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Arginine

Arginine  

Natural Standard Monograph, Copyright © 2014 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified health care professional before making decisions about therapies and/or health conditions.

Related Terms

  • 2-Amino-5-guanidinopentanoic acid, agmatine, Arg, arginine, arginine hydrochloride (intravenous formulation), Ark 1, decarboxylated arginine, dipeptide arginyl aspartate, HeartBars, L-arg, L-arginine, L-arginine aspartate, NG-monomethyl-L-arginine, Sargenor, Spedifen®.
  • Dietary sources of arginine: Almonds, barley, Brazil nuts, brown rice, buckwheat, cashews, cereals, chicken, chocolate, coconut, corn, dairy products, filberts, gelatin, meats, oats, peanuts, pecans, raisins, sesame seeds, sunflower seeds, walnuts.
  • Note: Arginine analogs (N(omega)-nitro-L-arginine methyl ester, N(G)-nitro-L-arginine methyl ester, N-monomethyl-L-arginine, dimethylarginine), and ibuprofen arginate are not specifically discussed in this monograph.

Background

  • L-arginine was first isolated in 1886, reportedly from the extract of a lupine (Lupinus spp.) seedling. Lupinus is a genus in the legume (Fabaceae) plant family.
  • Arginine is an amino acid normally made by the body. Arginine is also found in many foods that have protein.
  • Arginine becomes nitric oxide (a blood vessel-widening agent called a vasodilator) in the body. Early evidence suggests that arginine may help treat medical conditions that improve with increased vasodilation. These conditions include chest pain, atherosclerosis (clogged arteries), heart disease, heart failure, erectile dysfunction, peripheral vascular disease, and headaches from blood vessel swelling).
  • Arginine also triggers the body to make protein and has been studied for healing wounds, bodybuilding, enhancing sperm production, and preventing tissue wasting in people with critical illnesses. However, caution is warranted. Arginine use was associated with death in some people with heart conditions. Caution is also needed when using arginine to treat pre-eclampsia (high blood pressure in pregnancy).
  • Arginine hydrochloride has been used to treat metabolic alkalosis. This use should be under the supervision of a qualified healthcare professional.

Evidence

 

Uses based on scientific 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 professional.

Grade* 

Growth hormone reserve test / pituitary disorder diagnosis (arginine hydrochloride) 

Arginine is sometimes injected into a vein to measure growth hormone levels in people being tested for growth hormone deficiencies, such as panhypopituitarism, gigantism, acromegaly, or pituitary adenoma. The U.S. Food and Drug Administration (FDA) has approved this use.

A 

Inborn errors of urea synthesis 

People with inborn errors of urea synthesis may have high ammonia levels in the blood and metabolic alkalosis. There is strong evidence supporting the use of arginine for this condition. Arginine should be avoided in people with high arginine levels in the blood. A qualified healthcare professional should supervise use.

A 

Heart disease 

There is good scientific evidence that dietary supplementation with L-arginine may help people with coronary artery disease, angina, or clogged arteries, due to its effects on blood vessels. Larger, longer-term studies are needed to confirm these initial positive effects.

B 

Heart failure 

Arginine has been studied in people with heart failure. Longer-term studies are required to confirm the clinical benefit of L-arginine supplementation in people with heart disease.

B 

Peripheral vascular disease / claudication 

Peripheral vascular disease, also known as intermittent claudication, is a narrowing of blood vessels in the legs and feet caused by fatty deposits. This condition causes decreased blood flow to the legs and feet, resulting in leg pain and tiredness. A small number of studies report that arginine therapy may improve walking distance in people with claudication. Further research is needed.

B 

Adrenoleukodystrophy (ALD) 

Adrenoleukodystrophy (ALD) is a rare inherited metabolic disorder that involves damage to the nerves in the brain and the adrenal glands. This condition results in dementia and adrenal failure. Arginine injections may help manage this disorder; however, most study results are inconclusive. Further research is needed to evaluate the use of arginine in ALD.

C 

Altitude sickness 

Limited research has examined the effect of L-arginine on altitude sickness symptoms. Larger, well-designed trials are required before conclusions can be made.

C 

Anal fissures 

Early research suggests that arginine helps heal chronic anal fissures, which are small tears that develop in the anus. Additional studies are needed.

C 

Anxiety 

In limited research, the combination of L-lysine and L-arginine reduced symptoms of anxiety. The effect of L-arginine alone is unknown. Additional research is needed in this area.

C 

Autonomic failure 

Arginine has been studied for treating autonomic failure, a condition that may include low blood pressure. Its effect is unclear. Well-designed studies are needed.

C 

Birth outcomes 

The effect of L-arginine on birth outcomes has been studied. Additional research is needed before conclusions can be made.

