In by Raphikammer


Arginine was first isolated in 1895 from animal horn. It is

considered a nonessential amino acid under physiological

conditions; however, it may be classified as semi-essential

(or conditioned) in newborns, young children, or other

circumstances characterized by accelerated tissue growth

(e.g., infection, sepsis, trauma) when its production may

be too slow and not sufficient to meet the requirements

(1). Arginine is physiologically active in the L-form (L-Arg)

and participates in protein synthesis in cells and tissues.

It is essential for the synthesis of urea, creatine, creatinine,

and pyrimidine bases. It also strongly influences hormonal

release and has an important role in vascular dynamics,

participating in the synthesis of nitric oxide (NO).


Dietary arginine is particularly abundant in wheat

germ and flour, buckwheat, oatmeal, dairy products

(cottage cheese, ricotta cheese, nonfat dry milk, skimmed

yogurt), chocolate, beef (roasts, steaks), pork, nuts (coconut,

pecans, walnuts, almonds, hazel nuts, peanuts),

seeds (pumpkin, sesame, sunflower), poultry (chicken,

turkey), wild game (pheasant, quail), seafood (halibut,

lobster, salmon, shrimp, snails, tuna), chick peas, and

soybeans (2).

L-Arg, delivered via the gastrointestinal tract, is absorbed

in the jejunum and ileum of the small intestine. A

specific amino acid transport system facilitates this process

and participates also in the transport of the other

basic amino acids, L-lysine and L-histidine. About 60% of

the absorbed L-Arg is metabolized by the gastrointestinal

enterocytes, and only 40% remains intact reaching the

systemic circulation.

An insufficient arginine intake produces symptoms

of muscle weakness, similar to muscular dystrophy (3).

Arginine deficiency impairs insulin secretion, glucose production,

and liver lipid metabolism (4). Conditional deficiencies

of arginine or ornithine are associated with the

presence of excessive ammonia in the blood, excessive

lysine, rapid growth, pregnancy, trauma, or protein deficiency

and malnutrition. Arginine deficiency is also associated

with rash, hair loss and hair breakage, poor wound

healing, constipation, fatty liver, hepatic cirrhosis, and

hepatic coma (4).

Depending on nutritional status and developmental

stage, normal plasma arginine concentrations in humans

and animals range from 95 to 250 mol/L. Toxicity and

symptoms of high intake are rare, but symptoms of massive

dosages may include thickening and coarsening of

the skin, muscle weakness, diarrhea, and nausea.

The proximal renal tubule accounts for much of the

endogenous production of L-Arg from L-citrulline. In the

tubule, arginine reacts via the Krebs cycle with the toxic

ammonia formed from nitrogen metabolism, producing

the nontoxic and readily excretable urea (Fig. 1) (5). If this

mechanism does not efficiently handle metabolic byproducts

and if L-Arg intake is insufficient, ammonia rapidly

accumulates, resulting in hyperammonemia.

L-Arg undergoes different metabolic fates. NO,

L-citrulline, L-ornithine, L-proline, L-glutamate, and

polyamine-like putrescine are formed from L-Arg. Moreover,

the high-energy compound NO-creatinine phosphate,

which is essential for sustained skeletal muscle contraction,

is also formed from L-Arg (Fig. 2).

L-Arg, its precursors, and its metabolites are deeply

involved in the interaction of different metabolic pathways

and interorgan signaling. The amino acid influences

the internal environment in different ways: disposal

of protein metabolic waste; muscle metabolism; vascular

regulation; immune system function; healing and repair

of tissue; formation of collagen; and building of new bone

and tendons.

A leading role for arginine has been shown in the

endocrine system, vasculature, and immune response.

  • CO2 + NH4
  • +
  • NH2
  • NH2
  • C=O
  • 2ATP
  • 2ADP + Piz
  • NH4
  • +-GROUPS
  • ATP
  • AMP + Ppi + H2O
  • Figure 1 L-Arginine and Krebs cycle in the renal tubule.
  • 21
  • 22 Maccario et al.
  • Nitric Oxide
  • Nitric Oxide
  • Admatine
  • Aldehyde Agmatine
  • Agmatinase
  • Polyamines
  • Ornithine
  • Proline
  • Arginine
  • Group
  • Guanidine
  • HN
  • C NH
  • Protein
  • synthesis
  • Glycine
  • Guanidinoacetate
  • Pyrroline-5-carboxylate
  • Glutamyl-γ-′semialdehyde
  • Urea cycle Glutamine Glutamate
  • Creatine
  • Urea
  • Urea
  • NOS
  • NOS
  • Ca2+
  • ADC
  • ADC
  • OAT
  • Arginase-I
  • P-5-C
  • dehydrogenase
  • P-5-C
  • reductase
  • A-GAT
  • GMT
  • Glu synthase
  • DAO
  • NH3

