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Arginine (L-arginine) - Natural Medicine A-Z
Arginine (L-arginine)
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®.
 Overview Does It Work? Safety How to Use

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.

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

Grade*

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.

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.

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.

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.

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.

B

Migraine headache

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

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.

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.

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.

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.

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.

C

Burns

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

C

Chemotherapy adjuvant

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

C

High cholesterol

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

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.

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.

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.

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.

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.

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.

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)

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.

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.

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.

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.

C

Senile dementia

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

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.

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.

C

Altitude sickness

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

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.

D

Exercise performance

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

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.

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.

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.

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.

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 for this use (it may not work)

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.

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.

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