C 

Blood flow enhancement 

In limited research, L-arginine increased blood flow. Because of conflicting results from one study, additional research is needed.

C 

Breast cancer 

The therapeutic effect of arginine on breast cancer is unclear. Results from early human studies are mixed. High-quality studies are needed.

C 

Burns 

Arginine may improve immune function and protein function in burns . Further research is needed before a conclusion can be drawn.

C 

Cachexia (weight loss and muscle-wasting) 

A combination of beta-hydroxyl beta-methyl butyrate, glutamine, and arginine has been tested in people with cachexia associated with cancer, but conclusions could not be drawn. Further research is needed.

C 

Chemotherapy 

Early human studies suggest that arginine supplements may benefit people undergoing chemotherapy. Larger, high-quality studies are needed.

C 

Chest pain 

Limited human research reported that arginine taken by mouth improved chest pain in people with esophagus problems. Large, well-designed studies are needed.

C 

Cognitive function 

In early research, L-arginine increased cognitive function in elderly people with cerebrovascular disease (problems with blood vessels in the brain). Better-designed studies are needed.

C 

Critical illness 

The impact of L-arginine supplementation on critical illness is unclear. Further research is needed.

C 

Cyclosporine toxicity 

Results of early studies of the effect of L-arginine on cyclosporine toxicity in renal transplant are mixed. Additional research is needed in this area.

C 

Dental conditions 

In early research, arginine-containing toothpaste has reduced tooth sensitivity. An arginine-containing product was also effective in reducing dental caries. Additional research is needed to confirm these effects.

C 

Diabetes (type 2) 

The effect of L-arginine on type 2 diabetes has been investigated. Large, well-designed studies are needed to understand the effect of arginine on type 2 diabetes.

C 

Diabetic complications 

Early research indicates that L-arginine may play a role in reducing complications associated with diabetes. However, further research is required before conclusions can be made.

C 

Erectile dysfunction 

Early studies showed that arginine supplements helped treat erectile dysfunction (ED) in men with low nitrate or nitrite levels in their blood or urine. A combination of L-arginine, glutamate, and yohimbine hydrochloride was 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 are unknown. More research is needed with arginine alone.

C 

Exercise performance 

Despite common use by athletes, the effect of arginine for exercise performance enhancement has not been studied extensively. Well-designed studies investigating arginine alone are needed before conclusions can be made.

C 

Fetal development 

Preliminary research of pregnant mothers suggests that arginine supplements improve growth in smaller-than-average fetuses. Additional studies are needed.

C 

Gastrointestinal cancer surgery 

A combination of arginine, RNA, and omega-3 fatty acids may reduce the length of hospital stay and infections after surgery for gastrointestinal cancer. More research with arginine alone is needed.

C 

Heart protection during coronary artery bypass grafting (CABG) 

An arginine-supplemented blood solution used during surgery may help protect the heart in people undergoing coronary artery bypass grafting. Further research is needed before a firm conclusion can be drawn.

C 

High blood pressure 

Early research reported that arginine taken by mouth reduced blood pressure in people with high blood pressure. Larger, high-quality studies are needed before a conclusion can be made.

C 

High cholesterol 

Some research suggests that arginine may help treat high cholesterol. However, results are conflicting and more research is needed.

C 

Immune function 

L-arginine has immune effects in people undergoing surgery for colorectal cancer and in children with airway infections. In HIV, L-arginine in combination with omega-3 fatty acids and a nutritional supplement had no additional effects on immune response over a nutritional supplement alone. Additional well-designed research is needed.

C 

Infertility 

Limited research has investigated the effect of L-arginine on male and female infertility. Further research is required before conclusions can be made.

C 

MELAS syndrome 

Early studies found that supplementation with L-arginine significantly improved endothelial function in people with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke). Further research is needed in this area.

C 

Metabolic disorders 

Limited research suggests that L-arginine may decrease symptoms associated with creatine deficiency syndromes. Further research is required before conclusions can be drawn.

C 

Polycystic ovarian syndrome 

In early research, treatment with N-acetyl cysteine (NAC) and L-arginine restored some function in people with polycystic ovary syndrome. Further research is required before conclusions can be drawn.

C 

Pre-eclampsia (high blood pressure in pregnancy) 

Effects of L-arginine in women with pre-eclampsia are mixed. Longer-term treatment appeared to be more effective than short-term treatment. Further research is needed before a conclusion can be made.

C 

Pressure ulcers 

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

C 

Prevention of restenosis after coronary angioplasty (PTCA) 

Injection of L-arginine into surgically placed stents was investigated with mixed results. Early research suggested that L-arginine may or may not prevent restenosis (narrowing) in the arteries. Further well-designed studies are required.

