Arginine serves as a precursor in different metabolic pathways in different organs. In the immune response, the metabolism and availability of arginine is determined by the nitric oxide synthase and the arginase enzyme, which convert arginine to nitric oxide and ornithine, respectively (1).

It is an amino acid that comes from taking the protein diet and is an intermediate in the urea cycle in the liver. The anomalies in the production by the human body in producing nitric oxide produce various cardiovascular pathologies including hypetension, arteriosclerosis and angiogenetic disorders (2).

Other major studies

Stechmiller JK, Childress B, Cowan L. Arginine supplementation and wound healing. Nutr Clin Pract. 2005 Feb;20(1):52-61. doi: 10.1177/011542650502000152.

Abstract. Modern advances in nutritional therapies have led to the specific use of arginine supplementation for protein synthesis, cell signaling through the production of nitric oxide, and cell proliferation through its metabolism to ornithine and to polyamines. Arginine is classified as a nonessential amino acid that becomes a conditionally essential substrate in stressed adults. Arginine has been shown to enhance wound strength and collagen deposition in artificial incisional wounds in rodents and humans. A role for dietary intervention in the form of arginine supplementation has been proposed to normalize or enhance wound healing in humans. Although this hypothesis is frequently discussed, the therapeutic effect of arginine supplementation on chronic wound healing in humans is still undetermined and requires further objective evidence. Well-designed clinical trials are required to determine whether arginine supplementation is effective in enhancing healing of acute and chronic wounds in humans and how much arginine is recommended to meet metabolic needs during the phases of wound healing.

Popovic PJ, Zeh HJ 3rd, Ochoa JB. Arginine and immunity. J Nutr. 2007 Jun;137(6 Suppl 2):1681S-1686S. doi: 10.1093/jn/137.6.1681S.

Abstract. For many years, dietary arginine supplementation, often combined with other substances, has been used as a mechanism to boost the immune system. Considerable controversy, however, exists as to the benefits and indications of dietary arginine due in part to a poor understanding of the role played by this amino acid in maintaining immune function. Emerging knowledge promises to clear this controversy and allow for arginine's safe use. In myeloid cells, arginine is mainly metabolized either by inducible nitric oxide (NO) synthases (iNOS) or by arginase 1, enzymes that are stimulated by T helper 1 or 2 cytokines, respectively. Thus, activation of iNOS or arginase (or both) reflects the type of inflammatory response in a specific disease process. Myeloid suppressor cells (MSC) expressing arginase have been described in trauma (in both mice and humans), intra-abdominal sepsis, certain infections, and prominently, cancer. Myeloid cells expressing arginase have been shown to accumulate in patients with cancer. Arginase 1 expression is also detected in mononuclear cells after trauma or surgery. MSC efficiently deplete arginine and generate ornithine. Through arginine depletion, MSC may control NO production and regulate other arginine-dependent biological processes. Low circulating arginine has been documented in trauma and cancer, suggesting that MSC may exert a systemic effect and cause a state of arginine deficiency. Simultaneously, T lymphocytes depend on arginine for proliferation, zeta-chain peptide and T-cell receptor complex expression, and the development of memory. T-cells cocultured with MSC exhibit the molecular and functional effects associated with arginine deficiency. Not surprisingly, T-cell abnormalities, including decreased proliferation and loss of the zeta-chain, are observed in cancer and after trauma.

McNeal CJ, Meininger CJ, Reddy D, Wilborn CD, Wu G. Safety and Effectiveness of Arginine in Adults. J Nutr. 2016 Dec;146(12):2587S-2593S. doi: 10.3945/jn.116.234740. 

Abstract. l-Arginine (Arg) appears to have a beneficial effect on the regulation of nutrient metabolism to enhance lean tissue deposition and on insulin resistance in humans. The observed safe level for oral administration of Arg is ∼20 g/d, but higher levels have been tested in short-term studies without serious adverse effects; however, more data are needed in both animal models and humans to fully evaluate safety as well as efficacy. The primary objective of this review is to summarize the current knowledge of the safety, pharmacokinetics, and effectiveness of oral Arg in adults. Arg supplementation has been used safely in vulnerable populations, such as pregnant women, preterm infants, and individuals with cystic fibrosis. Several recent studies have shown beneficial effects of Arg in individuals with obesity, insulin resistance, and diabetes. Collectively, the data suggest that Arg supplementation is a safe and generally well-tolerated nutriceutical that may improve metabolic profiles in humans. © 2016 American Society for Nutrition.

