Arginine (L-arginine)
Contents of this page:
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- Background
- Synonyms
- Evidence
- Dosing
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- Safety
- Interactions
- Methodology
- Selected references
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Arginine |
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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.
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.
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 |
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.
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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.
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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.
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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.
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C |
| High cholesterol
Some research suggests
that arginine may help treat or prevent high cholesterol. More
research is needed.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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;
F: Strong scientific evidence against this use.
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
healthcare provider.
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
The below doses are based on scientific
research, publications, traditional use, or expert opinion. Many herbs
and supplements have not been thoroughly tested, and safety and
effectiveness may not be proven. Brands may be made differently, with
variable ingredients, even within the same brand. The below doses may
not apply to all products. You should read product labels, and discuss
doses with a qualified healthcare provider before starting therapy.
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
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 provider before starting a new therapy. Consult a
healthcare provider immediately if you experience side effects.
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
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 provider before starting a new therapy.
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.
Methodology
- This information is based on
a professional level monograph edited and peer-reviewed by
contributors to the Natural Standard Research Collaboration
(www.naturalstandard.com).
Selected references
- 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.
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