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arginine (generic name)

a hormone - treats Burns, Peripheral vascular disease / claudication, Infertility, Interstitial cystitis, Dental pain, Heart protection during ...
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Alternate Title

L-arginine

Category

Herbs & Supplements

Synonyms

2-amino-5-guanidinopentanoic acid, Arg, arginine, arginine hydrochloride (intravenous formulation), dipeptide arginyl aspartate, HeartBars, ibuprofen-arginate, L-arg, L-arginine, NG-monomethyl-L-arginine, Sargenor, Spedifen®.

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.

Background

L-arginine was first isolated in 1886. In 1932, scientists learned that L-arginine is needed to create urea, a waste product that is necessary for toxic ammonia to be removed from the body. In 1939, researchers discovered that L-arginine is also needed to make creatine. Creatine breaks down into creatinine at a constant rate, and it is cleared from the body by the kidneys.

Arginine is considered a semi-essential amino acid because even though the body normally makes enough of it, supplementation is sometimes needed. For example, people with protein malnutrition, excessive ammonia production, excessive lysine intake, burns, infections, peritoneal dialysis, rapid growth, urea synthesis disorders, or sepsis may not have enough arginine. Symptoms of arginine deficiency include poor wound healing, hair loss, skin rash, constipation, and fatty liver.

Arginine changes into nitric oxide, which causes blood vessel relaxation (vasodilation). Early evidence suggests that arginine may help treat medical conditions that improve with vasodilation, such as chest pain, clogged arteries (called atherosclerosis), coronary artery disease, erectile dysfunction, heart failure, intermittent claudication/peripheral vascular disease, and blood vessel swelling that causes headaches (vascular headaches). Arginine also triggers the body to make protein and has been studied for wound healing, bodybuilding, enhancement of sperm production (spermatogenesis), and prevention of wasting in people with critical illnesses.

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

In general, most people do not need to take arginine supplements because the body usually produces enough.

Evidence

DISCLAIMER: 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.

Growth hormone reserve test / pituitary disorder diagnosis: Arginine can be injected to measure growth hormone levels in people who might have growth hormone deficiencies, such as panhypopituitarism, gigantism, acromegaly, or pituitary adenoma. The U.S. Food and Drug Administration (FDA) has approved this use.
Grade: A

Inborn errors of urea synthesis: In patients with inborn errors of urea synthesis, high ammonia levels in the blood and metabolic alkalosis may occur, particularly among patients with ornithine carbamoyl transferase (OCT) deficiencies or carbamoyl phosphate synthetase (CPS) deficiencies. Arginine may help treatment by shifting the way the body processes nitrogen. Arginine should be avoided in patients with hyperargininemia (high arginine levels). Other drugs, such as citrulline, sodium benzoate, or sodium phenylbutyrate, may have similar benefits. However, dialysis may be needed at first. This use of arginine should be supervised by a qualified healthcare professional.
Grade: A

Coronary artery disease / angina: Early evidence from several studies suggests that arginine taken by mouth or by injection may improve exercise tolerance and blood flow in arteries of the heart. Benefits have been shown in some patients with coronary artery disease and chest pain (called angina). However, more research is needed to confirm these findings and to develop safe and effective doses.
Grade: B

Critical illness: Some studies suggest that arginine may be beneficial for people with critical or life-threatening illnesses when it is added to nutritional supplements. However, it is unclear what the specific role of arginine is in recovery. Because of the potential for harm, large doses of arginine should be avoided.
Grade: B

Heart failure: 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.
Grade: B

Migraine headache: Early studies suggest that adding arginine to ibuprofen (e.g., Motrin® or Advil®) therapy may decrease migraine headache pain.
Grade: B

Peripheral vascular disease / claudication: Intermittent claudication causes leg pain and tiredness because cholesterol plaques or clots develop in leg arteries and block blood flow. A small number of studies report that arginine therapy may improve walking distance in patients with claudication. Further research is needed.
Grade: B

Adrenoleukodystrophy (ALD): Adrenoleukodystrophy (ALD) is a rare inherited metabolic disorder that is characterized by the loss of fatty coverings (myelin sheaths) on nerve fibers in the brain and progressive destruction of the adrenal glands. This condition results in dementia and adrenal failure. Injections of arginine may help manage this disorder, although most study results are inconclusive. Further research is needed to evaluate the use of arginine in ALD.
Grade: C