Tapiero H, Mathé G, Couvreur P, Tew KD. I. Arginine. Biomed Pharmacother. 2002 Nov;56(9):439-45. doi: 10.1016/s0753-3322(02)00284-6. 

Abstract. L-Arginine (Arg) is classified as an essential amino acid for birds, carnivores and young mammals and a conditionally essential amino acid for adults. It is converted by arginase to L-ornithine, a precursor of polyamines and urea, which is important in the urea cycle. Arg serves as a precursor for creatine, which plays an essential role in the energy metabolism of muscle, nerve and testis and accounts for Arg catabolism and for the synthesis of agmatine and proteins. Via its ability to increase growth hormone secretion it influences immune function. Depending on nutritional status and developmental stage, normal plasma Arg concentrations in humans and animals range from 95 to 250 micromol/l. Systemic or oral Arg administration has been shown to improve cardiovascular function and reduce myocardial ischemia in coronary artery disease patients. It reduces blood pressure and renal vascular resistance in essential hypertensive patients with normal or insufficient renal function. Although Arg plasma concentrations are not altered in hypercholesterolemic individuals, oral or intravenous Arg administration can reverse endothelial dysfunction in hypercholesterolemic patients and in cigarette smokers. The main importance of Arg is attributed to its role as a precursor for the synthesis of nitric oxide (NO), a free radical molecule that is synthesized in all mammalian cells from L-Arg by NO synthase (NOS). NO appears to be a major form of the endothelium-derived relaxing factor (EDRF). NO and EDRF share similar chemical and pharmacological properties and are derived from the oxidation of a terminal guanidine group of L-Arg. Various mechanisms have been implicated in the defect in vascular relaxation. These include, increased diffusional barrier for NO, L-Arg depletion, altered levels of reactive oxygen, inactivation of NO by superoxide anions (O2-). The independent reactions of O2-, NO and their reaction yielding peroxynitrite are critical in the initiation and maintenance of the atherosclerotic state and contribute to the defect in vasorelaxation. NO also plays a role as a neurotransmitter, mediator of immune response and as signaling molecule. The NO synthesized by iNOS in macrophages contributes to their cytotoxic activity against tumor cells, bacteria and protozoa. Our aim here is to review on some amino acids with high functional priority such as Arg and to define their effective activity in human health and pathologies.

Suzuki T, Morita M, Hayashi T, Kamimura A. The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males. Biosci Biotechnol Biochem. 2017 Feb;81(2):372-375. doi: 10.1080/09168451.2016.1230007. 

Abstract. We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.

Luiking YC, Poeze M, Ramsay G, Deutz NE. The role of arginine in infection and sepsis. JPEN J Parenter Enteral Nutr. 2005 Jan-Feb;29(1 Suppl):S70-4. doi: 10.1177/01486071050290S1S70.

Abstract. Sepsis is a systemic response to an infection, with high morbidity and mortality rates. Metabolic changes during infection and sepsis could be related to changes in metabolism of the amino acid L-arginine. In sepsis, protein breakdown is increased, which is a key process to maintain arginine delivery because both endogenous de novo arginine production from citrulline and food intake are reduced. Arginine catabolism, on the other hand, is markedly increased by enhanced use of arginine via the arginase and nitric oxide pathways. As a result, lowered plasma arginine levels are usually found. Arginine may therefore be considered as an essential amino acid in sepsis, and supplementation could be beneficial in sepsis by improving microcirculation and protein anabolism. L-Arginine supplementation in a hyperdynamic pig model of sepsis prohibits the increase in pulmonary arterial blood pressure, improves muscle and liver protein metabolism, and restores the intestinal motility pattern. Arguments raised against arginine supplementation are mainly pointed at stimulating nitric oxide (NO) production, with concerns about toxicity of increased NO and hemodynamic instability with refractory hypotension. NO synthase inhibition, however, increased mortality. Arginine supplementation in septic patients has transient effects on hemodynamics when supplied as a bolus but seems without hemodynamic side effects when supplied continuously. In conclusion, arginine could have an essential role in infection and sepsis.

References___________________________________________________________________

(1) Wijnands KA, Castermans TM, Hommen MP, Meesters DM, Poeze M. Arginine and citrulline and the immune response in sepsis. Nutrients. 2015 Feb 18;7(3):1426-63. doi: 10.3390/nu7031426. 

