arginine might possibly have a role in increasing nitric oxide, which translates into an increase in vasodilation and coronary vessels flow, which, in turn, can positively impact coronary perfusion21.
Erectile dysfunction significantly limits the quality of life of a growing number of men. Given the increase in the conditions predisposing to the development of erectile dysfunction and given the aging of the male population, it is possible to mitigate the physical and psychological impact of erectile dysfunction by tackling risk factors through changes in the lifestyle combined with medical and surgical therapy in some patients.
Nitric oxide (NO) has been proven to relax the smooth muscles of the urogenital tract and is a well-known mediator of erection and of dilatation of the neck of the bladder and of the ureter. Oral high-dose L-arginine seems to determine a significant subjective improvement of the sexual function in men with this condition17,18.
1) J Chiropr Med. 2016 Sep; 15(3): 184–189. Published online 2016 Sep 10. PMCID: PMC5021928 PMID: 27660594. Therapeutic Benefits of l-Arginine: An Umbrella Review of Meta-analyses. Marc P. McRae, MSc, DC, FACN, DACBN.
2) J Nutr. 2007 Jun;137(6 Suppl 2):1650S-1655S. doi: 10.1093/jn/137.6.1650S.The pharmacodynamics of L-arginine. Böger RH.
3) Curr Opin Clin Nutr Metab Care. 2007 Jan;10(1):46-51. Effects of L-arginine supplementation on exercise metabolism. McConell GK
4) Version 2. F1000Res. 2014; 3: 306. Published online 2017 Jun 22. PMCID: PMC5510020. L-arginine supplementation and risk factors of cardiovascular diseases in healthy men: a double-blind randomized clinical trial. Naseh Pahlavani, Mostafa Jafari, Omid Sadeghi, Masoud Rezaei, Hamid Rasad, Hossein Ali Rahdar, and Mohammad Hasan Entezari
5) Pubchem. Compound Summary for CID 6322
6) J Nutr. 2004 Oct;134(10 Suppl):2880S-2887S; discussion 2895S. doi: 10.1093/jn/134.10.2880S. Arginine and endothelial and vascular health. Gornik HL, Creager MA.
7) J Clin Invest. 2001 Sep 1; 108(5): 717–724. Vascular endothelial dysfunction resulting from l-arginine deficiency in a patient with lysinuric protein intolerance. Yoshihiro Kamada, Hiroyuki Nagaretani, Shinji Tamura, Tohru Ohama, Takao Maruyama, Hisatoyo Hiraoka, Shizuya Yamashita, Akira Yamada, Shinichi Kiso, Yoshiaki Inui, Nobuyuki Ito, Yoshiro Kayanoki, Sumio Kawata, and Yuji Matsuzawa
8) Curr Opin Clin Nutr Metab Care. 2012 Nov;15(6):529-38. Regulation of brown adipose tissue development and white fat reduction by L-arginine.Wu Z, Satterfield MC, Bazer FW, Wu G.
9) Crit Rev Food Sci Nutr. 2013;53(11):1157-67. doi: 10.1080/10408398.2011.573885.L-arginine and nitric oxide in CNS function and neurodegenerative diseases.Virarkar M, Alappat L, Bradford PG, Awad AB.
10) Wound Repair Regen. 2003 Nov-Dec;11(6):419-23.Arginine physiology and its implication for wound healing.Witte MB, Barbul A.
11) Nutr Clin Pract. 2005 Feb;20(1):52-61.Arginine supplementation and wound healing.Stechmiller JK, Childress B, Cowan L.
12) Metabolism. 2002 Oct;51(10):1269-73.L-Arginine supplementation enhances diabetic wound healing: involvement of the nitric oxide synthase and arginase pathways.Witte MB, Thornton FJ, Tantry U, Barbul A.
13) Acta Cir Bras. 2016 Sep;31(9):586-596. doi: 10.1590/S0102-865020160090000003.Oral or topical administration of L-arginine changes the expression of TGF and iNOS and results in early wounds healing.Jerônimo MS, Barros AD, MoritaI VE, Alves EO, Souza NL, Almeida RM, Nóbrega YK, Cavalcanti FF Neto, Amorin R, Borin MF, Bocca AL.
14) Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].Effect of L-arginine on immune function: a meta-analysis.Review published: 2014.Bibliographic details: Kang K, Shu XL, Zhong JX, Yu TT. Effect of L-arginine on immune function: a meta-analysis. Asia Pacific Journal of Clinical Nutrition 2014;23(3):351-359.
