Arginine (L-arginine)
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| Arginine |
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L-arginine was first isolated in 1886. In 1932, L-arginine was found to be
required for the generation of urea, which is necessary for the removal of
toxic ammonia from the body. In 1939, L-arginine was also shown to be required
for the synthesis of creatine. Creatine degrades to creatinine at a constant
rate, and is cleared from the body by the kidney.
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Arginine is considered a semi-essential amino acid, because although it is
normally synthesized in sufficient amounts by the body, supplementation is
sometimes required (for example, due to inborn errors of urea synthesis,
protein malnutrition, excess ammonia production, excessive lysine intake,
burns, infection, peritoneal dialysis, rapid growth, or sepsis). Symptoms of
arginine deficiency include poor wound healing, hair loss, skin rash,
constipation, and fatty liver.
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Arginine is a precursor of nitric oxide, which causes blood vessel relaxation
(vasodilation). Preliminary evidence suggests that arginine may be useful in
the treatment of medical conditions that are improved by vasodilation, such as
angina, atherosclerosis, coronary artery disease, erectile dysfunction, heart
failure, intermittent claudication/peripheral vascular disease, and vascular
headache. Arginine also stimulates protein synthesis and has been studied for
wound healing, bodybuilding, enhancement of sperm production
(spermatogenesis), and prevention of wasting in people with critical illness.
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Arginine hydrochloride contains high chloride content and has been used for
the treatment of metabolic alkalosis. This use should be under the supervision
of a qualified healthcare professional.
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Most people likely do not need to take arginine supplements because the body
usually makes sufficient amounts.
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Arg, arginine, arginine hydrochloride (intravenous formulation), ibuprofen-arginate
(Spedifen®), L-arg, L-arginine, 2-amino-5-guanidinopentanoic acid.
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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.
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Dietary sources of arginine: Walnuts, filberts, pecans, Brazil nuts, sesame
and sunflower seeds, brown rice, raisins, coconut, gelatin, buckwheat,
almonds, barley, cashews, cereals, chicken, chocolate, corn, dairy products,
meats, oats, peanuts.
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
Intravenously administered arginine can be used to evaluate growth
hormone reserve in individuals with suspected growth hormone deficiency.
For example, in patients with suspected panhypopituitarism,
growth/stature abnormalities, gigantism/acromegaly, or pituitary
adenoma. This is a Food and Drug Administration (FDA) labeled indication
for arginine.
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A |
| Inborn errors of urea synthesis
In patients with inborn errors of urea synthesis, high blood ammonia
levels and metabolic alkalosis may occur, particularly in patients with
ornithine carbamoyl transferase (OCT) deficiency or carbomoyl phosphate
synthetase (CPS) deficiency. Arginine can be a helpful treatment by
shifting the way the body processes nitrogen, but should be avoided in
patients with hyperargininemia (high arginine levels). Other drugs may
have similar benefits, such as citrulline, sodium benzoate, or sodium
phenylbutyrate, although dialysis may be necessary initially. This use
of arginine should be supervised by a qualified healthcare professional.
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A |
| Adrenoleukodystrophy (ALD)
Adrenoleukodystrophy (ALD) is a rare inherited metabolic disorder
characterized by the loss of fatty coverings (myelin sheaths) on nerve
fibers in the brain, and progressive destruction of the adrenal gland.
ALD is inherited as an x-linked genetic trait that results in dementia
and adrenal failure. Injections of arginine have been proposed to help
manage this disorder, although most study results are inconclusive.
Further research is needed to evaluate the use of arginine in ALD.
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C |
| Burns
A randomized, controlled clinical trial designed to evaluate immune
function of patients suggests that arginine may help with the recovery
of immune function and protein function in partial-thickness burn
patients. Further research is necessary in this area before a conclusion
can be drawn.
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C |
| Coronary artery disease / angina
There is initial evidence from several studies that arginine taken by
mouth or by injection improves exercise tolerance and blood flow in
arteries of the heart. Benefits have been shown in some patients with
coronary artery disease and angina. A small randomized, controlled
clinical trial studied the effects of a medical food bar enriched with
L-arginine and a combination of other nutrients in the management of
chronic stable angina. The authors found that this arginine-rich medical
food, when used with traditional therapy, improves vascular function,
exercise capacity and aspects of quality of life in these patients.
However, further research is needed to confirm these findings and to
establish doses that may be safe and effective.
