For Patients & Caregivers
How It Works
Arginine is made in the body and also found in many protein-rich foods. Although it is used in clinical applications, evidence on its use for other conditions is lacking and in some instances may increase the risk for harm.
Arginine is an amino acid that is produced by the body. Clinical applications include its use during recovery from surgery, for heart and blood vessel conditions like angina or high blood pressure, and for some pregnancy complications. Arginine has also been used to enhance immune function and athletic performance or to improve conditions such as migraines and erectile dysfunction, but more studies are needed.
A few trials of arginine supplementation have been conducted in cancer patients. Some show that arginine-enriched nutritional formulas taken around the time of surgery may improve wound healing, enhance immune status, and reduce length of hospital stay. However, an analysis suggests that arginine supplementation may increase inflammatory biomarkers in certain subgroups, including cancer or older patients. Other studies suggest potential harm with long-term supplementation or in those who have had a heart attack. Therefore, additional studies are needed to determine the circumstances under which arginine supplementation could be safe and effective.
To treat angina, hardening of blood vessels, or high blood pressure
Some studies support the benefits of arginine for angina, atherosclerosis, and hypertension, but there are some conditions where supplementation may increase the risk for harm. Patients should therefore be managed by their treating physician.
To speed wound healing
Data on whether arginine can improve wound healing are mixed.
To improve immune function
Data on whether arginine can improve immune function are mixed.
To treat erectile dysfunction
Preliminary data suggest arginine may help improve sexual function in men, but more studies are needed.
To treat migraine headaches
Preliminary data suggest that arginine taken with ibuprofen may increase pain relief in patients with migraines, but more studies are needed.
- Patients who have had a heart attack should avoid using arginine, as one study suggests it may increase risk for additional harm.
- Long-term arginine supplementation in patients with peripheral artery disease may be harmful. Patients with this condition should be managed by their treating physician.
- Some evidence suggests an increase in breast tumor growth after taking arginine supplements, but more studies are needed to confirm this.
Do Not Take If
- You are taking medicine for high blood pressure, heart conditions, or erectile dysfunction: Arginine may have additional blood pressure-lowering effects.
- You are a cancer patient: There is some data suggesting increases in inflammatory biomarkers with arginine supplementation, so patients should use caution and discuss any use of arginine with their treating physician.
- You have had a heart attack: Patients with this condition should use caution and be managed by their treating physician.
- You have peripheral artery disease: Patients with this condition should use caution and be managed by their treating physician.
- Abdominal pain
- Large doses can increase removal of the amino acid lysine in urine.
- Throat pain and inflammation: In a 40-year-old woman after taking l-arginine, selenium, and vitamin E supplements. A few other cases have also pointed to arginine as the suggested cause.
- Acute pancreatitis: Cases in young adult men, attributed to use of arginine-containing products.
For Healthcare Professionals
Arginine is an amino acid that is synthesized in the body. Oral arginine has been used for various conditions such as hypertension, angina, atherosclerosis, migraines, and erectile dysfunction. Its vasodilatory properties are thought to be responsible for the beneficial effects. Arginine has also been used to enhance wound healing, immune function, and athletic performance.
Some studies support the use of arginine in coronary artery and peripheral artery diseases (10) (11) (12) (13), but long-term supplementation worsened PAD (14). In addition, oral supplementation in patients who had an acute myocardial infarction did not improve ejection fraction or vascular stiffness, and may be associated with higher mortality (38). A meta-analysis of arginine supplementation on markers for cardiovascular disease, obesity, or diabetes also did not find benefit, except perhaps in a select group of patients (39). Smaller studies suggest supplementation with arginine, glutamine, and HMB may benefit vascular endothelial function in older adults (33), but arginine supplementation alone did not improve blood flow or muscle performance in older women (34).
Along with antioxidant vitamins, arginine reduced preeclampsia incidence in high-risk women (28), but arginine supplements did not improve blood pressure or kidney function in women with preeclampsia (15). Preliminary data suggest potential benefit with arginine supplementation for erectile dysfunction (16) (40). Arginine combined with ibuprofen may increase pain relief in patients with migraines (17). Enteral arginine decreased shock in severely burned patients (4) and may be useful as adjunctive therapy in patients with active tuberculosis (29).
In cancer patients, preliminary results are mixed for perioperative enteral arginine-enriched formulas to improve wound healing (1) (41), and immune function (27) (35) (42), but other studies suggest such formulas may reduce complications and length of hospital stay (30) (36). Some data suggest a prophylactic arginine-containng supplement may reduce incidence of hand-foot syndrome in hepatocellular carcinoma patients taking sorafenib (43). Interestingly, arginine deprivation-based treatments are also being pursued as potential cancer treatments (31) (32) (37).
Although a meta-analysis did not find significant effects with arginine supplementation on inflammatory biomarkers, subgroup analysis suggests it may increase circulating C-reactive protein in cancer patients, those older than age 60 or with higher baseline CRP levels, or with use of enteral formulas (44). Additional studies are needed to determine the circumstances under which arginine supplementation could be safe and effective.
Mechanism of Action
Arginine is unique among amino acids for its vasodilatory properties (11). Arginine acts as a precursor for the synthesis of endogenous nitric oxide (NO) via the action of nitric oxide synthase (NOS). NO functions as a paracrine-signaling molecule mediating vasodilation and inhibition of platelet activation, monocyte and leucocyte adhesion, and smooth muscle cell proliferation. NO also helps to control vascular oxidative stress and redox-regulated gene expression (22). Arginine is also needed for the synthesis of creatine which is important in muscle contraction (22). In colorectal adenoma cells, arginine reduces the expression of survivin, an inhibitor of apoptosis, and induces iNOS expression (23).
- In patients who had an acute myocardial infarction, arginine supplementation may increase risk of mortality (38).
- Long-term supplementation may worsen peripheral artery disease (14).
- Limited studies suggest that arginine supplementation may increase breast tumor growth, but more research is needed to examine this (9) (21).
Supplement-induced esophagitis: In a 40-year-old woman after ingestion of l-arginine, selenium, and vitamin E supplements. A few other cases have also pointed to arginine as the suggested cause (45).
Acute pancreatitis: Upper abdominal pain and increased serum lipase levels in a young adult man, attributed to a protein shake containing arginine. The condition improved with treatment and cessation of the product (46). Another earlier case in a young adult had also been reported (47).