C 

Raynaud's phenomenon 

Early research in humans investigated the effect of arginine on blood vessel activity in Raynaud's phenomenon, a condition causing 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 unclear. Large, well-designed trials are needed.

C 

Recovery after surgery 

In early research, arginine combined with other supplements helped recovery after surgery. However, the role of arginine alone is unclear. More research is needed in this area.

C 

Respiratory infections 

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

C 

Scleroderma 

In early research, L-arginine may be useful for pregnant women with scleroderma (buildup of scar tissue in the skin). Further research is needed in this area.

C 

Sickle cell anemia 

Clinical studies investigating the effects of L-arginine on sickle cell anemia are limited. Early research suggests the potential for immune benefits. Further research is needed in this field.

C 

Transplants 

In human research, L-arginine improved kidney function in people with a kidney transplant, and improved quality of life and exercise tolerance in people with heart transplants. Additional clinical research is needed.

C 

Uterine disorders 

In early research, L-arginine improved endometrial thickness in people with a thin endometrium (the lining of the uterus). Further studies are required before conclusions can be drawn.

C 

Asthma 

Early research has suggested a lack of benefit in the use of arginine for asthma.

D 

Interstitial cystitis 

Arginine has been proposed as a treatment for interstitial cystitis (inflammation of the bladder). However, most studies found a lack of effect.

D 

Kidney disease or failure 

Overall evidence from early research fails to support the use of L-arginine for kidney disease or failure. Until the evidence is more consistent, conclusions cannot be made.

D 

Kidney protection during angiography 

The contrast media, or dye, used during angiography to map arteries may be poisonous (toxic) to the kidneys, especially in people with kidney disease. Early researcher has found a lack of evidence that injections of L-arginine protected the kidney from damage due to contrast agents.

D 

Wound healing 

In human research, arginine appeared to lack benefit in wound healing. Further research is required before conclusions can be made.

D 

Myocardial infarction (heart attack) 

Until potential safety issues are addressed, L-arginine should be avoided in people having a heart attack.

F 

 

*Key to grades: 

A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use (it may not work);
F: Strong scientific evidence against this use (it likely does not work).

For full grading rationale, click here.

Uses based on tradition or theory 

The below uses are based on tradition or scientific theories. 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 health care professional

Aging, AIDS/HIV, ammonia toxicity, amyotrophic lateral sclerosis (ALS), antibacterial, anti-inflammatory, antioxidant, anti-platelet agent, beta-hemoglobinopathies (blood disorder), cancer, cirrhosis, cold prevention, cystic fibrosis, depression, epilepsy, eye disorders, food uses, glaucoma, growth, gut disorders, heavy metal/lead toxicity, hemolytic uremic syndrome (blood disorder), hepatic encephalopathy (confused thinking due to liver disorders), hyperhomocysteinemia (high homocysteine in the blood), increased muscle mass, inflammatory bowel disease (IBD), liver disease, liver protection, lower esophageal sphincter relaxation, malaria, metabolic acidosis, migraine, mitochondrial disorders, neurological problems, obesity/weight loss, osteoporosis / osteopenia, pain, parasites, peritonitis (inflammation of the stomach lining), Peyronie's disease (abnormal curvature and scar tissue in the penis), pre-term labor contractions, pruritus (itching), rabies, sexual function in women, stomach motility disorders, stomach ulcers, stress, stroke, supplementation to a low protein diet, thrombotic thrombocytopenic purpura (blood disorder), trauma, ulcerative colitis, vaccine adjunct, vascular disorders.


Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare professional before starting a new therapy. Consult a healthcare professional immediately if you experience side effects.

Allergies

  • Avoid with known allergy or sensitivity to arginine. Symptoms may include rash, itching, or shortness of breath. Anaphylaxis (severe allergic reaction) has occurred after arginine injections. In clinical research, one patient experienced a mild allergic skin reaction to intravenous L-arginine. Hives have also been reported.

