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Arginine (L-Arginine)
by MedlinePlus

L-arginine was first isolated in 1886. In 1932, L-arginine was found to be required for the generation of urea, which is necessary for the removal of toxic ammonia from the body. In 1939, L-arginine was also shown to be required for the synthesis of creatine. Creatine degrades to creatinine at a constant rate, and is cleared from the body by the kidney.

Arginine is considered a semi-essential amino acid, because although it is normally synthesized in sufficient amounts by the body, supplementation is sometimes required (for example, due to inborn errors of urea synthesis, protein malnutrition, excess ammonia production, excessive lysine intake, burns, infection, peritoneal dialysis, rapid growth, or sepsis). Symptoms of arginine deficiency include poor wound healing, hair loss, skin rash, constipation, and fatty liver.

Arginine is a precursor of nitric oxide, which causes blood vessel relaxation (vasodilation). Preliminary evidence suggests that arginine may be useful in the treatment of medical conditions that are improved by vasodilation, such as angina, atherosclerosis, coronary artery disease, erectile dysfunction, heart failure, intermittent claudication/peripheral vascular disease, and vascular headache. Arginine also stimulates protein synthesis and has been studied for wound healing, bodybuilding, enhancement of sperm production (spermatogenesis), and prevention of wasting in people with critical illness.

Arginine hydrochloride contains high chloride content and has been used for the treatment of metabolic alkalosis. This use should be under the supervision of a qualified healthcare professional.

Most people likely do not need to take arginine supplements because the body usually makes sufficient amounts.

Synonyms

Arg, arginine, arginine hydrochloride (intravenous formulation), ibuprofen-arginate (Spedifen®), L-arginine, 2-amino-5-guanidinopentanoic acid.

Note: Arginine vasopressin is different from arginine/L-arginine, with an entirely different mechanism. NG-monomethyl-L-arginine is different from arginine/L-arginine, and functions as an inhibitor of nitric oxide synthesis.

Dietary sources of arginine: Walnuts, filberts, pecans, Brazil nuts, sesame and sunflower seeds, brown rice, raisins, coconut, gelatin, buckwheat, almonds, barley, cashews, cereals, chicken, chocolate, corn, dairy products, meats, oats, peanuts.

Evidence

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidence

Growth hormone reserve test / pituitary disorder diagnosis

Intravenously administered arginine can be used to evaluate growth hormone reserve in individuals with suspected growth hormone deficiency. For example, in patients with suspected panhypopituitarism, growth/stature abnormalities, gigantism/acromegaly, or pituitary adenoma. This is an FDA labeled indication for arginine.

Inborn errors of urea synthesis

In patients with inborn errors of urea synthesis, high blood ammonia levels and metabolic alkalosis may occur, particularly in patients with ornithine carbamoyl transferase (OCT) deficiency or carbomoyl phosphate synthetase (CPS) deficiency. Arginine can be a helpful treatment by shifting the way the body processes nitrogen, but should be avoided in patients with hyperargininemia (high arginine levels). Other drugs may have similar benefits, such as citrulline, sodium benzoate, or sodium phenylbutyrate, although dialysis may be necessary initially. This use of arginine should be supervised by a qualified healthcare professional.

Adrenoleukodystrophy (ALD)

Adrenoleukodystrophy (ALD) is a rare inherited metabolic disorder characterized by the loss of fatty coverings (myelin sheaths) on nerve fibers in the brain, and progressive destruction of the adrenal gland. ALD is inherited as an x-linked genetic trait that results in dementia and adrenal failure. Injections of arginine have been proposed to help manage this disorder, although most study results are inconclusive. Further research is needed to evaluate the use of arginine in ALD.

Burns

A randomized, controlled clinical trial designed to evaluate immune function of patients given 15mg of arginine orally suggests that arginine may help with the recovery of immune function and protein function in partial-thickness burn patients. Further research is necessary in this area before a conclusion can be drawn.

Coronary artery disease / angina

There is initial evidence from several studies that arginine taken by mouth or by injection improves exercise tolerance and blood flow in arteries of the heart. Benefits have been shown in some patients with coronary artery disease and angina. A small randomized, controlled clinical trial studied the effects of a medical food bar enriched with L-arginine and a combination of other nutrients in the management of chronic stable angina. The authors found that this arginine-rich medical food, when used with traditional therapy, improves vascular function, exercise capacity and aspects of quality of life in these patients. However, further research is needed to confirm these findings and to establish doses that may be safe and effective.

Critical illness

Some studies suggest that arginine may provide benefits when added to nutritional supplements during critical illnesses (for example, in patients being treated in intensive care units). However, it is unclear what the specific role of arginine may be in improving recovery. A randomized, controlled clinical trial was designed to study the effects of a high-protein formula enriched with arginine, fiber, and antioxidants in early nutrition therapy of critically ill patients. The study measured infections in the hospital intensive care unit (ICU), length of hospital stay, and death rates. Patients fed the high-protein diet enriched with arginine, fiber and antioxidants developed fewer hospital infections than patients fed a standard high-protein diet. There was no difference in length of ICU hospital stay or death rate.Overall the scientific data to date does not show benefit for only L-arginine supplementation, nor does it show harm. At this time there is no rationale for the routine supplementation of arginine alone to enhance recovery from serious illness. Because of the potential for harm, this amino acid should only be administered to critically ill patients in large doses under carefully monitored study conditions.

Dental pain (ibuprofen arginate)

A well-designed multicenter, randomized, controlled clinical trial found that ibuprofen-arginate (Spedifen®) reduced pain faster after dental surgery compared to conventional ibuprofen alone. The study included 498 patients who were given either ibuprofen-arginate, ibuprofen, or placebo after dental surgery. The degree of pain relief, onset of action, and tolerability of both ibuprofen-arginate and ibuprofen were compared. It was found that ibuprofen arginate relieved pain faster and adverse events with ibuprofen arginate were similar to those seen with ibuprofen alone. Another similar trial concluded that patients treated with ibuprofen arginate rated its overall effectiveness higher than those treated with ibuprofen alone. Adverse event profiles were similar across all treatment groups. Further research is merited in this area.

Erectile dysfunction

Early studies propose that men with low nitrate levels in their blood or urine may find arginine supplements to be useful for managing erectile dysfunction (ED). A randomized, controlled clinical trial reported improvements in patients with mild-to-moderate ED following use of a combination of L-arginine, glutamate and yohimbine hydrochloride. Notably, yohimbine hydrochloride is an FDA-approved therapy for this condition, and the effects caused by arginine alone in this combination therapy are difficult to determine. It is not clear what doses of arginine may be safe or effective in treating this condition, and comparisons have not been made with other agents used for ED.

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