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The special arginine: focus on its effects on health and applications in diseases

Introduction: arginine and metabolism

Arginine is one of the many amino acids that the body needs to function properly. Like other amino acids, L-arginine plays a role in building proteins. The body uses protein to help build muscle and rebuild damaged tissue. Consequently, the researchers investigated the effectiveness of L-arginine in treating severe wounds and tissue losses in severe illness. But in addition to building protein, the body uses L-arginine to make nitric oxide in the blood. Nitric oxide works by dilating blood vessels, allowing more blood to flow. This is why arginine supplemntation was believed to enhance sexual performances by conditioning the penis blood flow. Under normal circumstances, our body naturally produces L-arginine; this is why it is considered a semi-essential amino acid.

Arginine is an intermediate in the urea cycle, a metabolic pathway in the liver that processes nitrogen intermediates to produce urea, the final waste product of protein metabolism. In fact, urea is not as toxic as ammonia (which is the real end product of nitrogen metabolism) and is not sensitive to the body’s pH. Ammonia, on the other hand, can become ammonium ion (NH4 +) and as such remains trapped in the tissues, becoming toxic, especially for brain cells. This is the case of liver cirrhosis and various hereditary syndromes due to enzymatic defects in the urea cycle. Among these are citrullinemia, decifit of ornithine carbamyl transferase (OCT) and argininemia. The latter lacks the enzyme arginase, the last of the aforementioned pathway, so that blood arginine rises to levels that are not suitable for health.

Actions of L-arginine on health and pathologies

L-arginine has multiple molecular actions: it becomes part of proteins, produces nitric oxide and is a starting molecule for the synthesis of creatine and urea. These effects give L-arginine a number of potential benefits ranging from heart health and chest pain to helping build muscle, repair wounds and improve male fertility. Some supplements used in the student field may contain arginine among the constituents, and there is nothing strange that they work in improving attention or memory during intellectual effort. Although there are many claims about the benefits of L-arginine, not all of them are supported by scientific research studies.

Below are some examples of confirmed L-arginine benefits and uses:

  • treatment of erectile dysfunction due to circulatory defects
  • correction of hereditary defects in urea synthesis
  • treatment of heart disease and hypertension
  • blood sugar control in people with diabetes
  • gastroenteritis in premature infants.

Additionally, arginine may have the potential to help with other issues. Further research is underway to further evaluate L-arginine’s potential to relieve anxiety, improve intellectual performance, accelerate wound and burn healing and improve kidney function in people with congestive heart failure. There are some literature studies available that taking arginine supplements can accelerate wound healing, similar to taking glutamine supplements. One category of patients that could benefit from these effects would be diabetic patients with cutaneous dystrophies and diabetic arterial disease sores.

In this case, arginine could enhance the production of nitric oxide, improve blood flow and accelerate the repair of lesions. One condition that can be positively affected by the administration of arginine is Crohn’s disease, where it appears to promote the acceleration of intestinal mucosal healing in a similar way to how glutamine does. Arginine is also anti-inflammatory of the mucous membranes, it helps their reconstruction both through protein synthesis and with the production of nitric oxide. This mediator can locally dilate the capillaries and facilitate the blood supply to the damaged mucosa.

Other clinical indications for arginine

L-arginine is used to treat and prevent metabolic stroke in mitochondrial diseases, with recent long-term data suggesting clinical benefit when administered acutely to pediatric Leigh syndrome patients for metabolic stroke. In addition, it may improve survival and reduced debility when compared to the natural history of mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS). The arginine precursor L-citrulline leads to even greater nitric oxide synthesis, and is empirically co-administered in individuals with recurrent stroke-like episodes in these clinical conditions. A potential more effective combination seems arginine plus a lipophilic mitochondrial antioxidant like vitamin E or lipoic acid.