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C |
| Critical illness
Some studies suggest that arginine may provide benefits when added to
nutritional supplements during critical illnesses (for example, in
patients being treated in intensive care units). However, it is unclear
what the specific role of arginine may be in improving recovery. A
randomized, controlled clinical trial was designed to study the effects
of a high-protein formula enriched with arginine, fiber, and
antioxidants in early nutrition therapy of critically ill patients. The
study measured infections in the hospital intensive care unit (ICU),
length of hospital stay, and death rates. Patients fed the high-protein
diet enriched with arginine, fiber and antioxidants developed fewer
hospital infections than patients fed a standard high-protein diet.
There was no difference in length of ICU hospital stay or death
rate.Overall the scientific data to date does not show benefit for only
L-arginine supplementation, nor does it show harm. At this time there is
no rationale for the routine supplementation of arginine alone to
enhance recovery from serious illness. Because of the potential for
harm, this amino acid should only be administered to critically ill
patients in large doses under carefully monitored study conditions.
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C |
| Dental pain (ibuprofen arginate)
A well-designed multicenter, randomized, controlled clinical trial found
that ibuprofen-arginate (Spedifen®) reduced pain faster after dental
surgery compared to conventional ibuprofen alone. The study included 498
patients who were given ibuprofen-arginate, ibuprofen, or placebo after
dental surgery. The degree of pain relief, onset of action, and
tolerability of both ibuprofen-arginate and ibuprofen were compared. It
was found that ibuprofen arginate relieved pain faster and adverse
events with ibuprofen-arginate were similar to those seen with ibuprofen
alone. Another similar trial concluded that patients treated with
ibuprofen-arginate rated its overall effectiveness higher than those
treated with ibuprofen alone. Adverse event profiles were similar across
all treatment groups. Further research is merited in this area.
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C |
| MELAS syndrome
One study found that two years of supplementation with oral L-arginine
significantly improved endothelial function in patients with MELAS
(mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke).
Further research is merited in this area.
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C |
| Erectile dysfunction
Early studies propose that men with low nitrate levels in their blood or
urine may find arginine supplements to be useful for managing erectile
dysfunction (ED). A randomized, controlled clinical trial reported
improvements in patients with mild-to-moderate ED following use of a
combination of L-arginine, glutamate and yohimbine hydrochloride.
Notably, yohimbine hydrochloride is an FDA-approved therapy for this
condition, and the effects caused by arginine alone in this combination
therapy are difficult to determine. It is not clear what doses of
arginine may be safe or effective in treating this condition, and
comparisons have not been made with other agents used for ED.
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C |
| Gastrointestinal cancer surgery
Supplementation with an oral combination of arginine and omega-3 fatty
acids may reduce length of hospital stay and infections after surgery in
gastrointestinal cancer patients. There is conflicting evidence as to
when to give the combination (either before or after surgery). Both
strategies have been reported as superior to conventional treatment (no
artificial nutrition) at reducing infections after surgery and reducing
hospital stay.In a large, randomized, controlled clinical trial,
malnourished cancer patients were given oral enteral nutrition
supplemented by arginine, omega-3 fatty acids and RNA before surgery. It
was found that supplementation with the combination before surgery
reduced complications after surgery and hospital stay. A different
randomized, controlled clinical trial in patients with gastrointestinal
cancer studied the effects of an enteral diet supplemented with
arginine, omega-3 fatty acids and glutamine (administered after surgery)
on immune function and inflammatory response. This study reported the
supplement to be well-tolerated with positive effects on immune and
inflammatory response. Further research is needed to determine the
possible effects of arginine alone.
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| Heart failure (CHF)
Studies of arginine in patients with chronic heart failure have shown
mixed results. Some studies report improved exercise tolerance.
Additional studies are needed to confirm these findings before a firm
conclusion can be drawn.
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| Heart protection during coronary artery bypass
grafting (CABG)
Arginine-supplemented "blood cardioplegic solution" is
proposed to have protective properties for the heart. A randomized,
controlled clinical trial using this solution in patients undergoing
heart surgery (coronary artery bypass grafting) reports improved heart
protection. Further research is needed before a firm conclusion can be
drawn.
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C |
| High blood pressure
A small study suggests that arginine taken by mouth may dilate the
arteries and temporarily reduce blood pressure in hypertensive patients
with type 2 diabetes. Larger, high-quality studies are needed before a
recommendation can be made.
