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Alternate Title

Synonyms

Arg, arginine, arginine hydrochloride (intravenous formulation), ibuprofen-arginate (Spedifen®), L-arg, 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.

Background

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.

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 a Food and Drug Administration (FDA) labeled indication for arginine.
Grade: A

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.
Grade: A

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.
Grade: C

Burns: A randomized, controlled clinical trial designed to evaluate immune function of patients 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.
Grade: C

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.
Grade: C

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.
Grade: C

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 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.
Grade: C

MELAS syndrome: One study found that two years of supplementation with oral L-arginine significantly improved endothelial function in patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke). Further research is merited in this area.
Grade: C

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.
Grade: C

Gastrointestinal cancer surgery: Supplementation with an oral combination of arginine and omega-3 fatty acids may reduce length of hospital stay and infections after surgery in gastrointestinal cancer patients. There is conflicting evidence as to when to give the combination (either before or after surgery). Both strategies have been reported as superior to conventional treatment (no artificial nutrition) at reducing infections after surgery and reducing hospital stay. In a large, randomized, controlled clinical trial, malnourished cancer patients were given oral enteral nutrition supplemented by arginine, omega-3 fatty acids and RNA before surgery. It was found that supplementation with the combination before surgery reduced complications after surgery and hospital stay. A different randomized, controlled clinical trial in patients with gastrointestinal cancer studied the effects of an enteral diet supplemented with arginine, omega-3 fatty acids and glutamine (administered after surgery) on immune function and inflammatory response. This study reported the supplement to be well-tolerated with positive effects on immune and inflammatory response. Further research is needed to determine the possible effects of arginine alone.
Grade: C

Heart failure (CHF): Studies of arginine in patients with chronic heart failure have shown mixed results. Some studies report improved exercise tolerance. Additional studies are needed to confirm these findings before a firm conclusion can be drawn.
Grade: C

Heart protection during coronary artery bypass grafting (CABG): Arginine-supplemented "blood cardioplegic solution" is proposed to have protective properties for the heart. A randomized, controlled clinical trial using this solution in patients undergoing heart surgery (coronary artery bypass grafting) reports improved heart protection. Further research is needed before a firm conclusion can be drawn.
Grade: C

High blood pressure: A small study suggests that arginine taken by mouth may dilate the arteries and temporarily reduce blood pressure in hypertensive patients with type 2 diabetes. Larger, high-quality studies are needed before a recommendation can be made.
Grade: C

Immunomodulator: Preliminary study results suggest that arginine supplementation may enhance the immune response elicited by the pneumococcal vaccine in older people. More studies are needed to confirm these results.
Grade: C

Migraine headache: Preliminary studies suggest that adding arginine to ibuprofen therapy may decrease migraine headache pain.
Grade: C

Myocardial infarction: Study results of arginine supplementation after myocardial infarction (heart attack) are mixed. Further research is needed before a recommendation can be made. A cardiologist and pharmacist should be consulted prior to initiation of arginine therapy.
Grade: C

Peripheral vascular disease / claudication: Intermittent claudication is a condition characterized by leg pain and fatigue due to buildup of cholesterol plaques or clots in leg arteries. A small number of studies report that arginine therapy may improve walking distance in patients with claudication. Further research is needed before a firm conclusion can be drawn.
Grade: C

Pre-eclampsia (high blood pressure in pregnancy): Early study suggests that prolonged dietary supplementation with L-arginine may decrease blood pressure that is too high in pregnant women. Further research is needed to confirm these results.
Grade: C

Pressure ulcers: Studies of arginine for pressure ulcers show mixed results. Further research is needed before a conclusion can be drawn.
Grade: C

Recovery after surgery: One study suggests that arginine may provide benefits when used as a supplement after surgery. It is not clear what the specific role of arginine may be in improving immune function, or what dose is safe or effective.
Grade: C

Transplants: Dietary supplementation with L-arginine and canola oil has been associated with decreased rejection rates after the first month in renal transplant patients. Due to reductions in cardiac events, long-term benefits for patient survival may be particularly important. Further research is needed to confirm these results.
Grade: C

Wound healing: Arginine has been suggested to improve the rate of wound healing in elderly individuals. A randomized, controlled clinical trial reported improved wound healing after surgery in head and neck cancer patients, following the use of an enteral diet supplemented with arginine and fiber. Arginine has also been used topically (on the skin) to attempt to improve wound healing. Further research is necessary in this area before a firm conclusion can be drawn.
Grade: C

Acute mountain sickness (AMS): Based on preliminary study, L-arginine supplementation is not beneficial in the prophylactic treatment of AMS.
Grade: D

Cyclosporine toxicity: Animal studies report that arginine blocks the toxic effects of cyclosporine, a drug used to prevent organ transplant rejection. However, results from studies in humans have not found that arginine offers any protection from cyclosporine-induced toxicity.
Grade: D

Exercise performance: Overall, currently available study results conclude that arginine supplementation does not improve exercise performance.
Grade: D

Infertility: Although there are several studies in this area, it is not clear what effects arginine has on improving the likelihood of getting pregnant. Early evidence does not support the finding that arginine has any benefits in women who are undergoingin vitrofertilization, or in men with abnormal sperm.
Grade: D

Interstitial cystitis: Arginine has been proposed as a treatment for interstitial cystitis (inflammation of the bladder). However, most well-designed studies in humans have not found that arginine offers any improvements in treating symptoms such as urinary frequency or urgency.
Grade: D

Kidney disease: It has been suggested that arginine may be a useful supplement in people diagnosed with kidney failure. However, results from available studies do not support this claim. A small randomized, controlled clinical trial studied the ability of L-arginine to improve dilation of blood vessels in children with chronic renal failure. Results showed that blood vessel dilation (endothelial function) was not improved with oral L-arginine suggesting that dietary supplementation is not a beneficial or useful clinical approach in children with chronic renal failure.
Grade: D

Kidney protection during angiography: The contrast media or dye used during angiography to map a patient's arteries (or during some CT scans) can be toxic to the kidneys, especially to people with pre-existing kidney disease. A randomized, parallel, double-blind clinical trial studied the use of L-arginine to protect kidneys in patients with chronic renal failure undergoing angiography. The authors found no evidence that injections of L-arginine protect the kidney from damage due to contrast. Other therapies, such as N-acetylcysteine (NAC), have been found beneficial at protecting the kidneys from contrast-induced damage, particularly in patients at high-risk such as those with diabetes.
Grade: D

Asthma: Although it has been suggested that arginine may be a treatment for asthma, studies in humans have actually found that arginineworsensinflammation in the lungs andcontributesto asthma symptoms. Therefore, taking arginine by mouth or by inhalation is not recommended in people with asthma.
Grade: F