Arginine may enter the composition of fertility enhancers, combined with some B vitamins, coenzyme Q, zinc, selenium and vitamin E. Compared to other nutrients like taurine, vitamin D and Astragalus for which there is no unanimous consensus for effectiveness, arginine plus one of the aforementioned molecules may result effective in enhancing spermatogenesis. Finally, there is a role for arginine in oncology. Arginine may potentially derive from other aminoacids in our body; yet cancer cells seem “addicted” to arginine presence. This is why there have been attempts to cut arginine fueling to cancer cells with enzymes (e.g. arginase and arginine deaminase or ADI), similarly as it was done with asparaginase to cure leukemias.

However, here is a paradoxycal glitch: arginine may result helpful in enhancing immune function. It is proved that arginine supplementation in animals or human beings with cancers, help the immune system with their immune surveillance and better ability to fight tumors themselves. This is whis arginine restriction was not deemd optimal to cut-off arginine fueling to cancer cells. Rather, the enzymatic approach may result more specific to cancer cells than lymphocytes since ADI has been ingeneered to be invisible to immune recognition (ADI-PEG20). And isoform specific expression amongst immune cells and cancer cellss may help differentiate advantages over drawbacks.

Arginine as a food supplement

L-arginine is part of a regular diet. Red meats, fish, dairy products and eggs contain low amounts of L-arginine which help the body replenish its necessary resources, while legumes on average are richer. Normally a balanced diet together with the amount produced by our body, keep the need for arginine constant. The best natural source of L-arginine is high protein food. On average, animal proteins and dairy products can be the primary source of L-arginine. For vegetarians, foods with a lot of arginine include chickpeas, beans, lentils, peanuts, pumpkin seeds and soy. Occasionally, a person’s need for L-arginine can outweigh the body’s ability to produce or consume it naturally. This is often true of the elderly or people with certain medical conditions, for example kidney failure, heart disease and pressure sores. In these cases, L-arginine may be prescribed as an oral supplement.

Taking arginine beyond diet

Supplements with a high arginine content exist and usually also contain creatine, glutamine, taurine and other molecules that support cellular metabolism. They are popular among bodybuilders to improve muscle performance, relieve fatigue and accelerate post-workout recovery. They also find clinical use as cellular protectants or enhancers in the post-surgery, extensive burns, convalescence and also, more recently, myopathies on a genetic basis such as Duchenne muscular dystrophy. Several potential health conditions can benefit from increased L-arginine intake. Although L-arginine is considered safe in moderate doses, too much arginine can have serious side effects.

For example, if you have true bronchial asthma, taking arginine can trigger an asthmatic attack. In the case of idiopathic hypotension (constitutional low blood pressure), taking arginine can cause fainting due to a potential further lowering of blood pressure. It is important to understand how the supplement can interact with the body and other medications before taking it. Those who have liver and kidney problems should discuss with their doctor the possibility of using arginine as a supplement. In fact, it increases the ammonia and urea nitrogen load, being able to condition the progression of chronic renal failure or the state of health of those on dialysis.

  • edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

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Scientific references

Arribas-López E et al. Nutrients. 2021 ; 13(8):2498.

Barcelos I et al. Curr Opin Pediatr. 2020; 32(6):707. 

Rashid J et al. Paediatr Drugs. 2020; 22(3):279-293.

Nazarian B et al. Compl Ther Med. 2019; 47:102226.

McNeal CJ et al. Amino Acids. 2018; 50(9):1215-29.

Cereda E et al. J Nutr Health Aging. 2017; 21(6):655.

Iqbal F. Pak J Pharm Sci. 2015 Nov; 28(6):2207-11.

Martinelli D et al. Orphanet J Rare Dis. 2015; 10:29.

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Dott. Gianfrancesco Cormaci

Medico Chirurgo, Specialista; PhD. a CoFood s.r.l.
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di due brevetti sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento enzimaticamente neutralizzata (owner of patents concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (Leader of the R&D for the partnership CoFood s.r.l.) - Autore di articoli su informazione medica e salute sul sito www.medicomunicare.it (Medical/health information on website) - Autore di corsi ECM FAD pubblicizzati sul sito www.salutesicilia.it
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