Overview
L-arginine is a conditionally essential amino acid serving as the primary substrate for nitric oxide (NO) synthesis via the nitric oxide synthase enzyme. Nitric oxide is a crucial signaling molecule controlling blood vessel dilation, blood pressure, immune function, and cellular communication.
Primary applications focus on cardiovascular health and blood pressure support, erectile dysfunction (mild to moderate), athletic performance and muscle blood flow (mixed evidence), wound healing support (clinical use), and immune function enhancement.
Evidence quality is moderate for cardiovascular benefits and ED, mixed for athletic performance (citrulline might be superior), good for clinical wound healing.
Safety is generally good at typical doses (3-6 grams daily), though GI side effects are common at higher doses, and arginine supplementation is contraindicated after heart attack due to increased mortality risk in research.
What it means
Amino acid that makes nitric oxide (NO) - dilates blood vessels for better blood flow. Best evidence for heart health and mild erectile dysfunction. Typical dose: 3-6 grams daily. CRITICAL: Don't take after a heart attack - one study found increased death risk. L-citrulline often works better with fewer stomach issues.
Mechanisms, Evidence, and Practical Use
What it means
Arginine → nitric oxide → blood vessels relax → better circulation. Simple mechanism, solid science. But citrulline (converts to arginine) often raises blood arginine higher than arginine itself!
Nitric oxide synthesis is arginine's fundamental mechanism - arginine → nitric oxide + citrulline via nitric oxide synthase (NOS) enzymes. NO then activates guanylate cyclase, increasing cGMP, which causes smooth muscle relaxation in blood vessels (vasodilation).
Cardiovascular Health
For cardiovascular health, arginine (3-6 grams daily) improves endothelial function, reduces blood pressure (modest effects in hypertensive individuals), and enhances blood flow in peripheral artery disease. However, a major clinical trial (VINTAGE-MI) found arginine supplementation after heart attack increased mortality, creating an important contraindication. The trial was stopped early due to safety concerns and established arginine as contraindicated after recent MI. Mechanism unclear but might involve excessive NO production interfering with healing or interacting with other MI treatments.
What it means
Good for general heart health and blood pressure. BUT - if you've had a heart attack, arginine is dangerous. One trial was stopped early because more people died. Never take it post-MI.
Erectile Dysfunction
For erectile dysfunction, arginine (2.5-5 grams daily) shows benefits for mild to moderate ED in some studies, with effects comparable to or enhancing PDE5 inhibitors (Viagra, Cialis) when combined. Mechanism: improved blood flow to erectile tissue via NO. Effects are weaker than prescription ED medications but might help mild cases or when combined with pycnogenol or citrulline.
What it means
May help mild ED by improving blood flow. Not as strong as Viagra, but cheaper and available without prescription. Works better combined with pycnogenol or citrulline.
Athletic Performance (Mixed Evidence)
For athletic performance, despite widespread marketing, research on arginine supplementation (5-9 grams pre-workout) shows inconsistent results for strength, endurance, or muscle pump. Citrulline supplementation appears more effective at raising arginine levels and improving exercise performance, making it a better choice for athletic applications.
What it means
Gym marketing hypes arginine for "muscle pumps." Research is mixed at best. L-citrulline works better - raises blood arginine higher and has fewer stomach issues. Switch to citrulline for workouts.
Wound Healing
For wound healing, arginine supports collagen synthesis and immune cell function during wound repair. Supplementation (9-30 grams daily in medical formulations) accelerates healing in clinical populations (surgical patients, pressure ulcers). General wound support uses lower doses (3-6 grams).
Dosing and Administration
Dosing: 3-6 grams daily for cardiovascular health or ED. 5-9 grams pre-workout for athletic performance (though citrulline might be better). 9-30 grams for clinical wound healing applications under medical supervision. Divide large doses throughout day to minimize GI upset.
L-citrulline alternative: Citrulline converts to arginine in kidneys, bypassing liver first-pass metabolism. Research suggests citrulline (6-8 grams) raises blood arginine levels more effectively than equivalent arginine doses, with better GI tolerability. For athletic performance or NO production, citrulline is often preferred.
What it means
Pro tip: Citrulline (6-8 grams) raises blood arginine levels HIGHER than taking arginine itself, with way less stomach upset. For most uses, citrulline is smarter.
Safety and Contraindications
Safety: Generally well-tolerated but with notable side effects and contraindications. Common side effects: GI upset, diarrhea, bloating (dose-dependent, very common at doses above 9-10 grams), nausea, and allergic reactions (rare).
Contraindications: Recent heart attack (within months): contraindicated based on mortality study. Herpes virus infections: Arginine might promote viral replication (HSV, HPV) - those with recurrent herpes should avoid or use lysine concurrently. Low blood pressure: Excessive vasodilation. Asthma: Might affect airway reactivity in some.
Drug interactions: Blood pressure medications (additive hypotensive effects), blood thinners or antiplatelet drugs (arginine has mild antiplatelet effects), diabetes medications (might affect blood sugar), PDE5 inhibitors (Viagra, Cialis - additive vasodilation, use cautiously together).
L-arginine is valuable for cardiovascular health and mild ED with good mechanistic basis through NO production, but has important contraindications, GI tolerability issues at performance doses, and potential superiority of citrulline for some applications.
References
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.
Dong JY, Qin LQ, Zhang Z, et al. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J. 2011;162(6):959-965.