Anal fissures: Early studies suggest that arginine may help treat chronic anal fissures, which are small tears that develop in the anus. Additional studies are needed.
Grade: C

Autonomic failure: Arginine has been studied in autonomic failure, a condition that may include low blood pressure, but the effect is unclear. Well-designed studies will help clarify this relationship.
Grade: C

Breast cancer: It is unclear if arginine can help treat breast cancer patients. Results from early human studies are mixed. High-quality studies are needed.
Grade: C

Burns: Arginine may improve immune function and protein function in burn patients. Further research is needed before a conclusion can be drawn.
Grade: C

Chemotherapy adjuvant: Early human studies suggest that arginine supplements may be beneficial for patients undergoing chemotherapy. Larger, high-quality studies are needed.
Grade: C

Chest pain (non-cardiac): Small studies in humans suggest that arginine taken by mouth (not injected) may improve non-cardiac chest pain associated with esophageal motor disorders. Large, well-designed studies are needed.
Grade: C

Circulation problems (critical limb ischemia): Early human studies suggest that intravenous arginine may increase blood flow in patients with critical limb ischemia. This condition occurs when blood flow to the arms and/or legs is blocked. Large, well-designed trials are needed.
Grade: C

Dental pain (ibuprofen arginate): Some research suggests that ibuprofen-arginate (Spedifen®) may reduce pain after dental surgery faster or more effectively than ibuprofen (e.g., Motrin® or Advil®) alone. More research is needed in this area.
Grade: C

Diabetes (Type 1/Type 2): Early studies in humans suggest that arginine supplements may decrease the severity of diabetes. Large, well-designed studies are needed to understand this relationship.
Grade: C

Diabetic complications: Early studies in humans suggest that arginine supplements may help the body fight some long-term complications of diabetes, including heart disease and nerve damage. Well-designed studies are needed.
Grade: C

Erectile dysfunction: Early studies have shown that arginine supplements may help treat erectile dysfunction (ED) in men with low nitrate levels in their blood or urine. A combination of L-arginine, glutamate, and yohimbine hydrochloride has been used to treat ED. However, because a combination product was used, and yohimbine hydrochloride is an FDA-approved therapy for this condition, the effects of arginine alone are unknown. More research is needed with arginine alone.
Grade: C

Gastrointestinal cancer surgery: A combination of arginine and omega-3 fatty acids may reduce the length of hospital stays and infections after surgery in gastrointestinal cancer patients. Other research suggests that arginine, omega-3 fatty acids, and glutamine may boost the immune system and reduce inflammation after surgery. More research with arginine alone is needed.
Grade: C

Heart protection during coronary artery bypass grafting (CABG): Arginine-supplemented "blood cardioplegic solution" may help protect the heart. Further research is needed before a firm conclusion can be drawn.
Grade: C

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

High cholesterol: Some research suggests that arginine may help treat or prevent high cholesterol. More research is needed.
Grade: C

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

Intrauterine growth retardation: Early studies in pregnant mothers suggest that arginine supplements may improve growth in fetuses that are smaller than average. Additional studies are needed.
Grade: C

Kidney disease or failure: Study results are mixed as to whether arginine as a therapy by itself directly helps certain kidney diseases or failure. Arginine may be a helpful adjunct for kidney disease related conditions such as anemia in the elderly. Additional research is needed in this area.
Grade: C

MELAS syndrome: Early studies have found that long-term supplementation with L-arginine significantly improved endothelial function in patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke). Further research is merited in this area.
Grade: C

Myocardial infarction (heart attack): 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 before arginine supplements are taken.
Grade: C

Pre-eclampsia (high blood pressure in pregnancy): Early study suggests that long-term supplementation with L-arginine may decrease blood pressure that is too high in pregnant women. Arginine may also improve fetal health and growth during pre-eclampsia. 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