15) Science Signaling. Sci. Signal. 17 Aug 2010:Vol. 3, Issue 135, pp. Pe27 DOI: 10.1126/scisignal.3135pe27 Arginine: Master and Commander in Innate Immune Responses. Sidney M. Morris Jr.
16) J Nutr. 2007 Jun;137(6 Suppl 2):1681S-1686S. doi: 10.1093/jn/137.6.1681S.Arginine and immunity. Popovic PJ, Zeh HJ 3rd, Ochoa JB.
17) 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 J, Wollman Y, Chernichovsky T, Iaina A, Sofer M, Matzkin H.
18) Andrologia. 2011 Oct;43(5):303-6. doi: 10.1111/j.1439-0272.2010.01064.x. Epub 2011 Jul 27.Effect of exogenous l-arginine and ageing on NO and ET-1 in penile tissue of rat.Wu XJ, Song B, Zhang JH, Zhou ZS, Li LK, Li XM.
19) J Int Soc Sports Nutr. 2004; 1(2): 35–38. Published online 2004 Dec 31. doi: 10.1186/1550-2783-1-2-35 PMCID: PMC2129157 PMID: 18500948. The Ergogenic Potential of Arginine. Bill I Campbell, Paul M La Bounty, and Mike Roberts
20) Eur J Clin Nutr. 2017 Apr;71(4):544-548. doi: 10.1038/ejcn.2016.266. Epub 2017 Jan 25.The effect of l-arginine supplementation on body composition and performance in male athletes: a double-blinded randomized clinical trial.Pahlavani N, Entezari MH, Nasiri M, Miri A, Rezaie M, Bagheri-Bidakhavidi M, Sadeghi O.
21) J Int Soc Sports Nutr. 2004; 1(2): 35–38. Published online 2004 Dec 31. doi: [10.1186/1550-2783-1-2-35]. PMCID: PMC2129157. The Ergogenic Potential of Arginine. Bill I Campbell, Paul M La Bounty, and Mike Roberts
22) Sports Med. 2011 Mar 1;41(3):233-48. L-Arginine as a potential ergogenic aid in healthy subjects.Álvares TS, Meirelles CM, Bhambhani YN, Paschoalin VM, Gomes PS.
23) PLoS One. 2014 Apr 15;9(4):e94448. doi: 10.1371/journal.pone.0094448. eCollection 2014.L-arginine supplementation protects exercise performance and structural integrity of muscle fibers after a single bout of eccentric exercise in rats. Lomonosova YN, Shenkman BS, Kalamkarov GR, Kostrominova TY, Nemirovskaya TL.
24) Clin Physiol Funct Imaging. 2008 Sep;28(5):307-11. Epub 2008 May 28.The effect of L-arginine administration on muscle force and power in postmenopausal women.Fricke O, Baecker N, Heer M, Tutlewski B, Schoenau E.
25) J Bone Miner Res. 2013 Mar; 28(3): 497–504. Potassium citrate supplementation results in sustained improvement in calcium balance in older men and women. Kendall Moseley, MD, Connie Weaver, PhD, Lawrence Appel, MD, Anthony Sebastian, MD, and Deborah E. Sellmeyer, MD
26) Zhang L, Curhan GC, Forman JP. Diet-dependent net acid load and risk of incident hypertension in United States women. Hypertension. 2009 Oct;54(4):751-5. Epub 2009 Aug 10.
27) Dargent-Molina P, Sabia S, Touvier M, Kesse E, Bréart G, Clavel-Chapelon F, Boutron-Ruault MC. Proteins, dietary acid load, and calcium and risk of postmenopausal fractures in the E3N French women prospective study. J Bone Miner Res. 2008 Dec;23(12):1915-22.
28) Murakami K, Sasaki S, Takahashi Y, Uenishi K. Association between dietary acid-base load and cardiometabolic risk factors in young Japanese women. Br J Nutr. 2008 Sep;100(3):642-51. Epub 2008 Feb 18.
29) Zwart SR, Davis-Street JE, Paddon-Jones D, Ferrando AA, Wolfe RR, Smith SM. Amino acid supplementation alters bone metabolism during simulated weightlessness. J Appl Physiol. 2005 Jul;99(1):134-40. Epub 2005 Feb 3.
30) Diagnostica differenziale con bioimpedenza-Medical Device BIA-ACC-Biotekna. ECW=acqua extracellulare, ICW=acqua intracellulare, FFM=Fatt Free Mass:massa magra, Skeletal muscle FFM=massa muscolare, Tbprotein=Total Body Protein: proteine totali, ECM=extracellular matrix:matrice extracellulare.