Figure 2 L-Arginine metabolites. Abbreviations: ADC, arginine decarboxylase;

A:GAT, arginine:glycine amidinotransferase; DAO, diamine oxidase; Glu

synthase, glutamine synthase; GMT, guanidinoacetate-N-methyltransferase;

NOS, nitric oxide synthase; OAT, ornithine aminotransferase; P-5-C dehydrogenase,

pyrroline-5-carboxylate dehydrogenase; P-5-C reductase, pyrroline-

5-carboxylate reductase.


Endocrine Actions

L-Arg functions as a secretagogue of a number of important

hormones at the pituitary, pancreas, and adrenal levels.

The effects on growth hormone (GH), prolactin (PRL),

adrenocorticotropic hormone (ACTH), and insulin secretion

will be discussed in detail.

GH Secretion

Among the various factors modulating somatotropin

function, arginine is well known to play a primary stimulatory

influence. Arginine has been shown to increase

basal GH levels and to enhance the GH responsiveness

to growth hormone releasing hormone (GHRH) both in

animals and in humans throughout their life span (6–9);

its GH-stimulating activity occurs after both IV and oral

administration and is dose dependent; 0.1 and 0.5 g/kg

are the minimal and the maximal IV effective doses, respectively.

Moreover, a low orally administered arginine

dose has been shown to be as effective as a high IV dose

in enhancing the GH response to GHRH both in children

and in elderly subjects (10,11).

Arginine, directly or indirectly via NO, is likely

to act by inhibiting hypothalamic somatostatin (SS) release.

It has been shown that arginine—but not isosorbidedinitrate

and molsidomine, two NO donors—stimulates

GH secretion (12,13), suggesting that it does not exert its

effects through the generation of NO. Moreover, arginine

does not modify either basal or GHRH-induced GH increase

from rat anterior pituitary (14). On the contrary, it

potentiates the GH response to the maximal GHRH dose

in humans. Arginine can elicit a response even when the

response has been previously inhibited by a GHRH administration,

which induces an SS-mediated negative GH

auto feedback (7,8,15). Moreover, arginine counteracts the

GH-inhibiting effect of neuroactive substances that act by

stimulating SS release; it does not modify the GH-releasing

activity of stimuli acting via SS reduction (8). Again, in favor

of an SS-mediated mechanism is also the evidence

that ornithine, the active form of arginine, is unable to

modify plasma GHRH levels in humans (16). Moreover,

arginine fails to potentiate the increased spontaneous nocturnal

GH secretion, which is assumed to reflect circadian

SS hyposecretion and GHRH hypersecretion, respectively

(8). Arginine does not influence the strong GH-releasing

action of ghrelin, the natural ligand of GH secretagogue

receptors, which is supposed to act as a functional antagonist

of SS at both the pituitary and the hypothalamic levels


The GH-releasing activity of arginine is sex dependent

but not age dependent, being higher in females than

in males but similar in children, young, and elderly subjects

(8,19–23). Moreover, it has been clearly demonstrated

that arginine totally restores the low somatotroph responsiveness

to GHRH in aging, when a somatostatin ergic hyperactivity

is likely to occur (20–23). This evidence clearly

indicates that the maximal secretory capacity of somatotropic

cells does not vary with age and that the age related

decrease in GH secretion is due to a hypothalamic

impairment (20–23). This also points out the possible

clinical usefulness of this substance to rejuvenate the

GH/insulin-like growth factor-I (IGF-I) axis in aging. In

fact, the reduced function of the GH/IGF-I axis in aging

may account for the changes in body composition, structure,

and function. In agreement with this assumption, it

has been reported by some, but not all, authors that elderly

subjects could benefit from treatment with rhGH

to restore IGF-I levels within the young range (21,24). As

it has been demonstrated that the GH releasable pool in

the aged pituitary is basically preserved and that the age related

decline in GH secretion mostly reflects hypothalamic

dysfunction (21,23), the most appropriate, that is,

“physiological,” approach to restore somatotroph function

in aging would be a treatment with neuroactive substances

endowed with GH-releasing action. Among these

GH secretagogues, arginine received considerable attention.