Prevention of restenosis after coronary angioplasty (PTCA): Arginine has been injected in patients who had stents surgically inserted into arteries in order to widen them. Early research suggests that this therapy may help prevent the arteries from becoming narrow again (called restenosis). Additional studies are needed.
Grade: C

Raynaud's phenomenon: Early study in humans has looked at the effect of arginine on blood vessel activity in Reynaud's phenomenon, a condition that causes the blood vessels in the fingers, toes, nose, and ears to narrow in response to cold temperatures or stress. However, the effects of arginine are not clear. Large, well-designed trials are needed.
Grade: C

Recovery after surgery: Early study suggests that arginine may provide benefits when used as a supplement after surgery. However, the role of arginine in this condition is unclear. More research is needed to determine if this is safe and effective.
Grade: C

Respiratory infections: Early study suggests that arginine supplements may decrease the risk of respiratory (lung) infections. Large, well-controlled studies are needed to clarify this relationship.
Grade: C

Senile dementia: There is not enough information available to make a strong recommendation about the use of arginine in senile dementia.
Grade: C

Transplants: Dietary supplementation with L-arginine and canola oil has been associated with decreased rejection rates after the first month in kidney transplant patients. Because it may reduce the risk of heart problems, 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 the elderly. Research has shown that an enteral diet supplemented with arginine and fiber improved wound healing after surgery in patients with head and neck cancer. Arginine has also been applied to the skin in order to improve wound healing. Further research is necessary in this area before a firm conclusion can be drawn.
Grade: C

Altitude sickness: Based on early research, L-arginine supplementation is not an effective therapy to prevent acute mountain sickness (AMS).
Grade: D

Cyclosporine toxicity: Animal studies report that arginine blocks the poisonous (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 use of arginine as a fertility treatment in women who are undergoing in vitro fertilization or in men with abnormal sperm.
Grade: D

Interstitial cystitis: Arginine has been proposed as a treatment for interstitial cystitis or inflammation of the bladder. However, most human studies have not found that arginine improves symptoms, such as urinary frequency or urgency.
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 poisonous (toxic) to the kidneys, especially among people with kidney disease. Researchers have studied L-arginine as a way to protect the kidneys in patients with long-term kidney failure who were undergoing angiography. The authors found no evidence that injections of L-arginine protect the kidney from damage due to contrast.
Grade: D

Asthma: Although it has been suggested that arginine may treat asthma, studies in humans have actually found that arginine worsens inflammation in the lungs and contributes to asthma symptoms. Therefore, taking arginine by mouth or by inhalation is not recommended in people with asthma.
Grade: F

Tradition

WARNING: DISCLAIMER: The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.
AIDS/HIV (prevention of wasting), ammonia toxicity, anti-aging, anti-inflammatory, anti-platelet agent, anxiety, beta-hemoglobinopathies, cancer, chronic pain, cirrhosis, cold prevention, cystic fibrosis, endocrine disorders (metabolic syndrome), glaucoma, hemolytic uremic syndrome (HUS), hepatic encephalopathy, increased muscle mass, infantile necrotizing enterocolitis, infection, inflammatory bowel disease (IBD), ischemic stroke, liver disease, lower esophageal sphincter relaxation, metabolic acidosis, obesity, osteoporosis, pain, peritonitis, pre-term labor contractions, sepsis, sexual arousal, sexual function in women, sickle cell anemia, stress, stomach motility disorders, stomach ulcers, supplementation to a low protein diet, thrombotic thrombocytopenic purpura (TTP), trauma (recovery), tumors, ulcerative colitis.

Dosing

Dietary Sources of Arginine

Walnuts, filberts (hazelnuts), 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.

Adults (18 years and older)

There is a lack of standard or well-established doses of arginine, and many different doses have been used and studied. A common dose is 2-3 grams taken by mouth three times daily. In studies, 0.5-16 grams of arginine has been taken daily by mouth for up to six months. Arginine has been applied to the skin in order to improve wound healing.

Doses of arginine used intravenously depend on specific institutional dosing guidelines and should be given under the supervision of a healthcare provider.

Children (younger than 18 years)

Arginine supplements are not recommended in children because there is not enough scientific information available and because of potential side effects.