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| Immunomodulator
Preliminary study results suggest that arginine supplementation may
enhance the immune response elicited by the pneumococcal vaccine in
older people. More studies are needed to confirm these results.
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| Migraine headache
Preliminary studies suggest that adding arginine to ibuprofen therapy
may decrease migraine headache pain.
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| Myocardial infarction
Study results of arginine supplementation after myocardial infarction
(heart attack) are mixed. Further research is needed before a
recommendation can be made. A cardiologist and pharmacist should be
consulted prior to initiation of arginine therapy.
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C |
| Peripheral vascular disease / claudication
Intermittent claudication is a condition characterized by leg pain and
fatigue due to buildup of cholesterol plaques or clots in leg arteries.
A small number of studies report that arginine therapy may improve
walking distance in patients with claudication. Further research is
needed before a firm conclusion can be drawn.
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C |
| Pre-eclampsia (high blood pressure in pregnancy)
Early study suggests that prolonged dietary supplementation with
L-arginine may decrease blood pressure that is too high in pregnant
women. Further research is needed to confirm these results.
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| Pressure ulcers
Studies of arginine for pressure ulcers show mixed results. Further
research is needed before a conclusion can be drawn.
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| Recovery after surgery
One study suggests that arginine may provide benefits when used as a
supplement after surgery. It is not clear what the specific role of
arginine may be in improving immune function, or what dose is safe or
effective.
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| Transplants
Dietary supplementation with L-arginine and canola oil has been
associated with decreased rejection rates after the first month in renal
transplant patients. Due to reductions in cardiac events, long-term
benefits for patient survival may be particularly important. Further
research is needed to confirm these results.
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| Wound healing
Arginine has been suggested to improve the rate of wound healing in
elderly individuals. A randomized, controlled clinical trial reported
improved wound healing after surgery in head and neck cancer patients,
following the use of an enteral diet supplemented with arginine and
fiber. Arginine has also been used topically (on the skin) to attempt to
improve wound healing. Further research is necessary in this area before
a firm conclusion can be drawn.
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C |
| Acute mountain sickness (AMS)
Based on preliminary study, L-arginine supplementation is not beneficial
in the prophylactic treatment of AMS.
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D |
| Cyclosporine toxicity
Animal studies report that arginine blocks the toxic effects of
cyclosporine, a drug used to prevent organ transplant rejection.
However, results from studies in humans have not found that arginine
offers any protection from cyclosporine-induced toxicity.
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D |
| Exercise performance
Overall, currently available study results conclude that arginine
supplementation does not improve exercise performance.
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D |
| Infertility
Although there are several studies in this area, it is not clear what
effects arginine has on improving the likelihood of getting pregnant.
Early evidence does not support the finding that arginine has any
benefits in women who are undergoing in vitro fertilization,
or in men with abnormal sperm.
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D |
| Interstitial cystitis
Arginine has been proposed as a treatment for interstitial cystitis
(inflammation of the bladder). However, most well-designed studies in
humans have not found that arginine offers any improvements in treating
symptoms such as urinary frequency or urgency.
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D |
| Kidney disease
It has been suggested that arginine may be a useful supplement in people
diagnosed with kidney failure. However, results from available studies
do not support this claim. A small randomized, controlled clinical trial
studied the ability of L-arginine to improve dilation of blood vessels
in children with chronic renal failure. Results showed that blood vessel
dilation (endothelial function) was not improved with oral L-arginine
suggesting that dietary supplementation is not a beneficial or useful
clinical approach in children with chronic renal failure.
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D |
| Kidney protection during angiography
The contrast media or dye used during angiography to map a patient's
arteries (or during some CT scans) can be toxic to the kidneys,
especially to people with pre-existing kidney disease. A randomized,
parallel, double-blind clinical trial studied the use of L-arginine to
protect kidneys in patients with chronic renal failure undergoing
angiography. The authors found no evidence that injections of L-arginine
protect the kidney from damage due to contrast.Other therapies, such as
N-acetylcysteine (NAC), have been found beneficial at protecting the
kidneys from contrast-induced damage, particularly in patients at
high-risk such as those with diabetes.
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D |
| Asthma
Although it has been suggested that arginine may be a treatment for
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.