(2) Luiking YC, Ten Have GA, Wolfe RR, Deutz NE. Arginine de novo and nitric oxide production in disease states. Am J Physiol Endocrinol Metab. 2012 Nov 15;303(10):E1177-89. doi: 10.1152/ajpendo.00284.2012.

Arginine is an alpha-amino acid, one of the 8 essential amino acids in the human body. It is involved in protein synthesis and helps hormones maintain a healthy body and skin, and is involved in biological processes of the immune, cardiovascular and growth systems.

L-arginine is the L-isomer of arginine and is an L-alpha-amino acid.

Synthesised, it appears as a white crystalline powder that is easily soluble in water, slightly soluble in ethanol, insoluble in ether, darkens in colour at 230°C, disintegrates at 244°C.

What it is used for and where

It is an α-amino acid.

Amino acids play a key metabolic function in the human body and are constituents of proteins. 

As food additives they perform different functions: preservatives, flavour enhancers, food supplements and more.

Amino acids together with their salts are used in cosmetics as conditioning agents for both hair and skin (e.g. as moisturisers and other similar functions). Moisturisers are different in nature: the best are the natural ones that exploit the mechanism of integration between the ingredient and the skin by moisturising the horny hydrolipid film, i.e. the thin protective layer that covers the epidermis protecting it from harmful external microbes, keeping the skin moisturised and supple and its pH or acidity value between 4 and 6.  Then there are the occlusive moisturisers, usually derived from petroleum (Paraffinum, Paraffinum liquidum and others), but also triglycerides, lanolin oil, natural or synthetic waxes, fatty acid esters and others that create an artificial occlusive layer on the stratum corneum of the skin with the advantage of accelerating the protective process but with the disadvantage of preventing the skin's natural transpiration.

α-amino acids that have similar physical structures undergo similar changes with regard to solubility in water/ethanol mixtures, and technologies to separate α-amino acids from industrial residues, which may not even be innocuous, are constantly being improved. However, many data on the solubility in water-ethanol and ethanol of some α-amino acids are contradictory or even lacking, and the effects of ethanol on the solubility of amino acids may be different. Overall, the scientific literature considers that α-amino acids do not pose significant problems for human health when taken orally, except in people with certain genetic diseases.

Food safety: amino acid α generally considered safe.

Cosmetic safety: amino acid α generally considered safe when formulated to be non-irritant.

Medical

In ageing, growth hormones tend to work less and this results in less flexible and thinner skin. One remedy is injections of appropriate hormones, but this method is obviously quite different from what nature intended. An alternative and more natural remedy is to take a 'releaser', i.e. a component that has the function of stimulating the growth hormone: Arginine.

With regard to the cardiovascular system, this study highlights recent advances in the biological and clinical role of arginine, concluding that arginine may exert cardioprotective effects (1), and other studies point to its role in restoring endothelial function in atherosclerotic patients, in whom there are elevated levels of asymmetric dimethylarginine, thus the results confirm L-arginine as a potential therapy for cardiovascular disorders (2). Its use in hospitalised septic and critical patients has been controversial although the use of arginine has been shown to help a variety of critically ill patients (3).

In dental care many studies have focused on the effectiveness of arginine included in dental care products (toothpastes, mouthwashes) in preventing the development of new caries and the progression of existing caries, but the conclusions are mixed. Some believe that there is currently insufficient evidence to support a caries-preventive effect of the inclusion of arginine in these products (4), while other studies believe, albeit with very few well-conducted randomised controlled trials, that 1.5 per cent arginine and 1,450 ppm fluoride is effective in inactivating root caries lesions (5).

Arginine has proven to be of great help in wound healing and skin repair. 

Shockwave therapy or oral L-arginine therapy improved erectile dysfunction (6).

Cosmetics

Studies on arginine in the medical sector concerning its use as a tissue regenerator have led personal care cosmetics companies to include arginine in many creams and various preparations with the function of tissue regeneration, rejuvenation, elasticity and skin defence (7).

Safety

Arginine is generally considered to be a safe component in the scientific literature, however this recent study by researchers at the University of São Paulo, Brazil warns of the effects that may affect blood pressure and others caused by antiseptic mouthwashes containing chlorhexidine on L-arginine supplementation (8).