Safety

DISCLAIMER: Many complementary techniques are practiced by healthcare professionals with formal training, in accordance with the standards of national organizations. However, this is not universally the case, and adverse effects are possible. Due to limited research, in some cases only limited safety information is available.

Allergies

A severe allergic reaction, called anaphylaxis, has occurred after arginine injections. People with known allergies should avoid arginine. Signs of allergy may include rash, itching, or shortness of breath.

Side Effects and Warnings

Arginine has been well tolerated by most people in studies lasting for up to six months, although there is a possibility of serious side effects in some people.

Stomach discomfort, including nausea, stomach cramps, or an increased number of stools, may occur. People with asthma may experience a worsening of symptoms, which may be related to allergy, if arginine is inhaled.

Other potential side effects include low blood pressure and changes in numerous chemicals and electrolytes in the blood. Examples include high potassium, high chloride, low sodium, low phosphate, high blood urea nitrogen, and high creatinine levels. People with liver or kidney diseases may be especially sensitive to these complications and should avoid using arginine except under medical supervision. After injections of arginine, low back pain, flushing, headache, numbness, restless legs, venous irritation, and death of surrounding tissues have been reported.

In theory, arginine may increase the risk of bleeding. Patients using anticoagulants (blood thinners) or antiplatelet drugs, or with underlying bleeding disorders, should speak with their qualified healthcare providers before using arginine and should be monitored.

Arginine may increase blood sugar levels. Caution is advised in patients taking prescription drugs to control sugar levels.

Arginine may increase potassium levels, especially in patients with liver disease.

L-arginine may worsen symptoms of sickle cell disease.

Pregnancy and Breastfeeding

Arginine cannot be recommended as a supplement during pregnancy or breastfeeding because there is not enough scientific information available.

L-arginine has been used in pregnant women with high blood pressure (pre-eclampsia) until 10 days after birth, but it should not be used without supervision of an OB/GYN and pharmacist.

Interactions

Interactions with Drugs

Because arginine can increase the activity of some hormones in the body, many possible drug interactions may occur. The prescription drugs aminophylline and the sweetening agent xylitol may decrease the effect that arginine has on glucagon.

Estrogens (found in birth control pills and hormone replacement therapies) may increase the effects of arginine on growth hormone, glucagon, and insulin. In contrast, progestins (also found in birth control pills and some hormone replacement therapies) may decrease the responsiveness of growth hormone to arginine.

When used with arginine, some diuretics, such as spironolactone (Aldactone®), or ACE-inhibitor blood pressure drugs, such as enalapril (Vasotec®), may cause potassium levels in the blood to get too high. Monitoring of blood potassium levels may be required.

Arginine should be used carefully with drugs, such as nitroglycerin or sildenafil (Viagra®), because blood pressure may fall too low. Other side effects, such as headache and flushing, may occur when arginine is used with these drugs.

Because arginine may cause the stomach to make more acid, it may reduce the effectiveness of drugs that block stomach acid such as ranitidine (Zantac®) or esomeprazole (Nexium®).

In theory, arginine may increase the risk of bleeding when used with anticoagulants (blood thinners) or antiplatelet drugs. Examples include warfarin (Coumadin®), heparin, and clopidogrel (Plavix®). Some pain relievers may also increase the risk of bleeding if used with arginine. Examples include aspirin, ibuprofen (Motrin®, Advil®), and naproxen (Naprosyn®, Aleve®, Anaprox®).

It is also possible that arginine may raise blood sugar levels. Patients taking oral or injected drugs for diabetes should be monitored closely by their healthcare providers while using arginine. Dosing adjustments may be necessary.

Studies suggest that a combination of ibuprofen and arginine (ibuprofen-arginate/Spedifen®) has a faster onset of pain relief than ibuprofen alone. Use of other ibuprofen-based pain relievers, such as Motrin® or Advil®, with ibuprofen-arginate may increase the risk of toxic effects. Patients should consult their healthcare providers before combining these medications.

Interactions with Herbs and Dietary Supplements

Arginine may block the benefits of lysine in treating cold sores. It may increase the activity of growth hormone if used with ornithine.

In theory, arginine may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.

Arginine may raise blood sugar levels. People using other herbs or supplements that may raise blood sugar levels should be monitored closely by their healthcare providers while using arginine. Dosing adjustments may be necessary.