Side Effects and Warnings

  • Note: According to the U.S. Food and Drug Administration (FDA) website, pediatric overdose of arginine hydrochloride injection (R-Gene 10®) has been reported, due to packaging and labeling confusion. Revisions have since been made to the product's packaging. The new label warns that R-Gene 10® infusions should be used cautiously in children to prevent overdose, which may result in hyperchloremic metabolic acidosis, cerebral edema, or possibly death.
  • Arginine is likely safe when taken in levels normally found in foods.
  • Arginine may increase the risk of bleeding. Caution is advised in people with bleeding disorders or those taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary.
  • Arginine may change blood sugar levels. Caution is advised in people with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.
  • Arginine may cause hyperkalemia (abnormally high levels of blood potassium). Use cautiously in people with impaired kidney function or those at risk for hyperkalemia, including those with diabetes or using drugs that elevate potassium levels, such as potassium-sparing diuretics and potassium supplements. Fatal cardiac arrhythmias from hyperkalemia occurred in one person.
  • Use cautiously in children and in pregnant women, due to insufficient available evidence and safety data.
  • Use caution with phosphodiesterase inhibitors (e.g., sildenafil [Viagra®]).
  • Use with caution in postmenopausal women or people with the herpes virus, peripheral arterial disease and intermittent claudication, immune disorders, acrocyanosis (blue coloring of hands and feet), sickle cell anemia, hyperchloremic acidosis (acid-base imbalance in the body), gastrointestinal problems, muscle or joint problems, urinary disorders, asthma, cycstic fibrosis, methyltransferase (GAMT) deficiency (a genetic disorder), or at risk for headaches.
  • Avoid with known allergy or sensitivity to arginine.
  • Avoid in doses over 30 grams due to increased risk of toxic effects.
  • Avoid in women with high-risk pregnancies, as, in women with multiple diseases, intravenous arginine resulted in premature delivery, pre-eclampsia, and death in two cases.
  • Arginine may cause low blood pressure. Avoid use in those with low blood pressure or those using blood pressure-lowering agents.
  • Avoid with nitrates and spironolactone as well as in people with pulmonary hypertension, cancer, and those at risk for or with a history of heart attack.
  • Arginine may also cause bloating; diarrhea; hematuria (blood in urine), hives; hormonal changes; increased blood urea nitrogen, serum creatine, and serum creatinine; increased inflammatory response (in people with asthma or cystic fibrosis); leg restlessness, lower back pain; nausea, night sweats and flushing (with arginine withdrawal), numbness (with arginine injection); rash; reduction in hematocrit; severe tissue damage (with arginine injection); stomach and intestine discomfort; systemic acidosis; or venous irritation.
  • In people with heart disease or heart transplants, arginine may cause high white blood cell counts, increased post-heart attack deaths, lack of energy and strength, vertigo, or increased blood pressure.

Pregnancy and Breastfeeding

  • Use cautiously in pregnant or breastfeeding women, due to a lack of sufficient available safety and efficacy data.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare professional before starting a new therapy.

Interactions with Drugs

  • Arginine may cause low blood pressure. Caution is advised in people taking herbs or supplements that lower blood pressure.
  • Arginine may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants (blood thinners) such as warfarin (Coumadin®) or heparin, antiplatelet drugs such as clopidogrel (Plavix®), and nonsteroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).
  • Arginine may change blood sugar levels. Caution is advised when using medications that may affect blood sugar levels. People taking insulin or drugs for diabetes by mouth should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
  • Arginine may also interact with ACE (angiotensin-converting enzyme) inhibitors, agents for pain or for the heart, agents that affect the nervous system, agents that increase potassium levels (including angiotensin II receptor antagonists and heparin), agents that decrease the immune system, agents used to treat blood disorders, aminophylline, antacids, antibiotics, anticancer agents, anti-inflammatories, antimalarials, antiobesity agents, antiseizure agents, aspirin, cardiac glycosides, cholesterol-lowering agents, contraceptives (birth control), cyclophosphamide, cyclosporine, diuretics, estrogens, glucagon, growth hormones, H2 blockers, insulin, iron salts, isoproterenol, nicotine, nitrates, nitroderivatives, phenylephrine, phosphodiesterase inhibitors, potassium salts, progestin, propofol, proton pump inhibitors, sertraline, spironolactone, and stomach and intestinal agents.

Interactions with Herbs and Dietary Supplements

  • Arginine may lower blood pressure. Caution is advised in people taking herbs or supplements that lower blood pressure.
  • 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 change blood sugar levels. Caution is advised when using herbs or supplements that may also change blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.
  • Arginine may also interact with antacids; antibacterials; anticancer herbs and supplements; anti-inflammatories; antimalarials; antioxidants; athletic performance enhancers; branched chain amino acids; cardiac glycosides; cholesterol-lowering herbs and supplements; citrulline; conjugated linoleic acid (CLA); creatine; diuretics; gingko; green tea extract; herbs and supplements for the heart, obesity, pain, or seizures; herbs and supplements that affect the nervous system or reduce immune function; hormonal herbs and supplements; iron; lysine; magnesium; N-acetyl cysteine; omega-3 fatty acids; ornithine; phytoestrogens; pine bark extract; piplartine; Pycnogenol®; sodium; stomach and intestinal herbs and supplements; vitamin C; vitamin E; wound healing herbs and supplements; xylitol; and yohimbine.

Authors

Selected References

Natural Standard developed the above evidence-based information based on a 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.

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