In fact, the coadministration of arginine (even at

low oral doses) with GHRH (up to 15 days) enhanced

the GH responsiveness to the neurohormone in normal

aged subjects (11). However, the efficacy of long-term

treatment with oral arginine to restore the function of the

GH/IGF-I axis in aging has never been shown in elderly


Following the evidence that GHRH combined with

arginine becomes the most potent and reproducible stimulus

to diagnose GH deficiency throughout the lifespan

(25), GHRH + arginine is, at present, one of the two gold

standard tests for the diagnosis of GH deficiency (25,26).

In fact, the GH response to a GHRH + arginine test is

approximately threefold higher than the response to classical

tests and does not vary significantly with age (25,26).

Because of its good tolerability and its preserved effect in

aging, the GHRH + arginine test is currently considered

to be the best alternative choice to the insulin-induced

tolerance test (ITT) for the diagnosis of GH deficiency

throughout the lifespan (25).

L-Arginine 23

PRL Secretion

Among the endocrine actions of arginine, its PRL releasing

effect has been shown both in animals and in

humans after IV but not after oral administration (10,27).

The PRL response to arginine is markedly lower than

the response to the classical PRL secretagogues, such

as dopaminergic antagonists or thyrotropin-releasing

hormone (TRH) (6) but higher than that observed after

secretion of GH and other modulators of lactotrope

function (17).

The mechanisms underlying the stimulatory effect

of arginine on PRL secretion are largely unknown, but

there is evidence that this effect is not mediated by galanin,

a neuropeptide with PRL-releasing effect. In fact, galanin

has been shown to potentiate PRL response to arginine,

suggesting different mechanisms of action for the two substances


ACTH Secretion

Although some excitatory amino acids and their agonists

have been demonstrated to differently modulate

corticotropin-releasing hormone and arginine vasopressin

release in vitro and influence both sympathoadrenal and

hypothalamo-pituitary-adrenal (HPA) responses to hypoglycemia

in animals (29,30), little is known about arginine

influences on HPA axis in humans. Many studies have

shown that mainly food ingestion influences spontaneous

and stimulated ACTH/cortisol secretion in normal subjects

and that central 1-adrenergic-mediated mechanisms

are probably involved (31). In humans free fatty acids inhibit

spontaneous ACTH and cortisol secretion, but no

data exist regarding the effect of each nutrient component

on HPA function. Previous studies demonstrated that

arginine is unable to exert an ACTH-stimulatory effect in

humans via generation of NO (12) and our unpublished

preliminary data failed to demonstrate a significant effect

of arginine (30 g IV) on either ACTH or cortisol secretion

in normal subjects.

Insulin Secretion

Arginine is one of the most effective known insulin secretagogue

and it may be used with glucose potentiation

to determine a patient’s capacity to secrete insulin (32).

Arginine acts synergistically with glucose, and to a much

lesser extent with serum fatty acids, in stimulating insulin

release. A synergistic effect of arginine and glucose on insulin

secretion has been shown in humans (33,34), and the

combined administration of these two stimuli has been

studied in an attempt to test -cell secretory capacity in

diabetic patients (35).

A protein meal leads to a rapid increase in both

plasma insulin and glucagon levels (36). Administration

of arginine has a similar effect. An arginine transport system

is present in the -cell plasma membrane (37). When

arginine enters the cell, it causes ionic changes that depolarize

the cell and trigger Ca2+ uptake and exocytosis

of insulin-containing granules.

Several mechanisms for arginine-induced -cell

stimulation have been proposed. These include the

metabolism of L-Arg leading to the formation of ATP

(38,39), the generation of NO (40,41), and the direct depolarization

of the plasma membrane potential due to the

accumulation of the cationic amino acid (42–44).