Arginine should be used cautiously in patients taking potassium supplements because of the possible additive effect.

Attribution

This information is based on a professional level monograph edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com): Heather Boon, BScPhm, PhD (University of Toronto); Ethan Basch, MD (Memorial Sloan-Kettering Cancer Center); Michelle Corrado, PharmD (Harvard Vanguard Medical Associates); Dawn Costa, BA, BS (Natural Standard Research Collaboration); Sadaf Hashmi MD, MPH (Johns Hopkins School of Hygiene and Public Health); Jenna Hollenstein, MS, RD (Natural Standard Research Collaboration); Shaina Tanguay-Colucci, BS (Natural Standard Research Collaboration); Catherine Ulbricht, PharmD (Massachusetts General Hospital); Wendy Weissner, BA (Natural Standard Research Collaboration); Jen Woods, BS (Natural Standard Research Collaboration).

Bibliography

DISCLAIMER: Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

Abel T, Knechtle B, Perret C, et al. Influence of chronic supplementation of arginine aspartate in endurance athletes on performance and substrate metabolism - a randomized, double-blind, placebo-controlled study. Int J Sports Med 2005 Jun;26(5):344-9.

Angdin M, Settergren G, Liska J, et al. No effect of L-arginine supplementation on pulmonary endothelial dysfunction after cardiopulmonary bypass. Acta Anaesthesiol Scand 2001;45(4):441-8.

Bednarz B, Jaxa-Chamiec T, Maciejewski P, et al. Efficacy and safety of oral l-arginine in acute myocardial infarction. Results of the multicenter, randomized, double-blind, placebo-controlled ARAMI pilot trial. Kardiol Pol 2005;62(5):421-7.

Carrier M, Pellerin M, Perrault LP, et al. Cardioplegic arrest with L-arginine improves myocardial protection: results of a prospective randomized clinical trial. Ann Thorac Surg 2002;73(3):837-41; discussion 842.

Cartledge JJ, Davies AM, Eardley I. A randomized double-blind placebo-controlled crossover trial of the efficacy of L-arginine in the treatment of interstitial cystitis. BJU Int 2000;85(4):421-426.

Facchinetti F, Saade GR, Neri I, et al. L-arginine supplementation in patients with gestational hypertension: a pilot study. Hypertens Pregnancy 2007;26(1):121-30.

Houwing RH, Rozendaal M, Wouters-Wesseling W, et al. A randomised, double-blind assessment of the effect of nutritional supplementation on the prevention of pressure ulcers in hip-fracture patients. Clin Nutr 2003;22(4):401-405.

Kimber J, Watson L, Mathias CJ. Cardiovascular and neurohormonal responses to i. v. l-arginine in two groups with primary autonomic failure. J Neurol 2001;248(12):1036-41.

Kawano H, Motoyama T, Hirai N, et al. Endothelial dysfunction in hypercholesterolemia is improved by L-arginine administration: possible role of oxidative stress. Atherosclerosis 2002;161(2):375-80.

Oka RK, Szuba A, Giacomini JC, et al. A pilot study of L-arginine supplementation on functional capacity in peripheral arterial disease. Vasc Med 2005;10(4):265-74.

Polan ML, Hochberg RB, Trant AS, et al. Estrogen bioassay of ginseng extract and ArginMax, a nutritional supplement for the enhancement of female sexual function. J Womens Health (Larchmt) 2004;13(4):427-430.

Schramm L, La M, Heidbreder E, Hecker M, et al. L-arginine deficiency and supplementation in experimental acute renal failure and in human kidney transplantation. Kidney Int 2002;61(4):1423-32.

Schulman SP, Becker LC, Kass DA, et al. L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA 2006;295(1):58-64.

Suzuki T, Hayase M, Hibi K, et al. Effect of local delivery of L-arginine on in-stent restenosis in humans. Am J Cardiol 2002;89(4):363-7.

Yin WH, Chen JW, Tsai C, et al. L-arginine improves endothelial function and reduces LDL oxidation in patients with stable coronary artery disease. Clin Nutr 2005;24(6):988-97.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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