Arginine

Arginine, also called L-arginine, is an amino acid used by the body as a protein building block. It’s also an intermediate metabolite in the urea cycle and the nitric oxide cycle.^[1][2][3] The urea cycle removes excess ammonia, a toxic molecule, from the body, and the nitric oxide cycle produces nitric oxide, which is an important signaling molecule involved in vascular function.^[1][2][3] Although the body can synthesize arginine, it can also be obtained in the diet through protein-containing foods or dietary supplements.^[1][2][3]

Daily supplementation with arginine can reduce blood pressure in people with healthy blood pressure and people with hypertension (high blood pressure).^[4] Evidence also supports the use of arginine to help improve birth outcomes in pregnant women with conditions like hypertension and preeclampsia or a history of poor pregnancy outcomes. This includes reducing the risk of infants small for gestational age^[5] and intrauterine growth restriction of the baby.^[6] Arginine can also improve maternal outcomes by reducing the risk of preeclampsia in the pregnant mother.^[7][8] Additionally, arginine can reduce blood triglycerides,^[9][10] particularly in people older than 50 or in people with metabolic syndrome or type 2 diabetes.^[9]

In men with erectile dysfunction, daily supplementation with arginine can alleviate symptoms.^[11] Furthermore, the combination of arginine with phosphodiesterase type 5 inhibitors (PDE5Is), like Viagra, improves sexual function in men with erectile dysfunction more than treatment with PDE5Is alone.^[12]

Evidence also shows that daily supplementation with arginine might increase VO₂max, but the magnitude of improvement is negligible and unlikely to be clinically meaningful.^[13] Furthermore, most studies find no beneficial effect of arginine on exercise performance.^[14] It is only when highly-varied types of exercise (aerobic, anaerobic, resistance, etc.) and performance outcomes (time-to-exhaustion, time-trials, sprint time, 1-rep-max, reps-to-failure, etc.) are inappropriately pooled that meta-analyses find a performance benefit from arginine.^[14]

Animal studies show that neither oral nor intravenous delivery of arginine causes toxicity, even at high doses.^[15][16] However, supplementation with arginine has been reported to cause adverse gastrointestinal effects in humans, including nausea, vomiting, and diarrhea.^[17] For this reason, upper limit guidelines of approximately 20 to 30 grams per day have been proposed for supplemental arginine intake,^[18][19] but more long-term safety data in humans are needed to accurately define a tolerable upper intake level.

Nitric oxide is a key molecule involved in vasodilation, i.e., the relaxation and widening of blood vessels to increase blood flow to tissues that lack oxygen or nutrients.^[20][2] The beneficial effects of arginine on high blood pressure^[4][7][8] and erectile dysfunction^[11][12] are likely related to vasodilation because arginine increases nitric oxide synthesis.^[20][2][3]

A similar mechanism may explain how arginine might increase VO₂max.^[21][22][13] Additionally, nitric oxide might have direct effects on muscle contractile function.^[21][23] Furthermore, arginine’s role in the urea cycle helps with ammonia excretion^[1], the accumulation of which might induce fatigue during exercise.^[24][25][26]