A sustained Ca2+ influx is directly related to insulin

secretion following arginine uptake by cells. The

arginine-induced increase in Ca2+ concentration is inhibited

by the activation of ATP-sensitive potassium (K-ATP)

channels with diazoxide and seems dependent on the nutritional

status. These observations suggest that the K-ATP

channels, when fully open, act to prevent membrane depolarization

caused by arginine. The presence of a nutrient,

such as glucose, produces sufficient closure of K-ATP

channels to allow arginine-induced membrane depolarization

and activation of the voltage-activated Ca2+ channels


Nonendocrine Actions

Cardiovascular System

Increasing interest has been recently focused on NO. This

mediator, which is synthesized from L-Arg (45) by nitric

oxide synthases (NOS) (46), is a potent vasodilator

(47) and inhibitor of platelet adhesion and aggregation

(48). Three isoforms of NOS are described: neuronal NOS

(nNOS—NOS-1), inducible NOS (iNOS—NOS-2), and endothelial

NOS (eNOS—NOS-3). NOS-1 and NOS-3 are

expressed constitutively and they produce NO at low

rates (49). NOS-3 is responsible for a consistent vasodilator

tone and, although constitutive, can be regulated by

endothelial shear stress (50) and substances such as acetylcholine,

histamine, serotonin, thrombin, bradykinin, and

catecholamines. Calcium is required for NOS-3 activation

(51).NO production is mainly dependent on the availability

of arginine and NOS is responsible for the biochemical

conversion of L-Arg to NO and citrulline in the presence

of cofactors such as reduced nicotinamide adenine dinucleotide

phosphate (NADPH), tetrahydrobiopterin (BH4),

flavin mononucleotide, and flavin adenine nucleotide. Reduced production,

leading to vasoconstriction and increases

in adhesion molecule expression, platelet adhesion

and aggregation, and smooth muscle cell proliferation has

been demonstrated in atherosclerosis, diabetes mellitus,

and hypertension (52–54)—conditions known to be associated

with an increased mortality because of cardiovascular

disease. Taken together, these observations lead to the

concept that interventions designed to increase NO production

by supplemental L-Arg might have a therapeutic

value in the treatment and prevention of the endothelial

alterations of these diseases. Besides several actions exerted

mainly through NO production, arginine also has a

number of NO-independent properties, such as the ability

to regulate blood and cellular pH, and the effect on the

depolarization of endothelial cell membranes.

The daily consumption of arginine is normally about

5 g/day. Arginine supplementation is able to increase NO

production, although the Km for L-Arg is 2.9 mol and the

intracellular concentration of arginine is 0.8 to 2.0 mmol.

To explain this biochemical discrepancy, named “arginine

paradox,” there are theories that include low arginine levels

in some diseases (e.g., hypertension, diabetes mellitus,

and hypercholesterolemia), and/or the presence of enzymatic

inhibitors (55), and/or the activity of the enzyme

arginase (which converts arginine to ornithine and urea,

leading to low levels of arginine).

Recently attention has been given to the methylated

forms of L-Arg, generated by the proteolysis of

24 Maccario et al.

methylated proteins; they are represented by asymmetric

dimethylarginine (ADMA) and two symmetric dimethylated

derivatives: symmetric dimethylarginine (SDMA)

and monomethylarginine (MMA) (56). Only ADMA and

MMA, but not SDMA, exert inhibitory effects on NOS-3

activity (57). For this reason, ADMA is now recognized as

a new emerging cardiovascular risk marker and likely as

a causative factor for cardiovascular disease (58).

L-Arginine therapy in cardiovascular pathologies

showed contradictory results. However, it is now clear that

individual response to L-Argmaybe influenced by DMA.

In fact, no effects of L-arg therapy are demonstrated in patients

with low ADMA levels, whereas in patients with

high ADMA level, L-Arg normalizes the L-Arg to ADMA

ratio, thus normalizing the endothelial function (59).

Several studies demonstrated that L-Arg infusion

in normal subjects and patients with coronary heart disease

(60), hypercholesterolemia (61), and hypertension

(62) is able to improve the endothelial function, but the

results, although encouraging, are not conclusive because

of the short-term effects of IV arginine. However, arginine

does not affect endothelial function in patients with

diabetes mellitus. On the other hand, oral L-Arg has a

longer half-life and longer-term effects than L-Arg given

intra-arterially or intravenously (63). Thus, in the setting

of long-term health maintenance or symptom management,

the oral route would be preferred. Studies in animals

documented that oral L-Arg supplementation is able

to reduce the progression of atherosclerosis, preserving

endothelium function (64) and inhibiting circulating inflammatory

cells (65) and platelets (66) in animals with

hypercholesterolemia, and to decrease blood pressure and

wall thickness in animals with experimental hypertension

(67). On the other hand, studies in humans in vivo are

not so widely positive as the animal experimental data.