Grading rationale
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, ammonia toxicity, anti-aging, beta-hemoglobinopathies, cancer, cardiac
syndrome X, cold prevention, cystic fibrosis, dementia, diabetes, glaucoma,
growth hormone stimulation, hemolytic uremic syndrome (HUS), hepatic
encephalopathy, high cholesterol, increased muscle mass, infantile necrotizing
enterocolitis, infection, inflammatory bowel disease, ischemic stroke, liver
disease, lower esophageal sphincter relaxation, low sperm count, metabolic
acidosis, obesity, osteoporosis, pain, peritonitis, pre-term labor contractions,
pulmonary hypertension (high blood pressure in the lungs), Raynaud's phenomenon,
sepsis, sexual function in women, sickle cell anemia, stomach motility
disorders, stomach ulcer, stroke, supplementation to a low protein diet,
thrombotic thrombocytopenic purpura (TTP), tumors.
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.
Standardization:
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Intravenous arginine hydrochloride is available as a 10% solution (950 mOsm/L),
with 47.5mEq chloride ion per 100mL. There is no established standardization
for oral arginine products.
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Note: Most people likely do not need to take arginine supplements because the
body usually makes sufficient amounts.
Adults (18 years and older):
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Tablets/capsules : There are no standard or well-established
doses of arginine, and many different doses have been used and studied. A dose
that has been studied for treating coronary artery disease is two to three
grams taken by mouth three times daily for three to six months. For short-term
treatment, up to 10 grams for four weeks has also been used. A studied dose
for heart failure is 5.6 to 12.6 grams taken by mouth every day, divided into
two or three equal doses, taken for six weeks. For myocardial infarction, 3
grams of L-arginine three times per day for 30 days has been used. For
erectile dysfunction, 1.6 grams taken by mouth three times daily for six weeks
has been studied. For low sperm count, 4 grams daily for three months has been
used. For women undergoing in vitro (test tube)
fertilization, a dose of 16 grams daily by mouth has been studied, although
this therapy should be discussed with the healthcare provider coordinating the
in vitro program. For interstitial cystitis, 500 milligrams
taken by mouth three times daily for six weeks has been used. For the
long-term management of inborn disorders of the urea cycle, doses between 0.5
to 2 grams daily have been used. 8.5 grams of arginine daily has been studied
in patients with pressure ulcers for four weeks. For immune enhancement
following vaccination in the elderly, 15 grams daily arginine for four weeks
has been used.
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Intravenous : 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):
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Arginine supplements are not recommended in children because there is not
enough scientific information available and because of potential side effects.
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
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Anaphylaxis (severe allergic reaction) has occurred after arginine injections.
People with a known allergy should avoid arginine. Signs of allergy may
include rash, itching or shortness of breath.
Side Effects and Warnings
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Arginine has been well tolerated by most people in studies lasting for up to
six months, although there is a possibility of serious adverse effects in some
individuals.
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Stomach discomfort, including nausea, stomach cramps or an increased number of
stools, may occur. People with asthma may experience a worsening of symptoms
if arginine is inhaled, which may be related to allergy. Headache has also
been reported.
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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 disease 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.
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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 a qualified healthcare provider before
using arginine and should be monitored.
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Arginine may increase blood sugar levels. Caution is advised in patients
taking prescription drugs to control sugar levels.
Pregnancy and Breastfeeding
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Arginine cannot be recommended as a supplement during pregnancy and
breast-feeding because there is not enough scientific information available.
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L-arginine has been used in women with preeclampsia until day 10 postpartum
but should not be used without supervision of an OB/GYN and pharmacist.
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
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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 can decrease the effect that arginine has on
glucagon.
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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.
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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.
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Arginine should be used carefully with drugs such as nitroglycerin or
sildenafil (Viagra®) because blood pressure may fall too low. Other adverse
effects such as headache and flushing may occur when arginine is used with
these drugs.
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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®).
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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®).
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It is also possible that arginine may raise blood sugar levels. Patients
taking oral drugs for diabetes or using insulin should be monitored closely by
their health care provider while using arginine. Dosing adjustments may be
necessary.
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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 provider before combining these medications.
Interactions with Herbs and Dietary Supplements
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Arginine may block the benefits of lysine in treating cold sores. It may
increase the activity of growth hormone if used with ornithine.
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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.
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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 provider while using arginine. Dosing adjustments may be necessary.
Interactions with Laboratory Tests
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Consumption of L-arginine may alter IL-2 receptor, IL-6, TNF-alpha, platelets
and leukocytes as well as creatine kinase-MB mass and troponin T levels.