For more information:

Arginine studies

Typical commercial product characteristics L-arginine

Appearance	White powder
pH	10.5~12.0
Boiling Point	367.6±52.0°C at 760 mmHg
Melting Point	222°C
Flash Point	176.1±30.7°C
Vapor Pressure	0.0±1.8 mmHg at 25°C
Refraction Index	1.601
PSA	125.22000
LogP	-1.79
Water Solubility	148.7 g/L
Loss on drying	≤0.5%
Residue on ignition	≤0.1%
Chloride	≤0.02%
Sulfate	≤0.02%
Other amino acids	≤0.4%
Ammonium	≤0.02%
Arsenic	≤1ppm
Iron	≤10ppm
Heavy metals	≤10ppm
Chemical Risk

• Molecular Formula    C₆H₁₄N₄O₂
• Linear Formula     H₂NC(=NH)NH(CH₂)₃CH(NH₂)CO₂H
• Peso molecolare   174.204 g/mol
• Exact Mass    174.111679
• CAS   74-79-3  
• EC Number    200-811-1
• UNIII    94ZLA3W45F
• DSSTox Substance ID  DTXSID6041056
• IUPAC  (2S)-2-amino-5-(diaminomethylideneamino)pentanoic acid
• InChl=1S/C6H14N4O2/c7-4(5(11)12)2-1-3-10-6(8)9/h4H,1-3,7H2,(H,11,12)(H4,8,9,10)/t4-/m0/s1
• InChl Key      ODKSFYDXXFIFQN-BYPYZUCNSA-N
• SMILES   C(CC(C(=O)O)N)CN=C(N)N
• MDL number  MFCD00002635
• PubChem Substance ID    24278014
• Beilstein    1725413
• eCl@ss    32160406
• ChEBI  16467
• RTECS  CF1934200
• NCI    C62008
• FEMA    3819
• JECFA    1438    
• RXCUI    1091
• FEMA     3819

Price

100 g          $72.80

1 kg            $550.00

Synonyms: 

• L-(+)-Arginine
• L-arginine
• L(+)-Arginine
• L-Arginin
• L-Arg
• Polyarginine
• (S)-2-Amino-5-guanidinopentanoic acid
• Argamine
• H-Arg-OH
• Argivene
• (L)-Arginine
• Detoxargin

References________________________________________________________________

(1) Mangoni AA, Rodionov RN, McEvoy M, Zinellu A, Carru C, Sotgia S. New horizons in arginine metabolism, ageing and chronic disease states. Age Ageing. 2019 Nov 1;48(6):776-782. doi: 10.1093/ageing/afz083. 

(2) Gornik HL, Creager MA. Arginine and endothelial and vascular health. J Nutr. 2004 Oct;134(10 Suppl):2880S-2887S; discussion 2895S. doi: 10.1093/jn/134.10.2880S. 

(3) Rosenthal MD, Carrott PW, Patel J, Kiraly L, Martindale RG. Parenteral or Enteral Arginine Supplementation Safety and Efficacy. J Nutr. 2016 Dec;146(12):2594S-2600S. doi: 10.3945/jn.115.228544. 

(4) Ástvaldsdóttir Á, Naimi-Akbar A, Davidson T, Brolund A, Lintamo L, Attergren Granath A, Tranæus S, Östlund P. Arginine and Caries Prevention: A Systematic Review. Caries Res. 2016;50(4):383-93. doi: 10.1159/000446249.

(5) Wierichs RJ, Meyer-Lueckel H. Systematic review on noninvasive treatment of root caries lesions. J Dent Res. 2015 Feb;94(2):261-71. doi: 10.1177/0022034514557330. 

(6) Gallo L, Pecoraro S, Sarnacchiaro P. Adjuvant daily therapy with L-arginine 2,500 mg and tadalafil 5 mg increases efficacy and duration of benefits of low-intensity extracorporeal shock wave therapy for erectile dysfunction: A prospective, randomized, single-blinded study with 1-year follow-up. Investig Clin Urol. 2022 Jan;63(1):83-91. doi: 10.4111/icu.20210317.

(7) Kocic H, Arsic I, Stankovic M, Tiodorovic D, Ciric V, Kocic G. Proliferative, anti-apoptotic and immune-enhancing effects of L-arginine in culture of skin fibroblasts. J Biol Regul Homeost Agents. 2017 Jul-Sep;31(3):667-672.

(8) Batista RIM, Nogueira RC, Ferreira GC, Oliveira-Paula GH, Damacena-Angelis C, Pinheiro LC, Tanus-Santos JE. Antiseptic mouthwash inhibits antihypertensive and vascular protective effects of L-arginine. Eur J Pharmacol. 2021 Sep 15;907:174314. doi: 10.1016/j.ejphar.2021.174314.