Actually, although the majority of the data is in normal

subjects, individuals with a history of cigarette smoking

and patients with hypercholesterolemia and claudication

demonstrate beneficial effects of oral L-Arg administration

on platelet adhesion and aggregation, monocyte adhesion,

and endothelium-dependent vasodilation (68,69).

Other studies do not show any benefit (70,71); therefore,

no definitive conclusions can be drawn. Taken together,

the studies show a major effect when L-Arg supplementation

was given in subjects with hypercholesterolemia,

probably because of an increase in NO production via reduction

of the ADMA intracellular concentration, which

is increased in the presence of LDL hypercholesterolemia.

In conclusion, despite several beneficial effects on

intermediate end points, particularly in hypercholesterolemic

patients, there is no evidence for a clinical

benefit in the treatment or prevention of cardiovascular

disease. More data, derived from large-scale prospective

studies evaluating the effect of long-term treatment with

L-Arg, are needed. Future perspectives of pharmacological

intervention are represented by the regulation of the enzyme

dimethylarginine dimethylaminohydrolase responsible

for the ADMA metabolism (57), the arginase (72),

and the endothelial cell L-Arg transporter (73).

Immune System

Many studies, in animals as well as in humans, have

shown that arginine is involved in immune modulation. In

fact, this amino acid is a component of most proteins and

the substrate for several nonprotein, nitrogen-containing

compounds acting as immune modulators.

There is clear evidence that arginine participates in

the cell-mediated immune responses of macrophages and

T lymphocytes in humans through the production of NO

by inducible nitric oxide synthase (iNOS-–NOS-2), which

occurs mostly in the macrophage (74,75), and through the

modulation of T-lymphocyte function and proliferation

(76,77). At intracellular levels, arginine is metabolized by

two different enzymatic pathways: the arginase pathway,

by which the guanidino nitrogen is converted into urea to

produce ornithine, and the NOS pathway, which results

in oxidation of the guanidino nitrogen to produce Land

other substances (78,79).

It has been shown that macrophage superoxide production,

phagocytosis, protein synthesis, and tumoricidal

activity are inhibited by high levels of arginine in vitro and

that sites of inflammation with prominent macrophage

infiltration, such as wounds and certain tumors, are deficient

in free arginine (80). In particular, a decrease in

arginine availability due to the activity of macrophage derived

arginase rather than the arginine/NO pathway

may contribute to the activation of macrophages migrating

at inflammatory sites (80). Arginine metabolism in the

macrophages is activity dependent. At rest, macrophages

exhibit minimal utilization of arginine and lower NOS-2

expression or arginase activity, whereas in activated cells,

arginine is transported into the cell, and NOS-2 expression

and arginase are induced by cytokines and other stimuli

(81). The types of stimuli that induce NOS-2 and arginase

are quite different. In vitro and in vivo studies demonstrated

that NOS-2 is induced by T-helper I cytokines (IL-

1, TNF, and -interferon) produced during activation of

the cellular immune response, such as severe infections or

sepsis (74,75), whereas arginases are induced by T-helper

II cytokines (IL-4, IL-10, and IL-13) and other immune regulators

aimed at inducing the humoral immune response

(82,83). Thus, in disease processes, where inflammatory

response predominates, NOS-2 expression and NO production

prevail. Under biological circumstances where Thelper

II cytokine expression is prevalent, arginase activity

and the production of ornithine and related metabolites

would predominate.

In vitro studies in animals demonstrated depressed

lymphocyte proliferation in cultures containing low levels

of arginine and maximal proliferation when arginine is

added at physiological plasma concentration (77,84), but

the molecular details have not been completely defined.

It has also been shown that supplemental arginine

increased thymic weight in rodents because of increased

numbers of total thymic T lymphocytes. On the other

hand, in athymic mice, supplemental arginine increased

the number of T cells and augmented delayed-type hypersensitivity

responses, indicating that it can exert its effects

on peripheral lymphocytes and not just on those within

the thymus (76).

The immunostimulatory effects of arginine in animal

studies have suggested that this amino acid could be

an effective therapy for many pathophysiological conditions

in humans, able to positively influence the immune

response under some circumstances by restoring cytokine

balance and reducing the incidence of infection.


In healthy humans, oral arginine supplementation

shows many effects on the immune system, including

increase in peripheral blood lymphocyte mitogenesis,

increase in the T-helper–T-cytotoxic cell ratio and, in

macrophages, activity against microorganisms and tumor

cells (85). Furthermore, the delayed-type hypersensitivity

response as well as the number of circulating natural

killer (NK) and lymphokine-activated killer cells are

increased (85–87). Therefore, it has been hypothesized

that arginine could be of benefit to patients undergoing

major surgery after trauma and sepsis and in cardiovascular

diseases, HIV infection, and cancer (88). In

fact, short-term arginine supplementation has been shown

to maintain the immune function during chemotherapy;

arginine supplementation (30 g/day for 3 days) reduced

chemotherapy-induced suppression of NK cell activity,

lymphokine-activated killer cell cytotoxicity, and lymphocyte

mitogenic reactivity in patients with locally advanced

breast cancer (89). It must be noted that chronic administration

of arginine has also been shown to promote cancer

growth by stimulating polyamine synthesis in both animal

and human studies (89). On the other hand, NO has

been shown to inhibit tumor growth. Thus, the real effect

on cancer processes depends on the relative activities of

NOS and arginase pathways that show variable expression,

depending on the stage of carcinogenesis (91).

These data clearly indicate the involvement of arginine

in immune responses in both animals and humans.

Large clinical trials are needed to clarify the clinical application

and efficacy of this amino acid in immunity and



The available form of supplemental L-Arg is represented

by the free base, the Clsalt (L-Arg hydrochloride-–L-Arg-

HCl) and the aspartate salt of the amino acid (92).

L-Arg is stable under sterilization condition and its

administration is safe for mammals in an appropriate dose

and chemical form (91).

Oral L-Arg (up to 9 g of Arg-HCl per day for adults)

has no adverse effects on humans but higher doses can

lead to gastrointestinal toxicity, theoretically increasing

local production of NO and impairing intestinal absorption

of other basic amino acids (91). Moreover, the local

NOproduction may be particularly dangerous if intestinal

diseases are present (92).

Oral L-Arg supplement is commonly used to increase

GH release and consequentially physical performance;

moreover, it has been hypothesized that L-Arg

supplement could lead to improved muscular aerobic

metabolism and less lactate accumulation, enhancing NOmediated

muscle perfusion.

However, in a clinical trial, arginine supplement in

endurance-trained athletes did not show any difference

from placebo in endurance performance (maximal oxygen

consumption, time to exhaustion), endocrine (GH,

glucacon, cortisol, and testosterone concentrations), and

metabolic parameters (93).

In another study, the association “arginine plus exercise”

produced a GH response approximately 50% lower

than that observed with exercise alone, suggesting that

the acute use of oral L-Arg prior to exercise blunts the GH

response to subsequent exercise (94).

No effects on NO production, lactate and ammonia

metabolism, and physical performance in intermittent

anaerobic exercise were shown in well-trained male athletes

after short-term arginine supplementation (95). It has

been hypothesized thatNOproduction is not modified by

arginine supplementation in athletes because they may

have higher basal concentrations of NO than general population;

in fact, basal NO production can be increased by

regular exercise training, without any pharmacological intervention


There are many interesting clinical perspectives on

arginine supplementation therapy, especially in critical

care setting (96), treatment and prevention of pressure

ulcers (97), hypertension (59), and asthma and chronic obstructive

pulmonary disease (98), but further studies are

required to clarify which categories of patients may benefit

from this treatment (99).


From an endocrinological point of view, the simple classification

of arginine as an amino acid involved in peripheral

metabolism is no longer acceptable. In fact, besides other

nonendocrine actions, it has been clearly demonstrated

that arginine plays a major role in the neural control of

anterior pituitary function, particularly in the regulation

of somatotrophin secretion. One of the most important

concepts regarding arginine is the existence of an arginine

pathway at the CNS level, where this amino acid represents

the precursor of NO, a gaseous neurotransmitter of

major importance. On the other hand, NO does not necessarily

mediate all the neuroendocrine or the peripheral

arginine actions.

In the past years, new discoveries have led to a rapid

increase in our knowledge of the arginine/NO system,

from a neuroendocrine and nonendocrine point of view.

Up to now, there is no evidence for the utility of L-Arg

supplement for muscle strength or exercise performance

in humans. However, several other aspects still remain to

be clarified; the potential clinical implications for arginine

have also never been appropriately addressed and could

provide unexpected results both in the endocrine and in

the cardiovascular fields.


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